ADHD Atten Def Hyp Disord (2017) 9(Suppl 1):S1–S55 DOI 10.1007/s12402-017-0224-y
ABSTRACTS
Springer-Verlag Wien 2017
6th World Congress on ADHD: From Child to Adult Disorder
20–23 April 2017 Vancouver Canada
Editors: Manfred Gerlach, Wu¨rzburg, Germany Peter Riederer, Wu¨rzburg, Germany Luis A. Rohde, Porto Alegre, Brazil Andreas Warnke, Wu¨rzburg, Germany
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Introduction Dear Colleagues and Friends, On behalf of the World Federation of ADHD, we are pleased to welcome you to the 6th World Congress on ADHD: From Child to Adult Disorder in Vancouver, Canada, from 20 to 23 April. Every second year, the World Congress on ADHD attracts numerous delegates from all over the world who want to learn about the latest research findings and perspectives. The World Congress makes it possible to listen to world-renowned speakers, presenting the most recent information on ADHD and related disorders, and to share experiences and knowledge with old and new friends. The Scientific Programme Committee has once again created an excellent scientific programme, consisting of outstanding Plenary Lectures and parallel Hot Topic and Research Consortia Symposia, Late Breaking News, and Guided Poster Tours. In two new formats, the Grand Round and the Pro and Con debate, clinical cases and controversies on long-term effects of ADHD treatment will be discussed by some of the most reputed ADHD experts. Furthermore, to provide a friendly and interactive atmosphere, Educational Seminars and Meet the Expert Sessions will take place in the afternoons. Of all abstracts submitted by young scientists, the best eight have been selected by the Scientific Programme Committee. The authors have been invited to give a presentation during one of the two Young Scientist Sessions. With this approach, we intend to highlight the importance of original scientific contributions of our young colleagues at the congress. In this volume, abstracts of the Young Scientist Sessions (YS), the Free Communication Session (FC), and the Guided Poster Tours (P) are published. Submitted abstracts have not been modified in any way. We have organised altogether 21 Guided Poster Tours to make sure that the presentations of the different topic categories can be represented uniformly. These topics are: Aetiology, epidemiology, diagnosis, comorbidity, autism spectrum disorders, electrophysiology, pathophysiology, neuroimaging, experimental models, non-pharmacological treatment, pharmacological treatment, quality of life/caregiver burden and miscellaneous. We would like to encourage you to not only view these selected posters, but to also engage in active discussions and to exchange ideas with our young colleagues. We thank all the speakers, contributors and sponsors. We are very excited to welcome you to Vancouver and hope that you will take part in our exceptional scientific programme. We promise you an unforgettable learning experience with the most recent and authoritative information on all aspects of ADHD. Thank you very much for your participation! With kind regards, Luis Rohde Congress President President World Federation of ADHD
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Manfred Gerlach Chairmen Scientific Programme Committee
Abstracts
Thursday, 20 April 2017, 14.00 h–15.30 h YS-01 Young Scientists&Session I YS-01-001 A genome-wide association study of a cognitive endophenotype of ADHD in a communitybased paediatric sample C. Burton*, J. Crosbie, L. Erdman, B. Xiao, A. Dupuis, A. Paterson, L. Strug, P. Arnold, R. Schachar *Toronto, Canada Objectives: The power of genome-wide association studies (GWAS) of Attention-Deficit/Hyperactivity Disorder (ADHD) is reduced by clinical/genetic heterogeneity and insufficient clinical sample sizes. Using a cognitive endophenotype for ADHD, such as response inhibition, could decrease heterogeneity and increase power. Novel methods such as the hypothesis-driven GWAS (GWAS-HD) could also help to identify possible biological pathways involved in response inhibition (e.g., central nervous system [CNS] development). The GWAS-HD conducts genome-wide hypothesis testing while prioritising single nucleotide polymorphisms (SNPs) within genes involved in the hypothesised pathway. We conducted a GWASHD to test the role of SNPs involved in CNS development on response inhibition measured in a large community paediatric sample. Methods: Salivary DNA and performance on a measure of response inhibition (stop signal reaction time [SSRT] from the stop signal task) were collected on 17,263 youths (6–17 years old) visiting a science museum. We genotyped 5366 unrelated Caucasians using Illumina HumanCoreExome beadchips, and analysed 4.970 samples at 5,162,437 imputed and genotyped SNPs. For the GWAS-HD, individual SNPs in the CNS development set were tested using stratified false discovery rate (SFDR) while the whole gene set was tested using permutation tests for association with SSRT. Results: Ninety-four percent (94%) of the sample passed QC (n = 4687). Several SNPs approached genome-wide significance (p = 1.3 9 10-7). The set of CNS development SNPs were significantly associated with SSRT. Conclusions: SNPs that alter CNS development may be involved in response inhibition, and potentially ADHD (yet to be tested). Measurement of cognitive endophenotype such as response inhibition in a large community sample is a feasible and potentially powerful alternative strategy for psychiatric genetics.
YS-01-002 Parental psychiatric problems increase severity of ADHD symptoms and comorbidity in their children K. Bang Madsen*, K. Romvig Øvergaard, B. Ørbeck, C. Obel *Aarhus, Denmark Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is highly heritable, and studies have found parental ADHD symptoms to be strongly associated with severity and comorbidity of child ADHD symptoms. However, most studies have been cross-sectional. The aim was to examine whether parental reports of own childhood psychopathology influenced the risk of an ADHD diagnosis, severity of symptoms and comorbidity in their children in a longitudinal cohort study.
S3 Methods: Our study was based on the Danish national birth cohort (DNBC) and included parents of 41,666 children. Parental reports on own childhood psychiatric symptoms were collected at age 6 months of their child. At 7-year follow-up parents completed the strength and difficulties questionnaire (SDQ) measuring severity of child ADHD symptoms and comorbidity with the SDQ subscales; hyperactivity/ inattention (H/I), conduct, emotional, and impact. ADHD diagnosis was identified through follow-up in Danish registers until child age 12–14 years. Associations were analysed using Cox Proportional Hazards regression and linear regression models. Results: Adjusting for child’s gender, civil and socio-occupational status, children from families with reports of childhood hyperactivity in both mothers and fathers were in significant higher risk of an ADHD diagnosis [Hazard ratio (HR) 2.47; 95% CI 1.76; 3.45]. Maternal conduct and anxiety problems similarly increased the risk of offspring ADHD (HR 2.17; 95% CI 1.22; 3.84 and HR 1.81; 95% CI 1.51; 2.17, respectively), but not the severity of H/I symptoms. Children with an ADHD diagnosis had significantly higher symptom scores on the H/I scale (p \ 0.001), the conduct scale (p \ 0.001), and emotional scale (p \ 0.05) if both parents had hyperactivity symptoms in childhood. Only paternal hyperactivity increased severity of impairment in children with ADHD (p \ 0.05). Conclusions: Parental psychopathology, in particular ADHD symptoms, increases risk of ADHD diagnosis in their children and affects severity of ADHD symptoms and comorbidity.
YS-01-003 Adverse family life events during pregnancy and ADHD symptoms in 5-year old offspring M. Rydell*, A. Sjo¨lander, H. Larsson, T. Reichborn-Kjennerud *Stockholm, Sweden Objectives: To clarify if prenatal exposure to adverse life events in the family is associated with ADHD symptoms in 5-year old children, and to assess if such an association remains after controlling for shared familial factors. Methods: This study is based on 37,147 children (including 6.423 siblings) whose mothers participated in the Norwegian mother and child cohort study during pregnancy and at the child&s age of five. During pregnancy, mothers reported whether they had experienced the following events: Problems at work; financial problems; divorced/ separated; conflicts with family/friends; seriously ill/injured; someone close seriously ill/injured; serious accident/fire/robbery; or lost loved ones. ADHD symptoms were reported by parents at the child&s age of five using the Conners parent rating scale—revised: Short form. Linear regression models were used to compare mean ADHD scores (range 0–3) among children prenatally exposed to life events with those unexposed. Parental age at birth, marital status and child&s year of birth were included in adjusted models. To adjust for unmeasured familial confounding, fixed-effect models were used to compare mean ADHD scores among exposure-discordant siblings. Sibling analyses were adjusted for parental age at birth, parity and child&s year of birth. Results: Children exposed to adverse life events had higher ADHD scores at age five. The strongest effect was observed for financial problems, and the weakest for having lost loved ones (mean differences 0.10 [95% CI 0.08–0.11] and 0.02 [95% CI 0.01–0.04] respectively in adjusted models). Comparing exposure-discordant siblings resulted in attenuated estimates that were no longer statistically significant (e.g. mean difference for financial problems -0.02 [95% CI -0.07–0.02]). However, wide confidence intervals for specific life events hamper full interpretation of these results.
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S4 Conclusions: Prenatal exposure to adverse life events in the family is associated with ADHD symptoms in 5-year old children. Some associations seem to be explained by familial confounding.
YS-01-004 Evidence of concurrent and prospective associations between early maltreatment and ADHD through adolescence R. Gonzalez*, M. Velez-Pastrana, E. McCrory, J. Aguila, G. Canino, H. Bird *London, UK Objectives: An emerging body of work suggests a link between childhood maltreatment and Attention-Deficit/Hyperactivity Disorder (ADHD). However, there remains a lack of clarity regarding the role of early trauma in the early course of the disorder. We aimed to examine associations between maltreatment experiences and ADHD diagnosis, sex differences, and to estimate the risk between repetitive maltreatment exposure and ADHD through adolescence. Methods: Data were obtained from the Boricua youth study, a longitudinal study of 2.491 children and adolescents of Puerto Rican background. Neglect, physical, emotional and sexual abuse, and foster placement were regressed on ADHD diagnosis measured at each wave using the diagnostic interview schedule for children-IV. Multilevel regressions estimated the effects of exposure on ADHD, adjusted by age, sex, income, household education, parental psychopathology, comorbidity and ADHD medication status. Results: Emotional abuse and foster placement had robust associations with ADHD diagnosis. For girls, physical abuse had a three-fold increase in the odds of having ADHD diagnosis; for boys, associations were observed only for emotional abuse. Prospective models examining repetitive exposure suggested increased probability for ADHD persistence. Conclusions: Associations between early maltreatment and ADHD were robust. Different categories of maltreatment increase the likelihood of ADHD for girls and for boys. Increased exposure to maltreatment may predict symptom persistence. Interventions addressing ADHD must consider the effects of both sex and family environment.
Friday, 21 April 2017, 14.30 h–16.00 h P-01 Aetiology I P-01-001 Effect of blood lead concentration on Attention-Deficit/Hyperactivity Disorder in Korean children: A Mendelian randomisation study S. Bae*, H. Lim, H. J. Kwon, M. Lim, M. Ha, J. Sung *Cheonan, Republic of Korea Objectives: Several studies have shown that Attention-Deficit/ Hyperactivity Disorder (ADHD) in children is associated with their lead exposure and that exposure has an important role in aetiology as well as a genetic predisposition. In order to assess a causal association of lead exposure on ADHD in children we used a Mendelian randomisation method. Methods: The participants were recruited from the children’s health and environmental research study, 2005–2010, which is a longitudinal
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Abstracts study with up to three follow-ups. We used Korean version of Attention-Deficit/Hyperactivity Disorder rating scale (K-ARS) to assess symptoms and defined ADHD cases as those with K-ARS score over 19. We used rs1805313 (ALAD) for instrumental variable (IV). Blood lead concentration was log-transformed to make asymptotic normal distribution. Two-stage least square (2SLS) was used for a Mendelian randomisation modelling. Results: Of 1.828 participants, 1750 participants were included in the final analyses. We observed a positive significant association between blood lead level and K-ARS score after adjusting for age, sex, residential area, paternal education level, household income, parental marital status, familial psychiatric disease history, and environmental tobacco smoke (b = 0.47, 95% CI 0.10–0.85), but not with suspected ADHD (OR 1.05, 95% CI 0.94–1.17). We checked IV assumption to confirm that IV was not associated with any possible confounders except age. F-statistic for first linear regression model for IV and log lead level was 18.46. With suspected ADHD outcome model, the association was positive but not significant (OR 4.57, 95% CI 0.46–45.55, p = 0.196). In continuous K-ARS score model in 2SLS, we could not find a significant association (b = 0.62, SE = 4.33, p = 0.886). Conclusions: We could not find positive causal associations of blood lead level on ADHD in Korean children. Those non-significant estimates may be due to the lack of power. Further Mendelian randomisation studies with collaboration to increase power are needed.
P-01-002 DLGAP1 gene is associated with cognitive flexibility in children with Attention-Deficit/ Hyperactivity Disorder Z. Fan*, Y. Qian, Y. Wang, S. Chang, l. Yang *Beijing, People´s Republic of China Objectives: Seven hundred eighty-eight (788) ADHD children and 136 healthy controls were enrolled. The difference of shifting time by trail making to explore the association of DLGAP1 gene with cognitive flexibility in Attention-Deficit/Hyperactivity Disorder (ADHD) children. Methods: Seven hundred eighty-eight (788) ADHD children and 136 healthy controls were enrolled. The difference of shifting time by trail making test between ADHD and controls was analysed using the analysis of covariance (ANCOVA), with IQ, sex, age as covariates. Both the associations of SNPs with cognitive flexibility and three symptom traits of ADHD were conducted using an additive linear regression model by PLINK with the same covariates as ANCOVA. Results: Compared with controls, children with ADHD showed longer shifting times in the trail making test, suggesting poorer cognitive flexibility function (P = 0.011). Twenty-four SNPs have been found to be associated with TMT in ADHD cases. Among them, two SNPs (rs2049161, P value = 5.08e-7, adjusted P value = 1.63e-4, rs16946051, P value = 5.18e-7, adjusted P value = 1.66e-4) survived multiple tests and were validated in another cognitive flexibility related trait. Eight SNPs showed nominal significance to associate with ADHD-related symptoms. Validation in other psychiatric disorders, regulatory function of the SNPs, and DLGAP1 related interaction network were presented to support the association of DLGAP1 with cognitive flexibility in ADHD. Conclusions: Children with ADHD showed cognitive flexibility deficit in comparison with control groups. DLGAP1 gene is involved in the variation of cognitive flexibility in ADHD children. The relation between gene DLGAP1 and ADHD is worth further exploration.
Abstracts
P-01-003 A meta-analysis on association between lead exposure and ADHD and its symptom domains in children M. Ha*, S.-E. Oh, K.-M. Lee *Cheonan, Republic of Korea Objectives: A well-known neurotoxicant for developing brain, lead, has been reported as having an association with ADHD in epidemiologic studies. We aimed to summarise current evidence of association between lead exposure and ADHD and its symptom domains. Methods: A systemic review and meta-analysis was performed by searching databases of PubMed and Scopus, using several combinations of searching words including lead and ADHD without limitation of publication year in accordance to the guideline provided by the meta-analysis of observational studies in epidemiology. Among 548 searched, and after excluding papers that did not meet inclusion criteria, 39 original papers of 46 study populations were selected for the meta-analysis. The summary effect size (EF) was presented as standardised regression coefficient and Hedge&s G after transformation of various types of effect estimates. The quality assessment on each paper was done by two independent reviewers using the modified short form of Research Triangle Institute. Results: Lead exposure significantly associates with ADHD in overall (EF = 0.255, 95% CI 0.158–0.292), inattention (0.133, 0.076–0.190), and hyperactivity (0.284, 0.172–0.396) symptom domains in random models. The sensitivity analyses according to study design, types of biological samples the lead levels were measured, i.e., blood, teeth, and hair in children, showed consistent results except for lead level in cord blood. By analysing the level of children&s blood lead, the highest ES did not show in the range between 5 and 10 ug/dL (0.338, 0.033–0.644), rather in the range\5 or[10 lg/dL of blood lead levels. Conclusions: Lead exposure can be significantly associated with ADHD in children and more strongly with the hyperactivity symptom domain.
P-01-004 The interaction of aryl hydrocarbon receptor nuclear translocator like (BMAL1) and acetylserotonin O-methyltransferase (ASMT) affects the cognitive functions of male children with Attention-Deficit/ Hyperactivity Disorder J. Jin*, L. Liu, H. Li, Q. Gao, Y. Wang, Q. Qian *Beijing, People´s Republic of China Objectives: To explore the correlation between interaction of aryl hydrocarbon receptor nuclear translocator like (BMAL1) and acetylserotonin O-methyltransferase (ASMT) and the cognitive functions of male children with Attention-Deficit/Hyperactivity Disorder (ADHD). Methods: A total of 870 Chinese Han ADHD children were recruited. Cognitive functions were evaluated using Rey-Osterrieth complex figure test (RCFT) for working memory, and intelligence test (IQ) was conducted using the C-WISC. Correlation between genes and cognitive functions was analysed using generalised multifactor dimensionality reduction (GMDR). Results: Significant interaction effect of BMAL1 and ASMT was found on cognitive functions (p values varied from 0.005 to 0.033). In detail, the interaction of rs12421530 and rs1982350 of BMAL1 and rs6588810 of ASMT has effect on total IQ (test accuracy = 57.83%, p = 0.005), verbal IQ (test accuracy = 56.22%, p = 0.008), AIQ
S5 (test accuracy = 55.55%, p = 0.016) and BIQ (test accuracy = 56.63%, p = 0.009) in male children with ADHD. What&s more, the interaction of rs1982350 of BMAL1 and rs6588807 and rs6588810 of ASMT has effect on structural forgotten score of RCFT (test accuracy = 60.07%, p = 0.008), and the interaction of rs1982350 and rs12421530 of BMAL1 and rs6588807 of ASMT has effect on detail forgotten score of RCFT (test accuracy = 57.17%, p = 0.033) in male children with ADHD as well. Conclusions: Our present results suggest the influence of interaction of ASMT and BMAL1 on cognitive functions in male ADHD children.
P-01-005 Evidence of the involvement of ITGA1 in the aetiology of ADHD from SNP-set based analyses: A two-stage association study in Chinese Han population L. Liu*, L. Zhang, H. Li, Z. Wang, X. Xie, J. Mei, J. Jin, J. Shi, L. Sun, S. Li, Y. Tan, L. Yang, J. Wang, H. Yang, Q. Qian, Y. Wang *Beijing, People’s Republic of China Objectives: Some genome-wide association studies have been applied to Attention-Deficit/Hyperactivity Disorder (ADHD), but no genome-wide significant association has been found yet. The genetic heterogeneity and missing genomic coverage may account for the missing heritability. In this study, we improved the genomic coverage by combining two arrays and considered the synergetic effect of multiple SNPs to detect the hiding risk genetic variants for ADHD. Methods: A two-stage association study was performed. All subjects were of Chinese Han descent. In the discovery stage, 1033 ADHD patients and 950 healthy controls were genotyped by both affymetrix genome-wide human SNP array 6.0 and illumina infinium human exome bead chip to generate a more powerful SNP-set with better genomic coverage especially for those nonsynonymous variants. In addition to the analyses for individual SNPs, we collected adjacent SNPs as SNP-sets to evaluate their synergetic effect defined by either genes or successive sliding windows. Four candidate susceptibility SNPs were further replicated in an independent cohort with 1.441 ADHD patients and 1.447 healthy controls. Results: Analyses for individual SNPs did not find any genome-wide significant association. Although gene-based SNP-set analyses failed to detect any association, two adjacent windows located in ITGA1 were found to be associated with ADHD (p = 8.33E-7; 8.43E-7, respectively). The quantitative trait analysis also proved their association with ADHD core symptoms and executive functions. The association was further validated by the follow-up replications for the selected four SNPs: rs1979398 (p = 2.64E-6), rs16880453 (p = 3.58E-4), rs1531545 (p = 7.62E-4) and rs4074793 (p = 2.03E-4). The expression quantitative trait loci analyses indicated that these four SNPs may influence the expression of ITGA1 in some ADHD-related brain regions, such as hippocampus, thalamus, etc. Conclusions: Our results suggest that the genetic variants in ITGA1 may be involved in the aetiology of ADHD and SNP-set based analysis is a promising strategy to detect those underlying risk genetic factors.
P-01-006 Executive function mediated the association between NRXN1 gene polymorphism and ADHD Q. Lu*, L. Liu, H. Li, Y. Huang, L. Yang, Y. Wang *Beijing, People’s Republic of China
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S6 Objectives: Children with Attention-Deficit/Hyperactivity Disorder (ADHD) usually display executive function (EF) deficits, including set shifting, working memory, and response inhibition. NRXN1 gene was a candidate gene for many neuropsychiatric disorders including ADHD, which was essential for glutamatergic pathway and the function of prefrontal cortex (PFC) mediated by N-methyl-D-aspartate (NMDA) receptors. The aim of this study was to explore the association between NRXN1 single nucleotide polymorphism (SNP) and executive function of ADHD. Methods: A total of 729 Han Chinese ADHD children and 121 Han Chinese unaffected children were involved in the analysis. ReyOsterrieth complex figure test, Stroop color and word test, trail making test (TMT) were used to evaluate working memory, response inhibition and set shifting (including shifting time) respectively. Association between the genotype of SNP and EF was analysed with plink. Mediation analysis was used to evaluate the relationship of SNP, a diagnosis of ADHD and EFs. Results: In ADHD cases, three SNPs existed nominal significance in association with shifting, including rs2602003 (P = 0.000061), rs1592728 (P = 0.010) and rs4971652 (P = 0.044), in which rs2602003 survived multiple test correction. rs2602003 was also associated with the scores of Rey complex figure test (for structure immediate, P = 0.024), for detail immediate, P = 0.015, for detail delayed, P = 0.046. rs4971652 also showed nominal significance in association with word interference time (IW) (P = 0.0094). Mediated analysis exhibited that set shifting was the only intermediary variable between rs2602003 and ADHD, the effect size was 0.085, while IW had a complete mediating effect between rs4971652 and ADHD, the effect size was 0.088. Conclusions: The NRXN1 gene polymorphism rs2602003 is associated with set shifting of EF in ADHD children. Set shifting acts as a complete mediator in the relationship between rs2602003 and ADHD.
P-01-007 Neonatal umbilical artery cord blood pH value and ADHD, by Apgar score and gestational age S. H. Mikkelsen*, J. Olsen, B. H. Bech, C. Wu, M. Gissler, Z. Liew, C. Obel, O. A. Ara *Aarhus, Denmark Objectives: Although perinatal asphyxia is a major risk factor for neonatal and childhood morbidity and mortality, it has not been investigated much in relation to Attention-Deficit/Hyperactivity Disorder (ADHD). We examined if perinatal asphyxia, measured by umbilical artery cord blood pH value, was associated with childhood ADHD. Further, we aimed to test if the combination of umbilical artery cord blood pH value and Apgar score may be a better predictor of ADHD than umbilical artery cord blood pH value and Apgar score in isolation. Additionally, we aimed to test if the consistent association between preterm birth and ADHD may be explained by low umbilical artery cord blood pH value. Methods: A large population-based cohort including 295.687 children born in Finland between 1991 and 2002 was followed until 31 December 2007. ADHD was identified by an ICD-10 diagnosis of hyperkinetic disorder (HKD). We examined the risk of ADHD given varying pH values using Cox regression taking time trends into consideration. Results: PH value below 7.10 (compared to pH value C7.20) was statistical significant associated with increased risk of ADHD. In the adjusted analysis children with an umbilical artery cord blood pH value \ 7.10 had 23% (HR 1.23, 95% CI 1.02;1.48) higher risk of ADHD compared with children with an umbilical artery cord blood pH value C7.20. Among children with a gestational age below 32 weeks, a tendency towards higher risk was observed with an
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Abstracts umbilical artery cord blood pH value \7.15 compared to C7.15, but the difference did not reach statistical significance. Among children with an Apgar score of 0–3, the pH value did not contribute much to the association. Conclusions: Perinatal asphyxia defined by low pH value at birth may predict an increased risk of ADHD in childhood. When stratifying by gestational age and Apgar score, the association between pH value and ADHD was homogenous.
Friday, 21 April 2017, 14.30 h–16.00 h P-02 Aetiology II P-02-001 Airway allergic diseases increase the risk of Attention-Deficit/Hyperactivity Disorder in schoolaged children independent of sleeping problems C. Shen*, X. Jiang, K. Li, F. Li *Shanghai, People’s Republic of China Objectives: To explore the effects of airway allergic diseases on the risk of Attention-Deficit/Hyperactivity Disorder (ADHD) in schoolaged children. Methods: The diagnosis history of ADHD and Airway allergic diseases, as well as general information on school-aged children from nine cities in China were collected from parental reports using clusterstratified methods. The Chinese version of children&s sleep habits questionnaire (CSHQ) was used to measure sleeping problems. Subjects were divided into three groups based on airway allergic diseases, i.e. control group (neither allergic rhinitis nor bronchial asthma), single airway allergic disease group (either allergic rhinitis or bronchial asthma), mixed airway allergies group (both allergic rhinitis and bronchial asthma). Multiple logistic regression model was used for analysing the effect of airway allergic diseases and other related risk factors on ADHD in school-aged children. Results: Airway allergic diseases significantly increase the risk of ADHD. The odds ratio of ADHD in children with a single airway allergic disease is 2.197 (95% confidence interval [CI] 1.823–2.648), and the odds ratio of ADHD in children with mixed airway disease is 3.150 (95% CI 2.082–4.76). Furthermore, the odds ratio of ADHD in children with single or mixed airway allergies changed little after adjusting sleeping problems. Conclusions: Airway allergic diseases increase the risk of ADHD in Chinese school-aged children and the effect was independent of sleeping problems.
P-02-002 Early anaesthetic exposure and the risk of ADHD D. Silva*, J. Tan, R. Srinivas Jois, L. Colvin *West Perth, Australia Objectives: Although ADHD is predominantly a genetic condition approximately 40% variance may be due to environmental factors. Early environmental risk factors which may include exposure to general anaesthetic can impact on brain development. Our study investigates the risk of early exposure to one or more anaesthetics in children subsequently diagnosed and treated with stimulant medication for ADHD.
Abstracts Methods: Population information was collected on 10,850 nonAboriginal children \18 years (cases) who had been prescribed stimulant medication in WA for ADHD and were recorded on the monitoring of drugs dependency system (MODDS). A stratified random sample of birth records with no linkage to MODDS formed a comparison group (25,240). Case and comparison records were linked to the midwives notification system and the hospital morbidity database, which identified children who received an anaesthetic during their hospital admission. De-identified linked data files were provided for analysis. Results: Twenty-three percent (23%) of non-Aboriginal children subsequently diagnosed with ADHD and 16% of their non-ADHD counterparts had received a general anaesthetic under four years of age. Children who received one anaesthetic under four years of age had an increased risk of being diagnosed with ADHD compared with their non-ADHD counterparts (OR 1.40; 95% CI 1.31–1.50). Having one or more general anaesthetics under four years of age increased this risk almost two-fold (OR 1.85; 95% CI 1.67–2.06) when adjusted for sex, maternal age, birth weight, marital status, socio-economic status and year of birth. Females appeared to have a higher risk compared to their male counterparts. Conclusions: Although population studies are unable to show the causal direction of environmental exposures there is evidence that early exposure to anaesthetic and multiple exposures may increase the risk of being diagnosed with ADHD. Applying the developmental origins of health and disease (DoHAD) concepts to children with ADHD may assist in understanding environmental risks that may need to be explored further.
P-02-003 Association of NOS1 ex1f-VNTR, serum nNOS and serum NO level with Attention-Deficit/ Hyperactivity Disorder D. Xu*, L. Liu, H. Li, Q. Qian, Y. Wang *Beijing, People’s Republic of China Objectives: Several studies have implicated an important role of the nitrinergic system in Attention-Deficit/Hyperactivity Disorder (ADHD). NOS1 gene codes for the neuronal nitric oxide synthase (nNOS), which produce nitric oxide (NO), a gaseous messenger molecule. In the present study, we evaluated the association of NOS1serum nNOS level—serum NO level with adult ADHD (aADHD). Methods: A total of 34 aADHD and 33 healthy controls (HC) were included in the study. Genotyping of NOS1 ex1f-VNTR was performed by PCR amplification and product size determination by sequencing, and then long (L) and short (S) alleles were dichotomised as described by Reif et al. (2006). The concentration of serum nNOS and NO level in aADHD and HC groups was detected using the human NOS1/nNOS ELISA Kit (catalogue number: HG40221, TSZ) and human nitric oxide (NO) ELISA kit (catalogue number: HG025661, TSZ), respectively. Analysis of covariance (ANCOVA), Pearson correlation was performed as appropriate using SPSS 17.0. Results: No difference of genotypic or allelic distribution for ex1fVNTR was found between aADHD and HC groups. Comparison of serum nNOS and NO level also did not yield statistically significant difference; however, the levels in aADHD group seemed higher visually. High correlation was found between serum nNOS and NO levels (P \ 0.001). We further analysed the genotypic effects of NOS1 on the serum nNOS/NO levels. The results indicated that in aADHD subjects, S/S carriers showed higher serum nNOS (P = 0.026) and NO level than L-carriers (P = 0.003). In addition, marginal correlations of the serum nNOS and NO level were found with IQ of aADHD.
S7 Conclusions: Our present finding suggested the potential association of NOS1—serum nNOS—serum NO level with aADHD. However, the association of ex1f-VNTR S/S genotype with higher serum NO/ nNOS level was to some extend inconsistent with that reported in Caucasian population. This needs to be further investigated and discussed.
P-02-004 Interaction effect between rs3785143 of NET1 and rs1611115 of DBH on the aberrant resting-state functional connectivity in the prefrontal-amygdala circuit in boys with ADHD L. Liu*, X. Yu, L. Sun, Q. Zhao, N. Ji, Q. Cao, Z. Wu, L. Yang, Q. Qian, Y. Wang *Beijing, People’s Republic of China Objectives: Our previous study found that the aberrant resting-state functional connectivity (RSFC) of prefrontal cortex (PFC) and amygdala may be associated with emotional lability (EL) in boys with ADHD (PMID: 27503948). In addition, genetic variants of noradrenergic genes (NET1) may influence the EL symptoms in children with ADHD (5th World Congress on ADHD). Our present study is to explore whether these genetic variants of the noradrenergic system and their interactions are associated with the aberrant imaging features. Methods: Thirty-two boys with ADHD of Chinese Han descent were included. Twenty-two aberrant RSFCs of amygdala subregions with PFC in boys with ADHD observed in our previous imaging study were analysed as dependent variables. Genotyping was performed using a Taqman allelic genotyping assay for four SNPs including rs3785143 (NET1), rs1611115 (DBH), rs4680 (COMT) and rs1137070 (MAOA). Genotypic effects of individual markers and interactions were analysed using analysis of covariance (ANCOVA) with age, IQ and head motion as covariance by SPSS17.0. Results: Two SNPs, rs1611115 and rs3785143, showed genotypic effects on the RSFC between left superficial amygdala (SFA) and right dorsal-lateral PFC (DLPFC) (P = 0.001; 0.031 respectively). The SNP rs1611115 also showed association with the RSFC between right SFA and right DLPFC (P = 0.019). The SNP rs3785143 showed genotypic effect on the RSFC between right SFA and dorsal PFC bilaterally (P = 0.030). In addition, interaction between rs3785143 and rs1611115 showed strong effect on the RSFC of right SFA with dorsal PFC bilaterally (P = 5.52E-07). Specifically, among the subjects carrying the risk C allele of rs1611115, the rs3785143/T carriers showed reduced negative RSFC when compared to the rs3785143/CC carriers (P = 2.30E-04, g2p = 0.501). Conclusions: Combined with our previous findings, the genetic variants of the noradrenergic system may influence the EL in children with ADHD by medicating the RSFC in the PFC-Amygdala circuit. Replications in larger sample size are needed.
P-02-005 Parenting factors and family-level adversity as predictors of ADHD symptom trajectories in childhood and adolescence and outcomes R. Gonzalez*, M. Velez Pastrana, H. Bird, G. Canino *London, UK Objectives: Parental characteristics and behaviours may impact the course of childhood ADHD. Cross-sectional studies suggest that early
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S8 family adversity may moderate ADHD outcomes. Nevertheless, there is a paucity of longitudinal research that explores the relationship between early parenting factors and family-based adversity and ADHD symptom trajectories. We examine the role of parenting factors and early maltreatment on ADHD symptom trajectories and their outcomes using a well-characterized and ample longitudinal sample. Methods: We analysed data from 2.491 children followed for three waves from the Boricua youth study, a longitudinal study of children and adolescents of Puerto Rican background. ADHD diagnosis was measured at each wave using the diagnostic interview schedule for children-IV. We describe the average and classes of developmental trajectories of ADHD symptoms through childhood and adolescence from first wave (ages 5–13) and examine family-level predictors and outcomes at third wave associated with the trajectories. Predictors include: Parental distress, parent–child relationship, monitoring, physical and emotional abuse and adverse life events. Outcomes include comorbidity, substance misuse and delinquency. Models were adjusted by age, sex and time-varying income, household education, parental psychopathology and ADHD medication status. Results: Preliminary results using structural equation modelling show the average trajectory and slope were significant (p \ 0.001), suggesting variability in initial values of ADHD symptoms and in their rate of change (fit indices: V2 3.52(1), RMSEA 0.032, CFI 0.99 and TLI 0.98). Emotional (p \ 0.01), physical abuse (p \ 0.001), and number of adverse life events (p \ 0.001) at wave one were associated with the population average trajectory of symptoms. Using general growth mixture modelling, we identified four trajectories of ADHD symptoms (high, increasing, decreasing, and low). We are currently examining predictors of the four symptom trajectories and outcomes at wave 3. Conclusions: Results underscore the role of parenting factors, early adversity and family environment in the course and development of offspring ADHD.
P-02-006 Glutamatergic network gene mutations in children and adolescents with Attention-Deficit/ Hyperactivity Disorder (ADHD) J. Elia*, C. Kim, M. Khan, D. R. Mazzotti, H. Hakonarson, C. Anderson, L. Squirez, L. Squires *Wayne PA, USA Objectives: To estimate prevalence of rare, recurring copy number variants (CNVs) of specific metabotropic glutamate receptor (GRM) and related network genes in a pediatric population with ADHD and to explore associated phenotypes. Methods: Multiple lines of evidence support glutamatergic involvement in ADHD pathogenesis, including significant association between ADHD occurrence and loss-of-function mutations (CNVs) in GRM gene family and interacting genes (Elia J et al. Nature Gen 2012; 44:78–84). A multicenter (n = 23), noninterventional study enrolled children/adolescents with ADHD, collecting saliva samples for analysis (273 genes) by Children’s Hospital of Philadelphia genotyping laboratory. Phenotypic assessment was based on questionnaire-directed interview to elicit ADHD symptoms and medical history, ADHD treatment history, psychiatric comorbidity, development/education history, and current behaviours of concern. Results: Of 1013 children/adolescents with ADHD (6–\12 yrs, n = 291; 7–12 yrs, n = 722), 220 subjects were mutation-positive
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Abstracts (Prevalence: overall, 22%; children, 26%; adolescents, 20%). The demographic profile of mutation-positive subjects was consistent with expectations for a clinical pediatric/adolescent ADHD population— predominantly male and ADHD Combined as most common presentation. Mutation-positive subjects were significantly more likely to have parent-reported disruptive behaviors, anger control issues, and inappropriate movements. Conclusions: In this clinical US population of children/adolescents with ADHD, the 22% observed prevalence of glutamatergic network mutations suggests that a substantial proportion of ADHD population may be candidates for glutamate-modulating therapy. GRM mutation positive subjects displayed a higher prevalence of behaviors associated with emotional dysregulation. The study population has been increased to nearly 2000 subjects to better characterize the potential relationship between mutation status and phenotypic traits and comorbidities. Results of an interventional trial of the glutamate modulator AEVI-001 in adolescents with GRM mutation-positive ADHD will enhance understanding of targeting glutamatergic pathways in ADHD. Study sponsored by Aevi Genomic Medicine.
P-02-007 The effect of ITGA1 on brain white matter and cognitive phenotype in Attention-Deficit/ Hyperactivity Disorder X. Sun*, C. Zhao, Q. Cao, G. Gong, L. Yang, Y. Wang *Beijing, People’s Republic of China Objectives: According to recent genome-wide association studies and meta-analysis of ADHD, ITGA1 gene plays a significant role in neuron projection morphogenesis, which may be involved in neurodevelopment. We aimed to investigate the association of ITGA1 with ADHD on brain and cognitive phenotype. Methods: 115 individuals (age 8.3–15.8 years) were recruited, including 55 ADHD patients and 60 control boys. Magnetic resonance scanner (3T, Siemens) was used to collect MRI data in the Imaging Center for Brain Research, Beijing Normal University. Three hypotheses were assumed to explain the phenomenon: 1) diagnosis 9 polymorphisms interaction effect; 2) diagnosis main effect; 3) polymorphism main effect. Voxel-based analysis were performed, which analysed the whole brain white matter fractional anisotropy (FA) images. As for cognitive score and FA value of every individual, a general liner model was applied to confirm the existence of the significant interaction. The diagnosis and SNP main effect have to be tested if the interaction did not exist. Results: The ADHD patients and health control boys showed significant diagnose main effect in ADHD-RS-IV score (full scale, inattentiveness and hyperactivity/impulsivity: p \ 0.001), one behavioural score of executive function (inhibition: p = 0.019), and Rey complex figure test (recall structure score and recall detail score: p \ 0.001). Significant SNP main effect was discovered in one behavioural score of executive function (working memory: p = 0.013). Significant interaction on FA value were uncovered in one cluster covering the left posterior corona radiate, the posterior of thalamic radiation, splenium of corpus callosum. Conclusions: A variant of ITGA1 gene might be involved in the biological mechanism of ADHD through influencing the corona radiate and corpus callosum, then neuropsychological phenotype of inhibition and working memory.
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P-03-002 Discordance between parent-reported child behaviour and ADHD diagnosis K. Bang Madsen*, M. Ravn, J. Arnfred, J. Olsen, C. Obel *Aarhus, Denmark Objectives: A scientific and public debate is ongoing regarding whether Attention-Deficit/Hyperactivity Disorder (ADHD) is being systematically diagnosed in conformity with current diagnostic criteria. Misdiagnosis and under-identification have been reported, but this problem remains poorly researched. We estimate the extent of discordance between parent-reported child behaviour and ADHD diagnosis and report the socio-demographic characteristics of children where discordance exists. Methods: Using the Danish national birth cohort (DNBC), a 7-year follow-up of parents of 51,526 children was conducted. Parents completed questionnaires including the strength and difficulties questionnaire (SDQ). ADHD diagnosis was identified through followup in Danish registers until child age 12–14 years and ADHD behaviour through the SDQ. The association between socio-demographic characteristics and children with discordant diagnosis and behaviour was examined using logistic regression analyses. Results: Of the 1373 ADHD-diagnosed children, 39% did not exhibit ADHD behaviour. Conversely, of the 1.028 children with ADHD behaviour, 55% had no ADHD diagnosis. Children with ADHD behaviour and no diagnosis were more likely to be girls (OR: 1.90; 95% CI 1.53; 2.37) and to live in certain regions of the country (OR: Capital vs. Southern region: 1.88; 95% CI 1.42; 2.48) than children with an ADHD diagnosis. Children with a diagnosis and normal behaviour were more likely to have mothers with a high socio-occupational status (OR: low vs. high: 1.77; 95% CI 1.22; 2.56) and to be older at the time of diagnosis (OR: B6 vs. C11 years: 11.38; 95% CI 7.28; 17.79), and less likely to have mothers with hyperactivity problems (OR: 0.49; 95% CI 0.36; 0.68) than children with an ADHD diagnosis and concordant behaviour. Conclusions: Our results corroborate previous studies suggesting the existence of under-identification and potential misdiagnosis of ADHD. Our results also underline the significance of socio-demographic factors as drivers in ADHD diagnosis.
P-03-003 What drives the Turkers? Prevalence of ADHD in the online gig economy M. Bosman*, J. Swart *Walnut CA, USA Objectives: This study reports on the prevalence of ADHD in an online gig economy population. Amazon mechanical turk offers companies access to gig workers who perform often relatively simple tasks (filling out surveys, selecting pictures, transcribing handwritten texts, etc.) for fees as low as $ 3.50 per hour. The validity of the use of Turkers (as mechanical turk workers call themselves in online forums) in social sciences research has been described extensively. As far as we know, the prevalence of ADHD among Turkers has not been reported previously. Methods: Positioned as marketing research for an online self-help initiative, 184 respondents limited to the United States completed the online survey, which included demographic questions, the General Health Questionnaire-12 (GHQ-12), the adult ADHD self-report scale (ASRS), and others.
S9 Results: During a non-ADHD-related marketing study, we unexpectedly found a high prevalence of ADHD as estimated by the ASRS scores. Representing just more than half of the overall sample, those somewhat likely and extremely likely to qualify for a diagnosis of ADHD, respectively at 36.4 and 19.0%, are significantly overrepresented compared to the point prevalence among adults in the general public as reported by the DSM-V and elsewhere. Conclusions: We found that ADHD is disproportionately prevalent among workers in Amazon’s online gig site mechanical turk. Future research will have to show what the reasons for this overrepresentation are. Some possibilities are the need to supplement income from regular jobs; and thrill-seeking behaviour (as by their nature the mechanical turk gigs are short and unpredictable). A relevant follow-up question is whether the online gig work enables workers with ADHD to earn a reasonable income, or whether, in fact, it distracts them from seeking jobs with a better earning potential.
P-03-004 Treatment for ADHD among adolescents with ADHD in the United States, 2014 M. Danielson*, S. Visser, J. Holbrook, A. Chronis-Tuscano, G. DuPaul *Atlanta, USA Objectives: To characterize lifetime and current rates of ADHD treatments among a nationally-drawn sample of U.S. adolescents with ADHD, including differences by demographic and clinical factors. Methods: This study&s data source is the 2014 national survey of the diagnosis and treatment of ADHD and Tourette syndrome (NSDATA), a follow-back parent survey to the 2011–2012 national survey of children&s health. Children reported to have ever received an ADHD diagnosis in the 2011–2012 survey were eligible to participate in the ADHD module of NS-DATA. These analyses focus on ADHD treatment, categorized into four types: Medication, school services, psychosocial interventions, and alternative treatments. The results presented here are for adolescents aged 12–17 years with current ADHD (n = 1725). Results: Medication and school services were the most common treatments received by adolescents with current ADHD, with 62 and 61% currently receiving each treatment, respectively. Social skills training was the most common psychosocial treatment ever received (34%), followed by parent training (29%), peer intervention (28%), and cognitive- behavioural therapy (17%). Among alternative treatments, 8% of adolescents with ADHD were currently taking dietary supplements, and 11% had ever received neurofeedback. Prevalence of current medication usage was similar across most demographic and clinical subgroups, but there were significant differences in the receipt of school services and psychosocial treatments by current ADHD severity, ADHD symptom presentation, and presence of co-occurring conditions. Of treatment types recommended by clinical guidelines (current medication, current school services, lifetime psychosocial intervention), 60% were receiving treatment from at least two of the three categories, while 8% had received none of the three. Conclusions: This study provides rates of various types of treatment received by adolescents with current ADHD. Future analyses will examine differences between treatments recommended by clinical guidelines and current clinical management to identify potential gaps in the treatment of adolescents with ADHD.
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P-03-005 Clinical characteristics of adults with ADHD W. Hayashi*, T. Tokumasu, A. Iwanami, G. Arai, N. Saga, H. Ota, H. Suzuki *Tokyo, Japan Objectives: In recent years, the importance of medical treatment and care for adults with Attention-Deficit/Hyperactivity Disorder (ADHD) is becoming increasingly recognised. In child and adolescent cases, hyperactivity and impulsivity often results in earlier doctor consultations. On the other hand, despite no overt maladjustment shown in their student life, adults with ADHD tend to visit hospitals when social maladjustment becomes clinically evident at the point of active social involvement such as starting work. In those adult cases, the intellectual level is often above normal and inattention is often the main clinical feature. The clinical importance of adult ADHD lies in its highly frequent comorbidities with numerous psychiatric disorders. Despite overseas data reporting major depression, bipolar disorders, and anxiety disorders to be highly comorbid with ADHD, there are few studies investigating those comorbidities in Japan. In Showa University Karasuyama Hospital, we have established specialised outpatient unit and short-care for ADHD where we focus on diagnosis and treatments for adults with ADHD. Methods: In this study, we conducted a retrospective review of the medical records of patients visiting our ADHD outpatient unit. In addition to background characteristics, we investigated the past history of psychiatry consultation, previous medical diagnosis, and comorbid psychiatric disorders. Results: Among the 237 patients (146 male, 91 female, the mean age of 30.6) visiting the outpatient unit between April 2015 and March 2017, 170 patients were diagnosed with ADHD according to the DSM-V criteria, of which males and patients in their twenties were the two most prominent. Despite more than 70% having a past history of psychiatric consultation, less than 30% had been previously diagnosed with ADHD. Conclusions: We will report further findings with an increased number of cases in the future.
P-03-007 The prevalence, distribution and comorbidity of ADHD in children and adolescents aged 6–16 in Hunan Province, China X. Luo*, Y. Shen, B. S. Man Chan *Beijing, People’s Republic of China Objectives: To understand the prevalence, distribution, and comorbidity of ADHD in children and adolescents aged 6–16 in Hunan Province in 2014. Methods: 17,071 patients aged 6–16 were enrolled using stratified cluster sampling and two-stage epidemiological methods, screened using child behavior checklist (CBCL), and diagnosed using mini international neuropsychiatric interview for children and adolescents (MINI-Kid 5.0), with final verification using DSM-IV criteria. Results: Prevalence of ADHD was 4.96%; boys, 7.10% and girls, 2.66%. The difference between genders was statistically significant (P \ 0.001). Prevalence of group 6–11 years ranked highest (5.7%), followed by group 12–14 years (4.6%), and group 15–16 years (3.6%); the difference between age groups was statistically significant (P \ 0.001). (2) There are three subtypes of ADHD: predominantly inattentive type (ADHD-I), hyperactive/impulsive type (ADHD-HI), and combined type (ADHD-C). Prevalence of ADHD-I ranked highest (1.86%), followed by ADHD-C (1.69%), and ADHD-HI
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Abstracts (1.41%); the difference between subtypes was statistically significant (P = 0.004). Prevalence of ADHD-C and ADHD-HI decreased with age; this difference was statistically significant (P \ 0.05). (3) 48.17% (408) of patients had comorbidities; 36.36% had one, 8.50% had two, and 3.31% had more than two. The most common comorbidities were oppositional defiant disorder (25.15%), conduct disorder (18.18%), and generalised anxiety disorder (6.38%). 20.55% of girls and 10.03% of boys had comorbid anxiety disorders; 9.13% of girls and 2.23% of boys had comorbid major depressive disorders. Conclusions: (1) The prevalence of ADHD among children and adolescents in Hunan is 4.96%, is higher in boys, and occurs highest in younger children. (2) Prevalence of ADHD-I ranks highest. (3) Nearly 50% of patients have comorbidities; oppositional defiant disorder, conduct disorder, and anxiety disorder being most common. Females with ADHD are at greater risk of anxiety disorders and depressions.
Friday, 21 April 2017, 14.30 h–16.00 h P-04 Epidemiology II P-04-001 Parental body mass index and behavioural problems in offspring: A Danish national birth cohort study S. H. Mikkelsen*, L. Hohwu¨, J. Olsen, B. H. Bech, Z. Liew, C. Obel *Aarhus, Denmark Objectives: Maternal obesity has been associated with increased risk of offspring behavioural problems. We examined if this association may be explained by familial factors by comparing associations for maternal body mass index (BMI) with associations for paternal BMI. Methods: We studied 38,314 children born by mothers enrolled in the Danish national birth cohort during 1996–2002. Data on maternal BMI was collected at 15 weeks of gestation and paternal BMI when the child was 18 months old. When the child was seven years old, The strengths and difficulties questionnaire was filled in by the parents. We estimated odds ratio (OR)’s for behavioural problems in offspring born to overweight/obese parents. Results: We found maternal BMI associated with offspring behavioural problems. Maternal BMI between 25.0 and 29.9 and maternal BMI C 30.0 were associated with a 33% (OR 1.33, 95% CI 1.13–1.57) and 83% (OR 1.83, 95% CI 1.49–2.25) higher risk of total difficulties in offspring, respectively. Paternal obesity was also found associated with higher risk of offspring behavioural problems, but a tendency of stronger associations was observed with maternal prepregnancy obesity. Conclusions: Our results suggest that part of the association between maternal BMI and behavioural problems can be accounted for by genetic and social factors, but environmental risk factors may also contribute to the aetiology of behavioural problems.
P-04-002 Parental age and ADHD S. H. Mikkelsen*, J. Olsen, B. H. Bech, C. Obel *Aarhus, Denmark Objectives: Previous studies have suggested that young mothers more often have children with ADHD. We used sibling comparisons to examine the nature of this association and to investigate if this
Abstracts association is explained by early environment or genetic and socioeconomic factors. Methods: A large population-based cohort including all singletons born in Denmark from 1 January 1991 through 31 December 2005 was followed from birth until 30 April 2011. Data were available for 94% (n = 943,785) of the population. Offspring ADHD was identified by an ICD-10 diagnosis of hyperkinetic disorder (HKD). We used sibling-matched Cox regression to control for genetic and socioeconomic factors. As an important methodological strength, we controlled for time trends including the increase in ADHD diagnosis during the study period. Results: In the population cohort we found that children born by parents 20 years or younger had more than twice the risk of being diagnosed with ADHD compared to children with parents between 26 and 30 years of age. When comparing full siblings, the associations were attenuated, but we found a trend of increased risk of ADHD with decreasing maternal age, which was not seen for paternal age. Conclusions: Sibling comparisons suggested that the associations between both maternal and paternal age and ADHD are partly explained by common genetic and socio-economic factors. The trend of increased risk of ADHD with decreasing maternal age, but not with paternal age, may be linked to pregnancy or early life environmental factors. Even though only a smaller part of the association can be attributed to environmental factors, there is a public health interest to support young parents through their first years of parenthood.
P-04-003 ADHD prevalence according to schools of a Brazilian country town
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P-04-004 Can we resolve varying ADHD prevalence estimates in the U.S.? A closer look at NSCH 2007 and 2008 and 2011–2012 M. Song*, N. Dieckmann, J. Nigg *Portland, USA Objectives: ADHD prevalence is widely discrepant among population surveys (C11%) and epidemiological evaluations (2–6%). Estimates of changes in prevalence over time also vary, from a steady change (in surveys) to no change (epidemiological investigations). We aimed to clarify these discrepancies by re-examining a major U.S. survey of case identification rates, the national survey of children’s health (NSCH). Methods: Using NSCH 2007/2008 and 2011/2012 (n = 68,301 and 70,609) we stratified identification of ADHD by: Current status, severity, psychiatric comorbidity, and ADHD medication usage. Using those criteria, identifications were coded into four ‘‘confidence’’ levels: ‘‘Definite,’’ ‘‘Probable,’’ ‘‘Doubtful,’’ and ‘‘No ADHD‘‘. Results: In the 2011/2012 NSCH, 5.49% of children aged 5–17 had ‘‘Definite’’ ADHD; 7.83% were definite/probable. This was an increase from 4.04 and 6.06% (respectively) five years earlier. Definite rather than unlikely cases were the primary drivers of change over time. Conclusions: This analysis enhances understanding of the discrepancy between epidemiological and case identification rates for ADHD in the U.S. When cases seen as low confidence identifications (e.g., mild, never treated) are considered false positives, case identification drops from around 11 to 5–8%, closer to, but still higher than, epidemiological estimates. Growth in case identification, however, was primarily within the definite category, suggesting the increase was not due to broadening DSM-V criteria or changes in clinician thresholds. Discussion will consider methodological issues.
N. Perin Darim*, P. Da Silva Fucuta *Sao Jose´ Do Rio Preto, Brazil Objectives: ADHD students need special care throughout their educational development, and it is essential that school professionals are aware of the diagnosis. However, in Brazil this knowledge is held mostly by health professionals. To find out the knowledge of schools regarding the student&s diagnosis and treatment, a research was carried out in a Brazilian country town. Methods: All the schools were invited to participate, the schools that agreed were visited and answered a questionnaire. From the 252 schools invited, 72% (181) agreed to participate, so this research reached 62,899 students. Results: The prevalence of students with ADHD was 1.32% (833 students) and the ones medicated with methylphenidate were 1.2% (762); 25% of the medicated students didn&t have a diagnosis known by the schools. Out of the 833 ADHD students, 77% were boys and the student&s ages varied from 2 to 25 years. Among the medicated, 89 were less than 6 years old, and this goes against the indications of the leaflet of Ritalin (the medicine taken by the majority of those students) as its efficiency and safety at that age is not yet known. Conclusions: As demonstrated, at this specific city, the prevalence level known by the schools is lower than the average; almost all the schools related difficulties to connect with the parents, so they think that there are more students medicated and diagnosed and that the parents do not inform; that can seriously harm the educational process of the student. This kind of research has never been conducted and is extremely necessary in Brazil, so that it is possible to help the ADHD students by diagnosing and treating, but also by conveying reality outside the doctors&offices.
P-04-005 Are we confusing immaturity with AttentionDeficit/Hyperactivity Disorder in children? F. Ulberstad*, H. Bostrom *To¨reboda, Sweden Objectives: Since ADHD decision-making can be impacted by relative age, we examined if objective measures of typical ADHD symptoms also differ between children of different relative age. Methods: Anonymized records from a database containing objective tests of typical ADHD symptoms (Qb test) in consented individuals (6–12 years) were analysed. The tests had been performed in conjunction with assessment of ADHD in Sweden (n = 6066) and the UK (n = 5905) from April 2011 to April 2015. The total number of tests performed for each month of birth were calculated. In Sweden, the oldest children in a class are born in January and the youngest in December, whilst in the UK the oldest children in a class are born in September and the youngest in August. Therefore, relative age was set to one for Swedish children born in January and for UK children born in September. Results: More tests were performed in the relatively younger children indicating that these children more often are assessed for ADHD. A Chi square test of children with relative age of 1 versus 12 showed a statistical significant effect of 38.5% in Sweden and 36.5% in the UK (p \ 0.001). When the objective gender and aged matched performance scores for hyperactivity, inattention and impulsivity were analysed per relative age, no statistically significant difference could be observed for any of the objective symptoms.
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S12 Conclusions: This study confirms that relatively younger children more often are assessed for ADHD than their older peers. However, there was no difference in objective age and gender matched symptoms of ADHD between these children. Therefore, it seems as if the reason behind why more relatively immature children are assessed for and sometimes receive a diagnosis of ADHD is biased by subjective decisions influenced by relative age.
Friday, 21 April 2017, 14.30 h–16.00 h P-05 Diagnosis I P-05-001 Structure of the French version of the adult ADHD symptoms rating scale and validation against the DIVA interview H. Caci* *Nice, France Objectives: Three scoring methods are used for the adult ADHD symptoms rating scale (ASRS) but a short review of the literature shows their ability to efficiently screen for ADHD has rarely been confronted with a formal clinical diagnosis. To date, the French version has not been fully validated. Methods: 105 adults were included and underwent a thorough clinical evaluation including the ASRS and the DIVA, a widely accepted clinical interview for ADHD in adults, according to both DSM-IV and DSM-V criteria. The underlying structure of the ASRS was thoroughly investigated by Confirmatory Factor Analysis. The characteristics attached to all three scoring methods (e.g. sensitivity, specificity, positive and negative predictive values, and accuracy) were compared. Results: The best-fitting structure is a bifactor model with a general ADHD factor and three specific factors (and the impulsivity factor specified according to the ICD-10) that explains a very small amount of the variance. The full score scoring method has worse properties than the screener and the 2-stage scoring method, which yielded to a more realistic estimate of prevalence in a previous study. The screener has the highest sensitivity (81.6%) while the 2-stage scoring method has the highest specificity (98.1%). When using DSM-V criteria, the prevalence is 27% higher and all characteristics of the three scoring methods for the ASRS are smaller. The screener still has the highest sensitivity (80.0%) and the 2-stage scoring method still has the highest specificity (90.0%). Furthermore, whatever the version of the DSM, our results contradict the common notion that hyperactivity decreases with age. Conclusions: ADHD is best conceived as a one-dimensional construct. The screener and the 2-stage scoring method are able to efficiently screen for ADHD although the latter yielded to more realistic estimate of prevalence in a previous study.
P-05-002 From Mona Lisa to IKEA: From the perspective of adults with ADHD G. H. Bahn*, R. Hwangbo, S. W. Cho, S. Y. Lee, M. Hong *Seoul, Republic of Korea Objectives: With a growing awareness of ADHD, diagnosis of adults has increased. However, lack of diagnostic tools, comorbidities,
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Abstracts inaccurate childhood history, and more make the diagnosis difficult and in many ways incomplete. Familiarising the public with examples from the mass media is an effective way to overcome such impediments. An adequate example would be the increase of a public attention and consideration towards autism after the release of ‘‘Rain Man.’’ In this paper, the authors analysed historical figures and celebrities in an effort to communicate with the general population more effectively and to develop a long-term therapeutic plan. Methods: We have studied figures that were classified as ADHD in related websites and those who claim themselves as ADHD. Including Donald Trump, a total of 109 subjects were analysed since 2011. Based on biographies and related articles, socio-demographic information, comorbidities and the compatibility with ADHD according to DSM-IV-TR and Utah criteria were analysed. The probability of ADHD was divided into four stages: Compatible, likely, less likely, and not compatible. Results: Of 109 subjects, 12 were women (11.0%), and the common occupations were artists or athletes (42.2%). The most common comorbidity was depression, narcissistic personality disorder, and substance use disorder. The probability of ADHD was compatible 25.7%, likely 37.6%, less likely 32.1%, and not compatible 4.6%. Conclusions: The research based on information gathered by nonmedical personnel definitely has its limits but we can use the analysis of characters as empirical data to establish considerations in longterm follow-up, like factors affecting social adaptation in ADHD, and to learn more about treating ADHD patients beyond the current DSM diagnostic criteria.
P-05-003 Two ADHD scales as predictors of anxiety and intolerance of uncertainty in individuals diagnosed with ADHD A. Fine*, K. Fotinos, K. Nasiri, M. Mohamed, I. Epstein, I. Szpindel, C. Cameron, S. Cook, T. Sternat, M. Katzman *Toronto, Canada Objectives: To examine the predictive nature of ADHD severity, as measured by the ASRS and Brown ADD scale, on intolerance of uncertainty (IU) and generalised anxiety measures in patients diagnosed with ADHD. Participants should be able to recognise ADHD symptoms as predictors of anxiety severity and intolerance of uncertainty. Furthermore, participants should gain an understanding of treatment options for individuals with comorbid GAD and ADHD. Methods: Between January 2015 to September 2016, outpatients (n = 72) referred to a tertiary care clinic completed self-administered questionnaires as part of their initial intake assessment. The Brown ADD scale, adult ADHD self-report scale (ASRS), intolerance of uncertainty scale (IUS), generalised anxiety disorder 7 (GAD7), and Penn state worry questionnaire (PSWQ) were included. Psychiatric diagnoses were confirmed by the treating physician and the mini international neuropsychiatric interview plus 5.0.0 (MINI plus). Correlation and linear regression analyses were conducted. Results: Statistical analyses suggested that in individuals with ADHD with or without a comorbid diagnosis of GAD, the Brown ADD scale is significantly correlated with and significantly predicts scores the IUS (p \ 0.05) and PSWQ (p \ 0.05), but is not correlated with the GAD7 (p [ 0.05). The ASRS was not significantly correlated with the IUS, GAD7 or PSWQ. Conclusions: Overall, in contrast to the ASRS, the Brown scale appears to be a promising predictor of intolerance of uncertainty and generalised anxiety measures in individuals with ADHD. This suggests a potential predictor of how the neurobiology of comorbid ADHD may present in patients with GAD. Specifically, the positive
Abstracts correlation between intolerance of uncertainty, anxiety and the Brown scale in this population is suggestive of deficits in top-down prefrontal regulation of anxiety severity. Furthermore, distinguishing between subsets of GAD patients by examining IUS and Brown scores may lead to individualised treatment options.
P-05-004 A comparison of screening instruments to identify adult Attention-Deficit/Hyperactivity Disorder D. Kim*, K.-y. Kim, H.-J. Kim, H.-m. Kim, Y.-J. Lee, D.-h. Song *Seoul, Republic of Korea Objectives: The aim of this study was to determine the validity of three screening instruments for adult Attention-Deficit/Hyperactivity Disorder (ADHD). Methods: This study included 52 adults with ADHD-like symptoms who visited Severance hospital in South Korea. All patients completed Conners adult ADHD rating scale-Korean (CAARS-K). Among them, 45 patients conducted digit span (DS) and 31 patients conducted continuous performance test (CPT). Each patient completed a clinical interview with an expert psychiatrist and diagnosis was made according to the diagnostic and statistical manual for mental disorder-IV (DSM-IV). Sensitivity and specificity were calculated for each of the tools to examine the validity of the screening instruments. Results: Of the 52 patients, 32 were diagnosed with ADHD. Nine patients (45%) of the Non-ADHD group had mood disorder. Male to female ratio was higher in the ADHD group compared with that of the non-ADHD group. Sensitivity and specificity of the individual tools were; for CAARS-K 0.750 and 0.40; for digit span 0.037 and 0.889; for CPT 0.333 and 0.770 respectively. The sensitivity increased to 0.889 when CAARS-K and CPT were both conducted. Conclusions: Adult ADHD affects a great deal in daily function. Variety of comorbidity and difference in symptomatology compared with that of a child delays the detection. CAARS-K is an adequate screening tool for adult ADHD which could advance the diagnosis. Using CPT additionally could effectively identify ADHD in adult.
P-05-005 ADHD core symptom assessment in adults with ADHD, depression, addiction or borderline personality disorder using the Qb test P. M. Wehmeier*, M. Bender *Weilmu¨nster, Germany Objectives: The aim of this study was to assess core symptoms of ADHD in adults with ADHD, depression, addiction or borderline personality disorder (BPD) using the Qb test in a routine clinical setting. This test is a computer-based continuous performance test (cb-CPT) combined with an infrared motion-tracking device. The Qb test was approved by U.S. Food and Drug Administration (FDA) in 2012 to aid in the assessment and evaluation of treatment interventions in patients with ADHD. Methods: Adult patients with ADHD, depression, addiction or BPD were assessed at baseline (T1) and endpoint (T2). Due to the observational study design, the observation period was not defined. Outpatients and inpatients, patients on or off medication and patients with or without psychoeducation were all eligible for the study. The primary hypothesis was that there would be statistically significant
S13 differences between the four groups in terms of ADHD core symptoms as measured using the Qb test. The secondary hypothesis was that there would be statistically significant differences between assessments at T1 and T2 as a result of the specific interventions. Results: A total of 644 adult patients with ADHD, depression, addiction or BPD were included in this observational study. There were statistically significant differences between the four groups in terms of ADHD core symptoms as measured using the Qb test (p \ .05). There were statistically significant differences between assessments at T1 and T2 as a result of the specific interventions (p \ .05). The Qb test showed no statistically significant difference between patients with ADHD alone and patients with ADHD and comorbid depression. The Qb test showed a statistically significant difference between patients with medication for ADHD in terms of hyperactivity (p \ .001) and Attention-Deficit (p \ .01). The Qb test showed no statistically significant difference between patients with medication for ADHD in terms of impulsivity (p = .238). Conclusions: The Qb test is a computer-based continuous performance test (cb-CPT) combined with an infrared motion-tracking device that facilitates the assessment and evaluation of treatment interventions in patients with ADHD. This study demonstrates the clinical utility of the Qb test in the assessment and treatment of adults with ADHD, depression, ddiction or BPD in a routine clinical setting.
P-05-006 Normative survey data for the parent rating of evening and morning behaviour scale, revised (PREMB-R) in youths with and without a history of ADHD S. Faraone*, T. Wilens, R. Nullmeier, N. DeSousa, F. Sallee, B. Incledon *Syracuse, USA Objectives: The validated parent rating of evening and morning behavior scale, revised assesses at-home early morning (PREMB-R AM) and late afternoon/evening (PREMB-R PM) functioning in children with Attention-Deficit/Hyperactivity Disorder (ADHD). The objectives were to: (1) obtain normative data for the PREMB-R AM and PM, and (2) determine whether parent ratings differentiate youths without and with a history of ADHD, and are affected by age, gender, or comorbidities. Methods: A normative survey was conducted with 1200 respondents derived from a representative U.S. sample of primary caregivers of youths (6–17 years; n = 50 per age/gender category) using an online questionnaire. Caregivers were enrolled if their children/adolescent never had ADHD, had a past history of ADHD, or currently had untreated ADHD. Caregivers rated their child’s at-home functional impairments on the 3-item PREMB-R AM and 8-item PREMB-R PM, with each item rated on a 4-point scale (0 = none; 3 = a lot). Differences in total and individual item scores were determined by an ANOVA with post hoc comparisons and Chi squared test, respectively. Results: Of the 700 children (6–12 years) and 500 adolescents (13–17 years) rated by a caregiver (mothers/step-mothers: 68.9%), 1079 had no history of ADHD, 40 had a history of ADHD, and 81 had current untreated ADHD. PREMB-R AM/PM scores were significantly higher for children versus adolescents (P = 0.042/P \ 0.001), and those with C1 comorbidity versus no comorbidities (both P \ 0.001); however, there were no gender differences. There were significant differences in the total score distributions between youths without ADHD, with a history of ADHD, and with current untreated ADHD in PREMB-R AM (mean ± SD: 2.27 ± 2.13, 4.07 ± 2.69,
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S14 and 4.19 ± 2.39; P \ 0.001) and PREMB-R PM (mean ± SD: 5.05 ± 4.80, 10.27 ± 6.70, and 12.53 ± 5.77; P \ 0.001), and across all individual items (P \ 0.001). Conclusions: PREMB-R AM and PREMB-R PM discriminate between youths without and with a history of ADHD. Age and comorbidities, but not gender, had significant effects.
P-05-007 Parent ratings on the before school functioning questionnaire (BSFQ) in youths with and without a history of ADHD: Results from a normative survey S. Faraone*, T. Wilens, R. Nullmeier, N. DeSousa, F. Sallee, B. Incledon *Syracuse, USA Objectives: The validated before school functioning questionnaire (BSFQ) assesses dysfunction in early morning, before school activities associated with Attention-Deficit/Hyperactivity Disorder (ADHD) in children/adolescents. The objectives were to: (1) obtain normative data, and (2) determine whether parent BSFQ ratings differentiate youth without and with a history of ADHD, and are affected by age, gender, or comorbidities. Methods: A normative survey was conducted with 1200 respondents derived from a representative U.S. sample of primary caregivers of children/adolescents (6–17 years; n = 50 per age/gender category) using an online questionnaire. Caregivers were enrolled if their child: (1) never had ADHD, (2) had a past history of ADHD; or (3) currently had untreated ADHD (no treatment during past 3 months). Using a severity scale of 0–3 (0 = none; 3 = severe), caregivers rated their child&s at-home early morning functional impairments on the 20-item BSFQ (maximum score = 60). Differences in total and individual item scores were determined by an ANOVA with post hoc comparisons and Chi squared test, respectively. Results: Of the 1200 youths (children [6–12 years]: n = 700; adolescents [13–17 years]: n = 500) rated by a caregiver (mothers/stepmothers: 68.9%), 1.079 had no history of ADHD, 40 had a history of ADHD, and 81 had current untreated ADHD. There were no differences in the total score distributions between males and females (P = 0.554); however, scores were 23.7% higher for children versus adolescents, and 54.4% higher for youths with C1 comorbidity versus no comorbidities (both P \ 0.001). There were significant differences in the total score distributions between youth without ADHD, those with a history of ADHD, and those with current untreated ADHD (mean ± SD: 12.70 ± 11.00 vs. 21.17 ± 14.58 vs. 29.60 ± 13.15, respectively; P \ 0.001), and also across all 20 items (P \ 0.001). Conclusions: Normative data suggest that the BSFQ discriminates between youths without and with a history of ADHD. Age and comorbidities, but not gender, had significant effects.
P-05-008 ADHD: Are we over medicalising childhood? A qualitative exploration of school teachers in South Africa T. Mgutshini*, O. Babalola *Pretoria, South Africa Objectives: The current paper reports on a qualitative study that aimed to explore how school teachers&beliefs about ADHD influenced their involvement in the early identification of school children
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Abstracts presenting with behaviours suggestive of attention deficit and hyperactivity. Methods: School teachers (n = 24) and school officials (n = 9) from three metropolitan primary schools in Johannesburg, South Africa were interviewed individually (n = 24) and took part in focus group discussions (n = 4), to assess their beliefs about ADHD and most specifically how their cultural beliefs have influenced their involvement with the early identification of children presenting with noteworthy attention deficits. Results: The study presents a number of noteworthy findings. Firstly, most of the school teachers and officials believed that ADHD was over-diagnosed and was often identified with little acceptance of alternative causal explanations. ADHD was seen as a contradiction of core South African cultural norms and needed to be considered in the context of Zulu, Xhosa and other South African cultures. Finally, acceptance of ADHD was impacted by pre-existing cultural alternatives and there was a need for Western medicine and traditional culture to reach a compromise intervention model to guide teachers and school officials. Conclusions: ADHD acceptance is significantly impacted by preexisting cultural health beliefs and there is a need to normalise Western concepts related to ADHD, with existing cultural norms.
P-05-009 Validation of the short form of the Barkley deficits in executive functioning scale (BDEFS) in Spanish speaking adults: Confirmatory factor analysis and measurement invariance M. Velez-Pastrana*, R. Gonzalez, G. Roman *San Juan, Puerto Rico Objectives: ADHD, characterized by deficits in executive functioning (EF), is one of the most common mental health disorders in children. ADHD and EF deficits often persist across the lifespan and may cause serious impairment, significant disease burden, reduced quality of life and inordinate societal costs. EF is a core component of self-regulation, associated with outcomes in education, health, wealth and crime. Although self-report measures readily assess EF in adults, most of them are lengthy and only available in English. Our study aimed to confirm the factor structure of the short 20-item Spanish language version of the Barkley deficits in executive functioning scale (BDEFS). Methods: Four hundred fifty-two (452) Latino community adults (65.5% female) completed the BDEFS and the ASRS. The BDEFS&89 items assess five dimensions of EF in daily life: Time management, organisation, problem solving, self-restraint, motivation, and emotion regulation. We conducted CFA on the 20-item short version, and tested measurement invariance via multiple group analysis for gender, history of inattention and education. We used a MIMIC model with age, ADHD symptoms and income as covariates. Results: The CFA fit indices were very good. All indicators had significant loadings on their respective factors. We achieved partial invariance by gender and education, and strong invariance by history of inattention. Age was inversely associated with time management (p \ 0.01), and positively associated with motivation (p \ 0.05). ADHD symptoms were associated with increased scores on all 5 BDEFS factors (p \ 0.001). Conclusions: To our knowledge, this is the first examination of the short 20-item form of the BDEFS in any language. Our CFA demonstrates a factor structure remarkably consistent with the original English language BDEFS. Results support the theory of EF that underlies the instrument. Study has important clinical and research applications, as quick, efficient methods of assessing EF impairments
Abstracts in adults are needed, and full versions of extant EF scales seem cumbersome.
Friday, 21 April 2017, 14.30 h–16.00 h P-06 Diagnosis II P-06-001 First validation of the QbMini to measure symptoms of ADHD in 5-year old children T. Gu¨nther*, S. V. Noemi Zaplana Labarga, K. Hoberg *Aachen, Germany Objectives: The diagnosis of ADHD in preschool age is difficult and only a few methods for this age group are available. However, an early detection of the disorder is important to minimise negative consequences of the disease in the future. The aim of this ongoing study is the validation of the ,,QbMini‘‘. Methods: The ‘‘QbMini’’ is an age appropriate adaptation of the ‘‘Qb test’’ (for details see www.qbtech.com). This computer-based test measures the attention and impulsivity by a continuous performance test and the hyperactivity by recording the movements with an infrared camera. Until now, the QbMini and ADHD behavioural scales were conducted with 56 healthy 5-year-old children, 16 children with ADHD and 28 children with other developmental disorders. Results: Comparing the QbMini and the behaviour questionnaires, significant correlations (r [ .439) were found between the parameters and scales which measure the same construct (hyperactivity and inattention). Even more interesting, the behavioural inattention ratings were strongly correlated with the hyperactivity scores of the QbMini (r = .482). This suggest that the inattention scores of the behavioural rating scales are influenced by the hyperactive behaviour of the children. In the classification analyses, the QbMini could differentiate between healthy (n = 56) and diseased children (n = 54) for the symptoms of hyperactivity (area under ROC curve .849; good) and inattention (.772; fair). The area under the ROC curve for impulsivity was only .684 (poor). In contrast, the QbMini could not distinguish between children with ADHD and children with other developmental disorders (all areas \.592). Conclusions: The first results of this study suggest that the QbMini is a valid instrument to measure symptoms of hyperactivity and inattention at preschool age. However, for a valid diagnosis of ADHD at this age group more additional clinical information is necessary.
P-06-002 Towards evidence-based assessments: Clinical utility of rating scales and cognitive test methods in diagnostic assessment and treatment evaluations in children and adolescents with Attention-Deficit/ Hyperactivity Disorder P. Gustafsson*, P. Tallberg *Lund, Sweden Objectives: The aim of this study was to examine if clinical utility in diagnostic assessments and treatment evaluations could improve by combining different methods. Methods: Two populations from two different child and adolescent psychiatry (CAP) clinics in Sweden were studied. Retrospective data
S15 were collected from clinical records. Concerning diagnostic utility, we compared children with (n = 78) and without (n = 40) ADHD. Sensitivity, specificity, and the area under the receiver operator characteristic (ROC) curve were calculated to evaluate classification accuracy of the Swanson, Nolan and Pelham—IV questionnaire (SNAP-IV), the Conners continuous performance test (Conners; CPT II) and the quantitative behaviour test (Qb test). Concerning treatment evaluation, we compared the results from parent ratings of SNAP-IV and Qb test before and after initiation of medical treatment and in the follow-up one year later for 43 children with ADHD. Dose titration for 56 children were assessed with the Qb test. The Mann–Whitney U-test was used for group comparisons and Spearman rank-correlation and logistic regression for analysing associations. Sensitivity, specificity, positive predictive values and negative predicted values were calculated for the SNAP-IV parameters, the different Qb test scores and their combinations. Results: The Conners CPT II and the SNAP-IV showed statistically significant diagnostic classification accuracy. A combination of SNAP-IV and Conners CPT II variables yielded better classification accuracy compared with either method alone. Using the Qb test when parent ratings were inconclusive, led to a good sensitivity when predicting treatment outcome one year later. Conclusions: The SNAP-IV and Conners CPT II contributed to the diagnostic assessment of ADHD. Qb test was found to be useful in evaluating central stimulant treatment when parent ratings were inconclusive. To combine rating scales and performance-based assessment methods seems useful.
P-06-003 Assessment of executive functioning in children and adolescents: Validation of the Spanish language Barkley deficits in executive functioning scale for children and adolescents (BDEFS-CA) P. Purcell Baerga*, M. Velez Pastrana, J. J. Bauermeister *San Juan, Puerto Rico Objectives: ADHD is one of the most common mental health disorders in children and tends to persist into adulthood. ADHD is characterized by deficits in executive functioning (EF). EF and ADHD have a broad impact on interpersonal functioning, impairment, and quality of life throughout the lifespan. EF impacts day-to-day problem solving tactics used in school and work settings. In addition, EF may also affect a person&s self-esteem and self-perception, indispensable for living a healthy and fulfilling life. This study aimed to translate the BDEFS-CA for Spanish speaking children and adolescents and examine its factor structure. Methods: Four hundred seventy-four (474) adult parents of children aged 6–17 completed the BDEFS-CA online through the PsychData portal. The BDEFS-CA is a 70-item parent-report scale that measures deficits in EF in daily life activities. It includes the following five subscales: Self-regulation of emotion, self-organisation/problem solving, self-management to time, self-motivation, and self-restraint/Inhibition. socio-demographic, health history data, and data on child ADHD were collected. Exploratory factor analyses and inter-scale correlations were conducted, as well as correlations with child ADHD symptoms. Results: The Spanish language version of the BDEFS-CA presented a 5-factor structure as expected. Results are consistent with the original English language version and with what has been published about the BDEFS adult version in Spanish. Cronbach&s alphas ranged from .939 to .987. High to moderate correlations were found between the five subscales and ADHD symptoms. Scale inter-correlation patterns were as expected.
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S16 Conclusions: The BDEFS-CA is a valid and reliable measure of deficits in EF for Spanish speaking children and adolescents. An increase in early detection and diagnosis of EF deficits is essential to improve treatment strategies in children and adolescents with ADHD.
P-06-004 Neurobiological marker for child and adult ADHD diagnoses H. Super*, J. Can˜ete, S. V. Faraone, P. Asherson, J. A. Ramos-Quiroga *Barcelona, Spain Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders affecting 3–7% of school-aged children worldwide. In the last decade it has become clear that ADHD is a chronic disease where about 50–60% of ADHD cases persist into adult life. ADHD is associated with a range of clinical and psychosocial impairments. In children hyperactivity, impulsivity and inattention are the core symptoms of ADHD. In adults these core symptoms are also present but inattention is more prominent. Correct diagnosis of ADHD remains challenging, especially as several other psychiatric and medical disorders show the similar symptomology. The diagnosis of ADHD is clinic-based upon a cluster of symptoms and criteria established by guidelines such as the DSM-V. However, objective markers are needed to support the clinical ADHD diagnosis in children and adults. Recent studies suggest that a neurobiological marker (eye vergence, i.e. where the eyes move in opposite directions) can detect ADHD in children and adults. The eyes converge during orienting attention (Sole´ Puig et al. PLoS One, 2013), as evidenced by visual event-related potentials at parietal locations (Sole´ Puig et al. PLoS One, 2016). This attention related vergence is impaired in ADHD patients (Sole´ Puig et al. PLoS One, 2015). Methods: We review the neurobiology and current findings of eye vergence and the relevance of these measurements for the clinical diagnosis of ADHD. Results: Neural circuits underlying eye vergence and attention largely overlap. Using machine learning, eye vergence measurements can classify ADHD in children and adults with high ([90%) accuracy. Conclusions: Eye vergence is a promising candidate for an objective clinical diagnosis of ADHD.
P-06-006 Standardized cross-cultural assessment of ability and disability in ADHD: The new WHO ICFCY core sets S. Bo¨lte*, S. Mahdi, M. Selb *Stockholm, Sweden Objectives: To report the results of the ICF core set consensus conference for ADHD. Preparatory studies had yielded 132 ICF candidate categories for ADHD. This evidence was used as a starting point to generate a comprehensive, a common brief, and three agespecific WHO ICF ADHD core sets. Methods: Twenty ADHD experts, representing all six WHO-regions and various disciplines, were invited to participate in the 3-day consensus conference held in Stockholm in November 2016. The experts followed a three-stage decision-making and consensus process to decide on the ICF categories that should be included in the ICF
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Abstracts core sets for ADHD. In the first stage, the experts prioritized and selected ICF categories to be included in the comprehensive ICF core set. The second stage consisted of defining the common brief core set for ADHD. The third stage involved developing age-specific brief core sets for ADHD: ages 0–5 years, 6–16 and 16+ years. Results: Finally, 72 s level categories were included in the comprehensive ICF Core Set with 35 categories from the activities and participation component, 29 environmental factors, and 8 body functions. The common brief ICF core set included 38 categories; 14 activities and participation categories, 17 environmental factors and 7 body functions. The brief ICF core set for the ages 0–5 consisted of 47 categories, while the 6–16 age group had 55 categories and the adult group 52 categories. Detailed category-wise results will be made available at http://www.icf-core-sets.org/. Conclusions: When defining the ICF core sets for ADHD, a large number of categories were selected across all of the ICF components (except body structures) supporting the notion that ADHD impacts wide ranges of functions and participation, and is associated with many contextual factors. From these core sets, assessment tools will be derived for future usage in clinical, research, educational setting as well as health care administration.
P-06-007 Can eye movements differentiate between adult patients with ADHD and bipolar disorder? A. Marin*, D. Munoz, S. Soncin *Kingston, Canada Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) and bipolar disorder (BD) share emotional and cognitive deficits that can appear similar, which makes the differential diagnosis of these conditions sometimes difficult. This study aimed to compare and contrast cognitive and emotional processes in adult patients with ADHD or BD, seeking a better insight as to how these processing systems may interact to cause dysfunction and how differences in this interaction can better characterize. Methods: All experiments were approved by our institution’s human research ethics board. Patients included 22 ADHD and 20 BD participants who were diagnosed and recruited from a psychiatric adultoutpatient clinic. To be eligible, patients had to meet DSM-IV criteria for either ADHD or BD. 21 controls were screened for psychiatric symptoms with the MINI 5.0.0. Patients and healthy controls performed an interleaved pro- and anti-saccade task (look towards versus looking away from a visual target, respectively). Task irrelevant emotional faces (fear, happy, sad, neutral) were presented on a subset of trials either before or with the target. After establishing baseline performance on the pro- and anti-saccade tasks, we considered how emotional stimuli may modulate behaviour. Results: The ADHD group made more direction errors (looked in the wrong direction) than controls (p = 0.0017) Presentation of negatively valenced (fear p = 0.044, sad p = 0.053) and ambiguous (neutral, p = 0.003) emotional faces increased saccadic reaction time in BD only compared to controls, while longer presentation of sad faces modestly increased group differences. Conclusions: The anti-saccade task differentiated ADHD from controls. Emotional processing further impaired processing speed in BD. These results suggest there are diagnostic specific differences in how emotion regulation and executive functioning interact, with the inhibitory signal at the cortical dorsolateral prefrontal level being impacted by the dysfunction in the emotion processing network in BD.
Abstracts
Friday, 21 April 2017, 14.30 h–16.00 h P-07 Comorbidity P-07-001 Psychiatric comorbidity in adult AttentionDeficit/Hyperactivity Disorder: Its prevalence and clinical implications R. Nakagawa* *Tokyo, Japan Objectives: ADHD is associated with a high percentage of comorbid psychiatric disorders in every lifespan. However, it is less clear that prevalence of each comorbid disorder and associations between comorbid disorders and clinical and demographic characteristics of ADHD in adult patients. The objectives of this study are to show the presence of comorbid disorders in adult ADHD and to evaluate relationship between comorbid disorders and clinical and demographic characteristics in adult ADHD patients. Methods: By using the data obtained from post-marketing surveillance of methylphenidate Extended-Release tablets for adult ADHD, prevalence of psychiatric comorbidities were evaluated. Patients’ age, gender, type of ADHD, treatment history and scores of the Conners’ Adult ADHD Rating Scales at the baseline were used as clinical and demographic variables for exploratory analyses. We applied Support Vector Machine algorithm to examine whether clinical and demographic characteristics relate to presence of comorbid disorders. Furthermore, a principle component analysis was done to extract major dimensions underlying variations of comorbid disorders patterns. The protocol of this study was assessed by an internal review board including the ethical aspects, and was approved by the Pharmaceuticals and Medical Devices Agency. Results: Data from 567 patients with adult ADHD were utilized for the analysis. 274 patients (48.32%) of them had no comorbidity, however 184 patients (32.45%) had single comorbidity and 109 patients (19.22%) had multiple comorbidities. The most common comorbid was developmental disability including Pervasive developmental disorder and Autism Spectrum Disorder (24.69%. Results of exploratory analyses will be presented. Conclusions: Psychiatric comorbidities are present at a high prevalence in patients with adult ADHD in Japan. Results of exploratory analyses seem to be important for understanding underlying pathogenesis of comorbidities with ADHD.
P-07-002 Trait anhedonia: A risk factor for undetected Attention-Deficit/Hyperactivity Disorder and suicide in adult depressed patients T. Sternat*, K. Fotinos, A. Fine, C. Cameron, I. Epstein, M. Katzman *Toronto, Canada Objectives: Depression and suicide are among the leading causes of disability and death respectively. Research suggests that approximately 11% of adolescents experience depression. Depressed adolescents are six times more likely to attempt suicide compared to non-depressed counterparts. Adolescents with Attention-Deficit/ Hyperactivity Disorder (ADHD) are more likely to develop adult depression. As core symptom of depression, anhedonia, is common in ADHD and associated with poorer treatment response to antidepressants. The aim of this study was to determine predictive factors and
S17 clinical features associated with the development of treatment-resistant depression (TRD) and suicidal symptoms in adults. Methods: Data was collected from consecutive referrals (n = 160) to a mood and anxiety clinic. Patients referred for ADHD were excluded from the analysis. Diagnosis was established through the mini international neuropsychiatric interview plus 5.0.0 and a semi-structured interview. One-way analysis of variance and t-tests were performed to examine predictive factors related to TRD and increased risk for suicide. Results: The results indicated that 34% of patients referred for TRD had undiagnosed ADHD and 55% presented with chronic anhedonia. Clinical features included SSRI failure (44%), suicide ideation (62%), and suicide attempts (16%). The number of failed psychiatric medications (p \ 0.001), SSRI failures (p = 0.020), and number of SSRI failures (p = 0.032) was predictive of ADHD. Chronic (p = 0.002) and present (p = 0.003) anhedonia predicted SSRI failure. Chronic anhedonia predicted increased suicide ideation (p = 0.05) and attempts (p = 0.036). Conclusions: This study demonstrated that trait anhedonia or low hedonic tone may be a link between TRD and ADHD, which may predict poorer treatment outcomes in a subset of patients treated with SSRIs. Low hedonic tone may increase the risk of suicidality. These findings emphasise the importance of screening depressed patients who fail SSRI treatment for ADHD and low hedonic tone in order to assure safety and optimal outcomes.
P-07-003 Childhood bipolar disorder masquerading as Attention-Deficit/Hyperactivity Disorder with episodic obsessive compulsive disorder: A case report with a review of the literature P. Kumar*, S. Tsheringla, S. Naskar, N. Mallik *Kolkata, India Objectives: Introduction: Contemporary literature suggests that among all the comorbidities of childhood bipolar disorder, AttentionDeficit/Hyperactivity Disorder ranks the highest with a prevalence of 60–90%. In pre-pubertal years of a child, the manifested symptoms of BPAD may often mimic that of ADHD (often called ‘complex’ ADHD), thus confusing the clinicians. BPAD in this age group usually has a non-episodic, ultra-rapid or ultradian cycling with a chronic course unlike episodic illness of adult BPAD that makes the diagnosis difficult. OCD comorbid with BPAD shows higher frequencies of depressive and panic episodes, higher rates of sexual obsessions and runs an episodic course. Methods: Case: Six-years-old female child with a normal birth and developmental history and significant family history of mood disorders presented with low mood, school refusal, clinging behaviour and obsessional sexual thoughts. She has started on fluoxetine to which she responded well. Subsequent follow-up showed remission in her symptoms, but she was found to have hyperactivity with scores on ADHD rating scale significant enough to start her on atomoxetine. After four months, she presented with prominent hypersexual behaviour (speech and actions), over-talkativeness, excessive cheerfulness, decreased sleep and increased obsessions. On examination, she was restless with prolixity in speech, increased goal-directed activity as observed in her activities (drawings). Parent CMRS-P score was 26. She was diagnosed as a case of paediatric BPAD with a differential diagnosis of antidepressant and or atomoxetine induced manic switch with comorbid OCD. The patient was managed with a combination of rational pharmacotherapy and psychotherapy.
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S18 Conclusions: This case illustrates the complexity of comorbidities in children. There is a need to have caution while diagnosing and treating ADHD in cases of co-morbid OCD and depression in preadolescent children keeping in mind the masquerading presentation of Bipolar disorder in this age group. Furthermore, this case is an example of probable antidepressant and or atomoxetine induced manic switch at a very early age.
P-07-004 Metabolic control in adolescents with type 1 diabetes and Attention-Deficit/Hyperactivity Disorder J. Macek*, T. Battelino, M. Bizjak, C. Zupanc, N. Bratina *Ljubljana, Slovenia Objectives: Diabetes mellitus type 1 (T1D) incidence is increasing in paediatric population. Beside a regulated diet, regular exercise and frequent daily self-monitoring of blood glucose., patients with T1D need lifelong insulin therapy. Risk for chronic complications is significantly reduced with good metabolic control, measured by glycated haemoglobin (HbA1c) level below 7.5% (58 mmol/mol). Due to poor metabolic control, some children were also referred to a child and adolescent psychiatrist to evaluate for psychiatric comorbidities as a potential cause; a significant proportion of patients exhibited several symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). To the best of our knowledge, the prevalence of ADHD among adolescents with T1D has not been studied systematically yet. We aimed to identify adolescents with T1D and ADHD and assess the effect of ADHD on metabolic control. Methods: This cross-sectional case–control study included 101 patients (11–17 years old) with T1D. development and well-being assessment (DAWBA) questionnaire and subsequent psychiatric clinical examination were used to identify a group with T1D and ADHD. Indicators of metabolic control were collected from available medical documentation for preceding 12 months and compared between cases (patients with T1D and ADHD) and controls (T1D patients without ADHD). Results: ADHD was diagnosed in 12 out of 101 adolescents with T1D. We found a statistically significant difference (p = 0.022) in HbA1c between the two groups—higher in the group with T1D and ADHD (8.4% or 68.3 mmol/mol) than in the control group (7.8% or 61.7 mmol/mol). Conclusions: We found that metabolic control was significantly poorer in adolescents with ADHD in comparison to those without. These results suggest that adolescents with T1D and ADHD should be recognised early and offered appropriate treatment as well as an additional support in home and school environment to prevent the potential negative impact of ADHD on metabolic control and subsequent clinical outcome.
P-07-005 ADHD in young patients with type 1 diabetes: Pay attention or pay more E. Merzon*, I. Merhasin, S. Vinker *Tel Aviv, Israel Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder, which may alter self- management of chronic medical conditions. The aim of our study was to analyse metabolic control, hospital admission rate and total medical costs among young patients with type 1 diabetes mellitus (T1DM) and
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Abstracts ADHD as compared to young diabetics without ADHD in Israeli health maintenance organization (Leumit health services). Methods: We conducted a retrospective cohort study, analysing data from all paediatric patients (\18 years) with T1DM (N = 230) in the Leumit Health Services. Prevalence of comorbid ADHD was 10.5% (N = 24). Diabetic patients with ADHD were compared to diabetics without ADHD using stratified analyses. Risk ratio for hospital admission was calculated using multivariate regression models adjusting for demographic confounders. Results: There was no significant difference between young diabetics with ADHD as compared to diabetics without ADHD in age [13.2 (CI 12.1–14.5) y.o. vs. 12.9 (CI 12.5–13.5) y.o.], female gender [50.0 vs. 50.1%], weight [48.51 (CI 45.74–51.28)kg vs. 48.5 (CI 38.62–51.71)kg] & height [1.5 CI 1 (1.48–1.54)cm vs. 1.51 (CI 1.44–1.59) cm]. Diabetics with ADHD had significantly higher HbA1c [(9.9(CI 9.19–10.60)% vs. 8.1 (CI 7.92–8.41)%)], were related to higher socio-economic level [8.95 (CI 7.91–11.01) vs. 6.87 (CI 6.32–7.43)], and more often used insulin pump (66.7 vs. 63.1%). As well, their annual total medical costs were higher [22,350 (CI 16,397–28,302) NIS vs. 16,830 (CI 14,422–19,237) NIS]. Risk ratio for annual hospitalisation of young diabetics with ADHD as compared to diabetics without ADHD was 2.55 (1.04–6.23). Conclusions: Young T1DM patients suffering from ADHD showed poor glycemic control, higher hospital admission rates and total medical costs, as compared to diabetics without ADHD. Youngsters suffering from comorbidity of ADHD and T1DM probably need special attention, education and follow-up.
P-07-006 ADHD diagnosis and addictive use of computer gaming in young children from Frenchspeaking and German-speaking countries F. W. Paulus*, S. Ohmann, M.-C. Saiag, S. Finck, B. Janthur, B. Pollitt, N. Gaddour, A. Guedria, C. Zix, D. Purper-Ouakil, J. M. Mu¨ller, M. Mathot, H. Caci, A. von Gontard *Homburg/Saar, Germany Objectives: Playing video games has become a common activity for children. As the association between computer game playing and ADHD has not yet been studied in young children, the aim of this study is to analyse and to compare addictive computer game playing and media use in French-speaking and German-speaking young children diagnosed with ADHD. Methods: Parents of 463 children (73.9% boys; mean age 6.2 years, SD 1.2, range 4.0–8.0) with a diagnosis of ADHD (N = 323) or another ICD-10 diagnosis (control group, N = 140) filled out a standardised ADHD questionnaire (19 items), a media use questionnaire (9 items), and an 11-item addictive computer game playing questionnaire. The data were assessed in French-speaking (Paris, Strasbourg, Forbach, Monastir, Nice, Montpellier) and Germanspeaking (Homburg/Saar, Neuwied/Rhein, Dillingen, Mu¨nster, Vienna) child psychiatric or neuropaediatric institutions. Results: We found considerable differences between the ADHD group and the control group in access to computer or ownership of a stationary or portable game console. Young children with ADHD had significantly higher computer addiction scores (t = 3.96; p \ .001) compared with children with other ICD-10-diagnoses. In the Frenchspeaking countries, the computer game addiction scores (t = 7.79; p \ .001) and the ADHD symptom scores (t = 2.38; p = .02) for children diagnosed with ADHD were higher than in German-speaking countries. Conclusions: When taking a historical approach or assessing young children with ADHD, the use of video games and addictive game
Abstracts playing should regularly be explored. We detected differences between French-speaking and German-speaking countries concerning the magnitude of addictive video game playing. We also discovered that diagnosis of ADHD in French-speaking countries implied a higher symptom intensity than in German-speaking countries.
P-07-007 Understanding the heterogeneity and comorbidity of Attention-Deficit/Hyperactivity Disorder (ADHD) and autism spectrum disorders (ASD) using emotion recognition subtyping F. Waddington*, C. Hartman, Y. de Bruijn, M. Lappenschaar, A. Sluiter-Oerlemans, J. Buitelaar, B. Franke, N. Rommelse *Nijmegen, The Netherlands Objectives: Emotion recognition problems have been reported in ADHD and ASD, however, the results are inconsistent for both disorders across visual and auditory domains (Bora & Pantellis, 2016; Uljarevic & Hamilton, 2013). In that, emotion recognition problems appear to be a cross-disorder trait that can be utilised to understand the heterogeneity and comorbidity of ADHD and ASD. Subtyping approaches based on emotion recognition problems may be fruitful in parsing heterogeneity. In this study, we thus aimed to identify emotion recognition subtypes and to utilise these to explore the overlap and differences in emotion recognition problems across the two disorders, to gain further understanding of their overlap and substructure. Methods: A total of 111 ADHD test persons, 153 ASD test persons, 191 non-affected siblings, and 220 independent controls completed visual and auditory emotion recognition tasks. Factor mixture modelling was used to identify classes of emotion recognition subtypes. Proportions of ADHD and ASD test persons, their non-affected siblings, and controls were then compared across emotion recognition performance classes. Results: The classes identified demonstrated significant differences in their emotion recognition profiles in regard to their performance on identifying emotions across modalities. Importantly, each class contained a proportion of ADHD and ASD test persons, their nonaffected siblings, and controls. As expected, larger proportions of controls were found in classes with faster and more accurate emotion recognition performances, whereas larger proportions of ADHD and ASD test persons were found in classes with slower and less accurate performances. However, participants with ADHD and ASD showed similar levels of impairment in emotion recognition. Conclusions: In this study, we found the heterogeneity of emotion recognition performance across disorders confirmed. Emotion recognition problems are strongly related to both ADHD and ASD. Furthermore, the results suggest that emotion recognition problems may increase the risk of developing these disorders.
P-07-008 ADHD and impact on type 1 diabetes E. Midtlyng*, T. Skrivarhaug, T. Naerland *Oslo, Norway Objectives: For individuals with ADHD the ADHD-related impairment often persists into adulthood (1). An increase in health-risk behaviour for adolescents with ADHD is reported, in particular in combination with other chronic conditions (2) and combined with conduct disorder (3). Type 1 diabetes (T1D) is a severe chronic
S19 condition where the glycemic regulation has stopped to work and it is a challenge for both the patients and their parents to substitute the child’s glycemic regulation with a strict treatment regimen. Focus on attention and learning is therefore of great importance. How neurocognitive problems affect the outcome of T1D is an increasing body of knowledge (2). The recent German-Austrian Study with 56,000 T1D patients show that patients with comorbid ADHD (2.8%) suffered twice as often from diabetic ketoacidosis compared to the patients without ADHD, and they also have significant higher metabolic balance (HbA1c). There is a need for further research to better understand the impact of ADHD on diabetes control and complications and a closer collaboration between pediatric diabetologists and pediatric psychologists/psychiatrists (4). Objectives of the study. Describe how neurodevelopmental problems typical for ADHD affect the T1D treatment and the metabolic control for individuals with ADHD and T1D.Compare scores on Health-related quality of life between individuals with T1D and ADHD and individuals with T1D without ADHD. Investigate the effect of a strict treatment regimen forT1D on learning and self-regulation for individuals who also have ADHD.Evaluate the levels of HbA1c after onset of medical treatment for ADHD and the impact of ADHD on school performance for individuals with T1D. Methods: Based on clinical examinations, neuropsychological tests and questionnaires our study will be linked to data from The Norwegian Childhood Diabetes Registry and Norwegian Prescription Database. Results: Study under planning.
P-07-009 Substances use and functional impairment among college students with ADHD in Quebec J. Lagace´ Leblanc*, L. Masse´, C. Plourde *Trois-Rivie´res, Canada Objectives: This research project aims to develop knowledge about students with ADHD in post-secondary institutions in Quebec. More specifically, the study focuses on functional impairment in several spheres of life in this population. It also examines the prevalence of drug and psychoactive medication use, as well as the interaction of its variables with the functioning of the individual. Methods: Participants in this study were students aged 17–55 years (M = 24.1, SD = 7.06) from seven colleges and two universities in the province of Quebec. The sample consisted of 243 students, 56.4% of whom were studying at a general and vocational college and 43.6% at university at the time of the study. The students were contacted by e-mail via the adapted services of their respective institutions, in order to answer the following questionnaires from an online computer platform: Questionnaire de renseignements ge´ne´raux [General information], the French version of Weiss functional impairment rating scale—self-report (WFIR-S), DE´BA-A—De´pistage/E´valuation du besoin d’aide—alcohol (version 1.9) [assessment and screening of assistance needs—alcohol], DE´BA-D—De´pistage/E´valuation du besoin d’aide—drogues (version 1.8) [assessment and screening of assistance needs—drugs]). Results: Self-concept was the area with most functional impairments in students (M = 1.54, SD = .80) and work appeared to have the least number of impairments (M = .70, SD = .49). In addition, the MANOVA showed a significant effect with medication (F (7, 224), 3.48, p \ .001, g2 = 0.098): non-medicated students (M = .95, SD = .36) had higher scores on items compared to students taking medication for the disorder (M = .91, SD = .40). MANOVA results revealed significant difference according to the severity of alcohol
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S20 consumption (F(14,446), 3.119, p \ .001, g2 = .089). Students with high-risk alcohol drinking (M = .10, SD = .37) reported more functional impairments than students with low-risk drinking (M = .89, SD = .38) or no risk (M = .89, SD = .45). MANOVA also revealed significant difference according to the severity of drug use (F(14,446), 4.441, p \ .001, g2 = .122). Students with high-risk drug use (M = 1.01, SD = .355) had higher scores on items, regardless of the functional area examined, than students with lowrisk drug use (M = .94, SD = .37) or no risk (M = .87, SD = .40). Conclusions: ADHD-related functional impairment among college and university students was found to be generally low with the exception of self-concept which points to the importance of providing student support in this area. In addition, absence of medication for the disorder would be linked to greater functional impairments associated with ADHD. Finally, students with ADHD reporting alcohol and/or drug use manifest generally more functional impairments in their lives than those with low or no risk drinking.
Friday, 21 April 2017, 14.30 h–16.00 h P-08 Autism spectrum disorders P-08-001 The ability of theory of mind in adults with Attention-Deficit/Hyperactivity Disorders G. Arai*, T. Morita, M. Ota, D. Ikuse, T. Tokumasu, N. Saga, T. Morii, W. Hayashi, H. Ota, A. Iwanami *Tokyo, Canada Objectives: Theory of mind (ToM) is the ability to attribute mental states such as beliefs or desires to oneself and others and to understand that others have different mental states from one’s own. Questions about ToM-deficits in individuals with autism spectrum disorder (ASD) have generated a large number of empirical studies. On the other hand, some studies showed that the ability of ToM is impaired in children with Attention-Deficit/ Hyperactivity Disorders (ADHD) in comparison with neurotypical children. However, there only exist few studies concerning ToM in adults with ADHD. Methods: In the present study, we evaluated spontaneous ToMability in neurotypical adults and adults with ADHD without intellectual deficiency using an eye tracking task similar to a previous study of Senju et al. (2009). Results: We made a prediction that eye movements in neurotypical adults anticipate the behaviours of an actress in the display on the basis of her false belief, however, eye movements in persons with ADHD did not anticipate her behaviour. Contrary to our expectation, there is no significant difference in ToM-ability among the two groups. Conclusions: In our other study, we made comparison between the neurotypical group and the ASD group using the same task. The result suggested that spontaneous ToM-ability is higher in the neurotypical group than in ASD group. Some studies showed that individuals with ASD of higher verbal ability can pass conventional ToM tasks. We considered that these individuals may have acquired the ability to reason explicitly about ToM by compensatory learning and pass conventional ToM tasks, however, they couldn&t carry out spontaneous ToM tasks flawlessly. The result of the present study indicates that the spontaneous ToM-ability is higher in individuals with ADHD. In addition, there may be some differences between ASD and ADHD regarding essential ToM-abilities.
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P-08-002 Working memory in Attention-Deficit/ Hyperactivity Disorder and autism spectrum disorder M. Horovitz*, R. Penna, A. Moscrip, B. Kriley, S. Ejankowski, Y. Tava´rez, E. Balic, M. Howell, Y. Torres, M. Hoeschele, S. Willbanks *Jacksonville, USA Objectives: Executive functioning (EF) impairments are a hallmark of Attention-Deficit/Hyperactivity Disorder (ADHD) and autism spectrum disorder (ASD). Historically, ASD and ADHD were thought of as mutually exclusive, and there was confusion with regard to apparently overlapping symptoms. Previous versions of the diagnostic and statistical manual (DSM) excluded the diagnosis of ADHD in children with ASD. However, current research and clinical practice recognises the need to conceptualise and treat both conditions, if present, and comorbid diagnosis is now recognised in DSM-V. While there are well established bodies of research analysing EF deficits in both groups, current research aims to analyse the EF profiles in individuals with comorbid diagnoses. This will promote better understanding of the interrelationship of these two conditions, as well as promote more targeted treatment efforts. The objective of the current research study was to analyse working memory profiles in groups of children diagnosed with ADHD, ASD, and dual diagnoses of comorbid ADHD and ASD. Methods: A one-way, between groups ANOVA analysed working memory scores from standardised intelligence tests across three samples of children: ADHD only diagnosis (n = 65), ASD only diagnosis (n = 23), and ASD + ADHD diagnoses (n = 36). All participants received services at an outpatient interdisciplinary treatment clinic and had received previous comprehensive psychodiagnostic evaluation. The age range was 4–18 and children were excluded if FSIQ \ 60. Results: Analysis revealed group membership to significantly affect working memory scores, F(2121) = 3.52, p \ .05, with similar scores in the ADHD only (M = 95.30) and ASD only (M = 97.00) groups, along with lower working memory scores in the ASD + ADHD group (M = 87.09). Conclusions: While further research is needed with larger samples, current research results suggest a possible compounding effect of impairment in working memory when both ADHD and ASD are present.
P-08-003 Gaze movements for social attention dissociating children with Attention-Deficit/ Hyperactivity Disorder and autism spectrum disorder in a visual exploration task C. Ioannou*, D. Seernani, H. Hill, G. Boccignone, T. Foulsham, N. Dundon, N. Cilia, C. Saville, S. Bender, C. Fleischhaker, M. Biscaldi, U. Ebner-Priemer, C. Klein *Freiburg, Germany Objectives: According to a recent review and meta-analysis (ChitaTegmark, 2016), the main factor determining gaze control of patients with autism spectrum disorder (ASD) in tasks requiring social attention is social content, defined as the number of people in the scene, as well as their relationship, level of activity and interaction. However, to our knowledge, the study of gaze movements for social attention has been restricted to patients with ASD and rarely included those with Attention-Deficit/Hyperactivity Disorder (ADHD). Given
Abstracts current discussions of potential aetiological overlap between ASD and ADHD (Biscaldi et al. 2015; Rommelse et al. 2011), the present study compares these two clinical groups with regard to their gaze movements during visual exploration of social stimuli differing in complexity. Methods: The subjects of the study are children and adolescents with ADHD, ASD and healthy controls (n = 90; 10–13 years; all native German speakers). Pictures of real-life social interactions, differing in complexity (one person vs. four persons interacting, two pictures each) were presented for 120 s each. To ensure task engagement, participants were told to pay attention to the pictures so as to answer questions following their presentation. Groups will be compared across levels of social complexity in fixation durations, dwell times, transitions between areas of interest and further parameters of gaze control. Results: Preliminary results suggest ASD and ADHD patients differ in both dwell times for socially significant areas of interest and in transitions between them. Scatter of fixations in clinical groups will be further investigated. Conclusions: Our study compares for the first time ASD and ADHD in gaze movements during exploration of social interactions and will therefore contribute to the discussion of potential overlap between these disorders regarding the dynamics of gaze behaviour.
P-08-004 Are there significant associations between the severity of ADHD symptoms and of autistic traits in children and adolescents with ADHD? ´ s. D. a´ Neystabø, A. Kier, R. A. Fløtum Jespersen*, A J. R. Møllegaard Jepsen, T. Sto´ra´ * To´rshavn, Faroe Islands Objectives: To examine potential relationships between the severity of ADHD symptoms and that of autistic trait (AT). Methods: Sample: 93 children (59% boys; age range 5–17) ICD-10 diagnoses: F.90.0 Disturbance of attention and activity (N:66) F.90.1 Hyperkinetic conduct disorder (N:3) or F.98.8 Attention deficit disorder without hyperactivity (N:24). Exclusion criterion: Autism spectrum disorder (ASD) diagnosis. The children were consecutively recruited as they were referred for clinical evaluations in an outpatient clinic at the national hospital of the Faroe Islands. The severity of ADHD symptoms was operationalised by using the ADHD-RS questionnaire and AT was operationalized by using the social responsiveness scale. The children&s parents completed both questionnaires. We used Pearson bivariate correlation analyses and linear multiple regression analysis to examine the associations of interest. Results: There was a significant positive correlation between the severity of AT and that of the total ADHD symptoms (r = .650; p \ .001). Both the severity of the inattentive symptoms (r = .527; p \ .001) and that of the impulsive/hyperactive (I/H) symptoms (r = .609; p \ .001) correlated significantly with the severity of AT. A multiple regression analysis with AT as the dependent variable and the inattentive and I/H symptoms severity as independent variables showed a significant association between AT and both ADHD symptom dimensions—with the I/H symptoms (b = .457; p \ .001) contributing more to the model than the inattentive symptoms (b = .278; p = .004). Conclusions: In line with previous reports (Kotte et al. 2013; Taylor, Charman, & Ronald 2015) the ADHD symptoms severity is significantly associated with that of subclinical AT in children and adolescents with ADHD and without comorbid ASD. The significant associations between the severity of ADHD symptoms and that of AT may reflect impairments in underlying neural systems that lead to both types of behaviour.
S21 References: Kotte, A., Joshi, G., Fried, R., Uchida, M., Spencer, A., Woodworth, K. Y., Biederman, J. (2013). Autistic traits in children with and without ADHD. PEDIATRICS, 132(3), e612–622. doi: 10.1542/peds.2012-3947 Taylor, M. J., Charman, T., & Ronald, A. (2015). Where are the strongest associations between autistic traits and traits of ADHD? Evidence from a community-based twin study. Eur Child Adolesc Psychiatry, 24(9), 1129–1138. doi: 10.1007/s00787-014-0666-0
P-08-005 Dissociation of Attention-Deficit/Hyperactivity Disorder and autism evidence from intra-subject variability in gaze control D. P. Seernani*, C. Ioannou, H. Hill, G. Boccignone, T. Foulsham, N. Dundon, N. Cilia, C. Saville, S. Bender, C. Fleischhaker, M. Biscaldi, U. Ebner-Priemer, C. Klein *Freiburg, Germany Objectives: Potential aetiological overlap between Attention-Deficit/ Hyperactivity Disorder (ADHD) and autism spectrum disorder (ASD) is a current topic of research in neurodevelopmental disorders that requires systematic comparisons between these groups (Biscaldi et al. 2015; Rommelse et al. 2011). Among the most consistent findings in the ADHD literature is increased intra-subject variability (ISV), that is moment-to-moment fluctuation of performance, which has, so far, almost exclusively been studied with manual-motor responses. Here, we broaden the study of ISV from reaction time tasks with manual responses to the ISV of gaze control. Methods: Children and adolescents with ADHD, ASD and healthy controls, aged 10–13 years (n = 90; all native German speakers) were invited for an ocular-motor testing session including a visual search and a gaze cueing task. In the visual search task, participants are required to find a Portuguese target word shown above a grid with multiple Portuguese German word pairs and to indicate its position by pressing response keys matching the search array. In the gaze cueing task, participants play the game ‘I spy’, and are required to follow the gaze of an on-screen face in order to correctly locate the target object. Fixation durations, saccadic latencies, saccadic amplitudes and initiation of search will be used to derive measures of ocular-motor ISV. Results: Preliminary results suggest dissociation between ADHD and ASD, with only the ADHD group showing significantly higher ISV in ocular-motor parameters of the visual search as well as the gaze cueing task. Conclusions: Our study will show to what extent increased ISV (a) can be found in the ocular-motor domain and (b) is specific to ADHD.
P-08-006 Discriminating power of the social responsiveness scale in autism spectrum disorder and Attention-Deficit/Hyperactivity Disorder C. Stordeur*, E. Acquaviva, A. Boele, H. Peyre, R. Delorme *Paris, France Objectives: We aimed to find out how the social responsiveness scale (SRS) could differentiate between patients with ASD and/or ADHD. Methods: The total scores and the five subscales of the SRS were compared between four groups of subjects (n = 123): ADHD, ASD + ADHD, ASD and typical neurodevelopment (TD). The crossdiagnostic validity was studied using ROC curves analysis.
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S22 Results: We found a significant difference in the SRS total scores when comparing ADHD versus ASD + ADHD (p = 0.005) and ADHD versus ASD (p = 0.032). The social cognition and autistic mannerisms sub-scores were the most discriminating between the ADHD and ASD groups. Conclusions: The SRS autistic mannerisms and social cognition subscores may be the most clinically relevant for the differential and comorbid diagnosis of ASD and ADHD.
P-08-007 Clinical correlates of ADHD and autism spectrum disorder J. Bhagia*, B. Koplin, L. Halldner Henriksson *Rochester, USA Objectives: To analyse the prevalence of ASD symptoms in children with clinically diagnosed ADHD including atypicality, withdrawal, and functional communication. This data was then compared to the results of children diagnosed with both ADHD and ASD in order to find a correlation of disorders and/or symptomatic behaviour. Furthermore, the project aimed to evaluate the use of BASC-2 rating scale to screen ASD in ADHD children. Methods: BASC-2 results and clinical records of a total of 50 children, 30 children with ADHD and 20 children with ADHD and autism were reviewed. These patients were seen in a U.S. specialty clinic for ADHD where BASC-2 forms were collected from parents and teachers. These forms gathered data in the categories of hyperactivity, inattention, atypicality, withdrawal, and functional communication. Both rating scales and clinical records were reviewed to confirm the diagnoses of ADHD and ASD. Results: As expected, children with only ADHD scored very high in hyperactivity and inattention with 73 and 90% of children scoring ‘‘significant’’ within these categories respectively, according to their parent’s BASC-2 rating scales. However, 50% children had significant atypicality, withdrawal, and functional communication scores, characteristics typically associated with ASD based on both parent and teacher rating scales. When this data was compared to the ratings of children diagnosed with both ADHD and ASD, both the prevalence of ‘‘significant’’ symptoms as well as the mean score within each of the categories was higher. Conclusions: While the rating scores of ADHD patients in the categories of atypicality, withdrawal, and functional communication do not reach the same levels as patients diagnosed with both ADHD and autism, they are still significantly elevated. Therefore, while it does not appear that these patients have clinically diagnosed autism, it is clear that ADHD is causing symptoms that mimic borderline ASD behavioural and social concerns, a problem that needs proper attention and further evaluation.
P-08-008 Facets of intra-subject variability in Attention-Deficit/Hyperactivity Disorder and autism spectrum disorder C. Klein*, G. Salunkhe, B. Feige, C. W. Nicholas Saville, N. M. Dundon, S. Bender, A. Berger, C. Fleischhaker, M. Biscaldi *Freiburg, Germany Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental disorders
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Abstracts that have been studied mainly in isolation from each other so far. However, factors like high comorbidity and familiality suggest a potential aetiological overlap between them. To address this question, we tested patients with ADHD and ASD for putative cognitive endophenotypes of ADHD (working memory, inhibition, temporal processing), with a special focus on intra-subject variability (ISV). Methods: Each n = 40 healthy control (age: 10.23 ± 1.58; 87.50% male; IQ: 107.20 ± 18.33), patients with ADHD (age: 10.29 ± 1.44; 87.50% male; IQ: 104.73 ± 18.74) and patients with ASD (age: 10.40 ± 1.75; 87.50% male; IQ: 106.65 ± 20.37; n = 19 with comorbid ADHD, ‘‘ASD+’’; n = 21 without, ‘‘ASD-’’) was administered 0-/1-back tasks, a stop signal task and a time reproduction task. Linear mixed-model ANOVAs were used to compare these groups in measures such as reaction times (RT), ISV of RT or accuracy. Results: Results show the largest group differences for measures of ISV, indicating that both the ADHD and the ASD group were significantly more variable than healthy controls for all cognitive tasks. Overall, the ASD group showed the greatest within-group heterogeneity in various measures of ISV. Most notably, the ASD + group exhibited greater ISV than both the ASD- and the ADHD groups. Conclusions: The results of the present study suggest that increased ISV is a commonality of ASD and ADHD and that the comorbid ASD + group shows greater ISV than expected. Results will be discussed with reference to aetiological models of ADHD and ASD and the potentially nosologically special status of the comorbid ASD + group.
P-09-002 Associations between P3 responses and continuous performance test in children with Attention-Deficit/Hyperactivity Disorder S.-J. Hung*, M.-H. Hsieh, C. Gawrilow, S. S.-Fen Gau *Chiayi, Taiwan Objectives: To investigate the associations between P3 responses induced by a go/no-go task (Paul et al. 2007) and behavioural performance on the continuous performance test (CPT) in children with Attention-Deficit/Hyperactivity Disorder (ADHD) and typically developing (TD) children. Methods: We assessed 21 children with ADHD (mean ± SD = 9.84 ± 1.27 years) and 20 TD children (mean ± SD = 10.49 ± 1.12 years) with two neuropsychological tasks (i.e., go/no-go task and continuous performance test, CPT), which were randomly administered. Electrophysiological data were recorded while participants were performing the go/no-go task. Behavioural variables (i.e., omission errors, commission errors, reaction time [RT], and reaction time standard errors [RTSE]) measured by the CPT and event-related potentials (i.e., P3 latencies and amplitudes at electrode sites-Fz, Cz, and Pz) evoked by the go and no-go stimuli were collected. Correlations between behavioural variables and P3 responses were calculated. Results: Regarding the correlations between the CPT performance and P3 responses, different patterns were observed between groups. For children with ADHD, significances were found between P3 latencies at Fz and RTs (r = .493, p \ .05), P3 latencies at Cz and RTs (r = .566, p \ .01), and P3 latencies at Cz and RTSEs (r = .524, p \ .05). In the control group, pronounced associations existed between P3 latencies at Fz and omission errors (r = -.584, p \ .01), P3 latencies at Fz and RTSEs (r = -.601, p \ .01), and no-go P3 latencies at Fz and omission errors (r = .482, p \ .05). Conclusions: The results provide evidence to support that some similar and some different mechanisms or strategies are involved when children with ADHD and TD children perform the neuropsychological tasks. Future studies with larger sample sizes are warranted to validate the current findings.
Abstracts
P-09-003 Periodic limb movements onset latency and ferritin levels in children with ADHD E. Konofal*, D. Janka, M. Lecendreux, C. Delclaux *Paris, France Objectives: There is evidence that Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with sleep problems in children. Impressive publications have previously described restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) in children with ADHD. It has been reported that RLS at rest, during the evening, temporary removed during mental occupation or movement and PLMS, at a rate of[5 per hour of sleep, affected mostly severe cases of ADHD. In these children, direct correlations between symptoms of ADHD and mechanism of sleep disruption, iron status dysregulation, underlying a hypothetical common dopaminergic deficit, has been hypothesised. However, this association was only analysed by using actigraphy or polysomnography, but not by using the simple PLMS index. The temporal evolution of periodic leg movements (PLM) and the relationship of their severity effect on diurnal ADHD symptoms has never been investigated. The aim of our study was to evaluate the predictive impact on RLS and ADHD symptoms severity of the temporal evolution of PLM patterns during sleep. Methods: A group of 50 school-aged (10.3 ± 2.7 years) randomised children (14G, 36B) with ADHD, without specific sleep complaints expressed, not clinically referred for a diagnosis of RLS underwent systematic one-night video-polysomnography. PLM were detected following standard criteria and the PLMS index calculated. PLM analysis was done separately by each sleep cycle. PLMs nocturnal variation was also considered in light of slow wave activity (SWA). Results: Most of these children with ADHD (65%) had a PLMS index [5 (range 1.2.7–28.1). A tendency of positive correlation between PLMS index (11 ± 10) and ADHD-RS score (42 ± 10) is found, but above all, with the application of the PLM temporal analysis, we showed that the distribution PLM declined from the first to the last sleep cycle, and especially in those with the most severe diurnal symptoms of ADHD. Children with a ADHD-RS score up to 40 (14/ 31) expressed polysomnographically a very short PLM Onset Latency (\1 min after sleep onset latency) associated with a decrease in SWS period at each sleep cycle ([20% of total sleep time) and the lowest ferritin (\30 microg/L) (p \ 0.01). Conclusions: The PLM temporal analysis and PLM distribution during sleep seem to indicate that the most severe ADHD children have a short PLMOL, the lowest ferritin levels and a reduction of SWS density. Low ferritin level and common mechanism generating RLS, PLM and ADHD should be speculated. This study suggests that there is an association between PLMOL, SWS reduction, the severity of ADHD symptoms and iron deficiency expressed by low ferritin levels. Sleep recording and temporal analysis of PLMs could play a role in pharmacological management and demonstrate a causal association between ADHD, RLS and PLMS. Iron supplementation should be suggested also.
P-09-004 Resting-state EEG correlates of ecological executive function in adults with ADHD H. Li*, C.-M. Wang, Q.-H. Zhao, F. Huang, Q.-J. Qian, Y.-F. Wang, L. Sun *Beijing, People’s Republic of China Objectives: The purpose of the present study was to investigate the abnormalities in resting-state EEG in adults with ADHD, and the
S23 relationships between EEG characteristics and self-ratings of ecological executive function (EF), defined as indicators to reflect everyday life EF deficits. Methods: Thirty-three adults diagnosed with ADHD in childhood according to DSM-IV and 30 carefully matched health control subjects were recruited and recorded with EEG signals during an eyeclosed resting state condition. The absolute and relative power in delta (1–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), and beta (13–30 Hz) bands were analyzed. Meanwhile, the self-ratings of behavior rating inventory of executive function were used to measure the ecological EF and their correlation with EEG power. Results: Compared to control adults, the ADHD group exhibited significantly higher global theta activity (F = 3.28, P = 0.041), higher central beta activity (F = 3.20, P = 0.003), and lower central alpha activity (F = 10.55, P = 0.002). There were different correlations between EEG and EF scores in two groups. In ADHD group, working memory scores positively related to the absolute theta power in left frontal brain (r = 0.43, P = 0.014), Emotional Control scores positively related to relative beta power in bilateral central brain(left: r = 0.55, P = 0.001; right: r = 0.37, P = 0.033), Shift scores positively related to relative theta power (r = 0.44, P = 0.011) and negatively related to relative alpha in left central brain (r = -0.39, P = 0.026). While in the control group, the correlation only existed in Emotional Control scores and central relative beta power (left: r = 0.62, P \ 0.001; right: r = 0.54, P = 0.002). Conclusions: This study demonstrated the resting-state EEG abnormalities remain in adults with ADHD. And their correlations with ecological EF imply the resting-state EEG might have the clinical value to assess the daily EF deficiencies in adults with ADHD.
P-09-005 Evoked ERP P300 and theta/beta ratio analysis between predominantly inattentive and combined ADHD F. Mulas Delgado*, P. Roca Rodriguez, P. Ortiz Sanchez, R. Gandia Beneto *Valencia, Spain Objectives: Diagnosis of ADHD is based in clinical criteria but there is strong research over the identification of neurophysiological correlates that may help better defining presentations and endophenotypes of the disorder, specially referred to the analysis of evoked components. It has been shown that combined and inattentive subtypes could show some differences in EEG and the topography and development of cognitive evoked component P300. Nevertheless, there’s still controversy about the existence of core differences in latency and amplitude between ADHD subtypes. Furthermore, from the Q-EEG and brain mapping, the American Food and Drug Administration (FDA) stated the ADHD classification by the theta/beta ratio analysed from the spectral power, showing significant high correlation when clinical correspondence was found. Objectives: To explore differences in theta/beta quotient, and in latency and amplitude of visual ERP P300, between children diagnosed as ADHD combined and inattentive presentation. Methods: 55 patients diagnosed of ADHD aged 5–18 years (combined group = 28 and inattentive group = 27). Component P300 was registered and analysed in Cz by a visual oddball task, setting latency msecs and amplitude in lV. Theta/beta ratio was calculated from EEG spectral absolute power. Results: We neither found statistical meaningful differences between ADHD-C and ADHD-I groups in P300 latency, nor a P300 amplitude. The theta/beta ratio showed no difference between groups
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S24 Conclusions: Our results do not allow conclusion about a different profile of visual ERP P300 between ADHD combined and inattentive presentations. Findings over the theta/beta ratio suggest this quotient could not be able to discriminate between these clinical presentations, suggesting that an underlying neurophysiological common base could exist. Further evaluation is needed, with higher sample size and other clinical features.
P-09-006 Intra-subject variability of behavioural and electro-cortical measures of performance in Attention-Deficit/Hyperactivity Disorder G. Salunkhe*, B. Feige, C. Saville, N. Dundon, B. Albrecht, S. Bender, A. Berger, C. Fleischhaker, M. Biscaldi, C. Klein *Freiburg, Germany Objectives: Increased intra-subject variability (ISV) is a consistent finding in Attention-Deficit/Hyperactivity Disorder (ADHD) which may occur due to increased lapses in attention, represented as slow or absent reaction times (RTs). Attentional lapses have been linked with poor suppression of the default mode network (DMN), which is usually attenuated during goal-directed task performance. Furthermore, deficits in performance, like slow RTs and errors, may be associated with slow (\0.1 Hz) quasi-periodic synchronisation of DMN structures. Methods: ADHD patients (n = 18) and age and IQ-matched healthy controls (n = 18), 12–13 years old, participated in two EEG sessions using the Flanker Task. EEG was recorded from 64 channels of the 10–10 system with a DC amplifier (Brain Products, Germany). All participants completed 48 blocks containing 72 trials each. For each participant, scores of behavioural (RTs, accuracy) and electro-cortical variables (P300 amplitude and latency) were aggregated across the 24 blocks of a single EEG session, separately for congruent versus incongruent flankers. Results: Preliminary behavioural and electro-cortical results for 12 patients and 12 controls show increased behavioural ISV and reduced P300 amplitudes in ADHD. During task-initiation, both groups have lower overall mean RTs and P300 amplitudes; higher accuracy in congruent trials and lower accuracy in incongruent trials. This is also followed by low frequency performance fluctuations in both patients and controls. Fast Fourier transform (FFT) on trial-wise averages of behavioural and EEG data will be employed in further analyses to identify the frequency spectrum of P300 amplitude and behavioural performance fluctuations. Conclusions: The results of our study have replicated previous findings about increased ISV in ADHD. Our further analyses will shed light on the temporal characteristics of ISV at both the behavioural and electrophysiological levels and will be discussed in the context of concurrent theories of increased ISV in ADHD.
P-09-007 A causal link between attentional selection and reading ability in Attention-Deficit/Hyperactivity Disorder L. Sun*, E. Wang, X. Luo, M. Sun, Y. Tao, H. Li, Q. Qian, Z. Wu, Y. Song, Y. Wang *Beijing, People’s Republic of China Objectives: Children with Attention-Deficit/Hyperactivity Disorder (ADHD) have been reported at significantly higher risk of showing
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Abstracts reading disorder or difficulties. However, the neural substrate underlying this phenomenon has yet to be characterized. Here, we report a first attempt to identify the relationship between electroencephalographic (EEG) markers of spatial attention and reading ability in children with ADHD. Methods: EEG data of 915-year-old children with ADHD (n = 38) and typically developing (TD) controls (n = 36) were collected while they searched for a shape circle target among diamonds. Additionally, rapid automatized naming task were conducted to evaluate the reading ability of children. Results: Children with ADHD showed slower response times than TD children on rapid automatized naming task. For event-related potentials (ERPs), the shape target elicited smaller N2pc in children with ADHD compared with typically developing children. The smaller N2pc amplitude predicted lower levels of reading ability in children with ADHD but not in the TD children. Moreover, the early occipital P1 component did not show significant difference between the two groups. However, the P1amplitude was negatively correlated with the reading ability in TD children but not in the children with ADHD. Conclusions: The correlation between the N2pc decrement and poor reading ability in ADHD suggests that their reading problems might in part be due to the impaired attentional selection. On the other hand, the early visual P1 component might play important roles in the development of reading for the TD children. Our findings provide a neurophysiological basis for the subjective reports of reading difficulty in children with ADHD and highlight the importance of visual spatial attention in higher neurocognitive functions.
P-09-008 Reduced N1 and P3 amplitudes in the attentional network task are related with attentional impairment in non-medicated adult ADHD patients M. Garcia Valdecasas Colell*, A. Galvao Carmona, M. C-J Stehle, E. Ahlers, M. Vazquez Marrufo, A. H. Neuhaus *Seville, Spain Objectives: The aim of this study was to assess neural basis of the attentional impairment using the attention network test (ANT) in a sample of non-medicated adult ADHD patients compared to healthy controls. Methods: Continuous electroencephalography (EEG) was recorded in 16 non-medicated adult ADHD patients and 16 healthy adults during the ANT performance. We examined the cue and target-related P1, N1 and P3 components. Results: General slowing was found for ADHD group (F(1.30) = 15.94; p \ 0.001) with a specific slowing effect in the spatial condition (p \ 0. 01). Worse accuracy in the orienting and alerting conditions of the ANT task were found (p \ 0.001). No significant P1 amplitude nor latency effects were found between or within groups (p [ 0.05). Significant group effect for the N1 amplitude (F(1, 30) = 20.31; p \ 0.001) was found. ADHD group showed lower amplitudes (} = -2.51 lV ± 2.87) in comparison to the control group (} = -7.43 ± 5.33 lV) for all the conditions. Regarding the N1 latency, significant Cue x Group Interaction (F(2,60) = 5.94; p \ 0.01) was found. Lastly, significant Congruency x Group interaction effect (F (1,30) = 13.34; p \ 0.001) was found for the P3 amplitude. Conclusions: General slowing using the ANT for the non-medicated adult ADHD patients, as well as their worse accuracy in the alerting
Abstracts and orienting conditions of the task were found. General reduced N1 amplitude for the ADHD group and no modulation of the N1 latency across cue conditions suggest neural impairment at this level of attentional processing. Lastly, lower P3 amplitude for the ADHD group suggests difficulties when processing conflict in this clinical population. EEG analysis using the ANT task evidence several levels of attentional impairment in ADHD adults.
Friday, 21 April 2017, 14.30 h–16.00 h P-10 Pathophysiology adult P-10-001 Temperamental differences in adults with and without a childhood diagnosis of ADHD U. Jain*, S. Jain *Kota, India Objectives: Adults identified with ADHD in adulthood are often denied a diagnosis unless there has been a confirmed diagnosis in childhood (very relevant to insurance coverage of medications). The DSM-V has changed the criterion to having symptoms before the age of 12 but, in fact, temperamental differences using the temperament and character inventory can be compared to determine their relevance. Methods: As a secondary finding in a study looking at personality disorders comorbid with ADHD, n = 154 ADHD adults—five groups: A) n = 65 (no ADHD inattentive (ADHD-I) as a child) + ADHD-I adult B) n = 39 (no ADHD combined (ADHD-C) as a child + ADHD-C adult), C) n = 12 ADHD-I as child/adult, D) n = 32 ADHD-C as child/adult and E) n = 6 ADHD-C as child and ADHD-I as adult. Group A and C were compared as were groups B and D. Group E was too small. Results: No differences in age and gender between groups. In looking at temperamental differences group A versus C = NS, group B versus D NS. Conclusions: A pre-existing diagnosis should not be used to determine the stability or validity of the diagnosis. It is reasonable that the underlying temperamental characteristics of adult patients with ADHD remain stable.
P-10-002 Assessing attentional functions in adults with ADHD N. Saga*, T. Tokumasu, T. Morita, D. Ikuse, G. Arai, T. Morii, M. Ohta, Y. Ohmori, Y. Sawanobori, A. Sato, Y. Okajima, A. Iwanami *Tokyo, Japan Objectives: Many adults with ADHD do not perform well in their school or workplace because of impairments in their attentional functions. Previous studies have indicated that executive performance is associated with attentional functions. In the present study, we investigated attentional functions in adults with ADHD and the relationship between attention and clinical characteristics. Methods: Subjects provided written informed consent prior to participating in the study, which was approved by the ethics committee of the Faculty of Medicine of Showa University. Participants in this
S25 study comprised ten adults with ADHD (according to DSM-V criteria) and ten healthy adults. To confirm that the subjects were highfunctioning, intellectual ability was assessed using the Japanese version of the national adult reading test. The Conners adult ADHD rating scales—self-report version (CAARS), autism spectrum quotient (AQ), state-trait anxiety inventory (STAI), and self-rating depression scale (SDS) were used to assess symptoms in the subjects. To measure attentional function, we used several tasks from the test of attentional performance (TAP) version 2.3, developed by Zimmermann & Fimm. Results: As expected, there was a significant difference in ADHD index scores (p \ 0.01) between adults with ADHD (mean age: 37.3 ± 7.4 years, mean estimated IQ: 106.7 ± 13.3, mean ADHD index score: 81.0 ± 6.7) and healthy controls (mean age: 32.6 ± 7.2 years, mean estimated IQ: 111.1 ± 8.7, mean ADHD index score: 54.4 ± 15.7). In the ‘‘Sustained Attention’’ task, a subtest of the TAP, there was a significant difference between cases and controls in the mean reaction time (ADHD: 701.3 ± 82.1 ms, healthy controls: 580.4 ± 68.4 ms, p \ 0.01) and the number of omissions (clinical subjects: 11.5 ± 4.1, control subjects: 7.3 ± 7.4, p \ 0.05). Conclusions: Although estimated IQ scores suggested that subjects with ADHD were high-functioning, our results indicate that they show impairments of attentional functions compared with healthy people.
P-10-003 Poor quality of decision-making in adults with ADHD is linked to delay aversion and longer deliberation time L. Sorensen*, E. Sonuga-Barke, E. B. Brevik, D. Jensen, J. Haavik, A. J. Lundervold *Bergen, Norway Objectives: We have previously shown that children with ADHD’s suboptimal decision-making (DM) in the face of risk is related to their delay aversion (the motivation to avoid delay), and not to a predominant tendency to be impulsive (short deliberation time) or risk prone (Sørensen et al. 2016). In the current study, we extended our study to adults by using the same task—the cambridge gambling task (CGT). On the basis of the previous results we predicted that adults with ADHD would also show suboptimal choice patterns linked to delay aversion. Methods: A clinically recruited group of adults with ADHD (n = 29) and a group of healthy controls (HC) (n = 32) performed the CGT. The mean age of the sample was 34.49 years (SD = 8.28), with a female dominance (57.4%). The group differences in age and gender were non-significant. Univariate ANOVAs were conducted, with linear regression analyses as follow-up of significant between-group effects. Results: Adults with ADHD showed lower quality of DM scores than the HCs (p = 0.005). None of the other CGT scores were different between the groups. Delay aversion and longer deliberation times predicted this poorer quality of DM score, whereas the scores of risk taking or risk adjustment did not. Conclusions: Both adults and children with ADHD are less rational during DM. In both cases this is linked to delay aversion. It is possible that individuals with ADHD compensated for impulsive behaviour and slowed down their speed in DM. There is little evidence from our studies that ADHD is associated with risk proneness.
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P-10-005 To age or not to age: Neuropsychological deficits in adults aged 60 and over with AttentionDeficit/Hyperactivity Disorder Y. Holst*, D. Sjo¨wall, H. Christiansen, S. Kooij, D. Bijlenga, L. Thorell *Nacka, Sweden Objectives: The overall aim was to investigate neuropsychological deficits in older adults with ADHD in comparison with both younger adults with ADHD and healthy older controls. Methods: The study included 158 participants in three groups: Older adults (60–75 years) diagnosed with ADHD, older adults of the same age without any psychiatric disorders, and younger adults (age 18–45) with ADHD. Well-validated neuropsychological tests from either WAIS-IV or D-KEFS were used to assess the following neuropsychological deficits: Working memory, inhibition, switching, planning, fluency, and speed of processing. Self-ratings assessing executive functioning and delay-related behaviours were also included. Both variable- and person-oriented analyses were included. Results: Older adults with ADHD differed from healthy controls with regard to working memory, inhibition, switching, and delay-related behaviours (all ts [ 2.23, ds = .45–1.70). In comparison to younger adults with ADHD, they performed at a similar level with regard to working memory and planning (all ts \ 1.35, all ds \ .28), but significantly better with regard to inhibition, switching, fluency, and speed of processing (all ts \ 2.42, ds = .40–1.27). Despite several significant group differences relative to healthy controls, person-oriented analyses showed that a majority of older adults with ADHD performed within the average range on each test and 20% did not show a clear deficit in any neuropsychological domain. Conclusions: These results are an important contribution to the knowledge of neuropsychological deficits in older adults with ADHD. Our results are in line with current models of heterogeneity, which claim that only a subgroup of patients with ADHD has clear neuropsychological deficits. For older adults with ADHD who have working memory deficits, it will be important to assess their functioning across time as normal aging is related to working memory decline and these patients could therefore end up with very severe deficits as they grow older, which in turn could have serious negative effects on daily life functioning.
P-10-006 Suboptimal or risky decision-making in ADHD? A meta-regression analysis T. Dekkers*, J. Agelink van Rentergem, H. Huizenga, R. Shoham, A. Popma, Y. Pollak *Amsterdam, The Netherlands Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) has been related to a broad range of risk taking behaviours, such as risky driving, unsafe sex and substance abuse. Our recent meta-analysis on laboratory gambling tasks showed that groups with ADHD showed riskier decision-making than groups without ADHD. However, in most gambling tasks, risk and expected value were confounded, in that high-risk options were also characterized by low expected value. Recent studies suggest that ADHD might be characterized by suboptimal decision-making (i.e. not opting for the highest expected value), instead of risky decision-making. In the current study, we tested this hypothesis using meta-regression.
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Abstracts Methods: We performed a multilevel meta-regression analysis including 46 effect sizes from 35 studies (n ADHD = 1060; n Control = 987). As a moderator, we compared studies in which the risky alternative was disadvantageous in terms of expected value (k = 31) with studies in which the risky alternative was similar to or more advantageous than the safe alternative (k = 15). Results: The proposed moderator was significant (b1 = .36, p = .037), implying that only studies in which the risky alternative was also disadvantageous in terms of expected value yielded a significant effect size (SMD = .38, p \ .001), whereas studies in which the risky alternative was not disadvantageous did not (SMD = .03, p = .838). Conclusions: Our results contribute to a growing body of evidence that decision-making deficits in ADHD are not driven by risk seeking in itself, but are potentially driven by suboptimal decisionmaking, reflecting difficulties with regard to maximising expected value. The current results imply that interventions targeting risky behaviour of individuals with ADHD should target their perceptions about benefits and losses, in order to increase the quality of their decisions.
P-10-007 Neuropsychological computerised screening of Brazilian children with Attention-Deficit/ Hyperactivity Disorder M. Popi*, T. I. Riechi, H. Hamdam *Curitiba, Brazil Objectives: This research performed an analysis of the neuropsychological performance of children and adolescents with AttentionDeficit/Hyperactivity Disorder (ADHD) and controls properly enrolled in the public and private schools at Curitiba, Brazil. Methods: A clinical group of 38 participants (20 males and 18 females) with a diagnosis of ADHD without comorbidities and a control group of 170 subjects (67 males and 103 females) with no history of neurological impairment underwent neuropsychological computerised screening for children (NCSC). The work environment was in the Neuropediatric Ambulatory at Clinical Hospital (CENEP-HC), Laboratory of Neuropsychology of the Federal University of Parana´- Brazil (UFPR). Results: The analysis of results identify statistical differences between both groups. The ADHD group had poor results in the total score of NCSC and in eight of the ten analysed subtests (organisation acoustic-motor, tactile-kinesthetic ability, visual skills, oral expressive language, writing, reading, mathematical reasoning and immediate memory). Moreover, the results obtained by the ADHD group in temporal analysis also revealed poor results. The ADHD group also required more time to perform the test. There were significant statistical differences of neuropsychological performance between Brazilian children and adolescents with and without ADHD. The neuropsychological computerised screening for children (NCSC) discriminated children and adolescents suspected of ADHD. Conclusions: The NCSC demonstrated sensitivity in identifying patients with ADHD based on their cognitive performances in the total scores and in most subtests and times measured by the system. The final and practical objective of an appropriate evaluation instrument is to improve the preserved aspects of their cognitive functions, help them achieve quality of life in their own contexts and minimise academic failure. It is important to highlight that this population with ADHD can become productive, considering their limitations and cognitive deficits.
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P10-008 Visual attention in adult Attention-Deficit/ Hyperactivity Disorder Ann-Marie Agerbo Low*, J. le Sommer, B. Fagerlund, B. Glenthoj, J. R. Mollegaard-Jensen, S. Vangkilde, T. Habekost * Copenhagen, Denmark Objectives: Traditionally seen as a disorder of childhood, recent research indicates a prevalence rate of adult ADHD of 2.5%. The objective of this study is to utilise the Theory of Visual Attention (TVA) to (1) describe which aspects of visual attention are affected in stimulant medication-naı¨ve Adults with ADHD (AwADHD) and (2) identify whether specific aspects of attention are affected by stimulant medication in AwADHD. Methods: The study is a prospective, six week follow-up study with 38 stimulant medication-naı¨ve AwADHD, and 38 healthy controls (HCs) matched on age and parental socio-economic status (SES). Patients are recruited from the ADHD clinic at Glostrup Mental Health Center, and assessed with a range of cognitive and psychopathological measures before and 6 weeks after commencement of medication (methylphenidate). Cognitive measures include measures of visual attention (C: visual processing speed, K: visual apprehension span, t0: perception threshold, windex: spatial bias), and intelligence. Further, measures of anxiety, depression, and general psychopathology are undertaken. Results: At time of writing, results are available for 27 patients / 20 controls at baseline and follow-up, and a further 6 patients / 7 controls at baseline only. Patients and controls are similar in terms of age and parental SES, and significantly different in terms of ADHD symptoms and estimated IQ. At baseline, significant differences are found between ADHD and HCs on parameters C, t0 and K. windex is comparable. After 6 weeks of medication, patients improved significantly on all parameters of TVA, with the exception of windex. However, significant group x time interactions are only seen for parameter C. Conclusions: The results indicate that TVA parameters may be useful in delineating specific deficits of visual attention in AwADHD. Further, that parameter C may be specifically affected by medication. Final results will be presented at the ADHD World Congress in May.
Friday, 21 April 2017, 14.30 h–16.00 h P-11 Pathophysiology children and adolescents P-11-001 Time-on-task effects in children with and without ADHD: Depletion of executive resources or depletion of motivation? T. Dekkers*, J. Agelink van Rentergem, A. Koole, W. van den Wildenberg, A. Popma, A. Bexkens, R. Stoffelsen, A. Diekmann, H. Huizenga *Amsterdam, The Netherlands Objectives: Children with Attention-Deficit/Hyperactivity Disorder (ADHD) are characterized by deficits in their executive functioning and motivation. In addition, these children are characterized by enhanced time-on-task effects. However, it is unknown whether these time-on-task effects should be attributed to deficits in executive functioning, or to deficits in motivation. Some studies in typically developing (TD) adults indicated that time-on-task effects should be
S27 interpreted as depletion of executive resources, but other studies suggested that they represent depletion of motivation. We therefore investigated, in children with and without ADHD, whether there were time-on-task effects on executive functions like inhibition and (in)attention, and whether these were best explained by depletion of executive resources or depletion of motivation. Methods: The stop signal task (SST), which generates both indices of inhibition (stop signal reaction time) and attention (reaction time variability and errors), was administered in 96 children (42 ADHD, 54 TD; aged 9–13). To differentiate between depletion of resources and depletion of motivation, the SST was administered twice. Half of the participants was reinforced during second task performance, potentially counteracting depletion of motivation. Results: Multilevel analyses indicated that children with ADHD were more affected by time-on-task than controls on two measures of inattention, but not on inhibition. In the ADHD group, reinforcement only improved performance on one index of attention. Conclusions: The current findings suggest that time-on-task effects in children with ADHD occur specifically in the attentional domain, and originate in both depletion of executive resources and depletion of motivation. Clinical implications are that if children recognise depletion, they can be taught to take a short break or to switch to less demanding tasks. Moreover, therapists might keep sessions short and offer short breaks to prevent depletion. If time-on-task effects still occur, for example at school, these might be partly counteracted with reinforcement.
P-11-002 Behavioural sensitivity to changing reward frequency among Brazilian children with and without Attention-Deficit/Hyperactivity Disorder E. Furukawa*, B. Alsop, E. Casella, E. Caparelli-Da´quer, R. Costa, P. Galva˜o, L. Benevides, H. Juca´-Vasconcelos, P. Queiroz, G. Tripp *Okinawa, Japan Objectives: Altered reinforcement sensitivity has been hypothesised to underlie the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). Here we evaluate the ability of children with and without ADHD to adapt their behaviour when reward availability changes. Methods: Forty typically developing (TD) children and 32 diagnosed with ADHD completed a signal-detection task in which correct discriminations between two stimuli were associated with different frequencies of reinforcement. The response alternative associated with the higher rate of reinforcement switched without warning after children received 30 rewards. Children&s preference for the more frequently reinforced alternative (bias) was calculated for each block of ten reinforcements, compared separately for the initial and reversed reward distribution. Results: The ADHD and TD groups developed a bias towards the more frequently reinforced response alternative over the initial three blocks, albeit smaller for the ADHD group (F(1, 70) = 4.62, p \ .05). When the reward distribution reversed, the children’s response allocation followed suit with both groups; bias scores approaching zero during the first reversal block. The TD group bias remained stable for the remainder of the reversal phase. Conversely, the ADHD group developed a significant bias towards the now more frequently reinforced alternative (group x Block, F(1.86, 125.03) = 3.23, p \ .05). Conclusions: Both groups of children demonstrated behavioural sensitivity to the asymmetric reward distribution, developing a preference towards a more frequently reinforced alternative and shifting their behaviour when the reinforcement ratio reversed. The bias of
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S28 children with ADHD increased with time-on-task following the reversal, remaining stable for those without ADHD. We hypothesise the response allocation of children with ADHD is influenced more by recent response contingencies rather than by their history of reward on the task. Differences in the temporal influence of reinforcement contingencies should be considered in the management of ADHD.
P-11-003 A developmental change for the relationship between neuropsychological functions and the severity of ADHD and ODD symptoms in preschoolers: A 3-year follow-up study S.-L. Hwang-Gu*, Y.-C. Chen, S. S.-Fen Gau *Taoyuan City, Taiwan Objectives: The aim of this study was to investigate the developmental change for the relationship between neuropsychological functions—attention measured by Conners Kiddie continuous performance test (KCPT), inhibitory response measured by day/night Stroop, and delay aversion measured by delay choice task—and the severity of ADHD symptoms in preschoolers, both concurrently and longitudinally. Methods: Fifty-eight preschoolers (4–5 years old), 1/2 who had been identified as being at risk for developing ADHD as clinical referral by the child psychiatrists, completed neuropsychological tasks designed to measure attention, inhibitory control, and delay aversion. Behavioral symptoms were measured through parental ratings of DSM-IV criteria for ADHD and ODD. The neuropsychological tasks and behavioural rating were completed two times (time one was 4–5 years, the second time was 6–7 years after the participants entered elementary school). Results: Our results showed only attention and inhibitory control measured by the second time were associated with the severity of ADHD symptoms rated at time one and time two. There were no associations between neuropsychological functions and the ADHD symptoms in time one (age 4–5). Our results also did not show the association between delay aversion and ADHD symptoms, both concurrently and longitudinally. The ODD symptoms were not associated with neuropsychological function, both concurrently and longitudinally. Conclusions: The current study demonstrated that the neuropsychological functions might not be the important part to assess the ADHD symptoms in preschoolers, however, the performance of attention and inhibitory control might play a role to assess the ADHD symptoms in elementary school. The current study also demonstrated that neuropsychological functions might not relate to the ODD symptoms, no matter whether in preschoolers or school children.
P-11-004 Temperament and character profiles associated with internalizing and externalizing problems in children with Attention-Deficit/ Hyperactivity Disorder Y. S. Kwack*, N. R. Kang *Jejusi, Republic of Korea Objectives: This study was to investigate how temperament and character profiles are related to internalising and externalising problems in children with ADHD.
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Abstracts Methods: The subjects were 74 ADHD children (mean age 8.51 ± 1.92 years) diagnosed in according to K- SADS-PL. To evaluate their comorbid problems we used the child behaviour checklist (CBCL) and also, their temperament and character profiles were examined by JTCI (junior temperament and character inventory), and we analysed the difference of TCI scale scores between children who had both internalising and externalising problems (N = 16, male 84.2%) and the rest of the children as comparison group (N = 55, male 76.8%). Results: ADHD children who had both internalising and externalising problems showed a temperament profile significantly higher in novelty seeking (p = 0.004) and harm avoidance (p = 0.002), but scored significantly lower in self-directedness (p = 0.012), and cooperativeness (p = 0.009) than in the comparison group on JTCI. Conclusions: The results of this study suggest that specific patterns of temperament and character traits such as high novelty seeking and harm avoidance but low self-directedness and cooperativeness could be related to more severe comorbid problems in children with ADHD.
P-11-005 Executive function characteristic in children and adolescents with Attention-Deficit/Hyperactivity Disorder comorbid tic disorders W. Liao*, J. Jin, h. Li, L. Liu, L. Sun, J. Cheng, Y. Qian, Q. Qian, Y. Wang *Beijing, People’s Republic of China Objectives: To answer the question whether executive function (EF) deficits are specific to Attention-Deficit/Hyperactivity Disorder (ADHD) or whether such deficits are also associated with tic disorder (TD). Methods: A total of 112 ADHD comorbid tic disorder (ADHD +TD) children,112 pure ADHD children and 112 normal controls (criteria of diagnostic and statistical manual of mental disorders-fourth edition, DSM-IV) were collected as our samples. ADHD +TD group is comprised by 55 ADHD comorbid transient tic disorder (ADHD + TTD) children, 30 ADHD comorbid chronic tic disorder (ADHD + CTD) children, 11 ADHD comorbid Tourette syndrome (ADHD + TS) children and 16 ADHD comorbid unsubtyped tic disorder children. The former three groups (ADHD + TD, pure ADHD, and normal control) were matched by sex, age (less than 6 months) and IQ. The Rey-Osterrieth complex figure test, the trail making test, and the Stroop color word test were administered to assess working memory, shifting andinhibitory function respectively. Results: Both pure ADHD group and ADHD + TD group performed worse (P \ 0.05) in the aspects ofthe delay recalling structurescore, the immediate memory detail score, the delay recalling detail score of Rey complex figure test, time of number-letter part and shifting time of trail making test, the time of Stroops 2, 4, the errors of Stroop 4 and word interference than normal controls. Pure ADHD group performed worse(P \ 0.05) in the aspects of the time of thestructureand detail forgetting scorethan normal controls, too; the pure ADHD group also showed deficits in the aspects of the time of Stroops 2, and the errors of Stroop 4 compared with ADHD + TD group. The differences were significant (P \ 0.05). ADHD + TS group performed worse (P \ 0.05) in the aspects of the time of Stroops 2 than ADHD + TTD group and ADHD + CTD group. The other differences all were not significant (P [ 0.05). Conclusions: The findings support the hypothesis that ADHD is related to executive function deficit, particularly in the tests assessing working memory, shifting andinhibitory function, whether or not comorbid tics disorder.
Abstracts
Friday, 21 April 2017, 14.30 h–16.00 h P-12 Neuroimaging P-12-001 Differences in brain activation after mindfulness training in adults with ADHD: A fMRI study K. Bachmann*, P. So¨ro¨s, A. P. Lam, M. Kanat, E. Hoxhaj, S. Matthies, B. Feige, A. Philipsen *Bad Zwischenahn, Germany Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is a serious psychiatric disorder with a strong neurological basis, and has been associated with cognitive and behavioural impairments such as deficits in working memory performance. Psychopharmacological treatment with psychostimulants is the mainstay of treatment; however, non-psychopharmacological approaches are frequently soughtafter. Mindfulness meditation training (MT) has been shown effective in the treatment of ADHD. However, little is known about the neurobiological effects of MT in adults suffering from ADHD. The current study was set out to investigate the effects of MT on neural functioning in adults with ADHD during working memory performance. Methods: Brain imaging data from 22 women (43.5 ± 11.4 years.) and 18 men (36.6 ± 12.2 years.) with ADHD were analysed. ADHD was diagnosed by expert psychiatrists. Patients were randomised either in an 8-week mindfulness or psychoeducation group and underwent functional magnetic resonance imaging (fMRI) during a one-back working memory task before and after intervention, fMRI data analysis was carried out using FSL. Results: After intervention both groups showed significantly improved working memory performance compared to pre-intervention. For the psychoeducation group the analyses of the imaging data did not reveal any difference in brain activation during working memory performance after intervention relative to baseline. By contrast, the MT group showed significantly stronger brain activation associated with working memory performance after intervention compared to baseline in following areas: Left and right inferior parietal lobule, right posterior insula and the right precuneus. Conclusions: We performed a direct comparison of brain activation during a working memory task before and after psychoeducation or MT in adults with ADHD. MT employed as therapeutic intervention seems to correlate with stronger brain activation in brain areas that have been suggested to relate to ADHD symptoms in adults. Our results point out that MT might help adult patients with ADHD to regulate impaired brain functioning.
P-12-002 Altered resting perfusion and functional connectivity of default mode network in children with Attention-Deficit/Hyperactivity Disorder Q. Cao*, P. Wang, Q. Zou, Z. Wu, L. Yang, Y. Zang, Y. Wang *Beijing, People’s Republic of China Objectives: The aim of this study is to explore the association between functional connectivity (FC) and local metabolic activity, measured by cerebral blood flow (CBF), in default mode network (DMN) in children with Attention-Deficit/Hyperactivity Disorder
S29 (ADHD) simultaneously using resting-state functional magnetic resonance imaging (fMRI) and arterial spin labelling (ASL) MRI techniques. Methods: Resting-state fMRI and ASL MRI were carried out in 49 children with ADHD (M/F = 33/16, 9.09 ± 1.69 years) and 37 controls (M/F = 21/16, 9.66 ± 1.78 years). Independent component analysis (ICA) was implemented in resting-state fMRI to extract DMN (including anterior DMN and posterior DMN), and then a mask of DMN was generated from results of the one-sample t-tests of all the sample (PFWE \ 0.001). Then, the voxel value of FC and CBF were calculate in the DMN mask for individuals and two sample t test was used to compare the FC and CBF differences in DMN between ADHD and control groups, using gender, IQ, age and handedness as covariance. Results: Compared with controls, children with ADHD showed decreased FC in left posterior cingulate cortex (x -6, y -39, z 24; peak T 3.396, voxel with P \ 0.05, cluster size[84, P \ 0.05 corrected by AlphaSim) and increased CBF in almost the same location (x -3, y 27, z 42; peak T 3.412, voxel with P \ 0.05, cluster size [569, P \ 0.05 corrected by AlphaSim) in DMN. There were no other brain regions showed either FC or CBF differences between two groups. Conclusions: The children with ADHD not only showed abnormal FC but also had aberrant CBF in DMN in resting-state. The jointly assess resting CBF and FC may highlight new avenues for identifying imaging markers for ADHD.
P-12-003 Why methylphenidate is not effective in adult ADHD patients with cocaine dependence C. Crunelle*, F. Matthys, W. Van den Brink *Jette, Belgium Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is an important contributing factor in the pathophysiology of substance use disorders (SUD), and occurs more often in populations with SUD compared to the general population. Methylphenidate (MPH) blocks brain dopamine transporters (DAT) and reduces ADHD symptoms, including impulsivity and hyperactivity. However, treatment with methylphenidate is less effective in patients with ADHD and SUD compared to ADHD patients without SUD. We propose possible explanations for this reduced effectiveness by investigating the underlying neurobiology of patients with ADHD and SUD. Methods: Male ADHD patients with and without cocaine dependence participated in a 2-week trial with slow-release MPH (Concerta, 54 mg). We investigated neurocognitive functioning and grey matter volume, as well as DAT availability before and after MPH treatment using SPECT scan in order to address the binding capacity of MPH to the dopamine transporters. Results: Compared to ADHD patients without cocaine dependence, ADHD patients with cocaine dependence had smaller grey matter striatal (putamen) brain volumes and were more impulsive on measures of motor and cognitive impulsivity. In addition, lower available dopamine transporters and a reduced binding of methylphenidate to these transporters were observed in adults ADHD patients with cocaine dependence compared to ADHD patients without cocaine dependence. Conclusions: Neurobiological and neurocognitive differences are present between ADHD patients with and without SUD, which together may partially explain the reduced effectiveness of methylphenidate in adult ADHD patients with SUD.
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P-12-004 Prediction of ADHD with PET imaging and genetic data in a machine learning model A. Kautzky*, H. L. Sigurdardottir, C. Rami-Mark, T. Vanicek, G. M. James, G. Gryglewski, G. Kranz, M. Spies, T. Traub-Weidinger, M. Hacker, K. Papageorgiou, M. Mitterhauser, W. Wadsak, S. Kasper, R. Lanzenberger *Vienna, Austria Objectives: Considering the estimated heritability of 0.76 and the fact that the norepinephrine transporter (NET) represents a main treatment target for Attention-Deficit/Hyperactivity Disorder (ADHD), single nucleotide polymorphisms (SNPs) associated with noradrenergic (NE) transmission might impact ADHD etiopathology (Faraone et al. 2005; Del Campo et al. 2011). Here, we strove for a multivariate prediction model for ADHD based on SNPs as well as NET binding potential (BPND) measured with (S,S)-[18F]FMeNER-D2 and positron emission tomography (PET). Methods: Twenty patients with ADHD and 20 healthy control subjects (HC) were scanned by PET and genotyped for 12 SNPs within ADRA1A, ADRA2A and SLC6A2 using Sequenom iPLEX as described previously (Sigurdardottir et al. 2016). Five regions of interest (ROI) were defined according to Hammers maximum probability atlas, hippocampus, putamen, pallidum, thalamus and midbrain. The cerebellum was used as reference region. Subsequently, ‘‘randomForest’’ (RF) of the statistical software ‘‘R’’ was used to select the most informative set of predictors based on minimised out-of-bag (OOB) errors in a training sample of 30 subjects and classification of ADHD and HC was then performed in a validation sample of ten subjects. Results: Using hippocampus BPND, rs168924 and rs36021 of SLC6A2 as well as rs4732682 and rs17426222 of ADRA1A as predictors according to highest importance estimation by mean decrease in accuracy and lowest OOB errors resulted in the highest accuracy of 0.60 for OOB prediction, showing sensitivity of 0.55 and specificity of 0.65. Validating the model in the test set, we confirmed an accuracy of 0.60. Conclusions: Although prediction accuracy of 0.60 does not allow clinically relevant diagnostic power, the model clearly performed better than chance. Therefore, our results advocate the relevance of SNPs within ADRA1A and SLC6A2 for ADHD and might contribute to the generation of a PET-based classification tool for ADHS which could be of significant clinical value regarding high rates of comorbidities and difficult differential diagnosis.
P-12-005 Evidence for hyperactivity in the superior colliculus in Attention-Deficit/Hyperactivity Disorder R. E. Kitching*, P. G. Overton, M. Panagiotidi, J. Billington, A. B. Morland, T. Stafford *York, UK Objectives: The superior colliculus (SC) is a sub-cortical midbrain structure involved in attentional shifts and distractibility. As distractibility is often atypical within ADHD, it is possible SC functionality in ADHD is also atypical. Indeed, a recent theory suggests distractibility observed within ADHD could be attributed to dysfunction, specifically hyperactivity, of the SC (Overton, 2008). This experiment aimed to explore whether SC responses to visual stimulation were associated with ADHD traits. We predicted a positive correlation between ADHD traits and SC responses.
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Abstracts Methods: The present study uses fMRI to examine the relationship between SC responsiveness and inattention-ADHD traits, assessed with the ASRS questionnaire. Seventeen typically developed adults, who ranged along the continuum of inattention-ADHD traits, were shown radial motion and static dot stimuli presented unilaterally in the left or right hemifield, while they performed a central rapid colour counting task. Results: Responses in the left and right SC to motion versus static stimuli presented in the right hemifield, showed significant positive correlations with ADHD inattention traits (left hemisphere: r = .50 p = .020, right hemisphere: r = .45 p = .035), with those exhibiting higher levels of inattention traits showing larger motion responses compared to static. However, when the same stimuli were presented in the left hemifield, there was no significant correlation between left or right SC responses to motion versus static stimuli and ADHD inattention traits. Whole brain analyses also revealed positive associations between the left hemisphere early visual cortex response to right hemifield motion versus static stimuli and ADHD inattention traits. Again, no similar results were found for left hemifield presentation. Conclusions: The results found preliminary support the initial hypothesis that those with higher levels of inattention traits showed increased SC activity to motion distractors compared to static, suggesting SC dysfunction may underlie some ADHD distractibility. Interestingly, such results only occurred to right hemifield distractors, which may reflect the hemifield differences in spatial attention previously observed within ADHD.
P-12-006 White matter microstructural characteristics and genetic risk for ADHD Z. Wu*, M. Hoogman, Q. Cao, J. Bralten, H. Lemaıˆtre, M. Zwiers, L. An, L. Liu, L. Sun, Y. Zang, G. Schumann, L. Yang, B. Franke, Y. Wang *Beijing, People’s Republic of China Objectives: To investigate, whether the genetic risk for AttentionDeficit/Hyperactivity Disorder (ADHD) contributes to white matter microstructural characteristics in patients and healthy adolescents. Methods: Three different cohorts were used in the current study: 1) Primary cohort: 206 children recruited in Beijing (ADHD and controls, aged 8–15 years); 2) NeuroIMAGE cohort: 165 adolescents and young adults recruited in The Netherlands (ADHD and controls, aged 11–26 years); 3) IMAGEN cohort: 1232 adolescents of European descent (general population, aged 14 years). All individuals underwent diffusion tensor imaging (DTI), and blood samples of 1.52 individuals were collected and genotyped. Tract-based spatial statistics (TBSS) analysis was performed after careful data preprocessing and quality control. Data analysis was performed in several steps: 1) Voxel-based case–control comparison in the primary cohort to generate regions of interest (ROIs); 2) mean fractional anisotropy (FA) was extracted from all ROIs that came out of Step1 in both primary and NeuroIMAGE cohort; 3) candidate gene-set-based analyses were performed with genes involved in dopamine/norepinephrine, serotonin, and neurodevelopment pathways in both Chinese and NeuroIMAGE cohorts. In a second approach, we calculated a biologically informed polygenic risk score (PRS) of the target gene sets in the IMAGEN cohort using a genome-wide association study of a Chinese cohort (n * 2000) as a reference; whole TBSS skeleton voxel-based regression was done with the PRS score in male and female subjects separately since more males ADHD were present in discovery samples.
Abstracts Results: Decreased FA in anterior corona radiata in children with ADHD revealed in step 1 was associated with the dopamine/norepinephrine pathway in the primary cohort, but this was not replicated in the NeuroIMAGE cohort. The whole skeleton TBSS analysis in IMAGEN showed negative correlation between PRS and FA values in widespread regions in males but not females. Conclusions: ADHD-relevant, biologically informed genetic analysis revealed potential associations with white matter microstructure development in cases as well as in the general population.
P-12-007 The potential sex differences in the restingstate fractional amplitude of low frequency fluctuation in children with ADHD W. Yanfei*, S. Li, L. Lu, A. Li, C. QingJiu, L. HaiMei, Q. QiuJin, W. YuFeng
S31 Methods: The present study was approved by the ethics committee of Faculty of Medicine of Showa University. Subjects of this study were 63 outpatients with ADHD of Showa University Hospital. The diagnosis was made according to the criteria of DSM-V. The normal control group is comprised of 35 healthy adults. The intelligence quotient (IQ) scores of all participants of ADHD were evaluated using a Japanese version of the national adult reading test (JART). The relative [oxy-Hb] in the prefrontal cortex was measured during the category and letter fluency tasks, using multi-channel near-infrared spectroscopy (NIRS). Results: The two groups did not differ significantly in the numbers of correct response on the tasks. The mean total [oxy-Hb] change during the category fluency task did not differ significantly between the groups; however, during the letter fluency task, the mean [oxy-Hb] change in persons with ADHD was significantly lower than that in controls. Conclusions: These results suggested task-relevant or task-specific prefrontal dysfunction in persons with ADHD.
*Beijing, People’s Republic of China Objectives: To find out if the fractional amplitude of low frequency fluctuation (fALFF) is different between boys and girls with ADHD in resting-state functional magnetic resonance imaging. Methods: There were 38 children with ADHD in our study including 31 boys and seven girls. Forty-two well developed children were involved too, including 29 boys and 13 girls. Total scores of C-WISC and ADHD rating scale were used to measure intelligence quotient and the severity of ADHD. fALFF was measured for each child. Analysis of covariance (ANCOVA) was used to find out the difference between the group and the sex with intelligence quotient as covariance. Multiply comparison correction was made by a-sim (P \ 0.05 corrected). Results: Sex-by-group analysis reveal that fALFF is lower in the boys with ADHD in the left cerebellum (t = -4.76, t = -3.47) when compared to boys without it; girls with ADHD show a higher fALFF in bilateral cerebellum (t = 4.87, t = 6.22, t = 4.60, t = 4.16) when compared to girls without it. Only in girls with ADHD, fALFF in the insula (t = -4.41, t = -4.05) is lower and in the thalamus (t = 4.58) is higher than girls without ADHD. The correlation analysis indicates that there is a negative relationship (r = -0.89, P \ 0.05 corrected) between the fALFF of the left cerebellum of girls with ADHD and the scores of inattention symptoms. Conclusions: Sex difference existed potentially in the fALFF of children with ADHD. The decreased fALFF of the cerebellum might deteriorate the attention deficit symptom of girls with ADHD.
P-12-008 Reduced prefrontal activation in adult subjects with ADHD during a verbal fluency task: A near-infrared spectroscopy study A. Iwanami*, M. Ota, Y. Okajima, T. Morita, T. Tokumasu, N. Saga, G. Arai, W. Hayashi, B. Yamagata *Tokyo, Japan Objectives: Multi-channel near-infrared spectroscopy (NIRS) enables the non-invasive detection of spatiotemporal characteristics of brain function near the brain surface. NIRS has enabled bedside measurement of the concentrations of oxygenated ([oxy-Hb]) and deoxygenated haemoglobin ([deoxy-Hb]) in capillary blood vessels. In the present study, we used NIRS to detect changes in the [oxy-Hb] during two verbal fluency tasks.
P-12-009 Sexually dimorphic frontal lobe development in preschoolers with ADHD: Earlier anomalies in girls M. Mahone*, D. Crocetti, B. Dirlikov, K. Slifer, M. Denckla, S. Mostofsky *Baltimore, USA Objectives: By school age, children with ADHD have sexually dimorphic frontal morphology that underlies symptom presentation. To understand development of ADHD, biomarkers should be studied longitudinally in younger children, emphasising sex differences in trajectory. Methods: High-resolution anatomical images, acquired at 3.0T, were analysed in 60 preschoolers (31 with ADHD;17 boys, 29 typically developing—TD—19 boys), each seen for three imaging visits, one year apart, beginning at age 4 or 5 years. The ADHD group was diagnosed using modified DSM-IV-TR criteria and screened for language disorders. Frontal lobe subregions were generated using an automated protocol, from which regional grey matter volumes for premotor and prefrontal cortex (PMC and PFC—summed across hemispheres) were derived. Linear mixed effects analyses were used to examine longitudinal effects of group, sex, and time on PFC, PMC, and total cerebral volume (TCV), and associations with ADHD symptomatology. Results: At baseline, there were no group or sex differences in age or SES, and no sex differences in ADHD symptoms. Across visits, there were significant effects for sex (girls \ boys), and group (ADHD \ TD) for TCV, PMC, and PFC, but not for time. There was also a significant group-by-sex interaction for PFC. Examining within sex, ADHD-related reductions were observed for girls (but not boys), in TCV, PMC, and PFC. Within the ADHD group, reduced PMC volumes predicted hyperactive/impulsive ADHD symptoms in girls, but not boys. PFC volumes and TCV did not predict ADHD symptoms in either sex. Conclusions: Anomalous prefrontal morphology among preschool girls with ADHD parallels findings observed in older female cohorts. Conversely, reduced premotor volumes among preschool girls (but not boys), and female-specific associations with ADHD symptoms, reflect the opposite pattern observed in school-aged children. These patterns in young girls with ADHD highlights earlier ‘‘normalisation’’ of premotor anomalies that sets the stage for more rapid attenuation of hyperactive/impulsive symptoms.
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Friday, 21 April 2017, 14.30 h–16.00 h
Abstracts
P-13-002 Observed dysregulation behaviours in a robot systems-control model of ADHD and bipolar disorder
P-13 Experimental models I. Szpindel*
P-13-001 Decreased glial GABA and tonic inhibition in cerebellum of mouse model for ADHD B.-E. Yoon* *Cheonan, Republic of Korea Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is a psychiatric disorder that affects *5% of school-aged children; however, the mechanisms underlying ADHD remain largely unclear. G protein -coupled receptor kinase-interacting protein-1 (Git1) is associated with ADHD in humans and ADHD-like behaviours in mice. Hyperactivity in Git1 knockout (KO) mice is reversed by amphetamine and methylphenidate, psychostimulants commonly used to treat ADHD. Git1 deficiency in mice showed shifts in neuronal excitation-inhibition balance. However, glial GABA content and tonic inhibition mediated by glial GABA in mouse model for ADHD remains poorly understood. Therefore, we investigated amount of GABA and degree of tonic inhibition in Git1 KO mice. Methods: Animals. Hybrid strain of 129S1/SvlmJ and C57BL/6. We use the littermate mouse which are git1 wild type and knock out type. Immunohistochemistry. The tissues were rinsed with phosphate-buffered saline (PBS). After two washes in PBS, tissues were blocked with PBS containing 2% normal serum at room temperature. They were incubated for 18 h in PBS containing the primary antibodies at 4 C. The tissues were rinsed with PBS 3 times, incubated 2 h with PBS containing the secondary antibody, and mounted for confocal microscopy. Primary antibodies were chicken anti-GFAP antibody (1:500), and guinea pig anti GABA antibody (1:200). Secondary antibodies were Alexa 488 conjugated donkey anti chicken IgG (1:200), and conjugated Alexa 647 goat anti guinea pig (1:200). Electrophysiology. Whole-cell recordings were made from granule cell somata located in lobules 2-5 from cerebellar slices. The holding potential was -70 mV. Pipette resistance for granule cells was typically 10-12 MX. Results: In immunohistochemistry images, we observed decreased glial GABA intensity in Git1 KO mice compared to wild type mice. In analysis, intensity of GABA in glial cells (GFAP positive GABA pixel) in cerebellum of Git1 KO mice was decreased to 60% of wild type mice. Also, intensity of GABA in non- glial cells in Git1 KO mice was attenuated (GFAP negative pixel) to 60% of wild type mice. There is no difference in GFAP intensity between Git1 KO and WT (Ref. Figure A). From electrophysiological recording data, we observed decreased tonic current from cerebellar granule cells of Git1 KO mice (ADHD model mouse) compared to wild type mice. In analysis, tonic current of Git1 KO mice was decreased to 16% of that in wild type mice. There are no significant differences in tonic current but there is in full activation current. % of full activation in Git1 KO mice was diminished to 55% of wild type mice using treatment of 5mM GABA (Ref. Figure B). Conclusions: Our study identifies a previously unknown mechanism of GIT1 deficiency in mice cause hyperactivity disorder.
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*Toronto, Canada Objectives: To implement an operational, experimentally-observable model of behavioural systems-control to aid in the discovery and elucidation of underlying regulatory mechanisms and potential clinical application to human behaviour and its disorders. To refine and validate a rigorously derived qualitative systems-control heuristic which was previously shown to differentiate between ADHD and bipolar disorder (BPD) according to their stability equilibrium characteristics. Methods: An autonomous self-balancing robot was constructed in prototypic dynamically controlled inverted-pendulum configuration. Hardware abstracted microprocessor control with positional sensor input and motor output. Code implemented proportional-integralderivative (PID) error-feedback control only. Stable, dysregulated, and unstable control state tunings were achieved through PID variable adjustment without code modification. Four identical test robots were constructed and randomised for state-blinded behavioural observation by three independent evaluators through a progression of structured and unstructured contexts. Results: Stable state robots smoothly sustained balance, position, and collision immunity independent of context. Dysregulated, ADHD state robots balanced coarsely without falling, but wandered positionally with consistent sensitivity to environmental context and structure. Collision sensitivity was balanced by rapid recovery. These robots roamed widely until settling into or against stability ameliorating contexts or structures. Unstable, BPD state robots unpredictably and inconsistently achieved passed through unsustained stable and dysregulated balance states independent of context. Collision reactivity was high and physically violent. Conclusions: Robot model behaviours were consistent with control systems theory, the clinical stability heuristic and equilibrium conceptualisations of ADHD and BPD. Unexpected behaviourally analogous model observations such as contextual sensitivity, structural amelioration, and disturbance irritability in the dysregulated ADHD state robots and violent ferocity in the BPD states lends further credibility to the paradigm. It may also suggest alternative non-executive underlying mechanisms and a greater contributory role for regulatory control in the production of human behaviour and its disorders. Conceptually and clinically, this may help to explain and differentiate between the unstable and unbounded ferocity of BPD reactivity from the dysregulated, yet bounded, reactive irritability of ADHD.
P-13-005 Research progress of traditional Chinese medicine in treating Attention-Deficit/Hyperactivity Disorder: A review X. Han*, H. Yuan *Najing, People’s Republic of China Objectives: To review research progress of traditional Chinese medicine (TCM) in treating Attention-Deficit/Hyperactivity Disorder (ADHD).
Abstracts Methods: Eighty-eight sets of effective Chinese medicine compounds employed in clinical research articles retrieved from three main Chinese databases from 1st January 2005 to 1st November 2016 were data-mined. Experimental projects were searched in the Internetbased science information system of the National Natural Science Foundation of China (NSFC) up to November 2016. Results: TCM integrates disease identification and syndrome differentiation to treat ADHD, which presents primarily as a syndrome of deficiency of liver-and-kidney yin and hyperactivity fire of heart and liver. The top five of frequently applied herbs were respectively acorus tatarinowii rhizome, polygalae radix, prepared rehmanniae radix, os draconis, radix liquiritiae, and exhibited mainly tonic and sedative effects, with tastes of sweetness, bitterness, acridity, targeting meridians of liver, heart and kidney. Ten experimental projects funded by NSFC were mostly designed to test curative effects of Chinese medicine based on the theory of dysfunction of the dopamine system. The project, research on the relationship between ADHD and immunity based on gut-brain axis, aroused foci on the relationship among ADHD pathogenesis, gut microbiota and immune system. However, the animal model of ADHD, due to lack of differentiation of syndrome, was not applicable for the research of TCM completely. Conclusions: TCM offers individualised treatment for ADHD patients through syndrome differentiation, multi-target and multiapproach. TCM is a great treasure house, although it is difficult to make quality control for the large sample multicentre, randomized, double-blind controlled trials of Chinese medicine treatment of ADHD, which finally will affect the authenticity and scientific nature of the study results. We are only just beginning to decipher its value in the field of ADHD. A greater understanding of how TCM impacts ADHD could potentially lead to novel therapies that target disease prevention and cure at an early age.
P-13-006 The effects of GRIN2B and DRD4 polymorphisms on local functional connectivity in Attention-Deficit/Hyperactivity Disorder B. N. Kim*, J. H. Yoo, S. R. Park, H. B. Kim, C. H. Choi
S33 abnormalities in local functional connectivity and its dynamic repertoire.
Friday, 21 April 2017, 14.30 h–16.00 h P-14 Non pharmacological treatment—Childhood/ Adolescence I P-14-001 Good night project: Behavioural sleep interventions for children with ADHD: A randomised controlled trial H. Alammar*, I. Kellar, H. Nash, A. Weighall *Leeds, UK Objectives: To examine the efficacy of behavioural interventions in helping 60 primary caregivers from different cities in Saudi Arabia to manage sleep difficulties in school-aged children with ADHD. Methods: The present study is a randomised controlled trial (RCT). Primary caregivers will be randomly divided into one of two groups (intervention or control ‘usual care’). Those in the intervention group will receive training by psychologists in three sessions over 3 weeks, while those in the control group, ‘usual care’, will attend their usual appointments and no intervention will be used. Assessments will be completed at three time points, baseline, post intervention and at a follow-up of two months, using subjective and objective measures. Results: Baseline and post intervention assessments will be available in March 2017. Conclusions: Management of sleep difficulties could improve sleep and daily functions for these children and their families.
P-14-002 NIRS-based neurofeedback training in virtual reality/effects on behaviour and quality of life in children with ADHD
*Seoul, Republic of Korea Objectives: We examined the association of GRIN2B, an NMDA receptor-related gene, and the dopamine receptor D4 (DRD4) gene exon III variable number tandem repeats 2-repeat allele with local functional connectivity in ADHD subjects and controls. Methods: A total of 67 ADHD and 44 controls (aged 6–17 years) were recruited and the effects of diagnosis, genotype and the diagnosis-genotype interaction of the two genetic polymorphisms on the local resting-state functional connectivity using static regional homogeneity (ReHo) and the dynamic mean and standard deviation (SD) of ReHo were examined by a general linear model. The correlation between the variables of the ReHo analyses showing significant diagnosis-genotype interaction and neuropsychological test scores were examined. Results: There were significant diagnosis (p \ 0.001) and interaction (p = 0.02) effects of GRIN2B on static ReHo in the left superior parietal cluster, and the ReHo value was positively correlated with the children&s color trails test interference scores in the ADHD with T allele subgroup (p = 0.012). There were also significant diagnoses (p \ 0.001) and interaction (p = 0.03) effects of the DRD4 gene on the dynamic ReHo SD in the right superior parietal cluster. Conclusions: These results suggest that alterations in neurotransmission of glutamate and dopamine in ADHD may contribute to
F. Blume*, J. Hudak, T. Dresler, A.-C. Ehlis, J. Ku¨hnhausen, T. J. Renner, C. Gawrilow *Tu¨bingen, Germany Objectives: We investigate effects of a near-infrared spectroscopy (NIRS)-based neurofeedback training (NFT) and an electromyogram (EMG)-based biofeedback training (BFT) in a virtual reality (VR) compared to a 2D classroom environment in children with ADHD. We hypothesise to observe improvements in ADHD behaviour and health-related quality of life (QoL) in all three groups, with superior effects in both NFTs compared to BFT and in ecologically valid VR compared to the less valid 2D environment. Methods: Eighteen children with ADHD were randomly assigned to either NFT in VR (n = 7), NFT in 2D (n = 5), or BFT in VR (n = 6). Neurofeedback trainings teach self-regulation at the level of oxygenation in the dlPFC, whereas BFT teaches self-regulation of tension of both musculi supraspinatus. Each participant received 15 training sessions and participated in comprehensive pre- and a post tests including assessment of ADHD symptoms via parent and teacher ratings (Conners-3) and of QoL (Kid-KINDLR self-report questionnaire). Changes in cortical oxygenation were assessed using NIRS during a go/no-go task. Results: As data collection is still ongoing, we only provide preliminary results from the NFT conditions here. For NFT in VR,
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S34 parents report improvement of inattention and hyperactivity-impulsivity. Teachers report improvement of hyperactivity-impulsivity only. For NFT in 2D, parents report improvement of hyperactivityimpulsivity whereas teachers report increasing inattention and hyperactivity-impulsivity. Children in the VR condition report an increase in self-esteem and wellness at school. Children from the 2D condition report an increase in wellness at school only. Conclusions: First results suggest that NFT in VR is more effective than in 2D. However, more participants need to be included and data from the BFT condition and a follow-up test must be analysed in order to allow for valid conclusions. Further examinations will need to clarify the moderating roles of expectancies and parental commitment to treatment.
P-14-003 Restricted elimination diet in children with ADHD/acute and long-term effects H.-W. Clement*, N. Blazynski, L. Overdick, I. Kaiser, C. Clement, K. Schneider-Momm, E. Schulz, C. Fleischhaker *Freiburg, Germany Objectives: The meta-analysis of Sonuga-Barke et al. from 2013 includes all non-pharmacological interventions for ADHD along very critical, including the restricted elimination diet. Among them are works of the group of Buitelaar from The Netherlands that stand out with effect sizes 3–5. The aim of the present study is to evaluate whether under a standardised restricted elimination diet in children with ADHD, the symptoms can be reduced and whether the establishment of the diet in Freiburg according to the Dutch model is possible. Methods: Of 30 interested patient&s families, 18 patients diagnosed with ADHD according to ICD ten participated in this study. Age range was between 7.3 and 13.6 years, five girls and 13 boys. The length of the restricted elimination diet was four weeks. Primary endpoint was the change in ADHD rating scale score between baseline and the end of the diet phase. Secondary endpoints were parents and teachers abbreviated Connors rating scale. Group differences were calculated with ANOVA and subsequent student t-test. Results: The adherence to the diet was good, 16 of the 18 completed the diet phase. 10 of the 16 were responders with more then 40% improvement according to the ADHD rating scale. The total ADHD rating scale scores dropped to less then 50% from 31.56 ± 9.16 to 15.86 ± 8.04 (n = 16, MW ± SD). Significance was p \ 0.001, for inattention p \ 0.001, for hyperactive/impulsivity p \ 0.01, respectively. Parents Conners abbreviated rating scale data confirmed these findings. At one year follow-up about 50% of the responders still followed the dietary recommendations with persistent improvements. Conclusions: Taken together these data indicate that the restricted elimination diet followed by the reintroduction phase is a valid treatment option for children with ADHD.
P-14-006 Effects of white noise on academic performance in children with Attention-Deficit/ Hyperactivity Disorder M.-Y. Shih*, P.-L. Tsai, H.-I. Ma, Y.-S. Hwang, Y.-T. Huang, k.-C. Lin *Tainan, Taiwan Objectives: Previous studies have suggested that white noise may adjust arousal of children with Attention-Deficit/Hyperactivity
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Abstracts Disorder (ADHD) to an optimal level and enhance attention and memory performance. However, little is known about the benefit of white noise on academic performance in children with ADHD. The aim of the present study was to determine whether white noise could improve academic performance of elementary school children with ADHD. Methods: Seventeen children with ADHD in grades two through four and 17 typically development (TD) children matched for age and gender performed four academic tasks (dictation test, copy test, reading test and mathematics test) under white noise and silence condition within two weeks. Two-way repeated ANOVAs were done to compare test scores of two auditory conditions in both groups. Results: The ANOVAs showed that only the interaction effects of the dictation score (p = .052, g2p = .113) and the reading accuracy score (p = .060, g2p = .106) reached marginal significance, and the effect sizes were medium. Both scores in the silent condition were significantly lower in the ADHD group, but such disparity between the two groups disappeared under white noise conditions. Exposure to white noise led to significant improvements on dictation and reading performance for the ADHD group. Besides, the ADHD group had significantly lower scores than did the TD group on the copy and the mathematics tests under both conditions. Conclusions: We first provide evidence of the positive effects of white noise on academic performance in elementary school children with ADHD. Our findings suggest that white noise enhances dictation and reading performance in children with ADHD. We speculate these findings can be attributed to the nature of both tasks, which require more memory function. Future research with a larger population or using different academic tasks is needed to validate the findings of this study.
P-14-007 Tentative effectiveness of multi-systemic family intervention on irritability and disruptive behavior in children with ADHD M. Vuori* *Helsinki, Finland Objectives: Irritability and disruptiveness are the key features of oppositional defiant disorder (ODD) and frequently co-occur in clinically referred children with ADHD. The aim of the present study was to examine the effectiveness of multi-systemic family intervention on affective and behavioural difficulties in children with ADHD. Methods: The prospective observational study was conducted in Finland. The time-limited intervention programme is designed to link the home and school settings to address the needs of children with neurodevelopmental conditions. Of the 124 children involved in the study, 94 children (mean age = 9.4 years, 17% female) fulfilled diagnostic criteria for ADHD (28 children had co-occurring conduct disorder). Repeated measures were analysed using linear mixedmodel design. Results: By parent reports, irritability (t = -3.59, p = .001) and disruptive behaviour (t = -2.34, p = .021) in children decreased after one year of treatment regardless of gender and age of the child, and cooccurring conduct disorder. Significant main effect of gender of the child (t = 2.05, p = .043) indicated that boys showed higher levels of overt disruptive behaviour before and after the treatment relative to girls. Parental depression was related to higher levels of irritability (t = 3.36, p = .001) and disruptiveness (t = 2.24, p = .026) in children after controlling for other variables. By teacher report, children did not show improvements in irritability (t = -1.41, p = .165) or disruptive behaviour (t = -0.68, p = .501) in school settings. Conclusions: Cognitive-behavioural family-based treatments are associated with improvements in ODD symptoms in children with
Abstracts ADHD. Despite improvements, children with ADHD are at risk for continued affective and behavioural difficulties across settings, even when treated with intensive psychosocial interventions. In particular, there is need to focus on strategies aimed at strengthening children’s self-regulation skills and social adjustment in school settings.
P-14-008 Multilevel modelling of neurofeedback EEGlearning in children and adolescents with ADHD A. Zuberer*, F. Minder, R. Drechsler, D. Brandeis *Zurich, Switzerland Objectives: Over the past years neurofeedback (NF) has gained increasing popularity as a training method for children and adults with ADHD. Analyses of NF training efficacy usually focus on clinical pre-post improvements, but ignore specificity, e.g. whether or not children with ADHD gain control over their brain activity during the training sessions. It is still unknown why some children are ‘‘good learners’’, while others seem unable to regulate their brain activity. The goal of the present study was to evaluate factors that might influence EEG-learning performance and to analyse the impact of EEG-learning on clinical outcome. Methods: Forty-eight children with ADHD (aged 8–16 years; mean 11.1y, SD 2.1) participated in 15 double sessions of NF training of slow cortical potentials (SCPs). SCP NF training may be used to promote self-regulation of brain activity independently from individual EEG patterns, as short term changes of brain activity—either activation or deactivation—are fed back and trained. Stimulants were allowed on condition that the dose was kept stable during the training period. Severe comorbidities were excluded. For the analysis, a multilevel modelling approach with linear mixed effects models was deployed. Results: We found differential EEG-learning effects for both training conditions: children learned better to activate than to deactivate their brain activity. Moreover, EEG-learning was highly dependent on age and on medication. The inclusion of ADHD symptom severity or pre/post changes in ADHD symptom ratings did not improve the model fit. Conclusions: By using a linear mixed models approach, this analysis takes into account inter- and intra-subject variability and thereby results in more precise findings as compared to traditional methods. We also conclude that the association between EEG-learning and clinical outcome in NF training deserves further examination.
Friday, 21 April 2017, 14.30 h–16.00 h P-15 Non pharmacological treatment—Childhood/ Adolescence II P-15-005 Efficacy of a device that combines neurofeedback, motion biofeedback and cognitive attention training for ADHD in children: A randomised single-blind, controlled interventional study J. Johndrow*, S. Vaishnavi *Olympia, USA Objectives: To assess the impact of a device (NeuroPlus) that combines neurofeedback and motion biofeedback with cognitive attention
S35 training on cognitive and behavioural symptoms in children with ADHD. Methods: Subjects aged 8–13 years diagnosed with ADHD were randomised into the treatment group or control group. Out of 60 subjects screened, 26 subjects enrolled in the treatment group and 23 subjects in the control group. Subjects in the interventional group used the NeuroPlus system for 30 min, three times per week, for ten consecutive weeks (for a total of 30 sessions, with 900 min of system use). The control group had treatment as usual. Subjects could be on or off ADHD medications, but had to maintain their treatment as long as for the duration of the study. The outcome measures included objective testing results from the Quotient ADHD system, as well as results from the Conners-3 parent assessment. Results: The treatment group performed significantly better than the control group on Quotient Motor (p = 0.006, effect size 1.22), Quotient Attention (p = 0.026, effect size 0.54), and Quotient Global Index (p = 0.031, effect size 1.00). The treatment group also was significantly better than the control group on the following Conners-3 parent scores: Global index (p = 0.007, effect size 0.86), inattention (p = 0.006, effect size 0.86), Hyperactivity (p = 0.026, effect size 0.70), and learning problems (p = 0.031, effect size 0.67). The treatment group was not significantly different from the control group on oppositional defiance, executive functioning, and aggression on Conners-3. Conclusions: This study showed that a device that combines multiple modalities (neurofeedback, motion-based feedback, and cognitive attention training) can significantly improve core ADHD symptoms in children over ten weeks. The improvement was seen with both objective measures (as measured by the Quotient ADHD system), as well as subjective measures (as measured by the Conners-3 parent assessment). A larger trial with a longer assessment period may be beneficial to assess for long-term benefits.
P-15-006 Early identification of and facilitation for children with symptoms of ADHD in preschool R. Tangen*, K. Larsen, Y. Haugland *Oslo, Norway Objectives: Children with ADHD spend most of their day in kindergarten or preschool. To ensure positive development it is essential that preschool staff have good knowledge on facilitation and teaching of preschool children with ADHD. This study sought to increase knowledge on early identification of ADHD symptoms in preschool-aged children, and education and facilitation for those children for preschool staff, educational advisors and parents. The study investigated whether a teaching and supervision programme for professionals and parents would increase the knowledge of early symptoms associated with ADHD, and on facilitation and education for those children. Methods: The educational team and parents of 15 preschool children with symptoms associated with ADHD was included in the study. Pre-programme focus group interviews assessed participants& expectations, current knowledge and attitudes. In addition to serve as a baseline measure the information from these interviews influenced the content of the teaching and supervision programme (TSP). The TSP included lectures, group assignments with supervision, and bring-home assignments between teaching sessions. The themes for the teaching and supervision programme was; (1) General information on ADHD, (2) Assessment and parent-professional cooperation, (3) Facilitation for children with ADHD
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S36 symptoms, (4) Effective strategies for challenging behaviours, (5) Risk and success factors for inclusion. The post-programme focus group interviews assessed self-experienced learning and changes in attitudes. Results: The analysis of focus group interviews and notes of participating teams made during assignments indicates that participants experience increased knowledge on early identification of symptoms associated with ADHD in preschool-aged children. Further, the analysis clearly indicated that participation in the TSP lead to increased knowledge on facilitation and education of preschool children with symptoms associated with ADHD, and that the participation in this study leads to changes in educational practices. Conclusions: This study implemented a model to increase competence in professionals and parents on ADHD-related behaviours. This study indicates that this model is effective in increasing knowledge and alter practices.
P-15-007 The effect of cognitive computer training on cognition and symptoms in children with AttentionDeficit/Hyperactivity Disorder (ADHD): Results from a randomized, controlled trial A. Bikic*, J. F. Leckman, T. Ø. Christensen, N. Bilenberg, S. Dalsgaard *Odense, Denmark Objectives: To date very few trials have examined the effect of cognitive training targeting multiple cognitive functions. Our multicenter randomized clinical superiority single blind trial investigated the effect of a computer-training program targeting multiple cognitive skills, mainly executive functions, on cognition, symptoms and functional outcome. Methods: 70 children with ADHD, aged 6–13, were randomized to intervention or control group. The intervention group used ACTIVATETM for 40 min a day, six times a week for eight weeks and both groups received treatment as usual (TAU) and were assessed in regard to cognitive functions and symptoms after 8 weeks of intervention and in a 12- and 24-week follow-up. Results: There were no significant differences in the primary outcome, sustained attention or the secondary outcomes ADHD-RS and BRIEF. The intervention group showed a significant and sustained difference in an objective planning ability test (p = 0.006), that was sustained at the 12- (p = 0.035) and 24-week follow up (p = 0.017). An exploratory analysis showed that children with ADHD-Inattentive subtype presented significant improvements in planning ability, working memory, impulse inhibition and also on the parent-rated BRIEF metacognition index, while children with ADHD-combined subtype only showed planning ability improvements. Conclusions: Training multiple cognitive functions does not significantly improve sustained attention or ADHD symptoms, but it might durably improve the ability to plan and the intervention might be most effective for the ADHD-Inattentive subtype. Before dismissing cognitive training as a possible treatment option, it would be important to test more complex cognitive interventions that allow individually tailored training. Considering that ADHD is a very heterogenic disorder at the individual level, future studies with larger samples should also investigate effects of broader cognitive interventions at subgroup levels.
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P-15-008 Treating ADHD symptoms with auditory or vestibular stochastic noise: Empirical findings from humans and in rat models of ADHD G. So¨derlund*, F. Bergquist *Sogndal, Norway Objectives: Environmental noise is typically perceived as detrimental to cognitive performance. Counter to this notion, sometimes sensory noise improves neural function, and this appears more pronounced when function is impaired to start with. People with attention deficits and/or ADHD are especially vulnerable to distraction under many conditions, but may nevertheless improve performance when exposed to sensory noise. Our research group have in repeated studies shown improved performance on various cognitive tasks, both in ADHD patients and in inattentive people without a diagnosis. Based on these findings we have developed an iPhone/iPad application, Smartnoise, which utilize the benefits of noise exposure during demanding cognitive tasks, like school work. The Smartnoise tool is portable and easy to use in the classroom, but also at home during homework. This project aims to investigate whether an iPhone application can be used to facilitate schoolwork without interfering with the teaching or other possible distractors provided by the iPhone per se. Methods: The Smartnoise application contains three components: i) three cognitive tests that investigate whether the user benefits from noise or not; ii) my noise, the actual noise that should be used during work; iii) a feedback system, showing which subject they worked with, for how long, and how successful each session using the app has been. This data can be seen and analyzed in both the app and on our webpage www.smartnoise.se. Results: Results are yet to come. During this spring, we are running two pilot studies, one in Norway and one in Sweden to test the reliability of the application. Beyond this, we also like to get feedback from the users regarding whether there is a demand for additional functions within the application. A full scale randomized control trial is planned for autumn 2017.
P-15-009 Mental health integration in primary care: Preliminary results from an ADHD programme in a family health team W. Gomaa*, P. Robaey, K. Pajer, W. Gardner, M. McCann *Ottawa, Canada Objectives: Although integrating mental health care into everyday primary care practice is easy to promote, the process is not evident, especially with children. Our model of Mental health integration (MHI) promotes three essential primary care practice changes: (1) it improves the detection, monitoring, stratification and management of mental health and physical problems, (2) it matches and adjusts treatment and intervention by tracking evidence of complexity and inadequate response, and (3) it reinforces the active role of the patient in ongoing interactions with the team to promote adherence and selfmanagement. Methods: We implemented the MHI model in the context of the family health teams (FHTs) in Ontario, focusing first on ADHD detection, treatment and monitoring. FHTs are primary health care organisations that include a team of family physicians, nurse practitioners (NP), registered nurses, social workers, dietitians,
Abstracts and other professionals who work together to provide primary health care for their communities. The NP collects standardised diagnostic and outcome information and includes the PCP or other members of the team at each turning point of the follow-up. Medication is adjusted following the Texas children’s medication algorithm. She also defines the care management level, which involves a developmental paediatrician, or a child psychiatrist from a university affiliated outpatient clinic. Results: Primary outcomes are externalising (especially ADHD) and internalising symptoms, as well as quality of life. Feasibility data will be presented with regard to the resources required for the programme, human and data management needs, and the outcome changes after the programme implementation. Conclusions: This pilot study will allow proposing an ADHD integration programme that will be proposed to the 184 family health teams in Ontario, serving over three million Ontarians.
P-15-010 Effects of neurofeedback training on reducing emotional and behaviour problems in children with ADHD: A pilot study in Taiwan L. Y. Shyu*, C. B. Yeh, A.-T. Fu *Taipei, Taiwan Objectives: Emotional problems in children with ADHD are considered an important issue for clinicians. Researchers had found that emotion dysregulation was linked to the symptoms and neurobiological deficiency. Objectives of the current study were to examine the effects of neurofeedback (NF) training on reducing emotional and behaviour problems in children with ADHD. Methods: Participants were 18 children aged 7–12 years and their parents. NF training consisted of 40 sessions, were held 2–3 times per week. Each session lasted 60 min. NF comprised theta/beta training on the vertex (Cz). CBCL were rated by parents to evaluate children&s emotional and behaviour problems. CPT-II and WISC-IV were used to assess children&s cognitive function. Posttreatment evaluations were carried out after the last training session. Follow-up measurements were held six month after the last session. Conclusions: NF training adjusted abnormal EEG and was effective in improving intelligence, symptoms and emotional/behaviour problems in children with ADHD. Children learned that they have to keep focus and calm in order to get high scores during NF programmes. Again and again, after 40 sessions, children try to control their behaviours and emotions. In the future, this study will add control groups for a more complete comparison.
Friday, 21 April 2017, 14.30 h–16.00 h P-16 Pharmacological treatment children and adolescents I P-16-001 Effect of methylphenidate on attentional fluctuations and slowness in ADHD children with and without epilepsy P. Berquin*, L. Querne, E. Bourel-Ponchel, A.-G. Le Moing *Amiens, France
S37 Objectives: Methylphenidate is an effective treatment for children with epilepsy with ADHD criteria (EPIL + ADHD). Methylphenidate also improves performance during cognitive tasks. However, effects on sensorimotor versus attentional processes have been poorly investigated in these children. In ADHD, methylphenidate improved very slow response times (RT) which are linked to attentional fluctuations, rather than sensorimotor speed, as showed by RT-distribution analyses. The aim of the study was to compare the effect of methylphenidate on attentional fluctuations and sensorimotor processes in ADHD children and in children with epilepsy and ADHD. Methods: The study included 117 children equally divided in three groups (EPIL + ADHD; ADHD; Control) strictly appeared for age, sex and WISC-IV (diagnostic for EPIL + ADHD and ADHD referred to DSM-IV criteria assessed by a multidisciplinary evaluation). Children realised a visuomotor task with and without methylphenidate for EPIL + ADHD and ADHD groups. Parameters analysed were the errors, mu and tau: Mu estimating the sensorimotor speed and tau the skewness of very slow responses by ex-gaussian modelling of RT-distribution. Results: Statistical analyses after Holm-Sidak correction (k = 10, p and a \ 0.05) showed that methylphenidate improved errors (p \ 0.0001) and tau (p \ 0.0001) and had a marginal effect on mu in EPIL + ADHD and ADHD groups. Independently of methylphenidate, mu was higher in the EPIL + ADHD group than in the control group (p \ 0.001) (no difference was found for ADHD versus control groups). Methylphenidate normalised errors and tau in the ADHD group, but only errors in the EPIL + ADHD group (EPIL + ADHD and control groups differences for tau: p \ 0.005). Conclusions: The effects of methylphenidate were quite similar in EPIL + ADHD and ADHD groups: Methylphenidate strongly reduced errors and attentional fluctuations in both groups but the effect on sensorimotor processes was mild. The slowness during the task was not improved with methylphenidate in the EPIL + ADHD group. Methylphenidate improves attention but not sensorimotor processes in epileptic children with ADHD.
P-16-002 A posteriori individualisation of methylphenidate regimens in ADHD treatment P. Robaey*, G. Bonnefois, J. Li, F. Nekka *Ottawa, Canada Objectives: We first developed an a priori population pharmacokinetic (Pop-PK) strategy to assess the expected performance of a medication regimen (defined by the number, times and dosages) at group level. Probabilistic conceptualised time- and concentrationbased therapeutic indicators are computed and combined into a global performance index. We developed an a posteriori approach to select the best individualised regimen. Methods: A posteriori empirical Bayesian estimation approach is integrated into the previously developed a priori methylphenidate dose adaptation algorithm in order to optimise the dosing regimen for a population or a specific group. Five hundred (500) patients are simulated based on the population pharmacokinetic model. For each of the 500 in silico individuals the parameters of the model are estimated and our a priori algorithm used to select the optimal regimen with the best performance. Further, we relaxed the constraints on the coefficient of variations (CV) of the different Pop-PK parameters while keeping values within the range of CVs estimated by the PopPK model and estimated the performances for all models. Results: The most frequent regimen was the reference regimen but almost 40% of the patients needed a posteriori dose adaptation. Clearance was the only key parameter for individualising methylphenidate dosing regimens. In order to demonstrate the relation
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S38 between the Pop-PK parameters and the global performance, we simulated 1000 subjects and plotted the performance against the parameters. Considering an error risk of = 5%, an individual clearance below 210 L/h or above 420 L/h requires the use of the Small or the Large dose, respectively. For an error risk of = 1%, these clearance values should be below 230 L/h or above 370 L/h, respectively. Conclusions: The individualisation of the methylphenidate use is feasible based on Bayesian approach. To allow its clinical application, these in silico findings should be clinically confirmed.
P-16-003 Selecting the best option among comparable methylphenidate regimens using a performance-based algorithm P. Robaey*, S. Soufsaf, G. Bonnefois, J. Li, F. Nekka *Ottawa, Canada Objectives: We developed an a priori computational strategy to assess the expected performance of a medication regimen (defined by the number, times and strengths of doses) at group level. Probabilistic conceptualised time- and concentration-based therapeutic indicators are computed based on a therapeutic box (a time interval during which the drug concentration to be between predefined limits) and combined into a global performance index. As different long-acting formulations have different pharmacokinetic profiles, physicians are more frequently combining them with short-acting forms in order to meet the specific patient&s needs. Selecting which combination would best meet a patient&s need leaves a lot to subjective judgement. Our objective is to provide a performance-based algorithm to support the decision process. Methods: Based on a population pharmacokinetic model of the different methylphenidate formulations available, we simulated 1000 subjects and computed the corresponding global performance score. At first, we rank the regimens according to the proportion of subjects with a performance higher that 80%, and define the best one as the regimen with a significantly higher proportion of subject above this threshold. If regimens are equivalent, we select those with the lower total daily dose, and among them those with the lesser complexity (fewer formulations and administrations). Results: This computational approach allows finding different medication regimens with comparable performance and ranking them according to the criteria. The clinician can also give different weights to these criteria to facilitate the selection of the best regimen for a specific situation. Conclusions: This strategy allows a physician to select between different medication regimens to meet the needs of patients. When shifting from one long-acting formulation to the other, or from shortacting to long-acting, this algorithm allows selecting the optimal formulations, strengths, and times of administration.
P-16-004 Herb-drug interactions in paediatric Attention-Deficit/Hyperactivity Disorder: Examining the safety of herbal medicines
Abstracts herbal medicines and prescription drugs in paediatric ADHD patients. Methods: To gauge the prevalence and risk of herb-drug interactions among paediatric ADHD patients (aged 0–18 years), we systematically searched the FDAble database for adverse event reports involving commonly used herbal medicines with prescription drugs for ADHD. In-vitro enzyme inhibition assays were performed for screening and dose response relationships to determine the inhibitory potential of select herbal medicines on enzymes involved in ADHD drug metabolism. The phytochemical profile of select herbal medicines was obtained using high performance liquid chromatography to confirm presence of bioactive substances. Data will be analysed using one-way analysis of variance. Results: We identified 20 cases on FDAble database involving six herbal medicines. In-vitro data suggests ginger, goldenseal, green tea, kava kava, rhodiola, rosemary, and St. John&s wort exhibit high inhibitory potential for carboxyslesterase 1, cytochrome 2D6 and cytochrome 3A4; all responsible for metabolism of ADHD drugs. According to the dose response data, the lowest IC50 were that of goldenseal for cytochrome 2D6, rhodiola for cytochrome 3A4 and carboxylesterase 1, implying of all herbal medicines studied, they may be the most potent for the respective enzymes. Conclusions: While natural health products offer potential benefits and risks, additional research is vital to guide open discussion and evidence-based decision-making between physicians and families. Together, the in vitro and clinical AE data offer otherwise lacking insight on the safety of HM in paediatric ADHD.
P-16-005 A personalized medicine approach to ADHD: Patient factors in selecting ADHD pharmacological agents N. Amaladoss* *Hamilton, Canada Objectives: There are a number of varied compounds available for the treatment of ADHD, however clinical psychopharmacology and predicting treatment response remains somewhat of a challenge. Methods: This retrospective chart review conducted in a real world setting, involved analysis of patients treated with ADHD to review if there were any unique factors in the patient profile. Review and subsequent analysis were done at a ADHD specialist clinic. Results: The preliminary findings shed light on the heterogeneity of ADHD presentations with respect to symptomology, gender, ethnicity and comorbidities and offer predictors of response to various classes of medications currently available in the treatment of ADHD. Conclusions: No conflicts of interest to declare in the preparation of this poster presentation.
P-16-006 Factors related to dropout from methylphenidate of adolescents with ADHD D. Guizar-Sa´nchez*, F. De la Pen˜a-Olvera, L. Palacios-Cruz
H. Mazhar*, P. Robaey, S. P. Guntaka, R. Galeffi, R. Liu, C. Harris *Ottawa, Canada Objectives: This study aims to gauge the prevalence of herb-drug interactions causing clinical adverse events and determines the potential risk of herb-drug interactions from concomitant use of
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*Mexico-City, Mexico Objectives: The aim of this study was to determine which clinical and psychosocial factors are related to dropout from methylphenidate in patients with attention-ADHD. Methods: This longitudinal and prospective study was conducted in the adolescents outpatient clinic at the National Institute of Psychiatry
Abstracts in Mexico City. Patients of both sexes who were 13–18 years old, were included and parents were evaluated after signing informed consent. Clinical evaluations were used to established ADHD diagnosis, comorbidities, family functioning and side effects to medication. The international MINI interview was used for assessing parental diagnosis. Adolescents were evaluated at baseline, 6 and 12 weeks later. Response was defined as reduction [50% in the SNAP-IV scale at a minimum dose of 1 mg/kg/daily of methylphenidate. Dropout was defined as ‘‘any termination of the pharmacological treatment that was against the initial agreement or was not negotiated between patient and clinicians. Results: Eighty-seven adolescents were evaluated. 65% were females, aged 14.5 years (SD ± 1.4), 73% had comorbidity with externalised disorders, 72.5% presented low socio-economic status, and 65% reported moderate symptomatology. Forty-two patients dropped out before 12 weeks (average doses of methylphenidate of 1 mg/kg/daily): Twenty (20) dropped out after two weeks, 12 dropped out after four weeks and ten dropped out after eight weeks. Comorbid externalised disorders (X2 = 7.08, 3 gl, p = 0.03), poor family functioning (X2 = 10.46, 2 gl, p = 0.04) severity of ADHD symptomatology (X2 = 6.46, 3 gl, p = 0.009) low socio-economic status (X2 = 6.23, 2 gl, p = 0.02) and parental psychopathology (maternal ADHD) (X2 = 13.1, 2 gl, p = 0.001) were associated with dropout. In the final multivariate model, ADHD combined subtype (p \ 0.001), comorbid externalised disorders (p \ 0.001), and levels of maternal ADHD (p \ 0.03) symptoms were related to dropout versus continue treatment (after 12 weeks). Conclusions: This study provides evidence for the involvement of clinical characteristics, maternal psychopathology, and environmental stressors in dropout from methylphenidate. These factors need to be considered by the clinician in order to avoid dropout and increase the chances of success with methylphenidate treatment.
P-16-009 Is video-assisted methylphenidate dose finding for children with ADHD a suitable procedure for medical practitioners? Results after 4-year followup H.-J. Kuehle*, T. Glaser, G. Neuha¨user *Giessen, Germany Objectives: Video-assisted observation of facial expression changes and performance during math tests allows titration of optimal methylphenidate doses for children with ADHD (Ku¨hle et al. J Attention Disorders 10, 2007). In this study—conducted in a community-based outpatient paediatric practice—patients were followed-up for four years in order to evaluate the long-term benefit of this diagnostic procedure. Methods: All patients with an ADHD diagnosis, who underwent the video-assisted dose finding procedure in 2008, were invited for a 4-year follow-up study. 19/49 patients fulfilled all eligibility criteria for statistical analysis. DuPaul’s parents rating scales, school reports and physical condition at beginning, in-between the first year and four years after video-assisted dose determination were analysed. Results: Friedman’s two-factor variance analysis and Wilcoxon’s test for paired samples showed significant improvement of parent ratings of attention, impulsivity and hyperactivity during the first year of treatment, which remained stable during follow-up. School reports improved in the first year but returned to pre-therapy-levels after four years. All children grew on the same growth percentile of the time before therapy; blood pressure remained normal. Fifteen (15) patients maintained the dosage of the first determination; three patients lowered the single dose by 5, 7.5 and 10 mgs, two patients increased their single dose by 2.5 and 5 mgs.
S39 Conclusions: Video-assisted observation of involuntary behaviours in children with ADHD supports clinical diagnostic procedures and offers sustainable long-term benefit. Moreover, the methodology is applicable in community-based clinical practice and (though not measured) improves interaction between patient and parents and the treating physician.
P-16-010 Efficacy and safety of HLD200, a novel delayed-release and extended-release methylphenidate formulation, in children with Attention-Deficit/ Hyperactivity Disorder: Results from a pivotal phase 3 trial S. Pliszka*, V. Arnold, A. Marraffino, N. DeSousa, B. Incledon, F. Sallee, T. Wilens, J. Newcorn *San Antonio, USA Objectives: To determine whether evening-dosed HLD200 improves control of ADHD symptoms and at-home early morning and late afternoon/evening functional impairments versus placebo in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Methods: This was a pivotal, randomised, double-blind, placebocontrolled, phase 3 trial of HLD200 in children (6–12 years) with ADHD (NCT02520388). Subjects had current or prior response on methylphenidate. Following a screening/washout period, subjects were randomised (1:1) to HLD200 or placebo for three weeks. After one week, the initial 40 mg dose was titrated in 20 mg weekly increments to 60 and 80 mg, as tolerated, with a one-step down-titration permitted. The primary endpoint was the ADHD rating scale (ADHD-RS-IV) total score following three weeks of treatment. The key secondary endpoints were the before school functioning questionnaire (BSFQ) and parent rating of evening and morning behavior-revised, morning (PREMB-R AM) and evening (PREMB-R PM) following three weeks of treatment. Safety measures included treatment-emergent adverse events (TEAEs), with a focus on sleep and appetite. Results: Of 163 children enrolled across 22 sites, 161 were included in the intent-to-treat population. After three weeks, children on HLD200 versus placebo achieved a significant improvement in ADHD symptoms (least squares [LS] mean ADHD-RS-IV: 24.1 vs. 31.2; P = 0.002), and at-home early morning (LS mean BSFQ: 18.7 vs. 28.4; P \ 0.001; LS mean PREMB-R AM: 2.1 vs. 3.6; P \ 0.001) and late afternoon/evening (LS mean PREMB-R PM: 9.4 vs. 12.2; P = 0.002) functioning. No serious TEAEs were reported; 1 HLD200 and 4 placebo subjects had TEAEs leading to early withdrawal. Most common TEAEs (C10%) on HLD200 were decreased appetite and insomnia. Sleep-related TEAEs were mild or moderate in severity and transient (96.6% resolved). Conclusions: Evening-dosed HLD200 was well-tolerated and demonstrated significant improvements in ADHD symptoms and both at-home early morning and late afternoon/evening functional impairments versus placebo in children with ADHD.
P-16-011 Dose proportionality and effect of food on the pharmacokinetics of HLD200, a novel delayedrelease and extended-release methylphenidate formulation in healthy adults F. Sallee*, T. Liu, J. Gobburu, A. McLean, B. Incledon *USA
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S40 Objectives: Two independent phase 1, single-centre, single dose, open-label studies were conducted in healthy adults to investigate the dose proportionality and food effects on the pharmacokinetics of evening-dosed HLD200. Methods: Study 1 had two parts: (1) two-way crossover dose proportionality evaluation of a single HLD200 dose of 20 mg and 100 mg under a fasted state in 20 healthy adults who received a medium-fat breakfast the following morning; and (2) bioavailability assessment of HLD200 (100 mg) under a fasted state in 13 subjects from part 1 who received a low-fat breakfast the following morning. Study 2 was a randomised three-way crossover food effect study of HLD200 (100 mg) administered to 18 healthy adults in fasted and fed (high-fat meal) states, and sprinkled on applesauce. Blood samples were taken over a 48-h period following dose administration. Adverse events (AEs) were also assessed. Results: HLD200 demonstrated dose proportionality for Cmax and AUC between 20 mg and 100 mg. Breakfast fat content did not affect the pharmacokinetics (relative Cmax and AUC ratios for low- vs. medium-fat breakfast: 92.3 vs. 97.0%). While HLD200 taken with a high-fat meal decreased mean Cmax by 14% (12.2 vs. 14.2 ng/mL) and extended Tmax by *2.5 h (mean ± CV: 14.3 ± 11.9 vs. 16.7 ± 11.3% hours; median: 14.0 vs. 16.5 h) versus the fasted state, total exposure was equivalent (mean AUC: 175 vs. 180 ngh/mL). There were no significant differences in Cmax, Tmax, and AUC when sprinkled on applesauce (13.7 ng/mL, 14.6 h, and 183 ngh/mL) versus the fasted state. No severe AEs were reported; all AEs were consistent with those of MPH. Conclusions: Evening-dosed HLD200 was well-tolerated and demonstrated dose proportionality. HLD200 pharmacokinetics were not affected by breakfast fat content or when sprinkled on food, and the differences observed when taken with or without food were not clinically meaningful.
Friday, 21 April 2017, 14.30 h–16.00 h P-17 Pharmacological treatment children and adolescents II P-17-001 Double-blind, placebo-controlled study of the novel therapeutic AEVI-001 in adolescents with ADHD and glutamatergic network gene mutations R. L. Finding*, D. Fitts, L. Squires *Wayne PA, USA Objectives: Loss-of-function mutations (copy number variations, CNVs) in metabotropic glutamate receptors (GRMs) and related genes have been identified in *20% of children/adolescents with ADHD, representing a population in which glutamatergic dysfunction may play a key role in ADHD pathogenesis. Children/adolescents with mutation-positive ADHD (GRM + ADHD) may be candidates for glutamate-modulating therapy. We will report results of a Phase 2 study evaluating the efficacy and tolerability of the glutamate modulator AEVI-001 in adolescents with moderate severity GRM + ADHD. Methods: Phase 2 randomized, double-blind, placebo-controlled, parallel-group study of 6-week duration in subjects 12–17 yrs of age with moderate severity ADHD (baseline ADHD-RS-5 score: C28 without conventional ADHD therapy) and GRM biomarker-positive genotype (GRM + ADHD). All ADHD medications were discontinued with appropriate washout period before randomization. 4-wk dose
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Abstracts optimization period: 100-mg b.i.d. starting dose increased at weekly intervals based on clinical response to maximal dose of 400 mg b.i.d. Optimized dose (100 mg, 200 mg, or 400 mg b.i.d.) was maintained 2 wks. Results: 101 subjects were randomized 1:1 to placebo or study drug. Baseline characteristics: male, 63%; median age, 14 yrs; median age at ADHD diagnosis, 6 years; median yrs since ADHD diagnosis, 7 years; ADHD presentation: inattentive, 29%; hyperactive/impulsive, 2%; combined, 69%. Median Baseline CGI-S score, 4. Mean Baseline ADHD-RS-5 score, 38 (range 12–54). Efficacy and tolerability/safety results to be presented, including primary endpoint (ADHD-RS-5 total score change from Baseline to end of treatment as LOCF analysis) and secondary endpoint (number and percent of subjects ‘‘Improved’’ vs. ‘‘Not Improved’’). Analyses will also include % patients meeting responder criteria defined as C30% change from Baseline ADHD-RS-5 or CGI-I score of 1 or 2. Conclusions: Subject characteristics were consistent with expectations. Efficacy and safety/tolerability results will be presented. Study sponsored by Aevi Genomics Medicine.
P-17-003 The comparison of methylphenidate and atomoxetine on cognitive functions in children and adolescents with ADHD: A meta-analysis J. Ren*, Y. Li, S. Yue, J. Yue, Q. Li, M. Lv, L. Tie *Shaanxi, People’s Republic of China Objectives: The stimulant methylphenidate (MPH) and the nonstimulant atomoxetine (ATX) are the commonly prescribed medications for ADHD. However, the comparation of their impacts on cognitive functions is less clearly understood. Our aim is to conduct a meta-analysis comparing the effects of MPH and ATX on cognitive functions in children and adolescents with ADHD. Methods: A comprehensive search of the literature was undertaken until Sept 30, 2016 using search engines Ovid, PsycINFO, ISI Web of Science and PubMed/MEDLINE. Search terms used were ‘methylphenidate’, OR ‘stimulants’, AND ‘non-stimulants’, OR ‘atomoxetine’ AND specific neuropsychological names. Randomized controlled trial (RCTs) comparing efficacy of MPH with ATX on reaction time, reaction time variability, response inhibition and working memory in children and adolescents (5–18 years) with formal diagnosis were included. Data from included studies were extracted by two reviewer and entered into Revman 5. Using a random effects model and meta-analytic regression, we assessed for heterogeneity and publication bias and adjusted for intrastudy clustering. Effect sizes were calculated as standardized mean differences (SMDs). Results: Eight randomized controlled studies with a total number of 364 participants were included in the analysis. For these 8 studies, 36 data points were obtained. Meta-analysis did not find a statistically difference in efficacy between MPH and ATX on the four aspects of cognitive functions: reaction time, SMD = -0.12 [95% CI, -0.27 to 0.04], P = 0.14; I2 = 0%; reaction time variability, SMD = -0.30 [95% CI, -0.68 to 0.07], P = 0.11; I2 = 0%; response inhibition, SMD = -0.03, [95% CI -0.20 to 0.14], P = 0.71; I2 = 0%; working memory, SMD = -0.08 [95% CI -0.19 to 0.04], P = 0.20; I2 = 0%. Conclusions: These data suggest that MPH and ATX have comparable effects on various aspects of cognitive functions in treatment of ADHD in children and adolescents.
Abstracts
P-17-004 Cognitive function in children and adolescents with ADHD receiving lisdexamfetamine dimesylate in a 2-year safety study D. Coghill*, T. Banaschewski, C. Bliss, B. Robertson, A. Zuddas *Melbourne, Australia Objectives: To measure cognitive function in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) who received lisdexamfetamine dimesylate (LDX) for 2 years in study SPD489-404. Cognitive function was assessed using the Cambridge neuropsychological test automated battery (CANTAB). Methods: Participants aged 6–17 years received dose-optimised, open-label LDX (30, 50 or 70 mg/day) for 104 weeks (dose optimisation 4 weeks; dose maintenance, 100 weeks). Cognition was assessed in the safety population using four selected tests from the CANTAB (delayed matching to sample (DMS), spatial working memory (SWM), stop signal task (SST) and reaction time (RTI). A group-wise change of [5% from baseline was considered potentially clinically significant. Results: Of 314 enrolled participants, 314 (100%) received LDX and were included in the safety population, and 191 (60.8%) completed the study. Potentially clinically significant improvements from baseline to last on-treatment assessment (LOTA) were observed for DMS Median reaction time (mean percent change, -6.5), SWM total between errors (-32.6) and SST reaction time (-25.7). Changes from baseline to LOTA did not reach potential clinical significance for DMS percent correct (mean percent change, -1.3), RTI simple median reaction time (-2.6) or RTI 5-choice median reaction time (-3.1). Conclusions: LDX treatment over two years was not associated with deterioration in cognitive function in children and adolescents with ADHD. Although some improvements in cognition were observed, the lack of a control group makes these data difficult to interpret and additional studies are required.
P-17-005 Growth and sexual maturation in a two-year, open-label clinical study of lisdexamfetamine dimesylate in children and adolescents with ADHD D. Coghill*, I. Herna´ndez Otero, M. Johnson, P. Nagy, C. A. Soutullo, A. Zuddas, B. Yan, T. Banaschewski *Melbourne, Australia Objectives: Individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) may require long-term medication. Here we evaluate the impact of treatment with lisdexamfetamine dimesylate (LDX) on growth and sexual maturation in a 2-year trial in children and adolescents with ADHD (SPD489-404). Methods: Participants aged 6–17 years received dose-optimised, open-label LDX (30, 50 and 70 mg/day) for 104 weeks (dose optimisation, 4 weeks; dose maintenance, 100 weeks). Weight, height and body mass index (BMI) z-scores were derived using the Conners for disease control and prevention (CDC) norms. Sexual maturation was assessed using the Tanner scale (participant rated as closest to their stage of development based on standardised drawings). Results: Of 314 enrolled participants, 191 (60.8%) completed the study. Mean z-scores at baseline and last on-treatment assessment (LOTA) were 0.53 (standard deviation [SD], 0.963) and 0.02 (1.032) for weight, 0.61 (1.124) and 0.37 (1.131) for height, and 0.32 (0.935)
S41 and -0.27 (1.052) for BMI. In general, z-scores for weight, height and BMI shifted lower over the first 36 weeks and then stabilised. At both baseline and LOTA respectively, the majority of participants had z-scores within one SD of the CDC mean for weight (62.7 and 67.1%), height (53.8 and 59.8%) and BMI (61.5 and 60.4%). For weight and BMI, but not height, the proportion of participants below one SD of the CDC mean increased from baseline to LOTA. At LOTA, most participants remained at their baseline Tanner stage or shifted higher, based on development of hair (males, 95.5%; females, 92.1%) or genitalia/breasts (males, 94.7%; females, 98.4%). Conclusions: Consistent with previous studies of stimulants used to treat ADHD, z-scores for weight, height and BMI decreased, mostly in the first year, then stabilised. No clinically concerning trends of LDX treatment on sexual maturation or the onset of puberty were observed.
P-17-006 Weight and height in children and adolescents with Attention-Deficit/Hyperactivity Disorder: A longitudinal database study assessing the impact of guanfacine, stimulants or no pharmacotherapy W. Spalding*, T. Banaschewski, B. Feldman, P. Gustafsson, B. Murphy, M. Reynolds, D. Coghill, G. Schneider *Lexington, USA Objectives: This study assessed the real-world impact of long-term guanfacine therapy administered alone or adjunctive to a stimulant on weight and height in children and adolescents with Attention-Deficit/ Hyperactivity Disorder (ADHD). Methods: Using data from anonymized U.S. Department of Defense electronic medical records (January 2009–June 2013), mixed-model regression analyses of longitudinal weight and height measurements normalised to z-scores were conducted for three cohorts: guanfacine (first interval of guanfacine exposure), first-line stimulant monotherapy (first interval of stimulant exposure), and unmedicated (post-diagnosis interval). Patients were diagnosed with ADHD, were aged 4–17 years at index date (initiation of any ADHD medication, or diagnosis if unmedicated), and had weight/height measurements in the year before index date and during the analysis period. Patients in the guanfacine cohort were allocated to subgroups based on previous/concurrent stimulant exposure. Results: Across all cohorts, 47,294 patients were included in weight analyses (66.7% male) and 40,738 in height analyses (67.1% male). Guanfacine monotherapy did not lead to clinically meaningful deviations from normal z-score trajectories for weight (first-line, n = 943; non-first-line, n = 174) or height (first-line, n = 741; non-first-line, n = 138). For guanfacine adjunctive to a stimulant, weight (n = 1663) and height (n = 1.339) z-scores followed declining trajectories. First-line stimulant monotherapy led to declining weight (n = 32,999) and height (n = 28,470) z-score trajectories during the first 1–2 years and 3–4 years, respectively; weight z-scores subsequently returned to pre-index date levels. In patients not receiving ADHD medication, weight (n = 11,515) and height (n = 10,050) z-scores were stable. Conclusions: This study found little evidence that long-term guanfacine monotherapy, administered first-line or non first-line, was associated with deviations from normal growth. As expected, stimulant monotherapy resulted in initial reductions in growth which attenuated over time. Guanfacine adjunctive to a stimulant led to declining trajectories in weight and height z-scores.
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P-17-007 Treatment patterns, resource utilisation, and healthcare costs associated with the use of atypical antipsychotics or guanfacine extended release in stimulant-treated children and adolescents with ADHD in Quebec J. van Stralen*, J. Lachaine, L. Ben Amor, J. Burns *Ottawa, Canada Objectives: To assess treatment patterns, healthcare resource utilization (HRU) and healthcare costs in stimulant-treated children and adolescents with ADHD in Quebec who augmented with, or switched to, an atypical antipsychotic (AAP) or guanfacine extended release (GXR). Methods: This study used healthcare claims data from 1 January 2007 to 31 March 2016 from Quebec’s provincial health plan (re´gie de l’assurance maladie du Quebec [RAMQ]) database. Individuals aged 6–17 years with ADHD were included if they had received C1 stimulant prescription and subsequently filled their first AAP or GXR prescription (index medication), without a diagnosis for which AAPs are indicated. Results: Overall, 1.327 individuals were included (AAP, 1098; GXR, 229). At baseline, the mean age was approximately 10 years (AAP, 10.7; GXR, 10.1) and most participants were males (AAP, 77.1%; GXR, 76.4%). Twelve-month rates for discontinuing, augmenting or switching were 54.3, 22.5 and 11.7%, respectively, for AAPs, and 55.5, 17.0 and 17.5%, respectively, for GXR. With both AAPs and GXR, mean per patient total healthcare costs were significantly higher in the six months after than the six months before initiating the index medication. The mean number of all medical services used and mean all medical costs were significantly higher in the six months after initiating AAPs than the six months before, driven mainly by more psychiatric department visits and higher incurred costs. After initiating GXR, however, the mean number of all medical services used and mean all medical costs were unchanged or tended to be lower. Conclusions: In stimulant-treated children and adolescents with ADHD, augmenting with, or switching to AAPs or GXR was associated with similar rates of subsequent treatment changes and higher total healthcare costs for both AAPs and GXR; AAPs and GXR were not compared directly, however, all medical costs increased significantly for AAP-users but not for GXR-users.
P-17-008 Long-term safety and efficacy of guanfacine extended release in children and adolescents with ADHD J. Newcorn*, J. A. Ramos Quiroga, B. Dirks, J. Gu, M. Huss
Abstracts adverse events (TEAEs) were reported in 177 patients (82.7%). TEAEs reported in C10% participants were somnolence (77 [36.0%]), headache (61 [28.5%]), fatigue (43 [20.1%]) and nasopharyngitis (25 [11.7%]). No TEAEs of syncope were reported. Serious TEAEs and TEAEs leading to discontinuation were reported in 10 (4.7%) and 7 (3.3%) participants, respectively. There were no deaths. There were small changes from baseline to final assessment in mean (standard deviation) supine pulse (-5.5 [12.98] bpm) and blood pressure (systolic, 0.6 [9.32] mmHg; diastolic, 0.2 [9.17] mmHg). A decrease in ADHD-RS-IV total score was maintained throughout the 2-year study with a mean (standard error of mean) change from baseline of -19.8 (0.84; nominal p \ 0.0001) at the final on-treatment assessment. Conclusions: This 2-year European study confirms that GXR at doses up to 7 mg/day is well-tolerated during long-term use, with a safety profile similar to that previously observed. Improvements in ADHD symptoms were maintained throughout the study.
P-17-009 Clinical investigation of children with ADHD treated with atomoxetine oral solution T. Ichiyama*, N. Ishikawa, H. Matsufuji, H. Isumi, Y. Sugio *Shunan, Japan Objectives: Atomoxetine oral solution has been developed for patients who have difficulty swallowing capsules, and was first sold in Japan in November 2013. We investigated clinical features including validity, safety, and tolerability of the atomoxetine oral solution for children with ADHD. Methods: The subjects were 42 children with ADHD (male: female = 35: 7) who were treated with the atomoxetine oral solution in our hospital from December 2013 to November 2016. We investigated their clinical records retrospectively to analyse clinical features of the affected children, and validity, safety and tolerability of the atomoxetine oral solution. Results: The ages of diagnosing ADHD of the subjects were median 6.5 years (ranges 4.3–10.1 years). The ages of starting treatment with the atomoxetine oral solution for the subjects were median 6.9 years (ranges 4.3–13.6 years). The subjects who could continue to take the atomoxetine oral solution were 23 of 42 children (55%). The solution worked well in 18 of the 23 children (78%). Nineteen children discontinued to take the solution. The reasons were as follows: Twelve (12) children disliked taking the solution tasting bitter, four children were in bad humour, two children had suspected drug eruptions, and one child had continuous nausea. Conclusions: Our results suggest that the atomoxetine oral solution is useful for children with ADHD who cannot take capsules. It is likely that a bitter taste of the solution is its weakness.
*New York, USA Objectives: To assess the long-term safety and efficacy of the nonstimulant treatment guanfacine extended release (GXR) at doses up to 7 mg/day in children and adolescents (aged 6–17 years) with Attention-Deficit/Hyperactivity Disorder (ADHD). Methods: SPD503-318 was a phase 3, 2-year, open-label extension study for European participants of the GXR clinical trials SPD503315 and SPD503-316. Participants received dose-optimised GXR (maximum permitted dose: children, 4 mg/day; adolescents, 4–7 mg/day depending on weight). Results: Of 215 enrolled participants, 214 were included in the safety population and 133 completed the study. The mean age of participants was 11.7 years; 73.8% were male. Overall, treatment-emergent
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P-17-010 Increase in prescription rates of ADHD medication from pharmacy data within an urban child and adolescent specialist clinic in London: There was a decline in the use of newer preparations D. Perera*, O. Moghraby, M. Akhunbay-Fudge *London, UK Objectives: The literature shows an increasing trend in the prescription of psychotropic drugs used to treat Attention-Deficit/ Hyperactivity Disorder (ADHD) in children and adolescents between
Abstracts 1987 and 2016, especially in the United States. Few studies have addressed prescription rates in ADHD of both stimulant and nonstimulant medication. This study aims to investigate the prescription rates and trends of both stimulants and non-stimulants use for ADHD within an urban specialist child and adolescent clinic in London, United Kingdom (Lewisham). Methods: Prescription data from April 2015 to February 2016 was obtained from prescriptions issued at local pharmacies and expenditure attributed to Lewisham clinic for all medication. These were divided into stimulants (methylphenidate and dexamphetamine; extended- and immediate-release preparations) and non-stimulants (atomoxetine and clonidine). We also investigated individual medication trends. Individual drug unit costs were calculated to determine total numbers of units sold, with one drug unit assumed to be equivalent to a single prescribed dose per patient. Results: A total of 12,634 units were prescribed during the study period for an estimated 330 patients. Preliminary data demonstrated an absolute increase in medication prescribed (938–1688 units prescribed of all medication, per month). There was a trend towards the prescription of stimulants (83%) over non-stimulants (which declined), especially methylphenidate (93% of total stimulants). There was a decline in the use of a newer formulation (lisdexamfetamine) over the year (57%). Individual patient specific data was not available. Conclusions: There was a modest increase in prescribing rates. Rates of stimulant use was in line with widely reported evidence on efficacy. There was a greater tendency towards extended-release preparations but a decline in use of newer available formulations (lisdexamfetamine). Future studies are required to investigate trends in clinics locally and to obtain data on individual patient data. This will better inform future prescribing behaviour to improve quality of care.
Friday, 21 April 2017, 14.30 h–16.00 h P-18 Treatment adults P-18-001 Characteristics of a freelance community sample with ADHD and their views on online therapy M. Bosman*, J. Swart *Walnut CA, USA Objectives: Online therapy and self-help programmes have garnered much attention recently as a cost-effective and convenient solution to reduce the symptoms associated with a multitude of moderate psychiatric conditions, including Attention-Deficit/ Hyperactivity Disorder (ADHD). With a survey design, this research study set out to explore the characteristics and willingness of participants in the mechanical turk community to use online mental health self-help programmes and identify predictors of that behaviour. Methods: Positioned as marketing research for an online self-help initiative, 184 respondents limited to the United States completed the online survey, which included demographic questions, the General Health Questionnaire-12 (GHQ-12), the adult ADHD self-report scale (ASRS), and others. Results: As expected, the ADHD group scored higher on the GHQ-12 and expressed a higher willingness to enrol in an online therapy programme compared to the non-ADHD group. The mean age of the ADHD group was also lower, peaking in the 20s, while previous experience with mental health issues and conventional therapy
S43 predicted the participants&willingness to consider online therapy as an option. Representing just more than half of the overall sample, those somewhat likely and extremely likely to qualify for a diagnosis of ADHD, respectively at 36.4 and 19.0%, are markedly overrepresented compared to the point prevalence among adults in the general public as reported by the DSM-V and elsewhere. Conclusions: The research suggests that individuals in the online gig economy have a positive attitude towards online mental health selfhelp programmes. Those with self-test scores suggesting a high likelihood of ADHD tend to score lower on general psychological health and are more likely to have experienced mental health services. They are also even more amenable to try online self-help programmes than the non-ADHD gig workers. These findings are significant to target adults with ADHD in the online communities.
P-18-002 Stressed young males with ADHD: Transition to adult healthcare in a naturalistic setting J. Rademacher*, S. Dechering, S. Michalek *Du¨sseldorf, Germany Objectives: ADHD is associated with a broad range of negative outcomes and a high rate of persistence into adulthood. There is often an interruption in management of the disorder when adolescent patients are being transitioned to adult health care services. During this transition period, young adults are prone to divert their stimulant medication and develop substance abuse disorders. They face increased social demands and may feel overwhelmed. National guidelines for ADHD are well aware of this situation. It is recommended to ensure communication between primary and secondary care services. Methylphenidate should then be the first-line treatment. Behavioural psychotherapy should be considered for adults who are stabilised on medication but have persisting functional impairment. We report our findings on highly stressed young adult male patients who may benefit from metallisation-based psychodynamic group psychotherapy. Methods: A cross-sectional pilot study was conducted on 100 outpatients consecutively attending an ADHD clinic (Psychosomatic Medicine, Duesseldorf). Psychiatric ADHD diagnosis (DSM-V) was evaluated with the CAARS and the WURS scales. Psychiatric comorbidity was assessed clinically, psychological distress by use of the SCL-90-R (GSI), alexithymia with the TAS-20 (score [ 61) and personality disorders (SCID-II). Mini-ICF-APP social functioning scores were obtained. OPD-2 was used for analysis of relationship patterns. Results: Thirty-six (36) patients did not fulfil the criteria for ADHD, 33 patients were of the combined subtype, 27 were inattentive and four hyperactive. A subgroup of 25 male patients was identified by age (18–29 years), all with a prior diagnosis of ADHD. Eighty percent (80%) were receiving a stimulant therapy and/or behavioural psychotherapy with an interruption of their treatment before referral to our service (mean pause 35 months, SD 30). Comorbidity: Mood disorders (52%), (history) of substance use (48%), mainly cannabis (36%). Half of the patients (48%) were diagnosed with a personality disorder (avoidant 20%, dependent 16%). Psychological distress was high (mean GSI 1,16; SD 0,68), as was the proportion of patients with alexithymia (52%). MiniICF-APP social functioning scores indicated a low-moderate level of impairment. Most of the patients (72%) showed dysfunctional relationship patterns and had a history of aggressive behaviour (64%). Conclusions: For subgroups of patients with ADHD it may be useful to expand the scope of psychotherapy as outlined by the national guidelines. Mentalization-based group therapy for stressed young males with ADHD may be an ideal psychodynamic training ground
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S44 for deficits in social functioning. Thus, the treatment’s basic aim could be to re-establish mentalising when it is compromised by stress.
P-18-003 Clinical characteristics of an adult ADHD with comorbid anxiety disorder sample M. Van Ameringen*, B. Patterson, W. Simpson, J. Turna, K. Pullia *Hamilton, Canada Objectives: Adult ADHD is highly comorbid with mood and anxiety disorders at rates up to 85%. Stimulant medications are the first-line agents in the treatment of ADHD, yet only two studies have examined these agents within comorbid populations. Given the high degree of comorbidity between anxiety disorders and ADHD, and the limited evidence, we are conducting a prospective trial examining the stimulant lisdexamfetamine dimesylate (LDX) in adult ADHD with comorbidity. Methods: The study is randomized, double-blind, 18-week crossover trial of flexibly-dosed LDX in adults with ADHD and anxiety disorder or depression comorbidity. Outcome measures include the ADHD rating scale (ADHD-RS), the Barkley adult ADHD rating scale (BAARS-IV), the overall anxiety severity and impairment scale, the revised Padua inventory, the panic and agoraphobia scale, the GAD-7, the social phobia inventory, the quick inventory of depressive symptoms, the clinical global impression-severity scale (CGI-S), the Sheehan disability scale (SDS) and the Weiss functional impairment rating scale (WFIRS). Here, we present a preliminary analysis of the sample. Results: The sample, (n-40) was 48% male, mean age of 33.6 ± 11.4 years and mean scores on the ADHD-RS = 44.9 ± 6.0, CGI-S = 5.9 ± 0.6, BAARS-IV = 48.8 ± 9.4, suggestive of severe ADHD. GAD (92.5%), SAD (62.5%) and OCD (37.5%) were the most common comorbid conditions. No significant differences were found between males and females, symptom severity, comorbidity, ADHD subtype or impairment. A positive correlation was found between inattentive symptoms (BAARS-IV) and impairment: WFIRS r = 0.35, p = 0.03; SDS r = 0.60, p \ 0.001; while hyperactivityimpulsivity (BAARS-IV) were positively correlated to ADHD severity: ADHD-RS r = 0.59, p \ 0.001, CGI-S r = 0.57, p \ 0.001. Conclusions: Similar to previous findings, comorbidity had little impact on ADHD severity. This finding is contrary to the anxiety and mood disorder literature where comorbidity tends to increase the severity of the index disorder and has a significant impact on functional impairment and treatment response. Inattention symptoms appear to have a stronger impact on impairment, while hyperactiveimpulsive symptoms are stronger indicators of ADHD severity.
P-18-004 Comparing knowledge acquisition and practice change between ADHD and other health conditions among primary care clinicians G. Mattingly* *St. Charles, USA Objectives: Primary care clinicians receive little medical education about ADHD. This study compared knowledge acquisition and practice change between ADHD and other health conditions during day long primary care symposium provided by the National Association for Continuing Education (NACE) at eight different cities. Methods: Five hundred forty-four (544) clinicians completed presymposium evaluations to measure baseline knowledge. 1.221
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Abstracts clinicians participated in day long CME symposiums covering seven health related topics. Disease state knowledge was measured before and after each lecture. Clinicians also evaluated the clinical relevance of each lecture. The educational impact on the clinical management of patients was evaluated 4 weeks post-symposium. Results: Pre-symposium ADHD knowledge and practice confidence ranged from 2.60 to 3.03-poor to neutral, on eight assessed areas (5 point scale with 1 = Very Poor, 2 = Poor, 3 = Neutral, 4 = Good and 5 = Excellent) The lowest of any health care topic. The ADHD lecture had dramatic improvement in knowledge-87% gain, confidence-69% gain and practice strategy-82% gain. Compared to other health topics such as lipid management and congestive heart failure; post-test evaluations showed that ADHD had greater gains in knowledge (50, 38 and 87% respectively), confidence (46, 55 and 69%) and practice strategy (59% for CHF and 82% for ADHD). 97% of clinicians rated that they ‘‘learned new and useful strategies for patient care’’ and 99% said they would ‘‘implement new strategies that they learned in their practice’’ At 4-week follow-up 90% of clinicians stated they had changed practice behaviour and implemented new strategies to manage ADHD patients. Conclusions: Primary care clinicians had significant increases in knowledge, confidence and clinical comfort regarding the diagnosis and management of ADHD patients after receiving ADHD education during a general medical CME series. These gains were even more impactful than other health topics covered during the same symposium.
P-18-005 Comparison of knowledge uptake and active learning between ADHD and other health conditions among primary care clinicians receiving simulcast continuing medical education G. Mattingly* *St. Charles, USA Objectives: Primary care clinicians receive very little medical education about ADHD. This study evaluates the interest and impact of an ADHD lecture incorporated into a day-long primary care continuing medical education symposium simulcast provided by the National Association for Continuing Education (NACE). Methods: Six hundred ninety-three (693) primary care clinicians participated in simulcasts of day long CME symposium covering seven health related topics. Participants were required to complete knowledge and clinical management questions before and after each lecture to measure knowledge acquisition. Learner engagement could be measured real time during each lecture by monitoring participation, note taking and slide download. Results: As would be expected, learner engagement varied throughout the simulcast. Learner engagement also varied by health related topic. The ADHD lecture had high learner engagement with the highest slide download of any topic. The three most downloaded slides were (1) Adult ADHD medication guide, (2) Treatment options for heart failure and (3) Standards of care in diabetes management. ADHD also had the greatest ‘‘learner impact’’ as rated by a combination of slide downloads and note taking during any health topic. Conclusions: Primary care clinicians were actively engaged and showed more interest in ADHD education than other health topics during a day long primary care CME simulcast. Given access to care issues and limited prior ADHD medical education among most primary care clinicians, simulcast CME education with ‘‘active learning’’ can be utilized as a way to train primary care clinicians to better diagnose and manage patients they care of who have ADHD.
Abstracts
P-18-006 Cannabinoid therapy in a case of adult ADHD M. Koelle*, K. Heckel, G. Groen *Ulm, Germany Objectives: Stimulant therapy is the first-line pharmacological approach in adult ADHD. However, some patients do not respond to stimulants or alternative substances frequently used, such as SNRI. Cannabinoids are not recommended to treat ADHD and can result in severe adverse effects. However, some patients report symptom relief following cannabis consumption and there are clinical studies indicating a possible therapeutic efficacy of cannabinoids in other neuropsychiatric disorders, e.g. Tourette syndrome. Hence, cannabinoids may be a suitable therapeutic approach for selected ADHD patients. Methods: We report a case of adult ADHD who did not respond to stimulants and was effectively treated with cannabinoids. Results: The patient had a history of attentional problems, hyperactivity and impulsivity since primary school age. Various therapeutic approaches had failed and the patient was unable to work when he showed up in our hospital. Over the course of two years methylphenidate, amphetamine, lisdexamfetamine and atomoxetine were prescribed. There were no therapeutic effects of methylphenidate and adverse side effects occurred under amphetamine and lisdexamfetamine. Atomoxetine had no effect. Psychotherapy was helpful concerning lifestyle and general state of health but there was no effect on attentional problems and impulsivity. The symptoms were disabling, standard therapy failed and the patient reported improvement on cannabis in earlier days. Following careful evaluation and informed consent, cannabinoid therapy was started using cannabis sativa extract (oromucosal application). The patient reported clinical response on one spray per day (100 ll containing 2.7 mg Delta-9THC and 2.5 mg cannabidiol). After five months the patient started daily work again and the response was stable in clinical follow-ups. Conclusions: Despite the possible severe adverse effects, cannabinoids may be an effective treatment for adult ADHD in selected cases of adult ADHD.
P-18-007 Health-related quality of life and burden of illness at assessment in adult patients with AttentionDeficit/Hyperactivity Disorder: A chart review Y. Ginsberg*, M. Di Schiena, A.-C. Fredman, E. Medin, J. K. So¨derling, E. Ahnemark *Stockholm, Sweden Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) often persists into adulthood and is estimated to affect 3–4% of adults worldwide. Here we describe findings from an observational, crosssectional, retrospective chart review of adults newly diagnosed with ADHD in Sweden in 2013–2015. Methods: Participants enrolled from two specialist outpatient clinics in Stockholm were C18 years of age on diagnosis with ADHD. Data extracted from patient records included demographic and clinical characteristics, psychiatric diagnoses confirmed using the mini international neuropsychiatric interview (MINI), a rating of depres˚ sberg depression scale self assessment sion using the Montgomery A (MADRS-S), and an indication of health-related quality of life (HRQoL) was acquired using the self-assessed EuroQol 5-dimensions (EQ 5D) health preference instrument. Predictors of HRQoL were identified using multivariate linear regression adjusting for age, sex, education level and main income source.
S45 Results: The mean age at diagnosis of the 189 participants was 35.2 years (standard deviation [SD], 12.3), 107 (57%) were female and pharmacological ADHD treatment had been recommended for 146 (77%). Somatic comorbidities were present in 145 patients (77%), including 36 with pain and 32 with gastrointestinal problems, and 92 (49%) had psychiatric comorbidities, including 21 with comorbid depression and anxiety, 25 with anxiety only and 11 with depression only. The mean (SD) EQ-5D index score was 0.63 (0.28). In the study population, a significant decrease in EQ-5D index score (indicating poorer HRQoL) was detected with increased MADRS-S score, having several psychiatric comorbidities, female sex, not being educated to upper secondary/university level and not being in full/part-time employment. Conclusions: Individuals diagnosed with ADHD for the first time as adults have a substantial burden of illness and poor HRQoL. Patients with a high depression rating and multiple psychiatric comorbidities may have poorer HRQoL and require greater attention and resources in the management of their ADHD.
Friday, 21 April 2017, 14.30 h–16.00 h P-19 Quality of life/Caregiver burden I P-19-001 Ratio of topic initiation to topic maintenance in children with ADHD W. Al-Dakroury* *Riyadh, Saudi-Arabia Objectives: This study investigated verbal pragmatic skills in children with attention deficit hyperactivity disorder (ADHD). It examined quantitatively the topic related skills which is represented by ratio of topic initiation to topic maintenance in the children with ADHD compared to age-matched typically developing (TD) children. The authors decided to compare ratio of topic initiation to topic maintenance, rather than compare the amount of topic initiations and topic maintenance as separate phenomena to avoid the possible difference in the amount of verbal output between participants with ADHD and TD participants. The following research question was investigated, is the ratio of topic initiation to topic maintenance in children with ADHD higher than in typically developing children matched in age and gender? Methods: The participants were twenty 4–5 year old boys. Ten were typically developing and ten had a diagnosis of ADHD. A 30 min sample of speech during free play was collected from each child in conversation with an examiner. All sessions were recorded on DVD using two video cameras. Transcription and coding systems were used to analyze the data. Comparisons were made between the TD children and the children with ADHD using quantitative techniques. Results: The study results showed that children with ADHD have a significantly higher topic initiation to topic maintenance ratio compared to TD participants in the sessions with the examiner. Conclusions: The differences were interpreted as evidence of the negative effect of the core behavioural characteristics of ADHD on verbal pragmatic skills and the presence of weak discourse skills in children with ADHD compared to TD age-matched children. The clinical implications are that very careful attention is needed in assessing children with ADHD to determine the nature and the extent of their language-use difficulties. Language-use difficulties exhibited by children with ADHD may be associated with a lack of social competence, which will be reflected in their conversational skills.
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P-19-005 The positive aspects of ADHD: A small-scale qualitative investigation about the views of adult males with ADHD J. Sedgwick*, A. Merwood, P. Asherson, F. Mowlem *London, UK Objectives: To investigate positive aspects that can support high functioning, accomplishment and flourishing in ADHD life. Methods: A qualitative design comprising open ended interviews. The views of six adult males with ADHD were explored by asking them about the ‘‘advantages and disadvantages of ADHD.’’ The interviews were transcribed verbatim then analysed using thematic content analysis. Key issues of truth-value, applicability, consistency and neutrality were upheld. Results: The positive aspects of ADHD were characterized by six core themes (cognitive dynamism, courage, energy, humanity, resilience and transcendence), further defined by 19 sub-themes. These themes were validated by comparing them with the psychological traits catalogued in the character strengths and virtues (CSV) handbook. The CSV is a ‘‘handbook of the sanities’’ that underpins research and practice in positive psychology. Divergent thinking, hyper-focus, non-conformist, adventurous, self-acceptance and sublimation were positive aspects specific to ADHD. Conclusions: The sample size was small. This is not unusual for a qualitative study. A novel topic area was being investigated, this was the best method to use. The findings were discussed with reference to academic literature. This strengthened generalizability by highlighting the relevance of the findings to other fields of study. While divergent thinking was found to be a positive aspect of ADHD, it does oppose convergent thinking. Perhaps this explains why people with ADHD experience disadvantages within educational institutions that teach and value convergent thinking. The eminence of energy in ADHD life was also striking. Perhaps it is time to investigate how vital energy, which includes zest and vigour, could be used to promote happiness and well-being in ADHD life. ADHD is usually associated with functional impairment in a number of domains. This study shows that ADHD is not entirely maleficent, as positive aspects that can support high functioning, accomplishment and flourishing in ADHD life were found.
P-19-006 Impact on the family unit of early morning functional impairments in stimulant-treated children and adolescents with Attention-Deficit/Hyperactivity Disorder R. Schachar*, S. Faraone, R. Barkley, R. Nullmeier, F. Sallee *Toronto, Canada Objectives: To assess the impact of early morning functional (EMF) impairments of stimulant-treated youths with Attention-Deficit/ Hyperactivity Disorder (ADHD) versus those without ADHD on the family unit. Methods: An online survey was conducted with primary caregivers of children/adolescents (6–17 years) with and without ADHD. Youths with ADHD had to be currently taking a stimulant as their primary ADHD medication at a stable dose for C3 months and have ADHD symptoms during the Early Morning Routine (EMR)—from awakening until they leave for school—rated C2 on a 10-point scale (1 denoting ‘‘mild’’; 10 denoting ‘‘severe’’). Caregivers rated the
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Abstracts severity and frequency in family dysfunction resulting from their child&s EMF impairments. Groups were compared using logistic regression with ADHD status as the outcome and family impact measures as independent variables. Results: Three hundred caregivers of youths with ADHD who met all inclusion criteria and 50 caregivers of youths without ADHD completed the survey. Severity of EMF impairments was significantly higher in families of youths with ADHD versus those without ADHD (mean: 6.2 vs. 1.5; P \ 0.001), as was the number of school days/ week that their child had EMF impairments (median: 4 vs. 1; P \ 0.001). The majority of caregivers of youths with ADHD reported their child&s early morning ADHD symptoms (87%) and EMF impairment (77%) as moderate to severe. They also reported a significantly higher severity and frequency (up to 6- and 9.5-fold, respectively) in family dysfunction on all measured domains during the EMR versus caregivers of youth without ADHD. Nearly half of the caregivers expressed significantly higher concerns regarding the safety of their child with ADHD and siblings. Conclusions: Caregivers of stimulant-treated youths with ADHD report a significantly higher prevalence and severity of EMF impairments. These impairments exert a pervasive, negative emotional and functional impact on the entire family unit.
P-19-007 Health and economic outcomes in children of mothers with treated and untreated ADHD E. Merzon*, I. Merhasin, T. Merzon, S. Vinker *Tel Aviv, Israel Objectives: Data about health outcome in children born to mothers with Attention-Deficit/Hyperactivity Disorder (ADHD) is limited. The objective of our study was to investigate health and economic outcomes in children born to women, who had been diagnosed with ADHD. Methods: Medical data from all children born in the period from 1/01/2014 to 1/12/2016 were collected and linked to their mothers’ medical records using the electronic registry of a large Israeli health maintenance organization—Leumit Health Services. All women with the diagnosis of ADHD, as defined in International Classification of Diseases (ICD-10) were identified (n = 504), and divided into two groups: Those who purchased medications for at least 12 months, older than 18 years (n = 110) and those who did not (n = 394). A comparison group included children from other women, who had no ADHD diagnosis and had given birth during the same period (n = 4290). Main outcome measures were haemoglobin level, flu vaccinations; number of emergency room admissions; number of hospitalisations, length of hospital stays and total medical costs. Results: Children born to mothers with diagnosed, but untreated, ADHD as compared to children born to mothers with treated ADHD or mothers without ADHD had a significantly lower haemoglobin level (10.5 vs.10.9 & 11.7, p \ 0.001) and flu vaccination rate (21.4 vs. 22.6 & 35.4%, p \ 0.001). They had higher rates of emergency room admissions (1.01 vs. 0.88 & 0.54, p \ 0.001) and hospitalisations (0.65 vs. 0.25 & 0.22, p \ 0.001). Their hospital stays were longer (2.87 vs. 0.88 & 0.63, p \ 0.001) and medical costs higher (13,364 NIS vs. 4992 NIS & 4971 NIS, p \ 0.001). Risk ratio for hospitalisation of children of mothers with untreated ADHD was 3.22 (CI 95% 2.87; 3.63). Conclusions: Children of mothers with untreated ADHD had worth health outcomes and significantly higher medical costs as compared to children born to mothers with treated ADHD or mothers without ADHD.
Abstracts
P-19-009 Life satisfaction, personality traits and aggression in adults with Attention-Deficit/ Hyperactivity Disorder Z. Kupnicka*, G. Poraj, J. Kazmierski *Lodz, Poland Objectives: The primary objective of the current study was to examine if there are differences between people with and without adult ADHD with regard to life satisfaction, predisposition to aggressive behaviour and personality profile. The secondary objective was to assess the association between personality traits, aggressive behaviour, and the level of satisfaction with life among patients with ADHD. Methods: ADHD symptoms were self-reported with DSM-V criteria. Participants with adult ADHD (n = 52) and control group (n = 74) completed three questionnaires: Polish adaptation of life satisfaction questionnaire (‘‘Fragebogen zur Lebenszufriedenheit-FLZ’’), inventory of psychological syndrome of aggression (IPSA) and Polish adaptation of NEO five-factor inventory (NEO-FFI). To analyse the data ANOVA and Pearson&s correlation were used. Results: The results of the study show that adults diagnosed with ADHD, in comparison to adults without ADHD, declare lower general satisfaction in life, particularly in such areas as health, finance, relationships with friends and family, marriage, sex, themselves, housing and free time (p \ 0.05). They are also characterized by a higher level of aggression and more susceptible to particular aggressive behaviours (p \ 0.05). Adults with ADHD, compared to the control group, present a higher level of neuroticism and a lower level of extraversion. They are also less agreeable and conscientious (p \ 0.05). Life satisfaction in adults with ADHD has negative correlation with ADHD symptoms (r = -.453; p = 0.01), aggression syndrome (r = -.497; p = 0.01) and neuroticism (r = -.692; p = 0.01) and positive correlation with extraversion (r = .646; p = 0.01), agreeableness (r = .470; p = 0.01) and conscientiousness (r = .339; p = 0.14). Conclusions: According to the presented results, there are significant associations between aggressive syndrome scales, specific personality traits, and general life satisfaction in subjects with ADHD.
P-19-010 Inattention in primary school predicts high school academic achievement A. Lundervold*, J. Meza, M. Hysing, S. Hinshaw *Bergen, Norway Objectives: To investigate childhood inattentive behaviour as a predictor of future academic achievement in two diagnostically and culturally diverse samples, taking the impact of the child&s intellectual function into account. Methods: Samples: (a) a U.S. all-female sample predominated by youths with ADHD (Berkeley girls with ADHD longitudinal study [(BGALS], n = 202), and (b) a sample recruited from a Norwegian population-based sample (the Bergen child study [BCS], n = 93). Inattentive behaviour and intellectual function were assessed via the same measures in the two samples; academic achievement scores in high school were country specific. Hierarchical regression analyses within the two samples were followed by a mediation (intellectual function) and moderator (sex) analysis within the BCS sample according to the PROCESS procedure in SPSS.
S47 Results: Childhood inattentive behaviour predicted academic achievement in both samples, with the strongest effect in the BGALS sample. Intellectual function was another strong predictor, but the effect of inattention remained statistically significant in both samples even when intellectual function was co-varied. When sex was included as a moderator in the follow-up analysis (BCS sample), the direct effect of inattention was strong and not mediated by intellectual function in girls, while the direct effect was fully mediated by intellectual function in boys. Conclusions: The effect of early signs of inattention on future academic success was found across the two diagnostically and culturally diverse samples, supporting arguments for not restricting remediation procedures to a specific diagnostic group. The importance of intellectual function turned out to be a stronger predictor of academic achievement in boys than in girls. Future longitudinal multicentre studies with pre-planned common inclusion criteria should be performed to increase our understanding of the importance of inattention in primary school children.
Friday, 21 April 2017, 14.30 h–16.00 h P-20 Quality of life/Caregiver burden II P-20-001 Cognitive insights into ADHD: Exploring the relationship between ADHD, the knowledge of parents/schools, dysfunctional expectations, beliefs and stigmatization in Pakistan N. Vazir *Karachi, Pakistan Objectives: In Pakistan, there is an extreme dearth of awareness about the developmental needs of children, especially for those suffering from ADHD is sorely lacking. A comprehensive analysis of the published research literature of Pakistan demonstrates that so far no studies have been conducted on the significance of the knowledge of parents and teachers of ADHD. This study is an initial step to create awareness and tolerance for all those children who are different. The primary purpose of this study is to explore the existing knowledge and understanding (if any) of parents and teachers about ADHD. Moreover, to inquire how their cognition and belief towards mental health services for ADHD influences their decision to seek psychological assistance and medical help for their child&s treatment. Methods: Purposive sampling technique was used to select 150 (semi-literate) parents and teachers (untrained) of primary students (6–8 years) from lower middle class schools from three different towns of Karachi, Pakistan. Ten focus group interviews were conducted to collect data. Results: The findings of the study show cognitive dysfunction of parents due to lack of awareness and acceptance of learning disabilities, stigmatisation, cultural taboos, societal pressure and rigid thinking (tunnel vision). Eighty percent (80%) of the mothers outlined the lack of decision-making (especially in case of children&s disabilities) in a male dominant society. Moreover, mother&s attributed lack of professional help/inclusive schools in Pakistan as compared to developed nations where ADHD treatment is much more common. Conclusions: Our analysis shows that parents disregard the needs of their child over societal needs. This study is an investigation to identify and reach out to children, teachers and parents through awareness programmes and on-site psychological counselling.
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P-20-002 Financial decision-making in adults with ADHD D. F. Bangma*, J. Koerts, A. B. M. Fuermaier, C. Mette, M. Grabemann, M. Zimmermann, O. Tucha, L. Tucha *Groningen, The Netherlands Objectives: Previous studies suggest that adults with ADHD might have difficulties with financial decision-making (FDM). However, the ability to make financial decisions has never been examined in an objective standardised manner in these patients. The aim of the present study was to investigate multiple aspects of FDM in adults with ADHD using a comprehensive test battery. Furthermore, the associations between FDM and cognition of patients were explored. Methods: Adults with ADHD (n = 49) and healthy controls (n = 85) completed a neuropsychological test battery and seven FDM tests and questionnaires measuring financial competence, FDM capacity, FDM styles, the ability to apply rules, future decisions, risk taking and impulsive buying. Groups did not differ with regard to age, gender, years of education and income. Results: Adults with ADHD reported more often to have debts and less often to have a savings account than healthy controls. Furthermore, adults with ADHD showed significantly lower scores on financial competence and capacity tests and on a test measuring decisions with implications for the future compared to healthy controls (medium to large effects). Questionnaires revealed that adults with ADHD reported more often to experience the tendency to buy on impulse and the use of an avoidant or spontaneous decision-making style than healthy controls (medium to large effects). Within the group of adults with ADHD, moderate correlations were found between performances on FDM tests and questionnaires and on tests measuring processing speed, working memory and inhibition. Conclusions: Adults with ADHD were found to have difficulties with several aspects of FDM, i.e. evaluating financial problems (FDM capacity), understanding bank statements/protocols (financial competence), financial decisions with implications for the future and impulsive buying compared to healthy controls. These difficulties presumably result in less optimal personal finances of adults with ADHD. However, more research is needed to evaluate the daily life consequences of these difficulties with FDM.
P-20-004 The association between mental effort and performance in an ADHD-risk sample C.-F. Hsu*, J. Eastwood, M. Toplak
Abstracts performance was comparable. There was a significant negative correlation between real-time effort and performance accuracy in the ADHD-risk group, whereas the correlation in the control group was not significant, indicating that more effort required was associated with lower accuracy in the ADHD-risk group. Conclusions: These findings suggest that mental effort exerted on a challenging task can characterize individuals with ADHD-related difficulties. Investigating the experience of mental effort in ADHD may help people with problems to engaging in mental tasks and reframe our understating of ADHD.
P-20-005 ADHD and SLPs: A survey J. Roitsch*, S. Watson *Norfolk, UK Objectives: It is estimated that 30–50% of students with ADHD also have a specific learning disability. More specifically, as ADHD can negatively affect the language development of children, it is important to know how prepared Speech language pathologists (SLPs) feel about working with those students. Although self-assessments and perceptions of effectiveness are important to evaluation and treatment outcomes, few studies have queried how speech and language pathologists (SLPs) manage attention deficits within the clinical setting. Few researchers have interviewed school SLPs to determine their comfort levels in working with children with ADHD. The purpose of this research was to survey SLPs to determine the level of education and training that they received prior to working with children with ADHD and also to determine their comfort level when working with children with ADHD. Methods: For this study, a total of 86 school SLPs whose clinical caseload included students diagnosed with ADHD participated in an online survey. Results: Results revealed that only 27% (n = 22) of SLPs had received specific coursework in school prior to working with students with speech and language disorders who also have a diagnosis of ADHD. Nearly 61% (n = 51) of all SLPs surveyed had sought professional training regarding ADHD. Less than half (47%, n = 40) of the SLPs surveyed felt that they were adequately trained to work with children with ADHD. From the survey, 23% (n = 19) of SLPs reported that they rarely or never focused on executive functions during assessment and treatment sessions and 27% (n = 22) SLPs surveyed never assessed working memory capacity during initial evaluations. Conclusions: These results suggest the need for increased training to better equip SLPs to work with students with ADHD prior to entering the school systems.
*Taichung, Taiwan Objectives: The avoidance of mental effort is a symptom criterion for Attention-Deficit/Hyperactivity Disorder (ADHD), yet there is little research on the experience of mental effort in people with ADHDrelated difficulties. This study explored real-time ratings of mental effort and discomfort during a working memory task in young adults with and without ADHD-related difficulties. Methods: A sample of 235 undergraduate students (mean age = 21.02, 86 males) completed the ADHD self-rating scale (ASRS) and a cognitively effortful working memory task. Of these participants, 136 met criteria for the ADHD-risk group and 99 were in the control group. Participants were prompted to answer questions about their experience of effort and discomfort during the working memory task. Results: The ADHD-risk group displayed a significantly higher level of effort and discomfort compared to the control group even when the
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Friday, 21 April 2017, 14.30 h–16.00 h P-21 Miscellaneous P-21-004 Influence of parental depression and suicidal ideation on adolescents’ suicidal ideation: The 2008–2013 Korean national health and nutrition examination survey (KNHNE) Y. J. Lee*, S. Lee, K. Han *Seoul, Republic of Korea
Abstracts Objectives: It is well established that maternal depression or suicidal ideation predicts suicidal ideation among adolescents. However, the influence of paternal psychopathology has been less recognised. The aim of this study was to examine how parental depression and suicidal ideation contributes to suicidal ideation among adolescents. Methods: In this population-based cross-sectional study, 6.705 parents (2840 fathers, 3865 mothers) and their 4073 adolescents (aged 10–18 years) who participated in the 2008–2013 Korean National Health and Nutrition Examination Survey were enrolled. Depression and suicidal ideation were evaluated using questionnaires and surveys. Data were analysed using logistic regression to determine the association of suicidal ideation among adolescents with parental depression and suicidal ideation, after controlling for age and sex of parents. Results: Among adolescent with suicidal ideation, there were more girls (p \ 0.01) and more adolescents from urban residences (p = 0.02). Their sleep duration was less (6.85 vs 7.20 h; p \ 0.01), and they were more likely to have stress (61.8 vs 21.8%; p \ 0.01) and depression (34.6 vs 7.0%; p \ 0.00). The risk of suicidal ideation among adolescents of fathers with depression or suicidal ideation was 2.311 times (p \ 0.05) or 2.449 times (p \ 0.05) more than the risk associated with mothers with depression or suicidal ideation was 1.293 times (p [ 0.05) or 1.779 times (p \ 0.05), respectively. Conclusions: Parental depression and suicidal ideation were significantly associated with suicidal ideation among adolescents. The risk of depression and suicidal ideation among adolescents was higher when the father had suicidal ideation than when the mother had it.
P-21-006 A survey of adolescents to assess their knowledge of Attention-Deficit/Hyperactivity Disorder, how different medications work and enhance their understanding through an illustrated leaflet using the analogy of postmen C. Yemula*, A. Khan, S. Chaudhry, N. Yemula *Bedford, UK Objectives: Many adolescents with ADHD have a limited understanding of ADHD and how medications work to improve the ADHD symptoms. We sought to: 1. Ascertain their baseline knowledge of ADHD and how medications work 2. Find out if their knowledge improves after reading an educational leaflet 3. Obtain feedback if the leaflet is user-friendly Results: Out of adolescents (aged 12–16 years, 15 boys and three girls) who completed the survey, at baseline only 33% (n = 6) were aware of ADHD symptoms and 22% (n = 4) knew of chemicals helping with message transfer in the brain. Only 5.5% (n = 1) knew how medicine worked and 22% (n = 4) indicated how long it worked for. After reading the leaflet, 61% (n = 11) knew about ADHD symptoms, 77.8% (n = 14) understood about chemical messengers, 55.5% (n = 10) indicated how the medicine helped to improve messages in the brain and understood how long the medicine worked for. Providing feedback, 77.8% (n = 14) said the leaflet was easy to understand and 72% (n = 13) liked and understood the analogy of postmen as chemical messengers. Conclusions: Our adolescent patients indicated significant gaps in their knowledge of ADHD, chemical messengers and medications. Educating them is crucial and the leaflet is a useful free resource.
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P-21-007 A survey of parents of teenagers with ADHD to assess their baseline knowledge, how different ADHD medications work and to enhance their understanding through an illustrated leaflet using the analogy of postmen C. Yemula*, S. Chaudhry, A. Khan, N. Yemula *Bedford, UK Objectives: Parents often lack a full understanding of their child&s ADHD and how medications work. We sought to: 1. Ascertain their baseline knowledge of ADHD and how medications work 2. Find out if their knowledge improves after reading an educational leaflet 3. Obtain feedback if the leaflet is user-friendly Methods: We developed an innovative leaflet to explain how stimulants and non-stimulants work, using the analogy of postmen with illustrations. Mr Norda (Noradrenaline) and Mr Dopa (Dopamine), the postmen cross the bridge (synapse) to deliver letters (messages) from one nerve cell to another. In ADHD, several postmen go on strike (reuptake) but the medication helps them to get back to work, streamlining the transfer of messages and improving ADHD symptoms. At our ADHD clinics, parents completed questionnaires regarding their knowledge of ADHD and how the medication works before and after reading this leaflet. Results: Twenty-five (25) parents completed the survey. At baseline, 12% (n = 3) were not aware of what ADHD stands for, 32% (n = 8) lacked knowledge of ADHD symptoms and over half, 52% (n = 13) did not know about chemical messengers in the brain. A majority 64% (n = 16) were unaware of stimulant and non-stimulant medication and could not provide a basic explanation of how the medication works. After reading the leaflet, all knew the ADHD abbreviation and 92% (n = 23) understood ADHD symptoms and the role of chemical messengers. Interestingly, 96% (n = 24) knew about stimulants and non-stimulants, whilst 72% (n = 18) had learned how ADHD medication works. 72% (n = 18) found the leaflet easy to understand and 68% (n = 17) found the postman analogy helpful for children as well. Many parents provided positive comments. Conclusions: This small pilot study indicated that the leaflet could be a user-friendly resource to educate parents and improve their knowledge of ADHD, chemical messengers and how ADHD medication works.
P-21-010 Embelin-loaded nanolipid carriers ameliorate ethanol-induced experimental Attention-Deficit/ Hyperactivity Disorder in rats: Possible role of dopamine R. K. Narang*, R. Deshmukh, P. Kumar *Moga, India Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by difficulties in paying attention, excessive activity, or trouble controlling behaviour. Current clinical therapies for ADHD with fetal alcohol spectrum disorders (FASD) are limited, suggesting that alternative approaches are needed. Alteration in dopaminergic system and oxidative stress has been well implicated in ADHD pathology. Embelin, (benzoquinone) a major active constituent of Embelia ribes, has been reported to
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S50 possess anti-inflammatory, antioxidant, anticonvulsant and neuroprotective potential. Thus, we hypothesize that embelin could be useful in the management of ADHD. Therefore, we investigated the efficacy of embelin loaded nanolipid carriers to attenuate neonatal ethanol-induced locomotor hyperactivity and alterations in brain neurochemistry. Methods: From postnatal days (PND) 2–10, male rat pups received either 3 g/kg per oral ethanol or milk twice daily on alternate days. Embelin-loaded nanolipid carriers (10 mg/kg/oral) were administered from PND 20–25. On day 20 and 25, pups were evaluated for locomotor activity using open field test and actophotometer test. On day 26, animals were sacrificed and the cortex, hippocampus and striatal brain regions were used for evaluation of oxidative stress markers (lipid peroxidation, reduced glutathione and nitrite) and dopamine levels. Results: Post natal administration of ethanol caused significant locomotor hyperactivity (Two way ANNOVA; p \ 0.001) and produced elevation in oxidative stress markers and dopamine levels in cortical, hippocampal and striatal brain regions of rat pups (One way ANNOVA; p \ 0.001). Embelin loaded nanolipid carrier treatment significantly attenuated ethanol induced hyperactivity (Two way ANNOVA; p \ 0.01) and oxidative stress and restored the level of dopamine (One way ANNOVA; p \ 0.01) in different brain regions of rat pups. Conclusions: The observed beneficial effects of embelin may be due to its antioxidant potential and its ability to restore dopamine levels. Our findings suggest embelin-loaded nanolipid carriers could be useful in the management of ADHD like disorders.
P-21-013 The purple hex: Psychosis associated with abuse of propylhexedrine nasal inhalers by a young adult with history of ADHD seeking replacement for stimulant medication—with literature review and historical context A. Cohen*, C. Perkel *Brooklyn, USA Objectives: Propylhexedrine is a sympathomimetic drug structurally similar to methamphetamine. Currently it is widely available over the counter for under $10 as a Benzedrex brand nasal inhaler. We report the case of a young adult patient with a history of ADHD who developed psychosis after ingesting propylhexedrine in the form of the contents of nasal inhalers which he learned about through the Internet after seeking a replacement for stimulant ADHD medication. To our knowledge, the last case of psychosis associated with propylhexedrine use was published in 1972. This case highlights the potential for abuse of a widely available over the counter medication and the associated risk of psychosis. Physicians will learn to recognise and screen for the abuse of this ‘‘legal speed’’. It also highlights one patient&s quest to find a replacement for stimulant ADHD medication he found helpful and the role of the Internet in connecting individuals seeking similar effects. Methods: We present a case of a 26-year old patient with ADHD and marijuana/stimulant use disorder who presented with psychosis after daily ingestion of over the counter propylhexedrine—a sympathomimetic nasal decongestant available over the counter, as well as review of the literature on psychiatric symptoms associated with propylhexedrine use. A PubMed search using the words ‘‘propylhexedrine’’, ‘‘psychiatry’’ and ‘‘psychosis’’ was performed. Results: This is a case of a 26-year old man with past psychiatric history of ADHD, stimulant/K2/cannabis use disorders, who was
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Abstracts admitted after he presented with psychosis and suicidal ideation in the context of daily propylhexedrine ingestion. The patient stated he had prior diagnosis of ADHD treated as an adolescent with stimulant medication with good effect, but was lost to follow up in context of his mother&s substance abuse. The patient states he sought similar stimulant effects from methamphetamine purchased illegally but eventually found it cost prohibitive. He then turned to Internet message boards to find substances ‘‘like adderall’’ which could be obtained without seeing a physician. On learning about propylhexedrine, he began purchasing it from his local pharmacy, breaking open the inhalers and ingesting the contents. As his tolerance grew he moved on to stealing the inhalers to maintain his supply. On admission, the patient was disorganised and extremely aggressive and was treated with olanzapine. Over the course of hospitalisation, the patient showed improvement in psychosis and mood symptoms and was discharged to a inpatient rehab programme. Benzedrine amphetamine medication was a popular drug of abuse, immortalised in Jack Kerouac’s ‘‘On the Road’’. In 1949, amphetamine sulphate-based benzedrine was replaced by propylhexedrine containing Benzedrex inhalers after of reports of psychosis, sudden death and wide spread abuse associated with benzedrine use. Benzedrex inhalers are widely available over the counter at pharmacies for $5–8 and at least in New York are not subject to the same sales restrictions as pseudoephedrine. Structurally similar to methamphetamine, propylhexedrine has a salicyclic cyclohexyl group in place of amphetamine&s aromatic phenyl group, and provides local vasoconstriction with reportedly 1/12 the central nervous system stimulant effects of amphetamine. Subsequently it was thought to have a lower potential for abuse, but reports emerged in the early 1970s of psychosis associated with propylhexedrine ingestion likely due to increasing abuse after amphetamine and methamphetamine were scheduled, restricting their availability. Conclusions: Our patient, unable to obtain prescription stimulant medication which he had used for ADHD turned to a widely available over the counter medication and with chronic daily abuse he presented as floridly psychotic. While this drug is inexpensive and widely available, there is little information in the medical literature on the effects of its chronic use. Physicians need to be aware of its potential for abuse, particularly among adolescents who are increasingly abusing over the counter medications for their euphoric effects, or in the case of our patient, in a self described effort to replace a previously prescribed psychiatric medication.
P-21-014 Publications from Brazilian psychologists on ADHD, a categorization research N. Perin Darim*, P. Da Silva Fucuta *Sao Jose´ Do Rio Preto, Brazil Objectives: In Brazil ADHD has become a tricky field of research, especially when it comes to psychology. Publications communicate very different points of view, where there are researchers concerned about the ramifications of ADHD on development, others are questioning the existence of the disorder itself. The Federal Psychology Council (CFP) is the regulator, guide and supervisor of the profession in Brazil, and in 2012, it has started a campaign against medicalisation of childhood, affirming that if a kid is agitated it is because of the age, not because of a disease. Because of that, the publications of the last decade from Brazilian psychologists were researched. Methods: The selection of the publications read followed the picture. Results: The field that received most contributions from the publications read was Neuropsychology, followed by cognitive behavioural therapy and psychoanalysis; the majority of publications were field surveys comparing people with and without ADHD. The
Abstracts general conclusion about diagnosis and treatment of ADHD was that it has to be done by a multidisciplinary team, and that the challenge is to integrate school and family through the process. Conclusions: The medicalisation is the most common theme of the researches read so it indicates that the work of the Federal Psychology Council is taken under consideration by the psychologists, being against or in favour, which indicates there are discussions happening among professionals. The publications were categorized by themes and year of publication, 203 were read, 78 themes were chosen as categories and a summary was created listing the researches that mentioned each theme, and all of the researches received a short summary of its conclusions.
Friday, 21 April 2017, 16.00 h–17.30 h FC-01 Free Communication Session FC-01-001 Psychiatric comorbidities in male and female adults with ADHD B. S. Solberg*, J. Instanes, A. Halmøy, J. Haavik, K. Klungsøyr *Bergen, Norway Objectives: The prevalence of ADHD is higher in males than in females, particularly in children, but also in adolescents and adults. However, little is known about gender differences and risk of comorbid psychiatric disorders in adults with ADHD. Using population registries, we aimed to investigate gender specific risks of psychiatric comorbidities in adults with ADHD, and compared to the general population. Methods: Population-based study in Norway linking large national registries (medical birth registry of Norway, Norwegian patient register (NPR), Norwegian prescription database and national education database) containing all adult inhabitants born 1967–1994. ADHD cases were individuals being dispensed any ADHD drugs in 2004–2015 (n = 38,563; 42% females). The remaining adult population served as controls (n = 1487,545; 49% females). Psychiatric comorbidities were detected from NPR, 2008–2012, and gender differences in risk of four major psychiatric comorbidities were evaluated using Poisson regression analysis to adjust for confounders and evaluate interaction by gender. Results: Adult ADHD showed the strongest association with personality disorders and bipolar disorder, both in males (incidence rate ratios (IRR) 7.9; 95% confidence intervals 7.3–8.6) and IRR 7.7 (7.3–8.1), respectively) and females (IRR 7.7 (7.2–8.2) and IRR 7.3 (6.9–7.6), respectively). Substance use disorder (SUD) was also associated with adult ADHD: IRR 6.6 (6.4–6.9) in males and 6.6 (6.2–6.9) in females, while psychosis showed a weaker association: 3.9 (3.5–4.3) and 4.1 (3.6–4.7) in males and females, respectively. Estimates differed significantly by gender only for SUD (multiplicative interaction term: p = 0.005, likelihood ratio test). Within the ADHD group, the IRR for SUD and psychosis in females versus males were 0.6 (0.6–0.7) and 0.7 (0.6–0.8), respectively, while for bipolar and personality disorder the IRR were 1.5 (1.4–1.6) and 1.8 (1.7–2.0), respectively. These gender ratio estimates were similar among adults without ADHD. Conclusions: The risk of all four psychiatric comorbid conditions in adults with ADHD was high compared to controls. Significant gender differences were only found for SUD. The risk of severe psychiatric comorbidity in females compared to males did not differ significantly in adults with ADHD compared to controls.
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FC-01-002 Early food allergy and allergic symptoms on the risk of Attention-Deficit/Hyperactivity Disorder in Chinese children in school age F. Li*, X. Jiang, C. Shen *Shanghai, People’s Republic of China Objectives: To explore the association between early food allergy and allergic symptoms and Attention-Deficit/Hyperactivity Disorder (ADHD) in Chinese school-aged children. Methods: This is a cross-sectional survey. Cluster sampling was used for school-aged children selection from nine cities in China. Diagnosis of ADHD and allergic disease as well as demographic information of children were collected via a parent-administered questionnaire. Children were divided into non-food allergy (nonFA) group, single food allergy (FA) group, food allergy combined with one (FA + allergic rhinitis [AR]/bronchial asthma [BA]) and two allergic symptoms (FA + AR + BA) groups according to the previous diagnosis of food allergy and other allergic diseases. Difference in prevalence of food allergy in children with and without ADHD was analysed with univariate analysis, and multiple logistic regression model was used for analysing the effect of food allergy and allergic symptoms on ADHD in school-aged children. Results: A total of 22,018 children were enrolled, among which there were 9921 (45.1%) boys and the mean age was 8.81 & plusmn; 1.79 years. 979 (44.5%) children were diagnosed of ADHD, and more children with food allergy was observed in ADHD children than nonADHD ones (10.3 vs. 5.4%, P \ 0.001. Among 1223 children diagnosed with food allergy, there were 916 (74.9%), 226 (18.5%) and 81 (6.6%) children in FA, FA + AR/BA and FA + AR + BA groups, respectively. The prevalence of ADHD was 4.2, 6.7, 12.4 and 14.8% in non-FA, FA, FA + AR/BA and FA + AR + BA groups. Multivariate analysis data demonstrated that food allergy with or without allergic symptoms might be risk factors for ADHD (for FA, odds ratio [OR] = 1.589, 95% confidence interval [CI] 1.183–2.134, P = 0.002; for FA + AR/BA, OR 3.560, 95% CI 2.341–5.413, P \ 0.001; for FA + AR + BA, OR 4.087, 95% CI 2.060–8.106, P \ 0.001) in children. Conclusions: Increased prevalence of ADHD was observed in school-aged children with food allergy, furthermore, early food allergy and allergic symptoms was associated with ADHD.
FC-01-003 Psychomotor over-excitability as a predictor of inattention and hyperactivity-impulsiveness C. C. Kuo*, K.-C. Liang, W.-T. Soong, S. S.-Fen Gau *Taipei, Taiwan Objectives: According to Dabrowski’s theory, overexcitabilities are important factors in emotional development of gifted individuals. Gifted students with OEs usually present the same behaviour characteristics as hyperactivity-impulsivity, and some cases were diagnosed as ADHD. This presentation proposed to explore the correlations between OEs on ADHD. Methods: Eighty-six male students, aged 15–26 participated in this research. They were assigned to five groups according to their talent in mathematics and science, diagnosis of AS, and the IQ level. The applied instruments were the OEs scale and the ADHD self-report scale (ASRS). The Taipei Medical University-Joint Institutional Review Board approved this study before implementation (approval no.: 201103014). All the participants and their parents were informed
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S52 of the objectives and procedures of the study, including confidentiality and the voluntary participation of this study. All participants and their parents, if participants were younger than 20 years old, provided written informed consent before study implementation. Results: Our research results indicated psychomotor OE (psycho OE and physical OE), sensual OE (sensually sensitive OE and perfectionism OE), imaginational OE (creative OE and imaginational OE), and emotional OE correlated with ADHD significantly (.238 B r B .642, p \ .05). Among the prediction coefficients, physical OE is the top predictor to inattention and hyperactivity-impulsivity. Conclusions: We can conclude that POE combines with SOE, IOE and E OE predict ADHD significantly, this predictor differentiate the characteristics of ADHD and giftedness.
FC-01-004 From positive psychology to psychopathology: The continuum of ADHD C. Greven*, J. K. Buitelaar, G. A. Salum *Nijmegen, The Netherlands Objectives: Integration of positive psychology into clinical research and treatment has been slow. This integration can be facilitated by the conceptualisation of mental disorders as the high, symptomatic extreme of continuous normal variation. This assumes that there is a low, positive extreme, which is, however, unchartered territory. This study aims to examine how well current measures capture the low extreme of mental disorder continua, using ADHD as an example. Methods: The ability of three validated scales to capture ADHD as a continuous trait from low to high was examined using item response theory in a sample of 9.882 adolescents from the UK populationrepresentative twins early development study. These scales were: The strengths and weakness of ADHD symptoms and normal behaviour scale (SWAN), strength and difficulties questionnaire (SDQ hyperactivity), and Conners parent rating scale (Conners). Results: Only the SWAN reliably differentiated inter-individual differences between participants lying at any level of the continuous ADHD latent trait, including the low, positive end (z-scores from -3 to +3). The SDQ showed low reliability across the ADHD latent trait. In contrast, the Conners reliably differentiated individuals scoring at or above the mean to the high symptomatic range (z-scores from 0 to +3). The SWAN was the only measure to provide indicators of positive mental health, endorsed in the presence of particularly good attentive abilities. Conclusions: Scales such as the SWAN that reliably capture ADHD as a continuous trait, including the positive end, are important for not missing meaningful variation in population-based studies. Indicators of positive mental health may be helpful in clinical practice, as positive attributes can directly influence or buffer negative effects of psychiatric symptoms. The next step will be to examine whether the low extreme also reflects resilience, and to study the molecular genetic basis underlying the ADHD continuum captured by polygenic risk scores. Conflict of interest: Greven and Salum have no conflicts of interest. In the past three years, Buitelaar has been consultant to/member of advisory board of/and/or speaker for Janssen Cilag BV, Eli Lilly, Medice, Lundbeck, Shire, Roche, Novartis and Servier. He is not an employee, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties.
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FC-01-005 Persistence and prevalence of ADHD in elementary school children S. Go¨kc¸e*, Y. Yazgan, B. Ayaz, G. Charxaiu Bulut, H. Aslan Genc¸, E. Kayan, E. Atabey, S. Yilmaz, U. Kaytanli, D. Ayyildiz, B. Yildirim, C. Yusufoglu, E. Akin, T. Poyraz *Istanbul, Turkey Objectives: The American Psychiatric Association reported that the estimated prevalence of ADHD is 5% in school age children. However, many studies indicate that the prevalence rate among schoolaged children ranges between 1 and 20%. In this study, we aimed to estimate the prevalence and persistence rate of Attention-Deficit/ Hyperactivity Disorder (ADHD) in third and forth grades of elementary school in a representative school sample of children in Istanbul, Turkey, whose ADHD symptom data were reported from their teachers in previous grades. Methods: In this study we used a sample from our previous community-based study from Istanbul in which we investigated the association ADHD symptoms in 4.356 first and second grades with their school entry age. In that study 342 children estimated to have possible ADHD. Two years after that study we were able to reach 154 children and performed K-SADS. Results: 40.9% of (n: 63) the 154 children were diagnosed with ADHD. 79.3% of the children who were diagnosed with ADHD were from the sample who were estimated to have possible ADHD in previous study. 20% of the children who were diagnosed with ADHD were from the control group who had not possible ADHD in the previous study. 61.7% of the children who were determined to have possible ADHD in the previous study were diagnosed with ADHD. 17.8% of the children who were determined not to have possible ADHD, were diagnosed with ADHD. Conclusions: According to our results we can suggest that teacher reported positive ADHD symptoms in earlier classes might predict ADHD diagnosis sooner, but also that ADHD symptoms in earlier ages might remit with growing age.
FC-01-006 Excessive daytime sleepiness in AttentionDeficit/Hyperactivity Disorder versus narcolepsy: Subjective and objective measures in adults E. Konofal*, M. Lecendreux, C. Vernet, A. Brion, I. Arnulf *Paris, France Objectives: In clinical settings, adults with Attention-Deficit/Hyperactivity Disorder (ADHD) often complain about their sleep difficulties and some report an excessive daytime sleepiness. Previous findings have suggested a possible overlap between symptoms of hypersomnolence and ADHD. We compared the sleepiness and ADHD symptoms, as well as objective measures of sleep and daytime sleepiness between adults with ADHD, patients with narcolepsy (the disorder causing the highest level of sleepiness in human) and healthy controls. Methods: Twenty-five adults with ADHD (16 men, mean age: 37 ± 10 years old), 25 age- and sex-matched narcoleptic patients and 25 healthy subjects completed the Epworth sleepiness scale (ESS) and the Conners adult ADHD rating scale (CAARS). The 75 subjects underwent a nocturnal polysomnography followed by multiple sleep latency tests (MSLT) during daytime.
Abstracts Results: The mean ESS was lower in controls (5.6 ± 3.3) than in ADHD (12 ± 4) and in narcolepsy patients (17 ± 4, p \ .0001). The CAARS score was lower in controls (19 ± 10) than in narcolepsy (36 ± 10) and in ADHD patients (56 ± 8, p \ .00001). Despite similar total sleep time, sleep efficiency, duration of sleep stages and sleep fragmentation, the mean daytime sleep latency at the MLST was shorter in ADHD patients (11.5 ± 4.2 min) than in controls (15.5 ± 3.8 min) but longer than in narcolepsy patients (5.8 ± 3.8 min, p \ 0.0001). Conclusions: The subjective and objective levels of daytime sleepiness in adults with ADHD are intermediary between healthy controls and patients with narcolepsy, indicating a central impairment of arousals systems in ADHD. Conversely, some patients with narcolepsy have symptoms of ADHD, which could constitute a counter strategy to increase alertness (hyperactivity) or a consequence of altered vigilance (inattention, impulsivity).
Saturday, 22 April 2017, 14.15 h–15.45 h YS-02 Young Scientists& Session II YS-02-001 The collaborative life skills programme for Latinos-Familias Unidades Emprendimiento Retos y Tareas para el E´xito (CLS-FUERTE) L. Haack*, E. Araujo, L. Pfiffner *San Francisco, USA Objectives: Rates of ADHD service utilization are disproportionately low in certain world regions, such as Latin America. In response, the current study describes the first known effort to adapt a school-home psychosocial ADHD service programme for implementation and evaluation in Mexico. Methods: Prior to the current investigation, the collaborative life skills (CLS) Program—a twelve-week comprehensive ADHD programme incorporating parent management, child skills, and classroom management training delivered by school providers was translated into Spanish for implementation/evaluation in four United States (U.S.) schools. For the current investigation, we consulted a large Mexican school district about pilot-testing CLS in four Sinaloa schools. We made modifications to CLS based on implementation/ evaluation efforts in the U.S., as well as logistical needs of the participating school district. For example, the name was augmented to the collaborative life skills programme for Latinos-Familias Unidades Emprendimiento Retos y Tareas para el E´xito (CLS-FUERTE) following suggestions from Spanish speaking families in the U.S. In addition, the twelve-week programme was condensed to six weeks to accommodate the Mexican academic calendar. Results: The two schools randomized to receive CLS-FUERTE demonstrated high fidelity rates comparable to CLS fidelity in the U.S. Providers covered 98% of parent session elements and 92% of child session elements with high levels of competence (mean 4.78 for parent and 4.60 for child sessions out of 5). Clinician ratings of parental program adherence averaged 4.3 out of 5. Parent attendance averaged 81% and child attendance averaged 93%. All students had at least one teacher/family meeting. Teachers used the classroom challenge (CC) Behaviour chart an average of more days than not (mean 3.81) and parent signatures were obtained on a majority of CCs (70%). Conclusions: Efforts to implement CLS-FUERTE in Mexico appear promising and could serve as a critical step towards combating disparities for Latin American youths with ADHD.
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YS-02-002 Imaging genetics using PET: Effects of single nucleotide polymorphisms on NET binding in patients with ADHD and healthy controls T. Vanicek*, H. L. Sigurdardottir, C. Rami-Mark, G. M. James, A. Kautzky, G. S. Kranz, G. Gryglewski, M. Spies, T. Traub-Weidinger, M. Mitterhauser, W. Wadsak, M. Hacker, S. Kasper, R. Lanzenberger *Vienna, Austria Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent neurodevelopmental disorder strongly influenced by genetic background. Heritability is projected to be 0.76 (Faraone et al. 2005). Noradrenergic (NE) transmission is centrally involved in ADHD (Del Campo et al. 2011) and the norepinephrine transporter (NET) represents a main target for ADHD drugs (Hannestad et al. 2010). Our aim was to investigate possible effects of single nucleotide polymorphisms (SNPs) within NE genes on NET binding potential (BPND) in patients with ADHD compared to healthy controls (HC). Methods: Twenty adult, drug free patients with ADHD and 20 HC underwent (S,S)-[18F]FMeNER-D2 positron emission tomography (PET) once and were genotyped on a MassARRAY MALDI-TOF platform using the sequenom iPLEX assay. Selected regions of interest were identified from the Hammers maximum probability atlas and comprised the hippocampus, putamen, pallidum, thalamus, and midbrain with pons (including the locus coeruleus). Linear mixed models analysis was applied to investigate a genotype-dependent difference in NET BPND between groups. Results: We found no effects of the SNP rs1800544 of the ADRA2A gene or of the SNP rs3808585 of the ADRA1A gene on the NET BPND in sub-cortical brain regions in patients with ADHD. Conclusions: The findings of this genetic imaging study do not support the hypothesis that the investigated SNPs (rs1800544 and rs3808585) in the NE receptor have a significant effect on NET BPND in patients with ADHD. Although we did not find any effects of the investigated SNPs, recently published data of our group revealed a genetic influence of the NE system on NET binding in ADHD (Sigurdardottir et al. 2016). It is of critical interest to gain more knowledge of the genetic influence of the neurotransmitter systems in general and of the NE transmitter system in particular to enhance our understanding of the neurophysiology of ADHD.
YS-02-003 Integrity of insula subregion-based functional networks and their correlation with ecological executive function in adults with ADHD: A resting-state fMRI study Q. Zhao*, H. Li, X. Yu, F. Huang, Y. Wang, L. Liu, Q. Cao, Q. Qian, L. Sun, Y. Zang, Y. Wang *Beijing, People’s Republic of China Objectives: Few studies have focused on insula and insular subregions functional networks in adults with Attention-Deficit/ Hyperactivity Disorder (ADHD). Insula referred to executive functions, which were major impairments in patients with ADHD. This study evaluated the functional networks of insula subregions (anterior insula [AI], mid insula [MI], posterior insula [PI]) in ADHD and their correlation with self-ratings of ecological executive functions, including inhibit, shift and working memory. Methods: Resting-state functional magnetic resonance imaging (rsfMRI) data were acquired from 28 adults with ADHD and 30 matched typically developed (TD) controls. Resting-state functional
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S54 connectivity (RSFC) of insula subregions and their correlations with behaviour rating inventory of executive function-adult version (BRIEF-A) inhibit, working memory and shift scores were evaluated. Results: Compared with TD controls, altered RSFC were detected differently for AI and MI insular subregions in ADHD: altered RSFC of left AI with the right precuneus (p \ 0.05, TFCE corrected), right precentral gyrus, right inferior temporal gyrus, left lingual gyrus, right calcarine and left superior occipital gyrus; aberrant RSFC of right AI with left lingual gyrus, right middle temporal gyrus and left cuneus; altered RSFC of left MI with right and left lingual gyrus. Within TD controls, working memory (r = 0.557, p = 0.003) scores were positively associated with RSFC of left AI with right precuneus, negatively associated with RSFC of left AI with left inferior temporal gyrus, right calcarine cortex and superior occipital gyrus and RSFC of right AI with left cuneus. Inhibit scores were negatively correlated with RSFC of left AI with right calcarine cortex and RSFC of left MI with right lingual gyrus. Within ADHD, shift and working memory scores were negatively correlated with RSFC of left MI with right lingual gyrus. Conclusions: Diffuse alterations of insular subregion-based networks are associated with ADHD, and these alterations might be involved in the executive function impairments in ADHD, especially working memory.
YS-02-004 Developmental processes in waiting impulsivity K. Peters*, M. Romanos, S. Neufang *Wu¨rzburg, Germany Objectives: Waiting impulsivity (WI) is defined as the ability to regulate a response in anticipation of reward. WI can be assessed via the 5-choice serial reaction time task (5-CSRTT), which has recently been used as part of a translational model of ADHD [1]. Neural correlates of WI are the prefrontal cortex (PFC), the nucleus accumbens (NAcc) and prelimbic regions. In this study we addressed the developmental processes of WI using functional neuroimaging.
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Abstracts Methods: 5-CSRTT-performance and neural activation was compared between 27 typically developing (TD) boys, aged 9–12 years and 27 males (19–26 years) [2]. All subjects were of normal intelligence (Mchildren = 101 ± 13, Madults = 110 ± 17). In addition, we have started to collect data of ADHD patients, to date n = 14. Results: Comparison of the behavioural performance showed that TD boys performed significantly slower (Mchildren = 420.3 ± 37.3 ms, Madults = 371.5 ± 28.4 ms, t(54.2) = 5.67, p \ 0.05) than adults, and committed a higher number of premature responses (Mchildren = 2.4 ± 1.8, Madults = 0.9 ± 1.2, t(54.2) = 3.58, p \ 0.05), the predominant behavioural parameter of WI. Across all subjects we found a fronto-parieto-striatal network being activated with the NAcc reflecting reward processing and the PFC being involved in response inhibition. Group comparisons revealed a reduced PFC activation in children in the inhibition phases (right PFC: 38 42 8, t = 4.03, left PFC: -44 38 4, t = 3.49; p \ .05) and additional limbic activation at the beginning of a new trial (42 -6 -2, t = 3.81, p \ .05). Conclusions: Reduced prefrontal recruitment during inhibition is a common sign of immature top-down control in TD children. The enhanced limbic response in children at trial start can be interpreted as the excitement of getting a new chance to earn a reward. Both findings together reflect the imbalance between frontal and limbic development during brain development [3]. These results will furthermore be discussed in the context of preliminary findings of our ongoing study with ADHD patients. [1] Hayward A., Tomlinson A., Neill J.C. (2016). Low attentive and high impulsive rats: A translational animal model of ADHD and disorders of attention and impulse control. Pharmacol Ther. 158:41–51. doi:10.1016/. [2] Neufang, S., Akhrif, A., Herrmann, C. G., Drepper, C., Homola, G. A., Nowak, J.,… Romanos, M. (2016). Serotonergic modulation of ‘waiting impulsivity’ is mediated by the impulsivity phenotype in humans. Translational psychiatry, 6(11), e940. doi:10.1038/tp.2016.210 [3] Casey, B., Jones, R. M., & Somerville, L. H. (2011). Braking and Accelerating of the Adolescent Brain. Journal of research on adolescence: the official journal of the Society for Research on Adolescence, 21(1), 21–33. doi:10.1111/j.1532-7795.2010.00712.x
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AUTHOR INDEX
Alammar, H. P-14-001 Al-Dakroury, W. P-19-001 Almutairi, S. P-03-001 Amaladoss, N. P-16-005 Arai, G. P-08-001 Bachmann, K. P-12-001 Bae, S. P-01-001 Bahn, G. H. P-05-002 Bang Madsen, K. YS-01-002, P-03-002 Bangma, D. F. P-20-002 Berquin, P. P-16-001 Bhagia, J. P-08-007 Bikic, A. P-15-007 Blume, F. P-14-002 Bo¨lte, S. P-06-006 Bosman, M. P-03-003, P-18-001 Burton, C. YS-01-001 Caci, H. P-05-001 Cao, Q. P-12-002 Carrasco, X. P-09-001 Clement, H.-W. P-14-003 Coghill, D. P-17-004 Cohen, A. P-21-013 Crunelle, C. P-12-003 Danielson, M. P-03-004 Dekkers, T. P-10-006, P-11-001 Elia, J. P-02-006 El-lethey, H. S. P-13-007 Fan, Z. P-01-002, P-14-004 Faraone, S. P-05-006 Finding, R. L. P-17-001 Fine, A. P-05-003 Furukawa, E. P-11-002 Garcia Valdecasas Colell, M. P-09-008 Ginsberg, Y. P-18-007 Go¨kc¸e, S. FC-01-005 Gomaa, W. P-15-009 Gonzalez, R. YS-01-004, P-02-005 Greven, C. FC-01-004 Guizar-Sa´nchez, D. P-16-006 Gu¨nther, T. P-06-001 Gustafsson, P. P-06-002 Ha, M. P-01-003 Haack, L. YS-02-001 Han, X. P-13-005 Hayashi, W. P-03-005 Holst, Y. P-10-005 Horovitz, M. P-08-002 Hsu, C.-F. P-20-004 Hung, S.-J. P-09-002
Hwang-Gu, S.-L. P-11-003 Ichiyama, T. P-17-009 Ioannou, C. P-08-003 Iwanami, A. P-12-008 Jain, U. P-10-001 Jespersen, R. A. Fløtum P-08-004 Jin, J. P-01-004 Johndrow, J. P-15-005 Kautzky, A. P-12-004 Kazmierski, J. P-19-009 Khimani, Z. P-20-001 Kim, B. N. P-13-006 Kim, D. P-05-004 Kitching, R. E. P-12-005 Klein, C. P-08-008 Koelle, M. P-18-006 Konofal, E. P-09-003, FC-01-006 Kuehle, H.-J. P-16-009 Kumar, P. P-07-003 Kuo, C. C. FC-01-003 Kwack, Y. S. P-11-004 Lagace´ Leblanc, J. P-07-009 Lee, J.-S. P-14-005 Lee, Y. J. P-21-004 Li, F. P-02-001 Li, H. P-09-004 Liao, W. P-11-005 Liu, L. P-01-005, P-02-004 Loke, H. P-13-003 Lu, Q. P-01-006 Lukmonov, S. P-03-006 Lundervold, A. P-19-010 Luo, X. P-03-007 Macek, J. P-07-004 Mahone, M. P-12-009 Marin, A. P-06-007 Mattingly, G. P-18-004, P-18-005 Mazhar, H. P-16-004 Merzon, E. P-07-005, P-19-007 Mgutshini, T. P-05-008 Midtlyng, E. P-07-008 Mikkelsen, S. H. P-01-007, P-04-001, P-04-002 Mulas Delgado, F. P-09-005 Nakagawa, R. P-07-001 Narang, R. K. P-21-010 Newcorn, J. P-17-008 Ni, X. P-13-004 Paulus, F. W. P-07-006 Perera, D. P-17-010
Perin Darim, N. P-04-003, P-21-014 Peters, K. YS-02-004 Pliszka, S. P-16-010 Popi, M. P-10-007 Purcell Baerga, P. P-06-003 Rademacher, J. P-18-002 Ren, J. P-17-003 Robaey, P. P-16-002, P-16-003 Roitsch, J. P-20-005 Rydell, M. YS-01-003 Saga, N. P-10-002 Sallee, F. P-16-011 Salunkhe, G. P-09-006 Schachar, R. P-19-006 Sedgwick, J. P-19-005 Seernani, D. P. P-08-005 Shen, C. P-02-001 Shih, M.-Y. P-14-006 Shyu, L. Y. P-15-010 Silva, D. P-02-002 So¨derlund, G. P-15-008 Solberg, B. S. FC-01-001 Song, M. P-04-004 Sorensen, L. P-10-003 Spalding, W. P-17-006 Sternat, T. P-07-002 Stordeur, C. P-08-006 Sun, L. P-09-007 Sun, X. P-02-007 Super, H. P-06-004 Szpindel, I. P-13-002 Ta_Torun, Y. P-17-002 Tangen, R. P-15-006 Ulberstad, F. P-04-005 Van Ameringen, M. P-18-003 van Stralen, J. P-17-007 Vanicek, T. YS-02-002 Velez-Pastrana, M. P-05-009 Vuori, M. P-14-007 Waddington, F. P-07-007 Wehmeier, P. M. P-05-005 Wu, J. P-21-005 Wu, Z. P-12-006 Xu, D. P-02-003 Yanfei, W. P-12-007 Yemula, C. P-21-006 Yoon, B.-E. P-13-001 Zhao, Q. P-02-007 Zuberer, A. P-14-008
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