Eur Arch Psychiatry Clin Neurosci (2007) 257 1–40 DOI 10.1007/s00406-007-1001-2

ABSTRACTS

1st European Conference on Schizophrenia Research Perspectives from European Networks 26–28 September 2007, Du¨sseldorf, Germany Guest Editors: Wolfgang Gaebel, Wolfgang Wo¨lwer, Du¨sseldorf, Germany

EAPCN 1001

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EDITORIAL

Dear colleagues, During the last decades considerable progress has been achieved in the treatment of schizophrenia and in the investigation of the etiology and the pathomechanisms of this disorder. However, many questions concerning e.g. the pathogenesis, early recognition as well as optimal treatment regimens still remain unsolved. In order to answer some of the most urgent questions concerted national or European research actions have been initiated during the last years. Even more progress may be achieved if such networking would be more coordinated and concentrated. Against this background the German Research Network on Schizophrenia organizes for the first time the ‘‘European Conference on Schizophrenia Research - Perspectives from European Networks’’ to be held from 26 September, 2007 to 28 September 2007 in Du¨sseldorf, Germany. One focus of this year’s conference is on results from network research in particular concerning the prodromal and first-episode stages of schizophrenia. Several symposia will provide the basis for the scientific exchange on these issues. Moreover, a special workshop shall bring together existing networks in order to mutually learn from each other about research strategies, about experiences in transferring research results into practice as well as about unmet needs, and thus may hopefully offer a chance to promote joint European efforts in schizophrenia research. Though this focus on network research, all interested colleagues regardless whether they participate in a research network or not are most welcome to present their results and to participate in these sessions. The conference is supposed to launch a series of European conferences on schizophrenia research to be organized every two years in the future. We are proud that this concept gained support by international (WPA), European (AEP), and national (DGPPN) scientific societies. On behalf of the scientific committee I would like to invite you to participate in this conference and I would be happy to welcome you in Du¨sseldorf. Sincerely yours, Wolfgang Gaebel Congress President and Speaker of the German Research Network on Schizophrenia

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ORGANIZATION/COMMITTEES Organization German Research Network on Schizophrenia (GRNS) / Competence Network on Schizophrenia Speaker: W. Gaebel, Du¨sseldorf Vice-Speaker: H.-J. Mu¨ller, Munich Director of Head Office: W. Wo¨lwer, Du¨sseldorf Organizing Committee:

W. Gaebel, Du¨sseldorf W. Wo¨lwer, Du¨sseldorf V. Toeller, Do¨sseldorf

Scientific Programme Committee A. G. Awad, Toronto, Canada H. Beitler, Renningen, Germany F. Bengtsson, Linko¨ping, Sweden G. Buchkremer, Tu¨bingen, Germany H. v. d. Bussche, Hamburg, Germany P. Falkai, Go¨ttingen, Germany W. Fleischhacker, Innsbruck, Austria W. Gaebel, Du¨sseldorf, Germany H. Ha¨fner, Mannheim, Germany R. Holle, Munich, Germany M. Jorge, Sao Paulo, Brazil J. Klosterko¨tter, Cologne, Germany V. Larach-Walters, Santiago, Chile W. Maier, Bonn, Germany M. Maj, Naples, Italy S. R. Marder, Los Angeles, USA P. D. McGorry, Melbourne, Australia J. Mezzich, New York, USA H.-J. Mo¨ller, Munich, Germany F. Mu¨ller-Spahn, Basel, Switzerland Ch. Raida, Cologne, Germany W. Ro¨ssler, Zu¨rich, Switzerland P. Ruiz, Huston, USA G. Schliebener, Herford, Germany W. Wo¨lwer, Du¨sseldorf, Germany M. Wolfersdorf, Bayreuth, Germany

Congress President W. Gaebel, Du¨sseldorf

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CONTENTS Plenary Symposia

Oral Presentations

S-01

O-01 Neuroimaging and neurophysiology 11 O-02 Psychological treatment and rehabilitation 13 O-03 Genetic research 14 O-04 Course of schizophrenia and new strategies of care 15 O-05 Prodromal stage of schizophrenia 16

Future perspectives in diagnosing schizophrenia: Bridging the gap between phenomenology and neurobiology 5

Symposia S-02 S-03 S-04 S-05

Perspectives in early psychosis: Early recognition, early treatment 6 Functional and neurobiological disturbances during the early course of schizophrenia: Treatment and relation to outcome 7 Acute and long-term treatment: Treatment of first-episode schizophrenia 8 Neuropsychology of schizophrenia: Experimental approaches 10

Satellite Symposia SA-01 Prevention of functional disturbances: How to accomplish? 11

Poster Sessions P-01 P-02 P-03 P-04 P-05 P-06 P-07 P-08 P-09

Prodromal stage I 17 Treatment I 20 Neurobiology 21 Neurocognition / Neurofunction Miscellaneous 25 Prodromal stage II 27 Treatment II (side effects) 30 Neurocognition 32 Electrophysiology 34

Authors Index Workshops W-01 Network research in schizophrenia - A European perspective? 11

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Plenary Symposia S-01 Future perspectives in diagnosing schizophrenia: Bridging the gap between phenomenology and neurobiology S-01-01 Problems associated with the current classification and diagnosis of schizophrenia H.-J. Mo¨ller (Psychiatric Hospital Ludwig Maximilians University, Munich, Germany) The psychiatrist faces many problems when classifying and diagnosing schizophrenia. Diagnostic systems do not attempt to find homogeneous groups. Quite the opposite, the diagnostic entity of schizophrenia currently comprises a heterogeneous collection of interrelated and relatively distinct phenotypes. These variants relate to relatively distinct brain-behavioural modules each with either overlapping or separate aetiology, pathophysiology, course characteristics and treatment response. At present, over one hundred combinations of symptoms can lead to a diagnosis of schizophrenia according to DSM-IV. Furthermore, the requirements that need to be fulfilled for a diagnosis of schizophrenia are not the same in the different diagnostic systems; for example, ICD-10 requires characteristic symptoms to have been present for at least one month, DSM-IV for at least 6 continuous months, raising questions about the validity of each system. Studies have shown that the frequency of diagnostic groups in large patient samples not only depends on the diagnostic system applied but also on the particular version of that system. The schizophrenia/ bipolar dichotomy has validity problems since a large proportion of individuals fall into the overlap area between schizophrenia and bipolar disorder and are currently diagnosed as schizoaffective, or Psychotic/Mood Not Otherwise Specified. At the moment, people with schizophrenia are grouped into categories, whereas it may be more clinically relevant to group symptoms (e.g. positive symptoms, negative symptoms, depression, mania, cognitive decline and functional impairment) into dimensions. Some evidence suggests that a dimensional approach may be superior to a categorical approach in terms of clinical usefulness and prognostic ability, but the question of diagnostic usefulness still has to be clarified. Factors such as duration, time course and aetiopathogenesis (e.g., emotional, cognitive, social) are important for the treatment and outcome of schizophrenia but are not covered by current diagnostic systems.

S-01-02 The future role of cognition in the diagnosis of schizophrenia towards DSM-V R. Keefe (Duke University Medical Center, Durham/North Carolina, USA) Neurocognitive impairment is considered a core component of schizophrenia, and is increasingly under investigation as a potential treatment target. On average, cognitive impairment is severe to moderately severe compared to healthy controls, and almost all patients with schizophrenia demonstrate cognitive decrements compared to their expected level if they had not developed the illness. Compared to patients with affective disorders, cognitive impairment in schizophrenia appears earlier, is more severe, and is more independent of clinical symptoms. Although the DSM-IV-TR and ICD-10 descriptions of schizophrenia include several references to cognitive impairment, neither the diagnostic criteria nor the subtypology of schizophrenia include a requirement of cognitive impairment. This paper forwards for consideration a proposal that the diagnostic criteria include a specific criterion of ‘‘a level of cognitive functioning suggesting a consistent severe impairment and/or a significant decline from premorbid levels considering the patient’s educational, familial, and socioeconomic background’’. The inclusion of this criterion may increase the ‘‘point of rarity’’ with affective psychoses and may increase clinicians’ awareness of cognitive impairment, potentially leading to more accurate prognosis, better treatment outcomes, and a clearer diagnostic signal for genetic and biological studies. Future research will need to address the validity of these possibilities. The

reliable determination of cognitive impairment as part of a standard diagnostic evaluation will present challenges to diagnosticians with limited resources or insufficient expertise. Cognitive assessment methods for clinicians, including brief assessments and interviewbased assessments, are discussed. Given the current emphasis on the development of cognitive treatments, the evaluation of cognition in schizophrenia is an essential component of mental health education. S-01-03 Neural mechanisms of genetic risk for schizophrenia A. Meyer-Lindenberg (Central Institute of Mental Health, Mannheim, Germany), (National Institutes of Health, Bethesda, USA) Introduction: Schizophrenia is highly heritable, but the underlying genetic architecture is complex and the mechanisms by which genetic variation increases risk have long seemed elusive. As common risk alleles for schizophrenia become available through candidate and genome wide association study, a translational characterization of their impact on brain structure and function provides an important tool to discover new disease-associated mechanisms that can provide novel treatment targets. Methods: We describe an imaging genetics approach in cohorts of genotyped patients, first degree relatives, and controls studied using multimodal imaging in conjounction with genetics. Results: Our findings implicate genes and circuits related to dopaminergic neurotransmission (COMT, DARPP32), glutamatergic neurotransmission (GRM3) and neural plasticity (BDNF), among others, as contributing to genetic risk in the pathophysiology of schizophrenia. Conclusion: Convergent evidence implicates disturbed connectivity, reduced prefrontal signal to noise, and abnormal regulation of dopaminergic and glutamatergic neurotransmission in the pathophysiology of schizophrenia. Implications for treatment are discussed. S-01-04 The future contribution of genetics to the diagnosis of schizophrenia W. Maier (Klinik und Poliklinik fu¨r Psychiatrie und Psychotherapie, Bonn, Germany), D. Rujescu Genetics is currently providing the major cue to the etiology mulifactorial diagnsis like schizophrenia. Diagnosis of schizophrenia is exclusively based on psychopathological patterns and temporal criteria without reference to any explicit etiological determinant. Despite the limitations of this symptom based diagnosis it became possible through the tools of molecular genetic to identify a growing number of susceptibility genes and causal determinants. Yet, apparently the expected diagnostic specificity of schizophrenia associated genetic markers is becoming more and more questionable given the current state of evidence. A reason for this transnosological nature of genetic determinants might be that they are impacting on a set of neurobiological characteristics some of which are shared between diagnoses. Symptoms and symptom patterns are apparently too complex and under the additional influences of various environmental forces to show a specific relationship to DNA-sequence variations. We will give examples of susceptibility variants with specific and unspecific relationship to the diagnosis of schizophrenia and psychoses. This constellation raises the question of symptom based mental disorders can be rooted in distinct etiologies. Consequences for future diagnostic systems are discussed on. S-01-05 Functional psychopathology: A future framework for diagnosing schizophrenia W. Gaebel (University of Du¨sseldorf, Dept. of Psychiatry and Psychotherapy, Du¨sseldorf, Germany) Today, schizophrenia is diagnosed in a descriptive manner based on psychopathologically defined clinical symptoms. The functional origin of symptoms - if known at all - is rarely in-volved into the diagnostic process. For the future advancements of diagnostic systems consid-ering the functional basis of psychopathology be-

6 yond nosological categories may be of in-creasing importance. The aim of such an approach should be the development of a functional psychopathology, characterizing symptoms not only on a descriptive level but dissecting them in their component parts, i.e. psychological dysfunctions underlying these symptoms. Such an approach may help to elucidate the non-specificity of biological variables related to psychiat-ric disorders and may increase the chance of finding meaningful relations between biological and behavioural variables. Starting with a historical view on the development of psychopathology in the last century, the rediscovery of this approach in the field of evolutionary psychology with the concept of mas-sive modularity and its implementation in psychopathology and the classification of mental disorders will be described. A proposal for a modular connectionist diagnostic system of men-tal disorders is developed , which integrates modern neurobiological and genetic findings in psychiatry on the background of a biopsychosocial approach. S-01-06 Diagnosing schizophrenia - stigmatization included? W. Ro¨ssler (Universita¨tskrankenhaus, Abt. Psychiatrie, Zu¨rich, Switzerland) No other illness is subject to more negative public attitudes than mental illnesses. In consequence this leads to social exclusion and discrimination. These negative consequences are especially widespread among persons with schizophrenia, quite often even complicated through self-stigmatization. Although there is a superficial willingness of the general population to integrate mentally ill in everyday life for example as a colleague at work most people refuse to establish a personal relationship to mentally ill. This attitude is even more pronounced toward persons with schizophrenia. Furthermore persons with schizophrenia are the ones who are mostly labelled as dangerous or unpredictable. As such diagnosing schizophrenia is like diagnosing a second (invisible) disease Professionals do not display a decisively more positive attitude in this matter. We had the opportunity to interview more than 1000 professionals concerning their attitude toward mentally ill, in particular also with respect to different diagnostic groups like depression or schizophrenia. These results will be reported and discussed in the framework of anti-stigma programmes.

Symposia S-02 Perspectives in early psychosis: Early recognition, early treatment S-02-01 Early recognition, early treatment: State of the art S. Lewis (University of Manchester, United Kingdom) Early intervention for psychosis has become an international initiative for the improved treatment of young people in the earliest phases of psychotic illness. The rationale for this includes the perceived link between duration of untreated psychosis and clinical outcome, as well as the importance of tailoring specific interventions to young people with no prior experience of mental health services. The approach is based on specific interventions in three areas: drug treatments, psychological treatments and service level interventions. The experimental use of drug treatments or cognitive therapy to prevent transition to full psychosis in people seeking help for at risk mental states, or prodromal symptoms has recently been evaluated and it appears that both drug treatments and psychological treatments are likely to be effective.

S-02-02 Development and evaluation of an early recognition inventory H. Ha¨fner (Zentralinst. Seel. Gesundheit, Schizophrenieforschung, Mannheim, Germany), K. Maurer (Zentralinst. Seel. Gesundheit, Schizophrenieforschung, Mannheim, Germany)

Introduction: The Mannheim KNS project developed and validated the Early Recognition Inventory ERIraos, consisting in a Checklist for the pre-selection of people at risk by the GP and in a 110 items symptom list applied on the expert level. Methods: Inter-rater reliability studies were conducted (Kappas and PARs). The validity of the Checklist as measure of psychosis proneness was proved by the RASCH model. The determination of the prognostic validity is based on Logistic Regression Models using the criterion ‘‘transition to psychosis’’. Results: Overall, Checklist and Symptom List proved to be reliable and valid scales. With increasing Checklist scores the transition rates also increased systematically, but in the Regression Model only one Checklist symptom (‘‘mistrust’’) remained significant. For the Symptom List, the combination of significant symptoms in an overall model identified 12 (52%) of the patients with psychotic transition correctly and 153 (93%) of the patients without transition, with an overall correct rate of 92%. Conclusion: Based on the validation study, ERIraos now is under revision. Especially the checklist was changed considerably by the selection of more prognostic relevant symptoms. The symptom list has widely remained unchanged, but a variety of optional assessment procedures should enable the user for a more flexible use. S-02-03 The contribution of neurobiology to early recognition M. Wagner (Klinik und Poliklinik fu¨r Psychiatrie und Psychotherapie Bonn, Germany), W. Maier (Klinik und Poliklinik fu¨r Psychiatrie und Psychotherapie, Bonn, Germany), I. Frommann, J. Brinkmeyer, A. Bechdolf, S. Ruhrmann, W. Wo¨lwer, T. Decker, J. Klosterko¨tter Introduction: Early recognition is relevant for neurobiological theories on schizophrenia because research with ‘‘prodromal’’ subjects allows to study the sequential development of biological changes and psychopathological symptoms, and hence the mechanisms of the disease. However, whether neurobiological measures can improve early recognition has only recently been addressed. Methods: Comparing data from the German Research Network on Schizophrenia (GRNS) with recent international work, this talk will first give an update on neurobiological findings in prodromal subjects, focussing on neurocognition, event-related potentials, startle inhibition, antisaccades, MRI, MRS, and PET. In many measures, prodromal subjects have similar or attenuated neurobiological alterations like first episode patients with schizophrenia. For example, both early and late prodromal subjects show deficits in executive functioning, P300 amplitude reductions, and reduced pre-pulse inhibition of the startle response. But only some of these measures are statistically related to (predict) later psychosis in prodromal subjects. Results: Whether or not neurobiological measures may enhance predictive accuracy over and above the prediction possible on the basis of psychopathological symptoms appears to depend on the population studied and the imminence of conversion. Funded by the German Federal Ministry for Education and Research BMBF, German Research Network on Schizophrenia, grants 01 GI 9934, 01 GI 0234. S-02-04 Biomarker profiles in prodromal and first onset stages of schizophrenia M. Leweke (University of Cologne, Germany), S. Bahn (Cambridge Centre for Neuropsychiatric Research, United Kingdom) Abstract not received S-02-05 Psychological and pharmacological interventions for persons at risk of psychosis S. Ruhrmann (University of Cologne, Psychiatry & Psychotherapy, Germany), A. Bechdolf (University of Cologne, Psychiatry & Psychotherapy, Germany), M. Wagner, H.-J. Mo¨ller, W. Gaebel, W. Maier, J. Klosterko¨tter Introduction: Prevention has become a major task in treatment of psychosis. Within the German Research Network on Schizophrenia a unique two-phase approach was evaluated.

7 Methods: 128 patients being putatively in an early initial prodromal state (EIPS) of psychosis, defined by cognitive-perceptive basic symptoms or a combination of functional decrease and biological risk indicators, were randomized to either cognitive behaviour therapy (CBT) or supportive counselling (SC) for 12 months, with another follow-up after 24 months. 124 pa-tients being putatively in the late initial prodromal state (LIPS), defined by attenuated or transient full-blown positive symptoms, were randomized to either a needs-focused interven-tion (NFI) or a combination of NFI with amisulpride (AMI+NFI) for up to 24 months. Results: In the EIPS study, significant lower conversion rates were observed with CBT after 12 and 24 months. Both conditions produce a comparable significant symptomatic and functional improvement. In the LIPS study, combined treatment with amisulpride yielded a superior acute 12-weeks treatment effect on positive, negative, affective and functional measures. First analysis of six-months effects showed a significant lower conversion rate with AMI+NFI. Conclusion: Both treatment approaches appear to at least delay the onset of psychosis, opening up the opportunity to adapt indicated prevention to the current needs of the patients. S-02-06 The European prediction of psychosis study (EPOS) - design, recruitment and first results R. K. R. Salokangas (University of Turku, Department of Psychiatry, Finland) Introduction: An early detection and indicated early intervention in the prodromal phase of psychoses should considerably improve their course and outcome. However, the benefits of such programmes require an evidence-based evaluation on the basis of a sufficient sample-size. This is the main aim of the European Prediction of Psychosis Study (EPOS). Methods: In the six European centres, 16 to 40 year old persons attending specialised or general psychiatric services were examined. Inclusion criteria were the presence of APS, BLPS, at least 2 of 9 Basic Symptoms (BS), and Familial risk or Schizotypal Personality Disorder plus reduced functioning (FR+RF). Additional assessments related to psychopathological, neurocognitive, neurobilogical and psychosocial aspects and use of services were carried at baseline, 9-month and 18-month follow-up examinations. Results: 246 putatively prodromal persons were included into the final EPOS baseline set. APS were detected in 84,1%, BS in 69,9%, FR-RF in 16,7%, and BLIPS in 11,0%. Highest rates of APS or BLIPS were found for ‘unusual thought contents/delusional ideas’ (64,6%) and ‘suspiciousness/persecutory ideas’ (54,5%), and highest rates of BS for ‘unstable ideas of reference’ (44,3%), and ‘thought pressure’ (42,7%). Patients’ functioning and quality of life were also considerably decreased. In all, 200 persons were successfully followed up for 9 months and 164 persons for 18 months. The hazard rate for a conversion to psychosis was 20% after 18 months. Conclusion: The level of psychopathology and functional decline found among the EPOS high-risk patients underlines the need for indicated recognition and intervention programmes.

S-03 Functional and neurobiological disturbances during the early course of schizophrenia: Treatment and relation to outcome S-03-01 The association between premorbid functioning, duration of untreated psychosis and outcome among patients with first-episode schizophrenia spectrum psychosis M. Nordentoft (University Hospital Copenhagen, Denmark), P. Jeppesen, M. Bertelsen, P. Le Quack, M.-B. Abel, A. Thorup, L. Petersen, J. Øhlenschlæger, T. Østergaard Christensen, G. Krarup, P. Jørgensen Introduction: There is convincing evidence of an association between the duration of untreated psychosis (DUP) and outcome of schizophrenia, but the association may be confounded by other factors like poor premorbid adjustment. The ideal research design for testing the hypothesis of a positive effect of early detection and

intervention is a randomised controlled trial, which cannot be conducted for ethical reasons. Studies using quasi-experimental design and natural studies indicate that early intervention may improve outcome in schizophrenia. Methods: In the Danish OPUS-trial of first episode psychotic patients, duration of untreated psychosis was evaluated with IRAOS. 547 patients were interviewed at baseline and 77 percent, 66 percent and 56 percent were interviewed at one- , two-, and five years follow-up, respectively. Patients with schizotypal disorder and patients who were excluded, thus 423 patients with psychotic disorder who had data on DUP (measured by IRAOS) and on premorbid adjustment (measured by The Premorbid Adjustment Scale as ‘premorbid social adaptation’ and ‘premorbid school adaptation’) went into the analyses. Results: DUP mean was 117 weeks, median 48 weeks. A total of 334 patients (79%) were assessed after one year and 294 (70%) after two years. Longer DUP was independently associated with more psychotic symptoms at entry and at one-year and two-year follow-up (P < 0.001). Poorer premorbid social adaptation was independently associated with more negative symptoms at entry and one-year follow-up (P < 0.001). Poorer premorbid school adaptation was associated with poor vocational outcome. Longer DUP and poorer premorbid social adaptation were both associated with smaller social network, but the association with DUP was not significant after controlling for premorbid social adaptation. DUP was not related to cognitive function, measured at five-year follow-up, but the academic dimension of premorbid adjustment predicted cognitive function. Conclusion: The association of DUP and outcome of psychosis was highly consistent even five years after first presentation, supporting the case for programmes that aim to reduce DUP. The relationships between premorbid adjustment, negative symptoms and social and vocational outcome are indicative of another dimension of illness, which begins long before the psychosis breaks through. S-03-02 Dopamine D2 receptors binding potentials in neuroleptic-naive first-episode schizophrenic patients: Relation to treatment outcome B. Glenthoj (Center for Neuropsychiatric Schizophrenia Research, Glostrup, Denmark), H. Rasmussen, T. Mackeprang, C. Svarer, L. Pindborg, L. Friberg, W. Baare´, C. Videbæk Introduction: We have previously reported highly significant correlations between frontal D2/3-receptor binding potentials (BP) and positive schizophrenic symptoms in neuroleptic-naı¨ve first-episode (FE) schizophrenic patients(1). The aim of the present study was to examine the relation of regional D2/3-receptor activity to treatment outcome. Methods: Twenty-three neuroleptic-naı¨ve schizophrenic patients were examined with psychopathological ratings and single-photon emission computerized tomography (SPECT) using the D2/3receptor ligand [123I]epidepride before and after 3 months of treatment with low doses of either risperidone (mean dose 3.8 mg/ day) or the typical antipsychotic drug, zuclopenthixol (mean dose 9.6 mg/day). Results: The main finding was that frontal D2/3-receptor BP in the neuroleptic-naı¨ve schizophrenic patients predicted treatment outcome with regard to positive schizophrenic symptoms in the total group of patients and in the subgroup treated with risperidone (p < 0.01). Given, very uniform occupancies in the zuclopenthixol group we did not expect - and did not observe - significant correlations between extrastriatal D2/3-receptors and treatment outcome in this group. In addition we found that high D2/3-receptor BP values in the left thalamus predicted treatment outcome with regard to negative symptoms. The data further confirmed correlations between blockade of D2/3-receptors in the left thalamus and effect on positive symptoms and (negative) correlations between treatment-effect on negative symptoms and blockade of frontal as well as thalamic D2/3-receptors. Conclusion: The present data strongly support that schizophrenic symptomathology is influenced by frontal and thalamic D2/ 3-receptor activity and that antipsychotic drugs not only exerts their therapeutic actions via D2 blockade in the striatum but also via frontal and thalamic D2/3-receptors.

8 S-03-03 Brain imaging in first-episode schizophrenia A. Vita (Psychiatric Unit of Spedali Civili and University of Brescia, Italy), L. DePeri Over the last three decades, the application of structural and functional brain imaging techniques in psychiatric research has enabled to detect multiple brain abnormalities in schizophrenia. Meta-analytic reviews of quantitative Magnetic Resonance Imaging (MRI) studies in first-episode schizophrenia (FES) have demonstrated that some brain morphological changes are already present at the onset of illness, in particular smaller whole brain volume (d = .242), enlarged third (d = ).591) and lateral ventricles (d = ).323) and hippocampal volume reduction (d = .357 for the right hippocampus and d = .574 for the left hipppocampus) (Vita et al, 2006 and 2007). Along with volumetric brain abnormalities, findings of white matter disrupted connectivity have been reported in FES patients by means of Diffusion Tensor MRI, mainly in fronto-temporal regions. Patterns of decreased regional blood flow and glucose metabolism in the prefrontal, cyngulate and temporal cortex (both at rest and during activation tasks) have been well documented in functional neuroimaging studies performed with Single Photon Emission Tomography or Positron Emission Tomography. Moreover, an anomalous activation of the prefrontal cortex in FES patients has been reported also in several functional MRI studies. Taken together, the results of structural and functional brain imaging studies in FES suggest a pathophysiological trajectory of the disease characterized by an earlier involvement of temporo-lymbic and frontal structures followed by a later involvement of other cerebral regions in the course of the illness. S-03-04 The neurotoxicity of psychosis: A five-year longitudinal MRI study in first-episode schizophrenia W. Cahn (Univ. Medical Center Utrecht, Department of Psychiatry, The Netherlands), M. Rais, F. P. Stigter, N. E. van Haren, E. Caspers, H. E. Hulshoff Pol, Z. Xu, H. G. Schnack, R. S. Kahn Introduction: The cause of progressive brain volume changes in schizophrenia is not yet understood, but it is thought that psychosis could be neurotoxic. This MRI study examined first-episode patients with schizophrenia and related the duration of psychosis to the progressive brain volume changes over time. Methods: Patients with first-episode schizophrenia (n = 48) were included in this study. For all subjects MRI scans were obtained at inclusion (T0) and after five years (T5). Total brain, gray and white matter, lateral ventricle and third ventricle volumes were measured. Percentage of brain volume change was calculated. Duration of psychosis was estimated in months using data from IRAOS (T0 and T5) as well as the PANSS ratings acquired throughout the five year follow-up period and through close investigation of the medical records. Linear regression analyses were performed to examine the relation between duration of psychosis and progressive brain volume changes. Results: Duration of psychosis was significantly related to the progressive volume decreases in gray matter (b = ).05, p = .03) and progressive volume increases in lateral (b = ).38, p < .01) and third ventricles (b = ).39 p = .01). Conclusion: These findings suggest that progressive brain volume changes in schizophrenia are related to the duration of psychosis and underpin the hypothesis that psychosis is neurotoxic.

S-03-05 Mechanisms underlying hippocampal pathology in schizophrenia: Failure in synaptogenesis, neurogenesis or both? P. Falkai (Universita¨t Go¨ttingen, Psychiatrie / Psychotherapie, Germany), A. Schmitt, T. Wobrock, F. Pajonk, O. Gruber Volume reduction of the hippocampus is quite prevalent in schizophrenia and can be found in the different stages of the illness. Metaanalyses demonstrate a bilateral 6% volume reduction in chronic schizophrenia. Although this volume decrease is accom-

panied by clinically relevant deficits in episodic memory, the underlying mechanisms still are unclear. In a recent study examining the hippocampal volume in families uni- and multiply affected with schizophrenia a bilateral decrease was shown in family members suffering from schizophrenia and to a lesser extent in their first degree relatives. Interestingly the biggest effect was due to the atrisk-haplotype of Neuregulin-1, while obstetric complications formed an additional independent risk factor.

S-04 Acute and long-term treatment: Treatment of first-episode schizophrenia S-04-01 Treatment of first-episode schizophrenia: State of the art R. Emsley (University of Stellenbosch, Department of Psychiatry, Tygerberg, Cape Town, South Africa) Introduction: Aggressive treatment to remission after a first-episode of schizophrenia offers the best chance of achieving optimal outcomes. In the early phase of illness patients are more responsive to antipsychotic treatment, but at the same time more sensitive to side-effects. They are also at great risk for relapse, particularly as a result of non- or partial compliance. Methods: This presentation will examine data from several recently completed long-term studies assessing risperidone, olanzapine, quetiapine and haloperidol in first-episode schizophrenia. It will also present results of a study using long-acting risperidone in first-episode psychosis. Results: The studies show good short-term efficacy for all treatment modalities. However, high levels of weight gain are reported with all of the medications; extrapyramidal symptoms particularly with haloperidol and risperidone; and prolactin-related adverse events with haloperidol and risperidone. Also, all of the studies with oral medication have very high discontinuation rates indicating limited effectiveness of these oral antipsychotics. Conclusion: Keeping patients in treatment is the single most important aspect of attaining sustained remission. Effectively dealing with side-effects may be important in this regard. Various psychosocial interventions are effective in improving compliance. Long acting injectable antipsychotics should be considered in treating first-episode schizophrenia. S-04-02 Optimization of acute treatment in first-episode schizophrenia patients by new pharmacological treatments H.-J. Mo¨ller (Psychiatric Hospital Ludwig Maximilians University, Munich, Germany) Introduction: First episode schizophrenic patients are increasingly seen as a special sub-group with respect to treatment. Studies have shown that these patients respond very well to relatively low doses of neuroleptics. On the other hand, they have a greater risk of experiencing extrapyramidal-motor side effects. Methods: The efficacy of haloperidol and risperidone in first episode schizophrenic patients was compared in a randomised, double-blind, prospective 8-week study performed within the framework of the German Schizophrenia Network. The study design ensured that the smallest clinically effective dose was administered. The study participants were inpatients at various German university hospitals. Results: The main objective of the study was to investigate whether the efficacy and extrapyramidal-motor tolerability of a second generation antipsychotic such as risperidone is superior to that of the classical neuroleptic haloperidol when both are given at the lowest possible dose. It was hypothesised that risperidone would be superior with respect to negative and depressive symptoms, cognitive impairment and extrapyramidalmotor tolerability. Conclusion: The preliminary results of the study comparing risperidone and haloperidol will be presented, as well as comparative results from a large, naturalistic study on the acute treatment of patients with first and multiple manifestations.

9 S-04-03 Pharmacological long-term treatment strategies in first-episode schizophrenia: Are there advantages of new atypical antipsychotics compared to low-dose first generation antipsychotics? W. Gaebel (University of Du¨sseldorf, Dept. of Psychiatry and Psychotherapy, Du¨sseldorf, Germany), M. Riesbeck, W. Wo¨lwer, A. Klimke, M. Eickhoff, M. von Wilmsdorff, M. C. Jockers-Scheru¨bl, K. Ku¨hn, M. Lemke, A. Bechdolf, S. Bender, D. Degner, R. Schlo¨sser, L. G. Schmidt, A. Schmitt, M. Ja¨ger, G. Buchkremer, P. Falkai, S. Klingberg, W. Ko¨pcke, W. Maier, H. Ha¨fner, C. Ohmann, H. J. Salize, F. Schneider, H.-J. Mo¨ller Introduction: Second generation antipsychotics (SGAs) have proven superior to first generation antipsychotics regarding relapse prevention mainly in multiple-episode patients. Practice guidelines recommend SGAs as first-line treatment particularly in first-episode patients, although evidence for this group is still limited. Methods: Accordingly, treatment with risperidone or haloperidol in low dose was maintained in the first post-acute year (randomized double-blind design). In the scope of the German Research Network on Schizophrenia, 159 outpatients with first episode schizophrenia (ICD-10 F20) were enrolled in 13 psychiatric university hospitals in Germany. Results: Under both antipsychotics no relapse evolved. Post-hoc defined measures of ‘marked clinical deterioration’ likewise did not differ between drug groups. Both antipsychotics were equally effective regarding significant symptom reduction and improvement in quality of life. Side-effects were low on average, with a tendency for more pronounced extrapyramidal symptoms under haloperidol. The overall drop-out rate of 68%, however, was not significantly different. Conclusion: Against the background of an overall favourable outcome the hypothesized difference between risperidone and lowdose haloperidol in first-episode patients could not be supported. With regard to the high drop-out rate, special programmes are needed to keep schizophrenia patients in their early and ‘critical’ illness course in effective and safe treatment. S-04-04 Comparison of outcome in first episode schizophrenia with different low dose antipsychotic drug regimens (EUFEST) W. Fleischhacker (Psychiatrische Universita¨ts-Klinik, Innsbruck, Austria) Abstract not received

S-04-05 The MESIFOS trial; guided discontinuation versus maintenance treatment in remitted first episode psychosis: Relapse rates and functional outcome L. Wunderink (University of Groningen, The Netherlands), F. J. Nienhuis, S. Sytema, C. J. Slooff, H. Knegtering, D. Wiersma Introduction: To compare the consequences of guided discontinuation strategy and maintenance treatment in remitted first episode psychosis in terms of relapse rates and functional outcome. Methods: The study was conducted in seven mental health care organizations, covering a catchment area of 3.1 million inhabitants. A sample of 131 remitted first episode patients, aged 18 to 45 years, with a diagnosis of schizophrenia or related psychotic disorder was included. After six months of positive symptom remission they were randomly and openly assigned to discontinuation strategy or maintenance treatment. Maintenance treatment was carried out according to APA-guidelines, preferably using low dose atypical antipsychotics. Discontinuation strategy was carried out by gradual symptom-guided tapering of dosage and discontinuation if feasible. Follow-up was eighteen months. Main outcome measures were relapse rates, and social and vocational functioning. Results: Twice as many relapses occurred in discontinuation strategy (43% vs. 21%, P = 0.007). Of patients who received the

strategy 20% were successfully discontinued. Recurrent symptoms caused another 30% to restart antipsychotic treatment, while in the remaining patients discontinuation was not feasible at all. There were no significant advantages of discontinuation strategy regarding functional outcome, though vocational functioning tended to be better. Conclusion: Only a limited number of patients can be successfully discontinued. High relapse rates do not allow discontinuation strategy to be common practice. However, if relapse risk can be carefully managed by close monitoring, in remitted first episode patients guided discontinuation strategy may offer a feasible alternative to maintenance treatment.

S-04-06 Psychological interventions in first-episode schizophrenia patients S. Klingberg (Universita¨tsklinik fu¨r Psychiatrie und Psychotherapie, Tu¨bingen, Germany), G. Buchkremer, W. Gaebel Introduction: According to evidence based treatment guidelines psychological intervention is increasingly regarded as an important part of a comprehensive treatment approach for patients suffering from schizophrenic disorders. However, there is currently only limited evidence regarding efficacy of psychological treatment in first episode patients. Treatment strategies should therefore be evaluated separately for this subgroup of patients. 2.Methods: In the framework of the German Research Network on Schizophrenia a multicentric randomised clinical trial addressing the efficacy of a comprehensive cognitive behavioral treatment program (CBT) to reduce the relapse rate in first episode schizophrenia was conducted. The treatment was guided by a published treatment manual. The control group received a short information centered psychoeducation (ICP) representing a good standard treatment. Patients were eligible for participation if they participated also in a double-blind pharmacological treatment trial. n = 111 patients gave their written informed consent. Results: Participants are characterised by a low level of positive symptoms and high level of medication compliance. 33 of 54 CBT patients (61%) participated completely in the treatment as opposed to 43 of 57 patients (75%) participating completely in the short ICP. In total, patients attended more than 80% of the scheduled sessions. Analyses of session protocols and audio tapes showed that therapists adhered satisfactory to the treatment manual. The primary endpoint of this study is the relapse rate two years after inclusion. Up to this time, 3 ICP and 0 CBT patients relapsed. This difference is not significant. Additional analyses regarding to process of treatment and further endpoints will be reported. Conclusion: CBT achieved the optimal 0% relapse rate in first episode patients. However, psychoeducation alone might be sufficient for relapse prevention in this patient group with high treatment compliance. S-04-07 The Danish National Schizophrenia project (DNS): A large scale prospective investigation of aspects of psychodynamic and integrated treatment B. Rosenbaum (Centre of Psychiatry, Glostrup, Denmark) Introduction: The Danish National Schizophrenia project for persons with a first episode psychosis within the schizophrenia spectrum (F20-29) has initially collected data for 562 persons, included consecutively in a 2 years period (1997)1999). The investigation covers 45% of the Danish population. The study has prospectively investigated three types of treatment: psychodynamic psychotherapy, integrated treatment and Treatment as usual. Methods: The presentation will include results from the investigations of: psychopathology and social function; changes of interpersonal self-image in psychotherapy; changes in the neurocognitive test profiles; and the content and outcome of Treatment as usual. Results: Data will encompass inclusion and 2 years follow-up. Preliminary 5 years data will also be indicated. Conclusion: Conclusion: After two years will patients receiving integrated treatment and the psychodynamic treatment do better

10 than the group of patients getting Treatment-as-Usual. Integrated treatment is superior compared with the two other modes of treatment.

S-05 Neuropsychology of schizophrenia: Experimental approaches S-05-01 Uncontrollable voices and their relationship to gating deficit in schizophrenia V. Kumari (Institute of Psychiatry, Psychology, London, United Kingdom), E. Peters, D. Fannon, P. Premkumar, A. Anilkumar, E. Kuipers Introduction: Prepulse inhibition (PPI) of the startle response refers to the ability of a weak prestimulus to transiently inhibit the response to a closely following strong sensory stimulus. This effect is reduced in a number of disorders known to be associated with impaired gating of sensory, cognitive or motor information. The aim of our study was to investigate acoustic PPI in relation to the dimensions of auditory hallucinations in schizophrenia and schizoaffective disorder. Methods: Acoustic PPI was measured in 62 patients (26/62 with current auditory hallucinations) and 22 healthy participants. Results: Patients, as a group, showed reduced PPI compared to healthy participants. The presence of auditory hallucinations was associated with a marked PPI deficit if the patients felt that they had no control over their occurrence and that they were unable to dismiss them. Conclusion: Perceived un-controllability over auditory hallucinations is associated with a gating deficit in schizophrenia although they are theorised to result from impaired monitoring of inner speech. S-05-02 Backward masking: A potential endophenotype for schizophrenia A. Brand (Klinikum Bremen-Ost, Center for Psychiatry, Germany), E. Chkonia, M. Roinishvili, M. H. Herzog Introduction: Endophenotypes are quantifiable measures of a disease located between the genotype and the phenotype. Amongst other requirements, an endophenotype has to be associated with the disease. Moreover, performance in relatives must be worse compared with healthy controls (Gottesman and Gould, 2003). Methods: We compared performance in a backward masking task (shine through), a memory test (CVLT), an attention paradigm (CPT), and an executive functioning test (WCST). 54 medicated schizophrenic patients, 34 first-order relatives, and 27 healthy controls joined. Results: In all tests schizophrenic patients performed worse than healthy controls. When comparing first-order relatives and healthy controls, we found significant performance differences for the backward masking test but not for the CPT and the CVLT, and only a tendency for the WCST. Moreover, the diagnostic accuracy was poor for the three cognitive tests (measured by means of the AUC), whereas backward masking showed a sensitivity of 68% at 80% specificity (AUC = 0.758). Conclusion: Thus, we conclude that the shine-through backward masking paradigm fulfils two crucial requirements for an endophenotype of schizophrenia whereas other classical tests, according to our study, do not.

S-05-03 Genetic and neuroimaging studies of oculomotor endophenotypes U. Ettinger (Institute of Psychiatry at King’s College London, United Kingdom) Antisaccade deficits are a promising schizophrenia endophenotype. In this talk I will review studies that have demonstrated antisaccade deficits in sibling and twin pairs discordant for schizophrenia. I will then present a recent investigation of the relationship between brain function during eye movements and a single nucleotide polymor-

phism (SNP) in the catechol-O-methyltransferase (COMT) gene, a candidate gene for schizophrenia and brain function. The COMT val158met SNP (rs4680) was genotyped and the brain response during prosaccades (towards a target) and antisaccades (away from a target) was measured using fMRI in 36 healthy humans. There were no associations between genotype and blood oxygen level dependent (BOLD) response in areas showing task related activation. However, val158 carriers (N = 24) showed reduced BOLD response in deactivation (or default network) areas during antisaccades, whereas val158 non-carriers (N = 12) showed reduced BOLD response in a deactivation area during prosaccades. These findings suggest that COMT val158met genotype may affect the brain response as a function of task characteristic. The findings are compatible with a hypothesis on the role of COMT val158met genotype in tonic and phasic dopamine levels in cortex and differential behavioural effects on measures of stability (e.g. prosaccades) and plasticity (e.g. antisaccades) (Bilder et al 2004 Neuropsychopharmacology). S-05-04 Sensory and motor encoding strategies in N-back tasks: Implications for working memory deficits in schizophrenia S. Lis (Justus-Liebig Univ. Giessen, Psychiatric Hospital, Germany), S. Krieger, J. Apostolopoulos, B. Gallhofer, P. Kirsch Introduction: Working memory (WM) disturbances are regarded as a core neurocognitive feature of schizophrenia. Although schizophrenic patients perform poor in WM-tasks, there is still an ongoing debate whether impairments can be linked to WM-(sub-) functions or reflect dysfunction in other cognitive processes additionally required for task solving. Methods: A reaction-time-decomposition-approach including N-back-tasks was applied in 12 neuroleptically naı¨ve, first-episode schizophrenic patients and healthy controls (study1) as well as 36 healthy controls (study2). Results: The deficits of schizophrenic patients in N-back tasks can be traced down to impairments in elementary cognitive processes already involved in choice-reaction-tasks. This holds true only if patients and healthy controls apply comparable strategies to maintain information in a sensory code of WM. If the task permits the selection of the appropriate response before the delay, only healthy controls shift towards a motor strategy with faster reactions and higher accuracy. A second study manipulated experimentally the possibility to apply a motor representational code in healthy subjects. If motor coding was prevented, the deficits of schizophrenic patients could be simulated in healthy controls. Conclusion: The results suggest that depending on the features of N-back-tasks the deficits of schizophrenic patients can be traced down to alterations in cognitive processing that are most likely not attributable to WM dysfunction. S-05-05 Abnormal functional and structural connectivity in schizophrenia - experimental approaches and neurogenetic results A. Meyer-Lindenberg (Central Institute of Mental Health, Mannheim, Germany), (National Institutes of Health, Bethesda, USA), E. Bullmore, D. Bassett From Wernicke’s time, the etiopathogenesis of schizophrenia has been linked not to a localized brain dysfunction, but to a disturbance of neural interactions interfering with coordinated brain activity. New analysis techniques combined with the ability of neuroimaging for high-dimensional mapping of brain structure and activity allow the quantitative assessment of the longstanding ‘‘dysconnectivity’’ hypothesis of schizophrenia. In a series of studies, our laboratory has shown (a) abnormal functional connectivity patterns discriminate between patients and control (b) task-specific abnormalities between the hippocampal formation and DLPFC in schizophrenia (c) a contribution of abnormal hippocampal-prefrontal and striatal-prefrontal interactions to the genetic risk architecture of schizophrenia and (d) pronounced heritable abnormalities in structural connectivity indicating maturational dysregulation of the extended limbic vs. neocortical system in schizophrenia. Together, these findings confirm Wernicke’s idea and extend them from a unitary ‘‘dis’’connection to a

11 modality- and cognitive state related ‘‘dys’’connection theory of schizophrenia. S-05-06 Adaptive tasks: An experimental approach to deal with the performance-activation problem in neuroimaging studies P. Kirsch (University of Giessen, Centre for Psychiatry, Germany), D. Mier, K. Zygrodnik, C. Sauer, C. Esslinger, B. Gallhofer, S. Lis Neuroimaging studies on neuropsychological deficits in schizophrenia patients often produce inconsistent results. While some authors report hypoactivation in relevant brain structures, others report hyperactivation. Both deviations in brain activation are attributed to cognitive impairments of patients suffering from schizophrenia. However, depending on differences in task performance these activation differences between patients and normal control participants are difficult to interpret. Especially when hypoactivation is observed together with reduced performance, the neurobiological deviation can hardly be attributed to a deficit in the specific task but could also be due to other variables like reduced motivation or task involvement. Here we present as one approach to deal with this problem the usage of adaptive tasks. In adaptive tasks, each participant should work at his or her individual maximal performance level. Differences in brain activation can then be attributed to a biological deficit (in the case of hypoactivation) or its compensation (in the case of hyperactivation). The application of the adaptive task approach in two neuropsychological brain imaging experiments, a reward task and a face recognition task demonstrates its usability for neuroimaging studies on brain activation in schizophrenia.

Satellite Symposia SA-01 Prevention of functional disturbances: How to accomplish?

Oral Presentations O-01 Neuroimaging and neurophysiology O-01-01 Using neuroimaging to characterize patients with psychoses according to brain morphological, physiological and functional parameters O. Gruber (Georg August University, Psychiatry and Psychotherapy, Goettingen, Germany) Introduction: The application of modern neuroimaging techniques allows to determine brain structural and functional characteristics in psychiatric disorders. In part, these characteristics may serve as intermediate phenotypes, i.e. biological markers, which may help to clarify genetic and other pathophysiological factors that are involved in the pathogenesis of psychoses. Methods: In this talk, recent findings from studies using structural and functional MRI will be presented. Results: These findings highlight how genetic factors like the potential NRG1 risk haplotype HAPICE may contribute to the vulnerability for schizophrenia and other psychotic disorders. Furthermore, genetic polymorphisms of serotonergic and dopaminergic neurotransmission seem to differentially affect neurofunctional subsystems of working memory, which are considered to represent promising endophenotypes in schizophrenia and in bipolar affective disorder. Both functional (i.e. neurocognitive) and physiological (i.e. hemodynamic) parameters acquired during specific testing of working memory performance may provide important information for differential diagnosis between different types of psychoses. Finally, there is also evidence that brain imaging may help to predict clinical outcome, treatment response and the potential for relapse after treatment. Conclusion: Neuroimaging contributes to a better understanding of the pathophysiology of schizophrenia and other psychotic disorders, and may allow more individual and effective treatment planning in the future.

Supported by an educational grant of Janssen Cilag GmbH Abstracts not received

Workshops W-01 Network research in schizophrenia - a European perspective? W-01-01 Trends in schizophrenia research from the European perspective C. Ho¨schl (Prague Psychiatric Centre, Czech Republic) Although Europe (EC, WHO, EBC) starts networking also the research in applied neuroscience, the research of schizophrenia in EU still remains diverse and uneven on all levels (basic, clinical, public health policy). In European region, we stay now in front of defining gaps in the evidence base and setting up research priorities. More active harmonization of research activities across Europe would lead to filling in the gaps effectively according to particular assets of research teams. EU authorities should serve as a potential source and proponent of funding of such a process. Research teams have also to decide if further networks are needed over and above those that already exist and to look for new resources on EU level. They should also reflect why some networks have been more successful than others and determine whether there is a scope for existing networks to come closer together. The role of AEP will also be discussed. W-01-02 Health research in the 7th research framework programme of the EU D. Dollase (EU Liason Office of German Research Organisations (KoWi), Brussels, Belgium), A. Cesarlo Abstract not received

O-01-02 Duration of illness and working memory in schizophrenia: An fMRI investigation V. Kumari (Institute of Psychiatry, Psychology, London, United Kingdom), S. Elsabagh, P. Premkumar, A. Anilkumar Introduction: An association has previously been demonstrated between prefrontal cortex volume decreases and illness progression in schizophrenia, however, as of yet the impact of illness duration on the working memory neural network remains unexplored. We investigated the effect of ageing and duration of illness on working memory and related brain activations in schizophrenia. Since sex differences are known to exist with regards to cognitive deficits and clinical outcome in schizophrenia, possible sex-specific effects of duration of illness were also explored. Methods: Twenty-five patients with chronic schizophrenia and 25 healthy controls underwent functional magnetic resonance imaging during performance of an ‘‘n-back’’ task. Results: Patients performed significantly worse than healthy controls on the task but there was no effect of sex. Significant ageing effects in neural activation were apparent in healthy controls, but not in schizophrenia patients. Duration of illness was correlated negatively with activity in different neural regions in male and female patients, the most robust findings being decreased activation of the cerebellum in females and the dorsolateral prefrontal cortex in males. Conclusion: A longer duration of schizophrenic illness is associated with reduced dorsolateral prefrontal cortex activity in males and reduced cerebellum activity in females regardless of their performance and age.

12 O-01-03 Functional cerebral indicators of relapse: Results from the German research network on schizophrenia F. Schneider (RWTH Aachen University, Department of Psychiatry, Germany), U. Habel, M. Reske, T. Kellermann, T. Sto¨cker, N. J. Shah, K. Zilles, D. F. Braus, A. Schmitt, R. Schlo¨sser, M. Wagner, I. Frommann, T. Kircher, A. Rapp, E. Meisenzahl, S. Ufer, S. Ruhrmann, R. Thienel, H. Sauer, F. A. Henn, W. Gaebel Introduction: Within this multi-center project, 75 first-episode schizophrenia patients and 81 controls were investigated with fMRI while performing an n-back task. Subjects were reassessed after 6, 12 and 24 months. The aim of the study is to determine cerebral dysfunctions in patients along with their predictive value regarding relapse risk. Methods: We developed a fully-automated quality assurance of scanner hard-and software and a measure for in vivo data quality (Sto¨cker et al., 2005). Data of 48 patients and 57 controls were included into the analysis (Schneider et al., 2007). Results: During attention-related processes, there emerged hypoactivations in the ventrolateral prefrontal and temporal cortex and the thalamus. During working memory performance, parietal hypoactivations were prominent and were accompanied by poorer performance in patients. A hyperfrontality emerged in the ventrolateral prefrontal cortex. Further analyses reveal that patients without a genetic risk on the neuregulin gene exhibit stronger activations in frontal areas. This points to gene-related cognitive (dys)functions (Kircher et al., submitted). Each center performed an additional center-specific paradigm. In Aachen (Reske et al., 2007), a mood induction task was applied. Including data of two measurement time points, therapy-associated normalization of brain function was observed in fronto-temporal regions. Stable hypoactivations were reported too and may be related to persisting negative symptoms. O-01-04 Neuronal synchrony as a pathophysiological mechanism in schizophrenia P. Uhlhaas (MPI for Brain Research, Neurophysiology, Frankfurt, Germany), E. Rodriguez, F. Roux, C. Haenschel, K. Maurer, W. Singer Introduction: Schizophrenia is a neurodevelopmental disorder that is associated with neurocognitive deficits in multiple domains and an onset of psychotic symptoms during late adolescence. Methods: In the current study, we explored the role of neural synchrony in the pathophysiology of schizophrenia by examining neural synchrony in schizophrenia patients (N = 25), bipolar patients (N = 20) and age-matched controls (N = 25) as well as in a sample of healthy children and adolescents (N = 69). EEG-data were obtained during a Gestalt-perception task and analysed for induced and evoked spectral power as well as for phase-synchrony between 4-80 Hz. Results: The results showed that: 1) patients with schizophrenia are characterized by a deficits in long-range synchronization (Uhlhaas et al., 2006) 2) patients with schizophrenia showed reductions in evoked beta- and induced gamma-band oscillations that were specific to patients with schizophrenia 3) evoked and induced high-frequency oscillations, especially in the gamma-band, strongly increased during adolescence and were accompanied by marked changes in the topography and overall amount of phasesynchrony during the transition from adolescence to adulthood. Conclusion: These data indicate that dysfunctional neural synchrony may be related to cognitive dysfunctions and symptoms of schizophrenia. In addition, our developmental data indicate that cortical networks undergo important maturational processes during adolescence that may be related to the emergence of psychosis during this developmental period. O-01-05 Latency classification of the frontal MMN responses in schizophrenia V. Rodionov (Kfar Shaul Mental Hospital, The Neurophysiology Laborator, Jerusalem, Israel), R. Durst, M. Mager, A. Teitelbaum, S. Raskin, M. Shlafman, J. Zislin

Introduction: The aim of this study was investigation of MMNlatency in the 5–10Hz frequency range. Methods: A passive auditory oddball paradigm was applied to schizophrenics (67) and healthy subjects (55). The classification of the negative peaks latency of the differential Evoked Potential waveform (dEP) was performed using the cluster analysis. Results: Three types of negative dEP waves were identified: 1. N1-like (130–140ms). 2. N2-like (170ms). 3. 2-peak responses with the 1-st peak at 90–100ms and the 2-nd peak at 180–200ms. The N1-like response was obtained in controls and patients with the same percentage . The N2-like responses were significantly more frequent in healthy subjects and 2-peak responses were more frequent in patients. A significant dEP amplitude reduction in schizophrenics was revealed only in the N1-like response; a significant latency prolongation - only in the 2-nd peak of 2-peak responses. The only N1-like and 2-peak responses latency can be predicted linearly by the latencies of the response to deviant in both groups of subjects. Conclusion: The results indicate that the three types of the MMN-response defined are related to different types of cortical activity and these differ in healthy subjects and schizophrenics. O-01-06 ‘‘Mismatch negativity’’ in the visual modality is reduced among patients with schizophrenia J. Libiger (Med. School, Charles Univ., Psychiatry, Hradec Kralove, Czech Republic), A. Urban, J. Kremlacek, M. Kuba Introduction: Mismatch negativity is a negative deflection of amplitude in the course of event related potentials (ERPs), that is elicited by a deviant stimulus in a repetitive sequence of standard stimuli. MMN deficiency in the auditory modality has been investigated as an index of preattentional information processing in patients with schizophrenia. The significance of MMN in the visual modality is still a matter of controversy Methods: We investigated the ERP to visual motion stimuli in a group of 25 patients with the diagnosis of ICD 10 schizophrenia and a matched group of healthy controls. The area under curve (AUC) differences between responses to standard and deviant stimuli were computed. Results: In midline derivations significant amplitude reductions were detected in the summed ERP responses (Fz: P = 0,01, Wilcoxon test) to deviant stimuli of patients at the interval 100– 200 ms . However, among patients with shorter duration of schizophrenia (<2 years), there was no MMN reduction relative to controls. Conclusion: There is present an impaired generation of the visual MMN in patients with schizophrenia. Its significance as a marker of the cognitive decline and a dysfunction of magnocellular visual pathway needs to be clarified. This study was supported by research funding MSM 0021620816 of the Czech Ministry of Education.

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O-02 Psychological treatment and rehabilitation O-02-01 See page 36 O-02-02 A randomised controlled multi-centre study of Integrated Neurocognitive Therapy (INT) for schizophrenia patients M. La¨chler (University Hosp. of Psychiatry, Bern, Switzerland), D. R. Mu¨ller, V. Roder Introduction: Following the guidelines of the NIMH MATRICS initiative, we designed a cognitive-behavioural group therapy program (INT) as a further development of the cognitive component of Integrated Psychological Therapy (IPT). INT is partly computer based and intends to restitute and compensate neurocognitive and social cognitive (dys-)functions with a strong focus on the patients’ daily life context, on facilitating intrinsic motivation and resources. Methods: INT is currently being evaluated in an international randomised multi-centre study in Switzerland, Germany and Austria. A comprehensive assessment battery is applied before and after therapy and at a 1-year follow-up. Outcome data of 71 patients enrolled during the first study period are reported. Results: INT is highly accepted by the patients and drop-out rates are low. INT patients have superior outcomes in neuro- and social cognitive variables, negative symptoms, insight and social functioning compared to treatment as usual (TAU). Additionally, only the experimental group shows higher correlations between self-rated deficits in neuro- and social cognition and objective test performances at the post-assessment. Conclusion: This preliminary evidence of efficacy is encouraging. Further results, especially the follow-up data, have to confirm the significance of INT as a new cognitive remediation approach within a multimodal treatment concept. O-02-03 Psychological interventions for cognitive and emotional dysfunctions in schizophrenia - results from the German Research Network on Schizophrenia W. Wo¨lwer (University of Duesseldorf, Department of Psychiatry, Du¨sseldorf, Germany), N. Frommann, M. M. Dreher-Rudolf, A. Piaszek, S. Halfmann, M. Streit, R. Vauth Introduction: Dysfunctions concerning social cognition as well as impairments concerning basic cognition are well established in schizophrenia. Although these impairments have a significant relationship with poor social and vocational functioning, treatment approaches to overcome such dysfunctions are still rare. Methods: Four training strategies differing in targeted cognitive area (social vs. cold cognition) and in conceptual range (molecular vs. molar approach) were compared with treatment as usual in a two center RCT. A total of 113 schizophrenia patients finished the study. Outcome measures comprised facial affect recognition and basic cognitive functioning assessed by a neuro-psychological test battery. Results: Analyses revealed specific training effects in the form of a double dissociation: social cognition training improved facial affect recognition and understanding of social scenes and had only minor effects on memory, attention and executive functioning, with the molecular training being most effective in general. The two cold cognition trainings on the other hand improved attention or verbal memory, respectively, however did not improve social cognitive functions. Conclusion: Improvements in social cognition like facial affect recognition in schizophrenia patients is not obtainable with a traditional cognitive remediation programs focusing on basic cognition, but need functional specific training programs focusing on social cognitive processes. O-02-04 Remediation of neurocognition and social cognition in schizophrenia: Empirical evidence supporting combined treatment approaches D. R. Mu¨ller (University Hosp. of Psychiatry, Bern, Switzerland), M. La¨chler, V. Roder Introduction: Recent studies have shown empirical evidence of social cognition as a mediating factor between neurocognition and

functional outcome. But only a few therapy studies have investigated additional benefits in functional outcome of combined neurocognitive and social cognitive remediation. Integrated Psychological Therapy (IPT) for groups was one of the first comprehensive therapy programs to target deficits both in neurocognition (NC) and social cognition (SC). Methods: The aim of this meta-analytic study was to examine whether schizophrenia patients additionally benefit from NC when combined with SC in comparison to NC alone. 25 independent IPT studies implementing NC and SC subprograms were selected and quantitatively reviewed. Results: Effect sizes of NC and SC variables and functional outcome are significantly higher when NC and SC are combined, with the most pronounced effect in SC. Both treatment conditions (NC/SC combined and NC alone) obtain superior effects compared to control groups. Conclusion: In summary, the results indicate evidence of combined neurocognitive and social cognitive remediation. Further developments in IPT have to address more comprehensively neuroand social cognitive functions according to the recommendations of the NIMH-MATRICS initiative. O-02-05 Psychoeducation in schizophrenia: Does a preceding cognitive training enhance therapeutic effects? G. Pitschel-Walz (Technical University Munich, Psychiatry and Psychotherapy, Germany), J. Ba¨uml, S. Kraemer, T. Frobo¨se, A. Gsottschneider, C. Pohl, T. Jahn Introduction: Psychoeducation is a evidence based psychotherapeutic intervention for patients with schizophrenia. Psychoeducation can improve the knowledge about schizophrenia and patients get the chance to decide about their treatment more efficiently. In clinical routine settings the question arises whether even those patients who have cognitive deficits can derive any profit from the positive effects of psychoeducational interventions. Methods: The aim of the COGPIP study (supported by the German Research Foundation, DFG) is to examine, if the efficacy of psychoeducation in patients with schizophrenia is dependent on their cognitive performance and if a preceding cognitive training can enhance the therapeutic effects of psychoeducation. After informed consent patients are randomly allocated to either a standardized cognitive training (10 sessions within 2 weeks) or to routine occupational therapy. That follows a bifocal psychoeducational group programme (8 sessions within 4 weeks) for all study patients and their relatives. The effects of the cognitive training and of the psychoeducation are assessed directly after and in a 9-months follow-up. Results: The COGPIP study has started at February 2006. Up to now 78 patients gave informed consent. Results of the recruitment process and intermediate pre-post data are presented. O-02-06 Evaluation of 2 years’ residential care treatment for adolescents and young adults with schizophrenia M. Hemmerle (Prof. Chr. Eggers-Stiftung, Trialog, Essen, Germany), B. Ro¨pcke, C. Eggers, R. D. Oades Introduction: The Trialog project (Professor Eggers Foundation) offers 8 patients with early-onset schizophrenia (EOS) residential treatment aimed to support recovery and independence. This is a 2-year programme of outpatient care following discharge from a clinic. The main features include interactive and psychoeducational family care, coping with persistent symptoms, development of social and emotional competence, independent house keeping, and support of school and vocational training. Methods: To evaluate psychopathology along with social and neuropsychological function at the start, after 1 year and after 2 years on completion of the programme for 14 participants. Their progress was compared with 10 EOS patients who did not attend Trialog following discharge. Results: The programme of intense care was accompanied by a significantly greater decrease of positive and negative symptoms

14 with respect to the comparison group. Measures of social function showed a marked improvement. Neuropsychological indicators of working memory, attention and some executive functions also improved more than in the comparison subjects.Neither group showed changes in measures of intelligence or the subjective quality of life. Conclusion: We show the benefits of an intensive residential training programme for EOS patients. Only a follow-up study will be able to show if these improvements can be maintained.

O-03 Genetic research O-03-01 A complementary strategy to approach the genetics of schizophrenia D. Rujescu (University of Munich, LMU, Dept. of Psychiatry, Germany) Introduction: Schizophrenia is a common mental disorder, affecting 0,5–1% of the population. There is evidence for a strong genetic component in the etiology of schizophrenia, as demonstrated by family, twin and adoption studies. The relative contribution of genetic factors has been estimated to be up to 80%. Methods: We first aimed to identify further schizophrenia genes in a large case-control and family-based study. 800 patients with schizophrenia and 200 first degree relatives were included. Furthermore, 2000 community-based healthy volunteers entered the study. All subjects are screened by SCID and characterized by other specific instruments. Furthermore, we use endophenotypes as a complementary approach. The rationale for their use in gene discovery is that the endophenotypes associated with a psychiatric disorder are more elementary compared to clinical phenotypes. Our ongoing endophenotype project includes a broad range of schizophrenia endophenotypes. These comprise, among others, neurophysiological or neuropsychological endophenotypes. We assessed the other above-mentioned endophenotypes in over 500 subjects in this ongoing study. Results: We present here data on the influence of common genetic variations on individual differences in cognitive abilities. Conclusion: We will discuss the findings in the context of schizophrenia and cognitive performance. O-03-02 The role of NRG1 in genetics of schizophrenia in Iranian population S. A. Mohamad Shariati (Tarbiat Modares University, Genetics, Tehran, Iran), M. Behmanesh, A. Fathian, H. Glaehdari, Introduction: Several putative schizophrenia susceptibility genes have recently been identified. Significant associations between schizophrenia and neuregulin 1 (NRG1) was first reported in 2002 and studies in several populations have since independently reported positive associations to this gene. Several polymorphisms located in 5¢ region of NRG1 gene have been the subject of association studies in different population. However results haven’t been consistent. Methods: Here we investigated the association of SNP8NRG221533 in some Iranian schizophrenics and in same number in healthy matched controls. To avoid population stratification, we have selected both affected and healthy people from Ahwaz province of Iran which include a homogenous population. Diagnosis was made according to DSM-IV criteria by expert psychiatrist. For genotyping SNP8NRG221533, we devised a new costeffective method called Multiplex-Nested-PCR-ARMS. Four primers were designed in order to genotype given SNP in a single reaction of PCR. Results: Genotypic and allelic frequency determined in affected and normal people.Bby using statistical tests we are analyzing data to find significant differences. Final results will be presented in congress. Conclusion: Our study includes new homogenous Asian population and might bring supportive evidence for the association of NRG1 with schizophrenia.

O-03-03 Influence of the COMT Val158Met Polymorphism in the clinical outcome in schizophrenia P. Molero (King’s College London, Institute of Psychiatry, United Kingdom), F. Ortuno, P. Lopez-Garcia, A. Patino-Garcia Introduction: Genetic variation in the Catechol-O-Methyltransferase (COMT) gene may influence the susceptibility to schizophrenia and the response to neuroleptic treatment. The authors aimed to test for an association between a COMT rs4680 (Val158Met) genotype and an eventual influence in the clinical outcome and in the response to treatment. Methods: The genotypes for SNP rs4680 were determined in 207 patients with schizophrenia. The severity of psychotic symptoms was assessed by the PANSS scale, and the response to neuroleptic treatment after a period of observation of 6 months by the GAF scale. The relationship between the genotype and PANSS and GAF scores was done using Kruskal-Wallis test. Results: Val/Val patients showed a higher severity of the psychotic symptoms both al baseline and after the period of treatment, that was significant in all PANSS-subscales and in PANSS-T. Val/ Val patients showed a slightly worse response to the neuroleptic treatment than Val/Met and Met/Met patients (p = 0.03). Conclusion: Our results show an influence of the Val158Met polymorphism on the severity of psychotic symptoms and on the response to neuroleptic treatment. Bibliography: Molero et al. Clinical involvement of catechol-O-methyltransferase polymorphisms in schizophrenia spectrum disorders: influence on the severity of psychotic symptoms and on the response to neuroleptic treatment. The Pharmacogenomics Journal advance online publication (13 March 2007; doi10.1038/sj.tpj.6500441) O-03-04 Evaluating the role of epigenetic factors in psychiatric disorders P. J. Rogue (Universite Louis Pasteur, Medecine and CHRU / Biochimie, Strasbourg, France) Epigenetics involves the selective utilization of genome information through the activation or inactivation of functional genes. The corresponding mechanisms, which include gene-specific DNA methylation, imprinting and histone modifications, play a key role in such fundamental processes as the fine-tuning of neuronal connections during development or the transcriptional regulation underlying long-term memory. An increasing number of recent clinical and molecular observations indicate that epigenetic programming and chromatin remodeling may also be involved in psychiatric disorders. Thus Rett syndrome is a common neurodevelopmental disorder generally attributable to mutations in the X-linked MeCP2 gene, whose product binds specifically to methylated DNA and functions as a transcriptional repressor and as a regulator of alternative splicing. Likewise, in the adult nervous system, hypermethylation of the promoter regions of various genes (RELN DRD2 and HTR2A) has been suggested to play a role in schizophrenia. Epigenetic factors have also been related to stress-related disorders. Furthermore, chromatin structure modulation by signal transduction pathways clearly plays a role in psychotropic drug action. Indeed long-term exposure to these drugs has been shown to elicit long-term adaptations involving druginduced changes in gene transcription, and it is now well established that transcriptional regulation is determined not only by sequencespecific regulatory factors but also by a complex network of co-acting factors many of which interact with nucleosomal histones to modulate local chromatin architecture. Thus, drug-induced plasticity is ultimatly played out at the level chromatin. In this presentation, the relevance of epigenetic mechanisms to psychiatric disorders and psychotropic drug action will be discussed. O-03-05 The influence of dysbindin (DTNBP1) gene variants on negative symptoms and prefrontal activation during working memory performance in schizophrenic patients F. Schlagenhauf (Charite´ (CCM), Department of Psychiatry, Berlin, Germany), D. Mu¨ller, S. Bu¨ttner, J. Wrase, J. Gallinat, A. Heinz, I. Puls

15 Introduction: Genetic risk factors play a key role in the pathogenesis of schizophrenia as is shown by concordance rates of 60% in monozygotic twins. However, the genes involved still remain unknown due to the multifactorial etiology of the disease; genetic heterogeneity and multiple external contributing factors play a major role. In recent years, a number of genetic association studies were published that tried to establish a link with specific clinical symptoms. Methods: In the first part of this study the negative symptoms of 129 schizophrenic patients were investigated with different neuropsychological tests. Furthermore, all patients were genotyped for dysbindin (dystrobrevin-binding protein, DTNBP1), a gene that has shown to have an effect on negative symptoms of schizophrenic patients in prior studies. For a replication study, 79 schizophrenic patients and 77 healthy controls were genotyped for DNBP1. The influence of the dysbindin genotype on prefrontal activation during a working memory task was investigated in a sub-sample using functional magnetic resonance imaging (fMRI). Results: Our preliminary results show an association between a SNP in intron 1 (rs1018381) and the severity of negative symptoms (p = 0.018). Future research is needed to clarify if genetic variations in this region have an effect on gene expression. Conclusion: Our study gives further evidence that DTNBP1 plays a role for development or extent of negative symptoms in schizophrenic patients. O-03-06 A model of schizophrenia T. Schelde (Frederiksberg Hospital, Department of Psychiatry, Denmark) Abstract: The objective of the study was to develop a model for a behavioural and physiological understanding of schizophrenia. Methods: Design and method (T. Schelde, JNMD, 2000) were based on objective observations of 11 schizophrenic patients and literature searched in PUBMED. Statistical analysis of the objective observations between schizophrenics and controls were made by the Man-Whitney test. Results: It seems that four already known hypotheses constitute a coherent model for the illustration of the etiology and the physiological dynamics of schizophrenia. Hypothesis 1 points to a dysfunction of gene G72 on chromosome 13 which leads to a low concentration of serum D-serine. Hypothesis 2: Because of the deficiency of serum D-serine - which is a potent agonist of the glycine site on the NMDA receptors - these become hypofunctional which may be a crucial factor in schizophrenia. Hypothesis 3: As a function of NMDA hypofunctionality the GABAergic neurons are hypoactive. That is, the concentration of GABA is too low to brake the accelerator cells (dopaminergic, serotonergic, and noradrenergic neurons). Hereby - during stressing conditions - the arousal level of the accelerator cells becomes increased corresponding to psychosis. Hypothesis 4 indicates that stress causes an increased influx of Ca++ into the accelerator cells which leads to psychosis; later on the psychosis may change to a depression like state. Conclusion: With the genetic starting point in G72 a possibility of hypofunctional NMDA receptors and a hypoactivity of the GABAergic neurons may contribute to the disease of schizophrenia.

O-04 Course of schizophrenia and new strategies of care O-04-01 Longitudinal analyses of psychotic experiences in the Zurich Study V. Ajdacic-Gross (Psychiatric Univ. Hospital, Clinical and Social Psychiatry, Zurich, Switzerland), W. Ro¨ssler, A. Gamma, K. Landolt, N. Stulz, J. Angst Introduction: This study presents analyses of longitudinal data over 20 years from the Zurich Study. The analyses examined predictors and correlates of psychotic symptom experiences in the general population. Methods: The Zurich Study is based on a stratified community sample of 591 persons born in 1958 (women) and 1959 (men). The

data were collected at six time points: 1979, 1981, 1986, 1988, 1993 and 1999. We analysed SCL-90-R items on psychotic experiences and paranoid ideation. We related them to the SCL depression subscale, to problems in childhood and youth as well as to cannabis use. The modeling was done with latent growth models. The analyses were performed with Mplus. Results: The SCL items were first transformed into two new subscales representing ‘‘schizophrenia nuclear symptoms’’ and ‘‘schizotypal signs’’. These subscales covary over time. Moreover, they covary with the depression subscale. However, they differ regarding their associations with risk factors (problems in childhood / youth and cannabis use). Conclusion: Expression of psychotic symptoms in populations is continuous and shows different levels of severity and persistence. The causes of and pathways to clinical psychotic disorder can be studied on different levels of the continuum, that is, mostly long before the disorder becomes clinically relevant as a psychotic disorder. O-04-02 Beyond the critical period: A longitudinal study of outcome in the eight years after a first episode of psychosis N. Crumlish (Stanley Research Unit, Cluain Mhuire Family Centre, Dublin, Ireland), P. Whitty, M. Clarke, S. Browne, M. Kamali, M. Gervin, O. McTigue, A. Kinsella, J. L. Waddington, C. Larkin, E. O’Callaghan Introduction: The critical period hypothesis proposes that symptomatic and psychosocial deterioration occurs primarily during the early years of psychosis, including the period of untreated psychosis. We tested two logical conclusions of the hypothesis: that outcomes stabilize beyond the critical period, and that the duration of untreated psychosis (DUP) correlates with medium- to long-term outcomes. Additionally, we investigated the relationship of duration of untreated illness (DUI) to outcome. Methods: This was a prospective, naturalistic, cohort study, with assessments at presentation, four years, and eight years. Our sample comprised 118 people consecutively referred with first-episode nonaffective psychosis to a community-based, geographically defined, urban catchment area psychiatric service in Dublin. Results: Negative and disorganised symptoms improved between four and eight years. Global functioning (GAF) improved by 4.6 points, and continuing GAF recovery was predicted by DUI. Shorter DUP predicted remission, lower positive symptom scores and better social functioning. Shorter DUI predicted lower negative symptom scores, higher GAF, and better occupational functioning and quality of life. Conclusion: These results provide qualified support for the critical period hypothesis. As DUI independently predicted eightyear outcome and recovery between four and eight years, the critical period could include the prodrome as well as early psychosis.

O-04-03 Schizophrenia - neuropsychological aspects of suicidal behaviour D. Cosman (University of Medicine, Clinical Psychology, ClujNapoca, Romania), M. Manea, S. Nica, B. Nemes, H. Coman Introduction: The suicide rates in schizophrenia patients are 10– 15% whereas the estimation of suicide attempts is 28–50%. The suicide risk factors are divided in: general factors (male gender, family history of suicide, stress, alcohol or substance abuse), schizophrenia related factors (poor functioning, prominent positive symptoms), depression related factors (depressed mood, hopelessness, impulsivity). Methods: A clinical sample of 67 patients with schizophrenia was assessed. Among them, 19 patients presented a life long history of deliberate self-harm. The control group included a clinical population (n = 48) without suicidal behaviour. We performed the assessment of schizophrenia (PANSS, GAS), depression (MADRS), suicidal risk (BSS, SAD PERSONS scale), severity of suicidal ideation (Beck Hopelessness Scale), quality of life (Multicultural Index of Quality of Life), neuropsychological markers with CogTest battery (Penn’s Emotion Acuity Test-PEAT, Word List Memory-WLM, Face Memory Test-FMT, Set Shifting Test-SST).

16 Results: Suicidal behaviour in schizophrenia patients was significantly correlated with depressive symptoms (helplessness, hopelessness) accompanied by positive symptoms (delusions) and also with poor global functioning. Some neuropsychological markers (abstract thinking, reduced capacity to maintain information on-line, working memory, facial emotions discrimination) were significantly correlated with hopelessness and suicidal ideation. Conclusion: The most significant neuropsychological dysfunction is represented by altered WLM and PEAT which is present in schizophrenia patients with self-harm behaviour even if they have an intact IQ. O-04-04 Improving outpatient treatment in schizophrenia: Effects of computerized guideline implementation - results of a multicenter-study within the German Research Network on Schizophrenia B. Janssen (Rheinische Kliniken Du¨sseldorf, Psychiatry and Psychotherapy, Germany) Introduction: Schizophrenia clinical practice guidelines are developed to give expert- and evidence-based advice to practicing psychiatrists to improve the management of this disorder. However, the use of these guidelines in everyday health care can be described as nonsatisfying. Within the project ‘‘Guidelinesupported quality management in outpatient treatment’’ we investigated whether guideline adherence and quality of outcome can be improved by implementing a computer-based decisionsupport-system. Methods: The experimental group consisting of 15 psychiatrists in private practice documented the treatment of schizophrenic patients using the guideline-based algorithms which were interactive and case-specific shown on PC-screen as soon as predefined triggers were met. The control group in Munich documented treatments via paper-pencil providing treatment-as-usual. Two further physician groups served as additional comparison groups: one also documented electronically, however without guideline support, the second group carried out additional quality circles while using the paper-pencil approach. Results: As a result of the intervention we observed a strong initial but time-limited improvement regarding core features of outpatient treatment in schizophrenia in the experimental group. Conclusion: The findings suggest that decision-support-systems, despite their limitations, can be used to enhance treatment outcome in schizophrenia outpatient care. O-04-05 Enforcing antipsychotic treatment in the community setting - does it work? S. Lanquillon (West Australian Country Health, Mental Health, Busselton, Australia), D. Fischer-Barnicol Introduction: In Australia treatment of outpatients can be legally enforced by ordering treatment in the community setting (CTO). But are CTOs effective? a) What factors predict success or failure of enforced treatment? b) What factors predict psychotic and social deterioration after a CTO has lapsed? Methods: Design: Ongoing study with follow-up of schizophrenic patients in rural communities. Patients are assessed before, during and after being under a CTO. Methods: Social and treatment variables are assessed with various instruments, e.g. DIP-DIS, psychopathometry and analysed statistically, e.g. logistic regression analysis. 48 patients included so far. Results: First results show a) patients’ acceptance of medicolegal enforcement and intensity of contacts with mental health staff to be most predictive of outcomes under CTO. b) drug abuse the strongest predictor of psychotic relapse and social deterioration after CTO has lapsed because patients then tend to stop antipsychotic medication. Conclusion: First results whether to make a CTO or not suggest to focus more on - the patient’s acceptance of enforced treatment the available resources of community mental health services for the required treatment intensity, while ongoing drug abuse under successfully enforced antipsychotic treatment seems to be an argument to extend enforced treatment.

O-04-06 Health promotion in mental health settings - a European network of mental health services H. Berger (Walter Picard Klinik, Riedstadt, Germany) Introduction: The Task Force on mental health promotion in psychiatric services is an europeanwide network of psychiatric services, which commits to promote mental health and mental disease prevention within psychiatric services. It’s existing since 1998, is supported by WHO Europe and part of the HPH-Network Methods: The members of the task force work together at four stages: 1. Developing models of good practice 2. Evaluation of these models of good practice 3. Developing standards of mental health promotion Results: The network is endued with a broad range of experience in mental health promotion and mental disease prevention especially for patients with schizophrenic disorders. Some promising projects need to be evaluated in depth. Conclusion: The network is a helpful instrument in detecting models of good practice of mental health promotion and mental disease prevention especially for patients with schizophrenic disorders

O-05 Prodromal stage of schizophrenia O-05-01 Premorbid schizoid-schizotypal traits and early onset schizophrenia course M. Kotlicka-Antczak (Medical University of Lodz, Psychiatry, Poland), J. Rabe-Jablonska Introduction: The objective of the study was to find associations between the occurrence and intensity of premorbid schizoid and schizotypal traits (PSST) and the schizophrenia course and symptoms. Methods: The presence and intensity of premorbid schizoidschizotypal traits of 50 DSM-IV schizophrenics with their first schizophrenia episode in adolescence, and schizoid-schizotypal traits (SST) of 30 healthy controls were measured using the Scale for Assessment of Premorbid Schizoid and Schizotypal Traits by Alice Foerster. Based on multiple evaluations with PANSS, the symptoms’ profile and the course of schizophrenia were determined. Results: We distinguished two groups of patients: with prominent negative and prominent positive symptoms. Schizophrenic patients with prominent negative symptoms and a chronic schizophrenia course showed significantly more SST since their childhood, compared both with the patients with prominent positive symptoms and the controls. The occurrence of SST in the premorbid period in the patients with prominent positive symptoms and in the controls were similar. Conclusion: The findings show that PSST are associated with a specific symptoms’ profile (prominent negative symptoms) and a chronic course of schizophrenia. They suggest that schizophrenia may be a pathogenetically heterogeneous disorder.

O-05-02 Symptoms of the early course influencing the time until transition to psychosis. Applying the Cox model on data of the ERIraos symptomlist K. Maurer (CIMH, Schizophrenia Research, Mannheim, Germany), G. Trendler, F. Ho¨rrmann, H. Ha¨fner Introduction: We have been interested if there are predictive symptoms influencing the duration of time from first treatment contact until the transition to psychosis. Methods: To study this question methods of event history modelling (Survival Analysis) are available. Especially, if there is no assumption about parameters of the survival function, the Cox Model may be suitable, as it only assumes that proportions of the hazards influenced by the covariates are constant over time.

17 Results: Based on the Cox Model, an overall model of predictors, identified in several section-specific analyses, results in eight significant covariates by entering the variables together and in five significant covariates by entering them stepwise. The symptoms consistently identified by both methods are ‘‘increased sexual interest’’, ‘‘early wakening’’, ‘‘odd behaviour’’, ‘‘rumination (without inner resistance)’’ and ‘‘loud thoughts / thought broadcasting’’. Conclusion: It was possible to identify a set of significant covariates influencing the time until psychotic transition. These variables are widely identical to those of a Logistic Regression Model to predict the binary criterion ‘‘transition to psychosis’’. O-05-03 Basic symptoms and UHR criteria: Testing a sequential model of symptom development retrospectively F. Schultze-Lutter (University of Cologne, Dept. of Psychiatry, Germany), S. Ruhrmann, V. Veith, J. Klosterko¨tter Introduction: A model of symptom development during the prodromal phase of psychosis assuming the succession of ‘unspecific symptoms - predictive basic symptoms (BS) - attenuated psychotic symptoms (APS) - (transient) psychotic symptoms’ was studied retrospectively in first-episode psychosis patients. Methods: Onsets of phases were defined by first occurrence of any of their respective symptoms. Group means were inspected for time differences as well as influence of socio-demographic and clinical characteristics. Results: Due to a reverse mean occurrence of BS and APS, the hypothesized sequence did not show for all 126 patients but, descriptively, for the male group, those at least 21 years old at onset of illness, with higher education and with 1st-degree relative with no psychiatric or a psychotic disorder. Graduation in particular but also family history and age at onset of illness predicted report of the hypothesized sequence best. Conclusion: The proposed sequential model was retrospectively supported for subgroups of patients. Whether this reflects true group characteristics or an effect of retrospective assessment, i.e., a recognition and recall bias, will show in prospective studies. However, the results also broadly support the notion of BS as a complementary approach to an earlier detection compared to the UHR criteria. O-05-04 Identifying children at risk for schizophrenia: A necessary step to new prospective investigations aiming to clarify aetiological processes S. Hodgins (Forensic Mental Health Science, Inst. of Psych., Kings College London, United Kingdom), K. Laurens Introduction: Four lines of evidence indicate that conduct problems in childhood are antecedents of schizophrenia. Among adults with schizophrenia, there are strong associations between Conduct Disorder prior to age 15 and violence. Some evidence suggests that males with childhood Conduct Disorder who develop schizophrenia are less neurologically impaired than other men with schizophrenia. We plan to conduct a prospective, longitudinal investigation to examine the developmental trajectory from conduct disorder to schizophre-nia. Presently, there is no cost effective strategy to identify children-at-risk for schizophrenia with no family history of the disorder. Methods: Questionnaires were developed to identify 9 to 11 year-old children with the putative antecedents of schizophrenia: motor and/or speech delays, emotional and/or behavioural problems, and psychotic-like-experiences. Results: 548 children and 264 care-givers completed questionnaires. 9.2% of boys and 4.1% of girls experienced the triad of antecedents. The prevalence of the triad of antecedents was higher among African-Caribbean children, as compared to white British children, and a trend suggested that the prevalence was lower among children of South Asian and Oriental origins. Conclusion: The sensitivity and specificity of this method of identifying children-at-risk for schizophrenia can only be tested by a longitudinal investigation. Initial results, however, are promising.

O-05-05 Coping in putatively prodromal persons and healthy controls J. Paruch (University of Cologne, Psychiatry & Psychotherapy, Germany), S. Ruhrmann, F. Schultze-Lutter, H. Picker, H. Graf von Reventlow, M. Neumann, V. Veith, A. Bechdolf, J. Klosterko¨tter Introduction: According to vulnerability-stress-model, coping plays an important moderating part in aetiopathology of psychosis. Methods: Coping strategies were investigated in 30 putatively prodromal persons (PP) and in 29 healthy control persons (HC). Results: Compared to HC, PP showed significant impairments in coping strategies in terms of a higher tendency to adopt potentially strain enhancing (passive) strategies and a lower tendency to adopt potentially strain reducing (active) strategies. The influence of depression on coping was clearly circumscribed. Conclusion: PP exhibited substantially impaired coping resources. Results thereby suggest that coping is yet constricted before first episode. Recent findings on biological indicators of HPA-axis hyperactivity as correlatives of high risk status which can predict transition to psychosis support such a suggestion. Since Literature also assumes that coping repertoire may alter with the course of the illness, i.e. passive coping prevailing in initial or relapse prodrome and active coping becoming more likely with ongoing adaptation to the illness, it is supposable that adaptive coping is not necessarily the same for patients and control persons. Thus, enhancing active coping and practising a differentiated use of active and passive coping should be individualized sub-goals of cognitive behavioural interventions in (evolving and manifest) psychosis. O-05-06 Premorbid adjustment and clinical symptoms in patients with first episode psychosis R. Pollice (University of L’Aquila, Dept. of Experimental Medicine, Italy), E. Di Giovambattista, A. Di Pucchio, M. Mazza, D. Ussorio, A. Tomassini, R. Roncone, M. Casacchia Introduction: The aim of this study, has been to identify the presence of premorbid adjustment alterations and the possible correlation with symptoms and clinical severity in a sample of in-patients with first-episode psychosis. Methods: This study enrolled 53 consecutive first episode psychosis patients over a period of 24 months with Schizophreniform Disorder DSM-IV diagnosis. They were interviewed and evaluated with the BPRS 24-Items, and with the Clinical Global Impression (CGI). The premorbid adjustment level has been evaluated, with the Premorbid Adjustment Scale (PAS) (Cannon-Spoor, Potkin And Wyatt, 1982). Total sample has been subsequently subdivided, on the basis of the definitive diagnosis, identifying two groups of patients: the first with diagnosis of Schizophrenia (S group), and the second with diagnosis of Bipolar Disorder (B group). Results: Our results show a progressive deterioration of premorbid adjustment, from the childhood to the adult age. Our findings, moreover, showed a positive correlation between the mean scores of PAS areas concerning the slow adolescence and the adult age and showed a positive correlation between the PAS area which investigates the general adjustment and the severity of the psychopathologic, as noticed by the BPRS and by the CGI Severity. Conclusion: Our study seems to confirm the presence of adjustment and general functioning deterioration in premorbid phase. Schizophrenic patients seem to show a precocious and progressive deterioration in social adjustment, presenting less interest in the life as regards the group of Bipolar patients.

Poster Sessions P-01 Prodomal Stage I P-01-01 Development and implementation of an early detection and intervention programme for persons at-risk for psychosis J. Klosterko¨tter (University of Cologne, Dept. of Psychiatry, Germany), W. Maier, H. Ha¨fner, S. Ruhrmann, A. Bechdolf, F. SchultzeLutter, M. Wagner, K. Maurer

18 Introduction: Within the last two decades, an early detection of and intervention in psychosis prior to its first frank manifestation has become one of the main topics in the research on psychosis, incl. the German Research Network on Schizophrenia, GRNS. Yet, little effort has been made towards carefully transferring results into clinical practise. Methods: Within the third funding period of the GRNS, such a transfer of current knowledge into clinical practise will be approached following three steps: product development, product evaluation and product dissemination. Results: Thereby, the assessment of the state of knowledge about an early detection and intervention as well as the needs of different target groups, i.e. mental and other health care professionals, relatives, patients and other lay-persons interested in this topic such as teachers, will generate the basis for the product development. The tailor-made test versions of the product will again be tested and evaluated by representatives of the target groups. Conclusion: Following this, the modules ‘Early detection’, ‘Early psychological intervention in the early initial prodromal state’ and ‘Early pharmacological intervention in the late initial prodromal state’ will be finalized and distributed P-01-02 Who initiates first help-seeking? Results from a retrospective study of first-episode psychosis A. Niedersteberg (Marienhospital, Dept. of Psychiatry, Duisburg, Germany), F. Schultze-Lutter, S. Ruhrmann, V. Veith, J. Klosterko¨tter Introduction: Pathways to care were studied retrospectively in firstepisode psychosis patients with special emphasis on the initiation of the first help-seeking contact. Methods: 126 in-patients with diagnosis of a first psychotic episode were interviewed in remission about symptom onset and help-seeking prior to first admission. Results: 120 patients had sought help before first admission, 117 recalled who had initiated or suggested help-seeking. The majority of help-seeking was initiated by the patient him-/herself (45%) or had been suggested by parents or siblings (34%), rarely by partners (4.3%), children (0.9%), friends (3.4%), colleagues or neighbours (1.8%) or other persons (10.8%). Thereby, help at a psychiatric/ neurological private praxis was mainly sought when the contact had been suggested by parents (42.9%), siblings (40.0%) or partners (80.0%). With regard to the mean time to admission, only selfinitiated help-seeking, mainly at GPs (30.2%), occurred before the onset of psychotic symptoms. Conclusion: Especially young people still at risk to develop psychosis as regards their age should be targeted by public campaigns raising the awareness to early symptoms of the developing illness and, simultaneously, reducing potential obstacles to help-seeking such as fear of stigmatization. In addition, the awareness of GPs to complaints of potential prodromal character should be raised. P-01-03 Pathways to psychosis: A comparison of the pervasive developmental disorder subtype multiple complex developmental disorder and the ‘‘At Risk Mental State’’ M. Sprong (University Med. Center Utrecht, Child and Adolescent Psychiatry, The Netherlands), P. Schothorst, H. Swaab, H. Van Engeland Introduction: The comparison of high-risk populations with different developmental pathways to psychosis may lend more insight into the heterogeneity of the manifestation of the psychotic syndrome, and possible differing etiological pathways. The aim is to compare high-risk traits and symptoms in two populations (12–18 yrs old) at risk for psychosis, i.e. 1) help-seeking adolescents presenting with putatively prodromal symptoms meeting the criteria for At Risk Mental State (ARMS), and 2) adolescents with Multiple Complex Developmental Disorder (MCDD), a pervasive developmental disorder subtype characterized by severe, early childhoodonset deficits in affect regulation, anxieties, disturbed social relationships, and thought disorder.

Methods: 80 ARMS and 32 MCDD adolescents were compared on putatively prodromal symptoms and autism traits. In addition, both high-risk groups were compared with 82 healthy controls on schizotypal traits. Results: Interestingly, 78% of the adolescents with prepubertal diagnoses of MCDD now in adolescence met the criteria for putatively prodromal state. Moreover, although the high-risk groups clearly differed in early developmental and treatment histories as well as autism traits, they did not differ with regard to any schizotypal traits and early prodromal symptoms, and most of the late prodromal symptoms. Conclusion: These data confirm the notion that there are different developmental pathways to psychosis, and that a biologicalgenetic vulnerability for psychosis exists in subjects with MCDD P-01-04 Vulnerability to psychosis delays recovery from of depression results of the RADEP study R. K. R. Salokangas (University of Turku, Department of Psychiatry, Finland), S. Luutonen Introduction: We studied occurrence of and recovery from depressive symptoms and their association with psychotic and manic symptoms. Methods: Altogether 563 patients attending primary care (PrC) and 163 patients attending psychiatric outpatient care (PsC) filled in a questionnaire including lists of current depressive and lifetime manic and psychotic symptoms. Patients with depressive symptoms were interviewed with the same checklists 6 months after baseline examination. Results: Both at baseline and follow-up, depressive symptoms correlated significantly with psychotic and manic symptoms. In multivariate analyses, when the effects of background, health and functioning were taken into account, baseline depressive symptoms associated significantly with lifetime psychotic symptoms. Depressive symptoms at follow-up associated significantly with psychotic symptoms occurred during the follow-up period. In the PrC sample, this association was significant even when the effect of baseline depressive symptoms was controlled. Conclusion: Vulnerability to psychosis, indicated by occurrence of psychotic symptoms, increases the risk of depressive symptoms in the patients attending primary care. Occurrence of psychotic symptoms delays recovery from depressive symptoms. Therefore, in treatment of depressive patients, also a possible vulnerability to psychosis should be taken into account. P-01-05 Increased abnormal involuntary movements in ‘‘at high risk of developing psychosis group’’ a comparative study V. Sanchez (Hospital Clinic, Psychiatry, Barcelona, Spain), M. R. Broome, L. R. Valmaggia, P. Dazzan, P. McGuire Introduction: Extrapyramidal signs and symptoms (EPSS) were described in schizophrenia before antipsychotic drugs. Studies of chronic schizophrenic patients never exposed to neuroleptic medication and first-episode antipsychotic-naı¨ve patients, also reported higher rates of EPSS than in controls. Methods: The aim of the study was to determine the prevalence of EPSS in 40 subjects with a high risk of developing psychosis (ARMS) in South London. We compared EPSS in ARMS subjects with a group of 31 first episode naı¨ve patients (FE) and 26 healthy volunteers. AIMS was used to assess dyskinesia, SAS to assess parkinsonism and BARS for akathisia ANOVAs were used for group comparisons of total scores of the scales. Chi-square statistics was used for post hoc comparisons. Significance was set at p less than 0.05. Results: FE had a higher proportion of parkinsonism than both the ARMS group (X 2 = 8.74; p = 0.006) and controls. Both ARMS and FE had significantly higher proportions of akathisia than controls (X 2 = 5.92; p = 0.010 and X 2 = 5.00; p = 0.004 respectively Conclusion: Results suggest that some EPS are a correlate of increased vulnerability to psychosis, rather than of psychotic illness

19 per se. This is consistent with clinical, neuropsychological and neuroimaging studies of the ARMS

P-01-06 Emotion recognition in ultra-high risk individuals and the risk of early transition to psychosis M. Schloegelhofer (Univ. Hosp. Psychiatry, Biological Psychiatry, Vienna, Austria), M. Schaefer, K. Papageorgiou Introduction: Persons with first-episode schizophrenia have impaired recognition of emotions. In particular deficits in the recognition of fear and sadness, have been demonstrated (Edwards et al, 2001). It is unknown if affect perception deficits predate illness onset, and if such deficits predict transition to psychosis in individuals with subthreshold psychotic symptoms. Methods: We investigated the capacity to recognize facially expressed emotion and affective prosody recognition in 38 individuals at ultra-high risk (UHR) for psychosis (mean age=16.1, SD = 1.7 years) and 30 unaffected normal comparisons (NC) (mean age = 15.6, SD = 2.0 years). UHR individuals received state-of-art nonneuroleptic treatment. Clinical status regarding transition to psychosis was evaluated 12 weeks after baseline. We used the Positive and Negative Symptom Scale (PANSS) and SCID-IV to evaluate psychopathology. Student’s t-tests were used to compare summary scores across communication channels, facial affect and affective prosody recognition, for each assessed emotion. Results: At baseline assessment the UHR group showed a significant deficit for the recognition of ‘sadness’ as compared to the NC group. At 12-week follow up 8 (22.2%) UHR individuals were found psychotic. A deficit for the recognition of ‘neutral’ was associated with transition to psychosis. Conclusion: Our findings indicate that specific emotion recognition deficits can be observed in UHR individuals. Emotion recognition warrants further investigation in UHR populations. P-01-07 Is the ERIraos checklist a scale of psychosis proneness? Applying the RASCH model on checklist data K. Maurer (CIMH, Schizophrenia Research, Mannheim, Germany), G. Trendler, F. Ho¨rrmann, H. Ha¨fner Introduction: The 17-item Checklist for the pre-selection of people with an increased psychosis risk assesses symptoms of growing specificity. Therefore, it should be possible to depict individual psychosis proneness from the earliest symptom onset until the transition to psychosis on a single dimension. Methods: The probabilistic RASCH model was selected for this analysis. The RASCH model assumes that with growing severity (psychosis proneness) the probability of answering an item positively (having the symptom) systematically increases. RASCH scales are interval (difference) scales. Results: At the lower end of the scale we find the non-specific symptom restlessness and nervousness, depressive mood and social withdrawal, at the upper end hallucinations, self neglect and ideas of persecution. The result of this RASCH analysis successfully was cross-validated by different data sets. Conclusion: As the Checklist data are consistent with the assumptions of the RASCH model, the validity of the Checklist to measure proneness to psychosis from symptom onset until the transition phase was confirmed. The number of symptoms is a sufficient measure of the severity of the symptom status. P-01-08 Psychometric properties of the ‘Schizophrenia Proneness Instrument, Adult Version’ (SPI-A) H. Picker (University Cologne, Hospital of Psychiatry, Germany), F. Schultze-Lutter, S. Ruhrmann Introduction: To evaluate the psychometric characteristics of the 40items test version of the ‘Schizophrenia Proneness Instrument, Adult Version’ (SPI-A), classical and probabilistic analyses were performed as a mean to provide an informative basis for steps

towards an economic, yet valid revision of the SPI-A. Thereby, the discriminative properties of the 6 subscales were focussed. Methods: The sample contained of 146 potentially prodromal (51 with subsequent conversion to psychosis), 153 first-episode schizophrenic and 115 depressive subjects; the latter serving as a control group. Reliabilities and person-parameters were computed for subscales. Results: The total scale of the test version as well its subscales ‘overstrain’, ‘cognitive impediments’ and ‘cognitive disturbances’ showed satisfying reliabilities (Cronbach’s Alpha > .80), ‘dynamic deficits’ performed worst (Alpha = .69). Group comparisons of the mean Rasch Person-Parameters showed significant differences between both the (pre-)psychotic groups and the depressive group except for ‘dynamic deficits’. Significant differences in personparameters between converted and not (yet) converted prodromal subjects only occurred in ‘overstrain’ and ‘cognitive disturbances’. Conclusion: Already the test version of the SPI-A exhibited good psychometric properties in general and especially for cognitive disturbances thought to be most important in predicting psychosis. Yet, analyses showed good starting-points for revision, particularly regarding subscales with less optimal values. P-01-09 Alcohol and drug consumption: Prevalence and effect on the transition to psychosis F. Rausch (CIMH, Schizophrenia Research Unit, Mannheim, Germany), K. Maurer, F. Ho¨rrmann, H. Ha¨fner Introduction: The Early Recognition Inventory (ERIraos) comprises besides the Checklist and Symptom List a set of additional modules to assess further risk factors. The module ‘Drug Use’ includes information on stimulants and nicotine, alcohol consumption and illegal drugs. We report about alcohol and drug use in a sample of people at psychosis risk and the relation of abuse and transition to psychosis. Methods: Descriptive statistics are used to report the frequencies of alcohol and drug use (number and duration of episodes, amounts of alcohol, frequency of consumption). For alcohol the evaluation of diagnostic criteria (ICD 10: abuse and dependency) is possible. The association of abuse and transition to psychosis is analyzed by Cross Tabulations and Logistic Regression Analysis. Results: 25.4% of the patients report phases of alcohol consumption or of excessive drinking (mostly beer). 47.2% of the alcohol users report negative consequences of alcohol (work, household). Nearly 45% of the patients use drugs; 96.9% of them use cannabis. The results do not support the assumption that the use of alcohol or drugs increases the risk of a transition to psychosis. Conclusion: Probably the modules can be relevant for later transitions, therefore they should be kept in the set of ERIraos modules.

P-01-10 Impact of locus of control on cannabis abstinence M. Neumann (University Hospital of Cologne, FETZ, Germany), S. Ruhrmann, F. Schultze-Lutter Introduction: As use of cannabis has been identified as a major risk factor for psychosis, a 5-session group program for patients seeking help for mental problems associated with use of cannabis has been established at the Early Recognition and Intervention Centre for mental Crisis (FETZ), Cologne. The present study investigated the impact of locus of control on the outcome of the program. Methods: In 25 probands participating in the group program, the Questionnaire of Competence and Control Orientation (FKK) and the CIDI drug module were assessed. Effects on cannabis use were evaluated before the first session and after the program. Results: Frequency of cannabis consumption was significantly reduced (p < .000). A reduced cannabis consumption, defined as a 50% decrease in frequency/month, was achieved in 68% of cases (p < 0.001). Further analysis revealed significant correlations between reduction of cannabis consumption and the subscales for

20 internality (r = .681; p = 0.00) or self-concept of one’s own ability (r = .516; p = 0.01). Individuals with reduced cannabis consumption exhibited significantly higher median ranks in ‘self efficacy’ (p = .037 and ‘internality (p = .005). Conclusion: Associations between positive behavioural change and internal locus of control were shown. This highlights the importance to increase internal attribution in cannabis abstinence programs to modify behaviour.

P-02 Treatment I P-02-01 Invalidity family communication patterns in schizophrenia families F. Bahrami (Isfahan University, Isfahan, Iran), A. Zamani, N. Kassaiean Introduction: The main hypothesis is that schizophrenia and other psychological disorders have communication deviance in families that may engender inefficient patterns of thinking and information processing. Study of these communication patterns help us to determine pathological elements in their family relationship. Methods: The participants were 30 male schizophrenia inpatient and 30 homogeneous normal male that were randomly selected. Invalidity communication patterns questionnaire (ICPQ) was used that home reasonable validity and reliability (a = 0.92). ICPQ home 5 subscales includes invalidity in (value and attitude system, emotional expression, behavioral system, disqualification previous communication and family rules). Results: The findings showed that invalidity communication patterns totally score and all of the subscales were significantly in schizophrenia families more than control group (p < 0.05). Conclusion: It’s necessary to improve patalogical family communication patterns for treating schizophrenia patient. P-02-02 Multifamilyintervention - a new approach in the treatment of schizophrenia H. Berger (Walter Picard Klinik, Riedstadt, Germany) Introduction: Psychoeducation has proved to be a powerful instrument in the reduction of relapse-rates of patients with schizophrenic disorders. To strengten the effects it seems to be useful, to bring patients and their realtives together. This intervention discloses ways of intervention, which can’t be realized in conventional settings of psychoeducation. Methods: Patients with schizophrenic disorders and their relatives are trained in ten sessions in knowledge about the sickness and the therapy as well as in social skills, strategies to cope with the sickness and strategies to improve the familiar communication. The method was evaluated in terms of the training process itself and the outcome with regard to the wellbeing and the relapse rates Results: The relapse rates could be reduced from 60% before to 19% after the intervention within one year. The well being within the family improved significantly during and after the intervention Conclusion: Multifamilyintervention is a powerful instrument in regard of the reduction of relapse rates especially for families who are interested in active participation. Multifamilyintervention leeds to an effective empowerment of patients and their relatives. P-02-03 Prismatic communication A. Drees (Zentrum fu¨r Prismengespra¨che, Krefeld, Germany) Prismatic communication make it possible for psychotic and traumatised patients to get contact to their blocked feelings and to recover their trust of being accepted by society. The Therapist tries prismatically to help the patient by his ability to use his own feelings, his mood and his phantasies as elements of the patient and to enrich it by narrative dialogues. In institutions, expecially in hospitals and counselling centres, prismatic moodoriented Training-groups reduce the emotional tensions of the

staff and hereby minimises burn-out-syndromes. Prismatic communications evoke mood-aware-ness in the therapist as well as in the patient. For these patients and their therapists prismatic communication is the favoured therapeutic approach. The theory of mood, intuitive and metaphorical orientation enables us to distinguish between rational-, emotional- and prismatic forms of communications. P-02-04 Training of Affect Recognition (TAR) in schizophrenia: Generalizability and durability of training effects N. Frommann (University of Duesseldorf, Department of Psychiatry, Germany), J. Fleiter, M. Peltzer, A. Steinbring, W. Wo¨lwer Introduction: Impairments in affect recognition are known to be a trait-like characteristic in schizophrenia mostly unaffected by traditional treatment. Wo¨lwer et al (2005) developed a special Training of Affect Recognition (TAR) which proved to improve facial affect recognition. The present study tries to replicate and investigate the durability and generalizability of these effects. Methods: TAR is being compared with a Cognitive Remediation Training (CRT) aiming at improvement of basic neurocognition using a pre-post-control group design with two groups of n = 20 partly remitted schizophrenia patients each. Follow up assessment took place 4 weeks after the end of treatment. Beyond facial affect recognition TAR effects on prosodic affect recognition, on theory of mind (ToM) performance and on social competence within a role play were investigated with respect to generalizability of effects. Results: TAR (but not CRT) improved facial affect recognition. Effects largely persisted beyond the end of treatment. TAR also had positive effects on prosodic affect recognition and ToM performance but no significant effect on social interaction. Conclusion: TAR again proved to be an effective treatment with regard to social cognitive functioning. Though such social cognitive processes by definition underly social interaction, improvements in social cognition not necessarily enhance schizophrenics social competence. P-02-05 Affect recognition and violence in schizophrenia: Application of the Training of Affect Recognition (TAR) in forensic patients N. Frommann (University of Duesseldorf, Department of Psychiatry, Germany), M. Brand, W. Schmidbauer, W. Wo¨lwer Introduction: Impairments affect recognition are well known in schizophrenia and seem to be remediable by the Training of Affect Recognition (TAR). Since decoding facial affect seems to be a key function in social interaction it is of special interest if and how this function is associated with violence in schizophrenia. Methods: Impairments in decoding facial affect and its remediation by TAR is evaluated in an on going study at the central forensic clinic Haina. In a randomized waiting group design 20 patients are treated directly and 20 after a waiting period of two month. Affect recognition and psy-chopathology is assessed preand post treatment, and two and four month after treatment. Anamnestic data including history of violence and dissocial personality traits are assessed by standardized instruments as well as by interviewing and searching in files. Results: Preliminary analyses revealed forensic patients to have a deficit in affect decoding compara-ble to schizophrenics without forensic history from other studies. If the extend of violence is related to the amount of deficit can not be proven until yet. Conclusion: The study shows a good feasibility of treatment research in the forensic clinical treatment setting as well as a good acceptance of TAR by these patients. P-02-06 Illness concepts, insight into illness and compliance in schizophrenic patients: Their interrelation and meaning for the effectiveness of psychoeducative treatment interventions F. Schmidt (Charite Berlin CBF, Sozialpsych. Tagesklinik, Germany), K. Ko¨rtner, M. Dettling

21 Introduction: Patients’ subjective illness concepts and insight into illness seem to play a crucial role for the effectiveness of psychoeducative treatment programmes for schizophrenic disorders. However, little is known about whether, and how, these parameters can be influenced effectively and results concerning the interrelation of these constructs are equivocal. Comparative studies suggest that psychoeducational interventions are particularly successful if individual health beliefs are addressed and considered in the treatment process. A psychoeducative treatment programme for schizophrenic disorders including group as well as individual sessions was developed. The additional individual intervention programme is particularly designed to allow for an individualisation and consolidation of the topics discussed in the group sessions. Methods: A prospective randomised controlled trial with followups is carried out to evaluate the combined psychoeducative programme. In addition to classic outcome criteria such as relapse rate and psychopathology, different aspects of the patients’ illness concepts and health beliefs as well as insight into illness are assessed. Results: Preliminary data from the first year of the study regarding illness concepts, insight into illness and medication compliance will be presented. Conclusion: The results will be discussed with a special focus on the interrelation of these variables and their meaning for the effectiveness of psychoeducative treatment interventions.

P-02-09 Implication of the vascular factor in treatment resistance to patients with schizophrenia treated with antipsychotics D. G. Constantin Marinescu (University of Medicine, Psychiatry, Craiova, Romania), T. Udristoiu, D. Camen, A. Tiugan, A. Chimorghiachis, C. Radut Introduction: Negative symptoms and cognitive impairment are the main symptoms correlated with treatment resistance to antipsychotics. The neurobiological model of schizophrenia suggest the fact that the hypofrontal syndrome is an important marker for the persistance of negative symptoms and cognitive impairment. The hypofrontaliety is consequence of the signal dopaminergic deprivation, proportional to the antipsychotic’s capacity of blocking D2 receptors and the capacity to induce EPS. Vascular factor is not currently noticed in neurobiological studies for schizophrenia. Methods: Our studies (5 subjects) have shown the fact that the atypical antipsychotics with low capacity of blocking D2 receptors, but with a very high hypotensive potential, correlated with alpha-2noradrenergic blocking capacity, determines the onset of EPS and limited therapeutical efficiency demonstrated on PANSS, CGI, BPRS or cognition scales. Results: We evaluated the retinal central artery tension, demonstrating very low values and trancranial Doppler examination showed perfusion anomalies at the medial cerebral artery level to most of the subjects. The familial and personal history revealed the spectrum of cardio-velo-facial syndrome or an streptococcal infection. Conclusion: The early evaluation of the vascular function, the negative symptoms and the cognitive impairment and the presence of intracerebral vascular anomalies indicate the avoidance of atypical antipsychotics which can induce orthostatic hypotension.

P-02-10 Switching from branded to generic risperidone in patients with schizophrenia: An estimation of potential economic consequences in The Netherlands F. van Nooten (United BioSource Corporation, Health Care Analytics Group, Brussels, Belgium), C. Rijnders, R. Brown, M. van Agthoven Introduction: Risperidone will lose patent protection at the end of 2007, which opens the market for generic variants. However, since many schizophrenic patients suffer from paranoia, some of them will be less willing to take a different drug. Substitution of branded by generic drugs may therefore induce non-compliance, which is in its turn the most important predictor of relapse and hospitalisation in schizophrenia. We estimated potential economic consequences

when stable patients in the Netherlands using branded risperidone are switched to the generic version. Methods: A simple health economic model was developed, based on published data. A 1-year perspective was applied. Results: Due to a somewhat higher relapse rate after switching to generics, total per-patient drug and hospitalisation costs were estimated to be higher for the generic product compared to the branded product (euro; 5,110 and 4,680, respectively). Sensitivity analyses showed the stability of the result. Conclusion: Switching patients who are stabilised on branded risperidone to the generic version might cause higher costs. The analysis depends on assumptions, but given their evidence-based character, there is sufficient reason to believe that the result will hold in countries where only little differences will exist between the price of branded and generic risperidone after the patent expiry. P-02-11 Treatment of schizophrenia in breast cancer patients V. Sushko (Odessa State Medical Univ., Department of Psychiatry, Ukraine) Introduction: Antipsychotic therapy is the mainstay of treatment for people with schizophrenia. The increased serum prolactin is one of the side effects of antipsychotic treatment, can have a negative impact on treatment breast cancer patients with schizophrenia. In comparison with others atypical antipsychotics, aripiprazole may have a less risk of raised prolactin. Methods: This study evaluated the effects of aripiprazole for breast cancer patients with schizophrenia. Over two months, 29 breast cancer patients with schizophrenia after mastectomy were randomized to treatment with aripiprazole 20–30 mg/daily. Efficacy was assessed by improvement of psychotic symptoms, measured on the Positive and Negative Syndrome Scale. Prolactin levels were also determined at baseline and at the end of the study. Results: Aripiprazole reduced psychotic symptoms. PANSS total scores, positive scores, and general psychopathology scores declined. The results of the study showed that aripiprazole demonstrated a favorable profile of side effects: only slight changes of body weight, no prolactin elevation. Conclusion: A comprehensive review of all of the findings suggests that aripiprazole is an effective and well-tolerated treatment option for breast cancer patients with schizophrenia. Aripiprazole was effective in the treatment of productive psychotic and negative symptoms.

P-03 Neurobiology P-03-01 A case control study: No association between SLC6A3 (DAT1) with schizophrenia A. M. Foroughmand (University Ahwaz, Ahwaz, Iran) According to the dopamine hypothesis of schizophrenia’ schizophrenia is associated with increased activity in dopaminergic neurons. Dysfunc-tion of central dopaminergic neurotransmission has been suggested to play an important role in the etiology of schizophrenia. The Na+_Cl- dependent dopamine transporter (DAT1) is a central regula-tor of the time and course and synaptic concentration of released dopa-mine by rapid reuptake of dopamine into synaptic terminals and media-ting synaptic re accumulation of dopamine. In this study we thought to determine the possible association between the SLC6A3 gene (DAT1) core promoter diallelic polymorphic site -67 A/T and schizophrenia in western south of Iran. We use the case control study to determine possible association bet-ween -67A/T SNP and schizophrenia. Fifty unrelated male patient affected with schizophrenia were recruited for the study from golestsn and salamat hospitals in Ahwaz. Also fifty unrelated male controls were randomly selected as control group. Sub-sequently the allele and genotype frequencies of the polymorphism in two groups were studied. The genotype frequencies in the patient group were as follows: AA 68%, AT 24% and TT 8% versus the genotype fre-quencies in the control group were AA 78%, AT 10% and TT 12%. Ba-sed on this data alleiic frequency

22 were 83% for A, 17% for T in control group and 80% for A, 20% in patient group. According to this data and x2 test there is no association between DAT1 and schizophrenia. P-03-02 Association between reelin and schizophrenia and the influence of reelin on volumetric changes I. Puls (Charite (CCM), Dept. of Psychiatry, Berlin, Germany), F. Schlagenhauf, C. Liensdorf, J. Wrase, J. Gallinat, A. Heinz Introduction: Schizophrenia is a highly heritable disease, although the genes involved still remain uncertain. It is well described that an alteration in the cortical layers play a role in the pathogenesis of schizophrenia. Furthermore, expression studies showed that genes involved in the control of the cortical layer formation during the embryonic phase are dysregulated in schizophrenic patients. Reelin is known to be involved in the migration of cortical neurons during ontogenesis. Methods: In the patient-control study presented here 10 SNPs (single nucleotide polymorphisms) of reelin were genotyped in 158 subjects (79 schizophrenic patients and 77 healthy controls). All subjects received structural magnetic resonance imaging. Results: Our results show an association between rs17286505 (p = 0.006) and rs17150616 (p = 0.008) with the diagnosis of schizophrenia. This SNPs are located in intron 10 and exon 60, respectively (nucleotide exchange in exon 60 does not lead to an alteration of the amino acid sequence). Future research will establish if adjacent genes or associated haplotypes are functionally relevant. Conclusion: Further analyses will investigate the relationship between the two reelin SNPs and volumetric changes in cortical areas of schizophrenic patients as well as in healthy controls. Our study gives evidence that genetic variations of reelin play a role in the pathogenesis of schizophrenia. P-03-03 Decreased oligodendrocyte number in the hippocampus of schizophrenia patients - a stereological study A. Schmitt (University of Go¨ttingen, Department of Psychiatry, Germany), C. Steyskal, H.-G. Bernstein, B. Bogerts, P. Falkai Introduction: A decreased hippocampal volume is one of the most consisting findings in schizophrenia. Post-mortem stereological studies investigating total cell number or neuron number reported no differences in the hippocampus of schizophrenia patients. However, these studies investigated only total numbers of neurons and did not differentiate between different cell types. Methods: In this study we investigated stereologically pyramidal neurons, interneurons, oligodendroglia and astroglia using histological and morphological criteria of these subdivisions of cells on serial Cresyl Violet stained sections of the posterior hippocampus in 10 schizophrenia patients compared to 10 healthy controls. Volumes of pyramidal neurons, interneurons and oligodendrocytes and volumes of the entire subregions have been determined. Results: Total oligodendrocyte number was decreased in CA2/3, CA4 and subiculum, reaching statistical significance in the right CA4 subregion (p = 0.034). Pyramidal cell number was decreased in the left subiculum and pyramidal cell volume was decreased in left CA1. Volumes of the hippocampal subregions were decreased, not reaching statistical significance, but we detected significant correlations between oligodendrocyte numbers and volumes of the subregions. Conclusion: Oligodendrocyte pathology with decreased myelination may contribute to functional deficits in schizophrenia.. Our results support gene expression studies showing decreased expression of oligodendrocyte-related genes in schizophrenia and should be confirmed in a larger sample. P-03-04 Relationship between Kynurenines and S100b in CSF of schizophrenic patients M. J. Schwarz (Psychiatric Hospital of the University Munich, Germany), M. Riedel, S. Holdenrieder, M. Tischinger, N. Mu¨ller

Introduction: The so far only known endogenous NMDA receptor antagonist is kynurenic acid (KYNA), which may be crucially involved in the pathophysiology of schizophrenia. Kynurenine (KYN), the degradation product of tryptophan (TRP) is further metabolised either to KYNA, or to the neurotoxic intermediate 3-hydroxykynurenine (3-HK). Astrocytes play an important role in glutamate turnover and in production of KYNA. S100b as an astrocytic protein is an indicator of astroglial function and serum and CSF levels of this secretory protein are increased in schizophrenia. Methods: We investigated CSF samples of 100 patients (63 male, 37 female; mean age: 33.4 14 years) suffering from an acute episode of schizophrenia. CSF levels of TRP, KYN, KYNA, and 3-HK were simultaneously measured by HPLC. CSF levels of S100b were measured by immuno-assay. Results: There was a significant positive correlation between S100b and TRP, KYN, and 3-HK, while S100b was negatively correlated with KYNA. Conclusion: Our data indicate a functional relationship between the kynurenine pathway intermediates and astroglial function. According to our data, the neuroprotective KYNA may be involved in the prevention of S100b excretion, which is associated with dystrophic neurites. The combination of S100b and KYNA may therefore serve as a tool to discriminate between distinct schizophrenia subgroups. P-03-05 White matter abnormalities in subjects with ultra-high risk for schizophrenia and first-episode schizophrenic patients compared to healthy controls H. Witthaus (LWL Hospital, Department of Psychiatry, Bochum, ¨ zgu¨rdal, Y. Germany), M. Bru¨ne, C. Kaufmann, G. Bohner, S. O Gudlowski, A. Heinz, R. Klingebiel, G. Juckel Introduction: Schizophrenia is associated with neuroanatomical abnormalities. Gray matter decrease seems to predate first schizophrenic episode. Whether white matter abnormalities predate the onset of psychotic symptoms or develop progressively over the course of psychotic illness is unclear. We investigated this issue with voxel-based morphometry (VBM) of structural magnetic resonance images (MRI) to examine people at ultra high-risk (UHR) for the development of schizophrenic psychosis in comparison to first episode schizophrenic patients and healthy controls. Methods: White matter volume maps from high-resolution MR T1 weighted whole brain images were analyzed in a cross-sectional study using SPM2 in 30 UHR patients (25.1 ± 4.3 years old, 20 males), 23 first-episode schizophrenic patients (26.4 ± 6.1 years old, 17 males) and 29 healthy controls (25.7 ± 5.2 years old, 17 males). Results: UHR patients showed significant lower white matter volume in the right superior temporal lobe. First-episode patients with schizophrenia showed smaller white matter volume in the right superior frontal and left medial frontal gyrus, in the right middle temporal gyrus, in the occipital lobe bilaterally compared to UHR patients. Conclusion: This study provides first evidences for smaller white matter volume in the right temporal lobe of UHR patients. Further white matter abnormalities seem to appear after transition into first schizophrenic psychosis.

P-03-06 Gray matter abnormalities in subjects with ultra-high risk for schizophrenia and first-episode schizophrenic patients compared to healthy controls H. Witthaus (LWL Hospital, Department of Psychiatry, Bochum, ¨ zgu¨rdal, Y. Gudlowski, J. Germany), C. Kaufmann, G. Bohner, S. O Gallinat, M. Bru¨ne, A. Heinz, R. Klingebiel, G. Juckel Introduction: Many neuroimaging studies observed gray matter abnormalities in schizophrenic patients. However, it is still unclear whether certain abnormalities are already present in individuals at ultra high-risk (UHR) for transition into psychosis. We investigated this issue with voxel-based morphometry (VBM) of structural magnetic resonance images (MRI) and compared UHR

23 patients with first-episode patients with schizophrenia and healthy subjects. Methods: Gray matter volume maps from high-resolution MR T1 weighted whole brain images were analyzed in a cross-sectional study using SPM2 in 30 UHR patients (25.1 ± 4.3 years old, 20 males), 23 first-episode schizophrenic patients (26.4 ± 6.1 years old, 17 males) and 29 healthy controls (25.7 ± 5.2 years old, 17 males). Results: UHR patients showed significant lower gray matter volume in the anterior and middle cingulate gyrus bilaterally, in the left posterior cingulum, in the right inferior frontal and right superior temporal gyrus, as well as in the left and right hippocampus in comparison to healthy subjects. Conclusion: This study provides further evidence that gray matter brain volume especially in the anterior cingulate cortex (ACC) is already reduced in the prodromal state of schizophrenia in comparison to matched healthy controls.

P-03-07 Reduced temporal and prefrontal cortical thickness in adolescents with early-onset schizophrenia A. Lamprecht (Goethe University, Department of Psychiatry, Frankfurt, Germany), R. Bittner, A. Rotarskaja-Jagiela, F. Ha¨rtling, W. Singer, K. Maurer, R. Goebel, D. Linden, C. Haenschel Introduction: There is increasing evidence that reductions in cortical thickness are an important aspect of schizophrenia pathology. Cortical thinning appears to be particularly striking in frontal and temporal areas. Patients with an early onset of the disorder seem to be more strongly affected. Here we investigate differences in cortical thickness in adolescents with schizophrenia compared to healthy controls. Methods: High resolution MRI images (voxel size 1x1x1 mm3) were acquired from 17 adolescents with early-onset schizophrenia and 17 matched controls. The individual gray-white and pial surfaces were reconstructed. The distance between these surfaces was estimated to measure cortical thickness. A surface-based averaging technique was applied and between-group differences in cortical thickness were computed for prefrontal and temporal ROIs. Results: Patients had significantly reduced cortical thickness in temporal and prefrontal ROIs particularly in the left hemisphere. Thinning was especially marked in the superior temporal and middle frontal gyrus bilaterally as well as in the left inferior frontal gyrus. Conclusion: Our results confirm previous findings of frontal and temporal cortical thinning in schizophrenia. Compared to studies in adult patients, this effect seems to be more pronounced in our adolescent patients.

P-03-09 The place of neurotropic staffs in the correction of antioxydantic functions of different departments of brain T. Skachko-Volkova (Dnepropetrovsk State MedAcadem, Pharmacology, Ukraine), H. Zlenko, Y. Khomenko Introduction: It’s determined that different deviations in the brain functions are accompanied by peroxidation and accumulation of free radicals. The correcting actions of known neurotropic staffs in different stress situations can be explained by their influence on brain metabolic processes. Methods: Thus, we’ve investigated the activities of pyracetam, cavinton and melatonin in the conditions of brain ischemia and physical overload. The research work was performed on pubertal white mice. The indexes of peroxidation in neocortex, hippocampus and brain trunk were investigated. Results: The results showed that all neurotropic staffs reduced the contain of malonic dialdegid in neocortex, hippocampus and particularly in brain trunk. Simultaneously the components of antioxidant system increased by 30% (glutationperoxydasa, superoxyddismutasa). The life period of experimental animals enlarged same as their physical activity.

Conclusion: Obviously the correction of peroxidation-antioxidation balance importantly influences the neuroprotective activity of neurotropic staffs. P-03-10 B-lymphoblasts as an in vitro cell model for the study of nicotinic acethylcholine receptor regulation in schizophrenics in relation to nicotine abuse S. Ferrea (University of Du¨sseldorf , Hospital of Psychiatry, Germany), U. Henning, C. Luckhaus Introduction: Tobacco consumption is a highly addictive behaviour. In the general population about 30% are smokers. A distinct higher incidence of smoking is reported on schizophrenic subjects (60 to 80%). Nicotine induces and maintains tobacco addiction presumably by interacting with nicotinic acetylcholine receptors (nAChRs). Postmortem studies measuring the number of nAChRs in brain revealed, that smokers were characterized by a receptor increase, which correlates with the number of smoked cigarettes. In schizophrenics, a dysregulation of nAChRs-subtypes has been described, which could predispose them to smoking. nAChRs expression is not restricted to neuronal cells. These receptors are found on leucocytes, too. As in neuronal tissue, a higher number of nAChRs was reported for smokers. Native lymphocytes are, however, unsuitable for investigations of nAChRs under cell culture conditions, since nicotine-induced changes in vivo rapidly diminish, and lymphocytes are nonviable for longer time periods to allow for in vitro experiments. In contrast, B-lymphoblasts prepared from B-lymphocytes can be grown under defined culture conditions. We hypothesize, that an abnormal nAChRs regulation may be an underlying factor of nicotine addiction in schizophrenics. Our presentation shows first results on the use of B-lymphoblasts to study receptor regulation in vitro. P-03-11 Elevated glutamate in the hippocampus and reduced glutamate in the anterior cingulate gyrus of schizophrenic patients - a 1H-MRS study at 3 tesla K. Leopold (Univ.Hosp. Carl Gustav Carus, TU Dresden, Dept. of Psychiaty, Germany), M. Krebs, I. Ha¨ke, F. Schubert, F. Seifert, M. Scha¨fer, J. Gallinat Introduction: Recent findings have revitalized the glutamate hypothesis of schizophrenia. At the same time improved methods have emerged to selectively quantify glutamate in the brain using single voxel proton magnetic resonance spectroscopy (1H-MRS). This method allows a more profound examination of the role of this neurotransmitter in the schizophrenic brain in vivo. According to the glutamate hypothesis an elevation of glutamate levels in distinct gray matter regions of the brain is to be expected. This has been well substantiated in a recent MRS study at 2T where increased glutamate concentrations were found in the hippocampus of schizophrenic patients. Methods: We quantified glutamate in the hippocampus and different cingulate regions of 28 schizophrenic patients and 28 healthy controls using 1H-MRS. Results: In schizophrenic patients the glutamate concentration in the hippocampus voxel was significantly higher (12.1 mmol/l vs 10.4 mmol/l, p < 0.01) than in controls. The glutamate concentration in the anterior cingulate gyrus voxel was significantly lower (14.5 mmol/l vs 15.2 mmol/l, p < 0,05) in schizophrenic patients than in controls. There were no significant differences for the posterior cingulated gyrus voxels. Conclusion: The recently reported glutamate increase in hippocampus in schizophrenia was clearly confirmed. Our finding suggests dysfunctional glutamatergic neurotransmission with concomitant disturbed neuronal integrity in regions playing a key role in the pathophysiology of schizophrenia

P-04 Neurocognition / Neurofunction P-04-01 Reduced cortical inhibition in schizophrenia T. Wobrock (Georg-August-University, Psychiatry & Psychotherapy, Go¨ttingen, Germany), M. Schneider, D. Kadovic, P. Falkai

24 Introduction: Abnormalities in brain plasticity including abnormal information processing by disturbed cortical inhibition and facilitation in schizophrenia have been described in the past. Transcranial magnetic stimulation (TMS) provides a neurophysiological technique for the measurement of cortical excitability, especially of the motoneural system. Methods: 29 First-episode patients, 16 patients suffering from chronic schizophrenia with predominant negative symptoms, and 44 healthy controls were characterized by TMS, using the pairedpulse paradigm. The amplitude of the motor evoked potentials (MEP) of left and right first dorsal interosseus muscle (FDI) induced by stimulation of the contralateral primary motor cortex was measured with the interstimulus intervals (ISI) 3 and 15 ms (conditioning stimulus intensity 80% of resting motor threshold; test stimulus intensity with unconditioned MEP size of 1mV). Results: Patients with first-episode schizophrenia (p = 0.05, bilaterally, Whitney-Mann-U-Test) and patients with chronic disease (p = 0.031, left side, Mann-Whitney-U-Test) demonstrated significantly increased MEP amplitude at the inhibitory ISI of 3 ms. Conclusion: The result of decreased cortico-cortical inhibition investigated by TMS supports the hypothesis, that GABAergic deficit may be involved in the schizophrenic pathophysiology. This deficit seems to be detectable early in the course and persisting, although antipsychotic medication may be a confounding factor.

studies in adult-onset patients have implicated abnormal prefrontal and parietal activation. However, WM impairment in early-onset schizophrenia (EOS) has not been studied with fMRI. Methods: We investigated differences in brain activation during visual WM encoding, maintenance and retrieval in 17 adolescents with EOS and 17 matched controls using fMRI. Up to three abstract visual shapes had to be maintained for 12 seconds before comparing them to a test stimulus. Results: During encoding, controls showed greater prefrontal activation bilaterally, while patients had stronger activation in a network comprising the frontal eye fields and the intraparietal sulcus bilaterally. For maintenance, higher activation for controls was found in the left prefrontal cortex while activation in the right intraparietal sulcus was higher in patients. During retrieval patients showed stronger activation in both frontal and parietal areas. Conclusion: Our findings imply that in EOS the encoding of information is already impaired. Prefrontal cortical dysfunction in patients was observed during all WM task phases, but a change from hypo- to hyperactivation was observed during retrieval. Stronger activation of premotor and parietal areas in patients suggests a mechanism to compensate for prefrontal dysfunction.

P-04-02 Brain reward system activation and the relationship between motivation and emotion in schizophrenia P. Kirsch (University of Giessen, Centre for Psychiatry, Germany), D. Mier, S. Ronshausen

Introduction: Most studies testing emotion recognition have shown deficits in schizophrenia, especially in the recognition of negative emotions. However, poor performance of schizophrenia patients in emotion recognition coincident with altered brain activation might reflect enhanced processing demands rather than a dysfunction of the involved processes. Therefore, the aim of the present study was to analyse emotion recognition in schizophrenia with a task that ensures comparable subjective task difficulty. Methods: 12 medicated schizophrenia outpatients and 14 healthy control subjects matched for age, education and IQ were tested with an adaptive emotion recognition paradigm during fMRI scans. Results: Contrary to other findings, schizophrenic patients showed impaired recognition of happiness, but not of negative emotions. During the recognition of happiness there was a higher activation of the nucleus accumbens bilaterally. In contrast, during the recognition of anger and disgust, patients showed lower activity in emotion specific areas. Conclusion: Our data might reflect a recognition problem in schizophrenia for happiness, but not for negative emotions. The compensatory activation in the nucleus accumbens during the recognition of happy faces suggests that although patients need higher intensities to solve the task, the brain system for positive emotions has the capability to compensate and therefore allow successful processing of positive emotions.

Introduction: Altered functions of the dopaminergic system seem to be associated with psychotic as well as affective symptoms in schizophrenia. Recent studies suggest that dopamine mediates motivational rather than hedonic aspects of reward. To further clarify the relationship between motivational (reward anticipation) and emotional (reward consumption) processes in schizophrenia, the present study tested the association between dopaminergic reward system activation during motivational processes and brain activation to emotional stimuli by means of fMRI. Methods: A reaction time (RT) task with motivationally graded conditions, involving the anticipation to win money was used to investigate motivational and a emotional picture perception paradigm (PPP) with pictures differing in arousal and valence was presented to 20 schizophrenia patients and 13 controls. Correlations between the nucleus accumbens (NAcc) during the RT task and activations in emotion associated regions during the PPP were calculated. Results: In both groups there was an arousal modulated relationship between NAcc activation during the anticipation of reward and the activation in emotion related areas during the viewing of emotional pictures. For the positive valence this relationship was independent from arousal influences but only in schizophrenia patients. Conclusion: This result might reflect a stronger connection between motivational and emotional processes in reward in schizophrenia and demonstrates that the patients’ emotional deficits like anhedonia can be attributed to disturbances in motivational systems.

P-04-03 Visual working memory deficits in adolescents with early-onset schizophrenia investigated with event-related functional magnetic resonance imaging R. Bittner (Goethe University, Dept. of Psychiatry, Frankfurt, Germany), C. Haenschel, A. Roebroeck, F. Ha¨rtling, A. RotarskajaJagiela, R. Goebel, W. Singer, K. Maurer, D. Linden Introduction: Working memory (WM) deficits are a central feature of schizophrenia. Functional magnetic resonance imaging (fMRI)

P-04-04 Neuronal correlates of emotion recognition in schizophrenia D. Mier (Justus Liebig University, Cognitive Neuro Sciences, Giessen, Germany), S. Lis, C. Sauer, K. Zygrodnik, C. Esslinger, B. Gallhofer, P. Kirsch

P-04-05 Hypoactivity in bilateral Wernicke’s area in schizophrenia patients and their unaffected family members V. Oertel (University Frankfurt, Hospital of Psychiatry, Germany), A. Rotarska-Jagiela, M. Lindner, C. Altmann, C. Kno¨chel, V. van de Ven, C. Haenschel, K. Maurer, D. Linden Introduction: The aim of this study was to identify neuronal correlates for a defective neuronal network in the auditory information and language area. Methods: The study included 41 participants: 15 schizophrenic (SZ) patients (according to DSM-IV criteria, American Psychiatric Association, 1994), 11 first-degree relatives of SZ patients and 15 normal controls. A high-resolution 3D-anatomical measurement (MDEFT-sequence, 88 slices, voxel-size: 1*1*1 mm3; SIEMENS Allegra 3.0 TESLA Scanner), accompanied by a functional measurement with auditory stimulation (TR = 1000 ms, inter slice time 62, slice thickness = 5mm, 480 volumes, 16 slices), was performed. The auditory stimulation consisted of 13 text frag-

25 ments, alternating with a rest-condition. The subjects had to listen to the texts and press a button for onset and offset of stimulation. Results: The computed contrast-maps showed hypoactivity of Wernicke’s area bilaterally in SZ patients and their unaffected family members, followed by hyperactivity in the planum temporale (BA 42) of SZ patients in contrast to controls. In addition, the SZ patients showed a lower lateralization of language areas towards the left, followed by the first-degree relatives and the controls. The lateralization was correlated to the severity of symptoms (PANSS scores; Kay et al., 1987). Conclusion: The results showed a continuum of controls, firstdegree relatives and SZ patients. P-04-06 Impaired early-stage visual processing contributes to working memory dysfunction in adolescents with schizophrenia C. Haenschel (Goethe-University, Psychiatry, Frankfurt, Germany), R. Bittner, F. Ha¨rtling, A. Rotarska-Jagiela, K. Maurer, W. Singer, D. Linden Introduction: Working memory (WM) deficits are a central feature of schizophrenia. Working memory (WM) deficits in schizophrenia have mainly been associated with prefrontal dysfunction. However, the contribution of perceptual deficits and abnormalities in sensory areas has not been explored. Methods: We investigated differences in brain activation during visual WM encoding and retrieval in 17 adolescents with early onset schizophrenia and 17 matched controls using EEG and fMRI. Up to three abstract visual shapes had to be maintained for 12 seconds before comparing them to a test stimulus. Results: P1 amplitude was reduced in patients during encoding and retrieval. The amplitude of the P1 increased with WM load during encoding only in controls. In this group a stronger P1 amplitude increase predicted better WM performance. The P1 reduction was mirrored by reduced activation of visual areas in patients in fMRI. P370 during encoding and retrieval was also reduced in patients. Conclusion: P1 reduction indicates an early visual deficit in adolescents with schizophrenia. Our findings suggest that P1 is of particular relevance for successful WM encoding. Early visual deficits contribute to impaired WM in schizophrenia in addition to deficits in later memory related processes. P-04-07 Saccadic distractibility, as shown by the antisaccade task, is associated with genetic loading for schizophrenia N. Petrovsky (University Hospital Bonn, Psychiatry, Germany), F. Weiss-Motz, I. Frommann, S. Schulze-Rauschenbach, C. Weiler, E. Matuschek, A. Brockhaus-Dumke, J. Dreher, S. Ruhrmann, M. Wagner Introduction: Disturbances of the oculomotor system are promising endophenotypes for schizophrenia. Increased error rates in the antisaccade (AS-)task and prolonged AS-latencies have been found in patients with schizophrenia and in their first degree relatives. Methods: Patients with schizophrenia, parents of schizophrenic patients (with and without a second affected relative), and healthy control groups (matched for age, sex, and education) performed a prosaccade-task and an antisaccade-task. An overlap-paradigm was applied; eye movements were recorded using infrared oculography. Results: As expected, patients with schizophrenia made more AS errors. Furthermore, parents of schizophrenia patient also showed increased AS error rates. Interestingly, there was a trend for the parents which had a second affected relative (i.e. parents with a high presumed genetic risk) to make even more AS errors than the remaining parents. AS-latencies (from correct trials) were prolonged in patients and in their parents as well. No group differences were found for the prosaccade parameters. Exploratory analyses of the associations between AS-performance and the COMT Val158Met polymorphism yielded negative results.

Conclusion: These results support the idea that saccadic distractibility is not only strongly associated with disease status, but also with genetic loading for schizophrenia. Oculomotor measures may be used to test functional consequences of putative illnessrelated genes. P-04-08 Neurocognitive deficits in first episode schizophrenia patients and their siblings I. V. Miclutia (University of Medicine Cluj, Psychiatry, Cluj-Napoca, Romania), C. A. Popescu, R. Macrea, I. Craciun Introduction: Neurocognitive deficits are well documented in psychotic illnesses and there is evidence to suggest that such deficits are present in individuals long before they develop the illness. However, little is known about whether cognitive deficits in firstdegree relatives of schizophrenic patients are associated with familial loading for schizophrenia. Methods: The current study aims to investigate neuropsychological impairment in first episode schizophrenia patients and their siblings. Cognitive functioning in 30 first-episode schizophrenia patients, 20 unaffected siblings and 20 unrelated healthy controls was assessed using verbal fluency tests (letters and categories) and several computerized tests from the Cambridge Automated Neuropsychological Testing Battery (CANTAB). Results: The patients performed significantly poorer than controls on all cognitive measures. Unaffected siblings performed worse than healthy subjects (p < 0.01), but better than first episode subjects (p < 0.0001). Siblings were particularly impaired on measures of PAL (Paired Associates Lerning Test) and IED (Intra/Extradimensional Set Shift). Patients and siblings demonstrated impaired verbal fluency performance. Conclusion: These results support the hypothesis which states that cognitive deficits are an indicator of vulnerability to psychosis.

P-05 Miscellaneous P-05-01 Incidence of schizophrenia is not declining R. K. R. Salokangas (University of Turku, Department of Psychiatry, Finland), A.-M. Koivisto, H. Rantanen, H. Oja, M. Joukamaa Introduction: Since 1980s, several reports have suggested that the incidence of schizophrenia is decreasing. However, changes in capacity of mental hospitals have not always been taken into account. Our aim was to calculate annual first admission rates for patients with schizophrenia and compare them with psychiatric beds available during the area when the number of bed in mental hospitals sharply decreased in Finland. Methods: From the National Hospital Discharge Register, we identified 27 352 15 to 64 year old patients admitted for the first time for schizophrenia to mental hospital in Finland between 1980 and 2003. Annual rates per 100 000 people were calculated and compared with annual numbers of hospitalised patients and mental hospital days. Results: Annual incidence for schizophrenia decreased from 56.2 in 1980 to 26.4 in 1990, stayed stable between years 1990 and 1998 and slightly increased thereafter (27.0 in 1998 and 33.0 in 2003). Hospitalised incidence of schizophrenia correlated more strongly with numbers of hospitalised patients (r = 0.958) and hospital days (r = 0.848) than with year (r = )0.711). Conclusion: Annual incidence of hospitalised schizophrenia is at least partly a function of number of mental beds available. Since the beginning of 1990s, annual incidence of hospitalised schizophrenia in Finland seems to be increased, not decreased. P-05-02 Psychopathology of schizophrenia: A Riemann’ Turn Ahead ? N. Andersch (South London&Maudsley NHSTrus, Adult Psychiatry, United Kingdom) Introduction: In mid 19th century Euclidian Geometry found itself replaced by a whole group of virtual and previously unimaginable

26 spheres: the Riemann’ Geometries. This radical shift of paradigm allowed Einstein’s theories to emerge and modern mathematics to be developed. Psychopathology is in urgent need of a comparable turn - away from the narrow field of clinical observation to the more abstract spheres of relations and structures. Methods: The presentation focusses on the clinical and theoretical achievements of Kronfeld, Goldstein and Lewin towards a ‘New Psychopathology’ - all of them being influenced by Ernst Cassirer’s ‘‘Philosophy of Symbolic Forms’’. A special importance is given to Cassirer’s ‘‘Pathology of Symbolic Forms’’ and its clinical impact. Results: ‘Symbolic Forms’ are an artificial construct of culture. Its layers in this ‘Matrix of Mental Formation’ break down in crisis, thus allowing a fresh view on pathological phenomena. A model of the ‘Matrix’ is presented from which an altered concept of psychopathology can be deducted. Conclusion: The History of Science shows a shift of paradigm from astronomy via physics to chemical and biological understanding. ‘Symbolic Formation’ is the decisive element to explain the recent step to the uniqueness of the human race and its cultural achievements. There is a need to determine the ‘ontological status’ of this ‘symbolic link’. Its complex layers have to be read primarily as a ‘morphology of culture’.

P-05-03 Treatment of schizophrenia in somatic inpatients of general hospital V. Prokudin (Russian State Medical Univ., Psychiatry, Moscow, Russia), Y. Boyko Introduction: In General Hospital (1500 beds) Department of Psychiatry has been created (2 psychiatrists, 2 psychotherapeutists and psychologist). During last 10 years psychiatrists has consulted of 14436 somatic inpatients. 70,5% of somatic inpatients were suffered from light non-psychotic disorders and 29,5% - psychotic disorders. Methods: The ‘‘liaison-attachment model’’ was used for treatment of comorbid schizophrenia in General Hospital. According with this model psychiatrist discussed with internists the psychological and mental problems of their patients, and worked out the optimal way of treatment. Results: Schizophrenia was revealed as comorbid disease in 693 (4,8%) somatic inpatients suffering from different somatic diseases. We revealed some light variants of schizophrenia in somatic inpatients: residual, neurosis-like and with schizophrenic defect. All these inpatients were in therapeutic remission. Only 20 inpatients (3%) suffered from hard psychotic variants of schizo-phrenia with delusions and hallucinations were also revealed. The mild and atypical neuroleptics, modern antidepressants of 3rd generation as well as anxiolytics were used for treatment of co-morbid schizophrenia in General Hospital. Conclusion: Thus, the main amount of inpatients with comorbid schizophrenia (673) were completely and successfully treated in both somatic and mental status without any stigmatization and discrimina-tion and this improves the quality of life of such patients.

P-05-05 Reduction of stigma and discrimination because of schizophrenia – the antistigma - project of the GRNS A. Baumann (Dept. of Psychiatry, Rhineland State Clinics, Du¨sseldorf, Germany), H. Za¨ske, W. Gaebel Introduction: Stigma and discrimination intensify the burden of people who suffer from a mental illness, particularly of those with a schizophrenia. The World Psychiatric Association has initiated the ‘‘WPA Global Programme to Reduce the Stigma and Disctrimination Because of Schizophrenia – Open the doors’’. Within the GRNS project 4.2.2, the German Open the Doors Programme was implemented and evaluated. Methods: Prior to the implementation of antistigma interventions in 2001, a population attitude survey (N = 7225) was conducted to identify relevant intervention target groups and as

baseline for a follow-up survey in 2004 (N = 4622). The assessment included knowledge about symptoms and treatment of schizophrenia, stereotypes about and social distance towards people with schizophrenia. Results: An overall significant reduction of social distance towards people with schizophrenia was found, which was primarily located in those cities with antistigma programs. Further influencing factors could be identified (e.g., personal contact to people with a mental illness and knowledge of an antistigma program). Conclusion: Evidence for the success of antistigma programs on the population’s level could be provided. The focus of the third funding period lies in the transfer of the experiences made in the antistigma interventions which will be put down in a fact book. P-05-06 Relationship between insight in schizophrenia and psychosocial variables in community clinical case management S. Caton (Freundeskreis Nervenklinik Spandau e.V., Berlin, Germany), W. Kaiser Introduction: In the German phenomenological psychiatric tradition, Jaspers and Conrad addressed illness insight the middle of the last century. In this regard, it is odd that modern social psychiatry utilizes subjective evaluative criteria, but essentially omits asking the client if they think they’re ill. Since Jaspers and Conrad, there has been no German language study using the newer standardized instruments to address schizophrenic illness insight. Methods: A German version of Amador’s Scale of Unawareness of a Mental Disorder (SUMO) assessed the illness insight in schizophrenia. Relatlonships were explored between illness insight and the level of psychosocial functioning, support needs, subjective quality of life (sqol) and medication adherence. ThQ sampie (N = 43) was recruited from agencies providing residential clinical case management services in Berlin, Germany. Separate interviews were conducted with case managers and their clients. Pearson correlations and odds ratios were calculated for the relationship between variables. Results: Significant psychotic symptom misattributions in 50% (3/4 misattributions) or 80% (1/2 misattributions) of the sample. Correlation noticed between the SUMD-attribution-score and the GAF-score. Misattributions tor 3=4 of the symptoms predicted an OR of 6 to a GAF-score <40. Medication adherence was found to be independent of insight. Noticed was an inverse correlation between client rated needs for care and sqol. Conclusion: Lower insight in regards to misattributions of psychotic symptoms may predict low social functioning. Case manager interventions should begin with patient rated needs and be based in general on scientific evidence. P-05-07 Public attitudes towards people with a mental illness before and two years after the opening of a psychiatric day hospital and outpatient department H. Za¨ske (Dept. of Psychiatry, University of Du¨sseldorf, Germany), A. Baumann, W. Gaebel Introduction: In 2004, a psychiatric day hospital and outpatient department was opened in Du¨sseldorf. It has been debated, whether the structure of the mental health care services has an influence on local population’s attitudes towards people with a mental illness. Possible long-term attitude changes of the local population are examined. Methods: Before the opening of the day hospital and outpatient department, a representative postal survey was conducted in the neighbourhood and in control regions in Du¨sseldorf. The assessment comprised attitudes towards mental health services and attitudes towards people with schizophrenia and depression. In spring 2007, a follow-up survey was conducted. Results: In 2004, 3.600 letters were mailed. The response rate of approx. 14% was rather low (N = 489). Within the follow up, about 200 letters were sent back (response rate of 40%). Correlations between attitudes and variables of local particularities (distance to

27 the mental health service, social structure of the neighbourhood) and individual-related characteristics (e.g., the personal contact with the mental health service or with service users) will be analysed. Conclusion: Public attitudes towards mental health services are an important factor in the planning of new psychiatric services in communities. In this study, several influencing factors (locationand individual-related) are discussed. P-05-08 Relationship between quality of life, psychopathological symptoms, substance consumption and adherence to treatment in patients with schizophrenia I. Vanelli (Faculty of Medicine A.Avogadro, Dept. of Psychiatry, Novara, Italy), S. Pombo, E. Torre, P. Levy Introduction: To investigate the relationship between Quality of Life, Psychopathological Symptoms, Substance Consumption and Adherence to Treatment. Methods: The sample comprised 36 in-out patients: 10 woman (28%) and 26 men (72%), diagnosed with schizophrenia according to DSM-IV-TR, recruited in the Psychiatric Unit of Santa Maria Hospital in Lisbon (Portugal). Twelve had history of consumption. Subjects were evaluated with the WHOQOL-BREF, BPRS, MARS. Comparative and correlation analysis were performed (p = 0.01). Results: When we analyzed data, we found the following negative correlations: Suspiciousness, Unusual Thought Content, Suicide of BPRS with Physical Health and Psychological domains of WHOQOL-BREF; Suspiciousness, Unusual Thought Content and Self Neglect of BPRS with WHOQOL-BREF Social Relationship domain; Suspiciousness of BPRS with WHOQOL-BREF Environment domain. Data showed significant negative correlation between MARS and BPRS Hallucinatory Behavior and positive correlation with WHOQOL-BREF Environment Domain. There is no significant relationship between substance consumption, MARS and QoL. Conclusion: Our results suggest that there is a relationship between some domains of WHOQOL-BREF and some BPRS items. We didn’t evidence significant relationship between MARS and psychopathological measures. We didn’t find very significant relationship between BPRS and drug consumption.

P-05-09 Study of basic symptoms in schizophrenia patients in north west of Iran P. Molavi (Medical University of Ardebil, Psychiatric, Iran), H. Ghamarigivi, E. Rezaei Ghalechi, S. Saeedlou, R. Arab, S. Arshi Introduction: The objective of this research is studying the basic symptoms in schizophrenic patients of Ardebil city and determines the most frequent basic symptom and the most frequent type of schizophrenia in them. Also, providing a new classification of basic symptoms in these patients. Methods: This study is a descriptive – analytic one. A sample of 100 patients of both sexes was selected. we used a 44 item questionnaire which was provided through a combination of PANSS and Kitamura questionnaires. To screen we used MMPI test. The findings were analyzed by descriptive statistics and through the computer software SPSS. Also a PCA method of factor analysis was used to the hypotheses Results: The highest frequency was: single (62% = 49 patients), unemployed (52% = 52 patients), with no education (31% = 31 patients), negative family history (91% = 91 patients), with frequent admission (47% = 47 patients). The most frequent basic symptom in these patients was attention deficit, and social withdrawal was at second place. and the paranoid schizophrenia (44% = 44 patients). Conclusion: This study’s findings are similar to with DSM-IV and Bleulerand Kraepelin symptoms.Therefore, it seems that all of these systems introduce the different fields of a single diagnostic structure rather than antagonist ones. This study suggests that if we recognized emotional symptoms and restlessness, we should think of other psychotic disorders.

P-05-10 Insomnia and its role in schizophrenia P. Bosch (Radboud University Nijmegen, NICI, Venlo, The Netherlands), M. Van den Noort Introduction: It is generally known that schizophrenia is often accompanied by insomnia. But how important is insomnia within schizophrenia, and might the improvement of sleeping disorders be a bridge to improve life quality? Methods: An extensive literature review was conducted. Results: It was found that studies with a focus on insomnia in schizophrenia are quite rare. It is found that insomnia is seldom the predominant complaint, and therefore it receives less attention than it should. Sleeping disorders have an influence in life quality, and by treating them, patients will experience an enhanced life quality, thereby creating a better situation for them, their relatives, and even their therapy and possible outcome. Furthermore, during acute phases, sleep is extremely disturbed. Whether this correlation is bidirectional is unclear, but the implications might be large if it is. The results of our review will be presented to a greater extent at the conference. Conclusion: It is of the greatest importance to focus on the treatment of insomnia and other sleeping disorders, when treating patients with schizophrenia, or even with mental disorders in general. Improving sleep can improve life quality to a great extent, and can make the patients more open to therapy on the deeper lying problems. P-05-11 Investigative report from personal data of schizophrenic patients in Shiraz psychiatric centers Iran Y. Kalafi (Medical Univ. of Shiraz Iran, Dept. of Psychiatry, Iran) Introduction: Schizophrenia is a mental disorder that profoundly involves thought; perception, emotion and behaviour. An etiologically puzzling schizophrenia has long hold the attention of psychiatric epidemiologist. Methods: This is the retrograde study that carried on the patients that admitted final diagnosis of schizophrenia according to DSM-IV-R in shiraz (city) several psychiatric hospitals. Personal data such as age, sex, socio-economic educational status, prolongation and number of admitting, subtype disorder, marriage status, birth season was extracted. Results: 1762 patients (1299 males 463 females) from 1995–2005 that admitted with final diagnosis of schizophrenia that showed 80% of patients were in age group less than 33 y/o (mean age 28/8). Family members of 90% patients were more than 6 persons 90% was high school educated. Prevalence rate of schizophrenia among family member was 3.5%. More than 50% were admitted for first time. Prodromal symptoms of 30% patients were manifested more than 5 years. Conclusion: Our finding was showed that low percent female ratio male admission and low percent readmission of such disabling disorder and duration from early stage of disorder to admission; overall shows the importance of family role in care of these patients that needs more psycho and family education about disorder in comparison with developed countries.

P-06 Prodromal Stage II P-06-01 Softly, softly catchee monkey - starting an early detection service for persons at risk of psychosis F. Schultze-Lutter (University of Cologne, Dept. of Psychiatry, Ko¨ln, Germany), S. Ruhrmann, J. Klosterko¨tter Introduction: To introduce and characterize the establishment phase of an early detection centre for prodromal psychosis along with its detaining and promoting factors within a universal multipayer health care system. Methods: Across the first six years (1998–2003), analysis of clients’ characteristics with regard to the diagnostic evaluation; and, for an exemplary 12-months period (3-1-2002 to 2-28-2003),

28 analysis of the characteristics of telephone contacts with the service. Results: Following the first year of service, the percentage of persons meeting any prodromal criterion quickly levelled off between 40 to 50%, although the number of first contacts grew steadily over the first four years of service and only reached its staffdependent maximum after the introduction of a long-term awareness campaign. Rising steadily in number across the first three years, 872 persons, predominately of German citizenship and higher education, consulted the service until 2003, 326 with first-episode psychosis and 144 with no current or beginning psychosis. Of the 402 putatively prodromal patients, 94% reported predictive basic symptoms, 68.9% attenuated and 20.6% transient psychotic symptoms. Conclusion: Supported by public awareness campaigns, an early detection service is well received by its clients and private practitioners as reflected by the high number of referrals from this source.

P-06-02 Basic symptoms in the prediction of psychosis F. Schultze-Lutter (University of Cologne, Dept. of Psychiatry, Ko¨ln, Germany), S. Ruhrmann, H. Picker, J. Klosterko¨tter Introduction: Besides the ultra-high risk mental state, a promising complementary approach is based on the basic symptom concept; especially the presence of cognitive-perceptive basic symptoms. Methods: In the prospective evaluation study, 146 subjects (68.5% males, mean age 24±5 yrs.) with at least one of ten cognitive-perceptive basic symptoms were followed up on average 13±9 months (range: 1–37) for their psychopathology with the Schizophrenia Proneness Instrument, Adult version (SPI-A), the Structured Interview for Prodromal Syndromes (SIPS) and the PANSS. Results: 51 (34.9%) subjects hitherto developed a frank psychosis within 11±9 months on average, 85% of them had already exhibited attenuated psychotic symptoms (APS) according to the SIPS at baseline. Comparing baseline data of those with and without a development of psychosis (Mann-Whitney U-test, adjustment for multiple testing according to Holm’s sequential method), significant differences showed for the SPI-A ‘Cognitive Disturbances’; SIPS ‘Positive Symptoms’, ‘Negative Symptoms’ and ‘Disorganized Symptoms’ and PANSS ‘Negative Scale’. A classification equation (stepwise logistic regression analysis, backward Wald) including SIPS ‘Disorganized Symptoms’, PANSS ‘Negative Scale’ and SPI-A ‘Cognitive Disturbances’ and ‘Cognitive Attentional Impediments’ classified 73% of the cases correctly. Conclusion: The results underline the importance of self-experienced cognitive deficits in the early detection of psychoses.

P-06-03 Social and academic premorbid adjustment in first psychotic episode A. Barajas Velez (Hospital de Sant Joan de Deu, Unitat de Recerca, Barcelona, Spain), I. Banos Yeste, S. Ochoa Gu¨erre, J. Usall Rodie, V. Villalta Gil, A. Fargas Villanueva, M. Dolz Abadia, B. Sanchez Fernandez, J. A. Alda Diez, J. M. Haro Abad Introduction: The aim of this study is to analyze how the academic and social domains of premorbid functioning in patients with a first psychotic episode (FPE) associate with gender, age at onset, symptoms and cognitive functioning. Methods: Cross-sectional study of 24 consecutive cases with a FPE described as presence of two or more psychotic symptoms and an age range between 7 to 65 years old . Instruments used were a clinical and sociodemographic questionnaire, PANSS, ICG-SCH, PAS and a battery of cognitive tests. Data were analyzed using nonparametric tests. Results: No significant differences were found in gender and age at onset of FPE when associated to total and both domains of premorbid adjustment. Significant associations were obtained between the negative scale of ICG-SCH and social premorbid adjust-

ment (r = 0,41; p = 0,048) and between the depressive scale of ICGSCH and total premorbid adjustment (r = 0,41; p = 0,044). Significant correlations were obtained between total premorbid adjustment (r = 0,45; p = 0,037), social domain (r = 0,48; p = 0,025) and academic domain (r = 0,44; p = 0,038) with impulsivity (a CPT index). Conclusion: Our results give support to previous studies although attention does not only associate to the academic domain. Future studies assessing differences between these two domains may detect differential patterns of onset of psychotic episodes. P-06-04 Patterns of depression in subjects at high risk for psychosis H. Graf von Reventlow (University of Cologne, Department of Psychiatry, Germany), S. Ruhrmann, F. Schultze-Lutter, M. Heinimaa, P. Patterson, P. Dingemans, G. Juckel, D. Linszen, R. K. R. Salokangas, M. Birchwood, J. Klosterko¨tter Introduction: To further investigate the role of clinically relevant depression for an early recognition and treatment of psychosis, the European Prediction of Psychosis Study (EPOS) investigates the concurrent rates and severity of depressive symptoms and syndromes, as well as their correspondence to e.g. international ultra-high risk and other psychopathology indicators, sociodemographic variables, functional decline, and transition to psychoses. Methods: Relevant measures were obtained for 239 subjects at risk for psychosis in 6 centres in Finland, Germany, The Netherlands, and UK. Results: At baseline, 48.8% of the subjects fulfilled the criteria of any current SCID I DSM-IV affective disorder. Moreover, the sample showed a clinically relevant mean of 20.3 (±10.9) in the BDI sum score. Significant associations of observed and self-reported depression were found with e.g. the current level of functioning (r = ).325 and ).348, both p £ .001, respectively) and SIPS/SOPS 3.0 disorganized communication (r = .158, p £ .005, and .193, p £ .001, respectively). Conclusion: The results highly correspond to findings of retrospective studies on the early course of psychoses, and underline the relevance of affective disorders and especially depression in early recognition and early intervention. P-06-05 Assessment of self-reported early trauma as a risk factor for psychosis with the Trauma and Distress Scale (TADS) H. Graf von Reventlow (University of Cologne, Department of Psychiatry, Germany), R. K. R. Salokangas, P. Patterson, S. Luutonen, J. Huttunen, M. Heinimaa, M. Birchwood, D. Linszen, G. Juckel, S. Ruhrmann, J. Klosterko¨tter Introduction: Early trauma is currently broadly investigated as a risk factor for the development, maintenance and severity of psychosis. Sophisticated attempts are made to explain for presumed consequences of especially childhood interpersonal trauma on later psychosis. Methods: To investigate a range of possibly traumatic, adverse childhood experiences and perceived early interpersonal distress, the TADS, a 43-items self-rating questionnaire, was administered to subjects attending primary care (PrimC, n = 742) or community mental health care (PsychC, n = 178), and to subjects at high risk (HR, n = 240) for psychosis. Results: Elevated rates of pronounced adverse interpersonal childhood experiences were found in PsyC and HR samples (TADS early trauma sum score means of 21.4 and 23 compared to 12.2 in PrimC, p £ .000). Emerging associations between more gross trauma categories and transition into psychosis in the HR sample did statistically reach only trend level. Conclusion: Current results show that early adverse interpersonal experiences are markedly elevated in a HR sample. As the increase was comparable to a community mental health care sample, such early experiences seem to be primarily a risk factor for developing mental disorder in general. First preliminary analyses, however, did not yield a clear association with transition to psychosis.

29 P-06-06 Life events and the initial prodrome of schizophrenia H. Picker (University Cologne, Hospital of Psychiatry, Germany), F. Schultze-Lutter, S. Ruhrmann Introduction: The vulnerability-stress-coping-model of schizophrenia suggests an interaction between personal vulnerability and psychosocial stressors, e.g. life events, and should also apply to prodromal stages of the illness. Therefore, the number, kind, evaluation and associated subjective burden of life events in the potential initial prodromal state were studied. Methods: Putatively prodromal patients (n = 21) and controls with depressive disorders (n = 21) were compared for differences in quantity and quality of life events. Life events were retrospectively assessed with a self-rating version of the Munich Life Event List for negative and positive life events and life conditions within the last three years. Every event was evaluated on a 5-point rating scale for the subjective valuation and subjective burden. Results: The prodromal group showed a significant tendency to experience more severe stress (p = 0.007) and to give a more negative valuation of the events (p = 0.039) that occurred social contacts most. Conclusion: The results support the notion of a higher susceptibility to stress in prodromal patients. Furthermore, in line with findings of the ABC-study showing that social deficits seem to appear first in the area of social contacts, a significant accumulation of life-events in this area of life was reported by the putatively prodromal patients.

P-06-07 Competence and control orientation in putatively prodromal persons S. Ruhrmann (University of Cologne, Psychiatry & Psychotherapy, Germany), J. Paruch, F. Schultze-Lutter, H. Picker, H. Graf von Reventlow, M. Neumann, V. Veith, A. Bechdolf, J. Klosterko¨tter Introduction: Competence and control orientation (CCO) plays an important moderating part in the vulnerability-stress-coping model of processes leading to outbreak of psychosis. Methods: CCO was investigated in 41 putatively prodromal persons (PP) and in 29 mentally healthy control persons (HC). Results: Compared to HC, PP exhibited significantly lower internal control orientation, generalized self-concept of one’s own ability and self-efficacy, accompanied by significantly higher powerful others and chance control orientation as well as general externality of control orientation. Differences could not be explained by demographic characteristics or depression. Prodromal symptoms were not associated substantially with CCO. Conclusion: The lacking covariance between psychopathology and CCO paired with the significant differences to the HC sample suggest that CCO of PP could be generally more unfavourable in terms of a disposition for developing symptoms. This assumption fits well in recent findings on biological correlatives of CCO, which seem to be rooted in the dopamine receptor gene complex genotype and experience-based differences in dopamine metabolism. Since social learning also plays an important part in CCO development, this apparently health promoting construct should be targeted also in cognitive behavioural interventions in psychosis and its prodromal states.

P-06-08 Subjective quality of life in initial prodromal states of psychosis and its possible determinants – results from the German Research Network on Schizophrenia S. Ruhrmann (University of Cologne, Psychiatry & Psychotherapy, Germany), J. Paruch, A. Bechdolf, M. Wagner, H.-J. Mo¨ller, W. Gaebel, W. Maier, J. Klosterko¨tter Introduction: Subjective quality of life (QoL) is reduced in patients with schizophrenia as well as in persons in a putatively early initial prodromal state (EIPS). Methods: To determine whether QoL reduction is more marked in persons in a putatively late initial prodromal state (LIPS) than in

EIPS and in comparison with healthy controls (HC), 65 EIPS, 157 LIPS and 87 HC were assessed on subjective QoL. Demographics, symptoms, locus of control and coping strategies were assessed as possible predictors of QoL in initial prodromal states. Results: EIPS and LIPS both reported significantly lower QoL than HC in all assessed areas, while EIPS and LIPS did not differ significantly from each other. Furthermore, unspecific symptoms shaped up as strongest predictors of QoL. Conclusion: Impairment is startling serious yet in earliest stages of developing psychosis. With regard to subjective QoL, the distinction of early and late prodrome does not seem to be crucial, the experience of any prodromal symptoms inherently is the key variable. Since literature provides evidence that QoL in prodromal states is also lower than QoL in manifest psychosis, working models of changes in QoL in prodromal states should address processes of initial self-concept irritation and ongoing adaptation to illness. P-06-09 Schizotypal features and risk of psychosis - results of the EPOS group R. K. R. Salokangas (University of Turku, Department of Psychiatry, Finland), M. Heinimaa, J. Klosterko¨tter, S. Ruhrmann, H. Graf von Reventlow, D. Linszen, P. Dingemans, M. Birchwood, P. Patterson Introduction: It has been suggested that persons with schizotypal personality features are at risk of psychosis. Within the European Prediction of Psychosis Study (EPOS), we studied occurrence of schizotypal features in psychiatric outpatients at risk or not at risk of psychosis and in healthy controls. Methods: Within the EPOS project, in Turku Centre, we investigated psychiatric outpatients at current risk of psychosis (CROP; n = 49), psychiatric outpatients without risk of psychosis (NONCROP; n = 25), healthy controls (HC; n = 30). Risk of psychosis was defined by occurrence of basic symptoms, attenuated psychotic symptoms, brief, limited or intermittent psychotic symptoms or familial risk plus reduced functioning during the past three months. Schizotypal featured were assessed by the Schizotypal Personality Questionnaire (SPQ). Results: Total SPQ scores and its factors (cognitive-perceptual, interpersonal and disorganised) decreased linearly from CROP subjects via NON-CROP subjects to HCs (p < 0.001). In multivariate analyses, basic symptoms associated significantly with total SPQ scores and with all its factors. Positive symptoms associated with cognitive-perceptual factor and negative symptoms with interpersonal factor. Conclusion: Schizotypal personality features and its components increase the risk of psychosis. Subjective anomalous experiences, manifested in basic symptoms, are strongly associated with schizotypal personality features.

P-06-10 Prodromal symptoms prior to a first episode in schizophrenia and prior to a relapse: Comparison of prevalence and predictive validity M. Riesbeck (Heinrich-Heine-University, Dept. of Psychiatry, Du¨sseldorf, Germany), K. Maurer, H. Ha¨fner, W. Gaebel Different studies within the German Research Network on Schizophrenia have monitored prodromal symptoms both in patients at (ultra) high risk for a first episode in schizophrenia (initial prodromal symptoms) and in patients after the first episode, prior a relapse (relapse prodromal symptoms). Since prodrome assessment was based on comparable instruments, a comparison of initial and relapse prodromal symptoms was enabled. Regarding prevalence, initial prodromal symptoms were more frequent than relapse prodromal symptoms, potentially due to design related reasons (the presence of initial prodromes was an inclusion criteria for patients at (ultra) high risk) or the fact, that patients after the first episode receive antipsychotic treatment. However, prevalence rates of the initial and relapse prodromal symptoms are highly correlated (r > .60; p < 0.001). Regarding predictive validity, sensitivity and specificity scores

30 were computed. Whereas sensitivities of the 45 prodromal symptoms assessed were higher for he initial prodromes, specificities where higher for relapse prodromes. Nevertheless, both scores were also highly correlated between the initial and relapse prodromal symptoms (r > .50; p < 0.05). These results indicate that prodromal symptoms prior a first episode in schizophrenia and prior a relapse show some similarity.

P-07 Treatment II (side effects) P-07-02 Generic substitution of an atypical brand antipsychotic by a pharmacist will have a negative impact on patients with psychoses/schizophrenia E. Van Gent (GGNet Slingeland Hospital, Doetinchem, The Netherlands), B. Roman Introduction: The goal of this study is to gain insight into the reactions of people suffering from a psychotic disorder towards a generic version of their own antipsychotic if given to them by their pharmacist. Methods: Simulating a pharmacy setting, 106 adult outpatients with psychoses/schizophrenia currently taking an oral atypical antipsychotic were given (in random order) either their usual antipsychotic or a created ‘generic version’ of the same antipsychotic. When giving the ‘generic’ the ‘pharmacist’ could either or not tell that the medicine is essentially similar to the brand antipsychotic. Patients scored their intention to take the medicine as usual. Results: 73% of the participants would be unlikely to take the generic antipsychotic. Their mean score of the intention to take the generic version was 27 (very unlikely) on a scale of 100, versus 92 (will almost certainly take it) for the brand medication. Giving a short explanation increased the intention to a mean of 38 (p < 0.05). No difference was seen between patients having symptoms of paranoia in the past or at the time of the study. Conclusion: The differences between the brand and generic versions of antipsychotics has a negative effect on the acceptance of medication by patients suffering from psychoses/schizophrenia. Due to the nature of the disease switching of a branded antipsychotic to a generic by a pharmacist should not be done without acknowledgement of the psychiatrist and patient.

P-07-03 Weight management by modular group interventions. Outcome at 24 months in an Irish cohort with severe mental illness (SMI) C. Bushe (Eli Lilly, Clinical Research, Basingstoke, United Kingdom), C. Haley, D. McNamara, P. Devitt, M. Fleming McCrossan Introduction: Patients with SMI receive long term intervention with psychotropic agents often associated with weight gain. Weight and lifestyle management programmes may prevent, reduce or reverse weight gain, however most data is short-term. Categorical data is not often reported Methods: A group programme (Solutions for Wellness) designed to address weight and other cardiovascular risk factors commenced 2002 in Ireland. Each group provided open-ended access to referred SMI patients. Weekly group sessions consisted weighing, discussion and an 8-week rotational cycle of educational topics on aspects of weight, dietary choices and lifestyle changes. Groups were led by trained healthcare professionals. Data is reported up to 24 months Results: Data from 54 patients (27 male; 27 female) from 6 centres. Mean age 48.2 years (range 21–74). Schizophrenia 62%, Affective disorders 26%, other 12%. Patients completing 1 year 52% and 2 years 21%. Baseline mean weight 98.9 kg (SD 19.2) decreased to final visit weight 96.4kg (SD 18.4).Paired t -test p = 0.0030; CI Mean 2.53 (0.9–4.159). Weight increased in 11/54, maintained 7/54 and decreased 36/54. Conclusion: Weight gain in SMI patients is not inevitable and was found in only 20% of patients attending weight clinics in Ireland. Patients may benefit if similar interventions were widely available.

P-07-04 The effect of a weight management program to prevent increasing visceral body fat during treatment with olanzapine J. Thu¨nker (Heinrich-Heine University, Psychiatry and Psychotherapy, Du¨sseldorf, Germany), M. Mittrach, A. Klimke, H. Hauner, J. Cordes Introduction: Drug-induced weight gain and impairment of metabolic parameters is of high clinical relevance due to increased rates of morbidity. The principal objective of this trial is to investigate the effect of a preventive treatment program on weight gain in schizophrenic patients under olanzapine treatment. Methods: In a randomised open-label study, 77 schizophrenic patients (DSM-IV) were included and randomly assigned to a treatment and control group. Patients in the treatment condition received a behavioural group intervention twice a week. Topics of this intervention primarily included eating behaviour, activity and stress management. The long-term effects for another six months after intervention were evaluated. Results: The study will be completed in July 2007, so far we have analysed data for the intervention period. 57% of the randomised patients dropped out. During that phase both groups showed significant weight gain (p < .001). Visceral body fat operationalized by the waist circumference increased significantly in the standard group (p = .004), but not in the treatment group. We found further effects for blood pressure and eating behaviour. Conclusion: The preliminary results of this study suggest a preventive effect of weight management in schizophrenia. P-07-05 Long-term topiramate treatment in psychotropic drug induced weight gain: a retrospective chart review Y. Khazaal (Geneva, Switzerland) Introduction: Objective: Determining efficacy and tolerability of long term topiramate treatment of psychotropic drugs induced weight gain. Methods: A retrospective chart review of patients treated with an addition of topiramate in order to control psychotropic drugs (antipsychotic, lithium or valproate) induced weight gain. Results: The case series consisted of 100 patients. The mean final daily dose of topiramate was 186.8 mg/day and the median dose was 200 mg/day for a total treatment duration of 41 weeks. Adverse events lead to Topiramate discontinuation in 22% of subjects. A significant reduction of BMI was observed between the first and the last measure from 29.7 to 28 (t = 5.82, p < 0.0005). Reduction of BMI is greater in patients treated with antipsychotic drugs than in those treated with lithium or valproate alone. No difference was found between comorbid active substance abuse or dependence subjects and the others. Conclusion: In this retrospective case series, topiramate was found to be effective in reversing weight gain associated to antipsychotic, lithium or valproate. Tolerability of topiramate was an issue in some patients. P-07-06 Cognitive behavioral therapy for obesity and binge eating disorder associated to antipsychotic drugs Y. Khazaal (Geneva, Switzerland), E. Fresard, A. Chatton, D. Zullino Introduction: A previousrandomized controlled study [12-weeks cognitive and behavioral therapy (CBT) vs. Brief Nutritional Education (BNE)] has concluded to the effectiveness of CBT. The aim of the present paper is to confirm the previous results on a larger sample of patients, to assess the impact of the interventions on other cognitive dimensions as well as to assess potential clinical indicators of outcomes. Methods: A controlled study (12-week CBT vs. B N E) was carried out on 99 patients treated with an AP and who have gained weight following this treatment. Binge eating symptomatology, eating and weight-related cognitions, as well as weight and body mass index were assessed before treatment, at 12 weeks and at 24 weeks.

31 Results: The findings confirm the usefulness and the effectiveness of the proposed CBT program in treating binge symptomatology, cognitive distortions and obesity in patients treated with AP. Reduction of binge symptoms and maladapted cognitions appeared early, whereas the effect on weight appeared later during the follow-up observation. No differences on outcomes were found across pharmacotherapy characteristics, diagnostic categories, binge eating neither in severity of cognitive distortions. Conclusion: The proposed CBT treatment is useful for patients suffering from weight gain associated with AP treatments and even when a concomitant treatment with lithium or valproate is given. P-07-07 Reward system activation in schizophrenic patients switched from typical neuroleptics to olanzapine F. Schlagenhauf (Charite University Hospital, Department of Psychiatry, Berlin, Germany), G. Juckel, M. Koslowski, T. Kahnt, T. Dembler, B. Knutson, T. Kienast, J. Gallinat, J. Wrase, A. Heinz Introduction: High blockade of dopamine D2 receptors in the ventral striatum including the nucleus accumbens may interfere with reward anticipation and cause secondary negative symptoms such as apathy or anhedonia. This may not be the case with newer neuroleptics such as olanzapine, which show less dopamine D2 receptor blockade and a faster off-rate from the receptor. Methods: We used functional magnetic resonance imaging (fMRI) to assess the BOLD response in the ventral striatum of ten schizophrenics medicated with typical neuroleptics (T1) and after switching them to olanzapine (T2) and of healthy control subjects at corresponding time points during reward anticipation with a monetary incentive delay task. Results: During reward anticipation, healthy volunteers showed significantly higher ventral striatal activation compared to schizophrenic patients treated with typical neuroleptics (T1) but not olanzapine (T2), which was reflected in a significant interaction between group and session, indicating an increase in patients relative to controls from T1 to T2. In patients treated with typical neuroleptics, but not with olanzapine, decreased activation of the left ventral striatum was correlated with the severity of negative symptoms. Conclusion: Failure to activate the ventral striatum during reward anticipation was pharmacologically state-dependent and observed only in patients treated with typical neuroleptics but not with olanzapine, which may indicate that this drug did not induce secondary negative symptoms via interference with reward anticipation.

P-07-08 Working memory function and prefrontal cortex activation in schizophrenic patients switched from conventional antipsychotics to the atypical neuroleptic olanzapine F. Schlagenhauf (Charite University Hospital, Department of Psychiatry, Berlin, Germany), T. Wu¨stenberg, K. Schmack, M. Dinges, J. Wrase, M. Koslowski, M. Bauer, J. Gallinat, G. Juckel, A. Heinz Introduction: Dysfunctional activation of the dorsolateral prefrontal cortex (DLPFC) has been repeatedly showed in schizophrenic patients and may be related to a prefrontal dopamine deficit. Little is known about the modulation of DLPFC activation during antipsychotic treatment with conventional and second generation antipsychotics such as olanzapine. Methods: We measured activation of DLPFC during a working memory task in a longitudinal fMRI study in ten schizophrenic patients first when they received conventional antipsychotics and after they had been switched to olanzapine. An age- and gendermatched healthy control group was investigated at two corresponding time points. We analyzed the fMRI data with SPM5 in a 2x2x2 design (group x session x condition). Results: On the behavioral level schizophrenic patients performed significantly worse compared to the healthy controls at both time points. The fMRI data revealed an significant group by condition interaction in the bilateral DLPFC (P < 0.05 S.V.C.) and the

right parietal cortex, indicating a hypoactivation in the patient group. No other significant interaction was found in the whole brain SPM-analysis. Conclusion: Contrary to Honey et al. (1999), who described an increase in the DLPFC after switch from haloperidol to risperidone, we found rather a decrease than an increase in DLPFC activation in schizophrenic patients switched from conventional antipsychotics to olanzapine, which failed to reach statistical significance. P-07-09 Clozapine induces preadipocyte differentiation K. Fehsel (Heinrich-Heine-University, Psychiatry, Du¨sseldorf, Germany), C. Luckhaus Introduction: Psychoactive drugs and especially clozapine cause massive weight gain in patients. Recent studies focussing on the activation of neuropeptides which are involved in the appetite regulating network presented controversal results. We postulated a direct effect of clozapine on fat cells. Therefore we studied the influence of clozapine on progenitor fat cells. Methods: Preadipocytes were isolated from human subcutaneous adipose tissue samples and differentiated in differentiation medium with and without different psychoactive drugs. Differentiation was assayed after 8–15 days by cell counting, Oil red staining and determination of glycerophosphate dehydrogenase (GPDH) activity, an enzyme only expressed in mature adipocytes Results: Treatment of preadipocytes with clozapine induced rapide triglyceride accumulation in the cells without effect on cell proliferation. In differentiation medium clozapine and risperidon induced a significant rise in GPDH and an elevated number of differentiated cells. Lithium chloride and haloperidol did not affect standard differentiation. Conclusion: In conclusion, our results suggest a new explanation for weight gain in patients treated at least with clozapine: increased fat mass due to enhanced differentiation from progenitor fat cells to mature adipocytes. Green tea extract which effectively inhibited preadipocyte differentiation in vitro, might also help preventing this weight gain in vivo. P-07-10 Tranquilizing activity of the norbornene row amides L. Kasyan (Dnepropetrovsk National University, Organic Chemistry, Ukraine), V. Mamchur, H. Zlenko, T. Skachko, V. Palchikov, I. Tarabara Introduction: High rate of life of XXI age, abundance of information requires the research of new psychotropic facilities in particular tranquilizers. Methods: The row of monoamides of the norbornenedicarboxylic acid, including the fragments of p-nitroaniline, 2-aminothiazole, alpha- and beta-aminopyridines, aminoantipyrine, 3amino- and 3-methylaminosulfolan-1,1-dioxide, pyrrolidine, piperidine, dimethyl- and tetramethylpiperidine, and also morpholine have been studied in this work. Experiences were carried out on white mice. Results showed that the acute toxicity of the synthesized compounds varied from 123.0 to 1425.4 mg/kg. Action of preparations was studied on the test of increase of barbituric sleep duration caused by hexenale (60 mg/kg). Experimental animals for 30 mines to hexenale got the injection of preparation in a dose of 1/10 LD50, and to the controls animals entered isotonic solution of sodium chloride. Results: It was set that secondary amides either does not possess depremiric action ()15.0%) or a sedative effect is expressed poorly (21.0–107.1%). Among compounds with a tertiary amide group studied activity considerably increases at increase of the cycle size (on 118.3%) and at accumulation of methyl groups, and achieves of maximal value (498.3%) for derivative of tetramethylpiperidine. Conclusion: It is necessary to mark that explored compounds along with tranquilizing action show analgesic and anticonvulsive activity.

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P-08 Neurocognition P-08-01 Theory of mind in schizophrenia: The role of clinical symptomatology in understanding other people’s thoughts and intentions M. Abdel-Hamid (LWL Klinik Bochum, Germany) Introduction: A wealth of studies has demonstrated that patients with schizophrenia are impaired in reflecting upon their own and other persons’ mental states. This cognitive capacity has been termed ‘‘Theory of Mind’’ (ToM). Here, we tested the hypotheses that ToM deficits are selective and most strongly associated with positive and disorganised symptoms. Methods: We recruited 50 patients diagnosed with schizophrenia and 29 healthy controls, premorbid intelligence, executive functioning, ToM and psychopathology were examined. Results: Compared with healthy controls patients performed more poorly on tasks involving executive functioning and ToM abilities. Cognitive variables were were co-varied out but ToM deficits in the patient group remained significantly different from controls. The number of perseverative errors in the WCST and the PANSS-Disorganisation Factor accounted for almost half of the variance of the ToM total score in patients. Using median split procedures in the patient group for each of the novel PANSS factors, significant differences were found between low and high disorganisation scorers, with high scorers performing more poorly in measures of executive functioning and ToM. Conclusion: The study reconciles divergent theoretical approaches by Frith (1992) and Hardy-Bayle´ (1994), suggesting selective ToM deficits in patients with schizophrenia, with the most relevant associations of impaired ToM with the load on the disorganisation factor of the PANSS.

P-08-02 The sense of agency in schizophrenia: Disturbances in predicting action-effect relations can explain abnormalities in action awareness M. Voss (Charite University Hospital, Dept. of Psychiatry, Berlin, Germany), J. Moore, M. Hauser, D. Kunz, J. Gallinat, A. Heinz, P. Haggard Introduction: There has been some debate over the last years whether the conscious awareness of action is mainly a predictive process based on the motor command or whether retrospective mechanisms like inferential ‘‘sense-making’’ are more important. While empirical evidence suggests that the conscious experience of action results from a dynamic interplay between such mechanisms, its disturbances in schizophrenia remain elusive. Methods: To address this question, we have used the intentional binding effect (Haggard et al., 2002) to measure the extent to which perceptual estimates of action are influenced by subsequent effects in a population of schizophrenic patients. In our experiment, we varied the probability with which a simple manual action (a keypress) produced an effect (a tone). Results: In healthy volunteers, a high probability of causing an effect led to a predictive shift of the perceptual estimate of the action towards the effect, even on those trials where the action produced no effect. Conversely, when predictability of the effect to occur was low, temporal binding was seen only on those trials where the effect actually occurred. Schizophrenic patients showed absence of the predictive effect and a highly exaggerated temporal binding whenever an effect occurred. Conclusion: The result suggests a disturbance in predicting action-effect relations, which may lead to abnormalities in experiencing a sense of agency in schizophrenia. P-08-03 Poor premorbid adjustment and dysfunctional visual abilities predict theory of mind deficits in chronic stabilized schizophrenic outpatients R. Duno (Parc Tauli Hospital, Psychiatry, Sabedell, Barcelona, Spain), E. Pousa, K. Langohr, A. Tobena

Introduction: In the last two decades, deficits in Theory of Mind (ToM) have been demonstrated in schizophrenia by a number of studies. However, the mechanisms underlying these deficits are not well understood. Methods: The present study explored the relationship between ToM deficits, poor premorbid adjustment and visual-perceptual dysfunctions in a sample of sixty-five stabilized schizophrenic outpatients. Results: Ordinal regression analysis revealed an association between deficits in first order ToM tasks, poor social premorbid adjustment and a low performance on the Trail B test. In contrast to that, deficits in second order ToM tasks were related to male gender, a low performance on Block Design and clozapine treatment. The R-square values amounted to 0.311 and 0.582, respectively. Conclusion: These findings suggest that second order ToM tasks are more specific than first order ones to assess social cognition in schizophrenia. In addition, this data defines a homogeneous phenotypic subgroup, characterized by poor prognostic outcome factors, together with deficits in ToM ability and dysfunctional visual-perceptual capacities. These in turn may stem from an impaired contextual integration of sensorial and cognitive responses. P-08-04 Structural-dynamic features of cognitive functions in an estimation of efficacy of treatment of schizophrenia N. Govorin (Chita State Medical Academy, Psychiatry, Chata, Russia), A. Panina Introduction: Neurocognitave disfunction is the third group of symptoms of schizophrenia. Methods: 70 patients with paranoid schizophrenia (IDC-10, F 20.09) have been included into the study: 30 of them passed treatment with olanzapin, 20 recieved insulin therapy and 20 accepted haloperidol. The quantitative dynamic estimation of 15 cognitive functions before treatment in 2 and 4 weeks of therapy, and also registration of semiology on PANSS scale before realization of medical actions were carried out. Results: On the basis of the established correlation interrelations between neurocognitive disfunctions and clinical characteristics, coefficient of efficacy cut short of psychopathological semiology was calculated. At registration of parameters less than 0,7 in 2 weeks of treatment (0,6 - in 4 weeks), we saw the high degree of clinical cut short. Parameters from 0,7 up to 1,0 in 2 weeks of treatment (0,6 1,0 - in 4 weeks) the average degree of cut short, and more than 1,0 in 2 and 4 weeks - the low degree of cut short psychopathological semiology was shown. Conclusion: To summarise, dynamic features of cognitive functions is an objective estimation of efficacy of treatment of schizophrenia. P-08-05 Emotional and cognitive functioning in stable schizophrenic patients M. Jarema (Institute of Psychiatry, 3rd Department of Psychiatry, Warszawa, Poland), D. Kukulska, D. Parnowska Introduction: Negative symptoms and cognitive impairment are considered the crucial features in schizophrenia. Methods: We evaluated the relationship between the severity of negative symptoms and the cognitive functioning of sixty patients suffering from schizophrenia. The severity of positive symptoms was considered as mild (15 or less points in PANSSPositive subscale) while the severity of negative symptoms was moderate or more (> 21 points in PANSS-Negative subscale). The PANSS, the RSEB and the Calgary scales were used. Cognitive tests included: WCST, Stroop’s, the Verbal Fluency, the TMT tests, and the modified version of the Adjective Check List (ACL). Results: The severity of negative symptoms did not correlate neither with the subjective evaluation of emotions nor with the cognitive impairment. Patients with less severe emotional blunt-

33 ing showed better performance in the Verbal Fluency Test. The duration of schizophrenia and the number of previous psychiatric hospitalizations were connected with some cognitive impairment. Conclusion: In stable schizophrenic patients no correlation was found between negative symptoms and cognitive impairment. Only the length of schizophrenia and the number of previous psychiatric hospitalizations were the factors which correlate with some cognitive dysfunctions in stable schizophrenic patients.

P-08-06 Learning potential on the WCST in first-episode and chronic schizophrenia A. Pedersen (University of Muenster, Psychiatry, Mu¨nster, Germany), K. Koelkebeck, A. Siegmund, T. Suslow, K. H. Wiedl, V. Arolt, P. Ohrmann Introduction: A majority of studies show that patients with schizophrenia perform poorly on the widely used test of executive function – the Wisconsin Card Sorting Test (WCST). However, not all schizophrenic patients display cognitive impairments, and there is converging evidence that giving detailed instruction or reinforcement might remediate these deficits in at least some patients. Methods: This study examined whether differences in the learning potential on the WCST were related to other cognitive parameters or psychopathology. Fifty-nine first-episode inpatients with schizophrenia, 42 inpatients with chronic schizophrenia and 55 healthy control participants completed a test-train-test version of the Wisconsin Card Sorting Test as a measure of their learning potential. Results: ‘‘Nonretainers’’, who did not profit from detailed instruction, were identified not only in the group of chronic schizophrenic patients, but also in the group of first-episode patients, but not in the healthy control group. Neuropsychological examinations utilized standard test procedures for the cognitive domains of verbal intelligence (vocabulary test, WAIS-R), verbal learning and memory (AVLT), attentional speed and accuracy (FAIR), and reasoning (LPS-3); psychopathology was rated with the PANSS, CGI, CDSS, and GAF. Conclusion: In a sub-sample we implemented imaging techniques (fMRT, 1H-MRS) and established associations with different genotypes. We present first results from this study.

P-08-07 Are basic symptoms in schizophrenia associated with working memory deficits? One cross-sectional study in acute patients M. L. Vargas (Complejo Asistencial de Zamora, Psychiatry, Spain), N. Jimeno Bulnes Introduction: Basic symptoms in schizophrenia are closely related to the neurocognitive substrate of the disease. Working memory deficits have been proposed as nuclear in the schizophrenia acute states. The objective was to test the relationship between basic symptoms and working memory deficits. Methods: One cross-sectional study was carried out in a sample of 58 schizophrenia in-patients in acute state. Attention and working memory performance were measured with a neuropsychological battery consisting of the Trail Making Test A and B, Stroop Test, and Continuous Performance Test. Positive and Negative Syndrome Scale and several control clinical variables were analysed. Basic symptoms were studied with one semi-structured interview (Subjective Evaluation of Attention Control Errors) based on the Bonn Scale for the Assessment of Basic Symptoms and the classical concept of mental automatism. We defined three groups with respect to basic symptoms severity: absent (n = 13), mild (n = 16) and clearly present (n = 29). Results: Perceptive intrusions (57%), cognitive and verbal intrusions (36%), and thinking subjective deficits (36%) were the most frequent basic symptoms. Severity of basic symptoms was inversely associated with performance in Trail Making B (Jonckheere – Terpstra test of trend, p = 0.005, bilateral).

Conclusion: Some basic symptoms could be the subjective experience of working memory deficits in schizophrenia. P-08-08 Investigation of variables affecting Theory of Mind (ToM) abilities in a sample of schizophrenia patients K. Koelkebeck (University of Muenster, Department of Psychiatry, Germany), A. Pedersen, P. Ohrmann Introduction: There is empirical evidence that Theory of Mind (ToM), the capacity to infer one’s own and other persons’ mental states, is impaired in schizophrenia. Recent discussion raises the question, whether ToM dysfunction is an independent, trait-like deficit or is related to other variables, e.g. language abilities. Methods: 30 schizophrenia patients (DSM-IV) and 32 matched controls were assessed with a ToM paradigm (e.g. Castelli et al., 2000) presenting geometrical shapes moving in specific patterns (e.g. mocking) in animated videos. Psychopathology and neuropsychological data were assessed, and autistic and alexithymic traits as well as diplomatic and empathetic abilities were evaluated by specific questionnaires. Results: Examining the categories appropriateness of descriptions and the use of ToM-related vocabulary, schizophrenia patients revealed significant differential deficits compared to normal controls. Further analyses revealed correlations between these categories and verbal learning and memory, empathy abilities, autistic traits and alexithymia. Conclusion: Our results provide further evidence for a deficit of schizophrenia patients in the evaluation of social situations. Furthermore, ToM competence seems indeed to be related to language abilities, but appear to be also affected by other variables, for example empathy abilities, thus hinting on a more complex emotional and cognitive dysfunction.

P-08-09 The tolerability of rTMS treatment in schizophrenia with respect to cognitive function M. Mittrach (Heinrich-Heine University, Psychiatry and Psychotherapy, Du¨sseldorf, Germany), M. Arends, J. Thu¨nker, G. Kotrotsios, A. Mobascher, T. Wobrock, M. W. Agelink, W. Gaebel, J. Cordes Introduction: Change of cognition induced by rTMS treatment has not yet been a target in a larger sample of schizophrenic patients. In this study we want to prove the clinical efficacy of rTMS in partially remitted schizophrenic patients as an ‘‘add-on’’ therapy. A focus is set on the tolerability and safety of high frequency rTMS with regard to cognitive performance. Methods: 32 schizophrenic patients were randomly assigned to a verum (N = 18) and control group (N = 14). Patients in the verum group received 10Hz rTMS over the dorsolateral prefrontal cortex with an intensity of 110% motor threshold for 10 days (total stimuli 10000). The control group was treated with a sham coil. Psychopathology was rated on the CGI and the PANSS. The neuropsychological test battery consisted of the following tests: MWTB, TMT, WCST, D2 and KAI. Results: We found an improvement of schizophrenic psychopathology with significant effects on the CGI including severity code (p = .004) and state alteration (p < .001). The findings of the neuropsychological tests showed no significant effects, demonstrating that rTMS treatment did not impair cognitive performance. In some cognitive domains improvement was detected for the verum group. Conclusion: The stability of cognitive function suggests a good tolerance of rTMS treatment in schizophrenia. P-08-10 Neuropsychological and neurophysiological predictors of clinical course in first episode schizophrenia - results from the German Research Network on Schizophrenia W. Wo¨lwer (University of Duesseldorf, Department of Psychiatry, Du¨sseldorf, Germany), W. Gaebel, The German Study Group on First Episode Schizophrenia

34 Introduction: Although it has been reported that cognitive impairments in schizophrenia are prospectively predictive of outcome like social functioning and quality of life, the predictive validity of cognitive impairments regarding exacerbations in the course of the disorder is less clear. Methods: As part of a comprehensive multi-center study on acute and long-term treatment in n = 159 first episode schizophrenia (FES) patients, the present subproject aims at a longitudinal assessment of vulnerability indicators and an investigation of the relationship of these indicators with prodromal symptoms and clinical course. Assessments took place at inclusion into the longterm treatment study (T0), after 1 year of controlled drug and psychological treatment medication (T1). Results: Compared to healthy controls matched for age, gender and education FES showed the expected neuropsychological and neurophysiological impairments at T0 with only minor improvements during the first post-acute year. Impairments proved to be unrelated to prodro-mal symptoms with both kind of symptoms predicting poor clinical outcome to a comparable extent. Conclusion: Since the occurrence of a schizophrenic episode is suggested to depend on the degree of imbalance between vulnerability, stressors, and protectors a further improvement of relapse prediction can be expected by additional inclusion of stress and coping indicators.

P-08-11 The dreaming brain as a model for psychosis: An experimental approach using bizarreness as a cognitive marker I. Limosani (Azienda Ospdaliera San Paolo, Dipartimento di Salute Mentale, Milan, Italy), A. D’Agostino, M. L. Manzone, S. Scarone Introduction: Many observers have reported some qualitative similarities between the normal mental state of dreaming and the abnormal mental state of psychosis. In this study, the hypothesis of the dreaming brain as a functional model for psychosis was tested by focusing on cognitive bi-zarreness. This distinctive formal property of the dreaming brain was measured in reports derived from the dreaming and waking state of psychotic subjects and normal controls. Methods: Seven pictures of the Thematic Apperception Test (TAT) were administered as a stimulus to elicit waking fantasies in 30 schizophrenic and 30 normal subjects. A total of 420 waking reports was collected along with 244 dream reports in order to quantify the bizarreness fea-tures in the dream and waking state of both subject groups. Results: Two-way ANCOVA for repeated measures showed that cognitive bizarreness was signifi-cantly lower in the TAT stories of normal subjects than in those of schizophrenics and in the dream reports of both groups. Conclusion: The differences between the two groups indicate that - under experimental conditions - the waking mentation of schizophrenic subjects reflects a degree of cognitive bizarreness com-parable to that of dreams,. These results support the hypothesis that the dreaming brain could be a useful experimental model for psychosis.

P-09 Electrophysiology P-09-01 A new method of single trial analysis of the evoked responses in healthy subjects and schizophrenic patients V. Rodionov (Kfar Shaul Mental Hospital, A, Jerusalem, Israel), R. Durst, M. Mager, A. Teitelbaum, S. Raskin, M. Shlafman, J. Zislin Introduction: A novel method was applied to characterize the variability of the single trials evoked responses. Methods: A passive auditory oddball paradigm (pitch deviant) was applied to schizophrenics (53) and healthy subjects (47). Frontal response (Fz) to the deviant stimulus was analyzed in three frequency ranges (lowpass 10Hz, 15Hz, 20Hz). The bypass from a negative wave to the consequent positive wave was qualified within each given moment of single trial responses and

then marked as the specific NP-state. The percentage (NP) of NPstates occurrence calculated across the stimulus trials and exceeding 50% could be used as an index of the negative/positive front EP development at the post-stimulus time moment given. On the contrary, the fall of NP below 50% was the index of the positive/negative front EP. The peak deflection of the NP value from 50% was used as the characteristic of the ‘‘front stability’’ (FS). Results: The N200/P300a and P300a/N350 fronts had a significant lower FS-value and the P150/N200 – significantly higher FS in patients. The discriminant analysis of these data showed the 78.7% specificity of and the 83.0% sensitivity. Conclusion: It is suggested that the front stability of EP can be useful to distinguish the normal and pathology EP responses. P-09-02 Anomalies of auditory oddball ERP in the first episode patients I. Lebedeva (NMHRC, Laboratory of neurophysiology, Moscow, Russia), V. Kaleda, A. Barkhatova, M. Omelchenko Introduction: The aim of the study was to determine the anomalies of event-related potentials waves in auditory oddball paradigm in the first episode patients. Methods: The sample comprised 40 male patients (18–25 years), the control group comprised age-matched group of 20 mentally healthy male subjects. The patients were examined during the first week after admission to the clinic, on medication. Auditory ERPs were recorded in the standard auditory oddball paradigm (tones, 60 dB, 80% non-targets (1000 Hz) and 20% targets (2000 Hz)). Peak amplitudes and peak latencies of N100 and P200 to non-target stimuli, N100, N200, P300 to target stimuli were determined. Results: The most pronounced findings comprised prolongation and reduction of P300 (in almost all the tested leads) while reduction of non-target and target N100s and prolongation of N200 were found in several leads only (mostly temporal ones). There was not difference in P300 abnormalities between the patients with and without family loading of psychosis. Conclusion: The findings suggest that the first episode is characterized by marked disorders in the late neurophysiological ‘‘cognitive’’ processes while the impairment in the earlier processes is less pronounced and more localized. P-09-03 Correlations between mismatch negativity (MMN) and insight in schizophrenia A. Boxus (AASM, Psychiatry, Limoux, France) Introduction: Background: MMN is an event-related potential which reflects echoic memory. Thus it affects archaic mnemic processes

35 which can be the reflection of insight capacities. MMN amplitude is usually reduced in schizophrenia. MMN amplitude is correlated with the correct operation gabaergic. MMN could be thus an evaluation of insight capacities. The aim of this study was to investigate the correlation between MMN amplitude and cognitive insight in schizophrenia. Methods: Methods: 14 individuals (10 males and 4 females; mean age = 40.9 years [SD = 13.7]) with schizophrenic diseases (DSM IV) were evaluated. The studied parameters were: MMN amplitude and the BECK Cognitive Insight Scale. We classed patients in ‘‘bad insight’’ when agreement in BICS was slightly or not at all. Results: Results: mean MMN amplitude was -2.0 lVolt (SD = 1.4), distributed from -5.5 to -0.1 lVolt. We observed a correlation between MMN amplitude and a bad insight evaluated with the BICS (p < 0.05) Conclusion: Conclusion: These results have to be confirmed in a largest study but suggest that insight of schizophrenic patients may be, at least in a part, mediated through cognitive change indexed by MMN and could be evaluated with this objective test. MMN evaluation could therefore help psychiatrists for prognostic and therapeutic decisions. P-09-04 A topographic event-related potential follow-up study in first episode patients with schizophrenia J. Brinkmeyer (University of Duesseldorf, Germany), W. Gaebel, German Study Group on First Episode Schizophrenia Introduction: Reduced auditory P300 amplitude generally has been considered to be a trait marker of schizophrenia, independent of antipsychotic treatment and clinical symptoms. However, several seemingly well conducted studies have found P300 amplitude to be a state marker correlated with clinical symptoms. Methods: P300 amplitude and latency were recorded to infrequent auditory target stimuli from 33 first episode patients with schizophrenia (DSM-III-R) after admission (acute phase) and approximately 3 month later (remission) and 45 matched controls. Results: N200 amplitude did not differ among groups. P300 amplitude was significantly smaller in both previously treated and post treated schizophrenic patients compared to the control group. No significant effect of the treatment could be observed. P300 latency was also prolonged in previously treated and post treated schizophrenic patients. Conclusion: The present study suggests that ERP abnormalities, especially P300 amplitude reduction are already present prior to the administration of neuroleptic medication in the earliest stage of first episode schizophrenia. The results of the present study lend support to the view that P300 amplitude behaves as a trait marker. No evidence is found of a P300 clinical state marker. P-09-05 Cortical potentials with antisaccades in first-episode schizophrenia J. Brinkmeyer (University of Duesseldorf, Germany), W. Gaebel, German Study Group on First Episode Schizophrenia Introduction: Prefrontal cortical dysfunctions, including disturbances in visually antisaccade task, have been reported in neuropsychological and brain imaging studies of schizophrenia Methods: The cortical activation pattern of saccades and antisaccades was analysed in 27 first-episode schizophrenic inpatients and 18 healthy controls. Patients were treated two-year randomized double-blind with low-dose haloperidol or risperidone and were tested at the start of neuroleptic treatment and again 1 Year later (T1). Results: First episode schizophrenic patients performed worse number of correct antisaccades, higher antisaccadic latency and duration and didn’t improve the correct response rate on the second session (T0 vs T1). The ERP-waveforms were very similar across the groups and are preceded by three distinct cortical potentials, a presaccadic positive peak at about 100 msec, a negative peak at about 180 msec and a saccadic positive at about 300 msec.

N180 amplitude was significantly smaller at the posterior electrodes in schizophrenic patients. There was a significant main effect of medication state, such that patients with risperidone had more correct antisaccades after one year. Conclusion: Deficits in the voluntary control of spatial attention are observed during episodes of illness, and remain an enduring aspect of prefrontal dysfunction in schizophrenia even after treatment. P-09-06 Prolonged antisaccade latency in individuals clinically at risk for psychosis I. Frommann (University of Bonn, Psychiatry, Germany), S. Ruhrmann, J. Brinkmeyer, A. Hochrein, A. Brockhaus-Dumke, W. Wo¨lwer, J. Berning, A. Bechdolf, J. Klosterko¨tter, W. Maier, M. Wagner Introduction: Performance in the antisaccade task is sensitive for dorsolateral-fronto-striatal dysfunction. Schizophrenia patients, their relatives and people with high levels of schizotypal traits make more errors and are slower in this task. Methods: 120 high-risk participants (HRP) in an early (EIPS) and late (LIPS) prodromal state for schizophrenia, 30 medicated first-episode schizophrenia patients (FESP) and 50 healthy controls (HCON) underwent electro-oculographic assessment of antisaccades and prosaccades. Results: In the prosaccade-task latency was prolonged in FEPS as compared to the other groups. In the antisaccade-task, error rate was higher and latency was longer in FESP than in HCON and HRP. Antisaccade latency distinguished EIPS and LIPS from HCON. Furthermore, saccadic velocity was enhanced in HRPs compared to HCON and FESP. Conclusion: This study replicates deficits in the suppression of reflexive saccades and in the initiation of voluntary saccades in FEPS. The initiation deficit of voluntary saccades (i.e. antisaccades) is present also in EIPS and LIPS. This novel finding suggests that dorsolateral-fronto-striatal dysfunction is present in prodromal states of psychosis. Thus, antisaccade latencies could possibly be used as a biological vulnerability marker for psychosis. Fundes by BMBF, GRNS, grants 01 GI 9934, 0234 P-09-07 Differentially altered auditory P300 topography in individuals clinically at risk for psychosis I. Frommann (University of Bonn, Psychiatry, Germany), J. Brinkmeyer, S. Ruhrmann, E. Hack, A. Brockhaus-Dumke, A. Bechdolf, W. Wo¨lwer, J. Klosterko¨tter, W. Maier, M. Wagner Introduction: Schizophrenia patients and their relatives consistently show smaller auditory evoked P300 amplitudes. In this study P300 potentials in individuals with clinical high risk to develop psychosis were assessed. Methods: Using an oddball task, we examined P300 amplitude and topography in 100 high-risk participants (HRP) either in an early (EIPS) or late (LIPS) prodromal state for schizophrenia and 40 healthy controls (HCON). Results: P300 mean amplitude was generally reduced in the LIPS group and selectively at left temporoparietal electrode site in the EIPS group compared to controls. In the EIPS group, left-right hemispheric side difference at posterior temporal site was associated with worse verbal memory. HRPs with a family history of psychosis (n = 18) had smaller posterior P300 amplitudes compared to HRPs without a positive family history. HRPs who had experienced brief limited psychotic symptoms had smaller anterior P300 amplitudes compared to HRPs with attenuated positive symptoms only. Conclusion: These findings demonstrate that P300 amplitude is reduced in clinical HRPs prior to onset of psychosis. Especially left temporal P300 amplitude reduction appears to be a biological vulnerability marker. Anterior P300 may only be diminished after progression into a late prodromal state, when first psychotic symptoms appear. Funded by BMBF, GRNS 01 GI 9934, 0234

36 P-09-08 Relationship between P50 Suppression and the Cortical Silent Period B. Moeller (University of Greifswald, Psychiatry and Psychotherapy, Stralsund, Germany), J. S. Snyder, H. J. Freyberger, Z. J. Daskalakis Introduction: Deficient inhibitory neurotransmission has been demonstrated in schizophrenia through electroencephalography (e.g. P50 suppression) and transcranial magnetic stimulation (e.g., short interval cortical inhibition (SICI) and cortical silent period (CSP).It is not known whether these inhibitory paradigms are related despite evidence suggesting both are coordinated through gaminobutyric acid (GABA) inhibitory neurotransmission. Methods: We explored the neurophysiological relationship between P50 suppression, SICI and CSP in twenty-one healthy subjects according to previously published methods. Results: P50 suppression was significantly correlated with CSP (r = )0.49, p = 0.02) but not with SICI. Conclusion: As both P50 suppression and the CSP have been linked to the beta receptor subtype (GABAB) these data highlight the importance of this receptor subtype in the pathophysiology of schizophrenia. P-09-09 EEG dynamics in visuo-motor integration of schizophrenic patients S. R. Soekadar (University of Tuebingen, UKPP / Neurostimulation, Germany), C. Braun, A. Rilk, C. Arfeller, P. Bremme, C. Plewnia Introduction: It is hypothesized that cognitive functions are based on co-ordinated interactions of numerous neurons that are distributed across different specialized brain areas. Though, it is unclear how coordination between distant brain regions is achieved. In this context a large number of studies investigated the relevance of EEG power and synchrony in cognitive and executive processes, but only recently task- and performance-related synchronization phenomena were investigated in pathological brain states. Methods: Here we present a study that investigated the role of cortico-cortical coherence and power in schizophrenic patients in a visuo-motor integration task. Coherence, power and performance were compared between a group of schizophrenic patients (n = 11) and healthy controls (n = 15). Results: Whereas there was significant learning at the beginning of the task in both groups, only healthy controls improved their performance during the task. There was no difference in the nominal value of coherence between both groups, but we found significant changes in schizophrenia regarding the relative distribution of coherence within all frequency bands and less localized coherence patterns associated with poorer performance. Conclusion: We conclude that a decisive factor for effective visuo-motor integration is associated with the relative distribution of coherence across all frequencies and its specific localization across distributed neuronal networks.

Abstract received after deadline O-02-01 The need of integral assessment and management in the treatment plan of Schizophrenia: Rehabilitation needs unmet V. Larach-Walters (Universidad Andre´s Bello Santiago, Chile) Everyday practice and treatment of schizophrenia patients has focused mainly on drug treatment and budgets and resources are mostly assigned to this only aspect of treatment. This occurs in spite of our present knowledge about the different symptom domains of impairments that patients present and their relevance to outcome. In usual clinical work patients are still very insufficiently assessed, beyond the classic positive symptoms, some more in negative symptoms constellations, and specially absent when referred to neuropsychological impairments and social cognition, for which there are nowadays, well established evidence of their importance for integral recovery. New psychological treatment strategies targeting cognitive psychosocial domains may help to improve social functioning, work and quality of life. These new treatment strategies and target domains introduce the need of extensive training and modernization of impairment assessment and rehabilitation techniques for mental health teams and new resources. We will stress the facts behind these deficiencies, not only because of academic rigor, but because of its serious implications for treatment, psychosocial functioning, prognosis and therefore stigma for both patients and their families.

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Authors Index Abdel-Hamid, M. Abel, M.-B. . . . . Agelink, M. W. . . Ajdacic-Gross, V. Alda Diez, J. A. . . Altmann, C. . . . . Andersch, N. . . Angst, J. . . . . . . Anilkumar, A. . . Apostolopoulos, J. Arab, R. . . . . . . Arends, M. . . . . Arfeller, C. . . . . Arolt, V. . . . . . . Arshi, S. . . . . . .

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Baare´, W. . . . . . . . . . Bahn, S. . . . . . . . . . Bahrami, F. . . . . . . . Banos Yeste, I. . . . . . Barajas Velez, A. . . . Barkhatova, A. . . . . . Bassett, D. . . . . . . . Bauer, M. . . . . . . . . . Baumann, A. . . . . . Ba¨uml, J. . . . . . . . . . Bechdolf, A. . . . . . . . Behmanesh, M. . . . . . Bender, S. . . . . . . . . . Berger, H. . . . . . . . Berning, J. . . . . . . . Bernstein, H.-G. . . . Bertelsen, M. . . . . . Birchwood, M. . . . . . Bittner, R. . . . . . . . Bogerts, B. . . . . . . . Bohner, G. . . . . . . . Bosch, P. . . . . . . . . . Boxus, A. . . . . . . . . . Boyko, Y. . . . . . . . . . Brand, A. . . . . . . . . . Brand, M. . . . . . . . . . Braun, C. . . . . . . . . . Braus, D. F. . . . . . . . Bremme, P. . . . . . . . Brinkmeyer, J. . . . . . Brockhaus-Dumke, A. Broome, M. R. . . . . . Brown, R. . . . . . . . . . Browne, S. . . . . . . . Bru¨ne, M. . . . . . . . . . Buchkremer, G. . . . Bullmore, E. . . . . . . . Bushe, C. . . . . . . . . . Bu¨ttner, S. . . . . . . .

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Cahn, W. . . . . . . . . . . . . . . Camen, D. . . . . . . . . . . . . Casacchia, M. . . . . . . . . . . Caspers, E. . . . . . . . . . . . . Caton, S. . . . . . . . . . . . . . . Cesarlo, A. . . . . . . . . . . . . Chatton, A. . . . . . . . . . . . . Chimorghiachis, A. . . . . . . Chkonia, E. . . . . . . . . . . . . Clarke, M. . . . . . . . . . . . . Coman, H. . . . . . . . . . . . . Constantin Marinescu, D. G. Cordes, J. . . . . . . . . . . . . . . Cosman, D. . . . . . . . . . . . . Craciun, I. . . . . . . . . . . . . Crumlish, N. . . . . . . . . . . . .

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D’Agostino, A. . . . . . Daskalakis, Z. J. . . . Dazzan, P. . . . . . . . Decker, T. . . . . . . . Degner, D. . . . . . . . Dembler, T. . . . . . . . DePeri, L. . . . . . . . . . Dettling, M. . . . . . . . Devitt, P. . . . . . . . . . Di Giovambattista, E. Di Pucchio, A. . . . . . Dingemans, P. . . . . . Dinges, M. . . . . . . . Dollase, D. . . . . . . . Dolz Abadia, M. . . . Drees, A. . . . . . . . . . Dreher, J. . . . . . . . . . Dreher-Rudolf, M. M. Duno, R. . . . . . . . . . Durst, R. . . . . . . . . .

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Eggers, C. . . Eickhoff, M. Elsabagh, S. Emsley, R. Esslinger, C. Ettinger, U.

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Gaebel, W. . . . . . . . . . . . . . . . . . . . Gallhofer, B. . . . . . . . . . . . . . . . . . . . Gallinat, J. . . . . . . . . . . . . . . . . . . . Gamma, A. . . . . . . . . . . . . . . . . . . . German Study Group on First Episode Gervin, M. . . . . . . . . . . . . . . . . . . . Ghamarigivi, H. . . . . . . . . . . . . . . . Glaehdari, H. . . . . . . . . . . . . . . . . . Glenthoj, B. . . . . . . . . . . . . . . . . . . . Goebel, R. . . . . . . . . . . . . . . . . . . . Govorin, N. . . . . . . . . . . . . . . . . . . . Graf von Reventlow, H. . . . . . . . . . . . Gruber, O. . . . . . . . . . . . . . . . . . . . Gsottschneider, A. . . . . . . . . . . . . . Gudlowski, Y. . . . . . . . . . . . . . . . . .

. 5, 6, 9, 12, 26, 29, 33, 35 . . . . . . . . . . . . . 10, 11, 24 . . . . . . . 14, 22, 23, 31, 32 . . . . . . . . . . . . . . . . . 15 Schizophrenia . . . . 33, 35 . . . . . . . . . . . . . . . . . 15 . . . . . . . . . . . . . . . . . 27 . . . . . . . . . . . . . . . . . 14 ................... 7 . . . . . . . . . . . . . . . 23, 24 . . . . . . . . . . . . . . . . . 32 . . . . . . . . . . . . . 17, 28, 29 . . . . . . . . . . . . . . . . .8, 11 . . . . . . . . . . . . . . . . . 13 . . . . . . . . . . . . . . . . . 22

Habel, U. . . . Hack, E. . . . Haenschel, C. Ha¨fner, H. . Haggard, P. . Ha¨ke, I. . . . Haley, C. . . . Halfmann, S.

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12 35 25 29 32 23 30 13

38 Haro Abad, J. M. . Ha¨rtling, F. . . . . . Hauner, H. . . . . . Hauser, M. . . . . . Heinimaa, M. . . . Heinz, A. . . . . . . . Hemmerle, M. . . . Henn, F. A. . . . . . Henning, U . . . . . Herzog, M. H. . . . Hochrein, A. . . . . . Hodgins, S. . . . . . Holdenrieder, S. . Ho¨rrmann, F. . . . Ho¨schl, C. . . . . . Hulshoff Pol, H. E. Huttunen, J. . . . . .

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Ja¨ger, M. . . . . . . . . . . Jahn, T. . . . . . . . . . . Janssen, B. . . . . . . . . Jarema, M. . . . . . . . . Jeppesen, P. . . . . . . . . Jimeno Bulnes, N. . . . . Jockers-Scheru¨bl, M. C. Jørgensen, P. . . . . . . Joukamaa, M. . . . . . . Juckel, G. . . . . . . . . . .

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Ku¨hn, K. . . . . . . . . . Kadovic, D. . . . . . . . Kahn, R. S. . . . . . . . Kahnt, T. . . . . . . . . . Kaiser, W. . . . . . . . Kalafi, Y. . . . . . . . . . Kaleda, V. . . . . . . . Kamali, M. . . . . . . . Kassaiean, N. . . . . . Kasyan, L. . . . . . . . Kaufmann, C. . . . . . Keefe, R. . . . . . . . . . Kellermann, T. . . . . . Khan, R. S. . . . . . . . Khazaal, Y. . . . . . . . Khomenko, Y. . . . . . Kienast, T. . . . . . . . Kinsella, A. . . . . . . . Kircher, T. . . . . . . . Kirsch, P. . . . . . . . . . Klimke, A. . . . . . . . Klingberg, S. . . . . . . . Klingebiel, R. . . . . . Klosterko¨tter, J. . . . Knegtering, H. . . . . . Kno¨chel, C. . . . . . . . Knutson, B. . . . . . . . Koelkebeck, K. . . . . . Koivisto, A.-M. . . . . . Ko¨rtner, K. . . . . . . . Ko¨pcke, W. . . . . . . . Koslowski, M. . . . . . Kotlicka-Antczak, M. Kotrotsios, G. . . . . . Kraemer, S. . . . . . . . Krarup, G. . . . . . . . Krebs, M. . . . . . . . . . Kremlacek, J. . . . . . Krieger, S. . . . . . . . Kuba, M. . . . . . . . . . Kuipers, E. . . . . . . . Kukulska, D. . . . . . Kumari, V. . . . . . . . Kunz, D. . . . . . . . . .

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La¨chler, M. . . . . . Lamprecht, A. . . . Landolt, K. . . . . . Langohr, K. . . . . . Lanquillon, S. . . . Larach-Walters, V. Larkin, C. . . . . . . . Laurens, K. . . . . . Le Quack, P. . . . . . Lebedeva, I. . . . . . Lemke, M. . . . . . Leopold, K. . . . . . Levy, P. . . . . . . . Leweke, M. . . . . . Lewis, S. . . . . . . . Libiger, J. . . . . . . . Liensdorf, C. . . . Limosani, I. . . . . . Linden, D. . . . . . Lindner, M. . . . . . Linszen, D. . . . . . Lis, S. . . . . . . . . . Lopez-Garcia, P. . Luckhaus, C. . . . Luutonen, S. . . . . .

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Mackeprang, T. . . . . . Macrea, R. . . . . . . . . . Mager, M. . . . . . . . . . Maier, W. . . . . . . . . . . . Mamchur, V. . . . . . . . Manea, M. . . . . . . . . . Manzone, M. L. . . . . . Matuschek, E. . . . . . . . Maurer, K. . . . . . . . . . Mazza, M. . . . . . . . . . McGuire, P. . . . . . . . . . McNamara, D. . . . . . . . McTigue, O. . . . . . . . . . Meisenzahl, E. . . . . . . . Meyer-Lindenberg, A. . Miclutia, I. V. . . . . . . . Mier, D. . . . . . . . . . . . Mittrach, M. . . . . . . . . . Mobascher, A. . . . . . . . Moeller, B. . . . . . . . . . Mohamad Shariati, S. A. Molavi, P. . . . . . . . . . . . Molero, P. . . . . . . . . . Mo¨ller, H.-J. . . . . . . . . . Moore, J. . . . . . . . . . . . Mu¨ller, D. R. . . . . . . . Mu¨ller, D. . . . . . . . . . Mu¨ller, N. . . . . . . . . .

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.............. 7 . . . . . . . . . . . . 25 . . . . . . . . . . 12, 34 . . 5, 6, 9, 17, 29, 35 . . . . . . . . . . . . 31 . . . . . . . . . . . . 15 . . . . . . . . . . . . 34 . . . . . . . . . . . . 25 17, 19, 23, 24, 25, 29 . . . . . . . . . . . . 17 . . . . . . . . . . . . 18 . . . . . . . . . . . . 30 . . . . . . . . . . . . 15 . . . . . . . . . . . . 12 . . . . . . . . . . . .5, 10 . . . . . . . . . . . . 25 . . . . . . . . . . 11, 24 . . . . . . . . . . 30, 33 . . . . . . . . . . . . 33 . . . . . . . . . . . . 36 . . . . . . . . . . . . 14 . . . . . . . . . . . . 27 . . . . . . . . . . . . 14 . . . . . . 5, 6, 8, 9, 29 . . . . . . . . . . . . 32 . . . . . . . . . . . . 13 . . . . . . . . . . . . 14 . . . . . . . . . . . . 22

Nemes, B. . . . . . . Neumann, M. . . Nica, S. . . . . . . Niedersteberg, A. Nienhuis, F. J. . . Nordentoft, M. . .

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Oades, R. D. . . . . . . . . . . . O’Callaghan, E. . . . . . . . . . Ochoa Gu¨erre, S. . . . . . . . Oertel, V. . . . . . . . . . . . . . Øhlenschlæger, J. . . . . . . . Ohmann, C. . . . . . . . . . . . Ohrmann, P. . . . . . . . . . . . Oja, H. . . . . . . . . . . . . . . . Omelchenko, M. . . . . . . . Ortuno, F. . . . . . . . . . . . Østergaard Christensen, T. ¨ zgu¨rdal, S. . . . . . . . . . . . O

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39 Pajonk, F. . . . . . . Palchikov, V. . . Panina, A. . . . . Papageorgiou, K. Parnowska, D. . . Paruch, J. . . . . . . Patino-Garcia, A. Patterson, P. . . . . Pedersen, A. . . . . Peltzer, M. . . . . Peters, E. . . . . . . Petersen, L. . . . . Petrovsky, N. . . Piaszek, A. . . . . Picker, H. . . . . . . Pindborg, L. . . . . Pitschel-Walz, G. Plewnia, C. . . . . Pohl, C. . . . . . . Pollice, R. . . . . . . Pombo, S. . . . . Popescu, C. A. . . Pousa, E. . . . . . . Premkumar, P. . . Prokudin, V. . . Puls, I. . . . . . . . .

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Rabe-Jablonska, J. . Radut, C. . . . . . . . Rais, M. . . . . . . . Rantanen, H. . . . Rapp, A. . . . . . . . Raskin, S. . . . . . . . Rasmussen, H. . . . Rausch, F. . . . . . Reske, M. . . . . . . . Rezaei Ghalechi, E. Riedel, M. . . . . . Riesbeck, M. . . . . . Rijnders, C. . . . . . Rilk, A. . . . . . . . Roder, V. . . . . . . . Rodionov, V. . . . Rodriguez, E. . . . Roebroeck, A. . . . Rogue, P. J. . . . . . Roinishvili, M. . . . Roman, B. . . . . . Roncone, R. . . . . . Ronshausen, S. . . . Ro¨pcke, B. . . . . . Rosenbaum, B. . . . Ro¨ssler, W. . . . . . Rotarska-Jagiela, A. Roux, F. . . . . . . . Ruhrmann, S. . . . Rujescu, D. . . . . .

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Saeedlou, S. . . . . . . . Salize, J. H. . . . . . . . Salokangas, R. K. R. . Sanchez Fernandez, B. Sanchez, V. . . . . . . . Sauer, H. . . . . . . . . . Sauer, C. . . . . . . . . . Scarone, S. . . . . . . . Schaefer, M. . . . . . . . Scha¨fer, M. . . . . . . . Schelde, T. . . . . . . . Schlo¨sser R. . . . . . . . Schlagenhauf, F. . . . Schloegelhofer, M. .

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Schmack, K. . . . . . . . . . . Schmidbauer, W. . . . . . . Schmidt, F. . . . . . . . . . . Schmidt, L. G. . . . . . . . . Schmitt, A. . . . . . . . . . . Schnack, H. G. . . . . . . . . Schneider, F. . . . . . . . . Schneider, M. . . . . . . . . Schothorst, P. . . . . . . . . Schubert, F. . . . . . . . . . . Schultze-Lutter, F. . . . . . . Schulze-Rauschenbach, S. Schwarz, M. J. . . . . . . . . Seifert, F. . . . . . . . . . . . . Shah, N. J. . . . . . . . . . . Shlafman, M. . . . . . . . . Siegmund, A. . . . . . . . . Singer, W. . . . . . . . . . . Skachko, T. . . . . . . . . . . Skachko-Volkova, T. . . . . Slooff, C. J. . . . . . . . . . . Snyder, J. S. . . . . . . . . . . Soekadar, S. R. . . . . . . . . Sprong, M. . . . . . . . . . . Steinbring, A. . . . . . . . . Steyskal, C. . . . . . . . . . . Stigter, F. P. . . . . . . . . . . Streit, M. . . . . . . . . . . . . Stulz, N. . . . . . . . . . . . . Sushko, V. . . . . . . . . . . Suslow, T. . . . . . . . . . . Svarer, C. . . . . . . . . . . . . Swaab, H. . . . . . . . . . . . . Sytema, S. . . . . . . . . . . Sto¨cker, T. . . . . . . . . . .

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Tarabara, I. . . Teitelbaum, A. Thienel, R. . . Thorup, A. . . Thu¨nker, J. . . Tischinger, M. Tiugan, A. . . Tobena, A. . . Tomassini, A. Torre, E. . . . . Trendler, G. . . Udristoiu, T. . Ufer, S. . . . Uhlhaas, P. . Urban, A. . . . Usall Rodie, J. Ussorio, D. .

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Valmaggia, L. R. . van Agthoven, M. . van de Ven, V. . . . Van den Noort, M. Van Engeland, H. . Van Gent, E. . . . . . van Haren, N. E. . van Nooten, F. . . . Vanelli, I. . . . . . . . Vargas, M. L. . . . Vauth, R. . . . . . . . Veith, V. . . . . . . . Videbæk, C. . . . . . Villalta Gil, V. . . . Vita, A. . . . . . . . von Wilmsdorff M. Voss, M. . . . . . . .

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21 12 12 12 28 17

40 Waddington, J. L. Wagner, M. . . . . Weiler, C. . . . . . . Weiss-Motz, F. . . Whitty, P. . . . . Wiedl, K. H. . . . . Wiersma, D. . . . . Witthaus, H. . . . . Wobrock, T. . . . . Wo¨lwer, W. . . . . Wrase, J. . . . . . . Wunderink, L. . . Wu¨stenberg, T. . .

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. . . . . . . . . . . . 15 6, 12, 17, 25, 29, 35 . . . . . . . . . . . . 25 . . . . . . . . . . . . 25 . . . . . . . . . . . . 15 . . . . . . . . . . . . 33 .............. 9 . . . . . . . . . . . . 22 . . . . . . . . 8, 23, 33 . . 6, 9, 13, 20, 33, 35 . . . . . . . . 14, 22, 31 .............. 9 . . . . . . . . . . . . 31

Xu, Z. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Zamani, A. . Za¨ske, H. . . . Zilles, K. . . . Zislin, J. . . . Zlenko, H. . Zullino, D. . Zygrodnik, K.

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20 26 12 34 31 30 24