Eur Arch Psychiatry Clin Neurosci (2004) 254 [Suppl 1] : I/1–I/48

DOI 10.1007/s00406-004-1001-4

ABSTRACTS

Volume 254 Supplement 1 2004

ABSTRACTS

6. DREI-LÄNDER-SYMPOSIUM FÜR BIOLOGISCHE PSYCHIATRIE 21–24 October 2004, Bern, Switzerland University Hospital of Clinical Psychiatry, Bern, Switzerland

EAPCN 1001

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EDITORIAL

Biological Psychiatry is a continuously and dynamically developing clinical area which is based on the combination of basic and clinical neuroscience with the aim of gaining a better understanding of normal and pathological cerebral function and of the individual patient. The vision is that only by better understanding the etiology of psychiatric diseases will it be possible to improve both diagnosis and therapy of mental illness. Beside the often uncertain immediate effect of the treatment on psychiatric disorders, one additional important effect of the elucidation of the mechanisms responsible for pathological brain function is its contribution to the acceptance of psychiatric patients in society as suffering individuals affected by a disease which is not simply escapable by an effort of will, and thus to reduce the burden of the stigma of psychiatric diseases both for patients and their relatives. The “6. Drei-Länder-Symposium für Biologische Psychiatrie” is a meeting of the German, Austrian and Swiss Societies of Biological Psychiatry which is organized every fourth year alternating the venue between the three countries. This year, in 2004, the meeting was held at the University Hospital of Clinical Psychiatry in Bern, Switzerland, the so-called Waldau, which is a place of cure looking back on a history of more than 500 years. One major event was a plenary symposium under the title “Differential perspectives on biological psychiatry: views across the pond”. Since cooperations between universities within Europe but also in an intercontinental perspective are of increasing importance, the symposium was meant to present the views on biological psychiatry in the US from an European view and vice versa. Prof. F. Henn, Director of the Central Institute of Mental Health in Mannheim Germany took the European View and Prof. S. Heckers from Harvard Medical School and Associate-Editor of Archives of General Psychiatry took the American View on Europe. The President of the World Societies for Biological Psychiatry Prof. C. Hojaij chaired the symposium. By improving the understanding of different viewpoints the symposium aimed to facilitate the initiation of intercontinental research projects. The core of the meeting was 28 symposia which covered most aspects of today’s biological psychiatry. The topics of the symposia ranged from basic aspects such as molecular biology and genetics in psychiatry to more clinical themes like treatment strategies in psychiatric disorders. Clinically important aspects like the detection of early symptoms of first onset psychoses were discussed, but also issues like psychophysiological mechanisms responsible for some of the symptoms of psychiatric disorders, such as indications for disconnectivity of cerebral neuronal networks which account for normal brain function. In the area of mental diseases of the old age, the significance of the concept “mild cognitive impairment” was controversially discussed and its importance in the context of developing Alzheimer dementia was clarified. These are only a few examples of the topics covered by the meeting, a more complete synopsis is provided by the abstracts in this issue of the European Archives of Psychiatry and Clinical Neuroscience. Finally, but not least important, both free communications and poster sessions demonstrated that the young researchers in the subject of biological psychiatry are increasingly active and presenting new, interesting and innovative impulses to this area of psychiatric research. All together, symposia, free communications and posters provided a wellbalanced overview of the research themes which are studied in psychiatric hospitals and research institutions in the German-speaking countries, and demonstrated that even though the funds available for research are contin-

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uously decreasing, the research is still progressing and providing important and fascinating information about basic and clinical aspects of psychiatric diseases. Finally, the cooperative efforts of the three societies to organize this joint meeting has an implicit additional intention: To exchange ideas and concepts across borders, and to leave memory traces of the places where psychiatry takes place in Europe. This should contribute to the mutual understanding and inspire further developments. We hope that we were able to fullfill this expectation of the participants. The congress would not have been possible without the tireless and competent commitment of the people in the program committee and, in particular, the local organizing committee. We are deeply grateful for their formidable dedication and enthusiasm. W. Strik T. Dierks

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ABSTRACTS CONTENTS

Abstracts I/1 Abstracts received after editorial deadline I/45 Author index I/46

I/5 1 Mood disorders: myth and fact J Angst University Psychiatric Hospital, Epidemiological Research, Zurich, Switzerland

confirmed an age-related, region specific association of the 5-HT2A receptor gene with TD. The meta-analysis of published and reported studies was 1.65. As a consequence for clinical practice a pharmacogenetic test for TD could be a realistic possibility.

Below are some current approaches/myths regarding mood disorders and, on the other hand, the facts: 1) Antidepressants work selectively on depressive syndromes: non-sedative antidepressants should only be used to treat retarded depression and are not suitable for agitated depression. In fact, Mirtazapine (sedative) and Moclobemide (nonsedative) have been shown not to differ in their effect on agitated and retarded depressive patients. 2) There is a delay before antidepressants kick in. In fact, antidepressants work most powerfully during the first ten days, after which their effect declines steadily. Improvement during the first ten days is highly predictive of response after 4 to 6 weeks. 3) Depression remits much more quickly under antidepressants than under placebo. In fact, in responders to placebo and antidepressants the time course of the disorder is the same. The difference is that there are many more responders to antidepressants than to placebo. 4) Antidepressants trigger drug-induced hypomania and should not be used to treat bipolar depression. In fact, the switch to hypomania is attributable to the spontaneous course of the disorder. There are no statistical data (double-blind studies or meta-analyses) confirming significant differences in switch rates, and there would be none at all if computations were based on rates of remission. The more effective the treatment, the more likely is the switch into hypomania (ECT > TCA > SSRI > placebo). 5) Antidepressants are not suitable for long-term prophylactic treatment, especially not for treating bipolar disorders. In fact, combinations of mood-stabilisers and antidepressants significantly relieve depression and reduce suicide. Monotherapies are less effective than combination treatments. 6) Bipolar disorders can be broken down into BP-I, BP-II and a residual group (DSM-IV). In fact, Bipolar-I disorders are heterogeneous. Predominantly manic patients (M, Md) have a significantly better prognosis than do classic manic-depressive (MD) patients: they suffer fewer episodes, have more frequent remissions and are significantly less suicidal. 7) Bipolar patients are particularly prone to suicide. In fact, the suicide risk among bipolar patients is half that among pure depressives. 8) Depression is associated with alcohol abuse/dependency. In fact, the association is with bipolar disorders, not with major depression (MDD). 9) Depression is associated with migraine. In fact, migraine is significantly associated only with the atypical unipolar and bipolar forms of depression. 10) MDD are frequent and BP disorders rare (ratios between 5:1 and 10:1). In fact, at least a quarter (in the Zurich Study as many as half) of all mood disorders are bipolar (hypomania is often under-reported and under-investigated). 11) The WHO ranks depression as the most burdensome psychiatric disorder (measured in DALYs). In fact, bipolar disorders, with their high but hidden prevalence, probably represent quite as heavy a burden.

3 Morphometric evidence towards a dysfunction of cortico-cerebellar-thalamic-cortical circuitry (CCTCC) in first-episode schizophrenia S Bachmann1, C Bottmer1, V Magnotta2, J Pantel3, F Giesel4, M Essig4, J Schröder1 1 Dept. of Psychiatry, University of Heidelberg, Germany 2 Mental Health Clinical Research Center, University of Iowa Hospitals and Clinics, College of Medicine, Iowa City, IA, USA 3 Dept. of Psychiatry, University of Frankfurt, Germany 4 German Cancer Research Institute, INF 280, Heidelberg, Germany

2 New genetic findings in tardive dyskinesia H Aschauer Universitätsklinik für Psychiatrie Wien, Klinische Abteilung für Allgemeine Psychiatrie, Vienna, Austria Individuals differ considerably not only in the degree of response to psychotropic drugs but also in susceptibility to adverse effects. Tardive dyskinesia (TD) is a movement disorder that affects 20 % or more of chronic schizophrenic patients treated with classical antipsychotic drugs. Pharmacogenetic factors in TD are important at a pharmacokinetic or a pharmacodynamic level. Genes involved in drug metabolism were studied previously (e. g. cytochrome P-450 2D6). Neurotransmitter genes that have been studied include genes coding for dopamine D2 and D3 receptors, serotonergic receptor genes such as 5-HT2C and 5-HT2A receptors and others. A combined analysis supported the association with dopamine D3 receptor gene ser9 gly polymorphism. TD was significantly associated with DRD3 gly allele carrier status and with DRD3 genotype (both p-values = 0.04). The pooled odds ratio for DRD3 gly allele carrier status increasing susceptibility to TD was 1.33. Furthermore a recent combined analysis

“Cognitive Dysmetria”refers to the hypothesis of a dysfunctional cortico-cerebellar-thalamic-cortical circuitry in schizophrenia which manifests itself as positive and negative symptoms (Andreasen et al. 1996). Our study compared volumes of frontal cortex and cerebellum of 71 patients with DSM-IV diagnoses of first-episode schizophrenia, schizophreniform and schizoaffective disorder, respectively, to 41 healthy age- and gender-matched controls. MRIs were obtained with a 1.5 T Siemens Magnetom, for volumetric assessment the software BRAINS was used. Patients’ psychopathological symptoms were rated with the Positive and Negative Syndrome Scale (PANSS). ANCOVAs with intracranial volume serving as a covariate revealed significantly reduced cerebellar volumes in patients (p < 0.05), whereas frontal lobe gray matter volumes were larger in patients than in controls (left hemisphere: p < 0.01; right hemisphere: p = 0.06). Frontal lobe white matter volume was reduced in patients compared to controls (p < 0.001 bilaterally). There were no significant correlations between volumetric measurements and psychopathological symptoms on admission or remission of acute symptoms. Cerebellar changes have previously been described (Bottmer et al. in press) and support the concept of “cognitive dysmetria”. Our findings regarding the frontal lobes are in line with Garver et al. (2000) who found discrete volumetric alterations in the course of the disease with enlarged structures during the acute phase. 4 Pain perception in schizophrenia KJ Bär Klinik für Psychiatrie, Jena, Germany Objectives: A number of clinical observations indicate that pain processing might be disturbed in psychotic disorders such as schizophrenia. Schizophrenic patients may suffer from disturbing diseases and show only minor indications of pain. Very few studies have addressed the issue of pain perception in schizophrenia. The main objective of this study was the investigation of thresholds of warmth perception (WP), thermal pain perception (TPO) and tolerance (TPT) in schizophrenic patients, the interaction with neuroleptic medication and disease severity. Methods: We investigated 23 schizophrenic subjects who had not taken antipsychotic treatment for at least 8 weeks to the first point of the study and reassessed them a second time after introduction of neuroleptics.Acute symptoms of schizophrenia were measured using the scale for the assessment of positive symptoms and negative symptoms. WP, TPO and TPT were determined by an ascending Method of Limits, using a contact thermode. All patients and control subjects were studied on both arms on every occasion. Results: Schizophrenic patients showed a significant increase in thresholds of WP and TPO relative to healthy controls. Neuroleptics did not alter these pain thresholds. We found no correlation between pain perception and psychometric scales. Conclusion: Our findings demonstrate altered heat pain perception in schizophrenia. Since both WP and TPO were significantly different, we believe that our findings can be attributed to information processing abnormalities, and are not specific to pain perception. Fu-

I/6 ture studies should evaluate attention deficits in schizophrenia in relation to pain perception. 5 Pattern changes of prefrontal efferent terminal fields in the neocortex in an animal model of psychosis F Bagorda, V Witte, G Teuchert-Noodt Department of Neuroanatomy, Faculty of Biology, University of Bielefeld, Germany

7 Alcohol-associated hyperhomocysteinemia and the risk of previous withdrawal seizures K Bayerlein1, T Hillemacher1, W Sperling1, JM Maler1, B Mugele2, J Kornhuber1, S Bleich1 1 Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany 2 Klinikum am Europakanal, Department of Addiction, Erlangen, Germany

The prefrontal cortex (PFC) develops corticocortical efferents, originating from various pyramidal neurons. In a previous study we have shown that isolated rearing (IR) of gerbils and early intervention with a single dose of methamphetamine (MA) produce changes of dendrites and spine densities of the lamina (L) III and V pyramids. Since this animal model has also shown a lot of transmitter changes in prefrontal and other cortical areas, we asked if the glutamatergic projections coming from the prefrontal neurons might additionally be affected by interventions; we evaluated fibres by biocytin tracing techniques and computer-aided quantification. PFC pyramidal neurons developed a suppressive pattern of corticocortical efferents after both the IR and the MA intervention. A decreased density of fibres was detected in frontal (Fr2) and parietal cortex (Par1) after labelling pyramidal neurons in LV, and in Par1 and insular cortex (IC) after labelling of LIII neurons. If IR and MA were combined, the PFC pyramidal neurons developed quite another tracing pattern: an excessive labelling of corticocortical collaterals coming from LV pyramidal neurons in Fr2 and Par1, contrasted with reduced collaterals from LIII neurons. Thus, both interventions together produced a severe dissociation of corticocortical projections from PFC to somatomotoric and associative regions.

There is increasing evidence that chronic alcoholism is associated with hyperhomocysteinemia. Homocysteine is an excitatory amino acid that enhances the vulnerability of neuronal cells to excitotoxic and oxidative injury. The aim of this study was to determine total plasma homocysteine levels in actively drinking alcoholics and patients with early abstinence and to evaluate an association with a history of alcohol withdrawal seizures. Our study included two groups of patients with an established diagnosis of alcohol dependence. GROUP A comprised 56 consecutively admitted alcoholics who had been abstained from alcohol between 24 to 72 hours before hospitalisation. GROUP B consisted of 144 consecutively recruited alcoholics who were admitted acutely intoxicated for withdrawal treatment. Furthermore, groups were divided into two subgroups: patients with and without a history of alcohol withdrawal seizures. Alcoholics of GROUP B with a history of withdrawal seizures had significantly (p < 0.0001) higher homocysteine levels than actively drinking patients without seizures. Using a logistic regression analysis, withdrawal seizures in GROUP B but not in GROUP A patients were best predicted by a high homocysteine level at admission. Homocysteine levels on admission may be a useful screening method to identify actively drinking patients with the risk of alcohol withdrawal seizures in their medical history.

6 Mild cognitive impairment and Alzheimer’s disease: an investigation of the cerad-np test battery S Barth1, P Schönknecht1, J Pantel2, J Schröder1 1 Gerontopsychiatry Section at the University of Heidelberg, Germany 2 Psychiatry at the University of Frankfurt, Germany

8 The developmental concept of schizophrenia H Beckmann, H Jakob Department of Psychiatry and Psychotherapy, University of Wuerzburg, Germany

To investigate the psychometric properties of the CERAD-NP, neuropsychological deficits were compared between 49 patients with mild cognitive impairment (MCI), 80 patients with Alzheimer’s disease (AD), 36 with major depression (MD), and 26 elderly controls.All participants were outpatients of the memory clinic, Heidelberg University. All CERAD-NP subtests discriminated between controls and AD patients. The subtest verbal fluency and constructive apraxia differed significantly between mild and moderate AD, while the subtests assessing declarative (epsisodic) memory performance showed only minor, non-significant differences. The MCI patients took an intermediate position between controls and AD patients with significantly lower scores in verbal fluency and declarative memory performance than the controls. Relative to the controls, the patients with MD showed a decreased episodic memory performance but no evidence suggesting an impairment in other neuropsychological domains. Our results indicate that the CERAD-NP is a psychometric instrument which allows a sensitive discrimination between mild and moderate AD, MCI, MD and healthy controls. However, sensitivity of discrimination between different stages of dementia varies with respect to the different subtest.While the subtest for episodic memory showed floor effects already for mild dementia, subtests for verbal tasks and constructive apraxia were able to discriminate even between more advanced stages of the disease.

In recent years neuroimaging techniques have revealed various cerebral and structural deviances in patients with schizophrenic psychoses. The best established findings are the enlargement of the lateral ventricles and discrete structural deficits in temporobasal structures of the cortex. Neuropathological investigations have detected subcortical as well as cortical variances. Subcortically, the volume of the striatum and the globus pallidus have been found to be enlarged in schizophrenics. Among the cortical deviations, the cytoarchitectonic disturbances of the rostral entorhinal region have been well documented and are especially important. According to neuropathological criteria, they are derived from disturbances of prenatal cell migration within the central nervous system. Due to its close anatomical and function connection with the hippocampal formation and its being the assembly point of all sensory cortical areas, disturbances of this area could seriously impede the processing and filtering of information within the limbic system. The other hitherto reported structural anomalies, such as the disturbance of the radial order of hippocampal neurons, and the abnormal structures in the frontobasal orbital regions and the rostroventral insular, could be connected to the disturbances of migration within the entorhinal region; the former could be secondary, but still prenatal developments. Well documented are the architectonic changes in the rostral cingulate gyrus which is itself connected with the entorhinal region via the Papez circuit. These findings are supported and supplemented by the results of epidemiological studies which indicate a disturbance of brain development during the second trimenon of the prenatal period. Viral infections (e. g. influenza A2) of mothers during this critical period appear to play an especially important role. Nevertheless, the interaction between a genetic predisposition and exogenous noxious agents in such cases still needs to be clarified in our understanding of the etiology of schizophrenic psychoses.

I/7 9 White matter and configural memory: a diffusion tensor imaging study in healthy subjects S Begré1,2, A Frommer2, C Kiefer3, A Federspiel2 1 Inselspital Bern, Department of General Internal Medicine, Division of Psychosomatic Medicine, Inselspital, University of Bern, Switzerland 2 University Hospital of Clinical Psychiatry, Department of Psychiatric Neurophysiology, Bern, Switzerland 3 Inselspital Bern, Department of Neuroradiology, University of Bern, Switzerland Cognitive dysfunction is associated with various brain diseases.To investigate if visual memory performance would be linked to white matter connectivity we measured intervoxel coherence (IC) by diffusion tensor imaging (dti) in low and high test performers of the ReyOsterrieth complex figure test (ROCFT).Voxel-based t-test analysis of the IC values was used to identify neighboring voxel clusters with significant differences between the two groups.We detected multiple circumscribed significant clusters of voxels where the two groups differed in IC (p < 0.01). Using Pearlson correlation coefficient IC and memory performance were significantly correlated (r < 0.63). Our findings are showing the importance of well wired and lined up axons in certain brain regions supposed to be important for configural memory processing. 10 White matter connectivity in first episode schizophrenia and healthy controls S Begré1,2, A Frommer2, C Kiefer3, A Federspiel2 1 Inselspital Bern, Department of General Internal Medicine, Division of Psychosomatic Medicine, Inselspital, University of Bern, Switzerland 2 University Hospital of Clinical Psychiatry, Department of Psychiatric Neurophysiology, Bern, Switzerland 3 Inselspital Bern, Department of Neuroradiology, University of Bern, Switzerland Intervoxel coherence (IC) values depicted by diffusion tensor imaging were computed for 12 patients hospitalized with first episode schizophrenia and 12 age- and gender-matched healthy controls. Voxel-based t-test analysis of the IC values was used to identify neighboring voxel clusters with significant differences between the two groups. We detected 19 circumscribed significant clusters (P < 0.02). In 8 of these IC values for patients with schizophrenia were higher than those for the healthy controls, and in 11 clusters patients with schizophrenia registered lower IC values than the control group did. Furthermore, we have found a right-left asymmetry in IC values for patients with schizophrenia. We interpreted these white matter alterations in different regions to be disconnected fiber tracts that are already present early in schizophrenic disease progression. 11 White matter disconnectivity leads to neurofunctional disturbances in first episode schizophrenia S Begré1,2, A Frommer2, C Kiefer3, A Federspiel2 1 Inselspital Bern, Department of General Internal Medicine, Division of Psychosomatic Medicine, Inselspital, University of Bern, Switzerland 2 University Hospital of Clinical Psychiatry, Department of Psychiatric Neurophysiology, Bern, Switzerland 3 Inselspital Bern, Department of Neuroradiology, University of Bern, Switzerland Cerebral disconnectivity due to white matter alterations in patients with chronic schizophrenia assessed by diffusion tensor imaging has been reported previously. We used diffusion tensor imaging to investigate whether cerebral disconnectivity can be detected as early as the first episode of schizophrenia. We analyzed intervoxel coherence in first episode schizophrenic patients compared to healthy controls. Here we present data indicating that structural alterations correlate

with functional disturbances concerning memory functions and EEG-recordings. We detected several regions of significant difference in white matter connectivity between schizophrenics and healthy subjects. Furthermore, a significant correlation between connectivity on one hand and memory performance and EEG-recordings on the other was found. We interpreted white matter alterations in different regions to be disconnected fiber tracts of neurofunctional systems supposed to be involved in the functional processes we have measured by our paradigms. 12 Manipulations of the sleep-wake cycle as an antidepressant M Berger, D Riemann, U Voderholzer Department of Psychiatry and Psychotherapy, University Hospital of Freiburg, Germany Acute sleep deprivation for one night or even partial SD in the second half of the night improves mood in about 60 % of depressed patients the day after. In this respect, among all types of antidepressant treatments, SD elicits the fastest results, faster even than electroconvulsive therapy. The main limitation, however, is the transient nature of the effect, since the majority – but not all – of the improved patients experience a relapse after the next night of sleep.A variety of studies focussed on strategies to avoid relapsing and additionally treated the patients with light therapy, lithium, or other drugs. A further strategy has been to advance the sleep period to an unphysiological time. Several studies showed that a phase advance of the sleep period, over a course of either six or three nights consistently stabilized the antidepressant effect of SD in about 60 % of those patients who responded positively to SD. Up to now, only one study also included a control group which participated in a phase delay protocol after SD instead of a phase-advance protocol. Significantly more patients relapsed in the phase-delay protocol, supporting the hypothesis that sleeping at certain phases of the circadian rhythm, i. e., especially late in the night and in the morning, has depressogenic effects. The major limitation of the phase advance studies is that the effect has been shown over a period of one week; further studies have to include a follow-up over the course of four to six weeks. 13 PET measurements of regional a [11C]-methyl-L-tryptophan trapping in patients with Major Depression treated with citalopram augmented with pindolol A Berney1,2, M Nishikawa2, G Gobbi2, G Debonnel2, M Diksic2, C Benkelfat2 1 Department of Psychiatry, Lausanne University, Switzerland 2 Departments of Psychiatry, Neurology and Neurosurgery, McGill University, Canada Background: Positron emission tomography (PET) coupled with a[11C]-methyl-L-tryptophan (11C-aMtrp), is believed to provide an index of the brain regional rates of 5-HT synthesis. We investigated here the effects on 11C-aMtrp regional trapping of citalopram, augmented with the mixed 5-HT1A and b-adrenoceptor antagonist pindolol, in Major Depression patients. Methods: two-arm, randomized, double-blind study conducted in MDD patients receiving citalopram 20 mg/day augmented with either pindolol 2.5 mg tid or placebo from day 11 to 24. 11C-aMtrp PET measures were obtained at baseline, and after 10 and 24 days of treatment. Results: Voxel-wise approach: increases in trapping correlated with a reduction of HDRS-17 in the Cingulate Cortex (BAs 32 and 24), Precentral Gyrus (BA40), and the Medial Frontal Gyrus (p < 0.05; corrected). Volume-of-Interest approach: ANOVA revealed a Time x Treatment interaction in the DLPFC (F = 6.27 [1, 7]; p < 0.05), and a Time x hemisphere x Treatment interaction in the Caudate Nucleus (F = 13.06 [1, 7]; p < 0.01). Post-hoc comparisons indicated that addition of pindolol, relative to placebo, resulted in a significant increase in 11C-aMtrp trapping in those structures (p < 0.02). Conclusion: Pindolol augmentation in the pharmacotherapy of Major Depression may rely upon the enhancement of aspects of 5-HT neurotransmission/5HT synthesis.

I/8 14 Differences in activation of the dorsal raphe nucleus depending on performance of suicide H Bielau1, C Mawrin2, D Krell1, MW Agelink3, K Trübner4, R Davis5, P Danos1, B Bogerts1, HG Bernstein1, B Baumann1 1 Department of Psychiatry, Otto-von-Guericke-University, Magdeburg, Germany 2 Department of Neuropathology; Otto-von-Guericke-University, Magdeburg, Germany 3 Research Institute of Biological Psychiatry and Neuroscience, RuhrUniversity of Bochum, Germany 4 Institute of Legal Medicine, University of Essen, Germany 5 Department of Pathology, Upstate Medical University, Syracuse, NY, USA The serotonergic system has been implicated in the pathogenesis of mood disorders as well as in suicidal behaviour. It is unknown, whether raphe neurons, which are mostly serotonergic, show altered activity in patients with mood disorders who complete suicide as compared to those without suicidal behaviour. To measure cellular markers in the dorsal raphe nucleus in brains of 12 people with mood disorders and of 12 controls (C) stereological measurements were carried out of nucleolar organizer regions (NORs) and of serotonergic neuron numbers. Six patients died from suicide (S), the other six patients died from natural causes (NS). In the rostral subnuclei of the dorsal raphe there was a significant main effect of diagnostic group for the ratios of nucleolar organizer regions to nuclear area (NOR ratio) and a nearly significant effect for numbers of serotonergic neurons. Post-hoc tests revealed greater values for those dependent variables in S than in NS. NOR ratios were lower in NS compared to C. Dose equivalents of antidepressants correlated positively with NOR ratios and numbers of serotonergic neurons in the rostral part of the dorsal raphe. The present data suggest functional differences in the dorsal raphe of patients with mood disorders depending from suicidal behaviour. Antidepressants appear to contribute to cellular activation in the rostral part of the dorsal raphe. 15 Neurotransmitter alterations in rats persistently infected with borna disease virus T Bilzer1, U Gies2, H Weidemann1, O Planz3, L Stitz3 1 Institut für Neuropathologie, Universität Düsseldorf, Germany 2 Institut für Klinische Neuropathologie, Zentralkrankenhaus Bremen-Ost, Germany 3 Institut für Immunologie, BFAV, Tübingen, Germany. Rats experimentally infected with BDV display cortical dysfunctions such as learning deficiences and behavioural abnormalities. Prior to encephalitis significant reductions in choline-acetyltransferase (ChAT), acetylcholinesterase (AChE) and vesicular acetylcholine transporter (VAChT) activities were found in the cerebral cortex, hippocampus, amygdala and cholinergic basal forebrain nuclei (ChBFN). The striatum and medial septum remained unaffected. Immunocytochemistry revealed axonal degeneration in cortical and limbic projection areas of ChBFN. Other than normal adult rats, immunocompromised rats fail to develop encephalitis and show only slight behavioural abnormalities. However, reduced tyrosine hydroxylase (TH) labeling and RNA-expression in frontal and parietal cortex and in the hippocampus could be observed by day 30 to 40 postinfection. In summary, our data indicate that neurotransmitter alterations parallel BDV infection, also in the absence of inflammation. We conclude that the motor, mood, learning and memory disabilities in BDV-infected rats are the result of the cortical cholinergic denervation. Moreover, TH deterioration is an early marker of neurotransmitter alterations during BDV-infection.

16 Differential influence of sleep pressure on working memory and learning as measured by clinical neuropsychiatric tests (CANTAB®) K Blatter, M Münch, C Schröder, C Schnitzler, A Wirz-Justice, C Cajochen Centre for Chronobiology, Psychiatric University Clinic, Basel, Switzerland To extend studies showing decremental effects of increased sleep pressure on cognitive performance into the psychiatric domain, we utilised the clinical neuropsychiatric test battery CANTAB to evaluate the effect of differential sleep pressure on the Spatial Working Memory Task (SWM) and the Paired Associate Learning Task (PAL) in healthy older subjects (8 men, 7 women; 65.1 ± 6 y). They underwent two 40 h protocols under dim light (< 8 lux) and constant posture conditions in a balanced crossover design, either total sleep deprivation (SD) or sleep satiation using a 75/150min sleep-wake cycle (NAP). The tasks were carried out twice before and once after, and 12h and 34h into the protocol. With an age-matched control group in an ambulatory setting we partialled out confounding practice effects. Two-way rANOVAs (‘time course’, ‘condition’) revealed a significant main effect for ‘time course’ of the total number of errors in both tasks (p ≤ 0.01). There was no interaction for PAL (p > 0.6) but a tendency in SWM (p = 0.055, Eta2 = 0.54). Here a rather stable error rate in the sleep deprivation condition contrasted with errors diminishing across the nap protocol. This points to a performance-promoting role of sleep for working memory, but not for associate learning. 17 Pathobiochemistry and pathophysiology of alcoholism-associated hyperhomocysteinemia S Bleich, J Kornhuber Department of Psychiatry and Psychotherapy, Friedrich-AlexanderUniversity of Erlangen-Nuremberg, Erlangen, Germany There is evidence from in vitro and in vivo studies that homocysteine induces neuronal damage and cell loss by both excitotoxicity and different apoptotic processes. Clinical evidence suggests a strong relationship between higher plasma homocysteine levels and brain atrophy in healthy elderly subjects as well as in elderly at risk of and with Alzheimer’s disease. Chronic alcoholism leads to elevated plasma homocysteine levels, as shown by clinical investigations and animal experiments. In addition, an association between brain atrophy and increased levels of homocysteine in chronic alcoholism was shown. This may have important implications for the pathogenesis of alcoholismassociated brain atrophy. Furthermore, taking into account that high plasma homocysteine levels are helpful in the prediction of alcohol withdrawal seizures, early anticonvulsive therapy could prevent this severe complication. Homocysteine plays a role in a shared biochemical cascade involving overstimulation of N-methyl-D-aspartate (NMDA) receptors, oxidative stress, activation of caspases, DNA damage, endoplasmic reticulum and mitochondrial dysfunction. These mechanisms are believed to be important in the pathogenesis of both excitotoxicity and apoptotic neurotoxicity. The most important pathobiochemical and pathophysiological features of an ethanol-induced hyperhomocysteinaemia are reviewed. 18 Homocysteine and DNA methylation patterns in alcoholism S Bleich, B Lenz, D Bönsch Department of Psychiatry and Psychotherapy, Friedrich-AlexanderUniversity of Erlangen-Nuremberg, Erlangen, Germany Excitatory amino acids such as glutamate, aspartate, and homocysteine have been shown to be increased in patients with chronic alcoholism who underwent alcohol withdrawal. Furthermore, sustained hyperhomocysteinemia occurred in chronic alcoholics with an active drinking pattern. Long-term ingestion of large quantities of ethanol causes inhibition of methionine synthase activity due to its breakdown product acetaldehyde and it has been proposed that elevated blood levels of ethanol rather than nutritional factors are responsible

I/9 for changes in methionine metabolism. This conversion of homocysteine to methionine is a crucial reaction from the standpoint of conserving methionine and detoxifying homocysteine which may interfere with DNA methylation status by impairing de novo methionine synthesis. Taking into account that an increase in plasma homocysteine is associated with DNA hypomethylation the objective of this study was to measure DNA methylation in peripheral blood cells including general methylation status and methylation of 5’ CpG islands of alcohol-related genes. Preliminary results show altered methylation patterns in patients with chronic alcoholism compared to healthy controls. We conclude that the disruption of methylation patterns in DNA can lead to alterations in chromatine structure and especially in gene expression that can promote craving or neurotoxicity.

19 Bio-psychological personality traits as predictors for relapse J Boening1, GA Wiesbeck2, HG Weijers3 1 Addiction medicine, Psychiatric University Hospital, Wuerzburg, Germany 2 Department of Substance Use Disorders, Psychiatric University Hospital, Basel, Switzerland 3 University of Applied Police Sciences Sachsen-Anhalt, Germany Over the last decade the Wuerzburg Addiction Research Group was involved in the clinical testing of several substances (acamprosate, naltrexone, ritanserin, flupenthixol, neramexane, actol) to pharmacologically prevent relapse in primary alcohol-dependent patients without comorbidity. These experiences led us to a closer investigation of biopsychological personality traits as predictors for treatment response.We found that psychoticism (Eysenck’s Personality Questionnaire) and persistence (Cloninger’s TCI) were the most discriminating variables. Their combination correctly predicted relapse in 62 % and abstinence in 73 % of our sample. Looking for a classification rule to determine in which category an individual falls due to his personality scores (tree-based approach: CART). We found this: Alcohol-dependent men scoring low in psychoticism were at low risk for relapse – expecially when combined with a low sensation seeking score (Zuckerman’s SSS). On the other side, male alcoholics revealed an extraordinary risk for relapse when scoring high in psychoticism and low in persistence. A promising goal for future research might be to elucidate how these personality characteristics could be used for pharmacotherapeutical and/or psychotherapeutical treatment strategies.

20 Alpha-synuclein and craving – clinical and genetic aspects D Bönsch, U Reulbach, K Bayerlein, T Hillemacher, J Kornhuber, S Bleich Friedrich-Alexander-University of Erlangen-Nuremberg Department of Psychiatry and Psychotherapy Erlangen, Germany Background: Alpha synuclein has been found elevated in dopamine neurones of cocaine abusers, and in rats whose alcohol preference is inbred. Methods: The alpha synuclein mRNA expression level was measured by quantitative PCR (iCycler) in the blood of 75 male alcoholics undergoing alcohol withdrawal and 69 non-drinking healthy controls. Alcohol craving was assessed by the Obsessive-Compulsive Drinking Scale total score (OCDSts) including subscales for obsessive (OCDSos) and compulsive (OCDScs) craving for alcohol. Results: The alpha synuclein expression in patients with alcoholism (2.79 ∆CT; SD 1.69; p = 0.021) was significantly higher when compared with healthy controls (2.20 ∆CT; SD 1.59). Multivariate logistic regression analysis revealed that increased alpha synuclein levels significantly predict OCDSts (OR = 1.44, 95 %-CI: 1.01–2.06, p = 0.042) and especially OCDSos (OR = 1.74, 95 %-CI: 1.18–2.58, p = 0.005), but not OCDScs alcohol craving. Conclusions: Higher levels of alpha synuclein are associated with an increase in alcohol craving. Since alpha synuclein is involved in the regulation of dopaminergic transmission which has been causally

linked to craving, the present results provide a novel pathophysiological approach to the explanation of craving mechanisms. 21 Subgroups of schizophrenia determined by backward masking A Brand1, S Kopmann1, 2, MH Herzog2, 3 1 Center for Psychiatry and Psychotherapy, Hospital Bremen Ost, Bremen, Germany 2 Human Neurobiology, University of Bremen, Bremen, Germany 3 Laboratory for Psychophysics, BMI, EPFL, Lausanne, Switzerland Schizophrenia is a highly heterogeneous disorder. To unearth the causes of the disease, homogeneous subgroups have to be determined. Most studies address this issue based on psychopathology. Only very few studies attack this topic by searching clusters based on low level processing deficits. Using a novel paradigm of backward masking (shine-through effect), we performed a cluster analysis with 41 schizophrenic patients and 16 healthy controls. We found two significantly different groups: one performing low (LP) and one performance high (HP).All control subjects belong to the HP group whereas the schizophrenic patients are found in both groups. Patients in the HP group reveal less negative symptoms than the ones in the LP group. This indicates that low performance related to early visual processing might correspond to negative symptoms. On the other hand, both groups did not differ with regard to sustained attention or global cognitive performance. Thus, the shine-through effect, possibly combined with other tests, might be used to define the different subgroups of schizophrenia. 22 Sensitization in a recurrent excitatory network: biological and clinical implications for neuropsychiatric disorders HA Braun2, JC Krieg1, MT Huber1 1 Klinik für Psychiatrie und Psychotherapie 2 Institut für Normale und Pathophysiologische Physiologie, Universität Marburg, Germany Sensitization is an important phenomenon governing the initiation and progression of a variety of neuropsychiatric disorders. The relevance to understand sensitization phenomena is emphasized by findings that even single exposures to stimuli such as drugs can induce longlasting changes in neurobiology and behavior. Stimulus-Triggering of persistent activity is also discussed as a key mechanism in active memory and other cognitive tasks. Here, we combine these two lines of evidence and consider a computational model that represents sensitization in terms of a recurrent excitatory neuronal network (for previous work see Huber et al. J Psychiatr Res 2001;35:49–57 and Neuropsychopharmacology 2003;28:S13-S20).We show that the dynamics of even the simplest network design (i. e. a single self-coupled neuron) can represent many essential features of sensitization behavior as observed in clinical and experimental data. This is because of the included nonlinearities, kinetics and coupling features which determine the dynamical system behavior. We study the principal behaviors of the model and relate the included mechanisms to relevant biological principles such as different synaptic timescales, second messenger cascades and gene expression. Relevances for neuropsychiatric disorders are discussed including a comment on the potential use of biosimulation in psychiatric research. 23 Imaging genomics, Dopamin and Serotonin DF Braus NeuroImage Nord (NIN), University of Hamburg, Hamburg, Germany Advances in molecular biology opened up unexpected opportunities to explore the genetic basis of individual differences of complex behavioural patterns and to identify factors of vulnerability for neuropsychiatric illnesses and their interaction with environmental variables. At the same time, modern imaging methods offered new

I/10 opportunities for the non-invasive characterization of the brain, its microstructure (MRI, DTI), essential aspects of information processing (fMRI), and aspects of metabolism (MRS). On the behavioural level, neuropsychological methods have been developed, which allow improved characterising of cognitive and emotional processes. A combination of these three examination levels now allows to establish relationships between functionally relevant gene polymorphisms (e. g. 5-HTTPR, COMT val-met), emotional and cognitive processes and the neuronal networks and their connectivity as well as brain volume and metabolism. The first studies using this approach are very promising. They established for instance relationships between the function of the hippocampus-amygdala formation and polymorphisms of BDNF and 5-HTTPR, and between COMT and frontal brain functions respectively. It is interesting to note that all these relationships could be found in relatively small collectives. This emphasises the advantage of a direct characterisation of the brain physiology by imaging methods when exploring the functional significance of genetic variants in psychiatry. 24 MR-Spectroscopy in schizophrenia and affective disorder DF Braus, W Weber-Fahr NeuroImage Nord (NIN), University of Hamburg, Hamburg, Germany Magnetic resonance spectroscopy (MRS) is one of the techniques that is receiving more attention in psychiatry, especially when operating at field strength at or above 3 Tesla. MRS relies on the same nuclear magnetic resonance principles as MRI and functional MRI, but allows the relative quantification of certain compounds and their constituents in predefined brain regions. This metabolic information can be used to define the nature and extent of brain diseases, such as schizophrenia, dementia and affective disorder. In the last few years’ research application of MRS in psychiatry focuses on the understanding of the basic brain function as well as on the monitoring of treatment effects. In affective disorders, early reports have shown that lithium treatment leads to changes in brain choline (Ch) metabolism, probably because of the inhibition of choline transport across membranes. More recently, we have demonstrated that antidepressants as well as electroconvulsive therapy are normalizing a reduced hippocampal cytosolic choline signal in severely depressed patients indicating an increase in synaptic plasticity. In schizophrenic patients antipsychotic drugs (especially atypicals) seem to increase N-acetylaspartate (NAA), an intraneuronal marker of neuronal functional integrity, in frontal areas, suggesting that these drugs may modify the function of cortical neurons. 25 Prefrontocortical plasticity in analysis, simulation and disease M Butz Dep. Neuroanatomy, Fac. Biology, University Bielefeld, Germany In biological neural systems, structure and function are mutually dependent states. While the connectivity pattern determines the functional interaction of nerve cells, the neurons’ activity in a larger time scale modulates the synaptic spectrum. By compensatory local processes, the neurons develop their synaptic connection in such a way that all converge towards an average activity. This process can be simulated in silico by using a recurrent McCulloch-Pitts network. This network can be used to model morphogenetic processes in the developing and adult brain. We can demonstrate that the response of the prefrontal cortex to influences depleting the dopamine afference can be understood in terms of local compensatory mechanism. This issue is of practical importance since impairments in the prefrontal dopamine function are hallmarks of psychocognitive diseases like schizophrenia and hyperactivity. In accordance with neurobiological observations, local inhibitory neuroids cover for the loss of dopaminergic inhibition. Additionally, the model predicts a reduction of excitatory efferent connections. This prediction has been confirmed experimentally by an anterograde tracing study of prefrontal projections. In the future, such a model will be able to predict the sys-

temic effects of pharmacological interventions, thus providing enhanced tools for the treatment of psychocognitive disorders. 26 Neurochemical function of MRS-assessable compounds (NAA, choline, creatine, myo-inositol, glutamate/glutamine, lactate) in CNS physiology and pathophysiology D van Calker Department of Psychiatry and Psychotherapy, University of Freiburg, Germany Most compounds that can be quantitatively assessed by MRS are implicated in recent hypotheses on the pathophysiology of psychiatric disorders. Thus N-acetyl-aspartate (NAA) is a marker of neuronal resiliency that may have a role in neuron-glia signalling and/or osmoregulation. The decreased NAA levels in the dorsolateral prefrontal cortex of bipolar patients may be related to the morphometric alterations in post-mortem brains of such patients. Myo-inositol is considered a primal target in the action of mood stabilizers: All three mood stabilizers (lithium, carbamazepine, valproate) inhibit myo-inositol uptake thus inducing depletion of certain brain regions of myoinositol. Glutamate is not only an important excitatory (and potentially excitotoxic) neurotransmitter but also a “gliotransmitter” which is released from astrocytes in response to neurotransmitters and feeds back on neurons to regulate their activity. Glutamate is also involved in the coupling of neural activity to functional hyperemia and increased glucose utilization as visualized in brain imaging. Finally, the now identified role of lactate as an astrocyte-derived fuel for neurons, which is tightly coupled to synaptic activity, suggests that the assessment of lactate by MRS might be of value for the identification of potential alterations of energy supply and demand in neuropsychiatric disorders. 27 Connectivity between auditory areas in human brain O Chiry Max Planck Institute for Brain Research, Frankfurt am Main, Germany A plethora of approaches can be applied to investigate connectivity patterns in the central nervous system. Starting with degeneration techniques, the spectrum comprises multiple methods such as tracer injections and even the application of neurotropic viruses. Many of these techniques have been used to visualize connectivity between auditory areas in the supratemporal region in different species. These studies demonstrate an intense connectivity between the primary auditory cortex and the surrounding secondary areas in non-human primates. Also the connectivity between the thalamus and the auditory cortex could be demonstrated. However, tracing studies in the human brain can only be performed on post mortem material, which limits the choice of methods. Available techniques, such as injection with carbocyanine dyes, are limited in terms of distance and, thus, preclude the possibility of tracing long distance connections such as the thalamo-cortical projections. Nevertheless, shorter connections can be well studied. This tracing technique allows for the investigation of intra- and interareal connectivity in the cortical auditory areas. The results show that the auditory areas on the supratemporal plane are interconnected and hierarchically organised. It is anticipated that future developments in MR-techniques will lead to in-vivo visualization of such connections in the human brain.

I/11 28 Electroconvulsive therapy theoretical and practical clinical guide. Consensus paper of the Austrian society of psychiatry and psychotherapy A Conca1, H Hinterhuber4, M Prapotnik1, C Geretsegger6, R Frey5, A Hausmann4, P Hofmann3, S Kasper5, T Lahousen3, P König1, J Di Pauli1, B Pramsohler9, H Rittmansberger8, W Wagner7, R Pycha2 1 LKH Rankweil, Psychiatrie I, Austria 2 LKH Bruneck, Austria 3 Univ. Klinik für Psychiatrie Graz, Austria 4 Univ. Klinik für Psychiatrie Innsbruck, Austria 5 Univ. Klinik für Psychiatrie Wien, Austria 6 Christian Doppler Klinik Salzburg, Psychiatrie I, Austria 7 Zentrum für Seelische Gesundheit LKH Klagenfurt, Austria 8 OÖ Nervenklinik Wagner Jauregg, Austria 9 PrivatKlinik Villach, Austria The electroconvulsive therapy (ECT) consensus paper has been produced by the Austrian Task Force for Special Psychiatric Treatment Modalities of the Austrian Society of Psychiatry and Psychotherapy in collaboration with all psychiatric units of Austria prescribing ECT. It is intended as a theoretical and practical clinical guide to the good administration of ECT. There is high evidence that ECT is an effective treatment in severe and medication refractory depression. In schizophrenia, schizoaffective disorder and mania ECT efficiency is less studied but in treatment resistance well documented. Relating to severe catatonia ECT can be lifesaving. ECT has side effects. Although transient, special memory impairments are of importance. The stimulation technique during treatment series should be optimised and marked psychotropic medication avoided thus reducing incidence, frequency and severity of memory disturbances. ECT displays a high safety profile and does not cause morphological damages. Considering anaesthesiological and internal aspects there are no absolute contraindications. Mortality is defined through the risk of anaesthesia itself amounting to 1:30.000. For indications and administration of ECT a professional well-trained staff is indispensable. ECT exhibits selective and specific mechanisms of action; thus certain neurobiological changes occur in defined brain areas depending on the complexity of current’s configuration, the electrode placement and number of ECT series. In cases of compulsory detention and patient’s incapability of giving consent ECT is regulated by the Austrian Detaining Low section 3 from 1990. 29 Left prefrontal high frequency repetitive transcranial magnetic stimulation (rTMS) and the effect on schizophrenic psychopathology J Cordes1, M Arends1, A Mobascher1, M Jänner1, W Wölwer1, K Krieger1, MW Agelink2, A Klimke1, J Brinkmeyer1 1 Klinik und Poliklinik für Psychiatrie und Psychotherapie der Heinrich-Heine-Universität, Duesseldorf, Germany 2 Klinik für Psychiatrie, Psychotherapie und Psychosomatik an den Evangelischen Kliniken Gelsenkirchen, Ruhr-Universität Bochum, Gelsenkirchen, Germany Introduction: High or low frequency rTMS can excite or inhibit cortical areas of the brain. It has been used for physiological studies and as a treatment for depression. rTMS shows increasing evidence of successful treatment in schizophrenia. Most results demonstrate a reduction of negative symptoms following high frequency rTMS. But there is a small sample size of sham-controlled studies. The study was realized to evaluate the effects of rTMS on negative symptoms in schizophrenia. Methods: By using a sham-controlled randomized design 17 patients with schizophrenia were treated with 10 Hz rTMS over 10 days of the dorsolateral prefrontal cortex. The ratings were assessed at baseline before the first and after the 10th session with rTMS. The Positive and Negative Symptoms Scale (PANSS) was used to assess schizophrenic symptomatic. The UKU side effects scale and a neuropsychological battery were administered. The ratings were performed by a psychiatrist who was blind to the nature of treatment. Results: Seventeen schizophrenic patients (rTMS = 11, sham = 6)

completed the protocol. No serious adverse effects were reported. Negative symptoms were improved with rTMS relative to sham stimulation. There was no effect of rTMS in the positive symptom subscale in relation to sham stimulation. Discussion: Extracellular dopamine concentration in the Nucleus accumbens is decreased or increased following low- or high-frequency rTMS (Jackson 2001). A deficit in dopamine transmission in the prefrontal cortex might be implicated in the cognitive impairments and negative symptoms of schizophrenia (Weinberger 1988). The preliminary results of this study suggest a therapeutic effect of rTMS on negative symptoms in schizophrenia.

30 Effect of left prefrontal high frequency repetitive transcranial magnetic stimulation (rTMS) on cardiac autonomic nervous system (ANS) function in schizophrenia J Cordes1, M Arends1, A Mobascher1, J Brinkmeyer1, M Jänner1, W Wölwer1, K Krieger1, A Klimke1, MW Agelink2 1 Klinik und Poliklinik für Psychiatrie und Psychotherapie der Heinrich-Heine-Universität, Duesseldorf, Germany 2 Klinik für Psychiatrie, Psychotherapie und Psychosomatik an den Evangelischen Kliniken Gelsenkirchen, Ruhr-Universität Bochum, Germany Introduction: In schizophrenia the parasympathetic activity is significantly decreased, when the psychotic states are more pronounced (Toichi 1999). In healthy human subjects after slow rTMS heart rate variability (HRV) was significantly increased (Yoshida 2001). rTMS may activate the sympathetic nervous system. The study was realized to evaluate the effects of left prefrontal rTMS on ANS in schizophrenia. Methods: By using a sham-controlled randomised design 17 patients with schizophrenia were treated with 10 Hz rTMS over 10 days of the dorsolateral prefrontal cortex. The severity of schizophrenic symptoms was assessed by the positive and negative syndrome scale (PANSS). The 5-minute resting HRV was measured in both groups. HRV was serially measured during the third rTMS session. Results: Preliminary results indicate a significant increase in HRV in patients responding to rTMS. Discussion: Methodically it is difficult to distinguish between pure rTMS-related effects and secondary stress effects of the treatment. Our data suggest a direct association between psychopathological improvement to rTMS and corresponding changes of ANS function generated within the central autonomic network.

31 Influence of high frequency repetitive transcranial magnetic stimulation (rTMS) on electrophysiological correlates of facial affect recognition in schizophrenia and healthy humans J Cordes1, J Kotrotsios1, W Wölwer1, M Arends1, A Mobascher1, M Jänner1, J Brinkmeyer1 1 Klinik und Poliklinik für Psychiatrie und Psychotherapie der Heinrich-Heine-Universität, Duesseldorf, Germany Introduction: Deficits in recognition of facial expressions of emotions in schizophrenia have been widely described in literature (Morrison 1988). Longitudinal studies show that these deficits remain stable in the course of the illness, even in remitted states (Wölwer 1996). The electrophysiological activity of early components (P100, N170 and N240) might represent specific cerebral processes underlying decoding of facial expressions (Streit 1999). Disturbed facial affect recognition in schizophrenic patients might be a result of hypoactivity in inferior prefrontal areas (Streit 2001). The study was realized to evaluate the effect of left prefrontal high frequency rTMS on the facial affect recognition deficit in patients with schizophrenia. Methods: Using a sham-controlled randomized design 17 patients with schizophrenia and 16 healthy volunteers were included in the study. Patients were treated with high-frequency 10 Hz rTMS over 10 days. The ability to recognise emotional expressions of faces was tested. 32 electrodes EEG was recorded during performance of the

I/12 task. The measurements were made before the first, before and after the third and after the 10th session with rTMS. Results: In the spontaneous EEG we found a significantly increased activity in the inferior frontal gyrus, after verum rTMS treatment (p < 0.01). Patients significantly improve the identification rate of facial expressions after the verum rTMS treatment (p < 0.05). Of most interest is that we found as well significantly increased amplitudes at about 170ms (N170) and 240 ms (P240) after the verum rTMS treatment. No effect was observed in the sham group. Discussion: The EEG analyses indicate, that rTMS can influence cortical activities significantly. High frequency rTMS over the left dorsolateral prefrontal cortex may be a therapeutic approach to improve the recognition deficit in schizophrenia. 32 Influence of high frequency repetitive transcranial magnetic stimulation (rTMS) on serum monoamines in schizophrenia J. Cordes1, A. Mobascher1, M. Arends1, J. Brinkmeyer1, M. Jänner1, U. Henning1, M. W. Agelink2, A. Klimke1 1 Klinik und Poliklinik für Psychiatrie und Psychotherapie der Heinrich-Heine-Universität, Duesseldorf, Germany 2 Klinik für Psychiatrie, Psychotherapie und Psychosomatik an den Evangelischen Kliniken Gelsenkirchen, Ruhr-Universität Bochum, Gelsenkirchen, Germany Introduction: Plasma and serum indices of monoaminergic activity reflect partly the illness of schizophrenia (Oades, 2002). The blockade of dopamine receptors by neuroleptics leads to initial sharp increase and subsequent decrease in dopamine release and metabolism, as indicated by changes in plasma homovanillic acid (HVA) (Kendler, 1984). The study was realized to evaluate the effects of rTMS on serum monoamines in schizophrenia. Methods: By using a sham-controlled randomized design 17 patients with schizophrenia were treated with 10 Hz rTMS over 10 days of the dorsolateral prefrontal cortex. HVA and 3-methoxy-4-hydroxy phenyl glycol (MHPG) were serially measured in the serum during the third session with rTMS. Results: Preliminary data indicate a significant decrease of HVA during the course of a rTMS trial. In the sham group we found an increase of noradrenaline and the metabolite HVA. Discussion: Increased HVA levels were shown to be associated with negative symptoms (Zhang 2001). In the literature during antipsychotic treatment the concentrations of HVA and MHPG were significantly reduced only in the schizphrenics who responded to the treatment (Nagaoka 1997). We found an improvement of negative symptoms (PANSS) after treatment with rTMS. This was in line with the decrease of HVA during the course of a rTMS trial. In the sham group the increase of noradrenaline and HVA may reflect particularly an unspecific sympathetic activation by rTMS. 33 Role of the 5-HT1A-receptor in psychiatric disorders J Deckert Department of Psychiatry, University of Münster, Germany Serotonin is one of the pivotal neurotransmitters for mental disorders. Its effects are mediated via serotonin receptors, one of which is the serotonin 1A receptor (5-HT1A). The 5-HT1A receptor has been studied now for about 20 years using different paradigms and methodological approaches. Selective 5-HT1A agonists indicated a role for the 5-HT1A receptor in the pathophysiology of anxiety disorders on the basis of animal as well as human studies. The 5-HT1A knockout mouse subsequently was shown to be more anxious than its wildtype counterpart. Autopsy studies indicated a role for frontal 5HT1A receptor in the pathophysiology of schizophrenia and several of the newly developed atypical antipsychotics display a marked affinity for 5-HT1A receptors. More recently, the human 5-HT1A receptor gene was characterized. Several polymorphisms have been described. One of them, in the promotor region of the gene, was shown to be functionally relevant. Association studies revealed that this functional polymorphism may be a susceptibility variant for several

mental disorders, e. g. panic disorder and depression. This may be explained by the observation that this polymorphism codetermines the personality trait harm avoidance. Possibly, it modulates personality features in such a way that it is a vulnerability factor for several mental disorders. 34 Advantage of aripiprazole in a patient with Tourette’s syndrome S Dehning, M Riedel, N Müller Psychiatric Hospital, Ludwig-Maximilian-University, München, Germany Antipsychotics are still the first choice in pharmacotherapy. Increasing literature points out advantages of atypicals, at least regarding side effects [1].We describe a patient suffering from TS who withdrew treatment from different neuroleptics, thus leading to severe social consequences for many years. The 19-year-old patient suffered from motor and vocal tics since the age of six. We started treatment with 10 mg aripiprazole daily. In the first week motor and vocal tics showed marked improvement, after two weeks she was nearly tic-free for the first time. Amenorrhea or galactorrhea were not present during the next months, other side effects such as sedation or weight gain did not occur. Aripiprazole is an antipsychotic with a partial dopamine antagonism and agonism, showing effects on 5HT2A and 5HT1A receptors. The advantageous side-effect profile has been described earlier, however, no effects in TS have been observed. Reference 1. Robertson MM, Schnieden V, Lees AJ (1990) Management of Gilles de la Tourette Syndrome using sulpiride. Clin Neuropharmacol 13:229–235 35 Antidepressant efficacy and patient’s acceptance of a new formulation of mirtazapine (Remeron SolTab®) in depressed patients in the practice A Delini-Stula1, R Bischof1, A Desax2 1 ADI International Institute for Advancement of Drug Development, CH-Basel 2 Organon AG, CH-Pfäffikon In order to test the patient’s acceptance, compliance with treatment and the qualities of a new, easy dissolvable, oral formulation of mirtazapine (Remeron SolTab), a large (N = 1121) prospective, observational study of depressed patients was carried out in 184 Swiss centers. A specific self-assessment of the qualities and tablet acceptance (8-items check list) was done at the end of the study. PP population (N = 1056) was used for the analysis of drug acceptance. The analysis showed definite/probable preference for SolTab in 66 % of patients. Good and agreeable taste were appreciated by > 70 % and easy dissolution in the mouth by 84 % of patients. 67 % found that it is easier to use the SolTab and > 50 % of patients stated that they will be more compliant with this than conventional tablets. 72 % of patients were willing to continue the treatment with Remeron SolTab after study termination. In conclusion, the results of this study indicate that the use of Remeron SolTab may considerably improve the compliance of patients treated with mirtazapine in the daily practice. 36 A day-to-day experience with Mirtazapine (Remeron SolTab®), a new NaSSA antidepressant, in the treatment of depressed patients in the practice A Delini-Stula1, R Bischof1 and A Desax2 1 ADI International Institute for Advancement of Drug Development, CH-Basel 2 Organon AG, CH-Pfäffikon We report the results of a day-to day clinical experience with a new, improved formulation of mirtazapine (Remeron SolTab) in the

I/13 management of depression in the psychiatric practice in Switzerland. An open, multicentre, prospective observational study of 8 weeks duration in male and female patients (> 18 years old) with moderate to severe depression (1st episode, recurrent and chronic) was carried out in 184 Swiss centres and included 1121 patients. Antidepressant efficacy (CGI 7-points) and specific assessments (4-points scales) of the severity of anxiety and insomnia (early and late) were recorded at baseline, after 2 and 8 weeks of treatment. Spontaneously reported adverse events (AE) and the acceptance of the new formulation (8-items check-list) were recorded as well. ITT population (LOCF principle) was used for the analysis of the results. The results showed very good/good improvement in almost 70 % of patients. The drug was equally effective in mild, severe (> 50 % of included patients) and all form of depression. Anxiety and insomnia regressed early, linearly and highly significantly (p < 0.001) independently of initial severity. The most frequent AEs were sedative effects (8.4 %), weight increase (4.7 %), dizziness (2 %) and nausea/vomiting (1.3 %). The acceptance of the treatment was very good and in 72 % of patients the therapy was continued after study termination. This large, observational study demonstrated again antidepressant and,particularly,anti-anxiety and sleep-improving efficacy of Mirtazapine. The new Remeron SolTab formulation was also very well accepted by the majority of patients. 37 Role of glutathione deficit in the disconnectivity syndrome in schizophrenia: from pathogenetic mechanisms to therapeutic interventions 1KQ Do; 2P Bovet; 1JH Cabungcal; 1V Castagné; 3F Gheorghita; 3JP Hornung; 4F Schenk; 1P Steullet; 1M Tosic, 1M Cuenod 1Centre for Psychiatric Neuroscience, 1, 2Dept Adult Psychiatry; 3Dept Cellular Biology and Morphology, 4Inst Physiology, 1, 2, 3, 4Lausanne Univ; Switzerland. In the cerebrospinal fluid of 26 drug-naive schizophrenics (DSM-IIIR), we observed that the level of glutathione ([GSH]) and of its metabolite γ-Glu-Gln was decreased by 27 % and 16 % respectively. Using a new in-vivo method based on magnetic resonance spectroscopy, [GSH] was measured in the medial prefrontal cortex of 18 schizophrenics and found to be 52 % lower than in controls (n = 20). This is consistent with the recently observed decreased mRNA levels in fibroblasts of patients (n = 32) of the two GSH synthesizing enzymes (glutathione synthetase (GSS), and glutamate-cysteine ligase M (GCLM) the modulatory subunit of glutamate-cysteine ligase). Moreover, the level of GCLM expression in fibroblasts correlates negatively with the psychopathology (positive, general and some negative symptoms). Thus, the observed difference in gene expression is not only the cause of low brain [GSH], but is also related to the severity of symptoms, suggesting that fibroblasts are adequate surrogate for brain tissue. A hypothesis was proposed, based on a central role of GSH in the pathophysiology of schizophrenia. GSH is an important endogenous redox regulator and neuroactive substance. GSH is protecting cells from damage by reactive oxygen species generated, among others, by the metabolism of dopamine. A GSH deficit-induced oxidative stress would lead to lipid peroxidation and micro-lesions in the surrounding of catecholamine terminals, affecting the synaptic contacts on dendritic spines of cortical neurones, where excitatory glutamatergic terminals converge with dopaminergic ones. This would lead to spines degeneration and abnormal nervous connections or structural disconnectivity, possibly responsible for positive, perceptive and cognitive symptoms of schizophrenia. In addition, a GSH deficit could also lead to a functional disconnectivity by depressing NMDA neurotransmission, in analogy to phencyclidine effects. Present experimental biochemical, cell biological and behavioral data are consistent with the proposed mechanism: decreasing pharmacologically [GSH] in experimental models, with or without blocking DA uptake (GBR12909), induces morphological and behavioral changes similar to those observed in patients. Dendritic spines: (a) In neuronal cultures, low [GSH] and DA induce decreased density of neural processes; (b) In developing rats (p5-p16), [GSH] deficit and GBR induce a decrease in normal spines in prefrontal pyramids and in GABA-parvalbumine but not of -calretinine immunoreactivity in anterior cingulate. NMDA-dependant synaptic plasticity: GSH deple-

tion in hippocampal slices impairs long-term potentiation. Developing rats with low [GSH] and GBR have deficit in olfactory integration and in object recognition which appears earlier in males than females, in analogy to the delay of the psychosis onset between man and woman. In summary, a deficit of GSH and/or GSH-related enzymes during early development could constitute a major vulnerability factor in schizophrenia. 38 The role of pharmacogenetics in the pharmacological treatment of psychiatric disorders CB Eap, P Baumann Unit of Biochemistry and Clinical Psychopharmacology, Center of Psychiatric Neuroscience, University Department of Adult Psychiatry, Hospital of Cery, Prilly, Switzerland. Pharmacogenetics is the study of the variability of response to drugs due to genetic factors. It tries to answer the question why a standard dose of any drug will produce either no therapeutic response in some patients, or side effects or even toxicity in others. Thus, the implication of several isozymes of the cytochrome P450 family in the metabolism of psychotropic drugs, isozymes which present a genetic polymorphism with the existence of poor, extensive or ultrarapid metabolizers, largely explains the interindividual variability of the pharmacokinetics of psychotropic drugs. Examples of genetic polymorphism of cytochromes P450s, with clinical consequences for psychotropic drug treatment, will be presented. Polymorphism of other genetic factors (e. g. transporters, receptors) and the possible use of pharmacogenetic tests before or during a pharmacological treatment will also be discussed. 39 Effects of alprazolam on cholecystokinin-tetrapeptide (CCK-4) induced panic in healthy volunteers D Eser, P Zwanzger, S Aicher, C Schüle, TC Baghai, F Padberg, R Ella, HJ Möller, R Rupprecht Department of Psychiatry, University of Munich, Germany Introduction: Cholecystokinin-tetrapeptide (CCK-4) induces panic attacks both in patients with panic disorder and healthy volunteers.A reduction of CCK-4 induced panic has been demonstrated after treatment with antidepressants and after selective GABAergic treatment with vigabatrin and tiagabin. Although benzodiazepines are widely used as anxiolytics, no controlled study on their effects on CCK-4 induced panic is available so far. Methods: We investigated the effects of alprazolam on CCK-4 induced panic in a double blind, placebo-controlled study in 30 healthy volunteers. 26 subjects showed a marked panic response to CCK-4. These were rechallenged after pretreatment with 1 mg alprazolam or placebo one hour prior to the second CCK-4 challenge. Panic was assessed using the Acute Panic Inventory (API) and a DSM-IV derived panic symptom scale (PSS). Blood samples were taken for determination of ACTH and cortisol plasma levels. Results: We found a significant reduction of the API and PSS-score after alprazolam treatment compared to placebo. Moreover, compared to placebo we found a significant blunting of CCK-4 induced ACTH and cortisol release. However, also placebo treatment reduced both CCK-4 induced anxiety and HPA-axis activation to a certain extent. Discussion: In conclusion, our data show a marked reduction of CCK-4 induced panic and HPA-axis activation after pretreatment with alprazolam, which supports the hypothesis of a possible interaction of the GABA and the CCK system.

I/14 40 The role of gene expression in understanding the function of risk genes P Falkai, T Bayer Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum des Saarlandes, Germany The term “proteome” describes the protein complement of a genome. Proteomes of cells are dynamic and are directly affected by environmental factors, such as stress and/or drug treatment, or as a result of aging and disease. One of the distinct advantages of proteomic analysis, not attainable with RNA expression data, is the ability to fractionate the cell’s proteins into various subpopulations. In neuroscience, “neuromics” (proteomics in the central nervous system) is in its infancy, with a paucity of studies in the context of the brain. One of the objectives of this review is to illustrate the potential of neuromics to profile differences in the distribution of thousands of proteins as a function of disease markers. One possibility to identify differences in the proteome of patients with schizophrenia can be attained by profiling postmortem brain samples of key brain regions. We have built up a postmortem brain bank of patients with schizophrenia (n = 20) and non-psychiatric age and sex-matched control individuals (n = 30). One part of the tissues have been collected in a prospective manner, allowing to correlate not only age of onset and duration of disease, but also a variety of other parameters like drug intake, brain area volume and psychological scores with changes in the proteome. Several approaches have been carried out in the past to study the proteome in schizophrenia (Edgar et al., 1999; Johnston-Wilson et al., 2001; Marcotte et al., 2003; Kim et al., 2004). In the present attempt, we have the advantage to be able to compare brain areas from both hemispheres, in addition to unravel the influence of the factors collected prospectively. 41 Neurophysiological aspects of alcohol dependence and withdrawal AJ Fallgatter, AC Ehlis, J Böning, MJ Herrmann Dept. for Psychiatry and Psychotherapy, University of Wuerzburg, Germany Fast occurring emotional and cognitive processes are of great relevance in the brain mechanisms related to alcohol dependence and withdrawal. Based on their optimal time resolution, event-related potentials (ERPs) are suitable methods for the measurement of the neurophysiological basis of alcohol dependence and withdrawal. Besides the classical, nevertheless rather unspecific finding of reduced P300 amplitudes in the acoustic oddball-paradigm, there exist some newer approaches in patients with alcohol dependence: In 25 alcohol-dependent patients there has been described a loudness dependency of the so-called N1/P2 amplitude as a neurophysiological indicator of serotonergic neurotransmission in the CNS, which significantly correlates with Cloninger’s personality dimension “harm avoidance” being an also serotonergically modulated indicator of relapse (Herrmann et al., 2002). In some alcohol dependent patients a relapse is triggered by learned cues. ERPs have been applied to investigate neurophysiological correlates of such a cue reactivity. In 19 male alcohol dependent patients and 19 age- and gender-matched healthy controls the presentation of 15 alcohol specific and 15 neutral words has been used to measure ERPs with 21 scalp electrodes. Analysis of the data was performed in three time segments defined in a data-driven manner. Alcohol dependent patients were characterized by a specific cue reactivity, as they displayed significantly higher amplitudes in the ERPs elicited by alcohol specific as compared to neutral stimuli. Such a cue effect was seen also in opiate dependent patients as well as in “social drinkers” not fullfilling the diagnostic ICD-10 criteria for alcohol dependency, but not in healthy control participants (Herrmann et al., 2000, 2001). The so-called NoGo-anteriorisation (NGA) elicited in a Go-NoGo paradigm allows a stable and reliable functional measurement of prefrontal brain areas, in particular the cognitive areas of the anterior cingulated cortex (Fallgatter et al., 1997, 2002). Alcohol dependent patients investigated at the 10th day after beginning of a qualified withdrawal treatment were characterized by enlarged NGA values which normalized during the following weeks (Fallgatter et al.,

1998). This finding was interpreted as an indication of increased neuronal activity in the prefrontal cortex during cognitive activity in the early phase of a withdrawal. Based on these and other results, further ERP studies aiming on the selection of patients for a behavioural exposure treatment (cue reactivity) and on the clinical meaning of these neurophysiological parameters for the prognosis of the severity of the withdrawal (NGA) and the risk for relapse (N1/P2-amplitude) are warranted. 42 NIRS in psychiatry AJ Fallgatter, AC Ehlis, C Baehne, MJ Herrmann Dept. for Psychiatry and Psychotherapy, University of Wuerzburg, Germany Abstract NIRS is a non-invasive optical method for the assessment of cortical concentration changes in oxygenated (O2Hb) and deoxygenated (HHb) haemoglobin as indicators of cortical brain activation. The advantages of the NIRS method are that its application is fast, without any side-effects, relatively unsensitive for movement artifacts and possible in an adequate setting in particular for psychiatric patients (sitting, relaxed position, no narrowness, no noise). Results will be exemplified in an investigation of patients with Alzheimer’s disease (AD) measuring changes in O2Hb and HHb concentrations of the parieto-occipital cortex during a spatial task,the modified version of the Benton Line Orientation Task (Gur et al., 2000). 14 patients with AD and 14 exactly age- and sex-matched healthy subjects were measured with NIRS while they had to estimate the orientation of a given line or to name the colour of the line in the control condition. Both conditions consisted of three activation phases each lasting 30 seconds, with a 10 second baseline and a 20 second post resting period. For assessing the changes in O2Hb and HHb concentrations 24 NIRS channels over the parietal cortex were measured using the NIRS apparatus ETG-100 (Hitachi Ltd.). In healthy elderly subjects, O2Hb concentration significantly increased during the active phase compared to the baseline for both conditions, while the O2Hb concentration was significantly higher in the active phase for the line orientation condition as compared to the colour naming condition bilaterally parietooccipital. In contrast, patients with AD displayed a significantly diminished activation (less pronounced increase of O2Hb concentration) in the line orientation as compared to the colour naming condition. The results indicate a dysfunction of widely distributed areas of the parieto-occipital cortex in AD and further underscore the value of multi-channel NIRS for assessing cortical activation during cognitive tasks. Further studies addressing the value of the NIRS method for an early diagnosis as well as for the monitoring of therapeutic effects in AD are warranted. 43 Neurophysiological changes in schizophrenic diseases – altered response control AJ Fallgatter, A-C Ehlis, MJ Herrmann Dept. of Psychiatry and Psychotherapy, University of Wuerzburg, Germany In schizophrenic patients, an altered function of the anterior cingulate cortex (ACC) as an important region of the prefrontal cortex interconnected with limbic areas has been demonstrated during various cognitive activation tasks. Two- (NoGo-anteriorization; NGA) and three-dimensional topographical measures (source locations with the Low Resolution Electromagnetic Tomography; LORETA) of the event-related potentials elicited during the execution (Go) and the inhibition (NoGo) condition of the Continuous Performance Test allow an assessment of anterior cingulate function with extraordinary high interindividual stability and retest reliability. These methods revealed a significant brain electrical hypoactivity in the ACC of schizophrenic patients, but not in cycloid psychoses, as compared to ageand gender-matched controls. Both a neuropsychological index of ACC performance and the proposed electrophysiological measure of this region have been shown to be improved in patients treated with atypical but not with typical neuroleptics. These results support the

I/15 notion that a functional deficit of the ACC during response control is a core feature in schizophrenias, which can be improved by atypical neuroleptic treatment. 44 Measurement of evoked far-field potentials from the vagus nuclei in the brainstem – new diagnostic possibilities for neurodegenerative disorders? AJ Fallgatter, TM Ringel, AC Ehlis, MJ Herrmann Dept. for Psychiatry and Psychotherapy, University of Wuerzburg, Germany Recently, the vagus nuclei in the brainstem have come into the focus of interest in psychiatric and neurological research mainly for two reasons: Firstly, their function is altered early in the course of both in Alzheimer’s (Parvizi et al., 2001) and Parkinson’s disease (Del Tredici et al., 2002; Braak et al., 2003). Secondly, the electrical stimulation of the left vagus nerve in the neck by means of an implanted stimulator has proven to have additional therapeutic effects in both epilepsy and depression being resistant to standard pharmacological treatment. Based on these findings a method for the non-invasive measurement of far-field potentials from the vagus nuclei evoked by means of an electrical stimulation via a peripheral branch of the nerve in the outer ear is a potentially interesting diagnostic procedure. It has already been shown that such a Vagus Sensory Evoked Potential (VSEP) can be elicited in a reliable manner in younger and elderly healthy subjects (Fallgatter et al., 2003) and that its latency but not its amplitude measures correlate highly significantly with the age of the participants. Further studies are under way which systematically investigate changes in VSEP measures in patients with neurodegenerative and depressive disorders. 45 Fibre trajectography extracted from diffusion tensor imaging (DTI) A Federspiel, D Hubl, R Kreis, WK Strik and T Dierks University Hospital of Clinical Psychiatry, Dept. of Psychiatric Neurophysiology, Bern, Switzerland Inselspital, Dept. of Neuroradiology, Bern, Switzerland Diffusion weighted magnetic resonance imaging (DT-MRI) provides a method for the measure of diffusivity. The evaluation of the fiber tract trajectory is feasible (Conturo et al. 1999). Based on the calculation of a set of three eigenvectors we extract fiber trajectories using the gradient descent method. Data from six controls were acquired using DTI. The accuracy of the method for the construction of fibers was assessed using Monte Carlo simulation of DT-MRI data. Preliminary results are presented which shows that fiber reconstruction in DTI data is possible when the signal-to-noise ratio is Rici distributed (Basser and Pajevic 2000). References Basser PJ, Pajevic S (2000) Statistical artifacts in diffusion tensor MRI (DT-MRI) caused by background noise. Magn Reson Med 44:41–50 Conturo TE, Lori NF, Cull TS, Akbudak E, Snyder AZ, Shimony JS, McKinstry RC, Burton H, Raichle ME (1999) Tracking neuronal fiber pathways in the living human brain. Proc Natl Acad Sci U S A 96: 10422–10427 46 BOLD- and ASL- (Arterial Spin Labeling) -fMRI during visual stimulation A Federspiel1, C Kiefer2, TJ Müller1, H Horn1, M Wirth1, P Bianchi1, W Strik1, T Dierks1 1 University Hospital of Clinical Psychiatry, Dept. of Psychiatric Neurophysiology, Bern, Switzerland 2 Inselspital, Dept. of Neuroradiology, Bern, Switzerland In functional magnetic resonance imaging (fMRI) experiments blood oxygenation level dependent activity contrast (BOLD) and perfusion contrast obtained using arterial spin labeling (ASL) techniques are

used (Detre et al., 2002). The BOLD signal is the result of a complex interaction between changes in blood flow, blood volume, and oxygenation consumption originated by neural activity. In fMRI based on perfusion the contrast is a result of the utilization of magnetically labeled arterial blood water as a diffusible tracer for CBF measurements, in a manner analogous to that used for 15O PET scanning (Ye et al., 2000). The validity of ASL fMRI was recently demonstrated in a study using a finger tapping paradigm on normal controls (Wang et al., 2003). We investigated the quality of BOLD and ASL fMRI during visual stimulation on eleven controls. The aim of the present study was to determine the validity of both methods for visual “checker board stimulation”. Quantitative perfusion data during resting and stimulus condition are presented for primary visual cortex (V1). The temporal pattern of both, the BOLD signal and the CBF signal are highly correlated with the time pattern of the paradigm. 47 New candidate genes for heavy alcohol drinking and alcohol withdrawal derived from clinical findings and animal studies C Fehr1, A Tadic1, A Szegedi2, I Anghelescu2, T Sander3, K Lenzen3, K Buck4, LG Schmidt1 1 Department of Psychiatry, University of Mainz, Germany, 2 Department of Psychiatry, Charité – Campus Benjamin Franklin, University of Berlin, Germany, 3 Gene mapping center and Department of Molecular Genetics, Max Delbrück Center, Berlin, 4 Portland Alcohol Research Center, Oregon Health & Sciences University, Portland, Oregon, U. S. A. Behavior genetics in mice inbred strain crosses has yielded a detailed map of gene loci contributing to different ethanol-mediated behaviors such as ethanol preference drinking, ethanol place preference and ethanol withdrawal. High resolution mapping, gene sequencing and gene expression experiments identified the gene encoding the multiple PDZ domain protein (Mpdz) as a highly likely candidate gene for a quantitative trait locus (QTL) that accounts for 26 % of the genetic variance in acute alcohol withdrawal severity in mice (Fehr et al., J. Neurosci 22: 3730, 2002; Shirley et al., Nat. Neurosci. 7 [7]: 699–700). In the current study, we tested the association between the human MPDZ gene as well as other likely candidate genes identified by animal studies and alcohol dependence among alcohol dependent patients and healthy volunteers. MPDZ was not associated with severity of alcohol dependence and the experience of an ethanol withdrawal seizure. There were positive correlations between polymorphisms within the Syntaxin binding protein 1 gene (STXBP1), the human homologue of a mouse candidate gene for ethanol preference drinking, and some, but not all measures of heavy alcohol drinking. Testing candidate genes across different species will thereby increase our knowledge on their role for different alcohol phenotypes and alcoholism. 47 Diffusion tensor imaging (DTI) in patients with Fabry’s disease: preliminary results of a prospective study A Fellgiebel1, P Wille2, KM Müller1, C Whybra3, M Beck3, P Stoeter2, A Scheurich1, K Mann1, LG Schmidt1, MJ Müller1 1 Department of Psychiatry, University Mainz, Mainz, Germany 2 Institute of Neuroradiology, University Mainz, Mainz, Germany 3 Centre for Lysosomal Storage Disorders, Children’s Hospital, University Mainz, Mainz, Germany Background: Fabry’s disease (FD) is associated with extensive sphingolipid accumulation in vascular endothelium. Diffusion tensor imaging (DTI) is a new, sensitive technique to quantify pathological changes of brain tissue integrity. In an ongoing prospective study DTI findings will be related to frequently occurring cognitive and psychiatric symptoms in FD. Methods: Neuropsychiatric assessments, conventional MRI, and DTI scans were obtained from 16 FD patients and 10 age-matched controls. Mean Diffusivity (MD) and Fractional Anisotropy (FA) were measured in various brain areas.

I/16 Results: Except for right thalamic regions, FA values were consistently decreased in FD patients. FD patients showed significantly elevated MD values in the area of the right posterior cingulate fascicle and the left anterior thalamic nuclei. In other regions of interest nonsignificant elevations of MD values could be detected. DTI parameters were not related to gender or age. Correlations of DTI and neuropsychiatric variables will be presented. Conclusion: This is the first DTI investigation in FD. Decreased anisotropy indicating violation of white matter integrity and elevated diffusivity which can occur as a consequence of neuron cell loss could be detected in nearly all studied regions in FD patients implying widespread ultrastructural brain tissue disturbances possibly due to microvascular dysfunction.

49 In vivo [123I]-ADAM binding to serotonin transporters in the human brain and platelets: a correlation analysis L Franke1, M Plotkin2, H Amthauer2, R Felix2, R Uebelhack1 1 Department of Psychiatry, Campus Mitte 2 Radiology Clinic, Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, Germany Blood platelets seem to be a useful peripheral model for the investigation of central serotonergic mechanisms. To validate this hypothesis, we used the selective serotonin transporter (SERT) site ligand [123I]-ADAM and SPECT and examine 5 drug free depressed patients and 6 healthy subjects for the ligand binding in the brain and platelets in parallel. SPECT images and blood samples were obtained 2h and 4h after a bolus injection of [123I]-ADAM. Regions of interest (ROI) were drawn manually in areas corresponding to the midbrain, frontal cortex and cerebellum. Blood plasma and platelets were analyzed for total radioactivity. Whereas the platelet-bound total activity was highly correlated with the total activity in the midbrain and the cerebellum, the ratios of specific to nonspecific binding (ROI-cerebellum/cerebellum) were not related to the radioactivity measured in blood plasma or platelets. Although these findings are preliminary, the results indicate similarities in the availability of SERTs for the [123I]-ADAM binding in defined brain regions and platelets.

50 SSRI overdoses are remarkably less frequent than TCA overdoses in an emergency department R Frey1, J Kindler1, A Bur2, A Heiden1, A Laggner2, S Kasper1 1 Department of General Psychiatry, Medical University of Vienna, Austria 2 Department of Emergency Medicine, Medical University of Vienna, Austria Objective: From 1992 to 1997, 263 patients were hospitalized with pharmacological intoxications in the emergency ward at the Vienna General Hospital. In the same period SSRI surpassed TCA concerning prescription frequencies. The aim of the study was to examine the frequency and severity of suicidal overdose with special focus on antidepressants. Method: Retrospective data on all intoxicated patients admitted to the ED have been analysed. Antidepressants were divided in the following subgroups: tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), other antidepressants (OAD). Mono- and polyintoxications were analysed seperately. Intubation was supposed as major variable to reflect the severity of the intoxication. Results: All together, 130 monointoxications and 133 polyintoxications were hospitalized. 104 intoxications were caused by antidepressant medication (22 mono and 82 poly). Within this group, TCA were involved in 83 cases (22 mono and 61 poly), SSRI in 10 (10 poly), OAD in 11 (11 poly). From the total sample of 263 patients, 87 (33 %) had to be intubated (24 mono and 63 poly). Polyintoxications were significantly more often intubated than monointoxications (p < 0.001). In case of TCA overdose, there was no significant difference between the intubation rate in mono- (50 %) and polyintoxica-

tions (61 %). The intubation rate was 40 % in SSRI polyintoxications and 64 % in OAD polyintoxications. Conclusion: The main finding was a remarkably lower number of SSRI intoxications compared to TCA intoxications despite of approximately equal prescription frequencies in the observation period. The intubation rate in TCA monointoxications could not be compared to SSRIs or OADs since there were no monointoxications in the latter groups. 51 Effects of Amitriptyline, Fluoxetine, Tranylcypromin and Venlafaxine on rat aortal smooth muscle tone in vitro H Frieling1, D Pavlovic2, J Kornhuber1, C Lehmann2, S Bleich1 1 Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany 2 Department of Anaesthesiology and Intensive Care Medicine, University of Greifswald, Greifswald, Germany Background and Aim: Hypotension is an often seen side effect of antidepressive treatment. It still remains controversial whether this is a central or peripheral effect.We tested amitriptyline (AMI), fluoxetine (FLUO), tranylcypromin (TRAN) and venlafaxine (VENLA) for their vasoactive properties in an in vitro isometric preparation of rat thoracic aortal rings with and without endothelium (+ and – End). Material and Methods: The effects of cumulative concentrations (10nM-100µM) of the antidepressants on tension elicited by 20mM KCl were examined. We also tested the influence of preincubation (20min) with the substances (500nM) on KCl (5–100mM) induced contraction. Results: AMI, FLUO and VENLA produced complete relaxation of aortal preparations, those + End being more sensitive to FLUO (EC50: 5.57 ± 0.04 vs. 4.96 ± 0.03; + vs. -End; -logM; mean ± SEM; n = 4; P < 0.01).Tranylcypromin only produced small relaxation.Incubation with antidepressants had no significant effect on KCl-induced tension. However, AMI ( ± End) and VENLA (+ End) seemed to reduce maximum tension. Conclusion: We found that AMI, FLUO and VENLA have direct effects on vascular smooth muscle and that FLUO-induced vasodilation is partially endothelium-dependent. These results indicate that hypotension due to antidepressant treatment may partially be caused by peripheral, vascular effects of the drugs. 52 Neuropsychological aspects in delirium A Gabriel1, A Diefenbacher2, FM Reischies3 1 Klinik für Psychiatrie und Psychotherapie der Charité Berlin, Campus Mitte, Germany 2 Klinik für Psychiatrie und Psychotherapie des Königin Elisabeth Krankenhauses Herzberge, Berlin, Germany 3 Klinik für Psychiatrie und Psychotherapie der Charité Berlin, Campus Benjamin Franklin, Germany Objective: Few investigations exist that analyse neuropsychiatric deficits in delirium. The symptomatology is described rather homogeneously, due to the belief that delirium cannot be investigated because of the disturbance of consciousness. Methods: Using an extensive battery of tests we examined the cognitive status of 94 successively diagnosed delirious patients. According to the etiology three groups were assigned: 50 patients with an delirium in dementia (dd), 23 patients with an alcohol withdrawal delirium (awd) and 21 patients with a delirium due to other causes (doc). Results: There was a large neuropsychological heterogeneity among the three groups: the cognitive impairment of the dd patients differed significantly from the awd patients (p < 0.001 by ANOVA). One possible explication could be the underlying dementia. In addition different cognitive deficits could be demonstrated between awd and doc patients in the verbal fluency and in short time memory tests like repeating 10 words (p < 0.01 by ANOVA). Finally the testing of dd and doc patients yielded equal results in incremental addition and orientation scores. These observations point to the possibility that

I/17 differences in the cognitive functions of delirious patients are also due to dementia indepentend factors. Conclusions: A neuropsychological testing in delirium seems possible. Discussion: Following the findings we are discussing different neuropsychological tests helping to distinguish delirium according to its specific aetiology. 53 Brain-derived neurotrophic factor (BDNF) in depressive disorder N Gervasoni1, JM Aubry1, G Bondolfi1, C Osiek1, M Schwald2, G Bertschy1, F Karege2 1 Adult psychiatric service Department of psychiatry, University hospital of Geneva, Switzerland 2 Neuropsychiatric service Department of psychiatry, University hospital of Geneva, Switzerland BDNF is a member of the neurotrophin family. Its involvement in the pathophysiology of depressive disorders has been demonstrated over the past decade. BDNF is present outside the central nervous system, particularly in the platelets and at the serum level. Moreover, studies with animal models have shown that stress can diminish the expression of central BDNF and that this phenomenon can be counteracted by administering antidepressants. From these results arose the question of whether depression is accompanied by a diminished expression of BDNF at the level of the central nervous system.In a first study, we compared the levels of serum BDNF of 30 depressed patients with those of 30 healthy subjects, matched according to gender and age.We showed that BDNF concentrations were significantly lower in the depressed group as compared to the control group (22.6 ± 3 vs 26.5 ± 7 ng/ml, p = 0.01), although we observed a rather large overlap in the results of the two groups. We also showed that the more severe the depression, the lower the BDNF concentration. In a second study focussing on 26 patients and 26 controls, we showed that antidepressant treatment brought about a significant increase in serum concentrations of BDNF in depressed patients (22.5 ± 3.3 before treatment vs 24.4 ± 3.6 ng/ml after treatment). This increase was positively correlated with the weakness of the initial BDNF level on one hand and the severity of the initial depression on the other. In a third study, we examined whether the difference observed between depressed and control subjects for serum BDNF actually corresponded to a difference at the level of the platelet stocks of BDNF by measuring BDNF in whole blood (that is to say in the platelets and in the serum). Our results show that, when considering whole blood, there was no longer any difference between depressed and control subjects. This suggests that the difference observed at the serum level could correspond to a specific mechanism of release from the platelet stock. 54 Processing of positive versus negative emotion is incorporated in anterior versus posterior brain areas: an ERP microstate LORETA study LRR Gianotti, PL Faber, RD Pascual-Marqui, H Katayama, K Kochi, D Lehmann The KEY Institute for Brain-Mind Research, University Hospital of Psychiatry, Zurich, Switzerland. Time course and localization of brain electric incorporation of affective valence when reading emotionally loaded words was studied using event-related potential (ERP) microstate tomography (LORETA). Subjects were not aware of the study goal, but executed a memory task not directed to the words’ valence. The data (21 normals, 33 channels) while reading emotionally positive and negative words were transformed into potential maps. Microstate segmentation analysis during the 448 ms of word presentation classified the 113 ERP maps into 14 microstates (steps of information processing). Significant, global, topographic differences between positive and negative words were found in three of these microstates, #4 (90–122 ms), #7 (178–202 ms) and #9 (242–274 ms). These three microstates were further analyzed with LORETA functional tomography to identify the involved brain areas. LORETA revealed in all three microstates well-delimited areas of valence-driven, regional activation: In all three microstates, posi-

tive emotion words activated significantly more anterior brain areas than negative emotion words. But, there was no hemispheric preference: positive as well as negative word-evoked activity was clearly left hemispheric in microstates #4 and #9, but right hemispheric in microstates #7. These features were incorporated during nonattended, automated processing of emotional content while reading words merely for later recall. 55 Serotonergic and catecholaminergic candidate genes in suicidal behaviour and aggression-related traits I Giegling, HJ Möller, D Rujescu Molecular and Clinical Neurobiology, Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany Family and twin studies point towards a partial heritability of suicidal behavior and aggression-related traits. We investigated the role of a set of serotonergic and catecholaminergic candidate genes in these behaviors. 210 suicide attempters with various psychiatric disorders, and 420 healthy control subjects were included. The controls were randomly selected from the general population and had no relevant somatic and no psychiatric disorder. All subjects were administered standard psychiatric interviews including SCID as well as self-report questionnaires for anger-related traits. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin. With regard to a A218 SNP in the TPH gene, A-allele carriers in both groups showed higher scores for State Anger, Trait Anger and Angry Temperament. These findings replicate an earlier study closely, and the effect on anger was more pronounced in the high risk group of suicide attempters. Furthermore, a meta-analysis provided strong evidence for an association of suicide-related behavior with the A218 SNP in the TPH gene in Caucasians. Catechol-O-methyltransferase (COMT) is an enzyme involved in catecholamine inactivation. We examined a functional COMT (V158M) polymorphism in this gene.VVcarriers expressed anger more inwardly and reported more stateanger while MM-carriers expressed their anger more outwardly. Interestingly, also allele and genotype frequencies coding for M were higher among violent suicide attempters. 56 Increase of slow wave sleep and regulation of sleep-wake rhythm under Ziprasidone in patients with schizophrenia, first observations of an open clinical study M Giesler, A Thum, R Rocamora, M Huber, JC Krieg, U Hemmeter University Clinic Marburg, Clinic of Psychiatry and Psychotherapy, Marburg, Germany Ziprasidone is an atypical neuroleptic which exerts its action mainly by an 5-HT2a receptor-antagonism. Substances with 5-HT2a-antagonism increase slow wave sleep (SWS) which in schizophrenia may be related to the expression of negative symptoms. No information about the effects of ziprasidone on sleep EEG are available. In two patients with schizophrenia medicated with ziprasidone a large amount of SWS (1 patient 26 %, 1 patient 63 %) has been observed. Therefore, in two further patients sleep-EEG has been evaluated at baseline (unmedicated) and under treatment with 80 mg ziprasidone for one week. Both patients increased substantially with SWS compared to baseline (from 20 % to 30 % SWS). Furthermore, actography showed a regulation of sleep-wake pattern immediately after the application of ziprasidone in one patient. The observed augmentation of SWS under ziprasidone is in line with sleep EEG findings found with other 5HT2a-antagonists, such as ritanserin and may be related to the beneficial effect on negative symptoms with these substances.

I/18 57 Intermanual coordination as an index of interhemispheric transfer in relation to subgroups of patients with schizophrenic and other psychotic disorders I Gorynia, V Campman, R Uebelhack Department of Psychiatry and Psychotherapy Charité – Universitätsmedizin Berlin, CCM, Berlin, Germany Background: Interhemispheric transfer in psychotic patients is still a controversial issue. Based on the fact that intermanual coordination is associated with interhemispheric transfer, scores in intermanual coordination were investigated in patients with psychotic disorders. Method: Intermanual coordination was assessed by alternating finger-tapping in 73 adult right-handed in-patients with schizophrenic and other psychotic disorders and was compared with that of 75 healthy right-handed controls. Five clinical subgroups of patients whose diagnoses were based on the DSM-IV classification were specified. Results: Scores in intermanual coordination in the patients as a whole did not differ from those of the controls. When, however, different clinical subgroups and various manifestations of symptoms were taken into consideration, the scores among those subgroups differed significantly. For instance, patients with residual schizophrenia and chronic symptoms showed lower values in intermanual coordination than did patients with schizoaffective disorders and prevailing acute symptoms. Conclusions: The assessment of intermanual coordination may provide new insights into the functional coupling of both hemispheres in schizophrenic and other psychotic disorders and may be of a certain prognostic value. Because of its non-invasive, fast and simple application, this approach is thought to be especially suited for investigating acute psychiatric in-patients. 58 Combining functional neuroimaging and experimental neuropsychology to investigate the functional integrity of brain systems in psychiatric disorders O Gruber Department of Psychiatry, Saarland University Hospital, Homburg (Saar), Germany The interpretation of abnormal activation patterns in functional neuroimaging studies under specific task conditions is only possible when patients can perform the task correctly. This prohibits direct investigation of the neural correlates of cognitive deficits in psychiatric disorders. Therefore, in order to identify brain systems that are disturbed in different psychiatric conditions it is necessary to combine functional neuroimaging studies in healthy human subjects with corresponding behavioral experiments in patients.We will exemplify this methodological approach in the area of working memory which is impaired in patients suffering from different psychiatric disorders. First, we will review recent functional neuroimaging studies providing evidence for the co-existence of two working memory systems in the human brain which differ from each other in terms of their functional-neuroanatomical implementation and presumably also with respect to their evolutionary origin. We will then show results from behavioral and neuroimaging experiments in neurological patients with circumscribed brain lesions which served to validate our methodological approach. Finally, we will report behavioral investigations in patients with schizophrenia and affective disorders that revealed specific dysfunctions of these brain networks involved in working memory. The findings of these studies may help to improve diagnostic accuracy and therapeutic efficiency.

59 Regional Gene-Chip-Array study in sporadic Alzheimer’s disease patients E Grünblatt1, J Li1, T Arzberger2, M Neumann3, S Kneitz4, R Ravid5, W Roggendorf2, P Riederer1 1 Clinic and Policlinic for Psychiatry and Psychotherapy, Clinical Neurochemistry, University of Würzburg, Würzburg, Germany 2 Department of Neuropathology, Institute of Pathology, University of Würzburg, Würzburg, Germany 3 Institute of Neuropathology, Ludwig Maximilians University of Munich, Munich, Germany 4 Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany 5 Netherlands Brain Bank, Amsterdam, The Netherlands. Although the etiology of Alzheimer’s disease (AD) is still unknown evidence accumulates indicating causal genetic aberrations at least in subgroup(s) of AD. However, while only a small percentage of AD is in fact of familiar origin, most patients belong to the group of sporadic AD. If genetic alterations are suggested for the latter subtype one could hypothesize that environmental influences or endogenous metabolic disturbances induce those genetic failures. With the advance of microarray technology, one can observe relative gene expression of the entire known human genome, permitting discovery of novel genes and pathways involved in disease. This exploration-driven experimental approach is expected to lead to a deeper understanding of neurodegenerative disorders. Objectives: To assess gene expression in the AD and control ammon’s horn (hippocampus) cerebellum and gyrus frontalis medius (Gfm), and to relate differences in gene expression to individual clinical and neuropathological profiles. Methods: All tissue was obtained from the German Brain Bank Net and the Netherlands Brain Bank. We used Affymetrix U133 A & B oligonucleotide microarray chip sets to analyse gene expression in the hippocampus Gfm and cerebellum of AD subjects. Analysis of the gene expression was conducted on the VectorExpression (Invitrogen) software. Additionally, in order to confirm some of the genes alterations we used the quantitative real-time RT-PCR methodology. Results: We found that genes involved in energy metabolism, vesicular trafficking transporters, channels, receptors, cell cycle, translation proteins, signal transduction and regulatory proteins have been altered in the AD subjects in different patterns in each brain region. Conclusions: We demonstrate that gene expression pattern in post mortem brain regions [1] differs between brain areas and [2] comparison between controls and AD clearly demonstrates significant alterations at the level of gene expression indicating [3] that in sporadic AD gene failures are rather the consequence than the primary event in the cascade of cell death mechanisms. 60 What does PET tell us about the mechanism of action of antipsychotics? G Gründer1, 5, C Landvogt2, I Vernaleken1, HG Buchholz2, J Ondracek1, T Siessmeier2, S Härtter1, P Stoeter3, DF Wong6, 7, C Hiemke1, F Rösch4, P Bartenstein2 1 Department of Psychiatry, University of Mainz, Mainz, Germany 2 Department of Nuclear Medicine, University of Mainz, Mainz, Germany 3 Institute of Neuroradiology, University of Mainz, Mainz, Germany 4 Institute for Nuclear Chemistry, University of Mainz, Mainz, Germany 5 Department of Psychiatry and Psychotherapy, Technical University of Aachen, Aachen, Germany 6 Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, USA 7 Department of Psychiatry, Johns Hopkins Medical Institutions, Baltimore, USA Numerous PET and SPECT studies performed over the last twenty years have led to a profound understanding of the relationships between antipsychotic doses and plasma levels on the one hand and oc-

I/19 cupancy of (striatal) D2-like dopamine receptors on the other hand as well as with the associated clinical effects and side effects. These techniques also helped to generate hypotheses regarding the properties that make an antipsychotic “atypical”. Possible mechanisms of action include combined D2-/5-HT2 antagonism, preferential mesolimbic binding, fast dissociation from the D2 receptor, and finally, with the recent introduction of aripiprazole, partial agonism at D2 receptors. With the comparison of striatal and extrastriatal D2 binding of antipsychotics with novel radioligands it became possible to link antipsychotic actions to extrastriatal rather than striatal binding. Here we will present data on the striatal and extrastriatal D2 binding characteristics of amisulpride, aripiprazole, clozapine, quetiapine, and ziprasidone in the human brain, which demonstrate marked differences between these compounds. Finally, the presynaptic actions of acute and subchronic haloperidol were investigated in a series of [18F]FDOPA-PET studies both in normal volunteers and in schizophrenic patients. In conclusion, nuclear techniques are powerful tools for the investigation of the diversity of mechanisms of action of antipsychotic drugs. 61 Bipolar depression-treatment progress of the last 5 years H Grunze Department of Psychiatry, LMU Munich, Germany Despite the fact that depressed episodes dominate the long-term course of bipolar disorder and are accompanied by severe psychosocial impairment and suicidality, they had been neglected in clinical research for a long time. The use of antidepressants which appear effective against symptoms of depression independent from aetiology, had been discouraged due to the underlying assumption of a different biological basis of bipolar compared to unipolar depression. At the same time monotherapy with mood stabilisers, mainly lithium and lamotrigine, has been postulated despite the fact that their acute antidepressant efficacy appears not convincing in controlled studies. In contrast to typical neuroleptics, atypical antipsychotics may not only improve depressive symptoms in mixed mania but may also become, according to controlled studies, a promising treatment option for bipolar depression. However, further confirmative studies and experience from clinical practice is still needed. Further biological treatment options as augmentation with levotyroxine, sleep deprivation or ECT appear to be of equal efficacy in bipolar as in unipolar depression, but may also carry an increased risk of switch into (hypo)mania if not accompanied by mood stabiliser treatment. 62 Shared decision making in psychiatry. Results of a decision aid based study in the context of schizophrenia treatment J Hamann, W Kissling Klinik und Poliklinik für Psychiatrie und Psychotherapie der Technischen Universität München, Germany Patients suffering from schizophrenia probably constitute one of the populations most excluded from medical decisions. This might be due to their assumed or existing reduced decisional capacity. However, previous research on decisional capacity in schizophrenia shows that most patients can show performance equal to that of non-ill controls when adequately informed. In this cluster-randomised trial on the use of a decision aid on antipsychotic drug choice the feasibility of sharing treatment decisions with psychotic inpatients was evaluated. Patients in the interventional group (decision aid + “shared decision” between physician and patient on medication) are compared to patients receiving “usual care” in regard to their satisfaction with care, perceived involvement and knowledge. Baseline data on the full sample are presented. The ability of patients to participate in therapeutic decisions depended strongly on the psychopathology and the course of the illness. However, a considerable proportion of even seriously ill patients were able to successfully participate in decisionmaking. On discharge from hospital, patients in the interventional group had better knowledge of their illness. Patients reported higher perceived involvement when faced with the decision aid. However,

this difference was only statistically significant immediately after the intervention and diminished at the time of discharge. Patients with schizophrenia are in many cases able and willing to participate in important clinical decisions such as antipsychotic drug choice. Further, the use of a decision aid has a positive impact on several variables known to affect treatment adherence. However, the single use of a decision aid might not overall change treatment patterns during hospital stays. 63 Detection of Alzheimer’s disease in MCI – new MRI-based methods for the early diagnosis of AD H Hampel, M Ewers, SJ Teipel Klinik für Psychiatrie und Psychotherapie der Ludwig-MaximiliansUniversität, München, Germany MRI detects a characteristic pattern of cortical atrophy already in predementia stages of AD. Manual volumetric measures of medial temporal lobe structures discriminate between benign age-associated memory impairment and predementia AD within the continuum of mild cognitive impairment. These measurements, however, are very time consuming and therefore not cost-effective in a clinical setting. More recently,automated voxel-based approaches have been explored for their power to detect AD pathology in MCI. Both, rater-dependent and automated approaches have not yet been validated in a multicenter design in order to assess their clinical applicability. In the present study, we determined the multi-center reliability of rater-dependent and automated MRI processing using phantom tests and volumetric MRI of a healthy volunteer at 11 centers of the German Competency Network on Dementias (Kompetenznetz Demenzen).We found a high reliability of both types of measurements, suggesting a high power of multi-center diagnostic trials. Based on these findings, we investigated characteristic patterns of cortical atrophy to discriminate between AD and other types of dementia and to detect AD in MCI. After a first wave of data acquisition across 11 centers, re-examination of patients is planned within 12 months to determine rates of cortical and subcortical atrophy in predementia and clinical AD. 64 Predictive changes of sleep EEG and HPA system during long-term course of depression and possible implications of early detection such as stress regulation assessment in kindergarten children M. Hatzinger1, S. Brand1, U. Hemmeter1, M. Ising2, E. Holsboer-Trachsler1 1 Depression Research Unit, Sleep Medicine and Neurophysiology, Psychiatric University Hospital Basel, Switzerland 2 Max Planck-Institute of Psychiatry, Munich, Germany In depression characteristic changes in EEG sleep measures are well documented findings. However, the course and the predictive value of these alterations for long-term course of depression still warrant clarification. Thus, the present study aimed to identify predictive sleep EEG markers for long-term outcome. Since the hypothalamic-pituitary-adrenocortical (HPA) system plays a crucial role in depression, we evaluated HPA system function as well. In fifteen patients with depression, HPA system assessments using the DEX/CRH test and sleep EEG studies were conducted during a controlled antidepressant treatment study (TS) and during a follow-up (FU) investigation 3.8 ± 2.2 years later. Unfavorable sleep EEG measures during the TS were significantly associated with a worse long-term outcome of depression, as reflected by an increased number of episodes. Moreover, the identified unfavorable sleep EEG markers correlated with HPA system dysfunction. In conclusion, the long-term course of depression is related to sleep EEG variables during depression, and these sleep EEG markers are associated with HPA system regulation. In order to detect these possible vulnerability factors before the onset of disease we are actually conducting assessment of HPA regulation and sleep EEG in Kindergarten children in a longitudinal study approach. First results will be presented.

I/20 65 Brain imaging studies: insight into the neurobiology of alcoholism A Heinz1, M Reimold2, G Gründer3, T Siessmeier3, J Wrase1, R Bares2, HJ Machulla2, P Bartenstein3, K Mann4 1 Department of Psychiatry, Charité Campus Mitte, Berlin, Germany 2 PET Center, University of Tübingen, Germany 3 PET Center, University of Mainz, Germany 4 Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany Molecular brain imaging with PET and SPECT can be used to measure the neurobiological correlates of the disposition and maintenance of alcohol-dependence. A low response to the acute effects of alcohol is associated with a high risk for excessive alcohol intake and alcoholism. In a primate model of alcoholism, it was positively correlated with an increased availability of brainstem serotonin transporters, which was associated with high alcohol intake in a free choice paradigm. Mu-opiate receptors in the ventral striatum may mediate the appetitive effects of alcohol and were elevated among detoxified alcoholics. Chronic alcohol intake may be associated with a downregulation of central GABA-A receptors, which indeed was observed among detoxified alcoholics. Detoxified alcoholics also showed a reduced availability of dopamine D2 receptors in the ventral striatum, which was inversely correlated with alcohol craving and increased processing of alcohol-associated pictures in the medial prefrontal cortex. Brain imaging data also suggest that the neurotoxic effects of alcohol on brainstem serotonergic neurons are modulated by the genetic constitution of the regulatory region of the serotonin transporter. The neurotransmitter systems implied in these brain imaging studies are targets for medication to reduce the relapse risk among detoxified alcoholics. 66 The impact of GABAergic mechanisms in disturbed sleep wake regulation in depression U Hemmeter1, M Hatzinger2, E Seifritz2, E Holsboer-Trachsler2 1 Psychiatric University Clinic Marburg, Germany 2 Psychiatric University Hospital, Basel, Switzerland The antidepressant efficacy of sleep deprivation (SD) in depressed patients can be prevented by early morning naps and microsleep (MS) during SD. The GABA-Benzodiazepine receptor antagonist flumazenil augments vigilance and reduces NonREM-sleep pressure and NonREM sleep associated growth hormone secretion in early morning recovery sleep. Therefore, 27 patients with major depression were subjected to a partial sleep deprivation (PSD). In a double blind randomized design either flumazenil or placebo was orally applied during PSD. EEG was registered continuously for 60 hours by a portable device. Flumazenil significantly suppressed MS during SD and increased slow wave sleep in the recovery night.Antidepressant efficacy of PSD was not different between flumazenil and placebo during PSD, but better after the recovery night in patients treated with flumazenil. It is concluded that GABAergic mechanisms are involved in the regulation of MS and NonREM-sleep during PSD and may be associated with the antidepressant efficacy of PSD. 67 Intact and deficient visual information processing in schizophrenic patients MH Herzog1, 2, S Marbach1, 3, A Brand3 1 Human Neurobiology, University of Bremen, Germany 2 Laboratory for Psychophysics, BMI, EPFL, Switzerland 3 Center for Psychiatry and Psychotherapy, Hospital Bremen Ost, Germany In schizophrenia, many stages of information processing are deficient including cognitive and executive functions. It is, therefore, important to determine the earliest of these aberrant stages since “early” deficits may cause abnormal processing later on. To investigate these issues, we studied the two most fundamental processes in visual information processing: feature binding and figure-ground-segmentation. Using a

new visual backward masking technique, shine-through, we show that target processing can be strongly prolonged in the schizophrenic patient (more than ten times longer than in healthy controls). However, feature binding and figure-ground-segmentation are fast and intact. Hence, it seems that we can determine the stages where intact information processing turns into deficient processing. Aberrant processing, related to the magno cellular visual system, may partly but not completely explain these results. Preliminary data show, moreover, that prolonged target processing is a trait rather than a state marker. 68 Semantic processing abnormalities in formal thought disorder: preliminary fMRI results H Horn, A Federspiel, T Müller, M Wirth, T König, W Strik University Hospital of Clinical Psychiatry, Bern, Switzerland Formal thought disorder is one of the major symptoms in schizophrenia. Until now the pathophysiological foundations of this symptom are unknown. Several electrophysiological studies on schizophrenic patients with formal thought disorder showed abnormalities of the event related potential N400 as a sign for changes in semantic processing. To investigate this abnormality we used a N400 paradigm in an fMRI study. 18 schizophrenic patients and 18 healthy controls were investigated with a 1.5T scanner. Psychopathology was measured by the PANSS; additionally the degree of formal thought disorder was quantified by the Thought and Language Index. Stimulation consisted of a passive reading task (noun-noun word pairs) with 900 ms stimulus-onset asynchrony (SOA). Preliminary data will be presented. 69 Neuronal insulin signal transduction in sporadic Alzheimer disease. Therapeutic implications S Hoyer Institute for Pathology University of Heidelberg, Germany Nosologically Alzheimer’s disease (AD) is not one single disorder. 1. Early onset autosomal dominant familial AD has been documented in 334 families worldwide (by August 2004). The amyloid cascade hypothesis serves as the scientific basis of this form of inherited AD. 2. In contrast, millions of people suffer from sporadic AD worldwide. Different susceptibility genes along with the main risk factor aging may contribute to the causation of this form of AD. There is no evidence that the amyloid cascade hypothesis is valid for sporadic AD. Instead, there is evidence that a disturbance in the neuronal insulin signal transduction pathway controlling cerebral glucose metabolism (reduced acetylcholine synthesis and decreased ATP formation) may be a central and early pathophysiologic event in sporadic AD.The ageassociated arterial hypercortisolemia may be an important factor to damage the function of the neuronal insulin receptor. Both, the ATPdeficit and the reduced insulin signal transduction may induce abnormalities 1. in APP-metabolism in that more amyloidogenic derivatives are formed, and 2. in tau-metabolism in that tau-protein is hyperphosporylated. Thus, a therapeutic target should be to improve the function of the neuronal insulin receptor. In animal experiments, it is found that Ginkgo biloba (EGb 761) may improve ATP formation. Some recent findings indicated that EGb 761 may reduce the effect of cortisol, which may improve the function of the neuronal insulin receptor. 70 Robustness of rapidly changing “chaotic” disease patterns in affective disorders: a systems biology perspective MT Huber1, HA Braun2, JC Krieg1 1 Klinik für Psychiatrie und Psychotherapie 2 Institut für Normale und Pathophysiologische Physiologie, Universität Marburg, Germany During the longitudinal course of uni- and bipolar disorders with evolving illness episodes occur after shorter intervals of remission

I/21 and the cycling frequency can be accelerated. Despite large variability, the abstracted general principle is that illness patterns can evolve to fast fluctuating “chaotic” mood changes. Unfortunately, such mood states are hard to treat and one could ask, what makes this apparently instable patterns so robust with respect to intervention. We here take a systems biological perspective and address this problem by considering the principle of robustness in biological systems. Robustness is defined as the ability of a system to maintain stable functioning despite various perturbations such as internal and external stresses.One typical robustness mechanism is feedback control. Effective feedback mechanisms and their disturbances play a central role in normal mood regulation as well as affective disorders (e. g. HPA-regulation, sensitization or circadian rhythms). With a simple feedback model, we investigate – as an analogy to disease patterns – the robustness of rapidly fluctuating activity patterns with respect to external perturbations and internal system parameter changes. Our results show that such activity patterns behave surprisingly robust to external and internal stresses. The underlying generic mechanisms are discussed within the context of affective disorders. 71 Training of emotion recognition training in autism: A fMRI study D Hubl1, S Bölte2, S Feineis-Matthews2, D Prvulovic3, F Poustka2, T Dierks1 1 Department of Psychiatric Neurophysiology, University Hospital of Clinical Psychiatry, Bern, Switzerland 2 Department of Child and Adolescent Psychiatry, J. W. Goethe-University, Frankfurt/M., Germany 3 Department of Psychiatry, J. W. Goethe-University, Frankfurt/M., Germany Disorders of the autism spectrum are associated with impairments in facial affect recognition. In this functional magnetic resonance imaging (fMRI) study, we examined the neurobiological correlates of the effects of a computer-based training program on facial emotion recognition. The fMRI scans were conducted in 10 adolescent and adult individuals with higher functioning autism. Five of them were intensively trained in basic emotion detection over a period of five weeks, while the other five did not receive any comparable intervention. Two facial affect recognition measures on the behavioural level as well as blood oxygen level-dependent (BOLD) signal changes in the fusiform gyrus and other cortical regions known to be involved in visual processing of faces were assessed twice, at baseline and post training. Compared to the control group, the sample of trained subjects with autism showed marked improvements on both behavioural measures, which were accompanied by higher BOLD signals in the right medial occipital gyrus and superior parietal lobule. Results indicate that gains in facial affect recognition in autism are associated with higher activation in some cerebral regions being part of a compensatory facial processing network, not necessarily with an increase of activation in the fusiform face area. 72 Functional and structural connectivity in schizophrenic hallucinations D Hubl1, T Koenig1, W Strik1, A Federspiel1, R Kreis2, C Boesch2, SE Maier3, G Schroth4, K Lovblad4, T Dierks1 1 Department for Psychiatric Neurophysiology, University Clinic of Clinical Psychiatry, Bern, Switzerland 2 Department of Magnetic Resonance Spectroscopy and Methodology, Department of Clinical Research, University of Bern, Bern, Switzerland 3 Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA 4 Department of Neuroradiology, University of Bern, Bern, Switzerland Alterations in connectivity between frontal and temporal speech-related areas might contribute to the pathogenesis of auditory hallucinations. Connecting circuits between these regions are assumed to become dysfunctional during the generation and monitoring of inner

speech. To investigate the directionality of cortical white matter tracts we used magnetic resonance diffusion imaging. The aim was to investigate whether previously described abnormal activation patterns observed during auditory hallucinations relate to changes in structural interconnections between frontal and temporal speech-related areas. Fractional anisotropy was assessed in 13 patients prone to auditory hallucinations, in 13 patients without auditory hallucinations and in 13 healthy control subjects. In patients with hallucinations, we found significantly higher directionality in the lateral parts of the temporoparietal section of the arcuate fasciculus and in the anterior corpus callosum compared with control subjects and nonhallucinating patients. Comparing hallucinating patients with nonhallucinating patients we found significant differences most pronounced in left hemispheric fiber bundles, including the cingulate bundle. These results are discussed within the framework of findings on the functional neuroanatomy of auditory hallucinations. We postulate that during inner speech, the alterations of white matter fiber tracts in patients with frequent hallucinations lead to abnormal coactivation in regions related to the acoustical processing of external stimuli. This abnormal activation may account for the patients’ inability to distinguish self-generated thoughts from external stimulation. 73 FDG-PET in patients with Alzheimer’s disease and mild cognitive impairment during follow-up A Hunt1, P Schoenknecht1, M Henze2, U Haberkorn2, J Schroder1 1 Section for Geriatric Psychiatry, Ruprecht-Karls-University Heidelberg, Germany 2 German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit Nuclear Medicine, and Department of Nuclear Medicine, Ruprecht-Karls-University Heidelberg, Germany Introduction: Important topics in Alzheimer (AD) research include early diagnosis and the evaluation of the clinical course of mild cognitive impairment. PET is sensitive in AD; reduced activity (CMRglc) in frontotemporoparietal lobes and in posterior cingulum have been described. We measured CMRglc in AD, in MCI patients and in controls, and followed up these MCI patients after two to five years. Methods: 18FDG-PET was performed in 44 AD patients, 14 MCI probands and 14 controls. Using spm96 we correlated CMRglc in AD with MMSE, and compared CMRglc in AD with CMRglc in MCI and controls. We compared CMRglc in MCI with controls and CMRglc in MCI-convertors with CMRglc in controls. Results: Reduced MMSE was associated with reduced CMRglc in mainly left-sided frontotemporoparietal lobes (p < 0.05). The comparison AD versus controls showed reduced activity in AD in bilateral frontotemporoparietal lobes (p < 0.05). MCI probands had reduced activity compared to controls in the right precuneus, left posterior cingulate, bilateral middle temporal lobes and right angular gyrus (p < 0.05). At baseline subsequent MCI-convertors showed reduced activity in right parietal lobe, bilateral middle temporal lobes and in right precuneus (p < 0.05). Discussion: This study represents three major findings: first AD patients had reduced activity in frontotemporoparietal areas. Second, MCI probands could be distinguished from controls by a reduced activity in middle temporal lobes, precuneus and posterior cingulum. Third, MCI-convertors had reduced activity at baseline in right angular gyrus, bilateral middle temporal lobes and right precuneus compared to controls. The results confirm the significance of frontotemporoparietal lobes in AD, and indicate the importance of middle temporal lobes, precuneus and posterior cingulum in MCI.

I/22 74 Decreased prefrontal serotonin 2A receptor binding in at-risk mental states R Hurlemann1, 3, C Boy3, H Scherk2, PT Meyer3, H Herzog3, P Falkai2, K Zilles3, W Maier1, K Vogeley1, 3, A Bauer3 1 Dept. of Psychiatry, University of Bonn, Bonn, Germany 2 Dept. of Psychiatry, University of the Saarland, Homburg, Germany 3 Institute of Medicine, Research Center Juelich, Juelich, Germany In-vivo neuroreceptor imaging done initially in the development of psychosis is essential for an understanding of the neurobiology and treatment of schizophrenia. In this pilot study, we investigated the brain 5-HT2AR density of 6 subjects at risk of developing psychosis compared to 7 healthy control volunteers using [18F]altanserin, a specific 5-HT2AR antagonist, and positron emission tomography (PET). Group comparison demonstrates a substantial decrease of [18F]altanserin binding in orbitofrontal and prefrontal cortex for at-risk mental states. Although preliminary, these in-vivo radioligand data support findings of a reduced prefrontal 5-HT2AR density in schizophrenia and highlight the prefrontal cortex as a candidate marker region of early disturbances of serotonergic neurotransmission. 75 Differences in quality of life and course of illness between cycloid and schizophrenic psychoses – a comparative study B Jabs Klinik für Psychiatrie und Psychotherapie, Universität Würzburg, Germany Objective: Cycloid psychoses represent a nosological entity not adequately recognised by contemporary psychiatry. They present with full recoveries after each psychotic episode and, thus, have a favourable prognosis. Method: To verify this clinical observation, course, outcome, and quality of life (QoL, measured by the German version of the Lancashire Quality of Life Profile and the WHO-instrument WHOQOL) of 33 patients with cycloid psychosis and 44 schizophrenics were compared after a mean time of 13 years since first hospitalisation. For comparison of objective and subjective QoL measures, 48 healthy controls were included. Results: Concerning their course of the disease, schizophrenics were hospitalised significantly longer and received higher neuroleptic doses than patients with cycloid psychosis. The latter displayed significantly better scores in CGI-, GAF-, Strauss-Carpenter-Outcome- and PANSS-scale. In global QoL measures, cycloid psychotic patients were more satisfied with their QoL than schizophrenic patients, and did not differ significantly from healthy controls. Conclusion: Cycloid psychoses seem to exhibit a better prognosis than schizophrenia regarding course, outcome, objective, and subjective aspects of QoL. Thus, they appear to present a useful concept deserving more clinical and scientific attention. 76 Repetitive transcranial magnetic stimulation (rTMS) – a tool for the treatment of auditory hallucinations? M Jandla,b, J Steyera, M Webera, DEJ Lindenc, D Prvulovicb, D Selengab, J Rothmeierd, W Fröscherd, K Maurerb, WP Kaschkaa a Dept. of Psychiatry I, University of Ulm, Germany b Dept. of Psychiatry, University of Frankfurt a. M., Germany c Max-Planck-Institute for Brain Research, Frankfurt a. M., Germany d Dept. of Neurology, ZfP Weissenau, Ravensburg, Germany In a previous functional Magnetic Resonance study the authors could demonstrate the activation of Heschl’s gyrus during verbal auditory hallucinations (VAH). This study aimed at treating VAH specifically by repetitive Transcranial Magnetic Stimulation (rTMS). 14 patients, suffering from treatment resistant VAH were included in a randomized, 3-armed, cross-over, double blind, add-on rTMS study, using a figure-8-coil over CP5, CP6 and sham-position, respectively; duration 15 min, frequency 1 Hz, strength 100 % motoric threshold. Using the Psychotic Symptom Rating Scales, the hallucinations before and after

each stimulation session and during the 4-week follow-up periods were quantified. An electroencephalogram was acquired before and after each 5-day stimulation period, effects on its frequency bands were assessed by Low Resolution Brain Electromagnetic Tomography. During the active stimulation period, but not during sham, the hallucination score decreased significantly from 30.2 (2.8 SD) to 21.1 (13.1 SD). Theta activity in the left parietal lobe tended to increase, whereas alpha1 and full band activity in the right medial frontal gyrus tended to decrease. Conclusion: rTMS over the posterior portion of the superior temporal gyrus of the dominant hemisphere decreases the hallucination scores compared with sham in hallucinating patients during the period of stimulation with fade out during follow-up.

77 Pharmacovigilance study in psychiatry involving TDM and pharmacogenetics E Jaquenoud Sirot1, CB Eap2, P Baumann2 Psychiatrische Dienste Aargau AG, Klinik Königsfelden, Brugg, Switzerland Unité de Biochimie et Psychopharmacologie Clinique, Univ Dept Neurosciences, Prilly, Switzerland. The importance of genetic polymorphisms and drug interactions in relation to therapeutic response and susceptibility for adverse drug reactions (ADR) are increasingly recognized. This study comprises data of an ongoing dynamic cohort study of about 250 psychiatric inpatients with ADRs: Within an ethically approved pharmacovigilance project (AMSP) in the clinic Königsfelden, we continuously and actively collect side effects meeting the criteria serious, unexpected or leading to stop of the medication. All adverse event cases are assessed for their causality in relation to disease and drug therapy.We measure trough plasma levels during or immediately after the adverse event. If the plasma levels are at least 20 % lower or higher than the expected reference plasma levels (Baumann et al. Therapeutic Monitoring of Psychotropic Drugs. AGNP-TDM Expert Group Consensus Guidelines, Pharmacopsychiatry (in press)), we also assess the pharmacogenetic status of the patient for the cytochrome P450 isozymes. In about 20–25 % of the cases plasma levels of the medication lay at least 20 % above the given reference ranges. In some cases we find plasma levels as high as 5 times the upper recommended value. Pharmacogenetic polymorphisms could be identified in many of these cases. TDM and pharmacogenetic tests are useful for causality assessments of ADR cases. It is too early to give a recommendation for routine TDM and pharmacogenetic testing, with the exception of drugs like clozapine with an established therapeutic index. To understand if high plasma levels and their cause really lead to more ADRs, more studies are needed.

78 Monitoring of treatment effects with 1H-MRS in Alzheimer’s disease F Jessen1, F Träber2, W Block2, W Maier1, HH Schild2 1 Department of Psychiatry University of Bonn, Germany 2 Department of Radiology University of Bonn, Germany Proton magnetic resonance spectroscopy (1H-MRS) allows the detection of the neuronal amino-acid N-acetyl-aspartate (NAA). Numerous studies have reported a reduction of NAA in various brain regions in Alzheimer’s Disease (AD), which reflects neurodegeneration. Until recently, NAA was considered a marker of neuronal density. Novel studies in various disorders, however, have reported reversible NAA reduction with successful treatment. Thus, NAA is now considered a marker for neuronal viability rather than density. Based on these observation, we formulated the hypothesis, that NAA increase might correspond to treatment response with acetylcholineesterase inhibitors (Ache-I) in AD. We performed 1H-MRS of the medial temporal lobe (MTL) and the parietal lobe at baseline and after three months treatment with Donepezil in 17 AD patients. The effect on cognition was assessed with the ADAScog and the MMSE. We will re-

I/23 port the results with particular focus on individual treatment response.

open field test, in the novel object test and in social interactions. The validity and quality of this model will be discussed.

79 CPAP-therapy effectively lowers serum homocysteine in obstructive sleep apnoea syndrome W Jordan1, C Berger1, S Cohrs1, A Rodenbeck1, G Mayer2, PD Niedmann3, N von Ahsen3, E Rüther1, J Kornhuber4, S Bleich4 1 Department of Psychiatry and Psychotherapy, University of Goettingen, Germany 2 Hephata Klinik, Schwalmstadt-Treysa, Germany 3 Department of Clinical Chemistry, University of Goettingen, Germany 4 Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Germany

81 Serotonergic dysfunction of patients in the prodromal phase of a schizophrenic disorder as measured by loudness dependence of auditory evoked potentials (LDAEP) G Juckel,Y Gudlowski, J Gallinat, I Gorynia, S Özgürdal, F Forstreuter, H Witthaus, M Hauser, A Heinz Dept. of Psychiatry and Early Recognition and Intervention Center (ERIC), Charité, Campus Mitte Berlin, Germany

Reactive oxygen species (ROS) might be involved in hyperhomocysteinemia. Obstructive sleep apnoea syndrome (OSA) with episodic hypoxia-reoxygenation (EHR) is proposed as a pathophysiological model to investigate the generation of ROS. Furthermore, the assessment of serum total homocysteine (tHcy) in patients with OSA is highly relevant since both are strongly associated with stroke and cognitive dysfunction. Evening, nocturnal, and morning serum tHcy levels and cofactors of the Hcy metabolism (vitamin B6, B12, folic acid, and 5,10-methylenetetrahydrofolate reductase (677C > T) and (1298A > C) mutations) were measured in 16 untreated OSA patients and reassessed in 12 of these patients several months later while they were still on treatment with continuous positive airway pressure (CPAP). Seven of 16 untreated OSA patients showed tHcy levels exceeding 11.7 µmol/l. The circadian pattern of serum tHcy in untreated and treated patients (p < 0.001) implied a diagnostic impact of blood sampling time. CPAP-treatment reduced mean serum tHcy levels in patients by about 30 % (p < 0.005) and thus probably the (hyper)homocysteinemia-related cognitive dysfunction and the risk for cardio-/cerebrovascular diseases. We suggest that lower tHcy levels were attributable to CPAP supporting the assumption that EHR and the formation of ROS might be involved in tHcy generation in OSA. Interestingly, the reduction in tHcy concentrations following CPAP was larger than that which can be achieved with supplementation of folic acid or vitamin B12. 80 Prenatal influenza infection model of neurodevelopmental genesis of schizophrenia G Juckel Dept. of Psychiatry, Charité, Campus Mitte, Berlin, Germany The neurodevelopmental hypothesis of schizophrenia postulates disturbances in brain maturation in the second trimenon, resulting in limbic dysfunction and structural changes such as decreased volume in hippocampal and cortical regions due to neuropil reduction. A genetic vulnerability is supposed to interact with inflammatory and immunological reactions that interfere with brain development during pregnancy. In several but not all studies, children of mothers that suffered from influenza in the 2. trimenon showed an increased risk to develop schizophrenic disorders. Furthermore, the specific and unspecific immune systems show clear signs of overactivation in patients with schizophrenic disorders, and first studies show that antiinflammatory treatment can lead to improvement of schizophrenic symptoms. Fatemi and colleagues have developed a promising animal model of the inflammatory genesis of schizophrenia as model of the motherly influenza infection in mice. Descendants of female mice, who were exposed to a mouse-adapted influenza virus in the middle of pregnancy and had gone through a respiratory infection, show several changes in brain morphology, physiology and behavior after puberty (fertility) comparable to those of schizophrenic patients: volume reduction of neocortex and hippocampus with relatively raised cell number, pyramid cell dystrophy, wide ventricles, reduced reelin and immune reactivity, changes from nNOS and SNAP-25, changes in multiple genetic polymorphisms (microarray analyses), deficits in prepulse inhibition (PPI) within the acoustic startle response, in the

An enhanced serotonergic activity is discussed as important pathogenetic factor for schizophrenia. It is still unclear if even the prodromal state is characterized by such a serotonergic dysfunction. The possibility to proove this hypothesis is, however, limited due to the lack of valid indicators for the central serotonergic system. The socalled loudness dependence of auditory evoked potentials (LDAEP) is a measurement of activity of the auditory cortex in dependence of stimulus loudness and is mainly modulated, as often shown in the last years, by the serotonergic system: A weal LDAEP is correlated to high serotonergic activity and vice versa. The LDAEP (Cz) of 22 patients in the schizophrenic prodromal state from ERIC, of 16 patients with first episode of schizophrenia, of 14 patients with chronic course, and of 24 healthy controls was recoded with a 33 electrode montage. 70 sinus tones in five different intensity levels (79, 87.5, 96, 104.5 und 111 dB) were binaurally given via head phones. The LDAEP of the prodromal patients were significantly reduced in comparison to healthy controls (0.13 µV/dB vs. 0.18 µV/dB,p = 0.003),while there was no difference to the values of first episode and chronic patients (0.14 µV/dB and 0.12 µV/dB, respectively). This is the first empirical hint that the serotonergic neurotransmission is enhanced even in the prodromal phase of schizophrenia and underlies the important role of a disturbed serotonergic system in the pathogenesis of schizophrenia. 82 Neurophysiological findings in patients in the schizophrenic prodromal phase G Juckel, S Özgürdal, Y Gudlowski, J Gallinat, I Gorynia, M Staedtgen, F Forstreuter, H Witthaus, A Heinz Dept. of Psychiatry and Early Recognition and Intervention Center (ERIC), Charité, Campus Mitte Berlin, Germany Neurophysiological methods allow the examination of cognitive-cortical functioning in patients with schizophrenia. Event-related potential components as the auditory evoked P300, related to cognitive processes as attention and orientation, were found being reduced in amplitude in acute and chronic as well as in medicated and un-medicated patients in many studies. This decreased P300 amplitude is interpreted as consequence of reduction in fronto-temporal gray matter volume, also often found in various groups of schizophrenic patients. It is, however, unclear, whether the P300 amplitude reduction already appears before the schizophrenic psychosis is fully manifested. We studied 27 patients in the prodromal phase of a schizophrenic disorder (mostly showing attenuated psychotic symptoms or brief limited intermittent symptoms) as well as 16 first-episode and 16 chronic patients with schizophrenia and compare these groups with 26 healthy subjects. The event-related P300 was recorded during an auditory oddball paradigm, using 32 electrodes referenced to Cz. Groups significantly differed from each other concerning the P300 amplitude at Pz (F(3/74) = 2.85, p = 0.04). Post-hoc tests revealed significant lower P300 amplitudes of chronic patients compared to the healthy controls (p = 0.002). There were statistical trends for differences between prodromal and first-episode patients on the one hand and healthy subjects on the other side (p = 0.08 and p = 0.07 respectively). A trend analysis provided evidence for significant linear reduction in P300 amplitude from healthy (15.1 µV), prodromal (12.3 µV), first-episode (10.8 µV) to chronic state (9.1 µV). It is concluded that neurophysiological changes in form of reduction in P300 amplitudes take place also in the schizophrenic prodromal phase, i. e. before manifestation of full psychosis, and that these changes seem to

I/24 have a progressive course from prodromal to chronic state of schizophrenia. 83 Dissociating intention and success in verbal memory encoding: An event-related fMRI study M Jüptner1, S Heinze1,2, G Sartory2,A Hesse1,A de Greiff3, M Forsting3, BW Müller1 1 Clinic for Psychiatry and Psychotherapy, University of DuisburgEssen, Germany 2 Clinical Psychology, University of Wuppertal, Germany 3 Institute for Diagnostic and Interventional Radiology, University of Duisburg-Essen, Germany Verbal memory encoding is a fundamental cognitive function often disturbed in neurologic and psychiatric patients. While previous studies on verbal memory encoding focused on learning success, here we compared unsuccessful and successful verbal memory encoding to a reading baseline condition in an event-related functional magnetic resonance imaging study. N = 15 healthy subjects were presented 7 lists of 22 words. Subjects were instructed to recall these immediately after presentation of each list. Two additional lists were to be read only (baseline condition). Data were acquired on a 1.5T Siemens Sonata scanner. Data were analysed with SPM99 and random effects analysis. Unsuccessful intention to learn was associated with anterior thalamic, cingulate and left premotor activation. Successful intention was associated with additional left parietal activation. Bilateral frontal, left temporal and parietal activation emerged in the direct comparison of subsequently remembered versus forgotten words. Our results suggest that the intention to learn may be related to cingulate, thalamic and to left premotor activation. In contrast, encoding success may be associated with activation prefrontal, parietal and fusiform areas. This dissociation of brain activation related to encoding intention and success may prove to be valuable in the assessment of memory disturbances in psychiatric patient samples. 84 The Vienna transdanube aging (VITA) study: an age-stratified longitudinal population study of dementia in Vienna S Jungwirth1, P Fischer1, 2 1 Ludwig Boltzmann Institute of Aging Research, Vienna, Austria 2 Department of General Psychiatry, University Hospital for Psychiatry, Vienna, Austria The VITA (Vienna Transdanube Aging) study is a community based, prospective, interdisciplinary cohort-study (i. e. longitudinal design) of all 75-years-old inhabitants of the 21st and 22nd district of Vienna. It is supported and organized by the Ludwig-Boltzmann Institute of Aging Research. The main aim of the VITA is the improvement of the early diagnosis of Alzheimer dementia. Moreover we search for risk factors of cognitive decline in the elderly. Since 1. 5. 2000 probands have been investigated after having given written informed consent. At December 1st, 2003 the complete cohort of 606 probands had undergone the basic procedure, which lasted about 9 hours per proband. Since 1. 11. 2003 every subject is reinvestigated. In September 2004 about 400 participants of the basic investigation will have had their follow-up and about 80 cases of Alzheimer dementia will be detected. The main scientific question concerns the prediction of dementia in the elderly. Various variables (biochemical, genetic, imaging techniques (MRI, PET), neuropsychological, neurological, psychiatric) will be compared with each other concerning sensitivity and specificity of prediction of cognitive decline. Medical data (comorbidities, medication, operations, nutritions, addiction), and psychosocial data (life events, education, profession, psychosocial activities, physical activities) are also measured. The presentation will focus on medical data (vascular risk factors, MRI data, medication) and their significance for cognitive decline in the VITA.

85 Subjective well-being under antipsychotic treatment A Karow, I Schäfer, D Naber University Hospital Hamburg-Eppendorf, Department of Psychiatry und Psychotherapy, Hamburg, Germany The increasing interest in subjective well-being and quality of life of patients with schizophrenia represents a conceptual shift in therapeutic outcome criteria. Symptom reduction alone was the most essential outcome parameter for a long time. With the development of atypical antipsychotics more ambitious success criteria including the patients’ perspective are considered today. While effects on positive psychopathology do not differ markedly between typical and atypical antipsychotics, the lack of motor symptoms, the improvement of negative, affective and cognitive symptoms, and particularly the better subjective well-being and quality of life are major advantages for the new antipsychotic drugs. Patients’ attitudes and values, their clinical course as well as their previous experiences with medication may significantly affect the current subjective response to antipsychotics. Previous studies have shown that subjective well-being is inversely correlated with type and severity of psychopathology, especially depression and negative symptoms. Different antipsychotic side effects were related to reduced well-being, most importantly extrapyramidal symptoms (EPS), sexual dysfunctions, and psychic side effects and current research indicates that negative subjective well-being is possibly predictive for a less favourable symptomatic outcome. The assessment of subjective well-being is a new methodological approach to differentiate therapeutic effects from the patient’s perspective. 86 Nitric oxide and mitochondrial failure in Alzheimer’s disease U Keil1, A Bonert1, CA Marques1, I Scherping1, L Pradier2, C Czech3, F Müller-Spahn4, WE Müller1, A Eckert1, 4 1 Dept. of Pharmacology, Biocenter, University of Frankfurt, Frankfurt am Main, Germany 2 Aventis Pharma, Vitry sur Seine, France 3 Hoffman-La Roche, Basel, Switzerland 4 Neurobiology Research Laboratory, Psychiatric University Clinic, Basel, Switzerland We investigated effects of acute and chronic exposure to increasing concentrations of amyloid beta (Aβ) on mitochondrial function and NO production in vitro and in vivo. Our data demonstrate that PC12 cells and HEK cells bearing the Swedish double mutation in the amyloid precursor protein (APPsw), exhibiting substantial Aβ levels, have increased NO levels and reduced ATP levels already under basal conditions. Extracellular treatment of PC12 cells with comparable Aβ concentrations only leads to weak changes, demonstrating the important role of intracellular Aβ. In 3-month-old APP-tg mice, which exhibit no plaques but already detectable brain Aβ levels,reduced ATP levels can also be observed showing the in vivo relevance of our findings. Moreover, we could demonstrate that APP is accumulated in mitochondria of APPsw-PC12 cells. This accumulation might be directly involved in the impairment of cytochrome c oxidase activity and depletion of ATP levels in APPsw-PC12 cells. APPsw-HEK cells, which produce 30-fold increased Aβ levels compared to APPsw-PC12 cells, and 3-month-old APP-tg mice show already under basal conditions a significantly decreased mitochondrial membrane potential. Based on our findings, we suggest a hypothetical sequence of pathogenic steps linking mutant APP expression and amyloid production with enhanced NO production and mitochondrial dysfunction.

I/25 87 Mismatch responses in schizophrenia: a fMRI and whole-head MEG study TJ Kircher1, 4, A Rapp1, W Grodd2, K Mathiak3, 4 1 Department of Psychiatry, University of Tübingen, Germany 2 Department of Neuroradiology, University of Tübingen, Germany 3 Department of Neurology, University of Tübingen, Germany 4 Department of Psychiatry, University of Aachen, Germany Objective: Mismatch negativity (MMN) or field (MMNm) is an event-related brain response that is sensitive to deviations within a sequence of repetitive auditory stimuli. It is thought to reflect short-term sensory memory and is independent of higher level cognitive processes. MMN is reduced in patients with schizophrenia. Little is known about the mechanisms of this decreased response, the contribution of the different hemispheres and its locus of generation. Method: Groups of patients with schizophrenia (n = 12) and matched controls (n = 12) were studied. A novel MMN auditory oddball design was generated using the noise created by a functional Magnetic Resonance Imaging (fMRI) scanner, thus avoiding any interfering background sound. Stimuli were composed of amplitude (–9 dB) and duration (76 ms shorter) deviants in a randomized sequence. The scanner noise was recorded and applied to the same subjects in a whole-head Magnetoencephalography (MEG) device. Neuromagnetic and haemodynamic responses to the identical stimuli were compared between the patients and controls. Results: As expected,neuromagnetic mismatch fields were smaller in the patient group (p < 0.05). More specifically, a lateralization of duration mismatch to the right was only found in controls (between groups p < 0.05). For the relative amplitude of the BOLD signal (measured with fMRI), differences emerged only in the secondary (planum temporale), but not primary (Heschl’s gyrus) auditory cortex. Duration deviants achieved a right hemispheric advantage only in the control group (p < 0.001, between groups n. s.). A significantly stronger lateralization to the left (both groups p < 0.001) was found in the patients for the amplitude mismatch (between groups p < 0.01). Conclusions: The data support the view of altered hemispheric interactions in the formation of the short-term memory traces necessary for the integration of auditory stimuli. This process is predominantly mediated by the planum temporale (secondary auditory cortex). Altered hemispheric interaction of regions within the superior temporal plane could be in part responsible for language-mediated cognitive (e. g. verbal memory) and psychopathological (hallucinations, formal thought disorder) symptomatology in schizophrenia.

88 Brain microstates in psychiatric disorders T Koenig Department of Psychiatric Neurophysiology, University Hospital of Clinical Psychiatry Bern, Switzerland Essential parts of human cognition are covered, i. e. are not driven by external input and do not produce overt responses. The internal cognitive state may, however, be relevant for the appropriate evaluation of external information and selection of behavioral responses. Abnormal internal states may therefore be prior to abnormal perceptions and behavior. Brain activity unrelated to stimuli or responses can be measured and quantified by EEG. Physically, changes of EEG topography indicate a change of active brain regions and therefore assumingly a change of momentary cognitive state. When studying changes of EEG topography, one finds that these changes are discontinuous and separated by periods of quasi-stable topography of about 100 msec durations. These periods (microstates) assumingly represent basic steps of information processing. When studying EEG microstates in psychiatric patients, the duration and topography of the observed microstates change. In schizophrenics, there is a shortening of microstates that predominantly affects microstates with certain topographies, and the sequence of microstates deviates from the norm. In dementia, microstates with certain topographies recede,

while microstates with other topographies become more prominent. The changes of microstates in psychiatric patients can be related to observations made in microstates of normally developing children. 89 Disturbance of subcortical circuits indicated by white matter lesions – quantification of vascular components of dementia in the elderly using normative rating scales M Kreis, M Damian, B Krumm*, F. Hentschel Division of Neuroradiology and *Biostatistics, Central Institute of Mental Health, Faculty of Clinical Medicine Mannheim, University of Heidelberg Objectives: Microangiopathic lesions of the white matter (WML) disturb intracerebral circuits in structure and function. WML correlate with the clinical diagnosis of (vascular subcortical) dementia. To quantitate the extent of WML, we developed a rating scale with agedependent confidence ranges. We investigated the contribution to diagnosis of dementia. Methods: 338 patients with cognitive complaints from a memory clinic were diagnosed by physical and neuropsychiatric examination plus neuropsychology and neuroimaging using MRI (esp. FLAIR sequence). The WML were scored with a rating scale considering number, size and localization. The scores were compared with neuropsychological tests and confidence intervals were defined, depending on diagnosis and age. Using qualified raters, the reliability of the rating scale was determined by intra- and interrater-correlation using intracorrelation coefficient (ICC) and Cronbach alpha. Results: The reliability of the rating scale is given as a function of the defined area with values of 0.77–0.89 (ICC) and 0.98–0.99 (Cronbach alpha). WML-Scores and the confidence intervals are separating significantly the cognitively healthy from the demented ones. Conclusions: The use of a reliable rating scale for normal physiological and pathological WML with confidence intervals corrected for age allows a reliable and replicable quantification for the vascular component in dementia. 90 Overreporting of recent cocaine use in subjects entering an inpatient detoxification unit S Krenz, A Miozzari, D Misouni, A Buecking, Y Khazaal, D F Zullino Clinical Research Unit & Substance Abuse Unit University Department of Adult Psychiatry, Site de Cery, Prilly-Lausanne, Switzerland In most studies underreporting of drug use has been the major problem compared to overreporting. Overreporting may, however, occur more frequently in particular settings, e. g. in subjects entering a detoxification program. Methods: Self-reports (standardized semistructured interview) of recent drug use of 554 patients admitted consecutively to the drug detoxification unit of the University Department of Adult Psychiatry in Lausanne were compared to the results of the urine screening at admission. The subgroup of 237 patients declaring cocaine consumption during the 7 previous days was analyzed. “Overreporters” were compared to “Accurate Reporters” with regard to sociodemographic variables, and with regard to consumption and treatment history, social, legal, financial and familial context. Results: Among the patients who had reported recent cocaine consumption, only 38 % of urine tests were cocaine-positive. The retained variables of a stepwise logistic regression were: unemployment (OR 7.7; p < 0.01), previous stay in a therapeutic community (OR 0.46; p < 0.01) and the transmitting professional. Compared to patients transmitted by a physician in private practice, those being sent by a social worker presented a 4.3 times higher risk to overreport cocaine consumption (p < 0.01). The positive predictive value of the model was 75.2 %. Conclusions: The retained parameters predicting overreporting of cocaine consumption in subjects entering an inpatient detoxification program may suggest that patients being taken care of by a non-medical professional are more prone to overreport, excessively fearing withdrawal symptoms and hoping to receive more consideration

I/26 from the therapeutic team and to get more intensive pharmacological care. 91 Clinical outcome in patients with delusional depression after administration of either trimipramine or amitriptyline and haloperidol HE Künzel1, 2, K Held1, N Ackl1, M Ziegenbein1, M Uhr1, F Holsboer1, A Sonntag1, A Steiger1 1 Max-Planck-Institute of Psychiatry, Munich, Germany 2 Spinal Cord Injury Center, University Hospital Balgrist, Zürich, Switzerland Delusional depression is a very severe form of major depression with strong vegetative symptoms and a marked hyperactivity of the HPA system, often requiring a combination of antidepressive and neuroleptic treatment. Side effects as tardive dyskinesias caused by neuroleptic treatment or suicide ideation, reported under treatment with SSRIs are often observed in these patients. Therefore an alternative medication has to be found. The tricyclic antidepressant trimipramine is a hybrid of the antidepressant imipramine and the neuroleptic levomepromazine. The main neurobiological effects of trimipramine are an inhibition of the HPA axis and a stimulation of prolactin. To investigate the efficacy and tolerability in patients suffering from a delusional depression previously a 4 week open clinical pilot study was conducted. 15 inpatients suffering from a delusional depression were enrolled in the study. 2 patients dropped out: one patient because of an acute somatic disease and the other because of the worsening of the symptoms. Psychometric assessments (HAMD, MADRS, BPRS, CGI, BfS) were performed weekly. For neurobiological monitoring a Dex/CRH-test was performed before treatment and at the end of treatment. Additionally patients were monitored with ECG, EEG and clinical laboratory routine. Dosage was increased stepwise from 100 mg to 400 mg trimipramine. 8 patients were defined to be responders according to HAMD-criteria. Endocrinological assessment, performed with the Dex/CRH-test, showed a significant decrease in plasma cortisol and ACTH. The safety and tolerability was good. Encouraged by these results, a double-blind, randomized multicentre study comparing 6 weeks trimipramine monotherapy (daily dosage of the stepwise increase 200 to 400 mg) with a combination of amitriptyline (150 to 200 mg) and haloperidol (5 to 7.5 mg) (standard) was conducted. 19 centres in Germany, Switzerland and Austria participated in this study. 94 inpatients with a single or recurrent depressive episode with psychotic symptoms were enclosed. From this intention-to-treat sample 57 patients (33 with trimipramine, 24 with standard) fulfilled the per protocol criteria. Distribution of sex and age was equal among both study arms. Safety and tolerability were good for both treatments. No serious side effects were observed. The percentage of responders (HAMD at last observation ≤ 50 % vs Day 1) was 84.85 % in the trimipramine arm but only 70.83 % under standard treatment. Under trimipramine 54.5 % of the patients showed remission (HAMD ≤ 8) at the end of study period whereas only 45.8 % of the patients were rated to be remitters in the standard group.At Day 1 the HAMD score did not differ between groups (35.7 in each arm). The HAMD score decreased significantly after trimipramine and after standard. The difference in favour of trimipramine was 2.99 points at Day 42. Our findings suggest that trimipramine is superior to standard therapy. The view is corroborated that trimipramine monotherapy is a safe and tolerable alternative to combined medication of antidepressants and neuroleptics. 92 Pain processing in patients with Alzheimer’s disease: experimental evidence M Kunz Klinik für Psychiatrie und Psychotherapie der Universität Marburg, Germany Clinical studies,suggesting a less frequent pain report in patients with Alzheimer’s disease (AD), have raised the question whether AD might have impact on pain processing. To investigate this impact, experi-

mental studies are indispensable, because only in experimental settings noxious input and pain experience can be assessed independently.Experimental data suggest that the threshold for pain tolerance is markedly increased and the autonomic pain reaction is, at least in part, considerably diminished. On the other hand, pain threshold and pain event-related potentials remain largely unchanged. These findings should be only generalised with caution because in previous studies the pain experience was mainly assessed by use of verbal report. Consequently, only patients without communicational deficits could be included and more severe forms of dementia have not yet been studied.Therefore,non-verbal pain indicators are of particular importance in order to assess pain experience in all AD patients. For that reason, we assessed facial expression (FACS) and heart rate responses to noxious pressure and electrical stimuli in addition to self-ratings in AD patients and in matched healthy control subjects. In contrast to previous studies, we included AD patients with communicative impairments and with varying severity of dementia. The primary aim of our study was to find out whether the previous results obtained by self-report in mildly impaired and still communicative AD patients are consistent with our findings in more severely impaired AD patients. 93 Variations in pain sensitivity in patients with depression in the course of the disorder S Lautenbacher Physiological Psychology, Otto Friedrich University Bamberg, Germany There is ample evidence that acute depression in its severe form is associated with a decrease in pain sensitivity. A few data suggest that this hypoalgesia disappears in the course of remission, qualifying this change in pain sensitivity to being rather a state than a trait marker. The rate of change has not yet been determined. To compare fast and slow changes during remission in parallel, we studied the effects of sleep deprivation therapy over 3 weeks in patients with the only additional treatment being cognitive behavior therapy. Eighteen patients with major depressive disorder (MDD) were assigned either to 6 nights of total sleep deprivation or to a control condition without manipulation of night sleep. In parallel to the overnight improvement of depressive symptoms (self-rating) heat and cold pain thresholds normalized. However, the pain thresholds increased again after each recovery night, leading to a zig-zag pattern of short-term changes similar to that of depressive symptoms. Clinical pain complaints changed in a similar but inverse manner. The findings suggest that hypoalgesia shares the time course of the major symptoms of depression and that a temporary increase of pain complaints may result from the normalization of pain sensitivity during remission. 94 Mirtazapine reduces quickly “emotional pain” in depression F Lavergne1, A Gamma2, A Delini-Stula1, J Angst2 1 ADI International Institute for Advancement of Drug Development, CH-Basel and ADI-FL International Institute, F-Paris 2 University Psychiatric Hospital, CH-Zurich We report here the results of the analysis of an observational study in 4771 depressed patients with baseline depression MADRS score of > 20, treated for 6 weeks with mirtazapine (30 mg/day) in the dayto-day practice. Clinical Global Impression (CGI severity & improvement) and MADRS scales at weeks 1, 2 and 6 were used as efficacy measures. Results were analyzed descriptively in the ITT population. Survival analysis was applied for dichotomous outcome variables. The analysis of the CGI results showed that 82 % of patients improved (CGI decrease ≥ 1 point) already after 2 weeks and 95 % within 6 weeks. Most importantly the rate of improvement during the first 2 weeks was larger (> 2 %/day) than subsequently (< 0.5 %/day). MADRS also revealed early (within 2 weeks) regression of “painful, negative emotions” such as anxiety, sadness, inner tension and suicidal ideas. Survival analysis of the sustained ≥ 50 % decrease of the MADRS score showed that the treatment outcome was similar in all types of depression. Based on these findings we hypothesize that gen-

I/27 eralized, non-specific, early improvement of, particularly “painful emotions” in depression is of limited duration due to the counterbalancing homeostatic regulation.We assume therefore, that progressive increase of antidepressant dosage may overcome homeostatic mechanisms and increase the response to antidepressants. The “augmentation strategy” was indeed previously shown to increase the antidepressant efficacy of fluoxetine in initial fluoxetine non-responders. 95 Neurogenesis in compensatory neural networks: How to overstrain plasticity K Lehmann, M Butz, IE Dammasch Dep. Neuroanatomy, Fac. Biology, Univ. Bielefeld, Germany Owing to the ongoing neurogenesis and high synaptic turnover, the hippocampus is one of the most plastic structures in the brain. This structural plasticity corresponds to its function of funnelling and filtering all sensory information on its way into the associative cortex. The flexibility, however, entails a proportionate instability, making the hippocampus an open gate for maladaptations of the whole brain that result in neuropathological syndromes. In our research, we have characterised the hippocampal plasticity by relating the rates of cell proliferation, neurogenesis and synapse turnover. Furthermore, we have challenged the adaptive capacity of the system by subjecting it to a traumatising event and chronic deprivation. We could show how the combination of both insults disrupts structural balances not only within the hippocampal system, but also between the hippocampus and cortical areas. The mechanisms of hippocampal plasticity thus unveiled can be modelled in an abstract neuronal network which regulates its internal connectivity by compensatory actions. This in silico-simulation makes the regulatory mechanisms and functions of hippocampal neurogenesis tangible, and replicates the processes of aberrant development after heavy disturbances. It thus provides stunning insights into the possible origins of systemic neuropathological syndromes, especially epilepsy and schizophrenia. 96 Application and comparison of classification algorithms for recognition of Alzheimer disease in EEG C Lehmann1, T Koenig1, V Jelic2, T Dierks1 1 University Hospital of Clinical Psychiatry, Bern, Switzerland 2 Alzheimer Research Center, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden We explored the ability of a multitude of linear and non-linear classification algorithms to discriminate between the electroencephalograms (EEGs) of patients with varying degree of Alzheimer Disease (AD) and their age-matched control subjects. Power, SPHIO (global measurements of amplitude, frequency and complexity) and GFS (global field sychronisation) were calculated from recordings of resting eyes-closed continuous EEGs of 45 healthy controls, 116 patients with mild AD and 81 patients with moderate AD, recruited in two different centers (Stockholm, New York). The applied algorithms are: Principal component linear discriminant analysis (PC LDA), partial least squares LDA (PLS LDA), classification trees, nearest neighbour method (kNN), bagging, random forest, support vector machines (SVM) and feed-forward neural network. The algorithms are compared under different viewpoints, such as classifier accuracy (sensitivity and specificity), stability and ease of use, etc. This project is interesting under the view of modern applied statistics and neurophysiology and has a valuable impact on clinical procedures.

97 The intensity dependence of auditory evoked ERP components predicts response to Citalopram and Reboxetine treatment in major depression T Linka1, A Hesse1, S Bender1, G Sartory2, BW Müller1 1 Department of Psychiatry and Psychotherapy, University DuisburgEssen, Germany 2 Department of Clinical Psychology, University of Wuppertal, Germany The stimulus intensity dependence (IDAP) of auditory evoked Event Related Potentials (ERP) components has been suggested as an indicator of central serotonergic neurotransmission with relevance to pharmacological treatment. We evaluated the IDAP in 30 acutely depressed in-patients with major depressive episode (DSM IV) in the course of treatment either with the SSRI Citalopram (n = 16; 11 female, 5 male, mean age 39.4 ± 14.5 years) or with the SNRI Reboxetine (n = 14; 10 female, 4 male, mean age 45.2 ± 11.7 years). ERP were recorded 1 day before beginning antidepressant pharmacotherapy. Clinical symptoms of depression were assessed by means of Clinical Global Impression, Hamilton Depression Rating Scale (HDRS, 21 items) and Beck Depression Inventory at the day of ERP recording and after 3 to 4 weeks (mean: 25 days) of antidepressant treatment. Our data revealed a highly significant correlation between intensity slopes of the N1 amplitude prior to Reboxetine treatment (r = 0.86, p < 0.01 at Fz) and treatment-response (decrease of HDRS-Score): patients with a stronger decrease of HDRS-Score showed lower pre-treatment intensity slopes of N1-amplitude than patients within the higher intensity slope ranges. Conversely, for patients treated with Citalopram we found a significant inverse correlation (r = 0.56, p = 0.025 at Fz). 98 Selectivity of working memory impairments in schizophrenia S Lis, S Krieger, H Janik, J Wilhelm, B Gallhofer Klinik für Psychiatrie und Psychotherapie Justus-Liebig-Universität, Giessen, Germany Many studies of cognitive dysfunction in schizophrenia depicted impairments of the patient group in the paradigms applied. These are mostly interpreted as specific disturbances of the cognitive function under investigation. During the last years processes of working memory have been discussed as candidates for a prominently disturbed function. The aim of the present study is to analyze whether these impairments can be regarded as selectively disturbed or whether they result from deficits in elementary cognitive (sub-)processes prohibiting a successful solution of more complex tasks. 12 patients with firstepisode, drug-naïve schizophrenia and matched controls were studied. To assess working memory processes two types of N-back tasks (continuous-delayed-response (CDRT), continuous-matching (CMT)) were applied. To measure the contribution of basal cognitive sub-functions these are implemented into a visual reaction-time-decomposition-paradigm with simple-reaction-, discriminative-reaction-, and choice-reaction-tasks. In both N-back tasks patients had a lower accuracy and increased processing times. In CMT these deficits can be explained by a slowing already observable in choice-reaction. In contrast, additional deficits are observable in CDRT that point to different processing strategies in patients and controls. Our results demonstrate that deficits in complex cognitive tasks can be mimicked by dysfunction of elementary cognitive sub-functions. 99 Towards an individualized pharmacotherapy of alcohol dependence, pPoject PREDICT K. Mann, M. Smolka, B. Croissant,A. Diehl, U. Zimmermann,A. Heinz* Central Institute of Mental Health, Mannheim, University of Heidelberg, Germany *Dept. of Psychiatry, Humboldt University Berlin, Charité, Germany Previous attempts to identify predictors for the treatment response in alcoholism have mainly concentrated on social and personality vari-

I/28 ables. Project MATCH was such an attempt which finally failed. The same holds true for similar attempts in pharmacotherapy. Therefore, we set out for a large oligocentre trial “Project PREDICT”. 432 patients are randomly assigned to treatment with acamprosate, naltrexone or placebo. At baseline patients are assessed with a battery of interviews, questionnaires and biological examinations (e. g. genetics). Specific emphasis is put on patients’ individual pathways into relapse. It is determined whether relapse drinking respresented a positive reinforcer (“reward craving”) or a negative reinforcer (“relief craving”). This is assessed with questionnaires, the startle reflex and fMRI. We hypothesize that patients who are a priori identified as “positive reinforcers” better respond to naltrexone. Negative reinforcers should benefit most from acamprosate. Currently about 200 patients have been included. Preliminary analyses suggest that it seems indeed possible to distinguish between the two craving types. The equivalent of positive reinforcement in the startle reflex correlates with fMRI responses to cues with a positive valence of about 0.7. These methods might offer a platform for a targeted pharmacotherapy in alcoholism. 100 Depression in patients with Alzheimer’s disease J Marksteiner Department of General Psychiatry, University of Innsbruck, Austria Alzheimer disease is a progressive disease accounting for more than 50 % of patients with dementia. Besides cognitive and functional decline, neuropsychiatric disturbances are found in a majority of patients and may vary with the severity of dementia in probable AD. The frequency of major depression decreases in severe stages, while agitation, aggression, and psychosis are more frequent in late stages. A few small placebo-controlled antidepressant trials have been performed in patients suffering from dementia.Alzheimer patients without major depression (n = 44) and with major depression (n = 46) were included in a prospective, open-labelled 16 weeks study. The CERAD neuropsychology battery, the trailmaking part A and part B and a clock drawing test were used to test cognitive performance. The Cornell Scale for Depression in Dementia and the Geriatric Depression Scale were applied as depression rating scales. After 16 weeks, about half of the patients were classified as responders. In general, cognitive parameters did not significantly improve in patients recovering from depression. Alzheimer patients take benefit from treating depression with citalopram, improvement in cognition, however, may not be a major treatment outcome. 101 Adjunctive bright light in non-seasonal major depression K Martiny, M Lunde, M Undén, H Dam, P Bech Psychiatric Research Unit, Frederiksborg General Hospital, Denmark Objective: To test the effect of adjunctive bright light treatment in patients with non-seasonal major depression in a double-blind randomised clinical trial. Method: Patients with a DSM-IV diagnosis of major depression without fulfilling the seasonal pattern specifier were blindly randomised to 5 weeks of treatment with either 1 hour of bright light with 10,000 lux or 1/2 hour of dim red light with 50 lux in the morning. All patients were treated with 50 mg sertraline/day. The depression diagnosis was made by use of the M. I. N. I. Treatment took place at the patients’ home. Several measures were used to obtain the double-blinding. The patients were informed that light therapy could be of varying intensity and colour, without further specification. The patients were not in contact with other participants in the study. The instructions for the light therapy were delivered in a closed envelope to be opened at the patient’s home. The patients were instructed not to reveal any detail of the light treatment to the investigators.A secretary from another unit handed out the lamps in a slip-on cover. Light intensity for dim light treatment was reduced by use of a red film behind the screen and electronic dampening, but the external appearance of the lamp was, apart from the colour of the screen, identical with the bright light lamp. The patients were seen at weekly visits. De-

pression severity was assessed by use of the Hamilton Depression Rating Scale (17 item version), the Hamilton subscale (6 items), the Melancholia Scale (6 items) and the SIGHSAD (24 items). Seasonality was assessed by use of the SPAQ. Side effects were assessed by use of the UKU with supplementary items for light therapy. Results: In total, 102 patients were included in the study. Mean age was 44.6 years, male/female ratio was 0.44. The 7 atypical items from the SIGHSAD (except ‘reverse diurnal’) had a baseline score of 6.5. The SPAQ global seasonality score (GSS) was 9.4. On all four outcome scales the bright light group had a statistically significantly faster reduction of depression scores. Response and remission rates were statistically significantly higher for the bright light group. Thus, at Week 5, the response rate (50 % reduction on HAM-D17) was 66.7 % in the bright light group compared to 40.7 % in the dim light group. The remission rates (a score of less than 8 on the HAM-D17) were 41.7 % in the bright light group and 14.8 % in the dim light group. At the end of the study, the patients were asked to evaluate, in percent, the perceived benefit from the various treatment elements (psychosocial support, drug, light treatment and others). The benefit from light treatment was rated 22.25 % in the bright light group and 16.9 % in the dim light group. We interpret this as an expression of an acceptable blinding. Conclusion: This study confirms the effects of adjunctive bright light treatment in non-seasonal depression. The post-study evaluation implies a sufficient degree of blinding of light treatment conditions. 102 Paintings of an artist with Alzheimer’s disease: visuoconstructural deficits during dementia K. Maurer, D. Prvulovic Department of Psychiatry and Psychotherapy, University Clinic of Frankfurt, Germany Patients suffering from Alzheimer’s Dementia (AD) have increasing difficulties to orient in space and often fail to recognize basic realities and even their closest relatives. These symptoms lead to severe deterioration of everyday life and finally to total dependence. In this report we present the case of Carolus Horn, a famous German artist, who contracted with AD. The qualitative and quantitative analysis of changes in his artwork during disease progression gives an impressive insight into the patient’s visual world and how it becomes increasingly affected by delusional misperceptions, spatial errors and changes of colour-perception in the course of disease. Carolus Horn’s artwork lets us see the world through the patient’s eyes and thus helps us to better understand the consequences of visuospatial and cognitive changes in AD. 103 Towards a theory of human sciences G Medicus1, 2, 3 1 Psychiatrisches Krankenhaus des Landes Tirol, i.T, Austria 2 Gruppe Humanethologie in der Max-Planck-Gesellschaft,Andechs, Austria 3 Lehrauftrag “Einführung in die Humanethologie” Universität Innsbruck, Austria Interdisciplinarity in human sciences and the dialog among them is often characterized by a variety of contradictory fundamentals and hypotheses which sometimes seem unfounded from the view of neighbouring disciplines (e. g. between different schools of psychotherapy). This sometimes leads to disparagements of both the hypotheses and the disciplines. From a scientific approach, the situation is unsatisfactory. This sets out to present a fundamental orientation matrix for human sciences, which makes it possible to improve and structure the transdisciplinary discussion and learning process.

I/29 104 Autonomic changes in patients with chronic therapy-resistant depression before and after the application of a vagal nerve stimulator (VNS) N Messerli, T Schläpfer, C Frick, Z Stanga, H-U Fisch, K LaederachHofmann Autonomic Laboratory, Out-Patient Clinic for Psychiatry, Department of General Internal Medicine, University Hospital, Berne, Switzerland Introduction: Patients with depression show distinct abnormalities in autonomic functions and therefore are prone to higher cardiovascular risk. Aim: Fifteen patients (5m/10 f, aged 45.0 ± 11.0 yrs. (mean ± SD)) were investigated in this pilot study. All suffered from refractory major depression. Methods: Autonomic functions using standard non-invasive technique (TFM-systems, Graz) were assessed before, as well as 2 hours, 3, and 6 months after establishing the VNS stimulation. All patients were tested in resting and mental stress conditions (Stroop-Test). Transformed power values (ln) were used for total heart rate and midand high-frequency heart rate bands. Results: VNS patients had reduced total, mf-, hf-power values beforehand. ANOVA for repeated measures depicted a significant increase in total and hf power values (p < 0.05), whereas mf did not change. Baroreceptor sensitivity increased significantly from 3.24 ± 0.88 to 3.49 ± 4.19 ms/mmHg (p < 0.05) in resting conditions, and decreased from 5.20 ± 2.99 to 3.58 ± 2.67 ms/mmHg (p < 0.05) in mental stress conditions. In parallel, depression values (HRSD-21) were reduced significantly (p < 0.05). Conclusion: This VNS-study shows a significant effect on normalizing autonomic functions. Future research has to confirm its effects on subsequent morbidity and mortality as well as on depression and quality of life issues.

105 Prenatal immune challenge during mid-pregnancy in mice: Adult offspring behavioural consequences related to animal models of schizophrenia U Meyer, BK Yee, J Feldon Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zurich, Switzerland Epidemiological studies have demonstrated an association between maternal exposure to bacterial and viral infection during pregnancy and an increased incidence of schizophrenia among the offspring. The wide variety of infectious agents involved suggests that factors common to the infectious process, rather than the identity of a given infectious agent, are critical for the increased risk of developing schizophrenia. Cytokines released by the activation of the maternal immune system may play a central role in the neurodevelopmental origin of schizophrenia, since they are the main chemical mediators of the host defence response to bacterial and viral infection, and there is now substantial evidence that cytokines released by the mother can cross into the fetal circulation and impact the fetal brain. A variety of cytokines have been described to have important roles in the development of the central nervous system, having effects on the survival and differentiation of neurons, as well as on the modulation of neurotransmitter and neurotrophin secretion. It has therefore been proposed that the presence of increased levels of pro-inflammatory cytokines during embryogenesis is detrimental to normal brain development, leading to cytoarchitectural abnormalities in the adult brain. The experiments presented here are part of an animal model to study the influence of prenatal immune stimulation on the post-pubertal emergence of psychosis-related behaviour in mice. To induce an immune challenge during pregnancy that is comparable to the virally induced immune activation, pregnant mice were infected during mid-pregnancy with different doses of the cytokine releasing agent PolyI:C, a synthetic analogue of doublestranded RNA. Adult mice of PolyI:C-treated mothers were tested using behavioural paradigms described to be relevant for the modelling of psychosis-related symptoms. We demonstrated that PolyI:C-in-

duced stimulation of the maternal immune system during pregnancy dose-dependently resulted in abnormal offspring behavioural performance related to animal models of schizophrenia, including deficits in exploratory behaviour in the open field, deficiencies in prepulse inhibition (PPI), disruption of latent inhibition (LI), as well as abolished expression of the US-pre-exposure effect (USPEE), thereby replicating and extending similar findings in rodents (Borrell et al., Shi et al., Fatemi et al., Zuckerman et al., Fortier et al.). In all the behavioural tests conducted, a single prenatal administration of 5.0 and 10.0 mg/kg PolyI:C impaired adult behaviour, whereas the dose of 2.5 mg/kg only affected behavioural performance in the open field as well as LI. In conclusion, the findings from our laboratory together with findings reported by others suggest that behavioural sequela in adults following neurodevelopmental infectious stimuli represent an important advance in modelling schizophrenia because they mimic the long latency between the prenatal insult posited to occur in schizophrenia as well as the clinical diagnosis with regards to both positive and negative symptoms. The challenge remains to define the underlying mechanisms whereby prenatal immune activation can lead to neurodevelopmental abnormalities implicated in schizophrenia.

106 Altered superoxide dismutase (SOD)-coenzyme concentrations in post-mortem brain tissue of patients with major depression compared to controls – a post-mortem study TM Michel1, D Martin1, S Zwerina1, E Koutsilieri1, K Nara2, J Jecel1, P Riederer1 1 Clinical Neurochemistry, Dept. of Psychiatry and Psychotherapy, University Würzburg, Germany 2 Dept. of Pharmacology School of Medicine, Showa University, Tokyo, Japan A growing body of evidence suggests an association between major depression and selective as well as persistent structural changes and volume loss in distinct brain areas. Previous theories have emphasized on the role of oxidative stress on neuronal cell death. In this study we focused on alterations in oxidative stress related enzymes. We compared Coupper/Zinc- and Manganese-Superoxide Dismutase (SOD) concentrations in post-mortem brain tissue of patients with major depression and neuropsychiatric healthy individuals (7/7) using ELISA technique. We detected a two-fold higher Cu/Zn-SOD concentration in frontal cortex of patients with major depression compared to control group. Furthermore we detected a significant lower Cu/Zn-SOD concentration in the caudate nucleus in the patients group compared to the control group. We found no changes in Manganese-SOD enzyme concentration in any of the examined brain areas in the different groups. Our results show alterations of SOD enzyme levels, especially in brain areas where significant changes were described previously for patients with major depression. Our findings imply oxidative stress to occur in major depression.

107 Face processing in schizophrenic patients with or without person misidentification syndrome (PMS) TJ Müller1, A Federspiel1, H Horn1, M Wirth1, P Bianchi1, B Eichenberger2, W Strik1 1 University Hospital of Clinical Psychiatry, Waldau, Bern, Switzerland 2 Institute of Psychology, Dept. of Clinical Psychology and Psychotherapy, University of Bern, Switzerland Neuropsychological investigations in patients with prosopagnosia have given evidence of specific anatomical loci of face processing in temporo-occipital brain areas. Electrophysiological investigations showed face specific activation at about 170 ms after stimuli at vertex. At least, a large number of neuroimaging studies currently address their focus on clarifying how the brain processes face stimuli. In this context, the so-called fusiform-face area (FFA) has been found to be in centre of the face processing system. Impaired processing of faces

I/30 is known as an additional symptom in schizophrenia. This leads to social isolation by inadequate behaviour in everyday life. In a subgroup of acute schizophrenics, person misidentification is a prominent symptom. Patients mistake people or they believe to know people who they actually cannot know. With a face processing paradigm further developed from a study of our group an exploratory study showed that the task performance allowed for segregating controls, schizophrenics with and without PMS. Furthermore, a functional MRI study investigated whether the task performance is correlated with the BOLD activation and the perfusion as measured by ASL (arterial spin labelling) of the FFA or other brain regions that are presumably involved in face processing. Preliminary data show that schizophrenic patients have less reactivity to a checkerboard paradigm in the FFA as compared to normal controls. This underlines that face processing in schizophrenic patients is impaired at an early level of information processing. 108 Neuropsychological assessment of adult attention deficit/hyperactivity disorder (ADHD) BW Müller1, 2, K Gimbel, A Keller-Pließnig1, G Sartory2, M Gastpar1, E Davids1 1 Clinic for Psychiatry and Psychotherapy, University of DuisburgEssen, Germany 2 Clinical Psychology, University of Wuppertal, Germany The assessment of adults with ADHD has attracted scientific research recently and neuropsychological assessments revealed deficits in attention, executive and memory functions. Here we aimed to assess cognitive function in adult patients with ADHD. N = 30 adults with ADHD (20m/10f, age 33.9y) and 15 healthy control subjects matched for age, sex and education (5m/10f, Alter 32.9J) were assessed with measures of premorbid intelligence; motor function; response inhibition; verbal and nonverbal memory; problem solving; Trails A/B; covered shift of, sustained and divided attention and word fluency. Assessments of symptoms comprised self- and psychiatrist rated scales of ADHD, impulsivity, depression and anxiety. Patients were under methylphenidate treatment. Premorbid intelligence and multivariate analysis of overall cognitive function did not reveal significant differences between groups. Selective deficits were found in tests of response inhibition, verbal and nonverbal memory, the trail making test, covered shift of attention, in reaction to invalid cued targets and in reaction time measures in the divided attention task. Our results revealed deficits in executive control, memory and attention persisting under pharmacological treatment. Attention deficits were seen in reaction to non-valid target cues and in heightened reaction times in complex tasks. No deficits were evident in measures of sustained attention. 109 Attitudes towards different drug formulations in a psychiatric hospital: the view of patients and staff members MJ Müller, R Herr, C Maurer, KM Müller, LG Schmidt Department of Psychiatry, University of Mainz, Mainz, Germany Background: Limited compliance is an ongoing problem in the treatment of psychiatric patients even after the advent of newer and welltolerated drugs. New drug preparations (e. g. fast-dissolving drug formulations [FDDF], liquids, new depots) have been supposed to improve compliance in psychiatric patients. Methods: We investigated the attitudes towards several possible drug formulations (e. g., tablet, capsule, FDDF, unflavored and flavored liquid, subcutaneous, intramuscular, intravenous injection, depot injection, infusion, etc.) anonymously in 62 inpatients and 96 staff members of a psychiatric hospital. Individual acceptance ratings were obtained for different drug formulations using a questionnaire with 6-point scales (1 = very high, 6 = very low). Finally, the participants were asked for the most preferred drug formulation. Results: No substantial differences emerged between staff members and psychiatric inpatients regarding the acceptance of any single drug formulation. In both, patients and staff members, conven-

tional tablets received highest acceptance (patients 2.1 ± 1.2, staff 2.2 ± 1.1) and infusion therapy lowest acceptance ratings (patients 4.1 ± 1.6, staff 4.5 ± 1.3). The most preferred drug formulations in both groups were tablets (37 %), capsules (22 %), and FDDF (11 %). Conclusion: The study requires replication in patient groups with specified diagnosis; nevertheless, the issue and the findings should be considered when compliance enhancement programs are designed. 110 The role of immunology in Alzheimer’s disease N Müller Hospital of Psychiatry and Psychotherapy, Ludwig-Maximilian University Munich, Germany Several lines of evidence suggest that immunological/inflammatory mechanisms play a role in Alzheimer’s disease (AD). In healthy people, a relationship between cognitive performance and lower levels of inflammatory parameters has been described. In an animal model, mice deprived of mature T-cells develop cognitive deficits which were remediable by T cell restoration.Epidemiological studies indicate that anti-inflammatory drugs, especially the non-steroidal anti-inflammatory drugs (NSAIDs), decrease the risk of developing AD. Laboratory evidence suggests that inflammatory mechanisms contribute to neuronal injury in AD. It is known that the plaques of patients with AD are associated with activated microglia and increased expression and concentration of inflammatory proteins, e. g. Interleukin-1 (IL1), IL-6, C-reactive protein (CRP),
1-antichymotrypsin or tumor necrosis factor-
. Whether the inflammatory process is part of the pathophysiological mechanism or a secondary reaction to underlying processes is matter of discussion. The role of immunological alterations, inflammation, and possible therapeutic implications is discussed. 111 Clinical aspects of therapeutic drug monitoring (TDM) of olanzapine in the treatment of schizophrenia MJ Müller, J Reiss, S Härtter, C Hiemke Department of Psychiatry, University of Mainz, Mainz, Germany Background: TDM of many psychotropic drugs is useful to detect pharmacokinetic irregularities, interactions, toxicity, and non-compliance. Regarding newer atypical antipsychotics, the potential clinical benefit of TDM still has to be demonstrated. The present analysis shows advantages and limitations of clinical routine TDM of olanzapine (OLA) in the treatment of schizophrenia. Methods: In a naturalistic clinical study, OLA plasma levels detected by HPLC method in 97 inpatients with schizophrenia under OLA monotherapy (mean age 37.3y; 47 % female) were related to clinical response (CGI) and side-effects (UKU) taking into account gender, smoking habits, and BMI. Results: Mean daily OLA dose was 18.4 mg with a mean plasma level of 35.9 ng/ml. Women had significantly higher dose-corrected plasma levels than men (2.4 ± 1.3 vs. 1.8 ± 1.2 ng/ml:mg).Additionally, smokers had lower OLA plasma levels. Regarding clinical response (48 %) and occurrence of at least mild side-effects (32 %) no significant gender differences were found. 62 % of patients with OLA plasma levels between 20 and 40ng/ml vs. 44 % when plasma levels were outside this range showed a clinical response and an absence of side-effects (P = 0.02). Conclusion: TDM of OLA could be clinically useful to individually optimize treatment with respect to response and avoidance of side-effects.

I/31 112 Cyclooxygenase-2 inhibition as therapeutic approach in psychiatric disorders N Müller, M Riedel, M Schwarz Psychiatric and Psychotherapeutic Hospital, Ludwig-MaximiliansUniversity, München, Germany Cyclooxygenase-2 (COX-2) – constitutively expressed in the CNS – is suggested to have an important functional role in the CNS. COX-2 interacts with neurotransmitters such as acetylcholine, serotonin, and glutamate, but is also involved in the regulation of the immune system and in inflammation in the central nervous system (CNS) via effects of prostaglandins, in particular prostaglandin E2. Recently, a role for the new generation of selective COX-2 inhibitors in the treatment of psychiatric disorders is discussed. Until now, COX-2 inhibitors have failed to show therapeutic effects in Alzheimer’s disease, but studies from basic research point to a possible effect on cognition. A clinical effect of the COX-2 inhibitor Celecoxib on cognition was observed in schizophrenic patients. The therapeutic effect of Celecoxib add-on treatment to the atypical antipsychotic risperidone, however, is not restricted to cognition. A general effect on symptoms of schizophrenia was observed, this finding supporting the view that an immunological/inflammatory process is involved in the pathogenesis of schizophrenia. In depression, however, signs of inflammation have been described for many years. Although results of clinical studies with COX-2 inhibitors in depression are still lacking, clinical improvement of a depressive syndrome has been observed in patients, who have been treated with rofecoxib due to other indications. These preliminary clinical data are encouraging for therapeutic effects of the selective COX-2 inhibitors in psychiatric disorders, although these effects have to be confirmed in larger clinical studies. 113 Disturbed target detection in patients with schizophrenia. A simultaneous 61-channel EEG/fMRI-Study C Mulert1, S Karch1, L Jäger2, M Teutsch1, C Seifert1, S Propp1, O Pogarell1, HJ Möller1, U Hegerl1 1 Department of Psychiatry, LMU, Munich, Germany 2 Institute for Clinical Radiology, LMU, Munich, Germany The P300 component of the event-related potential is thought to reflect various cognitive processes including the allocation of attentional resources to incoming stimuli. Reduction of the auditory P300 amplitude is constantly found in schizophrenic patients. Besides it could be shown that the P300 amplitude correlated negatively with the severity of thought disorders. Thus the P300 appears to be a suitable functional parameter of thought disorders in schizophrenic patients. We combined ERP and simultaneously acquired functional MRI data to examine discrepancies in brain regions involved in information processing as well as in the time course of neural generators of the event-related potential between nine schizophrenics and matched normal controls. The EEG recordings showed the expected positive deflection about 350 ms after the presentation of infrequent stimuli in normal controls and a reduced P300 component in schizophrenics. Besides we could replicate findings of previous P300 studies revealing BOLD activations mainly in frontal, especially anterior cingulate cortex, SMA, insula, inferior and middle frontal gyrus as well as thalamus, temporal and parietal brain structures in healthy subjects. The functional MRI data of schizophrenic patients showed a reduced BOLD response in a widespread network of cerebral areas involved in task execution. There was a modest negative correlation between the extent of functional activation in the ACC/SMA region and thought disorders as well as negative symptoms (PANSS).

114 Lateral asymmetry in the mammalian brain: monoamines, plasticity and pathology J Neddens Neuroanatomie, Universität Bielefeld, Germany Currently, it is well accepted that various structural and functional properties of the brain are lateralised, being more or less unequally distributed between the left and right hemispheres. It had been argued for a long period of time that cerebral asymmetries should be a phenomenon unique to the human brain. Recent investigations fundamentally change this view. In addition, there is considerable evidence to argue that lateralised brain functions are already present early in life influencing postnatal development of experience-dependent characteristics of the hemispheres. Several authors proposed different hypothetical mechanisms that may regulate morphological and functional asymmetries in the development of the cerebral cortex. Disruption of this process may result in a somewhat malfunctional developing brain, with lateralisation being restricted to suband allocortical areas. We present results investigating the amount of lateralisation of monoaminergic fibre systems and alterations of the asymmetry following external stimuli during postnatal brain maturation. We assume that epigenetic factors might be important candidates in controlling development of adult lateralised brain functions and behaviour. Notably, because of the significant role of monoaminergic systems in various forms of psychopathology, there is an outstanding need for future research to further evaluate the part of serotonin and dopamine in orchestrating lateralised brain function in concert with other neurotransmitters. 115 Lateral asymmetry of monoaminergic innervation of the gerbil forebrain: adaption/maladaption to external stimuli J Neddens, J Lesting, A Busche, G Teuchert-Noodt Neuroanatomie, Universität Bielefeld, Germany Recent findings suggest that the ontogenesis of cortical laterality is influenced by epigenetic factors and that disturbances of the postnatal maturation of lateralised functions may be associated with certain psychopathological behaviours.We present several studies investigating the lateralisation of serotonergic and dopaminergic fibre systems in the forebrain of gerbils and alterations of the innervation pattern following postnatal exposition to acute and chronic external stimuli: A single high dose of methamphetamine at postnatal day 14, chronic exposure to social isolation and non-stimulating environment from day 30 to adulthood. Thereafter, immunohistochemistry and quantitative image analysis were used. We found lateralised serotonin innervation in prefrontal, insular, frontal motor, and entorhinal cortex, whereas in parietal somatosensory cortex no asymmetry occurred. Lateralised effects due to restricted environment and/or methamphetamine were found in prefrontal and entorhinal cortex as well as in dentate gyrus, in the amygdala and in nucleus accumbens. Concerning the dopaminergic innervation, lateralised effects occurred in the amygdala, whereas no effects were found in nucleus accumbens. In conclusion, it appears that external stimuli, such as rearing condition or early pharmacological challenge, differentially interfere with postnatal development of lateralised innervation of monoaminergic fibre systems in different areas of the mammalian forebrain. A subsequent maladaption of functional systems may result in aberrant behaviour and, finally, in psychosis. 116 Synaptic long-term plasticity is involved in the pathophysiology of depression C Normann Dept. of Psychiatry and Psychotherapy, University of Freiburg, Germany. Synaptic long-term plasticity (long-term potentiation, LTP; longterm depression, LTD) is a cellular model for learning and memory and a form of functional neuroplasticity. Recent results suggest a role

I/32 for LTP/LTD in the neurobiology of stress, fear conditioning and affective regulation. In patch-clamp experiments from hippocampal brain slices, we have shown that serotonin and noradrenaline both upregulate synaptic plasticity by different mechanisms. All marketed SSRIs are potent blockers of neuronal calcium channels, an effect which is independent from serotonin. By inhibition of calcium influx, SSRIs dose-dependently decrease LTD and upregulate synaptic transmission. Lithium inhibits LTD by acute modulation of PKC. These results suggest that several neurotransmitters, antidepressants and mood stabilizers share a common pathway by distinct mechanisms and upregulate synaptic transmission; an effect which is expected to be delayed and persistent. To control this hypothesis in depressed humans, we recorded visually evoked potentials (VEPs) in depressed patients and normal controls. We found decreased amplitudes of early VEPs in depression and a marked increase of early VEPs in normal controls which had been treated with sertraline for 3 weeks. The induction of an LTP-like potentiation of VEPs by high-frequency visual stimulation was compromised in depressed humans. We conclude that the regulation of synaptic plasticity and its pathology might play an important role in the pathophysiology of depression. 117 Deficient latent inhibition in unmedicated first-episode schizophrenia AT Orosz1, 2, J Feldon1, G Gal3; K Ludewig2, 4 1 Laboratory of Behavioral Biology, ETH Zürich, Switzerland 2 Department of Research, Psychiatric Services of Aargau Canton, Switzerland 3 Shalvata Mental Health Care Center, Hod Hasharon, Israel 4 Department of Psychiatry, Inselspital, University of Bern, Switzerland Latent inhibition (LI) has been considered to be a measure of information processing. We used a recently developed computerised within-subject, target-recognition LI paradigm which consists of three different stimulus conditions encompassing novel and preexposed stimuli (preexposed – “PE”, non-preexposed – “NPE”, random – “R”). The aim of this study was to find out if patients, at the beginning of their illness, show different latency times in the various conditions, indicating their ability to ignore irrelevant stimuli and to attend to important information.We investigated the performance of 11 first-episode schizophrenia patients and 17 healthy controls matched by age, gender and smoking habits in this LI paradigm. Between (schizophrenics vs. control) and within (different stimulus conditions) subjects analysis of variance, as well as Spearman correlation analysis for clinical variables, was applied. The healthy controls showed intact LI in terms of gradual reduction of latency time between the different conditions: NPE < PE < R. In contrast, the patient group exhibited similar latency times for all three conditions. This difference in LI-effect was highly significant between groups. The LIresults were correlated with psychopathology measures. In our study we were able to show that LI-effects are measurable by this novel test and that schizophrenics fail to show this effect. 118 Clinical genetic findings in cycloid psychoses. B Pfuhlmann Klinik und Poliklinik für Psychiatrie und Psychotherapie der Universität Würzburg, Germany Cycloid psychoses represent a clinically well characterised diagnostic category which can be distinguished from schizophrenic and affective psychoses regarding symptomatology and course.To clarify the nosological position of cycloid psychoses clinical genetic studies are an important tool. In a family study, all living and traceable adult firstdegree relatives of 45 cycloid psychotic, 32 manic-depressive and 27 control probands were personally examined by experienced psychiatrists blind to the index-proband’s diagnosis. Information about not traceable relatives was obtained by the “Family-History”-Method. Morbidity risks were calculated using the life-table method. Relatives of cycloid psychotic patients showed a significantly lower morbidity

risk of endogenous psychoses than relatives of manic-depressive patients, and did not differ significantly from controls with respect to familial morbidity. In a twin study, 22 twin pairs with cycloid psychotic index twins were systematically recruited among psychiatric inpatients in Lower Franconia. After establishing the diagnoses of the cotwins by an independent psychiatrist concordance rates were compared. Pairwise as well as probandwise concordance rates did not differ significantly between monozygotic and dizygotic subjects. In this regard cycloid psychotic twins differed clearly from twins with unsystematic schizophrenias who showed significantly higher concordance rates among monozygotic subjects.

119 Biological psychiatry and hermeneutics constitute a model of evidence-based mental health (EBMH) P Portwich University Psychiatric Services Bern, Switzerland Evidence-based medicine (EBM) gains increasing importance and its transfer to psychiatry is required. EBM has been criticised to favour RCTs and metaanalyses from biological research and thereby to neglect the individuality of the single patient and the variability of human experiences. An accurate look at EBM, however, reveals a sophisticated path of decision-making in clinical practice that includes different steps: Besides the search for the best evidence, a relevant step is marked by the following question: Is the intervention, recommended by the best evidence, appropriate for my single patient and does it really meet his very personal needs and desires? This step of EBM focuses on the concrete case and the patient’s specific history.We suggest a model of EBMH that equally stresses the search for the best evidence as well as the reflection of the single case. In particular, we suggest the integration of hermeneutics. Modern theories of professional practice support hermeneutics as a tool for client-centred decision-making: Hermeneutics are the method that focusses the comprehension of the single case as a unique phenomenon. Thus, hermeneutics may serve as a subtle method for patient-centred decisions and may – in this model of EBMH – complete the evidence, derived from biological psychiatry.

120 Duration of untreated psychosis and course of child and adolescent psychotic disorders U Preuss, H Meng, D Bürgi, W Felder, M Günter Dept. of Child and Youth Psychiatry, University of Bern, Switzerland Objective: To examine the development of course in children’s and adolescents’ first and early-onset psychotic illness in relation to the duration of untreated period before the first clinical diagnosis and initiation of psychiatric treatment. Method: These data are from a one year longitudinal, prospective, cooperative study from different sites in Austria, Switzerland, and Germany. 69 subjects were drawn from a 1-year observational study on individuals aged 11–18 with early onset psychotic disorders, schizophrenia, schizophrenia spectrum disorders, and affective disorder with psychotic symptoms. Diagnosis was derived from SCID I interviews and on basis of DSM-IV criteria for schizophrenia. Participant’s development was observed 3 times during treatment and after release. Results: Youths with schizophrenia (sz: n = 24), schizophrenia spectrum disorders (sp: n = 27), affective disorder, psychotic symptoms (af: n = 7) were included.DUP measured in estimates of patients, parents and investigators showed various sizes between informants and raters. Juvenile Psychosis’ DUP was shorter than DUP reported for adults (5–10 weeks instead of 100–450 weeks). Correlations between parents’ and raters’ estimates of DUP and a limited range of predictive value of DUP for symptoms and general measures for over all outcome after one year characterized the relevance of the duration of the untreated period in young first episode individuals, but only small predictive value from Duration of untreated psychosis on one outcome could be found. Other disorders were clearly differentiated

I/33 from psychotic disorders in symptoms, course, and outcome. Small samples limited proof in this domain. Conclusions: The concept of DUP is very general and may be of relevance for outcome, but DUP estimated retrospectively. This limits the evidence derived from analyses of DUP in relation to measures of course and outcome. Clinicians must be careful in overrating the length of DUP, but early recognition of psychotic disorders stays in first line tasks, until it is resolved whether DUP is of absolute relevance for severity and long-term outcome in psychosis or less important as considered today. 121 Homocysteinemia is not associated with schizophrenia, but with dementia and depression A Reif Department of Psychiatry and Psychotherapy of the Julius-Maximilians-University Würzburg, Germany Homocysteinemia – i. e., the elevation of homocysteine plasma levels – is meanwhile recognised to be a risk factor not only for atherosclerosis, but probably also for dementia and depression. To further explore a possible association between homocysteine elevation and psychiatric disorders, fasting homocysteine, vitamine B12 and folate were determined in an ethnically homogeneous female population suffering from endogenous psychoses or dementia. Homocysteine was within the reference range in females suffering from schizophrenia (mean, 11.6 ± 5.8 µmol/l).As shown in previous studies, homocysteinemia was associated with dementia of different aetiology (mean, 17.2 ± 6.7 µmol/l; χ2 = 23.39, p < 0.001, compared to the schizophrenia group), but also with depressive disorders (mean, 12.9 ± 3.8 µmol/l; χ2 = 6.88, p = 0.009). Generally, homocysteinemia was found more frequently in elderly subjects. B12 and folate levels did not differ between different diagnostic groups. On a molecular basis, methylenetetrahydrofolate reductase polymorphisms did not seem to increase the risk for endogenous psychoses. In conclusion, homocysteinemia appears to be an unspecific risk factor for organic brain disorders like dementia and possibly also “vascular depression”, but not for other endogenous psychoses. 122 Which factors are influencing drug compliance? – a multicenter study T Rhein1, S Weinmann2, B Janssen1 1 Rheinische Kliniken, Düsseldorf, Germany 2 Bezirkskrankenhaus, Günzburg, Germany Background: As schizophrenia is a chronic disease and psychotropic medication is generally administered chronically, subjective attitudes and long term adherence are of particular concern for medication choice. The aim of this multicenter study was to evaluate some patient-related and treatment-related factors associated with drug compliance in a naturalistic setting and to assess predictors for compliance. Method: Drug compliance was determined by using a scale consisting of seven categories within a structured interview. Individuals were asked by the treating physician before discharge to tell their opinion towards medication. In addition, their drug-related behaviour as observed by nurses and the physician was taken into account for the ratings. Results: In summary, we found a significant correlation between a low compliance and substance abuse, involuntary admission and a history of aggressive behaviour. Additionally, the perception that drugs are effective, seems of utmost importance for a good compliance. As expected, individuals with pronounced paranoid and those with prominent negative symptoms had a lower likelihood to follow medical advice. The Health Belief Model (HBM) considering health behaviour as a result of the interplay among certain construct factors may serve as an explanatory model also for our treatment compliance results.

123 Coordination between voluntary rhythmical movements of the forearm and breathing in patients with catatonic schizophrenia and healthy testpersons S Rudolph, D Ebert, P Bräunig Klinikum Chemnitz GmbH,Clinic for Psychiatry,Chemnitz,Germany Coordination between rhythmical movements of extremities and breathing is a sensitive indicator for central nervous controlling and programming of movements. Sinusoidal tracking movements of the forearm with small amplitudes inside the frequency range of spontaneous breathing rates (0.2–0.5 Hz) have been varied in steps of 0.1 Hz systematically. Breathing has been recorded in parallel using a respitrace setup. Phase relations between breathing and forearm movements and their statistical parameters were calculated. A group of 8 patients suffering from a catatonic schizophrenia (evaluated by a catatonic rating scale) was compared with a comparable group of healthy subjects. No differences of the breathing parameters in different resting positions of the body were detected between the patients and the health persons. The accuracy of the rhythmical tracking movements was reduced in the patients followed by diminished coordination between breathing and movement. In severe cases physiological coordination failed completely. In the patients the breathing process appeared not to be disturbed by carrying out the movements. Nevertheless breathing rates adapted to the forearm movement rates in healthy subjects following the phase attraction. The disturbed coordination between breathing and voluntary movements in the catatonic patients reveals a dissection of the unity of sensorimotor subsystems on the level of movement programming. 124 Findings of structural brain imaging in subjects at clinical risk for psychosis S Ruhrmann1, R Tepest2, K Vogeley2 1 Department of Psychiatry and Psychotherapy, University of Cologne, Germany 2 Department of Psychiatry and Psychotherapy, University of Bonn, Germany Research on brain morphology of subjects putatively in an initial prodromal state of psychosis indicates that aberrations of structure and volume are already present before a first episode and may further progress. The gyrification of the frontal lobe is of special interest in this context, as it is completed during fetal life and thus provides considerable information with respect to potential disturbances of neurodevelopment. Indeed, measurement of the gyrification index (GI) as ratio of inner and outer contour revealed a right frontal hypergyria in schizophrenia. GI was measured in 22 putatively prodromal subjects in comparison to 22 normal healthy controls and 22 patients with schizophrenia. Measurements were performed on standard 1.5 Tesla T1-weighted MR-images on three subsequent slices at the level of the genu corporis callosi and 1 mm anterior and posterior to that level perpendicular to AC-PC line. Contours were traced manually; image analysis was performed with Optimas6.0. Mean GI values revealed a significant right frontal hypergyria in the diagnostic groups of prodromal stages (p < 0.01) and schizophrenia (p < 0.01), both compared to healthy controls. There was no significant difference between persons at-risk and schizophrenia patients. In conclusion, the GI is a promising candidate for a multivariate model for the prediction of psychosis.

I/34 125 Altered expression of tau exon 10 and of the CDC2-like kinases clk2 in post mortem brain of patients with Alzheimer’s disease D Rujescu1, D Glatz1, F Berendt1, F Faltraco1, H Hampel1, S Stamm3, AM Hartmann1, HJ Möller1, P Riederer2 1 Molecular and Clinical Neurobiology, Dept. of Psychiatry, LMU Munich, Germany 2 Clinical Neurochemistry, University Clinic for Psychiatry, Würzburg, Germany 3 University Institute of Biochemistry, Erlangen-Nürnberg, Germany Pathological inclusions containing fibrillar aggregates of hyperphosphorylated tau protein are a characteristic feature in tauopathies, which include Alzheimer’s disease (AD). Tau is a microtubule-associated protein whose transcript undergoes alternative splicing in the brain. Exon 10 codes for the second of four microtubule-binding repeat domains, inclusion of which gives rise to isoforms containing four microtubule-binding repeat domains (4R) whereas exclusion leads to isoforms containing only three repeat domains (3R). Similar levels of 3R and 4R isoforms are found in normal adult cerebral cortex. This balance appears to be essential for neuronal function in maintaining learning and memory. Cell culture studies show that tau exon 10 usage is influenced by CDC2-like kinase (clk2). Alternative splicing of clk2 exon 4 generates two isoforms which differ in the presence (+ exon 4) or absence (– exon 4) of the kinase domain. We, therefore, hypothesize a change in the expression pattern of tau exon 10 and clk2 in Alzheimer’s disease. Tau exon 10 containing isoforms were up-regulated in the prefrontal and temporal cortex whereas the expression was unchanged in the occipital and supplementary motor cortex. The active, exon 4 containing clk2 isoforms were down-regulated in all brain regions. Our results show that changing pre-mRNAprocessing pathways could be a new therapeutic concept for tauopathies. 126 EEG/ERP topography and tomography in diagnosis and pharmacotherapy of depression B Saletu, P Anderer, GM Saletu-Zyhlarz Department of Psychiatry, Medical University of Vienna, Austria Our EEG mapping studies in depression demonstrated a decrease in absolute power in all frequency bands, an augmentation of relative delta/theta and beta and a decrease in alpha activity as well as a slowing of the delta/theta centroid and an acceleration of the alpha and beta centroid, reflecting a decrease in vigilance. In the alpha asymmetry index, depressed patients showed right frontal hyper- and left frontal hypoactivation. Low-resolution brain electromagnetic tomography (LORETA) identified cerebral generators responsible for these differences. Regarding antidepressants, at least 2 types of pharmacoEEG profiles were seen: a thymoleptic type with sedative effects and a thymeretic one with activating properties. In event-related potential (ERP)-LORETA, depressed patients showed reduced P300 source strength bilaterally temporally and medially prefrontally, reaching to rostral parts of the anterior cingulate. Contrarily, citalopram increased P300 source strength in the left prefrontal cortex and precuneus, reaching to the posterior cingulate. Similarly, ademetionine increased LORETA power also in dorsal frontal regions and the posterior cingulate cortex and decreased it in ventral limbic regions. These reciprocal limbic-cortical changes are similar to PET data after fluoxetine and opposite to alterations in depression. These findings will be discussed in the light of a key-lock principle regarding diagnosis and treatment of depression. 127 Nonorganic insomnia related to anxiety disorders and anxiolytics: from polysomnography to EEG tomography (LORETA) B Saletu, P Anderer, GM Saletu-Zyhlarz Department of Psychiatry, University of Vienna, Austria Sleep laboratory investigations in nonorganic insomnia related to generalized anxiety disorder (GAD) demonstrated significantly in-

creased wake-time during the total sleep period (TSP), more early morning awakenings, decreased total sleep time (TST) and sleep efficiency as compared with normals. Concerning sleep architecture, decreased S2 % and increased S1, S3 + S4 %, but no REM differences were observed. Subjective sleep quality and morning thymopsychic (but not noopsychic) measures was deteriorated. Benzo-diazepines generally induced opposite changes. Nonorganic insomnia related to panic disorder demonstrated decreased sleep efficiency, TST and S2, increased middle and late insomnia, S1, S3 + S4, snoring and periodic leg movements as compared with controls, but there were no REM changes. Subjective sleep quality, drive and fine motor activity in the morning were deteriorated. Blood pressure and pulse rate were increased. As compared with placebo, alprazolam induced changes that were opposite to the differences observed between patients and controls before treatment, thereby normalizing sleep and awakening quality.The above-described studies point to a key-lock principle in the diagnosis and treatment of insomnia due to anxiety disorders and neurophysiologically visualize processes at the receptor level (e. g. benzodiazepine agonists vs. inverse agonists). This was supported by daytime investigations utilizing EEG mapping and low-resolution electromagnetic tomography (LORETA). 128 Red wine polyphenol resveratol protects from β-amyloid neurotoxicity E Savaskan, G Olivieri, F Meier, E Seifritz, A Wirz-Justice, F MüllerSpahn Psychiatric Clinic, University of Basel, Basel, Switzerland Resveratrol (trans-3, 4’, 5-trihydroxylstilbene) is a natural grape-derived polyphenol present in red wine and various food products such as peanuts and mulberries. Resveratrol has cardioprotective and cancer chemopreventive properties. The present study aimed at elucidating the possible neuroprotective effects of resveratrol against β-amyloid peptide (Aβ)-induced neurotoxicity. Aβ has been implicated to a great degree in cell death during the course of Alzheimer’s disease. The neuroprotective capacity of resveratrol against Aβ-related oxidative stress was studied in a cell culture model. Resveratrol maintains cell viability and exerts an anti-oxidative action by enhancing the intracellular free-radical scavenger glutathione. The findings suggest that resveratrol may be a highly neuroprotective substance. 129 Relationship between hostility, anger, schizotypal personality traits and cannabis use M Schaub, L Boesch, R Stohler Psychiatric University Hospital Zurich, Substance Use Disorders Research Group Zurich, Switzerland Purpose: This study aimed at characterising the relationship between aggressiveness and schizotypal traits in students taking into account their demographic and drug use characteristics. SAMPLE: Six-hundred and seventy-five first and second year psychology students from the University of Zurich, Switzerland. Methods: While attending a mandatory main course lecture, all first and second year psychology students were informed about the aims of the study. They were encouraged to fill in a set of online questionnaires from the Internet, comprising an assessment of demographic and drug use characteristics, the Aggression Questionnaire (AQ), and the Schizotypal Personality Questionnaire (SPQ). Two hundred and five students participated. Students’ AQ sub-dimensions, cannabis use and social demographic characteristics were compared. Results: The SPQ-total-score was strongly associated with aggressiveness measured by the AQ. AQ-subscales hostility and anger explain a substantial part of the SPQ-total-score variance, while frequency of cannabis use does not. Conclusion: Higher levels of hostility and anger in otherwise healthy students are better predictors of higher schizotypal personality traits than cannabis use.

I/35 130 1H-MRS in individuals with at-risk mental states H Scherk1, F Jessen2, F Träber3, W Maier2, HH. Schild3, P Falkai1, W Block3 1 Saarland University Hospital, Department of Psychiatry and Psychotherapy, Homburg, Germany 2 University of Bonn, Department of Radiology, Bonn, Germany 3 University of Bonn, Department of Psychiatry and Psychotherapy, Bonn, Germany 1H-MRS

(proton magnetic resonance spectroscopy) allows to determine in vivo concentrations of brain metabolic substances like Nacetyl-aspartate (NAA), Creatine/Phosphocreatine (CR) and Choline (CHO). NAA is a marker for neuronal integrity and functionality. Several studies of schizophrenic patients showed reduced concentrations of NAA in the frontal and anterior cingulated cortex. A total of 20 atrisk individuals (9 male/11 female; mean age 26.7 ± 6.1 yrs.) recruited from the early-detection clinic in Bonn and 22 healthy comparison subjects (14 male/8 female; mean age 27.2 ± 5.9 yrs.) participated in a 1H-MRS study. None of the subjects had a history of neurological or psychiatric illness, alcohol or substance abuse, or had been exposed to psychoactive medication at any time. At-risk individuals did not meet diagnostic criteria for psychosis, however, clinical interviews elicited evidence of trait and state symptoms consistent with current research definitions of at-risk mental states. The ratios of NAA/CR and NAA/CHO in the prefrontal cortex were reduced in at-risk individuals compared to healthy controls. In this region no significant difference was found for the ratio of CHO/CR. In the anterior cingulated cortex the ratio of NAA/CR was reduced in at-risk individuals compared to healthy controls while ratios of NAA/CHO and CHO/CR were not different. In this study we could show that reduction of NAA is not only found in schizophrenics but also in drug-naïve patients with at-risk mental states. These alterations might reflect the early course of the disease and are not caused by chronic illness or neuroleptic treatment. Further longitudinal studies have to show if these alterations can predict the transition to psychosis. 131 Smooth pursuit eye movements in dementia HJ Schewe, R Uebelhack Department of Psychiatry, Charité – Universitätsmedizin Berlin, CCM, Berlin, Germany Smooth pursuit eye movement (SPEM) abnormalities are well known in psychiatric disorders, specially in schizophrenia. In dementia, however, they were investigated rarely. 15 patients of both sexes with a clinical diagnosis of dementia of the Alzheimer-type or vascular dementia were included in this study. Diagnoses were established using ICD-10 criteria. The degree of cognitive deficit was quantified by means of the Mini-Mental-State-Examination and ADAS-cog. Smooth pursuit eye movements were recorded by high-resolution infrared oculography. A red laser light spot moved continuously at 0.5 Hz across ±15° of visual angle in a pendular manner. Velocity gain, number of catch-up saccades, anticipatory saccades and square wave jerks were determined, correlated to the degree of cognitive deficit and compared to SPEM parameters of 15 healthy controls. Patients with dementia showed a significantly lower velocity gain and a higher number of catch-up saccades than healthy controls. We found significant correlations between disturbances in SPEM-functions and the degree of cognitive deficits. 132 First results from the European multicenter trial D03 for vagus nerve stimulation in refractory major depression TE Schlaepfer1, 2, M Wagner2, C Frick1, 2, M Kosel2, S SchulzeRauschenbach2, A Zobel2 1 Psychiatric Neuroimaging Group, Clinic for Psychiatry, University Hospital, Berne, Switzerland 2 Brain Stimulation Group, University Hospital Bonn, Germany Introduction: Vagus nerve stimulation (VNS) has been used for the treatment of refractory epilepsy. More recently it has been proposed

as a putative treatment in acute and maintenance of drug resistant major depression. Data from an open label multi-center pilot study (D01) suggest a potential clinical usefulness. Methods: We report data of an ongoing European trial (D03) following the same simple design as the D01 study. Results: The results from the D03 trial are significantly better: in the first 37 patients mean HRSD-28 score fell from 32.1 to 18.3 after three months of chronic stimulation; 46 % of the patients included reached the response criterion of reduction of depressive symptoms of 50 % or more as measured with the HRSD-28 scale. There is a clear indication that the further improvement of depressive symptoms within a period of one year, which has been demonstrated in previous studies, can be replicated in this study too. Conclusion: The preliminary data from pilot studies including the one presented here on VNS suggest a sustained antidepressant effect in treatment resistant major depression. If these findings can be confirmed in more rigorously designed studies, VNS could become an important treatment option for a subgroup of refractory patients. 133 Examining effective connectivity with fMRI datasets: perspectives and limitations R Schlösser Dep. of Psychiatry, University of Jena, Germany The analysis of functional imaging data in neuropsychiatric research has recently moved to the search for functional and effective connectivity within activated networks. Whereas the notion of functional connectivity involves the temporal correlation of neurophysiological events in different brain areas, the concept of effective connectivity is directed to model based assumptions about the effect which one neural system exerts over another. Structural equation modeling (SEM) has been successfully adopted to functional brain imaging data in a number of studies in the last years. For fMRI, the implementation of the method involves (a) selection of relevant functional “nodes”, (b) extraction of time series from these nodes, (c) designing a functional model, (d) determination of the covariance matrix, (e) estimation of path coefficients implied by the model and evaluation of the model fit, (f) decision about handling error variances, (g) employing statistical designs for group comparisons. The approach has been successfully applied to model information processing within corticocortical and cortical-subcortical-cerebellar networks in normal controls and schizophrenic patients. However, methodological issues remain to be solved including in particular aspects of stability in non-recursive models and non-normality of data distribution. Further extensions will have to look at causal effects and non-linear relationships within these networks. 134 Experimental investigation of pain processing in patients with borderline personality disorder using fMRI C Schmahl1, E Seifritz2 1 Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany 2 Department of Clinical Psychiatry, University Hospital Bern, Switzerland Background: Several studies revealed attenuated pain perception in patients with borderline personality disorder (BPD). Earlier findings suggest that sensory-discriminative pain components are unaffected and affective-motivational pain components may be altered in BPD. Studies in healthy subjects have revealed a pain circuit consisting of thalamus, somatosensory cortex, insula, and anterior cingulate cortex (ACC). We used fMRI and heat pain stimuli to localize alterations in pain processing in BPD. Methods: Seven patients with BPD according to DSM-IV and seven healthy age-matched female participants underwent functional MRI during heat pain stimulation. Two stimulus conditions were applied in a randomized fashion: First, a fixed temperature was used. Second, a temperature that was perceived equally painful by all participants was applied.

I/36 Results: All classical pain regions were activated by stimulation with heat pain in BPD patients as well as controls. During stimulation with equal subjective pain intensities we found a pattern of more deactivation in ACC (perigenual cingulate) and more activation in dorsolateral prefrontal cortex in BPD compared to controls. Conclusions: Results of our study are consistent with the idea that anterior cingulate and dorsolateral prefrontal cortex play a role in altered pain perception in patients with BPD. 135 Neural stem cells: importance of serotonin in adult neurogenesis A Schmitt Department of Psychiatry and Psychotherapy, University of Wuerzburg, Germany In recent years it has been increasingly recognized that the adult brain has the potential to generate new neurons, which integrate both structurally and functionally into preexisting neuronal networks. The discovery of this phenomen, which has been termed adult neurogenesis, represented a major paradigm shift in neurobiology; however, only little is known about the apparently complex mechanisms, which regulate adult neurogenesis. An evolving new concept attributes a role to neurogenesis in the pathogenesis of affective disorders and in the mechanisms of action of antidepressant drugs and electro-convulsive therapy. Serotonin (5-HT) affects genesis and differentiation of neurons both as neurotransmitter and as growth factor. The serotonin transporter (5-HTT), apart from being the target for clinically effective antidepressive therapy (e. g. SSRIs), fine-tunes serotonergic neurotransmission and in this way may contribute to neuroplasticity. There are several studies demonstrating that chronic administration of antidepressants such as SSRIs upregulate neurogenesis. In this context, the recently published findings that SSRI efficacy requires activation of 5-HT1A receptors strengthen the impact of 5-HT on adult neurogenesis. 5-HTT deficient mice represent an artificially hyperserotonergic environment, since released 5-HT is not taken back into the presynaptic neuron. Furthermore, 5-HTT KO mice show an increase in anxiety-like behavior and are less aggressive. Thus, this animal model represents a practical model to investigate the role of 5HT in adult neurogenesis as well as in mood and anxiety disorders. 136 The glutamate hypothesis of schizophrenia: post-mortem investigations and animal model A Schmitt Central Institute of Mental Health, Mannheim, Germany, Clinic of Psychiatry, Saarland University, Homburg, Germany The glutamatergic system may be involved in the pathophysiology of schizophrenia. The neurodevelopmental hypothesis may be assessed using animal models. In our animal study we investigated the impact of postnatal hypoxia on schizophrenia-related behavior prepubertal and in young adulthood as a model for obstetric complications in schizophrenia. After chronic postnatal hypoxia (11 % O2, 89 % N2), rats have been investigated using social interaction and prepulse inhibition of acoustic startle response. In adulthood, rats with postnatal hypoxia showed a reduced prepulse inhibition and reduced social interaction as well as social recognition. Social interaction may represent negative symptoms and reduced prepulse inhibition has been shown in schizophrenic patients. Changes in the glutamatergic system may underlie the behavioral alterations. Therefore, we investigated receptor binding and gene expression of subunits of the NMDA (N-methyl-D-aspartate) receptor. In the prefrontal cortex, receptor binding was decreased three days after hypoxia and NR1 subunit gene expression was increased after three days and in adulthood. These changes may be due to an NMDA receptor hypofunction, which was hypothesized in schizophrenia. By this mechanism, GABAergic interneurons may have been injured with consecutive decreased glutamatergic output in fronto-striatal projections. Consistent with these results are investigations in post-mortem tissue in the prefrontal cortex in schizophrenia.

137 The reeler mouse combined with environmental factors as a model for neurodevelopmental disturbances in schizophrenia A Schmitt, P Falkai Department of Psychiatry, University of Saarland, Homburg, Germany Mutations in mouse models provide new insights into mechanisms of neurodevelopmental disturbances in psychiatric diseases. Reeler mice possess an autosomal recessive mutation which leads to disturbed migration of GABAergic neurons to the cortex. The heterozygote reeler mouse has been viewed as a genetic and neurodevelopmental animal model of schizophrenia, since these mice exhibit behavioral alterations in early adulthood, which can be compared across species to illness-related behavior in schizophrenic patients. In these patients in post-mortem studies, reelin protein has been shown to be reduced and GABAergic neurons have been found to be decreased in the prefrontal cortex. However, the impact of environmental factors such as hypoxia during obstetric complications on neuronal migration is unknown. For creating a valid animal model with genetic and environmental factors we impose chronic, postnatal hypoxia to these mice and measure motor locomotion as well as working memory using radial maze. Gene expression and structural studies in the mouse brain will complete these investigations and may help to elucidate neurodevelopmental mechanisms in the pathophysiology of schizophrenia. In post-mortem studies of chronic schizophrenic patients, we additionally investigate gene expression of reelin for comparison with the animal model. 138 Neural correlates of cognition deficits in Alzheimer’s disease – A PET study of resting cerebral glucose metabolism P Schönknecht1, A Hunt1, M Henze2, S Barth1, U Haberkorn1, J Schröder1 1 Section for Geriatric Psychiatry, Ruprecht-Karls-University Heidelberg, Germany 2 German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit Nuclear Medicine, and Department of Nuclear Medicine, Ruprecht-Karls-University Heidelberg, Germany Alzheimer’s disease (AD) is characterised by several cognitive deficits such as episodic memory decline, language deficits, and apraxia. Although memory impairment has been addressed in recent neuroimaging studies the neural substrates of most cognitive deficits in AD remain unresolved. The neuropsychological test battery of the Consortium to Establish a Register for Alzheimer’s Disease (CERAD) is generally accepted to be a reliable neuropsychological test to reveal a broad spectrum of cognitive deficits in patients with AD. Positron emission tomography (PET) has been proved an adequate method for revealing the neural substrates of cognitive dysfunctions. 43 patients with mild cognitive impairment and manifest AD were investigated with 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG). In all patients, the neuropsychological test battery of the CERAD was applied. Using statistical parametric mapping significant correlations were calculated to assess the association of cerebral metabolic rate for glucose (CMRGlc) and neuropsychological test performance. Significant correlations between immediate memory scores and activation of left temporo-parietal and right temporal cortices occurred whereas constructional praxis test scores were significantly correlated with temporo-parietal cortices bilaterally. Irrespective of domain, delayed memory performance was associated with a larger network including frontal association cortices of both hemispheres. Verbal fluency and naming scores were significantly correlated with predominantly left temporo-parietal and frontal cortices. Findings provide further evidence that not only memory deficits but also impaired functions of language and constructional praxis involve different brain areas in AD. However, results of this study reflect both physiological and compensatory mechanisms of distinct neuropsychological functions which warrants further investigation.

I/37 139 Examining chromosome 3q29 in schizophrenia and bipolar affective disorder families A Schosser1, K Fuchs2, 4, F Leisch5, U Bailer1, S Kasper1, W Sieghart2, 4, K Hornik3, 5, HN Aschauer1 1 Department of General Psychiatry, University Hospital for Psychiatry, Medical University Vienna, Austria 2 Division of Biochemical Psychiatry, University Hospital for Psychiatry, Medical University Vienna, Austria 3 Department of Statistics and Mathematics, Wirtschaftsuniversität, Vienna, Austria 4 Brain Research Institute, Medical University of Vienna, Austria 5 Department of Statistics and Probability Theory,Vienna University of Technology, Austria Based on a genome scan (Bailer et al. 2002) conducted by our group, we detected a potential schizophrenia and bipolar disorder susceptibility locus on chromosome 3q29. Linkage analyses were performed using the GENEHUNTER program. Within the genome scan, a genomewide map of 388 microsatellite DNA markers was genotyped in five schizophrenia and three bipolar disorder Austrian families. Across the genome, p values associated with NPL [non parametric lod] scores resulted in evidence (i. e., p < 0.0007) for linkage at marker D3S1265 on chromosome 3q29 (NPL score Zall = 3.74, p = 0.0003). Within a follow-up linkage analysis (Schosser et al. 2004) using the same family sample, we genotyped eight additional SNP (Single Nucleotide Polymorphism) markers close to D3S1265; five of them, spanning 4.14 cM (centiMorgan), could be used for statistical analyses. The highest NPL score Zall observed was 1.93296 with SNP rs1835669, corresponding to p = 0.032166. By genotyping five further SNP markers in the same family sample, spanning 2.6 cM within the region of highest linkage of our follow up linkage analysis, we conducted an additional fine-mapping thus narrowing down our newly identified candidate region. The highest NPL score Zall observed was 4.03484 with SNP rs225, corresponding to p = 0.000096. In conclusion, at least in our family sample, we have a possible susceptibility locus for both disorders at chromosome 3q29. 140 Nocturnal renin levels in normal controls – effects of gender and sleep-deprivation P Schüssler, M Uhr, M Ising, J C Weikel, D A Schmid, K Held, S Mathias, A Steiger Max Planck Institute of Psychiatry, Munich, Germany Plasma renin activity (PRA) shows oscillations of about 90 min strongly linked to the Non-rapid eye movement-sleep (NREMS)- and rapid eye movement-sleep (REMS) cycles [1]. Total sleep deprivation (TSD) distinctly enhances sleep. We wanted to test the effect of TSD on PRA. Furthermore we assessed the gender effects, since previous studies were done in males only. We examined simultaneously sleep EEG [23:00–07:00] and PRA [20:00–07:00] in 17 healthy subjects (8 females, 9 males). A subgroup (n = 8) was retested after TSD. PRA concentrations were lower between 23:00 to 07:00 in females than in males.We observed a significantly negative association between REM latency and PRA indicating higher renin values in subjects with a short REM latency.An association existed between time spent in stage 1 and PRA area under the curve (AUC) during the second half of the night. During the first half of the night TSD increased the renin maximum and a trend towards increased PRA concentration was present (p = 0.093). Our data suggest that TSD results in elevated renin secretion. Furthermore a sexual dimorphism in renin secretion is demonstrated. References Brandenberger G, et al., Sleep J (1994) Research 3:30–35

141 Nocturnal ghrelin, ACTH, GH and cortisol secretion are enhanced after sleep deprivation in normal controls P Schüssler, M Uhr, M Ising, J C Weikel, DA Schmid, K Held, S Mathias, A Steiger Max Planck Institute of Psychiatry, Munich, Germany Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor [1]. Besides GH-releasing hormone (GHRH) and somatostatin it is thought to regulate GH release. We showed recently that ghrelin promotes slow wave sleep and the nocturnal release of GH, cortisol and prolactin in humans [2]. There are no data available about the pattern of ghrelin secretion during the recovery night after total sleep deprivation (TSD). Nocturnal ghrelin, GH, ACTH and cortisol plasma concentrations were determined and simultaneously sleep EEG was recorded [23:00–07:00] during sleep before and after one night of TSD in 8 healthy subjects (3 females, 5 males). Compared to baseline ghrelin secretion increased earlier after TSD and a trend occurred suggesting higher ghrelin secretion during the first half of the night. GH, ACTH and cortisol were also elevated after TSD. Our data support the view that ghrelin is a sleep promoting factor. To our knowledge the increase of ACTH after TSD is a novel finding. References 1. Kojima M, et al. (1999) Nature 402:656–660 2. Weikel JC, et al. (2003) Am J Physiol Endocrinol Metab 284: E407–E415 142 Candidate genes for schizophrenia and their implication with the glutamatergic system TG Schulze, M Rietschel Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany There is ample evidence for a strong genetic basis of schizophrenia from family, twin, and adoption studies. Whereas results for a variety of candidate gene association studies and some genome-wide linkage analyses remain controversial, there are consistent findings for genes found through systematic fine-mapping in replicated, chromosomal linkage regions such as the genes dysbindin on 6p, neuregulin-1 on 8q, and DAOA on13q. The gene product of DAOA, D-amino acid oxidase activator, interacts with D-amino acid oxidase, encoded by the gene DAAO on 12q. DAAO is ex-pressed in the human CNS and oxidizes D-Serine, an activator of NMDA-type glutamate receptors.A decreased concentration of D-serine in serum of schizophrenia patients was reported. These findings support the glutamate hypothesis of schizophrenia. Besides DAOA, the gene products of dysbindin, neuregulin-1, PRODH, i. e. proline dehydrogenase, and RGS4, i. e. regulator of G protein signalling-4 (PRODH and RGS4 have also been found associated with schizophrenia), are believed to be involved in glutamatergic signalling. We replicated the association between DAOA and schizophrenia and also with bipolar disorder in large German case-control samples. In further analyses, we found that the association with bipolar disorder was driven by cases with a life-time history of psychotic features, namely persecutory delusions.

I/38 143 Genetic analysis of glutamatergic signalling genes in alcohol dependence G Schumann1, M Soyka2, D Rujescu2, F Matsuda3, A Szegedi4, S Wellek1, N Dahmen5, U Preuss2, R Spanagel1, A Heinz4, FA Henn1, K Mann1, M Lathrop3 1 Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany 2 Dept. of Psychiatry, University of Munich, Germany 3 Centre National de Génotypage, Evry, France 4 Dept. of Psychiatry, Charité, Berlin, Germany 5 Dept. of Psychiatry, University of Mainz, Germany Alcohol dependence is a disorder with strong genetic influences and heritability estimates ranging between 40–60 %. Ethanol-induced glutamatergic signal transduction has been shown to influence pathophysiological mechanisms central to the development of alcohol dependence, including tolerance, withdrawal symptoms, craving, relapse and ethanol-related neurotoxicity. Ethanol acts specifically by inhibiting ionotropic N-methyl-D-aspartate (NMDA) receptors. Glutamatergic activation of NMDA-receptors initiates a Ca2+ -mediated signal transduction cascade which involves the Ca2+ -binding molecule calmodulin (Cam). Cam activates Calmodulin-dependent kinase (CamK) and the Ras pathway, leading to activation of the transcription factor CREB. Phosphorylation and expression of CREB and CamKIV in the nucleus accumbens and other brain structures relevant for ethanol dependence are influenced by ethanol consumption and withdrawal. Other proteins activated by NMDA receptors via PSD 95 include neuronal nitric oxide synthase (nNOS) and its effector GMP-kinaseII as well as Phosphatidyl Inositol Kinase 3 and the MAP kinase pathway. The goal of the present study is to systematically analyse genetic variations of NMDA-receptor subtypes and functionally related signal transduction genes which are known to be involved in glutamatergic neurotransmission in ethanol dependence in a large sample of German patients with alcohol dependence and unrelated controls. We attempted to include those NMDA-related genes where evidence for an alteration of alcohol drinking behaviour has been given in behavioural tests using knock-out mice. To this end we identified 10 genes involved in glutamatergic signal transduction and performed a SNP-discovery programme by sequencing analysis of the regulatory domains, exons and exon-intron boundaries of each gene. Next we performed haplotype analyses and genotyped those SNPs which account for the 95 % most frequent haplotypes in a sample of 600 patients with alcohol dependence and 500 controls. Genotypephenotype analysis with particular emphasis on oligogenic interactions was performed using a classical regression analysis. The results of this project will be presented. 144 Genetic Analysis of circadian rhythm genes PER1 and PER2 in patients with alcohol dependence G Schumann1, R Spanagel1, D Rujescu2, N Dahmen3, A Szegedi4, M Lathrop5, S Schreiber6, U Albrecht7, K Mann1, M Soyka2 1 Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany 2 Dept. of Psychiatry, University of Munich, Germany 3 Dept. of Psychiatry, University of Mainz, Germany 4 Dept. of Psychiatry, Charité, Berlin, Germany 5 Centre National de Génotypage, Evry, France 6 Dept. of Internal Medicine, University of Kiel, Germany 7 Dept. of Biochemistry, University of Fribourg, Switzerland Alcohol intake and alcohol dependence are thought to be linked to circadian rhythmicity in humans and animal models. Recently, an interaction of circadian rhythm genes and alcohol drinking behaviour was described. Per-1 knock out mice showed an increased loss of righting reflex (LORR) as a sign of increased alcohol sensitivity, while in wild type mice LORR was inversely correlated with Per-1 expression. Per-2 knock out mice showed increased alcohol intake as compared to wild type mice. We performed a SNP-discovery and frequency analysis of the human Per1 and Per2 genes and conducted association studies and haplotype analysis of the informative SNPs

identified in a total of 990 subjects. 18 genetic variations of the Per1 gene were identified in the regulatory domains, exons and exon-intron boundaries. Genotyping and haplotype analysis of 6 informative SNPs revealed no stable association with alcohol dependence or other relevant phenotypes. Negative results were confirmed using equivalence testing. In the case of Per2 we identified 11 gene variations, 6 of which were selected for genotyping in a sample of 215 patients with a detailed assessment of alcohol intake. We found a significant association of high vs. low alcohol intake with one SNP (p = 0.020, OR 2.155), and identified haplotypes consisting of 4 SNPs with a significant association between high vs. low amount of alcohol intake (p = 0.0075). Thus, our findings support the results of the Per2 mutant mouse studies and suggest a role of the hPer2 gene in the regulation of alcohol consumption in human alcohol dependent patients. 145 What can brain imaging tell us about craving? MN Smolka1, M Bühler1, S Klein1, D Hermann1, H Flor1, K Mann1, DF Braus2, J Wrase3, A Heinz3 1 Central Institute of Mental Health, Mannheim, University of Heidelberg, Germany 2 Dept. of Psychiatry, University of Hamburg, Hamburg, Germany 3 Dept. of Psychiatry at the Charité, University Medicine Berlin, Berlin, Germany While craving for abused substances, including alcohol and nicotine, has been clinically recognized as being an important component of dependence that plays a role in both the maintenance of drug consumption and as a cause for relapse, there is considerable inconsistency as to how the concept should be defined and measured. The growing body of information about the neuroscience of addiction has begun to elucidate specific brain regions and neural networks involved in the phenomenon of craving. Much of our knowledge about the neuroscience of addiction has been obtained from animal models. Brain imaging technology in humans has provided the means of translating knowledge gained in animal models of drinking and smoking to the human condition of alcohol or nicotine dependence. Data obtained with Functional Magnetic Resonance Imaging (fMRI) in alcoholics as well as in smokers will be presented. The relationship of cue-induced functional brain activity observed in the scanner to craving, severity of dependence and motivational factors will be highlighted. Moreover data concerning the association of cue induced brain activity in alcoholics and their future relapse potential will be presented and discussed with respect to their clinical relevance.

146 Gender-related differences of brain activity during a selective attention task – an fMRI study in depressive patients and healthy volunteers T Sobanski3, G Wagner1, G Sofianos1, N Bischoff2, ER Straube2, H Sauer1 1 Department of Psychiatry, University of Jena, Germany 2 Department of Psychology, University of Jena, Germany 3 Department of Psychiatry, THUERINGEN-Kliniken, Saalfeld, Germany Introduction: The aim of the present study was to assess gender-related differences of cerebral activity in major depression. Methods: Functional magnetic resonance tomography (fMRI) scans were performed in a group of 16 inpatients with major depression (8 males and 8 females) and a control group matched for age and gender. fMRI scans were assessed by block design during neurocognitive stimulation with a selective attention paradigm. Data were analyzed by the SPM99 software. Results: Healthy women showed stronger activations compared to healthy men in the visual cortex (BA 17, 18, 19), ventrolateral prefrontal cortex (VLPFC, BA 44), and circumscribed areas of the temporal und parietal lobes. Depressive women showed less additional activations compared to depressive men predominantly located in the VLPFC (BA 44). Vice versa healthy and depressive males exhibited

I/39 only few extra activations compared to females. Selective attention task performance did not differ within the four groups. Conclusions: Females used different strategies to carry out the paradigm or it might have taken them a stronger effort. In depressive females the ability to generate additional activations possibly was limited. The results demonstrate that gender-related effects should be considered as a variance factor in future neuroimaging studies in major depression. 147 Decreased cutaneous immune response in schizophrenic patients I Spellmann, M Riedel, M Strassnig, HJ Möller, N Müller Dept. of Psychiatry, University of Munich, Germany Introduction: The involvement of an alteration of the immune system in the pathogenesis of schizophrenia discussed has been for many years. In particular, there is evidence that the type-1 mediated cellular immune response is deficient in schizophrenia. We therefore hypothesized that the type-IV delayed skin hypersensitivity reaction, which is effected by the type-1 immune response, is attenuated in schizophrenia patients. Methods: A prospective case-control study was performed to assess skin reactivity of patients versus healthy controls.A standardized device with seven different antigens (multitest Merieux) was applied intracutaneously; after 48 hours, the skin reactions were quantified. Results: Schizophrenia patients showed significantly diminished skin reactions to antigens in comparison to healthy controls. Conclusions: The type-1 mediated cellular immune response is attenuated in schizophrenic patients. 148 IDO (indoleamine [2, 3]-dioxygenase) and depression B Sperner-Unterweger1, C Kohl2, D Fuchs3 1 Dept. of Biological Psychiatry, Medical University Innsbruck, Austria 2 Dept. of General Psychiatry, Medical University Innsbruck, Austria 3 Dept. of Medical Chemistry and Biochemistry, University Innsbruck, Austria Immune activation, mediated by interferon gamma (IFN), has been shown to influence the metabolism of the essential amino acid tryptophan, which can be metabolised in two different pathways, one resulting in serotonin and the other one ending up with kynurenine. Consequently, immunologically induced tryptophan degradation may elicit depressive symptoms when the availability of tryptophan becomes insufficient for normal serotonin biosynthesis. Furthermore, it has been suggested that the enzyme indoleamine 2,3-dioxygenase (IDO), which regulates tryptophan degradation to kynurenine, could represent an important link between the immunological network and the pathogenesis of depression. In this context, an activated monocyte/macrophage axis could be seen as a basis for the development of depressive symptoms in patients suffering from diseases with immune activation such as cancer, autoimmune diseases, infections and psychiatric symptoms in pregnancy and in the post partum period as well as in neurodegenerative disorders. 149 Psychophysiological reactivity to the modified Stroop task used as a smoking-related cue: differences between smokers and nonsmokers are related to anxiety traits DF Zullino, E Frésard, M Stankovic,Y Montagrin,Y Khazaal, F Borgeat Clinical Research Unit University Department of Adult Psychiatry, Site de Cery, Prilly-Lausanne, Switzerland Smokers have been found to display impairment in color-naming of smoking-related words in the modified Stroop task (MST), and this attentional bias to affect outcome in smoking cessation. Anxiety has consistently been associated to smoking. The objectives of the present study were to test the psychophysiological reactivity under the MST, used as a smoking-related cue, controlling for state and trait anxiety.

Methods: Subjects (25 smokers, 22 non-smokers) participated in a 30-minute laboratory session, during which they were submitted to two 120-second periods of MSTs (neutral words/smoking related words). Subjects were randomized as to the presentation order. Anxiety was assessed with the Spielberger’s State-Trait Anxiety Inventory = STAI-Y. Skin conductance data were collected via a ProComp+ /Biograph system. Results: Whereas in smokers, the response amplitude was significantly higher under presentation of smoking-related words (p = 0.037) compared to neutral words, no difference was found for nonsmokers. Smokers had higher anxiety trait scores than nonsmokers (40.2 ± 10.4 vs. 32.2 ± 6.9; p = 0.004), but did not differ with regard to state anxiety (30.4 ± 6.9 vs. 28.7 ± 7.1; ns). Trait anxiety itself was positively correlated to the skin conductance amplitude differences between the two experimental conditions (Spearman’s rho = 0.361; p = 0.013). In a multiple linear regression model with backward elimination, only the STAI-YB score was retained. Conclusions: The more important anxiety traits in smokers contribute to the differences in smoking-cues elicited skin conductance reactivity between smokers and nonsmokers. In order to enhance the efficiency of extinction strategies in treatments addressing smokingcues elicited conditioned responses anxiety should concomitantly be addressed. 150 Prenatal intracerebroventricular neurotoxic lesions as an animal model of schizophrenia U Sprick1, M Bouvier2, M. von Wilmsdorff2 1 Department of Psychiatry, Dortmund, Germany 2 Department of Psychiatry, Heinrich-Heine-University Düsseldorf – Rhineland State Clinics Düsseldorf, Germany Neonatal lesions of the ventral or dorsal hippocampus induce neuropathological and behavioral changes in adult rats. The aim of this pilot study was to show that there are also alterations in behavior and histological parameters after prenatal lesions of the dorsal hippocampus. Fetuses of Fisher rats were lesioned in utero by intraventricular (icv) injections of 2µl kainic acid (0.5 mg/ml NaCl) on day 18 of gestation.After birth the rats were weighted twice a week and tested for behavioural changes at week 8, 12, 16, 20 and 24. Histology with cresyl violet stains was done after cutting the perfused frozen brains. We noted a higher difference between the weights of lesioned and control male rats, while the weights of female rats did not differ significantly. In the “alcoven-test” lesioned animals left the box more quickly than controls from week 8 to 20 after birth while there was no difference in week 24. In the T-maze lesioned animals showed clear deficits in learning behavior. Scores of perseveration faults were especially high in female lesioned rats. In activity measures female animals were generally more active than male rats. The difference between lesioned and control animals was higher in male rats. Concerning social behavior male lesioned rats showed longer contacts to their partners than controls or female lesioned rats. The contacts of the male lesioned rats were independent from age or gender of their partners.Male lesioned and control animals induced more aggressive behavior in male partners and anxiety in female partners if these were adult rats from another litter. Histology showed that pyramidal cells in the CA3 region of the right hippo-campus had significantly greater volumes compared to the left side. Hippo-campal pyramidal cells of lesioned brains were smaller than those of controls. Further investigations are needed to investigate the influence of the lesion method and the course of behavioral changes before and after puberty before we address the question whether antipsychotic drugs can ameliorate behavioural deficits of lesioned rats, to prove that prenatal lesions can serve as a useful animal model for schizophrenia.

I/40 151 The role of neuropeptides and steroids in normal and disturbed sleep EEG and nocturnal hormone secretion A Steiger, IA Antonijevic, K Held, HE Kuenzel, H Murck, P Schuessler, J Weikel Max Planck Institute of Psychiatry, Munich, Germany Human sleep is characterised by distinct patterns of sleep EEG and of hormone secretion. In young normal controls near to sleep onset the major portions of slow-wave sleep (SWS) and growth hormone (GH) occur, whereas during the second half of the night REM sleep and cortisol preponderate. During depression and during normal ageing similar changes of sleep-endocrine activity are found. In a series of studies with simultaneous investigation of sleep EEG and hormone secretion in patients and controls we showed that peptides and steroids play a key role in normal sleep regulation and in the pathophysiology of disturbed sleep. In males a reciprocal interaction between GH-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) in sleep regulation was found. Changes in the GHRH/CRH ratio contribute to decreases of SWS and GH and hypercortisolism in depression and to similar changes during ageing. In females however GHRH disturbed sleep. Furthermore somatostatin impaired sleep in both sexes, whereas ghrelin, galanin and NPY promoted sleep. In females disturbed sleep was accentuated after the menopause and estrogen replacement therapy improved sleep in postmenopausal women. Subchronic treatment of multiple sclerosis with a glucocorticoid receptor ligand induced depression-like changes of sleep. CRH-receptor1 antagonism improved sleep in patients with depression. 152 Neurophysiological correlates of second language learning assessed with fMRI: preliminary data M Stein1, T Koenig1, Ch Lehmann1, D Hubl1, D Brandeis2, W Strik3, T Dierks1 1 Department of Psychiatric Neurophysiology, University Hospital of Clinical Psychiatry, Bern, Switzerland 2 Brain mapping Research, Department of Child and Adolescent Psychiatry, University of Zurich, Switzerland 3 University Hospital of Clinical Psychiatry, Bern, Switzerland The present study aimed at tracing changes in brain activity related to progress in second language learning. Therefore, brain activity evoked by visually presented language stimuli was measured before and after 3 months of intense language learning in 7 English-speaking exchange students in Switzerland. Stimulus material consisted of nouns in the participant’s native language (English, L1), her/his second language (German, L2) and an unknown language (Rumantsch). A total of 1200 words (400 per language) were divided in 4 sets of 300 words each (100 per language). The sets did not differ in mean wordfrequency and -length. Nouns were presented in randomized order visually on a computer screen. Brain Activity was measured using event-related functional magnetic resonance imaging (fMRI). Results are preliminary and explore differences between languages in the first and second measurement. 153 Diagnostic stability, course and outcome in cycloid psychosis: results of a 10-year follow up study G Stöber, N Reinhard, B Pfuhlmann Department of Psychiatry and Psychotherapy of the University of Würzburg, Germany The aim of the 10-year follow-up study was to investigate the stability of the initial diagnoses in cycloid psychoses. This would give new insights into course and prognosis of these atypical psychoses in a naturalistic setting and modern psychopharmacological treatment. As control group we included index cases with bipolar affective disorder. All index cases were regular in-patients, treated at a general ward at the Dept. of Psychiatry and Psychotherapy between May 1991 and April 1992. Inclusion criteria were age < 50 years and a final diag-

nosis of cycloid psychoses and manic depression during the index episode in May 1991–April 1992. We used a polydiagnostic approach with diagnoses according to ICD, DSM, and differentiated psychopathology. In total, we included 85 patients (33 males), 45 index cases suffered from cycloid psychoses (16 males, 36 %), and 40 cases (17 males, 43 %) from manic depression. At the index episode, the mean age was 30.1 years (range 18–46 years). The design of the catamnestic study included blindness of the re-investigator regarding the index diagnosis. At present we have re-evaluated 30 index cases and found a highly diagnostic stability in the 10-year catamnesis in manic depression as well as in cycloid psychosis. In both diagnostic entities, the outcome was excellent without serious residual symptoms. 154 Walter Morgenthaler’s collection – transitions between drawing and writing W Strik, A Altorfer University Hospital of Clinical Psychiatry, Bern, Switzerland The Museum of Psychiatry in Bern preserves about 2500 drawings and 1500 text sheets of patients hospitalized in the University Hospital of Psychiatry (Waldau) between 1880 and 1930. Walter Morgenthaler, a cultivated and broadly educated man employed as head-psychiatrist by Prof. Willhelm von Speyr (the third director of the hospital), searched through records of 275 patients to find material for his ideas concerning the psychodiagnostic value of artistic efforts of mentally ill patients. He found on the one hand drawings and on the other hand text sheets. However, he described a third group of creative compositions that include both elements together. In this respect, Morgenthaler differentiated transitions from drawing to writing (as phylo- and ontogenetic evolution) and from writing to drawing (as phylo- and ontogenetic regression). In one of his main publications 77 cases are described and discussed that meet the criteria of transitions. Besides this psychodiagnostic aim, Morgenthaler was engaged with the artistic value of “outsider creations”. In an exceptional appreciation for the intuitive qualities inherent in these works, Morgenthaler recognized the artistic power of many “cases” in his collection (e. g. Adolf Wölfli). The Museum of Psychiatry in Bern is engaged to show artworks from Morgenthaler’s collection and to continue the promotion of creative patients initiated by Walter Morgenthaler in connection with art therapists of the modern Psychiatric Hospital. 155 Anatomical disconnection of prefrontal efferents in an animal model of psychosis G Teuchert-Noodt, F Bagorda, J Neddens, A Busche Dep. Neuroanat. Fac. Biol., Univ. Bielefeld, Germany Though it is firmly established that psychiatric diseases are associated with structural brain abnormalities, it still remains to be shown that higher brain areas are indeed anatomically disconnected in psychosis. Isolated rearing (IR) in addition with a toxic dose of methamphetamine (MA) has served as the key model for our investigation of developing neuropsychiatric disorders that are likely to involve the whole limbic system and mismatch several transmitter systems. Based on previous results with the environment model it will be demonstrated that the malfunctional maturation of DA in the prefrontal cortex (PFC) is in a position to influence adaptive changes of postsynaptic pyramidal neurons and reduce corticocortical efferents to somato-motoric and limbic cortical areas (see Poster Bagorda, F. et al.). Quantitative immunocytochemistry gives proof that neuromodulatory transmitter systems in the same target fields adapt to the disarranged glutamatergic efflux from PFC. Only when both IR and MA are applied, an inversion of the DAergic balance between rostral and caudal limbic areas (Busche et al., 2004) coincides with an excessive overproduction of intrinsic projections coming from PFC lamina V pyramids. Thus, we offer a model for a gradual development of psychosis by progressively detracting prefrontal from distant cortical modules.

I/41 156 Structural changes of the corpus callosum in subjects with mild cognitive impairment PA Thomann1, T Wüstenberg2, FL Giesel3, E Kaiser1, P Schönknecht1, J Pantel4, M Amann3, M Essig3, J Schröder1 1 Section of Geriatric Psychiatry, University of Heidelberg, Germany 2 Department of Neurology, Humboldt-University of Berlin, Germany 3 German Cancer Research Center, Heidelberg, Germany 4 Department of Psychiatry and Psychotherapy, University of Frankfurt, Germany Purpose: Previous studies demonstrate a significant atrophy of the corpus callosum (CC) in patients with Alzheimer’s disease (AD). If structural changes of the CC already occur in mild cognitive impairment (MCI) has not yet been investigated. Patients and Methods: In the present study 21 subjects with mild cognitive impairment (MCI) (mean age 66.2 ± 0.75 years), 21 healthy controls (mean age 66.6 ± 0.6 years) and 10 age-matched patients with AD (mean MMSE 19.2 ± 3.85) were investigated using quantitative MRI. After drawing a horizontal line in the mid-sagittal T1 weighted slice from the most anterior to the most posterior point of the CC, it was divided in 5 parts (CC1–5) by constructing vertical lines of equal distance perpendicular to the horizontal line. Discussion/Results: The three groups did not differ significantly in intracranial volume. As expected the CC was significantly smaller in patients with AD than in healthy controls and subjects with MCI. Atrophy was most severe in the rostral parts (CC1–3). The subjects with MCI did not show significant difference in total callosal area compared to healthy controls, but significant smaller size in the two rostral segments (CC1 + CC2). These findings support the hypothesis that MCI may represent a preclinical stage of AD. 157 Polysomnographic studies in patients with Alzheimer and frontotemporal dementia, first results A Thum, R Rocamora,A Haag,A Becker,AM Giesler, CJ Krieg, U Hemmeter Psychiatric University Clinic Marburg, Germany Disturbance of sleep-wake pattern is a prominent feature in patients with dementia. In an ongoing study polysomnography was registered in 16 patients with Alzheimer (AD) and frontotemporal dementia (FTD). In five patients with a monotherapy of donepezil or galantamine over two months sleep EEG could be assessed twice. The preliminary results show that all patients present with a substantial sleep continuity disturbance, which exceeds the subjectively assessed sleep complaints. REM-sleep was less reduced in FTD than in AD. Sleep related apnea and periodic leg movements (PLMS) were frequently found. After cholinergic treatment sleep pattern tended to normalize and REM-sleep increased in some patients. No association between sleep EEG parameters and cognitive performance (CERAD) was observed. These results show that disturbance of sleep continuity is frequent in patients with dementia, probably intensified by sleep apnea and PLMS. Cholinergic treatment may exert beneficial effects on sleep pattern at least in some patients.

representing strength of encoding of auditory information (mismatch negativity as a function of deviant probability, N1 recovery) were investigated in schizophrenic patients and in healthy volunteers during ketamine and psilocybin challenge. Ketamine, but not psilocybine administration was associated with decreased MMN rise as a function of decreasing deviant probability and smaller maximal N1 amplitudes, but unchanged N1 recovery function. These findings are consistent with impairment of encoding during NMDA receptor blockade. In schizophrenic patients with pronounced deficits in episodic memory ERP deficits were highly similar to those induced by ketamine in healthy volunteers. These results support a role for NMDA, but not 5-HT2A receptor dysfunction in abnormal encoding of information in schizophrenia, consistent with previously demonstrated involvement of NMDA receptors in encoding of information. ERP studies during pharmacological challenges thus offer a unique tool to investigate abnormalities in information processing as they relate to schizophrenia. 159 Age-related alterations of visuospatial processing measured with fMRI P Vannini1, C Lehmann2, C Menzi2, T Jonsson3, C Kiefer2,4, L-O Wahlund1, O Almkvist1, T Dierks1, 2 1 Neurotec Department, Division of Clinical Geriatrics, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden 2 Department of Psychiatric Neurophysiology, University Hospital of Clinical Psychiatry, Bern, Switzerland 3 Department of Hospital Physics, Karolinska University Hospital, Huddinge, Stockholm, Sweden 4 Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Switzerland Functional MRI allows insight into age-related changes of brain function. These changes are interesting in that they can provide a better understanding of physiological and pathophysiological mechanisms behind age-related general cognitive decline. In this study, 32 elderly and 14 young subjects performed an angle discrimination task with increasing task demand using event-related fMRI. Task demand was modulated by presenting clocks with different angular disparity and length of the hands and measured by behavioral performance. An overall slower processing time was found for the elderly subjects. In both age-groups, brain activation was found in the cortical network subserving visuospatial processing in Brodmann area (BA) 7 within right and left superior parietal lobules (SPL). By using a quantitative approach to test for group-by-task condition interactions, and at the same time taking the individual responses into account, age-related slowing of processing speed could be related to a corresponding decrease in BOLD signal amplitude. The increase of BOLD signal amplitude with increasing task demand was more pronounced in the young group. Moreover, a constant relationship was found between processing time and BOLD signal change (i. e. the product) across age for each clock category, indicating that the total brain activity for visuospatial processing of one specific clock stimulus remains approximately constant during aging. Taken together, the results suggest that the neuronal network for visuospatial processing becomes less efficient and “slower” with aging.

158 Psychopharmacological challenge studies in healthy volunteers: a tool to investigate the neuropharmacology of auditory information processing in schizophrenia D Umbricht, FX Vollenweider, R Koller, K Bieber Psychiatric University Hospital Zurich, Research Department, 8029 Zurich, Switzerland

160 Hypericum perforatum affects glucocorticoid receptor mRNA levels in human blood cells (U 937) H Vedder, F Enning, S Fischer, J C Krieg Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg, Germany

Administration of the NMDA receptor antagonist ketamine and the 5-HT2A agonist psilocybin are associated with schizophrenia-like behavioral and cognitive effects suggesting an important role of these receptors in key aspects of schizophrenia. We investigated the role of these receptors in deficient encoding of auditory information as observed in schizophrenia. To this end event-related potential measures

Antidepressants are believed to restore disturbed neuroendocrine functions in major depression (MD) via normalization of corticosteroid receptor function. To examine a relevance of this mechanism for Hypericum perforatum, a herbal antidepressant, we here examined its effects on corticosteroid receptor mRNA levels in human blood cells as a peripheral model for its neuroendocrine effects in

I/42 MD. Under our conditions, Hypericum affected the cellular mRNA levels of the glucocorticoid receptor (GR)-α and of its inhibitory counterpart, the GR-β at concentrations similar to antidepressive treatment in the human. Under these conditions, the mRNA levels of the GR-α were up-regulated, whereas a decrease of GR-β mRNA levels was detectable.These data show that hypericum indeed affects GRmRNA levels in the human system, extending the antidepressive properties of hypericum to an improvement of GR-mediated cellular signal transduction. This mechanism has been suggested as an important way of action for a number of antidepressants. 161 Significance of iron metabolism in acute psychiatric in-patients Vetter Z1, König P1, Cordruvisch E2, Prapotnik M1, Di Pauli J1, Hausmann A3, Waschgler R4, Conca A1 1 Regional Hospital Rankweil, Department of Psychiatry I, Rankweil, Austria 2 Eli Lilly Regional Medical Center, Vienna, Austria. 3 University Hospital Innsbruck, Department of General Psychiatry, Innsbruck, Austria 4 Medical Laboratory Feldkirch Austria Background: Low serum iron levels have been reported in a variety of neuropsychiatric motor disorders correlated to dopaminergic transmission. As many psychiatric diseases accompanied by movement disturbances also are related to dysfunctional dopaminergic pathways, we investigated iron metabolism in a large group of acute psychiatric in-patients. Methods: We used a naturalistic and prospective study design. During a 24-months period, patients suffering from different diagnoses with catatonic symptoms were consecutively admitted to the study. Age, gender, and diagnoses according to ICD 10 were assessed. Blood samples were drawn immediately after admission. Results: 490 (257 females) patients; with a mean age of 38.3 years ( ± 13.3) were recruited. 238 patients (47.9 % f) were diagnosed as suffering from schizophrenia and 114 (63 % f) from affective disorders; 56 (62.5 % f) patients were affected by Borderline personality disorder, 31 (64.5 % f) by adjustment disorder and 53 (30.2 % f) by organic mental disorder. In 25.1 % of patients, hypoferremia and in 8.6 % hyperferremia was recorded. In comparison to other diagnoses (with the exception of personality disorder) significant lower mean values of iron were detected in patients with schizophrenia (df 5; F 11.18; p < 0.001). Furthermore 76 out of 238 schizophrenics displayed an absolute hypoferremia (32 %) and 10 a hyperferremia (4.2 %). A similar pattern of iron metabolism was observed in patients suffering from personality disorder.Within these groups the risk for hypoferremia in females is twofold (44.5 % f vs 18.9 % m).In contrast only 12.3 % of 114 patients suffering from affective disorders showed a hypoferremia and no gender differences were observed neither in this group nor in the remaining 138 of the sample. Conclusions: Our results indicate a high incidence of iron deficiency in diagnoses where a pathology of dopaminergic function is assumed such as schizophrenia and personality disorders. Predominantly women express this iron dysfunction. 162 Cortico-striato-thalamic loops in model psychosis and schizophrenia FX Vollenweider Psychiatric University Hospital, Zurich, Switzerland Increasing evidence indicates that cortico-striato-thalamic (CST) pathways are implicated in the pathophysiology of drug-induced and naturally occurring psychoses such as schizophrenia. In particular, brain imaging and behavioural studies into the effects of psychotomimetic drugs in healthy volunteers suggest that a disruption of information processing within CSTC-loops is central to psychotic symptom formation and cognitive deficits seen in drug- and nondrug-induced psychoses. This overview focuses on recent brain imaging and behavioral studies of sensory gating functions assessing similarities between the effects of hallucinogens 5-HT2A agonists (e. g.

psilocybin), dissociative NMDA antagonists (e. g. ketamine), and findings in schizophrenia patients. Challenge studies with psychotomimetic drugs in combination with other research strategies promise to increase our understanding how multiple brain regions and neurotransmitters interact and function in concert to produce psychotic reactions. References Vollenweider and Geyer (2001) BrainRes Bull 56:495–507 163 From model psychoses to novel hypotheses of schizophrenia FX Vollenweider Psychiatric University Hospital, Zurich, Switzerland: Psychotropic drugs that mimic to a certain extent the signs and symptoms of naturally occurring psychoses have played a key role in the formulation of novel hypotheses of schizophrenia. Specifically, behavioural and brain imaging studies with the dissociative NMDA glutamate receptor antagonist ketamine and the hallucinogenic serotonin 5-HT2A receptor agonist psilocybin have provided translational models for pathophysiologic and therapeutic hypotheses of schizophrenia. Recent basic and clinical research with these drugs suggests that their psychotomimetic effects may arise, in part, from their capacity to disrupt information processing within corticostriato-thalamic pathways. Moreover, recently it has been found that both 5-HT2A agonists and NMDA antagonists stimulate cortical activity through excess activity at non-NMDA i. e.,AMPA or kainate glutamate receptors. In fact, excessive prefrontal (hyperfrontality), limbic,striatal and thalamic activity was found in both drug-induced and unmedicated first episode schizophrenia. Given an emerging recognition of the importance of alterations in glutamatergic transmission in the actions of both serotonergic hallucinogens and NMDA antagonists, this overview concludes that novel compounds (e. g.AMPA antagonists) that act directly on glutamatergic systems should be evaluated for their capacity to replace or augment the efficacy of available treatments for schizophrenia. References Vollenweider FX (2001) Brain mechanisms of hallucinogens and entactogens. Dialogues in Clinical Neuroscience 3:265–279 164 Treatment of negative symptoms of schizophrenia with glutamateagonists M von Wilmsdorff Department of Psychiatry, Heinrich-Heine-University Düsseldorf – Rhineland State Clinics Düsseldorf, Germany Glutamate is the most abundant amino acid in the brain. It plays an important role as a well-established major excitatory neurotransmitter in the central nervous system. The reduced glutamate neurotransmission may be involved in the pathophysiology of schizophrenia where it is hypothesized that alterations in the glutamatergic system play an important neurobiochemical role. Phencyclidine (PCP), ketamine and other N-methyl-D-aspartate (NMDA) antagonists induce schizophrenia-like symptoms in normal volunteers and animal models, suggesting that endogenous dysfunction or dysregulation of NMDA receptors may contribute to the pathophysiology of schizophrenia. NMDA-agonists such as glycine and D-cycloserine have been investigated for effects on persistent negative symptoms of schizophrenia. In the literature recent studies provided the first comparisons of glycine and D-cycloserine effects within the same population, and suggest first that NMDA agonists are effective in the treatment of persistent negative symptoms of schizophrenia, and second, that full agonists, such as glycine and D-serine, may be more effective than partial agonists such as D-cycloserine. Similar findings are apparent when data are considered from all trials with NMDA agonists performed to date. Overall, the findings indicate that agents which potentiate NMDA transmission may be therapeutically beneficial in the treatment of negative symptoms of schizophrenia.

I/43 165 Switching antipsychotics in inpatient schizophrenia care – predictors and outcome S Weinmann1, B Janssen2 1 Bezirkskrankenhaus Günzburg, Germany 2 Rheinische Kliniken Düsseldorf, Germany Background: Within a pharmacoepidemiologic study characteristics of patients with schizophrenia switched from first (FGA) to second generation antipsychotics (SGA) or to antipsychotic polypharmacy in comparison to those maintained on FGA were investigated. The primary aim was to assess factors associated with antipsychotic switching and to compare disease course with regard to mental state and social functioning. Method: Adult inpatients with an ICD-10 diagnosis of schizophrenia or schizoaffective disorder were assessed in 7 psychiatric hospitals. For those patients (n = 847) with an antipsychotic prescription at discharge, t-tests, covariance and logistic regression analyses were used to evaluate the relationship between demographic and clinical characteristics, and antipsychotic switching. Results: Patients switched from FGA to SGA had fewer previous psychiatric admissions, a shorter illness duration, less substance disorders, a higher probability of competitive working, but more pronounced symptoms than those maintained on FGA. Mental state and social functioning after case-mix adjustment were more favourable in the group switched to SGA monotherapy, but not in those administered FGA and SGA concurrently at discharge. Logistic regression controlling for demographic and clinical variables revealed that a short disease duration, fewer previous psychiatric hospitalisations, voluntary admission and pronounced thought disorder were significantly correlated with FGA/SGA switching. Hospital differences were also observed.

166 Neramexane, a new NMDA-receptor antagonist in relapse prevention – results of a placebo controlled multicentre “proof of concept”-study GA Wiesbeck1, HG Weijers2, M Althaus3, K Mann4, J Boening5 1 Department of Substance Use Disorders, Psychiatric University Hospital, University of Basel, Switzerland 2 Fachhochschule der Polizei Sachsen-Anhalt, Aschersleben, Germany 3 Dept. of Clinical Research, Merz Pharmaceuticals GmbH, Frankfurt/Main, Germany 4 Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany. 5 Addiction Research Group, Psychiatric University Hospital, Wuerzburg, Germany Neramexane (1-amino-1,3,3,5,5-pentamethylcyclohexane) is a novel compound classified as uncompetitive NMDA receptor antagonist with moderate affinity to the MK 801 binding site. In humans, the substance revealed a favourable safety/tolerability profile while it led to a progressive decrease in operant responding for alcohol in an ethanol self-administration model in rats. The present study is the first to investigate the efficacy of neramexane in alcohol relapse prevention. A total of 236 alcohol-dependent men was randomised to a doubleblind, parallel-group, placebo-controlled international multicentre trial. After detoxification, patients were treated with 40 mg/day neramexane or placebo over a period of 12 consecutive weeks (treatment period) succeeded by another 12 weeks of follow-up. The continuous abstinence rate after 12 weeks of treatment was defined as the primary parameter of efficacy. Secondary parameters were time to first drink, cumulative abstinence duration, the amount of alcohol consumed, and the intensity of craving. Across all parameters, there was no difference in efficacy between neramexane and placebo. However, post-hoc analyses suggest a positive correlation between Neramexane plasma concentrations and continuous abstinence.

167 Neurochemical early and differential diagnosis of Alzheimer’s dementia J Wiltfang, P Lewczuk, JM Maler, J Svitek, A Smirnov, J Miertschischk, J Kornhuber Dept. of Psychiatry, University of Erlangen-Nuremberg, Erlangen, Germany. Neurochemical dementia diagnostics (NDD) is a rapidly developing field of clinical neurochemistry,and promises improved early and differential diagnosis of neurodegenerative diseases, like Alzheimer’s dementia (AD). Among potential NDD markers, amyloid βpeptides (Aβ peptides) and Tau protein(s), which are directly implicated in the pathogenic cascade of AD have meanwhile entered cerebrospinal fluid (CSF) routine diagnostics in specialized centers. Currently, NDD is confined to CSF and there is a high demand for blood assays. We will introduce a first blood assay for the simultaneous determination of six Aβ peptides in human plasma and we will provide a critical overview of NDD. 168 Advantages and problems of Pharmaco-EEG-Monitoring in clinical routine. G Wirtz, H Kleinlogel, T Dierks, W Strik University Hospital of Clinical Psychiatry, Bern, Switzerland Pharmaco-EEG is a reliable tool in clinical psychopharmacological research. Different classes of psychotropic drugs affect characteristically various frequency bands of the EEG.Although in psychiatric patients the antidepressive or antipsychotic therapeutic effect is delayed for several weeks, characteristic EEG-changes are observed within a few hours after application of the drug, predicting the therapeutic effect. In our clinical monitoring EEG and psychopathology (PANSS) was recorded at day 0 (if possible without medication), day 1, day 7 and day 28 after drug treatment. Electrodes were placed according to the International 10–20-system, impedances were below 10 kΩ, digitization rate 250 Hz and bandpass between 1 and 70 Hz. Six frequency bands were distinguished and the weighted mean frequency (centroid) between 1 and 32 Hz was computed. Over a period of two years we performed clinical Pharmaco-EEG monitoring in a sample of patients independent of age, gender or psychopathology. Patients starting psychopharmacologic treatment were included. As advantages of the method we found good tolerability and easy accessibility, early EEG-changes and, therefore, predictability of drug effects on psychopathology. The main problem was to record the EEG of non medicated patients. 169 Chronotherapeutics in affective disorders: an overview A Wirz-Justice Centre for Chronobiology, Psychiatric University Clinic, Basel Disturbances of circadian rhythms and sleep are important clinical features in affective disorders. Two chronotherapeutic approaches have been followed over the last thirty years with remarkably successful results and surprisingly little application in everyday clinical practice. Total or partial sleep deprivation (SD) in the second half of the night or phase advance of the sleep-wake cycle have rapid and profound effects on depressed mood in all diagnostic subgroups. SD combined with lithium, antidepressant drugs, pindolol, sleep phase advance, or morning light therapy (LT) attains ~60 % response rates without relapse, thus providing psychiatrists with new instruments to achieve rapid and sustained antidepressant response, also in bipolar patients. LT is the treatment of choice for seasonal affective disorder (SAD), and recent studies document accelerated and augmented response in non-seasonal, even chronic depression (as adjunct to medication). High-density negative air ion exposure is also antidepressant in SAD. Melatonin administered to depressed patients improves sleep, not mood. These nonpharmacological treatments have fewer side effects and contraindications than antidepressant drugs, and often produce improvement more rapidly. Chronotherapeutics may also bene-

I/44 fit nonseasonally depressed patients who cannot tolerate medication (e. g. antepartum), who experience relapse after initial response, or fail to respond to medication. 170 Narcolepsy – misleading disease? W Wittgens, M Schreiber Dept. of Geriatric-Psychiatry/KMR-hospitals, Duesseldorf, Germany Narcolepsy has a prevalence of 50/100000, but in mean about 15 years get lost up to correct diagnosis. Especially symptoms similar to depression can be difficult for clear diagnosis. During the last 2 years we detected 5 patients with narcolepsy admitted to our hospital because of “depression”. Symptoms like dizziness, sleep disorder, loss of vitalism, depressive mood, reduced attention can both exist in depression and narcolepsy. Kataplexia has a great variability, but can lead to correct diagnosis. As a result of our clinical view we think that narcolepsy is a differential diagnosis to depressive disorders, which is not to be ignored. In case of doubt, a sleep center should be involved in the diagnostic process. 171 Reversal effects of clozapine on reduced prepulse inhibition in mice with reduced hippocampal glutamatergic receptor densities – an animal model of schizophrenia? R Wolf Dept. of Psychiatry, Otto-von-Guericke-Universität Magdeburg, Germany The hypo-glutamatergic hypothesis of schizophrenia is based on studies with schizophrenic patients demonstrating deficits in post mortem hippocampal N-methyl-D-aspartate (NMDA) receptor gene expression and deficits in prepulse inhibition (PPI) that can be reversed by clozapine. Accordingly, we compared the two inbred mouse strains CPB-K and BALB/cJ with considerable difference in hippocampal NMDA receptor densities utilizing the sensorimotor gating paradigm. [1] CPB-K mice, known to have lower levels of hippocampal NMDA receptor density, displayed significant lower PPI in opposite to BALB/cJ mice. [2] By using a repeated measurement design, subchronic treatment over 2 weeks with the atypical antipsychotic drug clozapine at a daily dosis of 5 mg/kg, given intraperitoneally, displayed a significant increase in PPI levels in the CPB-K mice group while PPI in BALB/cJ remained statistically unchanged. In summary, we could confirm our working hypothesis: [1] lower levels of hippocampal glutamatergic receptor densities correspond to lower sensorimotor gating in CPB-K mice; [2] reduced PPI levels in CPB-K mice can be significantly reversed by subchronic antipsychotic treatment with clozapine. Therefore, further experiments should be performed in order to prove the CPB-K mouse strain to have construct, face and predictive validity as an animal model of schizophrenia. 172 Mild cognitive impairment – the neuropsychological perspective S Wolf1, E Rüther2 1 Poliklinik für Psychiatrie und Psychotherapie der Universität Göttingen, Germany 2 Klinik für Psychiatrie und Psychotherapie der Universität Göttingen, Germany The concept of “mild cognitive impairment”(MCI) has been in the literature for several years now. Early definitions of MCI focussed on abnormal scores in memory tests. A later definition recognized that there can be “amnestic MCI”, “single non-memory domain MCI”, or “multiple domains slightly impaired MCI”. Recently, clinical subtypes of MCI have been proposed to include prodromal forms of a variety of dementias. An increased risk of conversion to dementia is associated with these and similar MCI definitions. KN-Dem results confirm the notion of heterogeneous cognitive profiles in MCI patients. Instrumental and clinical data thereby may well argue for a non-pro-

gressive disorder: There are patients with mild focal memory deficits (beginning Alzheimer dementia or previous alcohol abuse or temporal lobe epilepsy), focal amnestic aphasia (semantic dementia or arteria cerebri media infarction), mild global cognitive deficits (frontotemporal dementia or depression or thalamus infarction) etc. It is discussed whether integration with instrumental data can better be accomplished by using accepted neurocognitive terms, than by referring to numerous MCI concepts. The use of “MCI” seems to be limited to research in the field of dementia at present. MCI is considered to be useful for describing the degree of impairment in activities of daily living, and less useful as a diagnostic entity. 173 Direct ethanol metabolites (EtG, EtS, PEth, FAEEs): Diagnostic and therapeutic implications FM Wurst1, GA Wiesbeck1, JW Metzger2, W Weinmann3, J Allen4, P Marques4, C Alling5, S Aradottir5, M Wolfersdorf6, F Pragst7, M Graf1 and the WHO/ISBRA study on biological state and trait markers of alcohol use and dependence* 1 Psychiatric University Hospital, University of Basel, Switzerland 2 Department of Hydrochemistry and Hydrobiology, University of Stuttgart, Germany 3 Institute of Legal Medicine, University of Freiburg, Germany 4 Pacific Institute for Research and Evaluation, Calverton, MD, USA 5 Department of Medical Neurochemistry, Lund, Sweden 6 State Mental Hospital Bayreuth, Germany 7 Institute of Legal Medicine, Humboldt University, Berlin, Germany *WHO/ISBRA Investigators: K M Conigrave, M Dongier, H Edenberg, C J P Eriksson, ML O S Formigoni, B F Grant, A Helander, P L Hoffman, K Kiianmaa, T Koyama, L Legault, T-K Li, M Monteiro, T Methuen, T Saito, M Salaspuro, J B Saunders, B Tabakoff, S Tufik, J B Whitfield, F M Wurst. Current biological state markers remain suboptimal with regard to sensitivity and specificity for monitoring recent alcohol consumption in various settings. Direct ethanol metabolites which appear to meet the need and each offering a characteristic time spectrum of possible detection of ethanol consumption have been studied mainly during the last decade. These markers include ethyl glucuronide (EtG), ethyl sulfate (EtS), phosphatidyl ethanol (PEth) and fatty acid ethyl esters (FAEE). We have initiated both basic and clinical research during the last ten years, including the participation in the WHO/ISBRA study and will report newer findings on the role of these biomarkers for screening, monitoring, motivational feedback, to improve knowledge on drinking patterns, differentiate moderate/social drinking from problematic/harmful drinking, differential diagnosis (e. g. elevated transaminases), evaluate treatment programmes and drug trials, elucidate the role of neuropsychological impairment following alcoholisation (i. e. hangover state) which plays a major role in accidents, disclose recent drinking in social drinkers in risky situations (driving, workplaces, pregnancy (FAS)). The complementary use of these markers together with other biological state markers and self reports is expected to lead to significant improvement in treatment outcome, therapy effectiveness, and health, social and socio-economic benefits that will be hard to overestimate.

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Abstracts received after editorial deadline Neurophysiology of attention deficit hyperactivity disorder: distinguishing inhibition and attention problems D Brandeis1, TH van Leeuwen1, K Imhof1, J Steger1, R Drechsler1, H-C Steinhausen1, T Banaschewski2 1 Department of Child and Adolescent Psychiatry, University of Zürich 2 Department of Child and Adolescent Psychiatry, University of Göttingen ADHD (Attention Deficit Hyperactivity Disorder) is defined by deficits of attention and inhibitory response control, but these deficits have proven difficult to distinguish.We illustrate that they can be separated by combining appropriate tests with topographic event-related potentials (ERPs) and control over severity and comorbid disorders.

Brain mapping of attention and response control in the cued continuous performance task (CPT A-X/O-X) was performed using ERP mapping. In several multicenter studies, children with ADHD differing with regard to severity and comorbidity with ODD/CD were compared. Deficits of attention to the cue A or O, and/or deficits of response control to the Go and NoGo stimuli were detected in all ADHD groups.Timing,topography and source localisation separated the distinct P300 components to cue, go, and NoGo signals. While attention deficits dominated in pure ADHD children, the subsequent response control deficits were more prominent in ADHD children with comorbid ODD/CD. Timing and topography of ERPs thus distinguished covert brain activation due to attention and response control. The results reveal that ADHD includes multiple attention and regulation problems rather than isolated inhibition deficits, and that the comorbid group display a unique, non-additive neurophysiological response pattern.

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Author Index

Ackl, N. . . . . . . . . . . . . . . . . . . I/26 Agelink, M. W. . . . . . . . . . I/8, I/11, I/12 Aicher, S. . . . . . . . . . . . . . . . . . I/13 Albrecht, U. . . . . . . . . . . . . . . . I/38 Allen, J. . . . . . . . . . . . . . . . . . . I/44 Alling, C. . . . . . . . . . . . . . . . . . I/44 Almkvist, O. . . . . . . . . . . . . . . . I/41 Althaus, M. . . . . . . . . . . . . . . . . I/43 Altorfer, A. . . . . . . . . . . . . . . . . I/40 Amann, M. . . . . . . . . . . . . . . . . I/41 Amthauer, H. . . . . . . . . . . . . . . . I/16 Anderer, P. . . . . . . . . . . . . . . . . I/34 Anghelescu, I. . . . . . . . . . . . . . . I/15 Angst, J. . . . . . . . . . . . . . . . I/5, I/26 Antonijevic, I. A. . . . . . . . . . . . . . I/40 Aradottir, S. . . . . . . . . . . . . . . . I/44 Arends, M. . . . . . . . . . . . . . I/11, I/12 Arzberger, T. . . . . . . . . . . . . . . . I/18 Aschauer, H. N. . . . . . . . . . . . . . I/37 Aschauer, H. . . . . . . . . . . . . . . . . I/5 Aubry, J. M. . . . . . . . . . . . . . . . . I/17 Bachmann, S. . . . . . . . . . . . . . . . I/5 Baehne, C. . . . . . . . . . . . . . . . . I/14 Baghai, T. C. . . . . . . . . . . . . . . . I/13 Bagorda, F. . . . . . . . . . . . . . . I/6, I/40 Bailer, U. . . . . . . . . . . . . . . . . . I/37 Banaschewski, T. . . . . . . . . . . . . I/45 Bär, K. J. . . . . . . . . . . . . . . . . . . I/5 Bares, R. . . . . . . . . . . . . . . . . . I/20 Bartenstein, P. . . . . . . . . . . . I/18, I/20 Barth, S. . . . . . . . . . . . . . . . I/6, I/36 Bauer, A. . . . . . . . . . . . . . . . . . I/22 Baumann, B. . . . . . . . . . . . . . . . . I/8 Baumann, P. . . . . . . . . . . . . I/13, I/22 Bayer, T. . . . . . . . . . . . . . . . . . I/14 Bayerlein, K. . . . . . . . . . . . . . I/6, I/9 Bech, P. . . . . . . . . . . . . . . . . . . I/28 Beck, M. . . . . . . . . . . . . . . . . . I/15 Becker, A. . . . . . . . . . . . . . . . . . I/41 Beckmann, H. . . . . . . . . . . . . . . . I/6 Begré, S. . . . . . . . . . . . . . . . . . . I/7 Bender, S. . . . . . . . . . . . . . . . . . I/27 Benkelfat, C. . . . . . . . . . . . . . . . . I/7 Berendt, F. . . . . . . . . . . . . . . . . I/34 Berger, C. . . . . . . . . . . . . . . . . . I/23 Berger, M. . . . . . . . . . . . . . . . . . I/7 Berney, A. . . . . . . . . . . . . . . . . . I/7 Bernstein, H. G. . . . . . . . . . . . . . . I/8 Bertschy, G. . . . . . . . . . . . . . . . I/17 Bianchi, P. . . . . . . . . . . . . . . I/15, I/29 Bieber, K. . . . . . . . . . . . . . . . . . I/41 Bielau, H. . . . . . . . . . . . . . . . . . I/8 Bilzer, T. . . . . . . . . . . . . . . . . . . I/8 Bischof, R. . . . . . . . . . . . . . . . . I/12 Bischoff, N. . . . . . . . . . . . . . . . . I/38 Blatter, K. . . . . . . . . . . . . . . . . . I/8 Bleich, S. . . . . . . . . I/6, I/8, I/9, I/16, I/23 Block, W. . . . . . . . . . . . . . . I/22, I/35 Boening, J. . . . . . . . . . . . . . . I/9, I/43 Boesch, C. . . . . . . . . . . . . . . . . I/21 Boesch, L. . . . . . . . . . . . . . . . . I/34 Bogerts, B. . . . . . . . . . . . . . . . . . I/8 Bölte, S. . . . . . . . . . . . . . . . . . . I/21 Bondolfi, G. . . . . . . . . . . . . . . . I/17 Bonert, A. . . . . . . . . . . . . . . . . I/24 Böning, J. . . . . . . . . . . . . . . . . . I/14 Bönsch, D. . . . . . . . . . . . . . . . I/8, I/9

Borgeat, F. . . . . . . . . . . . . . . . . I/39 Bottmer, C. . . . . . . . . . . . . . . . . I/5 Bouvier, M. . . . . . . . . . . . . . . . . I/39 Bovet, P. . . . . . . . . . . . . . . . . . . I/13 Boy, C. . . . . . . . . . . . . . . . . . . I/22 Brand, A. . . . . . . . . . . . . . . . I/9, I/20 Brand, S. . . . . . . . . . . . . . . . . . I/19 Brandeis, D. . . . . . . . . . . . . . I/40, I/45 Braun, H. A. . . . . . . . . . . . . . I/9, I/20 Bräunig, P. . . . . . . . . . . . . . . . . I/33 Braus, D. F. . . . . . . . . . . . I/9, I/10, I/38 Brinkmeyer, J. . . . . . . . . . . . I/11, I/12 Buchholz, H. G. . . . . . . . . . . . . . I/18 Buck, K. . . . . . . . . . . . . . . . . . . I/15 Buecking, A. . . . . . . . . . . . . . . . I/25 Bühler, M. . . . . . . . . . . . . . . . . I/38 Bur, A. . . . . . . . . . . . . . . . . . . I/16 Bürgi, D. . . . . . . . . . . . . . . . . . I/32 Busche, A. . . . . . . . . . . . . . . I/31, I/40 Butz, M. . . . . . . . . . . . . . . . I/10, I/27 Cabungcal, J.-H. . . . . . . . . . . . . . I/13 Cajochen, C. . . . . . . . . . . . . . . . . I/8 Campman, V. . . . . . . . . . . . . . . . I/18 Castagné, V. . . . . . . . . . . . . . . . I/13 Chiry, O. . . . . . . . . . . . . . . . . . I/10 Cohrs, S. . . . . . . . . . . . . . . . . . I/23 Conca, A. . . . . . . . . . . . . . . I/11, I/42 Cordes, J. . . . . . . . . . . . . . . I/11, I/12 Cordruvisch, E. . . . . . . . . . . . . . I/42 Croissant, B. . . . . . . . . . . . . . . . I/27 Cuenod, M. . . . . . . . . . . . . . . . . I/13 Czech, C. . . . . . . . . . . . . . . . . . I/24 Dahmen, N. . . . . . . . . . . . . . . . I/38 Dam, H. . . . . . . . . . . . . . . . . . I/28 Damian, M. . . . . . . . . . . . . . . . I/25 Dammasch, I. E. . . . . . . . . . . . . . I/27 Danos, P. . . . . . . . . . . . . . . . . . . I/8 Davids, E. . . . . . . . . . . . . . . . . I/30 Davis, R. . . . . . . . . . . . . . . . . . . I/8 de Greiff, A. . . . . . . . . . . . . . . . I/24 Debonnel, G. . . . . . . . . . . . . . . . I/7 Deckert, J. . . . . . . . . . . . . . . . . I/12 Dehning, S. . . . . . . . . . . . . . . . . I/12 Delini-Stula, A. . . . . . . . . . . . I/12, I/26 Desax, A. . . . . . . . . . . . . . . . . . I/12 Di Pauli, J. . . . . . . . . . . . . . I/11, I/42 Diefenbacher, A. . . . . . . . . . . . . . I/16 Diehl, A. . . . . . . . . . . . . . . . . . I/27 Dierks, T. . . . I/15, I/21, I/27, I/40, I/41, I/43 Diksic, M. . . . . . . . . . . . . . . . . . I/7 Do, K.Q. . . . . . . . . . . . . . . . . . I/13 Drechsler, R. . . . . . . . . . . . . . . . I/45 Eap, C. B. . . . . . . . . . . . . . . I/13, I/22 Ebert, D. . . . . . . . . . . . . . . . . . I/33 Eckert, A. . . . . . . . . . . . . . . . . . I/24 Ehlis, A. C. . . . . . . . . . . . . . I/14, I/15 Eichenberger, B. . . . . . . . . . . . . . I/29 Ella, R. . . . . . . . . . . . . . . . . . . I/13 Enning, F. . . . . . . . . . . . . . . . . I/41 Eser, D. . . . . . . . . . . . . . . . . . . I/13 Essig, M. . . . . . . . . . . . . . . . I/5, I/41 Ewers, M. . . . . . . . . . . . . . . . . . I/19 Faber, P. L. . . . . . . . . . . . . . . . . I/17 Falkai, P. . . . . . . . . . I/14, I/22, I/35, I/36

Fallgatter, A. J. . . . . . . . . . . . I/14, I/15 Faltraco, F. . . . . . . . . . . . . . . . . I/34 Federspiel, A. . . . . I/7, I/15, I/20, I/21, I/29 Fehr, C. . . . . . . . . . . . . . . . . . . I/15 Feineis-Matthews, S. . . . . . . . . . . I/21 Felder, W. . . . . . . . . . . . . . . . . . I/32 Feldon, J. . . . . . . . . . . . . . . I/29, I/32 Felix, R. . . . . . . . . . . . . . . . . . I/16 Fellgiebel, A. . . . . . . . . . . . . . . . I/15 Fisch, H.-U. . . . . . . . . . . . . . . . I/29 Fischer, P. . . . . . . . . . . . . . . . . I/24 Fischer, S. . . . . . . . . . . . . . . . . I/41 Flor, H. . . . . . . . . . . . . . . . . . . I/38 Forsting, M. . . . . . . . . . . . . . . . I/24 Forstreuter, F. . . . . . . . . . . . . . . I/23 Franke, L. . . . . . . . . . . . . . . . . I/16 Frésard, E. . . . . . . . . . . . . . . . . I/39 Frey, R. . . . . . . . . . . . . . . . I/11, I/16 Frick, C. . . . . . . . . . . . . . . . I/29, I/35 Frieling, H. . . . . . . . . . . . . . . . . I/16 Frommer, A. . . . . . . . . . . . . . . . . I/7 Fröscher, W. . . . . . . . . . . . . . . . I/22 Fuchs, D. . . . . . . . . . . . . . . . . . I/39 Fuchs, K. . . . . . . . . . . . . . . . . . I/37 Gabriel, A. . . . . . . . . . . . . . . . . I/16 Gal, G. . . . . . . . . . . . . . . . . . . I/32 Gallhofer, B. . . . . . . . . . . . . . . . I/27 Gallinat, J. . . . . . . . . . . . . . . . . I/23 Gamma, A. . . . . . . . . . . . . . . . . I/26 Gastpar, M. . . . . . . . . . . . . . . . . I/30 Geretsegger, C. . . . . . . . . . . . . . . I/11 Gervasoni, N. . . . . . . . . . . . . . . I/17 Gheorghita, F. . . . . . . . . . . . . . . I/13 Gianotti, L. R. R. . . . . . . . . . . . . . I/17 Giegling, I. . . . . . . . . . . . . . . . . I/17 Gies, U. . . . . . . . . . . . . . . . . . . I/8 Giesel, F. L. . . . . . . . . . . . . . . . . I/41 Giesel, F. . . . . . . . . . . . . . . . . . . I/5 Giesler, A. M. . . . . . . . . . . . . . . . I/41 Giesler, M. . . . . . . . . . . . . . . . . I/17 Gimbel, K. . . . . . . . . . . . . . . . . I/30 Glatz, D. . . . . . . . . . . . . . . . . . I/34 Gobbi, G. . . . . . . . . . . . . . . . . . I/7 Gorynia, I. . . . . . . . . . . . . . I/18, I/23 Graf, M. . . . . . . . . . . . . . . . . . . I/44 Grodd, W. . . . . . . . . . . . . . . . . I/25 Gruber, O. . . . . . . . . . . . . . . . . I/18 Grünblatt, E. . . . . . . . . . . . . . . . I/18 Gründer, G. . . . . . . . . . . . . . I/18, I/20 Grunze, H. . . . . . . . . . . . . . . . . I/19 Gudlowski, Y. . . . . . . . . . . . . . . . I/23 Günter, M. . . . . . . . . . . . . . . . . I/32 Haag, A. . . . . . . . . . . . . . . . . . I/41 Haberkorn, U. . . . . . . . . . . . I/21, I/36 Hamann, J. . . . . . . . . . . . . . . . . I/19 Hampel, H. . . . . . . . . . . . . . I/19, I/34 Hartmann, A. M. . . . . . . . . . . . . . I/34 Härtter, S. . . . . . . . . . . . . . . I/18, I/30 Hatzinger, M. . . . . . . . . . . . . I/19, I/20 Hauser, M. . . . . . . . . . . . . . . . . I/23 Hausmann, A. . . . . . . . . . . . I/11, I/42 Hegerl, U. . . . . . . . . . . . . . . . . . I/31 Heiden, A. . . . . . . . . . . . . . . . . I/16 Heinz, A. . . . . . . . . I/20, I/23, I/27, I/38 Heinze, S. . . . . . . . . . . . . . . . . . I/24 Held, K. . . . . . . . . . . . . I/26, I/37, I/40

I/47 Hemmeter, U. . . . . . . I/17, I/19, I/20, I/41 Henn, F. A. . . . . . . . . . . . . . . . . I/38 Henning, U. . . . . . . . . . . . . . . . I/12 Hentschel, F. . . . . . . . . . . . . . . . I/25 Henze, M. . . . . . . . . . . . . . . I/21, I/36 Hermann, D. . . . . . . . . . . . . . . . I/38 Herr, R. . . . . . . . . . . . . . . . . . . I/30 Herrmann, M. J. . . . . . . . . . . I/14, I/15 Herzog, H. . . . . . . . . . . . . . . . . I/22 Herzog, M. H. . . . . . . . . . . . . I/9, I/20 Hesse, A. . . . . . . . . . . . . . . I/24, I/27 Hiemke, C. . . . . . . . . . . . . . I/18, I/30 Hillemacher, T. . . . . . . . . . . . . I/6, I/9 Hinterhuber, H. . . . . . . . . . . . . . I/11 Hofmann, P. . . . . . . . . . . . . . . . I/11 Holsboer, F. . . . . . . . . . . . . . . . I/26 Holsboer-Trachsler, E. . . . . . . . I/19, I/20 Horn, H. . . . . . . . . . . . I/15, I/20, I/29 Hornik, K. . . . . . . . . . . . . . . . . I/37 Hornung, J.-P. . . . . . . . . . . . . . . I/13 Hoyer, S. . . . . . . . . . . . . . . . . . I/20 Huber, M. T. . . . . . . . . . . . . . I/9, I/20 Huber, M. . . . . . . . . . . . . . . . . . I/17 Hubl, D. . . . . . . . . . . . . I/15, I/21, I/40 Hunt, A. . . . . . . . . . . . . . . . I/21, I/36 Hurlemann, R. . . . . . . . . . . . . . . I/22 Imhof, K. . . . . . . . . . . . . . . . . . I/45 Ising, M. . . . . . . . . . . . . . . I/19, I/37 Jabs, B. . . . . . . . . . . . . . . . . . . I/22 Jäger, L. . . . . . . . . . . . . . . . . . . I/31 Jakob, H. . . . . . . . . . . . . . . . . . . I/6 Jandl, M. . . . . . . . . . . . . . . . . . I/22 Janik, H. . . . . . . . . . . . . . . . . . I/27 Jänner, M. . . . . . . . . . . . . . . I/11, I/12 Janssen, B. . . . . . . . . . . . . . I/33, I/43 Jaquenoud Sirot, E. . . . . . . . . . . . I/22 Jecel, J. . . . . . . . . . . . . . . . . . . I/29 Jelic, V. . . . . . . . . . . . . . . . . . . I/27 Jessen, F. . . . . . . . . . . . . . . I/22, I/35 Jonsson, T. . . . . . . . . . . . . . . . . I/41 Jordan, W. . . . . . . . . . . . . . . . . I/23 Juckel, G. . . . . . . . . . . . . . . . . . I/23 Jungwirth, S. . . . . . . . . . . . . . . . I/24 Jüptner, M. . . . . . . . . . . . . . . . . I/24 Kaiser, E. . . . . . . . . . . . . . . . . . I/41 Karch, S. . . . . . . . . . . . . . . . . . I/31 Karege, F. . . . . . . . . . . . . . . . . . I/17 Karow, A. . . . . . . . . . . . . . . . . . I/24 Kaschka, W. P. . . . . . . . . . . . . . . I/22 Kasper, S. . . . . . . . . . . . I/11, I/16, I/37 Katayama, H. . . . . . . . . . . . . . . I/17 Keil, U. . . . . . . . . . . . . . . . . . . I/24 Keller-Pließnig, A. . . . . . . . . . . . . I/30 Khazaal, Y. . . . . . . . . . . . . . I/25, I/39 Kiefer, C. . . . . . . . . . . . . I/7, I/15, I/41 Kindler, J. . . . . . . . . . . . . . . . . I/16 Kircher, T. J. . . . . . . . . . . . . . . . I/25 Kissling, W. . . . . . . . . . . . . . . . I/19 Klein, S. . . . . . . . . . . . . . . . . . I/38 Kleinlogel, H. . . . . . . . . . . . . . . I/43 Klimke, A. . . . . . . . . . . . . . I/11, I/12 Kneitz, S. . . . . . . . . . . . . . . . . . I/18 Kochi, K. . . . . . . . . . . . . . . . . . I/17 Koenig, T. . . . . . . . . I/21, I/25, I/27, I/40 Kohl, C. . . . . . . . . . . . . . . . . . . I/39 Koller, R. . . . . . . . . . . . . . . . . . I/41 König, P. . . . . . . . . . . . . . . I/11, I/42 König, T. . . . . . . . . . . . . . . . . . I/20 Kopmann, S. . . . . . . . . . . . . . . . . I/9 Kornhuber, J. . . I/6, I/8, I/9, I/16, I/23, I/43

Kosel, M. . . . . . . . . . . . . . . . . . I/35 Kotrotsios, J. . . . . . . . . . . . . . . . I/11 Koutsilieri, E. . . . . . . . . . . . . . . I/29 Kreis, M. . . . . . . . . . . . . . . . . . I/25 Kreis, R. . . . . . . . . . . . . . . . I/15, I/21 Krell, D. . . . . . . . . . . . . . . . . . . I/8 Krenz, S. . . . . . . . . . . . . . . . . . I/25 Krieg, C. J. . . . . . . . . . . . . . . . . I/41 Krieg, J. C. . . . . . . . . I/9, I/17, I/20, I/41 Krieger, K. . . . . . . . . . . . . . . . . I/11 Krieger, S. . . . . . . . . . . . . . . . . I/27 Krumm, B. . . . . . . . . . . . . . . . . I/25 Kuenzel, H. E. . . . . . . . . . . . . . . I/40 Kunz, M. . . . . . . . . . . . . . . . . . I/26 Künzel, H. E. . . . . . . . . . . . . . . . I/26 Laederach-Hofmann, K. . . . . . . . . I/29 Laggner, A. . . . . . . . . . . . . . . . . I/16 Lahousen, T. . . . . . . . . . . . . . . . I/11 Landvogt, C. . . . . . . . . . . . . . . . I/18 Lathrop, M. . . . . . . . . . . . . . . . . I/38 Lautenbacher, S. . . . . . . . . . . . . . I/26 Lavergne, F. . . . . . . . . . . . . . . . I/26 Lehmann, C. . . . . . . . . . I/16, I/27, I/41 Lehmann, Ch. . . . . . . . . . . . . . . I/40 Lehmann, D. . . . . . . . . . . . . . . . I/17 Lehmann, K. . . . . . . . . . . . . . . . I/27 Leisch, F. . . . . . . . . . . . . . . . . . I/37 Lenz, B. . . . . . . . . . . . . . . . . . . I/8 Lenzen, K. . . . . . . . . . . . . . . . . I/15 Lesting, J. . . . . . . . . . . . . . . . . . I/31 Lewczuk, P. . . . . . . . . . . . . . . . . I/43 Li, J. . . . . . . . . . . . . . . . . . . . . I/18 Linden, D. E. J. . . . . . . . . . . . . . . I/22 Linka, T. . . . . . . . . . . . . . . . . . I/27 Lis, S. . . . . . . . . . . . . . . . . . . . I/27 Lovblad, K. . . . . . . . . . . . . . . . . I/21 Ludewig, K. . . . . . . . . . . . . . . . I/32 Lunde, M. . . . . . . . . . . . . . . . . I/28 Machulla, H. J. . . . . . . . . . . . . . . I/20 Magnotta, V. . . . . . . . . . . . . . . . . I/5 Maier, S. E. . . . . . . . . . . . . . . . . I/21 Maier, W. . . . . . . . . . . . . . . I/22, I/35 Maler, J. M. . . . . . . . . . . . . . . I/6, I/43 Mann, K. . . . . . . I/15, I/20, I/27, I/38, I/43 Marbach, S. . . . . . . . . . . . . . . . . I/20 Marksteiner, J. . . . . . . . . . . . . . . I/28 Marques, C. A. . . . . . . . . . . . . . . I/24 Marques, P. . . . . . . . . . . . . . . . . I/44 Martin, D. . . . . . . . . . . . . . . . . I/29 Martiny, K. . . . . . . . . . . . . . . . . I/28 Mathiak, K. . . . . . . . . . . . . . . . I/25 Mathias, S. . . . . . . . . . . . . . . . . I/37 Matsuda, F. . . . . . . . . . . . . . . . . I/38 Maurer, C. . . . . . . . . . . . . . . . . I/30 Maurer, K. . . . . . . . . . . . . . I/22, I/28 Mawrin, C. . . . . . . . . . . . . . . . . I/8 Mayer, G. . . . . . . . . . . . . . . . . . I/23 Medicus, G. . . . . . . . . . . . . . . . I/28 Meier, F. . . . . . . . . . . . . . . . . . I/34 Meng, H. . . . . . . . . . . . . . . . . . I/32 Menzi, C. . . . . . . . . . . . . . . . . . I/41 Messerli, N. . . . . . . . . . . . . . . . I/29 Metzger, J. W. . . . . . . . . . . . . . . . I/44 Meyer, P. T. . . . . . . . . . . . . . . . . I/22 Meyer, U. . . . . . . . . . . . . . . . . . I/29 Michel, T. M. . . . . . . . . . . . . . . . I/29 Miertschischk, J. . . . . . . . . . . . . . I/43 Miozzari, A. . . . . . . . . . . . . . . . I/25 Misouni, D. . . . . . . . . . . . . . . . I/25 Mobascher, A. . . . . . . . . . . . I/11, I/12 Möller, H. J. . . . . I/13, I/17, I/31, I/34, I/39

Montagrin, Y. . . . . . . . . . . . . . . I/39 Mugele, B. . . . . . . . . . . . . . . . . . I/6 Mulert, C. . . . . . . . . . . . . . . . . I/31 Müller, B. W. . . . . . . . . . I/24, I/27, I/30 Müller, K. M. . . . . . . . . . . . . I/15, I/30 Müller, M. J. . . . . . . . . . . . . I/15, I/30 Müller, N. . . . . . . . . I/12, I/30, I/31, I/39 Müller, T. J. . . . . . . . . . . . . . I/15, I/29 Müller, T. . . . . . . . . . . . . . . . . . I/20 Müller, W. E. . . . . . . . . . . . . . . . I/24 Müller-Spahn, F. . . . . . . . . . . I/24, I/34 Münch, M. . . . . . . . . . . . . . . . . . I/8 Murck, H. . . . . . . . . . . . . . . . . I/40 Naber, D. . . . . . . . . . . . . . . . . . I/24 Nara, K. . . . . . . . . . . . . . . . . . I/29 Neddens, J. . . . . . . . . . . . . . I/31, I/40 Neumann, M. . . . . . . . . . . . . . . I/18 Niedmann, P. D. . . . . . . . . . . . . . I/23 Nishikawa, M. . . . . . . . . . . . . . . . I/7 Normann, C. . . . . . . . . . . . . . . . I/31 Olivieri, G. . Ondracek, J. Orosz, A. T. . Osiek, C. . . Özgürdal, S.

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I/34 I/18 I/32 I/17 I/23

Padberg, F. . . . . . . . . . . . . . . . . I/13 Pantel, J. . . . . . . . . . . . . . I/5, I/6, I/41 Pascual-Marqui, R. D. . . . . . . . . . . I/17 Pavlovic, D. . . . . . . . . . . . . . . . I/16 Pfuhlmann, B. . . . . . . . . . . . I/32, I/40 Planz, O. . . . . . . . . . . . . . . . . . . I/8 Plotkin, M. . . . . . . . . . . . . . . . . I/16 Pogarell, O. . . . . . . . . . . . . . . . . I/31 Portwich, P. . . . . . . . . . . . . . . . I/32 Poustka, F. . . . . . . . . . . . . . . . . I/21 Pradier, L. . . . . . . . . . . . . . . . . I/24 Pragst, F. . . . . . . . . . . . . . . . . . I/44 Pramsohler, B. . . . . . . . . . . . . . . I/11 Prapotnik, M. . . . . . . . . . . . I/11, I/42 Preuss, U. . . . . . . . . . . . . . . I/32, I/38 Propp, S. . . . . . . . . . . . . . . . . . I/31 Prvulovic, D. . . . . . . . . . I/21, I/22, I/28 Pycha, R. . . . . . . . . . . . . . . . . . I/11 Rapp, A. . . . . . . . . . . . . . . . . . I/25 Ravid, R. . . . . . . . . . . . . . . . . . I/18 Reif, A. . . . . . . . . . . . . . . . . . . I/33 Reimold, M. . . . . . . . . . . . . . . . I/20 Reinhard, N. . . . . . . . . . . . . . . . I/40 Reischies, F. M. . . . . . . . . . . . . . . I/16 Reiss, J. . . . . . . . . . . . . . . . . . . I/30 Reulbach, U. . . . . . . . . . . . . . . . . I/9 Rhein, T. . . . . . . . . . . . . . . . . . I/33 Riedel, M. . . . . . . . . . . . I/12, I/31, I/39 Riederer, P. . . . . . . . . . . I/18, I/29, I/34 Riemann, D. . . . . . . . . . . . . . . . . I/7 Rietschel, M. . . . . . . . . . . . . . . . I/37 Ringel, T. M. . . . . . . . . . . . . . . . I/15 Rittmansberger, H. . . . . . . . . . . . I/11 Rocamora, R. . . . . . . . . . . . . I/17, I/41 Rodenbeck, A. . . . . . . . . . . . . . . I/23 Roggendorf, W. . . . . . . . . . . . . . I/18 Rösch, F. . . . . . . . . . . . . . . . . . I/18 Rothmeier, J. . . . . . . . . . . . . . . . I/22 Rudolph, S. . . . . . . . . . . . . . . . . I/33 Ruhrmann, S. . . . . . . . . . . . . . . I/33 Rujescu, D. . . . . . . . . . . I/17, I/34, I/38 Rupprecht, R. . . . . . . . . . . . . . . I/13 Rüther, E. . . . . . . . . . . . . . . I/23, I/44

I/48 Saletu, B. . . . . . . . . . . . . . . . . . I/34 Saletu-Zyhlarz, G. M. . . . . . . . . . . I/34 Sander, T. . . . . . . . . . . . . . . . . . I/15 Sartory, G. . . . . . . . . . . I/24, I/27, I/30 Sauer, H. . . . . . . . . . . . . . . . . . I/38 Savaskan, E. . . . . . . . . . . . . . . . I/34 Schäfer, I. . . . . . . . . . . . . . . . . . I/24 Schaub, M. . . . . . . . . . . . . . . . . I/34 Schenk, F. . . . . . . . . . . . . . . . . I/13 Scherk, H. . . . . . . . . . . . . . I/22, I/35 Scherping, I. . . . . . . . . . . . . . . . I/24 Scheurich, A. . . . . . . . . . . . . . . . I/15 Schewe, H. J. . . . . . . . . . . . . . . . I/35 Schild, H. H. . . . . . . . . . . . . I/22, I/35 Schlaepfer, T. E. . . . . . . . . . . . . . I/35 Schläpfer, T. . . . . . . . . . . . . . . . I/29 Schlösser, R. . . . . . . . . . . . . . . . I/35 Schmahl, C. . . . . . . . . . . . . . . . I/35 Schmid, D. A. . . . . . . . . . . . . . . I/37 Schmidt, L. G. . . . . . . . . . . . I/15, I/30 Schmitt, A. . . . . . . . . . . . . . . . . I/36 Schnitzler, C. . . . . . . . . . . . . . . . I/8 Schoenknecht, P. . . . . . . . . . . . . I/21 Schönknecht, P. . . . . . . . . I/6, I/36, I/41 Schosser, A. . . . . . . . . . . . . . . . I/37 Schreiber, M. . . . . . . . . . . . . . . . I/44 Schreiber, S. . . . . . . . . . . . . . . . I/38 Schröder, C. . . . . . . . . . . . . . . . . I/8 Schroder, J. . . . . . . I/5, I/6, I/21, I/36, I/41 Schroth, G. . . . . . . . . . . . . . . . . I/21 Schuessler, P. . . . . . . . . . . . . . . . I/40 Schüle, C. . . . . . . . . . . . . . . . . . I/13 Schulze, T. G. . . . . . . . . . . . . . . . I/37 Schulze-Rauschenbach, S. . . . . . . . I/35 Schumann, G. . . . . . . . . . . . . . . I/38 Schüssler, P. . . . . . . . . . . . . . . . I/37 Schwald, M. . . . . . . . . . . . . . . . I/17 Schwarz, M. . . . . . . . . . . . . . . . I/31 Seifert, C. . . . . . . . . . . . . . . . . . I/31 Seifritz, E. . . . . . . . . . . . I/20, I/34, I/35 Selenga, D. . . . . . . . . . . . . . . . . I/22 Sieghart, W. . . . . . . . . . . . . . . . I/37 Siessmeier, T. . . . . . . . . . . . . I/18, I/20 Smirnov, A. . . . . . . . . . . . . . . . I/43 Smolka, M. N. . . . . . . . . . . . . . . I/38 Smolka, M. . . . . . . . . . . . . . . . . I/27 Sobanski, T. . . . . . . . . . . . . . . . I/38 Sofianos, G. . . . . . . . . . . . . . . . I/38 Sonntag, A. . . . . . . . . . . . . . . . . I/26

Soyka, M. . . . . . . . . . . . . . . . . . I/38 Spanagel, R. . . . . . . . . . . . . . . . I/38 Spellmann, I. . . . . . . . . . . . . . . . I/39 Sperling, W. . . . . . . . . . . . . . . . . I/6 Sperner-Unterweger, B. . . . . . . . . . I/39 Sprick, U. . . . . . . . . . . . . . . . . . I/39 Staedtgen, M. . . . . . . . . . . . . . . I/23 Stamm, S. . . . . . . . . . . . . . . . . I/34 Stanga, Z. . . . . . . . . . . . . . . . . . I/29 Stankovic, M. . . . . . . . . . . . . . . I/39 Steger, J. . . . . . . . . . . . . . . . . . I/45 Steiger, A. . . . . . . . . . . . I/26, I/37, I/40 Stein, M. . . . . . . . . . . . . . . . . . I/40 Steinhausen, H.-C. . . . . . . . . . . . I/45 Steullet, P. . . . . . . . . . . . . . . . . I/13 Steyer, J. . . . . . . . . . . . . . . . . . I/22 Stitz, L. . . . . . . . . . . . . . . . . . . I/8 Stöber, G. . . . . . . . . . . . . . . . . . I/40 Stoeter, P. . . . . . . . . . . . . . . I/15, I/18 Stohler, R. . . . . . . . . . . . . . . . . I/34 Strassnig, M. . . . . . . . . . . . . . . . I/39 Straube, E. R. . . . . . . . . . . . . . . I/38 Strik, W. . . . I/15, I/20, I/21, I/29, I/40, I/43 Svitek, J. . . . . . . . . . . . . . . . . . I/43 Szegedi, A. . . . . . . . . . . . . . I/15, I/38 Tadic, A. . . . . . . . . . . . . . . . . . I/15 Teipel, S. J. . . . . . . . . . . . . . . . . I/19 Tepest, R. . . . . . . . . . . . . . . . . . I/33 Teuchert-Noodt, G. . . . . . . I/6, I/31, I/40 Teutsch, M. . . . . . . . . . . . . . . . . I/31 Thomann, P. A. . . . . . . . . . . . . . I/41 Thum, A. . . . . . . . . . . . . . . I/17, I/41 Tosic, M. . . . . . . . . . . . . . . . . . I/13 Träber, F. . . . . . . . . . . . . . . I/22, I/35 Trübner, K. . . . . . . . . . . . . . . . . I/8 Uebelhack, R. . . . . . . . . . I/16, I/18, I/35 Uhr, M. . . . . . . . . . . . . . . . I/26, I/37 Umbricht, D. . . . . . . . . . . . . . . . I/41 Undén, M. . . . . . . . . . . . . . . . . I/28 van Calker, D. . . . . . . . . . . . . . . I/10 van Leeuwen, T. H. . . . . . . . . . . . I/45 Vannini, P. . . . . . . . . . . . . . . . . I/41 Vedder, H. . . . . . . . . . . . . . . . . I/41 Vernaleken, I. . . . . . . . . . . . . . . I/18 Vetter, Z. . . . . . . . . . . . . . . . . . I/42 Voderholzer, U. . . . . . . . . . . . . . . I/7

Vogeley, K. . . . . . Vollenweider, F. X. . von Ahsen, N. . . . von Wilmsdorff, M.

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I/22, I/33 I/41, I/42 . . . I/23 I/39, I/42

Wagner, G. . . . . . . . . . . . . . . . . I/38 Wagner, M. . . . . . . . . . . . . . . . . I/35 Wagner, W. . . . . . . . . . . . . . . . . I/11 Wahlund, L.-O. . . . . . . . . . . . . . I/41 Waschgler, R. . . . . . . . . . . . . . . I/42 Weber, M. . . . . . . . . . . . . . . . . I/22 Weber-Fahr, W. . . . . . . . . . . . . . I/10 Weidemann, H. . . . . . . . . . . . . . . I/8 Weijers, H. G. . . . . . . . . . . . . I/9, I/43 Weikel, J. C. . . . . . . . . . . . . . . . I/37 Weikel, J. . . . . . . . . . . . . . . . . . I/40 Weinmann, S. . . . . . . . . . . . I/33, I/43 Weinmann, W. . . . . . . . . . . . . . . I/44 Wellek, S. . . . . . . . . . . . . . . . . . I/38 Whybra, C. . . . . . . . . . . . . . . . . I/15 Wiesbeck, G. A. . . . . . . . . I/9, I/43, I/44 Wilhelm, J. . . . . . . . . . . . . . . . . I/27 Wille, P. . . . . . . . . . . . . . . . . . . I/15 Wiltfang, J. . . . . . . . . . . . . . . . . I/43 Wirth, M. . . . . . . . . . . . I/15, I/20, I/29 Wirtz, G. . . . . . . . . . . . . . . . . . I/43 Wirz-Justice, A. . . . . . . . . I/8, I/34, I/43 Witte, V. . . . . . . . . . . . . . . . . . . I/6 Wittgens, W. . . . . . . . . . . . . . . . I/44 Witthaus, H. . . . . . . . . . . . . . . . I/23 Wolf, R. . . . . . . . . . . . . . . . . . I/44 Wolf, S. . . . . . . . . . . . . . . . . . . I/44 Wolfersdorf, M. . . . . . . . . . . . . . I/44 Wölwer, W. . . . . . . . . . . . . . . . . I/11 Wong, D. F. . . . . . . . . . . . . . . . . I/18 Wrase, J. . . . . . . . . . . . . . . I/20, I/38 Wurst, F. M. . . . . . . . . . . . . . . . I/44 Wüstenberg, T. . . . . . . . . . . . . . I/41 Yee, B. K. . . . . . . . . . . . . . . . . . I/29 Ziegenbein, M. . . Zilles, K. . . . . . Zimmermann, U. Zobel, A. . . . . . Zullino, D. F. . . . Zwanzger, P. . . . Zwerina, S. . . . .

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. . . I/26 . . . I/22 . . . I/27 . . . I/35 I/25, I/39 . . . I/13 . . . I/29