Tag der Forschung der Psychiatrie und Kinder- und Jugendpsychiatrie

9. Dezember 2011 Präsentation aktueller Forschungsarbeiten

Psychiatrische Universitätsklinik Zürich Psychiatrische Poliklinik USZ Zentrum für Kinder- und Jungendpsychiatrie UZH

Inhalt Programm Seite 3 Übersicht über die Abstracts der Referenten Prof. Dr. med. Ulrich Schnyder Seite 5 Dr. med. Milan Scheidegger Seite 6 Fritz Frauenfelder, MNSc Seite 7 Christian Tackenberg, PhD Seite 8 Dr. sc. nat. Silvia Brem Seite 9 lic. phil. Diana Wotruba Seite 10 Übersicht über die Posterabstracts Psychiatrische Poliklinik USZ Ledermann et al. Seite 12 Morina et al. Seite 13+14 Oe et al. Seite 15 Pirrotta et al. Seite 16+17 Schumacher et al. Seite 18 Psychiatrische Universitätsklinik Zürich Klinik für Affektive Erkrankungen und Allgemeinpsychiatrie Zürich Ost Azzinnari et al. Seite 20 Grimm et al. Seite 21 Lott et al. Seite 22 Mokros et al. Seite 23 Schmidt et al. Seite 24 Schuepbach et al. Seite 25 Spinelli et al. Seite 26 Vonmoos et al. Seite 27 Psychiatrische Universitätsklinik Zürich Direktion Pflege, Therapien und Soziale Arbeit Baumeler et al. Seite 29 Frey Seite 30 Psychiatrische Universitätsklinik Zürich Klinik für Alterspsychiatrie Chadha Santuccione et al. Seite 32 Gietl et al. Seite 33 Kälin et al. Seite 34 Kulic et al. Seite 35 Minakaki et al. Seite 36 Preisig et al. Seite 37 Riese et al. Seite 38+39 Szodorai et al. Seite 40

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Zentrum für Kinder- und Jugendpsychiatrie, Universität Zürich Aebi et al. Seite 42 Ball et al. Seite 43 Drechsler et al. Seite 44 Grünblatt et al. Seite 45 Hauser et al. Seite 46 Iannaccone et al. Seite 47 Kronschnabel et al. Seite 48 Luechinger et al. Seite 49 Marinova et al. Seite 50 Nyffeler et al. Seite 51 Psychiatrische Universitätsklinik Zürich Klinik für Soziale Arbeit und Allgemeinpsychiatrie Zürich West Ajdacic-Gross et al. Seite 53 Brantschen et al. Seite 54 Brühl et al. Seite 55 Gholami et al. Seite 56 Herwig et al. Seite 57 Lay et al. Seite 58 Paust et al. Seite 59 Siemerkus et al. Seite 60

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Programm

9.00 Eröffnung und Begrüssung Im Hörsaal Z1 03 9.15 Resilience versus PTSD following traumatic exposure

Prof. Dr. med. Ulrich Schnyder Psychiatrische Poliklinik USZ

9.45 Exploring the antidepressant effects of ketamine: insights from multimodal

neuroimaging Dr. med. Milan Scheidegger Klinik für Affektive Erkrankungen und Allgemeinpsychiatrie Zürich Ost 10.15 Evaluation der Einführung von Pflegeklassifikationen in die Praxis Fritz Frauenfelder, MNSc Direktion Pflege, Therapien und Soziale Arbeit 10.45 Pause 11.15 Alzheimer in der Kulturschale Christian Tackenberg, PhD Klinik für Alterspsychiatrie 11.45 Bildgebung von Lesenlernen und Dyslexie Dr. sc. nat. Silvia Brem Zentrum für Kinder- und Jugendpsychiatrie, Universität Zürich 12.15 Funktionale Konnektivität im Resting State fMRI bei Personen mit erhöhtem

Risiko für eine psychotische Erkrankung lic. phil. Diana Wotruba Klinik für Soziale Psychiatrie und Allgemeinpsychiatrie Zürich West 12.30 Lunch

Im Lichthof

Posterpräsentationen im Mehrzweckraum Z0 03

14.30 Ende

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Abstracts der Referenten

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RESILIENCE VERSUS PTSD FOLLOWING TRAUMATIC EXPOSURE Schnyder, U.1 1Department of Psychiatry and Psychotherapy, University Hospital Zurich, Switzerland Keywords Trauma, PTSD, Resilience, Psychotherapy _________________________________________________________________________________ Introduction The clinical course and development of stress responses after exposure to traumatic events can be categorized into resistance, resilience, recovery, relapse-remission, delayed dysfunc-tion, and chronic dysfunction such as posttraumatic stress disorder (PTSD). More than half of trauma survivors can be referred to as resistant or resilient. However, our understanding of the psychological and neurobiological characteristics of resilience is still very limited. Most longitudinal studies in the field did not include neuroendocrine and neurophysiological as-sessments, nor did they use experimental designs. Methods We conducted two longitudinal studies of the psychosocial consequences of severe acciden-tal injuries, and a series of pilot studies into resilience. Results Less than 5% of patients suffering from PTSD were found. This was replicated in a second and much larger study, including patients with pre-traumatic psychiatric morbidity, and sub-jects who did not sufficiently speak the local language. Conclusion A comprehensive approach, linking the psychological process after trauma with neurobio-logical investigations over time, should be chosen to clarify under which circumstances resil-ience develops. We are currently planning a study looking into various predictors of resil-ience in survivors of physical violence. Multiple assessments will include discriminative con-ditioning tasks, cortisol and DHEA-S assays, psychophysiological measures of stress reac-tivity, and neuroimaging.

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EXPLORING THE ANTIDEPRESSANT EFFECTS OF KETAMINE: INSIGHTS FROM MULTIMODAL NEUROIMAGING Scheidegger, M.1 2, Grimm S.1 4 5, Henning, A.2, Walter, M. 6, Lehmann, M.1, Ametamey, S.7, Buck, A.8, Boeker, H.1, Boesiger, P.2, Seifritz, E.1 1University Hospital of Psychiatry, Clinic of Affective Disorders and General Psychiatry, Zu-rich, Switzerland 2Institute for Biomedical Engineering, University & ETH Zurich, Zurich, Switzerland 4Cluster Languages of Emotion, Freie Universität Berlin, Berlin, Germany 5Department of Psychiatry, Charité, CBF, Berlin, Germany 6Department of Psychiatry, Otto-von-Guericke University, Magdeburg, Germany 7University Hospital Zurich, Division of Nuclear Medicine, Zurich, Switzerland 8ETH Zurich, Institute of Pharmaceutical Sciences, Zurich, Switzerland Keywords multimodal imaging, depression, glutamatergic system, antidepressant drugs,

ketamine _________________________________________________________________________________ Introduction Ketamine is a potent NMDA receptor antagonist with rapid antidepressant properties at subanaesthetic doses, thus providing a valuable research tool for the investigation of the neurobiology of the glutamatergic system in major depressive disorder (MDD). Methods A total of 50 healthy subjects were investigated in three multimodal imaging studies includ-ing task fMRI, resting-state fMRI (rsfMRI), proton magnetic resonance spectroscopy (1H-MRS), arterial spin labeling (ASL), and positron emission tomography (mGluR5-PET). Pharmacological intervention consisted of an intravenous dose of either S-ketamine (0,25 mg/kg/h) or placebo. Results We report pharmacological changes in rsfMRI connectivity of the default-mode and affective network via the dorsomedial prefrontal cortex as well as changes in functional brain activa-tion during emotional picture viewing (IAPS) and cognitive processing (n-back) in core re-gions of the neurocircuitry of mood and cognition. Functional BOLD responses in prefrontal cortex were related to glutamatergic metabolite concentrations (1H-MRS) after ketamine administration. Conclusion We conclude that the antidepressant properties of ketamine might be explained by reversing some aspects of the dysrupted glutamatergic neurobehavioural plasticity in MDD. In future, this multimodal and pharmacological imaging approach will be validated in depressed pa-tients in order to assess its utility for the investigation of neurobiological mechanisms of anti-depressant drug action.

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EVALUATION DER EINFÜRUNG VON PFLEGEKLASSIFIKATIONEN IN DIE PRAXIS Frauenfelder, F. Psychiatrisches Universitätsspital Zürich, Forschung und Entwicklung DPTS Keywords standardisierte Pflegefachsprache, Implementierungsprozess, Prozessevalua-

tion _________________________________________________________________________________ Fragestellung Auf der Grundlage von standardisierten Fachsprachen kann die Qualität der Pflege in Form von Effizienz, Transparenz und Nachvollziehbarkeit gesteigert werden. Im Rahmen syste-matischen Vorgehensweise wurde das Basis-Assessment-instrument SEFW und die Pflege-klassifikationen NANDA-International (NANDA-I) und Nursing Outcomes Classification (NOC) in die alltägliche Pflegepraxis eingeführt und etabliert. Methode Anhand einer quantitativen Querschnittstudie mit Folgeerhebungen wurde der strukturelle Einsatz der implementierten Elemente evaluiert. Ergebnisse Von den 90 evaluierten Patientenfällen waren rund zwei Drittel vollständig und durchgehend anhand des Assessmentinstruments und der Klassifikationen dokumentiert. Bei 92.2% der Patienten fand sich ein dokumentiertes Assessment. In 88,9% der Fälle waren eine oder mehrere Pflegediagnose(n) vollständig beschrieben und bei 83.3% aller Patientinnen und Patienten die pflegerelevante Ergebnisse (NOC) definiert. In 87.8% der Fälle fanden sich die pflegerischen Interventionen in eigenen Worten dokumentiert. Die Analyse der fehlerhaften Dokumentationen ergab, dass es sich in den meisten Fällen um kürzlich eingetretene Pati-enten handelte oder dass sich die betroffenen Pflegeplanungen in Überarbeitung befanden. Schlussfolgerung Die standardisierten Fachsprachen konnten erfolgreich in das pflegerische Praxisfeld einge-führt und etabliert werden. Sie dienen zukünftigen als Basis für die weitere inhaltlich-fachliche Weiterentwicklung der Pflege insbesondere der Umsetzung von Evident Based Nursing.

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ALZHEIMER IN DER KULTURSCHALE Tackenberg, C.1, Brandt, R.2, Nitsch, R.M.1 1 Psychiatrische Universitätsklinik, Abteilung für psychiatrische Forschung, Zürich, Schweiz 2 Universität Osnabrück, Abteilung Neurobiologie, Osnabrück Keywords ex vivo Modell, Alzheimer’sche Krankheit, Amyloid-beta, Tau, Hippocampus,

Neurodegeneration, Synapse, Spine _________________________________________________________________________________ Fragestellung Die Alzheimer’sche Krankheit (AD) ist die weltweit häufigste neurodegenerative Demenzer-krankung. Charakteristisch sind extrazelluläre Plaques, bestehend aus dem amyloid-beta (Aβ) Peptid und intrazelluläre Tau Ablagerungen. Hirne von AD Patienten zeigen massiven neuronalen Zelltod sowie den Verlust von synaptischen Verbindungen. Ziel dieser Arbeit war es, den Beitrag von Aβ und Tau zur neuronalen und synaptischen AD Pathologie in einem Modellsystem zu untersuchen, sowie eine potentielle funktionelle Interaktionen beider Prote-ine zu erforschen. Methode Organotypische hippocampale (ex vivo) Gewebekulturen wurden von Aβ-produzierenden AD-Mausmodellen präpariert. Diese Kulturen wurden mit Sindbis Viren infiziert, um grün-fluoreszierenden Protein (GFP) oder GFP-gekoppeltes Tau in Neuronen zu exprimieren. Der Effekt von Aβ und Tau auf das neuronale Zellüberleben und die synaptischen Verknüpfun-gen, sowie die Signalwege, die zur Pathologie führen, wurden untersucht. Aβ induziert, unabhängig von Tau, einen Verlust von postsynaptischen dendritischen Dor-nen (Spines), vermittelt über synaptische NMDA Rezeptoren, Calcineurin und GSK-3β. Im Gegensatz dazu ist Aβ allein nicht toxisch, sondern benötigt Tau, um neuronalen Zelltod durch Tau Hyperphosphorylierung auszulösen. Der Aβ-vermittelte Effekt auf Tau wird durch Aktivierung von extrasynaptischen NMDA Rezeptoren hervorgerufen. Conclusion / Schlussfolgerung Hippocampale ex vivo Kulturen von Aβ-produzierenden AD-Mausmodellen in Kombination mit Virus-vermittelter expression von Tau ermöglichen die Analyse der pathologischen Me-chanismen, die zur neuronalen und synaptischen Degeneration in AD führen. Sie erlauben, potentielle therapeutische Ansätze in einem authentisch zentralnervösen System zu unter-suchen.

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BILDGEBUNG VON LESENLERNEN UND DYSLEXIE Brem, S.1,2 ,Bach, S.1,2 , Richardson, U.2, Brandeis, D.1

1 Hospital of Child and Adolescent Psychiatry, University Zürich, Neumünsterallee 9, 8032 Zürich, Switzerland 2 Agora Center, University of Jyväskylä, PO Box 35, 40014 University of Jyväskylä, Finland Keywords Lesenlernen, Dyslexie, Bildgebung, funktionelle Magnetresonanztomographie

(fMRT), Ereigniskorrelierte Potentiale (EKP) _________________________________________________________________________________ Einleitung Die Lese-Rechtschreibstörung „LRS“ betrifft ca. 5-10% der Kinder im Schulalter. Eine grobe Vorhersage mit Hilfe von sprachlichen Vorläuferfertigkeiten ist bereits vor der Schule teilwei-se möglich. Der Einbezug von spezifischen Markern aus der Bildgebung könnte jedoch die Prädiktion verbessern. Verschiedene Studien haben auf die wichtige Rolle des linken okzipi-to-temporalen Kortex für flüssiges Lesen hingewiesen. In dieser Studie haben wir deshalb untersucht, wie sich die Aktivität im visuellen Wortformsystem (VWFS) mit dem Lesenlernen entwickelt und ob Masse der VWFS Aktivität im Kindergarten die Prädiktion der Lesefertig-keiten in der Schule verbessern können. Methoden In dieser kombinierten fMRT und EKP Längsschnittstudie haben wir die Entwicklung der Le-sefertigkeiten und die damit assoziierten Veränderungen in der Schriftverarbeitung im Hirn vom Kindergarten in die 2. Klasse verfolgt und Kinder mit normalen, bzw. schlechten Lese-fertigkeiten verglichen. Resultate Eine Entwicklung der Schriftsensitivität im VWFS während dem Lesenlernen konnte mittels fMRT und EKPs gezeigt werden. Weiter verbesserte der Einbezug von EKP und fMRT Mas-sen im Kindergarten die Prädiktion der späteren Lesefertigkeiten im Vergleich zur Vorhersa-ge mit reinen Verhaltensmassen. Schlussfolgerung Diese Studie zeigt einerseits plastische Veränderungen im Hirn während dem Lesenlernen auf. Andererseits wird deutlich, dass eine Kombination von geeigneten Bildgebungs- und Verhaltensmassen die Vorhersage der Lesefertigkeiten verbessern kann.

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FUNKTIONELLE KONNEKTIVITÄT IM RESTING-STATE-FMRI BEI ERHÖHTEM RISIKO FÜR EINE PSYCHOTISCHE ERKRANKUNG Wotruba, D.1 2, Rössler W.1, Michels, L.2, Kollias, S. 2, Theodoridou, A.1, Heekeren, K.1 1Psychiatrische Universitätsklinik Zürich, Zürcher Impulsprogramm zur nachhaltigen Ent-wicklung der Psychiatrie (ZInEP), Schweiz 2UniversitätsSpital Zürich, Klinik für Neuroradiologie, Schweiz Keywords Early Detection, Risk Factors, Psychosis, Default Mode Network, Graph-

theoretical Analysis, Functional Connectivity, fMRI _________________________________________________________________________________ Fragestellung Bisherige Bildgebungsstudien stützen die Dyskonnektivitätshypothese der Schizophrenie, die eine Störung neuronaler funktioneller Netzwerke postuliert. Jedoch ist bisher wenig un-tersucht, inwieweit bereits im Risikozustand für eine psychotische Erkrankung Alterationen der intrinsischen funktionellen Konnektivität zu finden sind. Methode Ziel der Studie ist die Untersuchung der funktionellen Konnektivität im resting-state fMRI bei Probanden, welche ultra-high risk (UHR) Kriterien erfüllen (n=23) und Probanden im high-risk-state (HR), die Basissymptome berichten (n=50), sowie der Vergleich zu einer gesun-den Kontrollgruppe (HC) (n=17). Im Weiteren wird die funktionelle Konnektivität hinsichtlich ihrer Netzwerktopologie mit Hilfe graphentheoretischer Indizes analysiert, welche es erlaubt, die Netzwerk-Effizienz der funktionellen Konnektivität zu charakterisieren. Ergebnisse UHR zeigen eine im Vergleich zu HR verminderte funktionelle Konnektivität, was sich vor al-lem präfrontal sowohl auf die globale und die lokale Effizienz als auch auf die Kosten einzel-ner Komponenten auswirkt. Eine Hyperkonnektivität des funktionellen Netzwerkes im Ver-gleich zu HC konnte jedoch nur bei HR zwischen zerebellären und inferioparietalen Arealen zum rechten Präfrontalkortex festgestellt werden, was jedoch keinen Einfluss auf die Effi-zienz des Netzwerkes hat. Schlussfolgerung Erste Ergebnisse der Untersuchung weisen auf eine veränderte funktionelle Konnektivität bei Probanden im Risikozustand für eine psychotische Erkrankung hin und lassen ferner vermuten, dass die klinischen Auffälligkeiten von UHR-Probanden im Vergleich zu HR-Probanden mit einer geringeren Effizienz der Ruhenetzwerkaktivität assoziiert sind. Die symptomatische Unterteilung in HR und UHR zeigt somit auch in der Ruhenetzwerkaktivität ein differenzierteres Bild, in welchem einzig die HR zusätzliche funktionelle Konnektionen aufweisen. Befunde veränderter topologischer Eigenschaften des intrinsischen Netzwerkes könnten wichtige Hinweise zum besseren Verständnis der zugrunde liegenden pathophysiologischen Mechanismen liefern. Darüber hinaus könnten solche prospektiven Biomarker wertvolle dia-gnostische und prognostische Informationen darstellen.

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Posterabstracts Psychiatrische Poliklinik USZ

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IS FIBROMYALGIA A NEUROPATHIC PAIN DISEASE? Ledermann, K.1, Jenewein, J.1, Sprott, H.2, Hasler, G.3, Schnyder, U.1, Burger, C.4, Jo-hayem, A.4, Cservenyak, T.4, Kollias, S.5, Buck, A.4, Martin-Soelch, C.1 1Department of Psychiatry and Psychotherapy, University Hospital Zurich, Switzerland 2Clinic of Rheumatology and Institute of Physical Medicine, University Hospital Zurich, Switz 3 University Hospital of Adult Psychiatry, University Bern, Switzerland 4Department of Nuclear Medicine, University Hospital Zurich, Switzerland 5Institute of Neuroradiology, University Hospital Zurich, Switzerland Keywords: PET, Dopamine, pain perception, Fibromyalgia _________________________________________________________________________________ Introduction The aim of the study is to proof for a rationale whether FM is a neuropathic disease or not. Changes in presynaptic dopamine (DA) function in FM will therefore be analyzed and com-pared to healthy controls. Methods Striatal D2 receptor binding at rest using [11C]raclopride positron emission tomography (PET) in 15 women (6 FM patients and 9 controls) was measured. Regional PET measures were acquired in MRI-based regions of interest defined in the cerebellum, nucleus accum-bens, putamen and caudate nucleus. [11C]raclopride binding potential (BP) was computed as the ratio of striatal region/cerebellum tissue radioactivity concentrations. Additionally, [11C]raclopride BP was correlated with pain disability index (PDI) scores. Results Significantly lower D2 receptor BP in the left caudate nucleus (p

NEW APPROACHES IN TREATING PERSISTENT PAIN AND PTSD IN REFUGEES Morina, N.1, Maier T.2, Wittmann, L.1, Rufer, M.1, Schnyder, U.1, Müller, J.1 1Department of Psychiatry und Psychotherapy, University Hospital Zurich, Switzerland 2Psychiatric Services of the Canton St. Gallen-North (Wil, Switzerland) Keywords refugees, PTSD, persistent pain, treatment, Biofeedback, Narrative Exposure

Therapy _________________________________________________________________________________ Introduction Many refugees suffer from comorbid PTSD and persistent pain. To date, successful treat-ment approaches are lacking for the simultaneous treatment of both conditions. Pain-focused treatment with Biofeedback (BF) proved to be effective in this population. Therefore, we combined ten sessions of BF with ten sessions of Narrative Exposure Therapy (NET), which is an established exposure-based CBT-procedure for the treatment of refugees. Methods In this pilot study we treated 15 refugees (mean age 43.1; 9 males) suffering from persistent pain and PTSD. They were assessed before, immediately after, and 3-months after the in-tervention. Results Results show that the combined intervention proved to be feasible and the findings indicate a reduction in both PTSD symptoms and pain after the intervention. Furthermore, partici-pants seem to have improved their quality of life and CBT-BF appears to increase the moti-vation for a subsequent trauma focused therapy. Conclusion This proof of concept shows that BF is a promising additional treatment component for per-sistent pain in traumatized refugees, before starting trauma focused psychotherapy. This could be an important step to enhance the motivation for a subsequent trauma focused ther-apy and giving patients the feeling of a mastery over their symptoms.

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MENTAL HEALTH OF CHILDREN AND THEIR TRAUMATISED PARENTS AFTER THE KOSOVO WAR – PRELIMINARY RESULTS Morina, N.1, Müller, J.1 1Department of Psychiatry und Psychotherapy, University Hospital Zurich, Switzerland Keywords war conflict, traumatic experiences, mental health, quality of life, children, par-

ents _________________________________________________________________________________ Introduction Survivors directly or indirectly exposed to war experience a variety of stressors. They are at high risk to develop mental disorders, particularly long-term post-traumatic stress reactions. Literature shows that parental trauma and psychopathology affects not only the mental health of their children but also their school performance and social behavior, aggression and quality of life. The aim of this study was to examine the mental health of children living in a post-war zone and to assess the relationship between parents’ traumatic experiences and children’s mental health. Methods The study was conducted in Kosovo eleven years after the war. The sample included 94 families, with 147 parents and 94 children aged 10-18, all of them were living during and af-ter the war in Kosovo. Parents and children completed structured interviews and question-naires regarding their mental health, traumatic event types and quality of life. Results Preliminary results show that exposure to war trauma impacts on both parents’ and chil-dren’s mental health, whose emotional responses are inter-related. Particularly mothers’ well-being and fathers’ trauma severity seem to have the largest impact. Conclusion Parents’ well-being and mental health seem to be crucial for children’s mental health even more than a decade after the war. Specific support for children and their traumatized parents is necessary.

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LONG-TERM INFLUENCES ON STRESS-RELATED ENDOCRINE FACTORS AFTER SEVERE ACCIDENTAL INJURY Oe, M.1,2, Schnyder, U.1, Schumacher, S.1, Müller-Pfeiffer, C.1,3, Wilhelm, F.H.4, Martin Sölch, C.1 1Department of Psychiatry and Psychotherapy, University Hospital Zurich, Switzerland 2Department of Neuropsychiatry, Kurume University School of Medicine, Japan 3Psychiatric Services of the County of St.Gallen-North, Center of Education and Research (COEUR), Wil, Switzerland 4University of Salzburg, Department of Clinical Psychology and Psychotherapy, Salzburg, Austria Keywords Posttraumatic stress disorder, Dehydroepiandrosterone (DHEA), Dehydroepi-

androsterone sulphate, Cortisol, Neuroendocrine System, Psychological stress, Long-term survivors

_________________________________________________________________________________ Introduction Dehydroepiandrosterone (DHEA) and its metabolite dehydroepiandrosterone sulfate (DHEA-S), which are also adrenal gland products, have prominent effects on GABAA receptor activ-ity. The aim of our study was to test chronic/long-term DHEA(S) changes in participants who had developed PTSD after severe accidental injury. Methods We measured plasma DHEA and DHEAS concentrations as well as the DHEA-cortisol ratio in 13 survivors who developed PTSD after severe accidents 10 years ago but were remitted at the time of the investigation, 14 survivors who did not develop PTSD after a severe acci-dents 10 years ago (trauma-controls), and 16 age and gender matched healthy participants, who did not experience any traumatic events in their lifetime. Results A significant group effect was found for plasma DHEA concentration, but not for DHEAS concentration. Post-hoc tests evidenced a significantly lower DHEA concentration in trauma-controls compared to no-trauma. Conclusion It has been suggested that the increase in DHEA in PTSD is rather salutary than patho-physiologic, and there is indication that effective psychotherapy for PTSD elevates DHEA levels. Thus, the process of remission might have influenced DHEA concentration in the re-mitted PTSD group.

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PSYCHIATRIC COMORBIDITY IN PATIENTS WITH MEDICATION-OVERUSE HEADACHE (MOH) Pirrotta, R.¹, ³, Riederer, F.², Jenewein, J.¹, Lutz, K.4, Wittmann, L.¹, Martin Soelch, C.¹, Gantenbein AR², Ettlin, D.³, Sandor, P.² 1Department of Psychiatry and Psychotherapy, University Hospital Zurich, Zurich Switzer-land 2Department of Neurology, University Hospital Zurich, Zurich Switzerland 3Clinic for Masticatory Disorders, Removable Prosthodontics and Special Care Dentistry, Center for Oral Medicine, Dental and Maxillo-Facial Surgery, University of Zurich Switzer-land 4Institute of Psychology, Department of Neuropsychology, University of Zurich, Zurich, Swit-zerland Keywords Medication-overuse headache, depression, anxiety, addiction, relapse _________________________________________________________________________________ Introduction Anxiety and depression are often associated in patients with medication-overuse headache and are considered as risk factors for chronicity and relapse after withdrawal therapy. Less known is the prevalence and role of the addiction to medication. The objective of this study is to investigate psychiatric comorbidities in particular the presence of dependence to the headache’s medication compared to a control group. Methods Thirty-seven patients with MOH were tested at the admission using clinical scales for de-pression (BDI, MADRS), anxiety (HAS, STAI) and addiction (SDS, KFM) as well as a stan-dardised Interview (MINI) to assess the addiction. Forty-one age and gender matched con-trol subjects were tested once using the same procedure. The data were analysed using Chi-Square tests and independent sample T-tests. Results Patients showed compared to control subjects significant depression and anxiety scores and were significantly positive for addiction to the medication. No significant differences were found in the age and sex ratio. Conclusion Our patients were positive for addiction and evidenced a significant high score for anxiety and a high rate of depression compared to the control group, suggesting a negative effect of psychiatric comorbidities by the maintenance of the MOH. Further studies are required to understand the mechanism of the addiction.

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COGNITIVE FUNCTIONING, EMOTIONAL PROCESSING, MOOD AND PERSONALITY VARIABLES BEFORE AND AFTER STEREOTACTIC SURGERY: A STUDY OF EIGHT CASES WITH CHRONIC NEUROGENIC PAIN. Pirrotta, R.¹, Jeanmonod, D.², McAleese, S.³, Opwis, K.4, Jenewein, J.¹, Martin-Soelch, C.¹ 1Department of Psychiatry and Psychotherapy, University Hospital Zurich, Switzerland 2Department of Neurosurgery, Neurosurgical Clinic, Functional Neurosurgery, University Hospital Zurich 3Hoffmann-La Roche, Basel, Switzerland 4Department of Psychology, Center for Cognitive Psychology and Methodology, University of Basel, Basel Switzerland Keywords Pain, surgery, thalamus, neurocognition, neuropsychiatry _________________________________________________________________________________ Introduction Stereotactic central lateral thalamotomy is used in chronic intractable pain. However, it is not clear whether this intervention improves the emotional and cognitive impairments in chronic pain patients. Our aim was to investigate cognitive functions, emotional processes, and per-sonality variables before and after surgery compared to a control group. Methods Eight patients with intractable neurogenic pain were tested before and 3-month after surgery using neuropsychological tests including frontal functions, depression, anxiety, anhedonia, anger regulation, a personality test and two experimental tasks testing empathy and ability to recognize facial emotional expressions. Results Patients showed neuropsychological deficits, clinically significant depression scores, im-pairments of the mind reading’s ability and the ability to recognize facial emotional expres-sions at baseline according to the tests’ norms. The comparison with the control group be-fore surgery evidenced statistically significant differences to the cognitive assessments, de-pression and anxiety scores and to the somatic complaint subscale. Patients experienced a significant pain relief (30%) and improvement of the depression scores after surgery. Conclusion Our chronic pain patients evidenced a significant pain relief, neurocognitive and emotional improvements after surgery, indicating a positive effect of SCLT. However some deficits re-mained, suggesting a long history of chronic pain may be associated with long-lasting cogni-tive and emotional deficits.

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PTSD AND EYE-BLINK STARTLE 10 YEARS AFTER SERIOUS ACCIDENTAL PHYSI-CAL INJURIES: REMITTED VS. RESILIENT INDIVIDUALS Schumacher, S.1, Schnyder, U.1, Müller-Pfeiffer, C.1,2, Wilhelm, F.H.3, Martin Sölch, C.1 1Department of Psychiatry and Psychotherapy, University Hospital Zurich, Switzerland 2Psychiatric Services of the County of St.Gallen-North, Center of Education and Research (COEUR), Wil, Switzerland 3University of Salzburg, Department of Clinical Psychology and Psychotherapy, Salzburg, Austria Keywords startle, trauma, PTSD _________________________________________________________________________________ Introduction Subjects with post-traumatic stress disorder (PTSD) show increased physiological reactivity and reduced habituation to startle tones. Resilience is defined as a trait characteristic that moderates the negative effects of stress and therefore prevents people from developing PTSD. The aim of this study was to investigate if PTSD-remitted accident victims still show increased startle reactivity after complete symptom remission. Methods We tested 14 remitted PTSD patients 10 years after a severe accident (PTSD-remitted), 12 subjects who did not develop PTSD after a severe accident 10 years ago (PTSD-resilient) and 11 subjects who never experienced a serious traumatic event (non-trauma controls). Fif-teen 95-dB white noise startle tones were presented. The startle response was assessed as peak activity of the left musculus orbicularis oculi. Results There was no group difference in habituation and PTSD-remitted subjects did not show in-creased startle reactions. Surprisingly, PTSD-resilient subjects showed higher startle magni-tude than non-trauma controls. Conclusion Our results contradict evidence that increased startle reactivity might be a stable trait char-acteristic of people who develop PTSD after traumatic events and they suggests that ex-treme stress might induce changes in physiological reactivity even in psychologically resil-ient subjects.

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Posterabstracts Psychiatrische Universitätsklinik Zürich Klinik für Affektive Erkrankungen und Allgemeinpsychiatrie Zürich Ost

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PHYSIOLOGICAL, NEURAL AND BEHAVIOURAL EFFECTS OF STRESS IN MICE: MODELS FOR UNDERSTANDING DEPRESSION Azzinnari, D., Sigrist, H., Ineichen, C., Gschwind, T., Jörg, K., Seifritz, E., Pryce, C.R. Clinic for Affective Disorders and General Psychiatry, Preclinical Laboratory for Translational Research into Affective Disorders Keywords Depression, mouse model, stress, controllability, cytokine, corticosterone, c-

Fos, helplessness, anhedonia, ketamine _________________________________________________________________________________ Introduction Major adverse life events (stressors) are aetiological factors in depression but the mediating pathophysiology and altered neural function are not well understood. Animal studies are es-sential to test cause-effect hypotheses for the aetio-pathophysiology of stress-related de-pression and for identification of molecular targets for development of novel effective treat-ments. Methods In mice, controlled experiments were conducted to investigate effects of specific stressors (un/controllable painful stimuli, chronic social defeat) on depression-relevant physiology (e.g. blood cytokines, corticosterone), neuroanatomy (e.g. c-Fos expression in specific brain re-gions) and behaviour (e.g. helplessness, fear, reward sensitivity, fatigue, pain sensitivity). Results Exposure to the uncontrollability of painful stimuli caused deficits in motivation to attempt to escape such stimuli and cognitive acquisition of escape. Exposure to chronic social defeat caused these same motivational and cognitive deficits in control behaviour, indicative of generalised helplessness, and also caused increased emotionality. Furthermore, chronic so-cial defeat caused increased plasma titres of proinflammatory cytokines and corticosterone, increased body weight variability and increased pain sensitivity. Conclusion The mouse models developed exhibit validity with respect to aetiological and psychopatho-logical processes. In vivo and ex vivo studies will be conducted in these models to identify brain-region specific pathophysiological mechanisms and therefore novel targets for anti-depressant treatment. One current focus is the effects of stress on glutamate signalling and of pharmacological targeting of glutamate signalling on depression-relevant mouse behav-iour.

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EMOTIONAL- COGNITIVE PROCESSING AND BRAIN METABOLISM AFTER PHARMACOLOGICAL CHALLENGE WITH KETAMINE Grimm, S.1,2,3, Scheidegger, M.1,4, Henning, A.4, Walter, M.5, Weigand, A.2,3, Böker, H.1, Bajbouj, M.2,3, Seifritz, E.1 1 Department of Psychiatry, University of Zurich, Switzerland; 2 Cluster Languages of Emo-tion, Freie Universitaet Berlin, Germany; 3 Department of Psychiatry, Charité, CBF, Berlin, Germany; 4 Institute for Biomedical Engineering, ETH Zurich, Switzerland; 5 Department of Psychiatry, University of Magdeburg, Germany Keywords ketamine, fMRI, working memory, major depression _________________________________________________________________________________ Introduction Ketamine is a potent glutamatergic NMDA receptor antagonist with rapid antidepressant properties at subanaesthetic doses, thus providing a valuable research tool for the investiga-tion of the neurobiology of mood disorders. Methods This imaging study in 23 healthy subjects aimed at probing the neuropharmacological effects of a single intravenous subanesthetic ketamine infusion on fMRI-BOLD responses during a working memory task using affective stimuli compared to baseline conditions. Results Results showed that ketamine administration had no effect on working memory perform-ance. A valence- specific significant difference in task induced BOLD signal amplitude for negative stimuli could be found following ketamine administration in right, but not in left DLPFC. Reduced BOLD signal amplitudes for negative stimuli could be observed in PCC and left anterior insula. In right anterior insula ketamine induced reduced BOLD signal ampli-tude regardless of valence. Conclusion The valence- specific ketamine effect on BOLD signal in regions implicated in altered emo-tional and cognitive processing in mood disorders might be related to its rapid antidepres-sant properties.

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CULTURAL-INDEPENDENT ASSESSMENT OF CHRONIC STRESS AND COPING BEHAVIOR; CROSS-COMPARISON BETWEEN STUDIES OF 400+400 STUDENTS Lott P1, Braun S2, Chmetz F2, Kluckner V2, Mohr C3, Schrag Y2, and Stassen HH2 1Pasadena City College, Pasadena, USA 2Psychiatric University Hospital, Psychiatric Genetics, Zurich, Switzerland 3University of Lausanne, Dept. Of Psychology, Lausanne, Switzerland Keywords chronic stress, coping behavior, risk, depression, consumption behavior, physi-

cal health _________________________________________________________________________________ Introduction Normative results on coping behavior can be expected to help to identify that 10-15% sub-group of the general population that exhibits insufficient coping skills under chronic stress. The respective subjects may be at risk for developing depressive disorders Methods Normative studies on coping behavior (COPE) have been carried out at Los Angeles (learn-ing sample) and Lausanne (independent replication sample) with 400 students each. The students were asked to fill out the 28-item COPE and 63-item ZHQ questionnaires. We de-termined the intrinsic properties of the empirical data: noise level, dimensionality, and quanti-tative thresholds for the identification of subjects with insufficient coping skills. Of particular interest was the amount of variance that was explainable by the factors “consumption be-havior”, “regular exercises”, “physical health”, “psychosomatic disturbances”, and “mental health”. Results We found two highly reproducible dimensions (quantitative scales: “activity” and “defeatism”) classifying subjects with respect to their coping behavior under chronic stress. Subjects scoring low on the activity scale while exhibiting high defeatism scores were regarded as be-ing under risk for insufficient response to chronic stress. Conclusion Significant correlations between the ZHQ and COPE scales underlined the inter-relationship between personality traits on the one hand, and consumption behavior and general health on the other.

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A PROFILE OF PEDOPHILIC SEXUAL PREFERENCE BASED ON SELF-REPORT AND IMPLICIT MEASURES OF SEXUAL INTEREST Mokros, A.1, Schmidt, A. F.2, Habermeyer, E.1 1University Hospital of Psychiatry, Center for Forensic Psychiatry, Zurich, Switzerland 2University of Bonn, Department of Legal and Social Psychology, Bonn, Germany Keywords pedophilia, implicit measures, viewing time, implicit association test, latent pro-

file analysis _________________________________________________________________________________ Introduction Recent research based on self-report data seems to indicate that sexual interest in children among convicted child molesters was dimensional (Mackaronis et al., Psychol Assess, 2011). We tested whether pedophilic sexual interest was dimensional or taxonic in a mixed sample of male offenders and community controls (N = 258). Methods We used a battery of direct and indirect tests of sexual preference with respect to gender and sexual maturity. The test battery consisted of self-report (questionnaire data) as well as Implicit Association Tests (IATs) and viewing time measures of deviant sexual preferences for children over adults. Results Latent profile analysis provided evidence for a two-cluster solution. Cluster 1 (pedophiles) comprised 12% of participants (21% of child molesters). Individuals in cluster 1 had signifi-cantly higher mean scores on all three differential indices of sexual interest in children. Among the child molesters, probability of membership in cluster 1 correlated significantly with an index of sexual offense history against children (r = .38, p < .001, one-sided). Conclusion The multi-method assessment of deviant sexual interest yielded support for a categorical distinction of pedophilia. The results further render support for the utility of the test battery as a diagnostic aid in forensic assessment.

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NEURONAL CORRELATES AND PREDICTION OF NMDA RECEPTOR RELATED COG-NITIVE IMPAIRMENTS USING DYNAMIC CAUSAL MODELLING (DCM) Schmidt, A.1, Kometer, M. 1, Stephan K.E.2,3 Vollenweider, F.X. 1 1 Neuropsychopharmacology and Brain Imaging, University Hospital of Psychiatry, Univer-sity of Zurich, Zurich, Switzerland 2 Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich, Zurich, Switzerland 3 Wellcome Department of Neuroimaging,University College London, London, UK Key words: effective connectivity, dynamic causal modelling, perceptual learning, gluta-

mate, serotonin, psychosis _________________________________________________________________________________ Introduction Recent findings suggest that effective connectivity and synaptic plasticity is disrupted in schizophrenia. Mismatch negativity (MMN) is a suitable paradigm to investigate effective connectivity. Previous studies reported that MMN is disrupted in schizophrenia and after psychotomimetic doses of the NMDA antagonist S-ketamine in healthy subjects. However, the brain mechanism underlaying this S-ketamine-induced MMN disruption is hardly understood. Methods Dynamic causal modelling (DCM) was used to estimate effective connectivity during a row-ing MMN task to examine synaptic connection strengths in placebo and S-ketamine states in healthy subjects. Bayesian Model Selection was applied to identify the best DCM model given the data. Results S-ketamine disrupted MMN and reduced effective feedforward connectivity from the auditory cortex (A1) to the superior temporal gyrus (STG) (p < 0.001). Furthermore, we found that the S-ketamine-induced cognitive impairments can be predicted from the extent of the reduction in forward connectivity from the left A1 to the left STG (p < 0.03). Conclusion The findings demonstrate that DCM in combination with neurophysiological measures and pharmacological manipulations provides a promising framework to identify and understand further the role of different neurotransmitters in neuronal plasticity and may help us to de-velop diagnostic markers of neuronal connectivity and cognitive impairments.

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GENDER AND RAPID ALTERATIONS OF HEMISPHERIC DOMINANCE DURING PLAN-NING Schuepbach, D.1*, Duschek, S.2, Theodoridou, A.1, Grimm, S.1, Boeker, H.1, Seifritz, E.1 1Psychiatric University Hospital Zürich, Lenggstrasse 31, 8032 Zürich, Switzerland 2University of Munich, Department of Psychology, Leopoldstrasse 13, 80802 München, Germany Keywords Cerebral hemodynamics, functional transcranial Doppler, gender, lateralizati-

on, performance, planning _________________________________________________________________________________ Introduction Mental planning and carrying out a plan provoke specific cerebral hemodynamic responses as assessed by functional transcranial Doppler sonography (fTCD). Within the context of planning, rapid cerebral hemodynamic alterations and laterality, common and shared gender aspects have not been reported until now. Methods This fTCD study examined bilateral cerebral hemodynamics of the middle cerebral arteries (MCA) of male and female subjects performing a standard planning task. There were easy and difficult problems. Difficult mental planning elicited lateralization to the right hemisphere, a feature that was not observed during movement execution. Results Females shifted laterality to the left hemisphere during movement execution. Optimal per-formers of difficult problems yielded increased laterality change to the right during mental planning as compared to the rest of the sample. Conclusions Gender related laterality appears to be condition dependent, and change of laterality to the right may play a role in performance that was previously not reported. Those results are of relevance when considering laterality from a performance enhancement perspective of higher cognitive functions and also from psychiatric disorders with cognitive dysfunctions and abnormal lateralization patterns, such as schizophrenia.

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INCREASED SENSITIVITY TO EXTERNAL NEGATIVE FEEDBACK IN UNMEDICATED SUBJECTS WITH MAJOR DEPRESSION Spinelli, S.1, Spaeti, J.1, Brakowski, J. 2, Doerig, N. 3, Grosse Holtforth, M. 3, Seifritz, E.2 1Preclinical Laboratory for Translational Research into Affective Disorders, Clinic for Affec-tive Disorders and General Psychiatry, Psychiatric University Hospital Zurich, Zurich, Swit-zerland. 2Clinic for Affective Disorders and General Psychiatry, Psychiatric University Hospital Zurich, Zurich, Switzerland. 3Department of Psychology, University of Zurich, Zurich, Switzerland. Keywords negative feedback processing, major depression, fMRI Introduction Negative biases in emotional processing are a characteristic of major depression (MD). Neuroimaging studies in patients with MD have found functional abnormalities in prefrontal cortex (PFC) regions implicated in emotional regulation during negative events, and func-tional abnormalities were also found during negative feedback processing. Methods Here, negative feedback processing to an external event and to error was investigated in unmedicated subjects with MD and controls using fMRI and a modified version of the motion prediction task. Subjects were told that in 50% of the trials they would receive a feedback to their response (error feedback, depending on their answer they will win or lose 50 cents). In the other 50% of the trials, the feedback was associated with a coin toss (external feedback, the fact that their response was correct or incorrect had no relevance, i.e. they had no con-trol over the outcome). Results Compared to controls, unmedicated subjects with MD showed increased BOLD response in the left superior frontal gyrus (BA8) and the left middle/inferior frontal gyrus (BA44/45/46) when an external negative feedback was presented. Conclusion These results suggest an increased sensitivity to external negative feedback in unmedicated subjects with MD, specifically to uncontrollable feedbacks.

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COGNITIVE DEFICITS OF OCCASIONAL AND DEPENDENT COCAINE USERS Vonmoos, M.1, Hulka, L.1, Preller, K.1, Jenni, D.1, Stohler, R.2, Quednow, B.B.1 1Experimental and Clinical Pharmacopsychology, Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry Zurich, Switzerland 2Substance Use Disorders, Clinic for Genaral and Social Psychiatry, University Hospital of Psychiatry Zurich , Switzerland Keywords cocaine, chronic, recreational use, cognition, attention, memory, executive

functions _________________________________________________________________________________ Introduction Chronic cocaine users display cognitive deficits in attention, memory performance, and ex-ecutive functions. Imaging studies with cocaine users have found alterations in brain regions that are implicated in these cognitive domains. The cognitive performance of recreational and occasional users has rarely been investigated so far. Therefore, our study aims to ex-amine whether cognitive performance is already impaired in occasional cocaine users. Methods We assessed and compared the performance of recreational cocaine users (n=38), chronic cocaine users (n=20) and cocaine-naïve controls (n=38) in an extensive neuro-cognitive test battery (Cambridge Neuropsychological Test Automated Battery [CANTAB], Rey Auditory Verbal Learning Test [RAVLT], Letter Number Sequencing Task [LNST]). Results Chronic cocaine users display impairments in sustained attention/vigilance and verbal mem-ory tasks (both declarative and working memory). The visuo-spatial memory and executive functions seem to be less affected. Occasional cocaine users already display impairments in sustained attention, whereas the different memory components and executive functions are less affected. However, their memory performance is intermediate between controls and chronic users possibly indicating an initiating development of memory deficits. Conclusion These preliminary findings suggest that cocaine users suffer from impaired attentional proc-esses already at a recreational or occasional level of use. Correlations between cognitive test results and consumption parameters (duration, lifetime amount) indicate that memory and attentional deficits might be rather cocaine-induced than predisposed.

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Posterabstracts Psychiatrische Universitätsklinik Zürich Direktion Pflege, Therapien und Soziale Arbeit

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INTEGRIERTE PSYCHIATRISCHE BEHANDLUNG: INSTRUMENTE UND VERFAHREN FÜR DIE SOZIALE ARBEIT Baumeler, M., Hierlemann, F. KTI-Forschungsprojekt der Fachhochschule Nordwestschweiz, Hochschule für Soziale Ar-beit, Olten. Projektleitung: Dällenbach, R. /Sommerfeld, P. Projektbeteiligte PUK Zürich: Baumeler, M., Hierlemann, F. Keywords Klinische Soziale Arbeit, Methoden Integrierter psychiatrischer Behandlung,

Soziale Diagnostik – Screening-Evaluation _________________________________________________________________________________ Fragestellung Wie sehen die Evaluationsergebnisse des Screening-Einsatzes der ersten Testphase aus und was zeigt sich im weiteren Verlauf? Führt der Einsatz des Screening-Instruments in der zweiten Testphase - ausgefüllt durch die Patientinnen und Patienten - zu einer ähnlichen Gesamteinschätzung der sozialen Risiken wie die aus einer fachlichen sozialarbeiterischen Perspektive? Methode Das Screening-Instrument soll psycho-soziale Risiken erfassen und das Stellen der Indikati-on für die Intervention der klinischen Sozialen Arbeit gewährleisten. Zur Validierung des Screening-Instruments wird die Kriteriumsvalidität geprüft. Das bedeu-tet, dass die Übereinstimmung oder Abweichung des Ergebnisses aus dem Einsatz des Screening-Instruments anhand eines protokollierten Erstgesprächs durch die Sozialarbei-tenden (Expertise) beurteilt wird. Ergebnisse Das Screening-Instrument aus der ersten Testphase wurde überarbeitet. Aktuell läuft zur er-neuten Validierung des Screening-Instruments eine zweite Testphase in vier psychiatrischen Kliniken. Schlussfolgerung Validierung des Screening-Instrumentes der zweiten Testphase bis Dezember 2011 / Ab-schluss des Gesamtprojektes Juni 2012.

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PSYCHOEDUKATION: WIRKSAMKEIT VON PSYCHOEDUKATIVEN PROGRAMMEN BEI EINER SCHIZOPHRENIE ODER BIPOLAREN AFFEKTIVEN STÖRUNG Frey, B. Psychiatrische Universitätsklinik Zürich, Direktion Pflege, Therapien und Soziale Arbeit, Zü-rich, Schweiz Keywords psychiatrische Pflege, Psychoedukation, Schizophrenie, bipolare affektive Stö-

rung, Gewichtsmanagement _________________________________________________________________________________ Fragestellung Psychoedukation ist eine mögliche Therapieform für psychische Krankheiten. Unter Psy-choedukation versteht man in der Regel psychoedukative Gruppen, welche systematisch nach einem Manual durchgeführt werden. Dabei werden PatientInnen- bzw. Angehörigen-gruppen angeleitet, ihr Gesundheitsverhalten zu verbessern. Fragestellung: Welche psychoedukativen Programme sind wirkungsvoll bei erwachsenen PatientInnen mit einer schizophrenen Erkrankung oder einer bipolaren affektiven Störung? Methode Aufgrund der Literaturrecherche in der Datenbank Public Medline wurden elf experimentelle Studien einbezogen, welche in englischer oder deutscher Sprache in den Jahren 2001 bis 2008 publiziert wurden. Ergebnisse Die Studien wurden allesamt in Industrieländern durchgeführt, insgesamt vier davon prüften deutschsprachige psychoedukative Programme. In allen einbezogenen Studien konnten deutliche Zustandsverbesserungen der PatientInnen festgestellt werden. Die signifikanten Ergebnisse (p≤0.05) zeigten sich je nach Forschungsfrage in den folgenden Outcome-Parametern: Psychopathologie, Rückfälle, Compliance/Adhärenz, soziale Fertigkeiten, Ge-wichtsmanagement. Schlussfolgerung Wirksamkeit: Die nachgewiesene Wirksamkeit der Psychoedukation lässt die Folgerung zu, dass systematische, psychoedukative Gruppen bei schizophrenen und bipolaren PatientIn-nen als Behandlungsmöglichkeit angeboten werden sollten. Setting: Insgesamt erscheint es sinnvoll, die Psychoedukation vernetzt in stationären und ambulanten Settings anzubieten. Interdisziplinarität: Da die Psychoedukation auch in den Kompetenzbereich der psychiatri-schen Pflege gehört, sollten psychoedukative Gruppen idealerweise interdisziplinär angebo-ten werden.

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Posterabstracts Psychiatrische Universitätsklinik Zürich Klinik für Alterspsychiatrie

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ACTIVE VACCINATION WITH THE NOVEL APP-INTERACTING PROTEIN ANKYRIN G REDUCES -AMYLOID PATHOLOGY IN APP TRANSGENIC MICE

Chadha Santuccione, A.1, 7,, Merlini, M.1,2, Shetty A., 1,3, Tackenberg, C. 1, Bali, J.4, McAfoose, J.1, Kulic, L.1, Bernreuther, C.5, Grimm, J.1, 6, Glatzel, M.5, Rajendran, L.4, Hock, C.1 and Nitsch, R.M.1, 7 1 Division of Psychiatry Research, University of Zurich, Switzerland 2Current address: Gladstone Institute of Neurological Disease, San Francisco, USA 3 Current address: Department of Neurology, University of California, USA 4 Systems and Cell Biology of Neurodegeneration, Psychiatry Research, University of Zurich, Switzerland. 5Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 6 Current address: Neurimmune Therapeutics AG. Keywords Alzheimer’s Disease, Neurodegeneration, Ankyrin G _________________________________________________________________________________ Introduction

Sera antibodies against amyloid- peptide (A) in Alzheimer’s disease (AD) suggests a spe-cific immune response against AD-related antigens. To explore the spectrum of the immune response in AD we screened for serum antibodies against potential brain antigens using a brain protein-array. Methods Protein array screening, Western blotting, Immunoprecipitation, ELISAs, cell culture, siRNA silencing, brain fractionations, Organotypic hippocampal slice cultures, confocal microscopy. Results AnkyrinG (ankG), a neuronal cytoskeletal protein, was identified as a possible neuro-antigen among others. AnkG was present in -amyloid plaques and exosomal vesicles and its neu-ronal expression was higher in AD patients than in age-matched control subjects (HCS). Mo-reover, antibody response against ankG was higher in AD patients than in HCS. Active im-munization of APP-transgenic mice with ankG reduced brain -amyloid pathology and in-creased soluble A 42 levels. Antibodies against ankG reduced A-induced loss of dendritic spines in ex vivo cultures. We also found an interaction between ankG and APP, a de-creased APP cell-surface trafficking and a lower A production after ankG silencing. Conclusion

These data establish a role for ankG in -amyloid clearance and in APP metabolism. AnkG immunotherapy may provide a novel avenue for A-lowering therapy.

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IMAGING BRAIN BETA-AMYLOID IN ASYMPTOMATIC ELDERLY SUBJECTS Gietl, A.1, Kälin, A.1, Buck, A2.,Kuhn, F.2, Lüthi, M.L 1, Apaydin, S. 1, Gruber, E. 1, Ametamey S. 1, Nitsch, R. 1, Hock, C.1 1University Hospital of Psychiatry, Division of Psychiatry Research and Psychogeriatric Medicine, Zurich, Switzerland 2University Hospital Zurich, Division of Nuclear Medicine, Zurich, Switzerland Keywords PiB, PET, Amyloid, Alzheimer’s disease, Neuropsychology, MCI _________________________________________________________________________________ Introduction The cerebral deposition of beta amyloid is a central feature in Alzheimer’s disease. Cerebral amyloid load can be measured in vivo, using Pittsburgh Compound B (PIB). PIB PET Stud-ies have demonstrated AD like PiB-Binding in cognitively healthy subjects and MCI Patients. Methods Subjects are part of on-going observational longitudinal studies and diagnosed as HCS or MCI after extensive clinical and neuropsychological work up. PET scanning procedure was dynamic. The individual PET scan was stereotactically nor-malized and PiB uptake was quantified using predefined ROIs of a maximum probabilistic at-las. The ratio of cortical PiB uptake to cerebellar PiB uptake gives an estimate of the neocor-tical PiB Burden. Results To date 29 HCS and 9 MCI subjects underwent PiB Imaging. For preliminary analysis 18 HCS and 3 MCI subjects were quantitatively assessed. One HCS and two MCI subjects demonstrated a neocortical PiB Burden greater than 1.5, thus indicating elevated cerebral amyloid deposition. Conclusion We were able to detect elevated PiB Binding in HCS and to a higher proportion in MCI sub-jects. Longitudinal observation will help to assess the clinical significance of these findings with regard to cognitive decline.

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COGNITIVE AND IMMUNOLOGICAL MARKERS OF PRODROMAL ALZHEIMER’S DISEASE Kälin, A.M., Lüthi, M.L., Gietl, A.F., Kulic, L., Schreiner, B., Szodorai, A., Nitsch, R., & Hock C. 1Division of Psychiatry Research and Psychogeriatric Medicine, Psychiatric University Hos-pital, Zurich, Switzerland Keywords Mild Cognitive Impairment, Prodromal Alzheimer’s disease, Neuropsychology,

Immunology _________________________________________________________________________________ Introduction Subjects with mild cognitive impairment (MCI) are at increased risk for Alzheimer’s disease (AD). This study aims to determine neuropsychological and immunological markers of the conversion from MCI to AD. Methods Within the frame of a multicenter study performed jointly at sites in Zurich, Geneva, and Lausanne, 300 MCI outpatients are being recruited and followed over 3 years. The potential risk profiles of the currently included MCI subjects (n=68) were compared to data obtained within ongoing cohort studies on cognitively healthy elder subjects (HCS,n=153) and Alz-heimer’s disease (AD,n=100). Participants performed neuropsychological tests, from which five tasks (verbal delayed recall, categorical fluency, TMT-A, picture naming, figure copy) were used for analyses. Raw scores were z-transformed prior to analyses. Memory-B-cells (mBc) were isolated from peripheral blood samples of AD (n=31), MCI (n=47) and HCS (n=111), and were analyzed by FACS for beta-amyloid-reactivity. Results The subjects with MCI showed intermediate performance on the cognitive level between the HCS and AD group across all cognitive tests, with the delayed recall performance being the most discriminative test (HCS M=0.47, SD=0.95; MCI M=-1.53, SD=1.38; AD M=-2.75, SD=1.03). Interestingly, the reactivity of mBc against beta-amyloid was higher in subjects with MCI as compared to the HCS and AD group (X2(6)=77.05,p

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HUMORAL AND CELLULAR ADAPTIVE IMMUNE RESPONSES TO MISFOLDED BRAIN PROTEINS AND NOVEL BIOMARKERS IN PRODROMAL ALZHEIMER’S DISEASE Kulic, L.1, Schreiner, B.1, Szodorai, A.1, Kälin, A.1, Lüthi, M.L.1, Graf, C.2, Giannelli, S.2, Zekry, D.2, Gietl, A.1, Rizopoulos, Z.1, Becher, B.1, Nitsch, R.M.1, Hock, C.1 1University of Zürich

spitals and University of Geneva

eywords Alzheimer’s disease, MCI, Aβ, memory B cells, T cells, biomarkers _ ____

troduction of naturally occurring adaptive immune responses to misfolded brain proteins

ethods peripheral blood mononuclear cells (PBMC) were prepared freshly and memory

esults nts were characterized by an increased number of Aβ42-reactive mBc as com-

onclusion y results of this study point to a possible role of Aβ-directed humoral immune

2Geneva University Ho K___________ _________________________________________________________________ InThe discovery like Aβ in Alzheimer’s disease (AD) has contributed significantly to the recently proposed concept of ‘protective autoimmunity’ in neurodegenerative disorders. In this study, we aimed to further characterize naturally occuring Aβ-directed humoral and cellular autoimmune re-sponses in a population of mild cognitive impairment (MCI) patients included in an SNF-funded multicenter cohort study from Oct 2009 to Jul 2011. Moreover, we set up a novel multi-SPOT assay as a screening platform for new candidate plasma biomarkers in MCI pa-tients. MPlasma andB cells (mBc) were isolated and screened for Aβ42-reactivity using a FACS-based selection method. PBMCs from blood bank donors were used to set-up a culture system for the detec-tion of A42-reactive T cells. Plasma sAPPα and sAPPβ levels were determined using an MSD 2plex multi-SPOT kit. RMCI patiepared to HCS and AD patients. Moreover, we were able to successfully set up an assay to measure Aβ-reactive T cell responses. Lastly, increased plasma sAPPβ levels and an in-creased sAPPβ/sAPPα ratio have been identified by MSD technology as potential novel bio-markers in MCI. CThe preliminarresponses in early (pre-dementia) stages of AD. Further longitudinal analyses are required to determine the role of Aβ42-reactive mBc in the progression of AD. Analyses of mBc reac-tivity to other misfolded brain proteins in neurodegenerative diseases are planned. Our find-ing of increased plasma sAPPβ levels and an increased sAPPβ/sAPPα ratio in MCI patients will be confirmed in larger and independent patient populations and will be tested longitudi-nally for its predictive value as a potential novel biomarker of prodromal AD.

ON THE ORIGIN OF CYTOSOLIC PROTEINS IN TH CEREBROSPINAL FLUID Minakaki, G.1, Surendranath, V. 2, Jejelava, N. 1, Rajendran, L. 1 1 Zurich, University of Zurich/ Psychiatric University Hospital, Department of Psychiatry Re-search and Geriatric Psychiatry, 2Max Planck Institute of Molecular Cell Biology and Genet-ics, Pfotenhauerstr. 108, 01307, Dresden, Germany _________________________________________________________________________________ Introduction The CSF reflects the biochemical state of the central nervous system under both physiologi-cal and pathological conditions and for this reason, begs attention for the identification of biomarkers. Interestingly, in several neurodegenerative disorders including Alzheimer’s, Parkinson’s and Creutzfeld-Jacob disease- the levels of cytosolic, disease-related proteins are significantly altered and most importantly, these alterations can be correlated with dis-ease progression. How do cytosolic proteins get released from the cells? Release of such proteins in the CSF may either occur through stochastic cell lysis, or by the release of se-creted vesicles mediating intercellular communication, such as exosomes. In support of the latter, exosomes are constitutively secreted under both physiological and pathological condi-tions and have been reported to carry neurodegenerative disease-related proteins by sev-eral studies. Moreover, the presence of amyloidogenic proteins and the progressive spread-ing of the aberrant protein interactions which characterize neurodegenerative diseases, both emphasize the role of exosomes in mediating long-range transmission of the pathology. Identifying the origin of cytosolic proteins of the CSF may provide novel insight to the bio-logical significance of inter-cellular communication mediated via exosomes and propose new targets of therapeutic intervention. Methods We used an unbiased, systematic computational informatic analysis for the comparison of the CSF and exosome proteomes. Whole CSF and exosome proteomic profile was obtained from previous studies and was screened for overlapping proteins. Results Our analysis identified 664 proteins that are common to the human CSF and exosome pro-teome. Interestingly, further analysis and comparison of specifically cytosolic proteins re-vealed that almost 70% of the CSF cytosolic proteins are also secreted via exosomes. Conclusion Our results strongly suggest that a very significant amount of cytosolic proteins found in the CSF is actually contributed by exosomes.

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TAKING A LOOK IN SUPER SLOW MOTION AT MOTORIC NEURODEGENERATION IN AMYTROPHIC LATERAL SCLEROSIS Preisig, D. 1, McAfoose, J. 1, Krüger, M. 1, Läufer, T. 2, Neumann, M. 2, Nitsch, R.M. 1, Welt, T. 1 1University Hospital of Psychiatry, Division of Psychiatry Research, Zurich, Switzerland 2University of Zurich, Experimental Neuropathology, Institute of Neuropathology, Zurich, Switzerland Keywords Amyotrophic Lateral Sclerosis, video tracking, neurodegeneration, Transgenic

mice, SOD1, TDP-43, gait analysis, motor system _________________________________________________________________________________ The advanced quantitative high-speed video tracking system MotoRater generates compre-hensive, individual full body locomotor profiles by assessing body coordination and kinemat-ics. Transgenic mice modeling neurodegenerative motoric diseases (e.g. ALS) are filmed and tracked with 500 frames per second in four physiological conditions (walking, wading, swimming, skilled walking over a ladder) differing in the level of difficulty and therefore ex-tending the versatility and sensitivity of this system and reducing floor and ceiling effects. The device is measuring over 50 parameters, including movement speed, measures of intra- and inter-coordination of fore- and hindlimbs, posture, tail and limb strength, or stability. Indeed, the increased sensitivity of this novel technology provides unprecedented quantita-tive parameters to assess functional decline and recovery following therapeutic intervention in the same individual animal over time and is capable to differentiate between therapeutic neuro-restorative effects and compensation strategies. Additionally the system provides a basis for correlating functional deficits with neurodegen-erative processes in specific/dedicated neuronal networks. For example, swimming relies mainly on intrinsic spinal cord networks (central pattern generating networks) whereas skilled walking on a ladder or the tiptoeing gait during wading require a high degree of corti-cal processing/input and depends primarily on the integrity of corticospinal projections.

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PHOSPHORYLATION REGULATES APP INTRACELLULAR DOMAIN-MEDIATED NU-CLEAR SIGNALING Riese, F.1, Russi, N.1, Goodger, Z.V.1, Nitsch, R.M.1, Hock, C.1, Konietzko, U.1 1University Hospital of Psychiatry, Division of Psychiatry Research, Zurich, Switzerland Keywords Alzheimer, AICD, nuclear signaling, phosphorylation _________________________________________________________________________________ Introduction We previously demonstrated that the intracellular domain of the amyloid precursor protein APP (AICD) forms complexes with the adaptor protein Fe65 and the nuclear histone acetyl-transferase Tip60 (AFT complexes). AFT complexes localize to distinct nuclear spots which are believed to be involved in transcriptional regulation. This project aims to identify the role of phosphorylation in the regulation of AFP complex formation. Methods After visual quantification of AFT complexes in a cell culture system in the first phase of the project, we developed a visualization system based on bimolecular fluorescence comple-mentation (BiFC) in order to verify our findings with an independent experimental setup. To this aim, one half of the fluorescent protein citrine was fused to the C-terminus of APP, the other half to the C-terminus of Tip60. Complementation to a fluorescent citrine occurs only when both interaction partners are in close proximity, i.e. upon AICD nuclear translocation. Several mutations – either mimicking phosphorylation or preventing the phosphorylation at the respective sites - were introduced into APP whose impact on AFT complex formation was quantified by FACS analysis. Results Both visual and FACS quantification demonstrate that phosphorylation of APP regulates the formation of AFT complexes. In particular, our results indicate that phosphorylation at posi-tion Ser655 of APP increases nuclear signalling. In contrast, prevention of phosphorylation at position Thr668, which was previously found to regulate the binding of Fe65 to APP, showed no alteration of AFT complex levels. Likewise, several other possible sites of phos-phorylation including Y635, T654, T686 and Y687 showed no alteration in AFT complex for-mation, indicating that the effect of phosphorylation is dependent on specific positions. Conclusion Our novel BiFC-based assay allows quantification of AFT complex formation, thus enabling the study of posttranslational modifications of APP on AICD nuclear signaling. Our findings indicate that phosphorylation of APP is involved in the regulation of its function in transcrip-tional regulation. Our work therefore complements previous findings from other groups that showed the impact of phosphorylation on APP processing.

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HIPPOCAMPAL CAVITIES IN ELDERLY SUBJECTS PREDICT FUTURE DECLINE IN EPISODIC MEMORY Riese, F.1, Ballach, O.1, Suliman, H.1, Gertz, H.J.2, Hock, C.1, Wolf, H.1,2 1 Zurich, University of Zurich/ Psychiatric University Hospital, Department of Psychiatry Re-search and Geriatric Psychiatry 2 Leipzig, University of Leipzig, University Hospitals, Department of Psychiatry Keywords hippocampus, memory, pathophysiology, magnetic resonance tomography,

vascular lesions, visual ratings, atrophy, structural neuroimaging, neurora-diological markers

_________________________________________________________________________________ Introduction Hippocampal atrophy is a radiological marker of Alzheimer disease, and the hippocampus is routinely inspected in elderly patients with memory disorders. In addition to gross atrophy, small CSF-isointense “holes” within the hippocampus, termed hippocampal (hc) cavities, are frequently seen on MR images in elderly subjects. Their significance is unknown, and they are often considered incidental and benign. Methods Cross-sectional, longitudinal and serial MR Study embedded into a longitudinal field study (LEILA 75+). A total of 156 MRI scans from 107 subjects (74 nondemented) were analysed. Hc cavity numbers and volume were recorded from volumetric T1w MRI scans. Subjects we-re aged 75-85. Cognitive functions were assessed with the SIDAM and Clinical Dementia Rating. Confounding variables included hippocampal (hc) volume and hc atrophy ratings, brain volume, white matter lesions, and ApoE genotype.

Results The prevalence of hc cavities was 59% with no differences over cognitive groups and gen-der. The mean hc volume loss due to cavities was small (30mm3), which approximates

EBV IN INSULIN SIGNALING AND ALTERATIONS IN EBV RECEPTOR DENSITIES IN EARLY AD BRAINS Szodorai, A.1, Bock, T.2, Wollscheid, B.2, Hock, C.1, Nitsch, R.M.1 1University Hospital of Psychiatry, Division of Psychiatry Research, Zurich, Switzerland 2ETH Zurich, Institute of Molecular Systems Biology, Zurich, Switzerland Keywords EBV, insulin, MCI, B cell, TSC2 _________________________________________________________________________________ Introduction There is an increased risk for elderly people to develop both type 2 Diabetes and Alz-heimer's disease. The cause of insulin signaling defects in AD brains is not well understood so far. It is not clear which cellular mechanisms lead to the massive reduction and mislocali-zation of insulin receptors that contribute to insulin signaling resistance. On the other hand, a viral reactivation in aged people with unknown consequences has been described (e.g. for EBV). If viral reactivation in peripheral tissue or human brain can also influence insulin sig-naling resistance is not known so far. It is also not analysed if viral receptors might be al-tered in human tissue. Because EBV infects peripheral blood cells and possibly even neu-rons, we did study putative effects of EBV on insulin signaling pathways in human B cells from AD patients, MCI and healthy control subjects (HCS) as well as in primary rat neurons. EBV receptor densities were analysed in early, moderate and severe AD brains. Methods Human B cells were isolated from peripheral blood probes and "reactivated" with EBV con-taining media for two weeks. EBV treated human B cell extracts (1%NP40/PBS) were ana-lysed by gel electrophoresis, silver staining and mass spec analysis for band intensities. Changes in protein levels for insulin signaling cascade proteins were verified by IB and IC. Rat primary neurons were obtained from E18 WT embryos. EBNA1-ss- or scrambled oligos were coupled to quantum dots for IHC analysis of EBV genomes in human brain tissue or B cells. EBV receptor densities were analysed by IHC in early, moderate and severe AD brain sections. Results Preliminary results indicate that EBV treated B cells from AD patients showed a reduction in TSC2 levels (tuberous sclerosis complex 2) in comparison to HCS B cells. Foxa2 (in-)activation might be altered in primary neurons treated with B cells from AD patients plus EBV. Also young healthy control subjects showed reduced TSC2 levels after EBV reactiva-tion, but the levels could be rescued by exogenously added insulin. Preliminary analysis of human brain material by IHC indicates the presence of EBV genomes in brain and an in-crease of EBV receptor densities in early MCI brains. Conclusion This data indicates that EBV infection might take place in human brains of early MCI. EBV can lead tor insulin signaling defects in human peripheral blood cells from AD patients and rat primary neurons. A more systematic analysis of other up- and downstream signaling pro-teins of the insulin pathway, e.g. for insulin receptors, insulin receptor substrate, mTOR (mammalian target of rapamycin) will be undertaken.

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Posterabstracts Zentrum für Kinder- und Jugendpsychiatrie, Universität Zürich

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JUVENILE SEX OFFENDERS IN SWITZERLAND: DEMOGRAPHIC FACTORS, PSY-CHOPATHOLOGY, OFFENCE CHARACTERISTICS AND RECIDIVISM Aebi, M.1, Bessler, C. 1 1 University of Zurich, Child and Adolescent Psychiatry, Division of Child and Adolescent Fo-rensic Psychiatry Keywords Juvenile sexual offender, recidivism, psychiatric disorders _________________________________________________________________________________ Introduction The population of juvenile sex offenders (JSO) in the Canton of Zurich was described by a retrospective analysis of a consecutive sample of the police and judicial records between 2000 and 2008. Re-offence risk was assessed by the Juvenile-Sex-Offender-Assessment-Protocol (J-SOAP-II) and compared to sexual and general recidivism.

Methods A youth-adapted version of the Forensic-Psychiatric Documentation System (FDPS) has been used for data collection. Recidivism has been assessed by the official crime database of the Canton of Zurich until October 2009 (mean follow-up period 4.3 years; SD 2.5 years).

Results The population of JSO was found of heterogeneous nature. With exception of pornographic offences (35.9%), sexual coercion (32.8%) and sexual assaults against children (27.4%) were the most frequent crimes. Psychiatric assessments found frequent behavioral (43.6%) and emotional disorders (18.1%) but only one case of paraphilia. The J-SOAP-II and a sex-ual offense severity scale were significant but only moderate predictors of sexual (N=7), vio-lent (N=37) and general recidivism (N=101).

Conclusions JSO are a complex population and can not been compared to adult offenders according to offence characteristics and crime motivation. Developmental factors have to be included when assessing JSO. The J-SOAP-II was found rather limited for risk assessment in JSO.

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JUVENILE-ONSET OCD – PSYCHOSOCIAL ADAPTION Ball1, J., Zellmann2, H., Walitza, S1. 1 Department of Child and Adolescent Psychiatry, University Zürich, Neumünsterallee 9, 8032 Zürich, Switzerland 2 Department of Child and Adolescent Psychiatry, University Würzburg, Füchsleinstr. 15, 97084 Würzburg, Germany

Keywords early onset OCD, OCD in childhood and adolescence, follow-up study, psy-chosocial adaptation

_________________________________________________________________________________ Introduction Although obsessive compulsive disorder (OCD) and early onset OCD has a high prevalence, only a few studies on the course and furthermore less studies on psychosocial adaption in early onset OCD have been published up to now. The aim of this prospective follow-up study of OCD with onset in childhood and adolescence is to describe the long-term outcome of so-cial adjustment. Methods 48 of 58 former patients treated for OCD in the Department of Child and Adolescent Psy-chiatry of the University of Würzburg were assessed by standardised measures (dependend on age DIPS or SKID-I, CY-BOCS, Social Adjustment Self Report; Global Assessment Functioning Scale), after a follow-up period of 5.8 years. Results At follow-up, 45.8% of the participants fulfilled the criteria for OCD according to DSM-IV. The level of psychosocial functioning was closely connected to the severity of OCD, however im-pairment regarding social-communicative skills as well as partnership was found in the sam-ple as a whole. Conclusion A conclusion of the presentation that the latency between onset of OCD and consultancy seems to be relevant not only in the course of symptom development but also for the level of psychosocial adjustment. A great focus in therapy with OCD patients should be laid on OCD specific treatment, consideration of comorbide psychiatric disorders and on the mediation of social skills.

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ZUR DEUTSCHSPRACHIGEN NORMIERUNG UND KLINISCHEN VALIDIERUNG DES BEHAVIOR RATING INVENTORY OF EXECUTIVE FUNCTION (BRIEF) Drechsler, R. Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland Keywords Exekutive Funktionen, Fremdbeurteilungsskala, Selbstbeurteilungsskala, Nor-

mierungsstudie, BRIEF, klinische Validierung _________________________________________________________________________________ Fragestellung Die BRIEF (Gioia et al., 2000) ist eine in der Literatur häufig eingesetzte klinische Skala zur Beurteilung von Störungen exekutiver Funktionen im Alltag (Altersbereich 6 bis 16 Jahre). Es wird hier von der deutschsprachigen Normierung und klinischen Validierung der Skala berichtet. Methode Die Normierung wurde anhand von über 1000 Kindern und Jugendlichen aus der Schweiz, Deutschland, Luxemburg und Österreich durchgeführt. Berichtet werden hier Ergebnisse zur Konstruktvalidierung und zur Übereinstimmung von Eltern- Lehren und Schülerurteilen in der BRIEF. Die klinische Validität der BRIEF wurde ausserdem anhand von Stichproben von Kindern und Jugendlichen mit ADHS überprüft. Ergebnisse Eine faktorenanalytische Überprüfung der BRIEF bestätigte die von den Testautoren der Originalversion gefundene zweifaktorielle Struktur. Die Interraterübereinstimmung zwischen Lehrer- und Elternurteilen war niedrig bis moderat, die zwischen Eltern und Jugendlichen im mittleren Bereich. Diese Befunde decken sich mit Untersuchungen von anderen Skalen. Bei Kindern und Jugendlichen mit ADHS zeigen sich sowohl im Elternurteil, Lehrerurteil als auch im Selbstrating signifikante Unterschiede im Vergleich zu Kontrollprobanden. Schlussfolgerung Die deutschsprachige Version der BRIEF für Kinder und Jugendliche ist ein valides Instru-ment zur Erfassung von exekutiven Funktionsbeeinträchtigungen im Alltag.

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PILOT STUDY: GENETIC BIOMARKERS IN ADHD Grünblatt E1,2, Geißler J3, Taurines R4, Jacob CP2, Romanos M5, Renner T4, Müller M2, Bartl J2, Gross-Lesch S2, Riederer P2, Lesch KP3, Gerlach M4, Schmitt A2, Walitza S1 1 Hospital of Child and Adolescent Psychiatry, University of Zurich, Neumuensterallee 9, 8032 Zurich, Switzerland 2 Clinic & Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, D-97080 Würzburg, Germany 3 Institute of Molecular Psychiatry, Clinic & Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, D-97080 Würzburg, Germany 4 Department of Child and Adolescent Psychiatry and Psychotherapy, University of Würz-burg, D-97080 Würzburg, Germany 5 Hospital of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Univer-sity Hospital of Munich, Munich, Germany Keywords Genetic, ADHD, Peripheral, biomarker, RNA, Blood _________________________________________________________________________________ Introduction Attention-deficit hyperactivity disorder (ADHD) is a common behavioural disorder that affects not only children and adolescents but also adults. However, diagnosis of ADHD in absence of objective clinical characteristics leads to the idea of identification of peripheral biomarkers which is highly relevant for the diagnostic process and an individualized therapy in neuro-psychiatric disorders. Methods We explored the expression profile of a list of previously established candidate genes in pe-ripheral blood samples from child and adult-ADHD subjects and compared these results to those of aged matched healthy controls. Results DRD4-mRNA expression in the whole blood was significantly lower in ADHD children com-pared to healthy controls. In the adult ADHD, combining the gene expression levels of SLC6A3, DRD5, TPH1, and SNAP25 as predictors in a regression model resulted in sensi-tivity and specificity of over 80% (ROC: max R²=0.588, AUC=0.918, P

DECISION MAKING AND REWARD LEARNING IN HEALTHY ADULTS: A SIMULTANEOUS EEG/FMRI-STUDY Hauser, T.U.1, Iannaccone, R.1,2, Drechsler, R.1, Brandeis, D.1,2,3, Walitza, S.1,2 & Brem, S.1 1 Department of Child & Adolescent Psychiatry, University of Zurich, Switzerland 2 Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Switzerland 3 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany Keywords reward learning, EEG, fMRI, reward prediction error _________________________________________________________________________________ Introduction Decision making is crucial for wellbeing. Everyday decisions are guided by preceding ex-periences of rewards and punishments, which enable us to evaluate the best among differ-ent choice options. Recent results in studies with humans and monkeys strongly suggest fronto-striatal loops to be involved in reward-dependent learning processes. Furthermore, decision making as well as the activity of these neural loops seem to be disturbed in psychi-atric patients, e.g. in obsessive-compulsive disorder (OCD). Methods In this simultaneous EEG/fMRI-study, we used a probabilistic reversal learning task in healthy adults to investigate the neural correlates of decision making. To infer the adaptive learning processes, we used computational reinforcement learning models. Results Although several studies already investigated these learning processes with methods with good spatial resolution (i.e. fMRI), the knowledge about the exact timecourse is still meager. Here, we report preliminary results of simultaneous EEG and fMRI recordings, which en-abled us to determine the precise spatial as well as temporal components of decision mak-ing. Conclusion Using simultaneous EEG/fMRI-approaches in the field of decision making enables to deter-mine the precise spatial and temporal components of decision making. Using such methods allows us to better understand impaired reward learning processes found in psychiatric dis-orders, such as OCD.

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PERFORMANCE AND CONFLICT MONITORING IN YOUNG HEALTHY ADULTS: A SIMULTANEOUS EEG FMRI STUDY Iannaccone, R.1,2, Hauser, T.U.2, Brandeis, D.1,2,3, Drechsler, R.1, Walitza, S.1,2, Brem, S.1

1Department of Child & Adolescent Psychiatry, University of Zurich, Zurich 2Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich 3Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim

Keywords EEG, fMRI, Flanker, Error, ERN, Inhibition _________________________________________________________________________________ Introduction Performance and conflict monitoring are essential processes of daily life that allow us to adapt our behaviour as necessary for efficient and targeted actions. Functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) data revealed that error moni-toring and conflict processing is mainly controlled by the anterior cingulate cortex (ACC). Im-paired activity in this region and thus also impaired error processing and conflict monitoring capabilities were found in psychiatric patients suffering of ADHD and OCD. Methods We used combined EEG and fMRI recordings to study the modulation of brain activation in response to conflicting stimulation in a group of healthy adult volunteers by using a flanker interference paradigm with different levels of conflict (high conflict, low conflict and no con-flict) along with an inhibition and a control condition. Results Here, we report preliminary behavioral results along with differences in brain activation as revealed by ERPs and fMRI in response to different levels of conflict, response inhibition and error processing. Conclusion With simultaneous measurement of EEG and fMRI, we achieve not only high temporal but also high spatial resolution for studying error processing and conflict monitoring. This should improve our knowledge about the underlying causes of disturbed error processing found in ADHD and OCD.

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DELAYED PRINT TUNING IN DYSLEXIA: A SIMULTANEOUS EEG-FMRI STUDY IN ADOLESCENTS Kronschnabel, J.1, Schmid, R.1, Maurer, U. 1,2, Brandeis, D.1,3 1Department of Child and Adolescent Psychiatry, University of Zürich, Zürich, Switzerland 2Department of Psychology, University of Zürich, Zürich, Switzerland 3Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany Keywords: dyslexia, print tuning, N1, event-related, visual word form, development _________________________________________________________________________________ Introduction Tuning of visual activity for print yields an increased occipitotemporal N1 at 150-250 ms in the event-related potential (ERP) to words compared to symbol strings. When beginning to read, specialization for print is reduced in dyslexic children compared to normal readers. This reduction, however, has not been replicated in early adolescence despite ongoing read-ing impairments. To investigate the neural causes of persistent dyslexia, we tested whether impaired print specialization may re-emerge under faster, more age-appropriate stimulus presentation. Methods Words and symbol strings were presented to 22 adolescents (mean age 16.1 yrs) for either 700 or 100 ms (long vs. short condition), while keeping SOA constant (1950 ms). Using a block design, EEG (64 channels) data were collected in a magnetic resonance environment. Results Contrary to expectations, no superior print specialization re-emerged in normal readers. Rather, dyslexics exhibited more pronounced N1 amplitudes than normal readers with even higher left-hemispheric print specialization in short presentation conditions. Normal readers had more bilateral N1 topographies. No robust print tuning differences between groups were obtained in preliminary functional resonance imaging analyses. Conclusion Taken together, expectations were not confirmed. Higher print specialization activity in dys-lexics might result from delayed development of reading proficiency, or alternatively from re-cruitment of more wide-spread metabolic ressources. Supported by the Swiss National Science Foundation.

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BRAIN MATURATION CAPTURED BY CO-REGISTERED ELECTROPHYSIOLOGICAL (EEG) AND HEMODYNAMIC (FMRI) SIGNAL FLUCTUATIONS Luechinger, R.1, Michels. L2,3, Martin, E.2,4, Brandeis, D.1,4,5 1 Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland 2 MR-Center, University Children’s Hospital, Zurich, Switzerland 3 Institute of Neuroradiology, University Hospital of Zurich, Zurich, Switzerland 4 Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland 5 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany Keywords: EEG-fMRI, child, resting state; development; oscillations; thalamo-cortical cou-

pling _________________________________________________________________________________ Introduction In the human brain, the transition from childhood to adulthood is marked by profound neuro-developmental reorganization. Structural changes in gray and white matter are mirrored by changing electrophysiological activity (EEG). Little is known about the basis of this neuronal maturation, but simultaneous recording of EEG and fMRI may elucidate its functional corre-lates. Methods Simultaneous EEG-fMRI was used to better understand the maturational decrease of EEG activity and to potentially reveal novel markers of brain maturation. Data were collected from 19 children, 18 adolescents and 18 adults aged 8 – 31 years. A 10 min resting EEG/fMRI paradigm with alternating eyes-open/eyes-closed blocks of 2.5 min was used. The EEG maturation was analyzed in terms of power in 6 frequency bands. Band power fluctuation was correlated voxel-wise to the fMRI BOLD sign