Posterabstracts - Psychiatrische Universitätsklinik Zürich

Transcrição

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
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Übersicht über die Abstracts der Referenten
Prof. Dr. med. Ulrich Schnyder
Dr. med. Milan Scheidegger
Fritz Frauenfelder, MNSc
Christian Tackenberg, PhD
Dr. sc. nat. Silvia Brem
lic. phil. Diana Wotruba
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Übersicht über die Posterabstracts
Ledermann et al.
Morina et al.
Oe et al.
Pirrotta et al.
Schumacher et al.
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Klinik für Affektive Erkrankungen und Allgemeinpsychiatrie Zürich Ost
Azzinnari et al.
Grimm et al.
Lott et al.
Mokros et al.
Schmidt et al.
Schuepbach et al.
Spinelli et al.
Vonmoos et al.
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Direktion Pflege, Therapien und Soziale Arbeit
Baumeler et al.
Frey
Klinik für Alterspsychiatrie
Chadha Santuccione et al.
Gietl et al.
Kälin et al.
Kulic et al.
Minakaki et al.
Preisig et al.
Riese et al.
Szodorai et al.
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Zentrum für Kinder- und Jugendpsychiatrie, Universität Zürich
Aebi et al.
Ball et al.
Drechsler et al.
Grünblatt et al.
Hauser et al.
Iannaccone et al.
Kronschnabel et al.
Luechinger et al.
Marinova et al.
Nyffeler et al.
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Klinik für Soziale Psychiatrie und Allgemeinpsychiatrie Zürich West
Ajdacic-Gross et al.
Brantschen et al.
Brühl et al.
Gholami et al.
Herwig et al.
Lay et al.
Paust et al.
Siemerkus et al.
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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
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
10.45
Pause
11.15
Alzheimer in der Kulturschale
Christian Tackenberg, PhD
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
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Ende
Abstracts der Referenten
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RESILIENCE VERSUS PTSD FOLLOWING TRAUMATIC EXPOSURE
Schnyder, U.1
1
Department 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 dysfunction, 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 assessments, nor did they use experimental designs.
Methods
We conducted two longitudinal studies of the psychosocial consequences of severe accidental 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 subjects who did not sufficiently speak the local language.
Conclusion
A comprehensive approach, linking the psychological process after trauma with neurobiological investigations over time, should be chosen to clarify under which circumstances resilience develops. We are currently planning a study looking into various predictors of resilience in survivors of physical violence. Multiple assessments will include discriminative conditioning tasks, cortisol and DHEA-S assays, psychophysiological measures of stress reactivity, 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
1
University Hospital of Psychiatry, Clinic of Affective Disorders and General Psychiatry, Zurich, Switzerland
2
Institute for Biomedical Engineering, University & ETH Zurich, Zurich, Switzerland
4
Cluster Languages of Emotion, Freie Universität Berlin, Berlin, Germany
5
Department of Psychiatry, Charité, CBF, Berlin, Germany
6
Department of Psychiatry, Otto-von-Guericke University, Magdeburg, Germany
7
University Hospital Zurich, Division of Nuclear Medicine, Zurich, Switzerland
8
ETH 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 including task fMRI, resting-state fMRI (rsfMRI), proton magnetic resonance spectroscopy (1HMRS), 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 activation during emotional picture viewing (IAPS) and cognitive processing (n-back) in core regions 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 patients in order to assess its utility for the investigation of neurobiological mechanisms of antidepressant 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, Prozessevaluation
_________________________________________________________________________________
Fragestellung
Auf der Grundlage von standardisierten Fachsprachen kann die Qualität der Pflege in Form
von Effizienz, Transparenz und Nachvollziehbarkeit gesteigert werden. Im Rahmen systematischen Vorgehensweise wurde das Basis-Assessment-instrument SEFW und die Pflegeklassifikationen 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 Patienten handelte oder dass sich die betroffenen Pflegeplanungen in Überarbeitung befanden.
Schlussfolgerung
Die standardisierten Fachsprachen konnten erfolgreich in das pflegerische Praxisfeld eingeführt und etabliert werden. Sie dienen zukünftigen als Basis für die weitere inhaltlichfachliche 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
2
Psychiatrische Universitätsklinik, Abteilung für psychiatrische Forschung, Zürich,
Universität Osnabrück, Abteilung Neurobiologie, Osnabrück
Schweiz
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 Demenzerkrankung. 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 Proteine zu erforschen.
Methode
Organotypische hippocampale (ex vivo) Gewebekulturen wurden von Aβ-produzierenden
AD-Mausmodellen präpariert. Diese Kulturen wurden mit Sindbis Viren infiziert, um grünfluoreszierenden Protein (GFP) oder GFP-gekoppeltes Tau in Neuronen zu exprimieren. Der
Effekt von Aβ und Tau auf das neuronale Zellüberleben und die synaptischen Verknüpfungen, sowie die Signalwege, die zur Pathologie führen, wurden untersucht.
Aβ induziert, unabhängig von Tau, einen Verlust von postsynaptischen dendritischen Dornen (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 Mechanismen, die zur neuronalen und synaptischen Degeneration in AD führen. Sie erlauben,
potentielle therapeutische Ansätze in einem authentisch zentralnervösen System zu untersuchen.
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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 teilweise möglich. Der Einbezug von spezifischen Markern aus der Bildgebung könnte jedoch die
Prädiktion verbessern. Verschiedene Studien haben auf die wichtige Rolle des linken okzipito-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 Lesefertigkeiten in der Schule verbessern können.
Methoden
In dieser kombinierten fMRT und EKP Längsschnittstudie haben wir die Entwicklung der Lesefertigkeiten und die damit assoziierten Veränderungen in der Schriftverarbeitung im Hirn
vom Kindergarten in die 2. Klasse verfolgt und Kinder mit normalen, bzw. schlechten Lesefertigkeiten 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 Massen im Kindergarten die Prädiktion der späteren Lesefertigkeiten im Vergleich zur Vorhersage 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
1
Psychiatrische Universitätsklinik Zürich, Zürcher Impulsprogramm zur nachhaltigen Entwicklung der Psychiatrie (ZInEP), Schweiz
2
UniversitätsSpital Zürich, Klinik für Neuroradiologie, Schweiz
Keywords Early Detection, Risk Factors, Psychosis, Default Mode Network, Graphtheoretical Analysis, Functional Connectivity, fMRI
_________________________________________________________________________________
Fragestellung
Bisherige Bildgebungsstudien stützen die Dyskonnektivitätshypothese der Schizophrenie,
die eine Störung neuronaler funktioneller Netzwerke postuliert. Jedoch ist bisher wenig untersucht, 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 highrisk-state (HR), die Basissymptome berichten (n=50), sowie der Vergleich zu einer gesunden 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 allem präfrontal sowohl auf die globale und die lokale Effizienz als auch auf die Kosten einzelner Komponenten auswirkt. Eine Hyperkonnektivität des funktionellen Netzwerkes im Vergleich zu HC konnte jedoch nur bei HR zwischen zerebellären und inferioparietalen Arealen
zum rechten Präfrontalkortex festgestellt werden, was jedoch keinen Einfluss auf die Effizienz 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 HRProbanden 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 diagnostische und prognostische Informationen darstellen.
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Posterabstracts
11/60
IS FIBROMYALGIA A NEUROPATHIC PAIN DISEASE?
Ledermann, K.1, Jenewein, J.1, Sprott, H.2, Hasler, G.3, Schnyder, U.1, Burger, C.4, Johayem, A.4, Cservenyak, T.4, Kollias, S.5, Buck, A.4, Martin-Soelch, C.1
1
Clinic of Rheumatology and Institute of Physical Medicine, University Hospital Zurich, Switz
3
University Hospital of Adult Psychiatry, University Bern, Switzerland
4
Department of Nuclear Medicine, University Hospital Zurich, Switzerland
5
Institute of Neuroradiology, University Hospital Zurich, Switzerland
2
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 compared 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 accumbens, 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<0.04) could be shown in
FM patients compared to healthy controls. Between groups both putamen evidenced a trend
(p<0.08 for the right, and p<0.07 for the left putamen). Significant negative correlations between BP and PDI scores emerged in the left caudate nucleus as well as in both putamen.
Conclusion
These preliminary findings indicate firstly that FM patients show changes in D2 receptor
binding in regions correlating with pain perception, and secondly that these findings do not
match patterns of neuropathic pain conditions as reported in literature.
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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
1
Department of Psychiatry und Psychotherapy, University Hospital Zurich, Switzerland
Psychiatric Services of the Canton St. Gallen-North (Wil, Switzerland)
2
Keywords refugees, PTSD, persistent pain, treatment, Biofeedback, Narrative Exposure
Therapy
_________________________________________________________________________________
Introduction
Many refugees suffer from comorbid PTSD and persistent pain. To date, successful treatment approaches are lacking for the simultaneous treatment of both conditions. Painfocused 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 intervention.
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, participants seem to have improved their quality of life and CBT-BF appears to increase the motivation for a subsequent trauma focused therapy.
Conclusion
This proof of concept shows that BF is a promising additional treatment component for persistent pain in traumatized refugees, before starting trauma focused psychotherapy. This
could be an important step to enhance the motivation for a subsequent trauma focused therapy 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
1
Department of Psychiatry und Psychotherapy, University Hospital Zurich, Switzerland
Keywords war conflict, traumatic experiences, mental health, quality of life, children, parents
_________________________________________________________________________________
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 after the war in Kosovo. Parents and children completed structured interviews and questionnaires 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 children’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
1
Department of Neuropsychiatry, Kurume University School of Medicine, Japan
3
Psychiatric Services of the County of St.Gallen-North, Center of Education and Research
(COEUR), Wil, Switzerland
4
University of Salzburg, Department of Clinical Psychology and Psychotherapy, Salzburg,
Austria
2
Keywords Posttraumatic stress disorder, Dehydroepiandrosterone (DHEA), Dehydroepiandrosterone sulphate, Cortisol, Neuroendocrine System, Psychological stress,
Long-term survivors
_________________________________________________________________________________
Introduction
Dehydroepiandrosterone (DHEA) and its metabolite dehydroepiandrosterone sulfate (DHEAS), which are also adrenal gland products, have prominent effects on GABA A receptor activity. 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 accidents 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 traumacontrols compared to no-trauma.
Conclusion
It has been suggested that the increase in DHEA in PTSD is rather salutary than pathophysiologic, and there is indication that effective psychotherapy for PTSD elevates DHEA
levels. Thus, the process of remission might have influenced DHEA concentration in the remitted PTSD group.
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PSYCHIATRIC COMORBIDITY
HEADACHE (MOH)
IN
PATIENTS
WITH
MEDICATION-OVERUSE
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
1
Department of Psychiatry and Psychotherapy, University Hospital Zurich, Zurich Switzerland
2
Department of Neurology, University Hospital Zurich, Zurich Switzerland
3
Clinic for Masticatory Disorders, Removable Prosthodontics and Special Care Dentistry,
Center for Oral Medicine, Dental and Maxillo-Facial Surgery, University of Zurich Switzerland
4
Institute of Psychology, Department of Neuropsychology, University of Zurich, Zurich, Switzerland
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 depression (BDI, MADRS), anxiety (HAS, STAI) and addiction (SDS, KFM) as well as a standardised Interview (MINI) to assess the addiction. Forty-one age and gender matched control 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
1
Department of Neurosurgery, Neurosurgical Clinic, Functional Neurosurgery, University
Hospital Zurich
3
Hoffmann-La Roche, Basel, Switzerland
4
Department of Psychology, Center for Cognitive Psychology and Methodology, University
of Basel, Basel Switzerland
2
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 personality 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, impairments of the mind reading’s ability and the ability to recognize facial emotional expressions at baseline according to the tests’ norms. The comparison with the control group before surgery evidenced statistically significant differences to the cognitive assessments, depression 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 remained, suggesting a long history of chronic pain may be associated with long-lasting cognitive and emotional deficits.
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PTSD AND EYE-BLINK STARTLE 10 YEARS AFTER SERIOUS ACCIDENTAL PHYSICAL INJURIES: REMITTED VS. RESILIENT INDIVIDUALS
Schumacher, S.1, Schnyder, U.1, Müller-Pfeiffer, C.1,2, Wilhelm, F.H.3, Martin Sölch, C.1
1
Psychiatric Services of the County of St.Gallen-North, Center of Education and Research
(COEUR), Wil, Switzerland
3
University of Salzburg, Department of Clinical Psychology and Psychotherapy, Salzburg,
Austria
2
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). Fifteen 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 increased startle reactions. Surprisingly, PTSD-resilient subjects showed higher startle magnitude than non-trauma controls.
Conclusion
Our results contradict evidence that increased startle reactivity might be a stable trait characteristic of people who develop PTSD after traumatic events and they suggests that extreme stress might induce changes in physiological reactivity even in psychologically resilient subjects.
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Posterabstracts
Klinik für Affektive Erkrankungen und Allgemeinpsychiatrie Zürich
Ost
19/60
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, cFos, 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 essential to test cause-effect hypotheses for the aetio-pathophysiology of stress-related depression and for identification of molecular targets for development of novel effective treatments.
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 regions) 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 social 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 psychopathological 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 antidepressant treatment. One current focus is the effects of stress on glutamate signalling and
of pharmacological targeting of glutamate signalling on depression-relevant mouse behaviour.
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EMOTIONAL- COGNITIVE PROCESSING AND BRAIN
PHARMACOLOGICAL CHALLENGE WITH KETAMINE
METABOLISM
AFTER
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 Emotion, 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 investigation 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 performance. 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 amplitude regardless of valence.
Conclusion
The valence- specific ketamine effect on BOLD signal in regions implicated in altered emotional and cognitive processing in mood disorders might be related to its rapid antidepressant 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
1
Pasadena City College, Pasadena, USA
Psychiatric University Hospital, Psychiatric Genetics, Zurich, Switzerland
3
University of Lausanne, Dept. Of Psychology, Lausanne, Switzerland
2
Keywords chronic stress, coping behavior, risk, depression, consumption behavior, physical health
_________________________________________________________________________________
Introduction
Normative results on coping behavior can be expected to help to identify that 10-15% subgroup 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 (learning 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 determined the intrinsic properties of the empirical data: noise level, dimensionality, and quantitative 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 behavior”, “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 being 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
1
University Hospital of Psychiatry, Center for Forensic Psychiatry, Zurich, Switzerland
University of Bonn, Department of Legal and Social Psychology, Bonn, Germany
2
Keywords pedophilia, implicit measures, viewing time, implicit association test, latent profile 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 significantly 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 COGNITIVE 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, University 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
effective connectivity, dynamic causal modelling, perceptual learning, glutamate, serotonin, psychosis
_________________________________________________________________________________
Key words:
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 rowing 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 develop diagnostic markers of neuronal connectivity and cognitive impairments.
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GENDER AND RAPID ALTERATIONS OF HEMISPHERIC DOMINANCE DURING PLANNING
Schuepbach, D.1*, Duschek, S.2, Theodoridou, A.1, Grimm, S.1, Boeker, H.1, Seifritz,
E.1
1
Psychiatric University Hospital Zürich, Lenggstrasse 31, 8032 Zürich, Switzerland
University of Munich, Department of Psychology, Leopoldstrasse 13, 80802 München,
Germany
2
Cerebral hemodynamics, functional transcranial Doppler, gender, lateralization, performance, planning
_________________________________________________________________________________
Keywords
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 performers 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
1
Preclinical Laboratory for Translational Research into Affective Disorders, Clinic for Affective Disorders and General Psychiatry, Psychiatric University Hospital Zurich, Zurich, Switzerland.
2
Clinic for Affective Disorders and General Psychiatry, Psychiatric University Hospital Zurich,
Zurich, Switzerland.
3
Department 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 functional 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 control 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
1
Experimental and Clinical Pharmacopsychology, Clinic of Affective Disorders and General
Psychiatry, University Hospital of Psychiatry Zurich, Switzerland
2
Substance 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 executive 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 examine 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 memory 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 processes 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
28/60
INTEGRIERTE PSYCHIATRISCHE BEHANDLUNG: INSTRUMENTE UND VERFAHREN
FÜR DIE SOZIALE ARBEIT
Baumeler, M., Hierlemann, F.
KTI-Forschungsprojekt der Fachhochschule Nordwestschweiz, Hochschule für Soziale Arbeit, 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 Indikation für die Intervention der klinischen Sozialen Arbeit gewährleisten.
Zur Validierung des Screening-Instruments wird die Kriteriumsvalidität geprüft. Das bedeutet, dass die Übereinstimmung oder Abweichung des Ergebnisses aus dem Einsatz des
Screening-Instruments anhand eines protokollierten Erstgesprächs durch die Sozialarbeitenden (Expertise) beurteilt wird.
Ergebnisse
Das Screening-Instrument aus der ersten Testphase wurde überarbeitet. Aktuell läuft zur erneuten Validierung des Screening-Instruments eine zweite Testphase in vier psychiatrischen
Kliniken.
Schlussfolgerung
Validierung des Screening-Instrumentes der zweiten Testphase bis Dezember 2011 / Abschluss des Gesamtprojektes Juni 2012.
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PSYCHOEDUKATION:
WIRKSAMKEIT
VON
PSYCHOEDUKATIVEN
PROGRAMMEN
SCHIZOPHRENIE ODER BIPOLAREN AFFEKTIVEN STÖRUNG
BEI
EINER
Frey, B.
Psychiatrische Universitätsklinik Zürich, Direktion Pflege, Therapien und Soziale Arbeit, Zürich, Schweiz
Keywords psychiatrische Pflege, Psychoedukation, Schizophrenie, bipolare affektive Störung, Gewichtsmanagement
_________________________________________________________________________________
Fragestellung
Psychoedukation ist eine mögliche Therapieform für psychische Krankheiten. Unter Psychoedukation versteht man in der Regel psychoedukative Gruppen, welche systematisch
nach einem Manual durchgeführt werden. Dabei werden PatientInnen- bzw. Angehörigengruppen 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 OutcomeParametern: Psychopathologie, Rückfälle, Compliance/Adhärenz, soziale Fertigkeiten, Gewichtsmanagement.
Schlussfolgerung
Wirksamkeit: Die nachgewiesene Wirksamkeit der Psychoedukation lässt die Folgerung zu,
dass systematische, psychoedukative Gruppen bei schizophrenen und bipolaren PatientInnen 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 psychiatrischen Pflege gehört, sollten psychoedukative Gruppen idealerweise interdisziplinär angeboten werden.
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Posterabstracts
31/60
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
Current 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.
5
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg,
Germany.
6
Current address: Neurimmune Therapeutics AG.
2
Keywords Alzheimer’s Disease, Neurodegeneration, Ankyrin G
_________________________________________________________________________________
Introduction
Sera antibodies against amyloid- peptide (A) in Alzheimer’s disease (AD) suggests a specific 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 neuronal expression was higher in AD patients than in age-matched control subjects (HCS). Moreover, antibody response against ankG was higher in AD patients than in HCS. Active immunization of APP-transgenic mice with ankG reduced brain -amyloid pathology and increased 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 decreased 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
1
University Hospital of Psychiatry, Division of Psychiatry Research and Psychogeriatric
Medicine, Zurich, Switzerland
2
University 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 Studies 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 normalized and PiB uptake was quantified using predefined ROIs of a maximum probabilistic atlas. The ratio of cortical PiB uptake to cerebellar PiB uptake gives an estimate of the neocortical 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 subjects. 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.
1
Division of Psychiatry Research and Psychogeriatric Medicine, Psychiatric University Hospital, 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 Alzheimer’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<.00); moreover, the mBc
reactivity against beta-amyloid revealed a quadratic relationship with cognitive performance
in the delayed recall test (τ=-.18,p<.00).
Conclusion
Our results confirm that the delayed recall performance constitutes a sensitive and early
marker of cognitive decline with the capacity to separate HCS from subjects with MCI and
beginning dementia. Preliminary analysis of peripheral immune cells point to the possibility
that reactivity of mBc against beta-amyloid constitutes a potential biomarker of prodromal
AD.
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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
1
University of Zürich
2
Geneva University Hospitals and University of Geneva
Keywords Alzheimer’s disease, MCI, Aβ, memory B cells, T cells, biomarkers
_________________________________________________________________________________
Introduction
The discovery of naturally occurring adaptive immune responses to misfolded brain proteins
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 responses in a population of mild cognitive impairment (MCI) patients included in an SNFfunded 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 patients.
Methods
Plasma and peripheral blood mononuclear cells (PBMC) were prepared freshly and memory
B 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 detection of A42-reactive T cells. Plasma sAPPα and sAPPβ levels were determined using an
MSD 2plex multi-SPOT kit.
Results
MCI patients were characterized by an increased number of Aβ42-reactive mBc as compared 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 increased sAPPβ/sAPPα ratio have been identified by MSD technology as potential novel biomarkers in MCI.
Conclusion
The preliminary results of this study point to a possible role of Aβ-directed humoral immune
responses 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 reactivity to other misfolded brain proteins in neurodegenerative diseases are planned. Our finding 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 longitudinally for its predictive value as a potential novel biomarker of prodromal AD.
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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 Research and Geriatric Psychiatry, 2Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307, Dresden, Germany
_________________________________________________________________________________
Introduction
The CSF reflects the biochemical state of the central nervous system under both physiological 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 disease 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 secreted vesicles mediating intercellular communication, such as exosomes. In support of the
latter, exosomes are constitutively secreted under both physiological and pathological conditions and have been reported to carry neurodegenerative disease-related proteins by several studies. Moreover, the presence of amyloidogenic proteins and the progressive spreading 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 biological 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 proteome. Interestingly, further analysis and comparison of specifically cytosolic proteins revealed 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
1
University Hospital of Psychiatry, Division of Psychiatry Research, Zurich, Switzerland
University of Zurich, Experimental Neuropathology, Institute of Neuropathology, Zurich,
Switzerland
2
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 comprehensive, individual full body locomotor profiles by assessing body coordination and kinematics.
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 extending 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 intraand inter-coordination of fore- and hindlimbs, posture, tail and limb strength, or stability.
Indeed, the increased sensitivity of this novel technology provides unprecedented quantitative 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 neurodegenerative 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 cortical processing/input and depends primarily on the integrity of corticospinal projections.
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PHOSPHORYLATION REGULATES APP INTRACELLULAR DOMAIN-MEDIATED NUCLEAR SIGNALING
Riese, F.1, Russi, N.1, Goodger, Z.V.1, Nitsch, R.M.1, Hock, C.1, Konietzko, U.1
1
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 acetyltransferase 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 complementation (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 position 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 phosphorylation including Y635, T654, T686 and Y687 showed no alteration in AFT complex formation, 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 transcriptional 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 Research 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, neuroradiological 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 were 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 gender. The mean hc volume loss due to cavities was small (30mm3), which approximates <1%
of the hc volume. Hc cavities were associated with lower baseline memory performance. In
70 nondemented subjects, larger hc cavity volume was associated with more decline in episodic memory during follow-up. In multivariate models hc cavity volume remained a significant predictor of memory decline, independent of hc volume and baseline memory performance. There was no interaction effect with hc atrophy or volume. While hc cavities appeared
to be relatively stable over time, we provide anecdotal evidence for both incident and shrinking cavities.
Conclusion
In this longitudinal study, hc cavities significantly contributed to episodic (“hippocampal“)
memory decline in nondemented elderly. The etiology of hc cavities deserves further study
and presumably involves vascular mechanisms.
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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
1
ETH Zurich, Institute of Molecular Systems Biology, Zurich, Switzerland
2
Keywords EBV, insulin, MCI, B cell, TSC2
_________________________________________________________________________________
Introduction
There is an increased risk for elderly people to develop both type 2 Diabetes and Alzheimer'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 mislocalization 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 signaling resistance is not known so far. It is also not analysed if viral receptors might be altered in human tissue. Because EBV infects peripheral blood cells and possibly even neurons, 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 containing media for two weeks. EBV treated human B cell extracts (1%NP40/PBS) were analysed 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 reactivation, 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 increase 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 proteins 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
41/60
JUVENILE SEX OFFENDERS IN SWITZERLAND: DEMOGRAPHIC FACTORS, PSYCHOPATHOLOGY, OFFENCE CHARACTERISTICS AND RECIDIVISM
Aebi, M.1, Bessler, C. 1
1
University of Zurich, Child and Adolescent Psychiatry, Division of Child and Adolescent Forensic 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-AssessmentProtocol (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 sexual offense severity scale were significant but only moderate predictors of sexual (N=7), violent (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
early onset OCD, OCD in childhood and adolescence, follow-up study, psychosocial adaptation
_________________________________________________________________________________
Keywords
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 social adjustment.
Methods
48 of 58 former patients treated for OCD in the Department of Child and Adolescent Psychiatry 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 impairment regarding social-communicative skills as well as partnership was found in the sample 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, Normierungsstudie, 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 Instrument 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 Würzburg, D-97080 Würzburg, Germany
5
Hospital of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University 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 neuropsychiatric disorders.
Methods
We explored the expression profile of a list of previously established candidate genes in peripheral 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 compared 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 sensitivity and specificity of over 80% (ROC: max R²=0.588, AUC=0.918, P<0.001, 95% CI:
0.869–0.968).
Conclusion
In conclusion, such genes expression profiles could represent a potential method for estimating risk and could be of diagnostic value for ADHD. Nevertheless, further investigation in
larger independent population of ADHD patients is required.
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DECISION MAKING AND REWARD
SIMULTANEOUS EEG/FMRI-STUDY
LEARNING
IN
HEALTHY
ADULTS:
A
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
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
2
Keywords reward learning, EEG, fMRI, reward prediction error
_________________________________________________________________________________
Introduction
Decision making is crucial for wellbeing. Everyday decisions are guided by preceding experiences of rewards and punishments, which enable us to evaluate the best among different 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 psychiatric 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 enabled us to determine the precise spatial as well as temporal components of decision making.
Conclusion
Using simultaneous EEG/fMRI-approaches in the field of decision making enables to determine the precise spatial and temporal components of decision making. Using such methods
allows us to better understand impaired reward learning processes found in psychiatric disorders, 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
1
Department of Child & Adolescent Psychiatry, University of Zurich, Zurich
Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich
3
Mental Health, Mannheim
2
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 monitoring and conflict processing is mainly controlled by the anterior cingulate cortex (ACC). Impaired 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 conflict) 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
1
Department of Child and Adolescent Psychiatry, University of Zürich, Zürich, Switzerland
Department of Psychology, University of Zürich, Zürich, Switzerland
3
2
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 reading 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 dyslexics might result from delayed development of reading proficiency, or alternatively from recruitment 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
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
2
Keywords: EEG-fMRI, child, resting state; development; oscillations; thalamo-cortical coupling
_________________________________________________________________________________
Introduction
In the human brain, the transition from childhood to adulthood is marked by profound neurodevelopmental 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 correlates.
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 signal. In addition, the absolute power of the
fluctuating BOLD signal (0.1 – 0.8 Hz) was directly compared with the trajectory of EEG
power.
Results
Our results revealed that both EEG and BOLD amplitudes decrease strongly between childhood and adulthood while their functional coupling remains largely constant except for increasing thalamic activation and coupling.
Conclusion
Parallel decreases of BOLD and oscillatory EEG activity with largely constant functional
coupling represent a new marker of functional brain maturation.
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THE SEROTONIN 2A RECEPTOR FUNCTION ANALYSIS IN NEURONAL CELL
CULTURE
Marinova, Z., Walitza, S., Grünblatt, E.
Hospital of Child and Adolescent Psychiatry, University Zürich, Neumünsterallee 9, 8032
Zürich, Switzerland
Keywords serotonin 2A receptor, neuroblastoma SK-N-SH, extracellular signal-regulated
kinase, neuroprotection
_________________________________________________________________________________
Introduction
The serotonin 2A receptor (HTR2A) is implicated in obsessive-compulsive disorder, depression, the effects of hallucinogens and atypical antipsychotic drugs. The aim of the present
study was to further characterize HTR2A signalling.
Methods
Human neuroblastoma SK-N-SH cells were subjected to serum deprivation to induce cytotoxicity. Cells were treated with the HTR2A agonist (±)-2,5-dimethoxy-4-iodoamphetamine
(DOI) (0.05–20 µM), the selective HTR2A antagonist MDL11,393 (1 µM), the tyrosine kinase
inhibitor genistein (50 µM) and the extracellular signal-regulated kinase (ERK) inhibitor
U0126 (10 µM). Cytotoxicity was measured continuously and noninvasively for 72 hours with
xCELLigence. RT-PCR and western blot were used to determine mRNA and protein expression.
Results
SK-N-SH cells expressed HTR2A mRNA levels. DOI partially protected SK-N-SH cells
against serum deprivation induced cytotoxicity in the 0.05-5 µM dose range. This effect was
blocked by pretreatment with the HTR2A antagonist MDL11,939. DOI’s protection of SK-NSH cells was attenuated by inhibition of tyrosine kinases (with genistein) or the ERK pathway (with U0126). Furthermore, DOI transiently increased ERK phosphorylation, a sign of
ERK’s activation. High concentrations of DOI (20 µM) exerted toxic effects.
Conclusion
Our results suggest that the HTR2A receptor agonist DOI has protective effect against serum deprivation in SK-N-SH cells through activation of the ERK pathway.
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OXYTOCIN RECEPTOR GENE IS ASSOCIATED WITH AUTISTIC TRAITS IN HEALTHY
CHILDREN
Nyffeler, J.1, Walitza, S.1, Bobrowski, E.1, Taurines, R.2, Romanos, M.3, Gundelfinger,
R.1, Lange, K.W.4, Grünblatt E.1
1
Department of Child and Adolescent Psychiatry, University of Zurich, Switzerland
Department of Child and Adolescent Psychiatry, Psychosomatic and Psychotherapy, University of Würzburg, Germany
3
Department of Child and Adolescent Psychiatry, Psychosomatic and Psychotherapy, University of Munich, Germany
4
Department of Experimental Psychology, University of Regensburg, Germany
2
Keywords autism, oxytocin, genetics, association study
_________________________________________________________________________________
Introduction
Autistic patients show impairments in social interactions, communication and repetitive behaviours. Causes are unknown, but a strong genetic component is assumed. Several linkage studies point to the region of the oxytocin receptor gene, but the involvement of this locus is yet unclear.
Methods
We performed an association study with independent sample sets from Zurich and Wuerzburg. Samples from patients, siblings and controls were genotyped for two copy number
variations (CNV) and three single nucleotide polymorphisms (SNP) in the oxytocin receptor
gene.
Results
Previous findings of CNVs in patients could not be replicated in either sample. For
rs2268494 genotype distribution was significantly different between patients and controls of
the Wuerzburg set (p = 0.0154), but not in the Zurich set. In the later, controls, but not patients and siblings, carrying the T-allele of the rs2301261 scored lower in the autism screening questionnaire "Social Responsiveness Scale" (p < 0.01) compared to non-carriers.
Conclusion
From these findings we could show only a slight association of oxytocin receptor polymorphism and autism, but it might contribute to the potency of autistic traits in the general population at a subclinical level. These findings support the role of oxytocin receptor in autism,
but not as a causative locus.
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Posterabstracts
Klinik für Soziale Psychiatrie und Allgemeinpsychiatrie
Zürich West
52/60
CANCER CO-MORTALITY
DISORDERS
PATTERNS
IN
SCHIZOPHRENIA
AND
PSYCHOTIC
Ajdacic-Gross, V.1, Tschopp, A.2, Bopp, M.2, Gutzwiller, F.2, Rössler, W.1,3
1
Psychiatric University Hospital, Zurich, Switzerland
Institute of Social and Preventive Medicine, University of Zurich, Switzerland
3
Collegium Helveticum, University of Zurich and the Swiss Federal Institute of Technology,
Zurich, Switzerland
2
Keywords schizophrenia, psychosis, cancer, mortality, case control study, bootstrapping
_________________________________________________________________________________
Introduction
To determine the profile of cancer co-mortality in deaths registered with schizophrenia and
psychotic disorders and to answer the question whether specific cancers occur more or less
frequently than expected compared to other cancers. To develop an analysis approach applicable to common mortality statistics data when no linkage with morbidity or other registers
is possible.
Methods
The analysis covered Swiss mortality data from a 39-year period (1969-2007) and was confined to the most frequent cancers. The design comprised as a two-step case-control analysis with bootstrapping (1000 repetitions). The cases were defined by the cancerschizophrenia registrations for each specific cancer, and the controls were matched from the
remaining cases (matching criteria: sex, age, region, subperiod). The parameter that was
bootstrapped was the chi-sqare of the standardised mortality ratio (SMR).
Results
Cancers with deviant SMRs included stomach cancer (1.6; 2.2 after reweighing), lung cancer (0.8; 0.5 after reweighing) and breast cancer (1.6; 1.5 after reweighing).
Conclusion
The cancer profile in schizophrenia and psychotic disorders diverges from the profile in the
general population. The relatively low frequency of lung cancers is particularly paradoxical in
view of the smoking habits of schizophrenia patients.
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„PLACEMENT-BUDGETS“ FÜR SUPPORTED EMPLOYMENT ZUR FÖRDERUNG DER
INTEGRATION VON MENSCHEN MIT PSYCHISCHEN ERKRANKUNGEN IN DEN
FREIEN ARBEITSMARKT
Brantschen, E.1, Nordt, C..1, Kawohl, W.1, Bärtsch, B.1, Rössler, W. 1
1
Klinik für soziale Psychiatrie und Allgemeinpsychiatrie ZH West, Psychiatrische Universitätsklinik Zürich
Keywords Supported Employment, Berufsrehabilitation, psychische Erkrankungen, randomisierte Studie, ZInEP
_________________________________________________________________________________
Fragestellung
Viele Menschen in psychiatrischer ambulanter Behandlung gehen keiner Erwerbstätigkeit
nach. Als eines der besten Modelle der Arbeitsmarktintegration gilt derzeit das „Individual
Placement and Support“-Modell (IPS). In diesem Modell, oft Supported Employment genannt, sucht ein Job Coach zusammen mit den Betroffenen möglichst rasch einen Arbeitsplatz in der freien Wirtschaft, der dem Wunsch der Betroffenen entspricht und betreut diesen
weiter, so dass der Arbeitsplatz möglichst lange gehalten werden kann. Als Teilprojekt des
Zürcher Impulsprogramm zur nachhaltigen Entwicklung der Psychiatrie ZInEP ist die primäre
Fragestellung dieser Studie, ob eine Begrenzung des „Placement-Budgets“ zu einem
schnelleren Antritt einer Arbeitsstelle auf dem freien Arbeitsmarkt beiträgt.
Methode
In gesamthaft sechs Ambulatorien von psychiatrischen Kliniken des Kantons Zürich betreuen Job Coachs bis zu zwei Jahre lang Studienteilnehmende, denen eines von drei festgelegten „Placement-Budgets“ zugelost (25, 40 oder 55 Stunden des Job Coachs) wird. Das
Hauptzielkriterium ist die Zeitdauer, bis eine Stelle gefunden wurde, welche länger als drei
Monate gehalten werden kann. Zudem wird in sieben Erhebungen über drei Jahre untersucht, ob die Arbeitstätigkeit in der freien Wirtschaft zu einer Verbesserung des Befindens
und der Gesundheit beiträgt und wie sich die soziale Integration sowie die finanziellen Lage
entwickelt.
Ergebnisse
Die Rekrutierung konnte im geplanten Zeitrahmen per Ende Mai 2011 abgeschlossen werden. Gesamthaft konnten 116 Studienteilnehmende ins Job Coaching eingeschlossen werden. Da die Studie noch am Laufen ist, können derzeit noch keine Ergebnisse berichtet
werden.
Schlussfolgerung
Das Projekt ist gut gestartet und alles läuft nach Plan.
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NEUROBIOLOGISCHE MECHANISMEN DER ACHTSAMEN EMOTIONSREGULATION
WÄHREND DER ERWARTUNG EMOTIONALER STIMULI: EINE FUNKTIONELLE MAGNETRESONANZTOMOGRAPHIE-STUDIE
Brühl, A. B.1, Lutz, J.1, Hänert, S.1, Hittmeyer, A.1, Scherpiet, S.1, Russmann, H.1, Jäncke, L.2, Rufer, M.3, Grosse-Holtforth, M.4, Herwig, U.1,5
1
Psychiatrische Universitätsklinik Zürich, Klinik für Soziale Psychiatrie und Allgemeinpsychiatrie ZH West, Forschungsgruppe Klinische und Experimentelle Psychopathologie, Zürich,
Schweiz
2
Universität Zürich, Psychologisches Institut, Neuropsychologie, Zürich, Schweiz
3
UniversitätsSpital Zürich, Klinik für Psychiatrie und Psychotherapie, Zürich, Schweiz
4
Universität Zürich, Psychologisches Institut, Klinische Psychologie, Psychotherapie affektiver Störungen, Zürich, Schweiz
5
Universität Ulm, Klinik für Psychiatrie und Psychotherapie, Ulm, Deutschland
Keywords mindfulness, emotion regulation, amygdala, PFC, fMRI
_________________________________________________________________________________
Fragestellung
Verschiedene Emotionsregulationsstrategien werden im Rahmen der Psychotherapie psychiatrischer Erkrankungen angewandt. Auf neuronaler Ebene bewirken kognitive Emotionsregulationsstrategien einen regulierenden Einfluss präfrontaler Strukturen auf limbische
Strukturen wie die Amygdala. Achtsamkeit ist eine weitere Methode der Emotionsregulation.
In dieser Studie wurden die neurobiologischen Mechanismen einer achtsamkeitsbasierten
Emotionsregulationsinstruktion während der Erwartung und Wahrnehmung emotionaler Stimuli untersucht.
Methode
Mittels funktioneller Magnetresonanztomographie untersuchten wir 49 gesunde Probanden
mit einem emotionalen Antizipationsparadigma. Dabei wendeten 26 Probanden eine achtsamkeitsbasierte Emotionsregulationsstrategie an (Achtsamkeitsgruppe). 23 Probanden
führten keine explizite Emotionsregulationsstrategie durch (Kontrollgruppe).
Ergebnisse
Während der Erwartung negativer Stimuli zeigte die Achtsamkeitsgruppe gegenüber der
Kontrollgruppe stärkere Aktivierungen in medialen, dorso- und ventrolateralen präfrontalen
Hirnregionen und eine reduzierte Aktivität in der linken Inselregion. Während der Wahrnehmung negativer Bilder war in der Achtsamkeitsgruppe die Aktivität in limbischen Regionen
(erweiterte Amygdala, Insel) reduziert.
Conclusion / Schlussfolgerung
Achtsamkeitsbasierte Emotionsregulationsinstruktionen waren in der Erwartungsphase mit
präfrontaler Hirnaktivierung verbunden, die dann in der Wahrnehmungsphase nicht mehr
gesteigert war. Parallel fand sich durch die Achtsamkeit vor allem während der Konfrontation
mit negativen emotionalen Bildern eine reduzierte Aktivierung in limbischen Regionen
(Amygdala, Insel). Diese Ergebnisse sind ähnlich zu Befunden bei der Anwendung kognitiver Emotionsregulationsstrategien.
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QTC PROLONGATION IN METHADONE MAINTENANCE TREATMENT – HCV INFECTION AS A CONTRIBUTING FACTOR?
Gholami, N., Boesch, L., Stohler, R.
Psychiatric University Hospital of Zurich, Clinic of Social and General Psychiatry, Research
Group on Substance Use Disorders, Zurich, Switzerland
Keywords QTc-intervals, HCV-infection, methadone maintenance treatment.
_________________________________________________________________________________
Introduction
Several studies reported prolonged QTc-intervals of patients under methadone treatment,
including development of torsade-de-pointes arrhythmia and death. It is still not clear why
some patients develop critical extensions while others do not. Apart from pre-existing structural and other heart diseases and methadone dosage, several findings point to the importance of liver-function impairment including the presence of HCV-infection as a predictor of
longer QTc-intervals.
Methods
We therefore assessed QTc-intervals in a large sample of methadone maintained heroindependent patients taking account of HCV-infection status by means of a multivariate linear
regression model with QTc as the dependent variable.
Results
Racemic methadone dose and hepatitis C infections both independently prolong QTc-time.
Conclusion
Co-infection with hepatitis C virus greatly increases the likelihood of clinically significant QTc
prolongation in patients in methadone maintenance treatment.
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SELBSTREFERENZ UND EMOTIONSREGULATION BEI DEPRESSIVEN PATIENTEN
Herwig, U.1, Wetter, Th.2, Cattapan, K.3, Hittmeyer, A.1, Wanner, C.1, Hänert, S.1, Brühl,
A. B.1
1
Psychiatrische Universitätsklinik Zürich, Klinik für Soziale Psychiatrie und Allgemeinpsychiatrie ZH West, Forschungsgruppe Klinische und Experimentelle Psychopathologie, Zürich,
Schweiz
2
Psychiatrische Universitätsklinik Zürich, Klinik für Affektive Erkrankungen und Allgemeinpsychiatrie ZH Ost, , Zürich, Schweiz
3
Sanatorium Kilchberg, Kilchberg, Schweiz
Keywords self-referential, mindfulness, emotion regulation, major depression, amygdala,
PFC, fMRI
_________________________________________________________________________________
Fragestellung
Die Untersuchung „Selbst“-referenzieller Hirnaktivität könnte helfen, selbstbezogene Symptome bei affektiven Erkrankungen auf einer pathophysiologischen Ebene besser zu verstehen. Bei gesunden Probanden ging emotionale Introspektion im Vergleich zu Selbstreflexion
mit einer Aktivitätssteigerung in präfrontalen Regionen und einer Reduktion der AmygdalaAktivität einher. Dies entspricht einer Reduktion des emotionalen Arousals durch die emotionale Introspektion, die einer Achtsamkeitsintervention gleichkommt. Dies haben wir nun bei
depressiven Patienten untersucht.
Methode
20 depressive Patienten führten während funktioneller Magnetresonanz-Tomographie entweder eine 12 Sekunden währende Selbstreflexion („wer bin ich, was will ich“) oder eine
emotionale Introspektion („wie fühle ich mich, was spüre ich“) durch. Die Ergebnisse wurden
mit 20 gesunden Probanden verglichen.
Ergebnisse
Bei depressiven Patienten war bei emotionaler Introspektion gegenüber Selbstreflexion die
Aktivität in präfrontalen und parietalen kortikalen Mittellinienarealen inklusive Cingulum stärker. Die linke Amygdala war während emotionaler Introspektion vermindert und während
Selbstreflexion verstärkt aktiviert. Gegenüber gesunden Probanden zeigten die Patienten
bei emotionaler Introspektion im Vergleich zur kognitiven Selbstreflexion eine ausgeprägtere
medial und dorsolateral präfrontale Aktivierung.
Schlussfolgerung
Auch depressive Patienten sind in der Lage, durch die achtsamkeitsnahe emotionale
Introspektion ihre Amygdala-Aktivität herabzuregulieren. Dies unterstützt die Anwendung
achtsamkeitsbasierter Strategien in der Psychotherapie. Allerdings wiesen depressive Patienten stärkere präfrontale Aktivierungen auf, was auf mehr benötigte Ressourcen hinweisen
kann.
57/60
ZWANGSMAßNAHMEN IM RAHMEN PSYCHIATRISCHER VERSORGUNG BEI PERSONEN, DIE EINE GERICHTLICH VERHÄNGTE FREIHEITSSTRAFE VERBÜSSEN
Lay, B.1, Nordt, C.1, Rössler, W.1
1
Psychiatric University Hospital Zurich, Research Unit for Clinical and Social Psychiatry,Zurich, Switzerland
Keywords Zwangsmaßnahmen, psychiatrische Versorgung, Kriminalitäts-belastung
_________________________________________________________________________________
Fragestellung
Zwangsmaßnahmen in der Psychiatrie stehen ein einem Spannungsverhältnis zwischen der
Behandlungsbedürftigkeit des Patienten, grundlegenden Patienten-rechten und dem Sicherheitsbedürfnis der Allgemeinheit. Die epidemiologische Studie untersucht, ob Personen, die
aus dem Strafvollzug in die Psychiatrie aufgenommen werden, ein erhöhtes Risiko für
Zwangsmaßnahmen im Rahmen der psychiatrischen Versorgung aufweisen. Insbesondere
soll geklärt werden, wie klinische und soziodemografische Patientenmerkmale zur Prädiktion
von Zwangsmaßnahmen beitragen.
Methode
Für die Analyse wurde die Psychiatriestatistik des Kantons Zürich verwendet, die Daten einer Versorgungsregion von rund 1.3 Millionen Einwohnern umfasst. Eingeschlossen wurden
27'172 Patienten im Alter 15-80 Jahre, die in einem Untersuchungszeitraum von 7 Jahren in
stationärer Behandlung waren.
Ergebnisse
Personen aus dem Strafvollzug sind mit 58% Zwangseinweisung, 10% Zwangsisolation und
6% Zwangsmedikation wesentlich häufiger von Zwangs-maßnahmen der Psychiatrie betroffen; sie unterscheiden sich auch hinsichtlich psychopathologischer und sozialer Merkmale
signifikant von anderen Patientengruppen. Jedoch zeigen Multilevel-Analysen, dass eine
Aufnahme aus dem Strafvollzug das Risiko für Zwangsmaßnahmen nicht zusätzlich erhöht,
wenn für Hintergrundvariablen auf der Ebene der Patienten (insbesondere krankheitsbedingte Faktoren) kontrolliert und Klinik-Effekten Rechnung getragen wird.
Schlussfolgerung
Patientenmerkmale (insbesondere Kriminalitätsvorbelastung) leisten nur einen begrenzten
Beitrag zur Erklärung von Zwangsmaßnahmen. Insbesondere die nach Kontrolle von Patientenvariablen verbleibende hohe Heterogenität zwischen den Kliniken bezüglich der Anwendung von Zwangsmaßnahmen bedarf weiterer Klärung.
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HIGH RISK OF BIPOLAR DISORDER AND SCHIZOPHRENIA
Paust, T., Dvorsky, D., Fronius, A., Gerstenberg, M., Guntermann, A., Meyer, D., Metzler, S., Traber-Walker, N., Wotruba, D., Wyss, C., Heekeren, K., Theodoridou, A., Rössler, W.
University Hospital of Psychiatry Zurich, Switzerland
The Zurich Program for Sustainable Development
(ZInEP)
of
Mental
Health
Services
Keywords Early detection, psychosis, bipolar disorders, risk factors
_________________________________________________________________________________
Introduction
Part of the disability produced by psychotic illnesses especially schizophrenia and bipolar
disorder develops already during the prepsychotic period. Internationally employed definitions of the “at risk mental state” are existing, although upon different operationalization criterias. Until now the earliest clinical stages of psychotic disorder are non-specific and overlap phenotypically with other disorders.
Methods
In a prospectively longitudinal multi-level-approach (psychopathology-neuropsychologyelectrophysiology-genetic-MRI) subjects, at risk for schizophrenia or bipolar disorder, from
the Canton Zurich will be recruited. In our symptomatic high-risk group we target these individuals for intensive monitoring. The Canton Zurich has ca. 1’300’000 habitants. We recruit
area-wide and continue the recruitment by expanding the sample size to n=250.
Results
In a first step we have analyzed the recruitment strategies in the catchment area and implemented the regional early recognition centers. Continuous public relations are offered (telephone helpline, homepage, newspapers, schools, general practitioners, outreach centers).
In the first 12 months 120 individuals at risk were recognized and underwent a multi-levelexamination. Descriptive and analytical statistics will be performed. In a preliminary analysis
we found an overlapping between both criteria systems, about 60 percent of the individuals
met the risk criteria for both diseases (schizophrenia and bipolar disorder).
Conclusion
Our study provides a useful platform from which to investigate risk factors for these disorders, their similarities and differences. We want to provide more information into this theme
with our strategy to focus on the affective and non-affective disorders in this prospective longitudinal multi-level-approach.
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HIPPOCAMPAL GRAY MATTER DENSITY CORRELATES WITH DISORGANIZED SYMPTOMS IN SCHIZOPHRENIA
Siemerkus, J.1,2, Irle, E.2, Ruhleder, M.2, Lange, C.2, Weniger, G.1
1
University Hospital of Psychiatry Zurich, Switzerland
Department of Psychiatry and Psychotherapy, University of Göttingen, Germany
2
Keywords schizophrenia, psychopathology, disorganized symptoms, voxel based morphometry, hippocampus
_________________________________________________________________________________
Introduction
Nonuniform findings regarding the hippocampal volume or gray matter density in schizophrenia raise the question, if a dimensional psychopathology may lead to a better understanding of the structural alterations of the brain in schizophrenia. With this poster we focus
on disorganized symptoms and gray matter density alterations.
Methods
Structural T 1 -data of 63 patients with schizophrenia were analyzed using SPM5. After preprocessing and segmentation a score of disorganized symptoms was modeled as a covariate to calculate the positive correlation with the gray matter values. Imaging results were accepted as significant with α = 0.002 (uncorrected).
Results
Among other regions right and left hippocampus showed clusters of significant voxels correlating positively with the disorganized symptoms. The left hippocampal body contained a
cluster with 105 suprathreshold voxels (1.5 × 1.5 × 1.5 mm3) and a maximum [mean] value
of t = 3.91 [3.31]. The right hippocampal body contained a cluster with 21 suprathreshold
voxels and a maximum [mean] value of t = 3.42 [3.16].
Conclusion
The findings suggest a preserved hippocampal integrity or even gray matter density increase
in relation to disorganized symptoms. Our findings support the hypothesis of psychopathologically defined endophenotypes and further points to the importance of a dimensional
psychopathology in studying this complex disorder.
60/60
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Posterabstracts - Psychiatrische Universitätsklinik Zürich

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