Psykiatriens 9. Forskningsdag 6. november 2014, AUH Risskov

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1 Psykiatriens 9. Forskningsdag 6. november 2014, AUH Risskov AU AARHUS UNIVERSITET

2 Indhold Dagens program Side 3 Foredragsprogram Side 5 Abstracts foredrag Side 7 Posteroversigt Side 19 Abstracts posters Side 23 1

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4 Dagens program 12:00 Sandwich i Vandrehallen og postervandring i Den Ny Festsal 13:00 Velkomst og introduktion til dagen ved professor Per Hove Thomsen i Auditoriet 13:15 Foredrag i Auditoriet 15:15 Kaffepause i Vandrehallen og postervandring i Den Ny Festsal 16:00 Foredrag i Auditoriet 17:00 Dommerkomiteen voterer 17:15 Taler præmieoverrækkelse ved professor Per Hove Thomsen i Vandrehallen 17:30 Buffet i kantinen 18:30 Afslutning 3

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6 Foredragsprogram Moderator: Poul Videbech Jakob Linnet Forskningsklinikken for Ludomani, AUH Tre myter om dopamin og ludomani Pause Moderatorer: Per Hove Thomsen og Ole Mors Charlotte Ulrikka Rask Forskningsklinikken for Funktionelle Lidelser, AUH Helbredsangst hos unge association med helbredsproblemer og kontinuitet fra barndommen Thao Phuong Tran Translational Neuropsychiatry Unit, AU Sammenhængen mellem inflammation og depression; et funktionelt og morfometrisk, longitudinelt PET/MRI studie baseret på en rottedepressionsmodel Niels Okkels Afdeling M, AUH Risskov En gennemgang af 10 års prægraduat forskning i psykiatri Anne Mette Lange BUC, Risskov, Forskningsafsnittet De sociale og personlige omkostninger af ubehandlet ADHD hos voksne Pause Moderatorer: Povl Munk Jørgensen og Gregers Wegener Niklas W. Andersson Afdeling M, AUH Risskov Depression og risikoen for autoimmun sygdom: prospektive analyser på et landsdækkende repræsentativt sample Søren Dinesen Østergaard Afdeling P, AUH Risskov Klinisk og Psykometrisk validering af Psychotic Depression Assessment Scale Christina Weide Fischer Translational Neuropsychiatry Unit, AU Kronisk inflammation i rotter: adfærd og systemiske adaptationer Nicolai Ladegaard Afdeling Q, AUH Risskov Prosodi hos deprimerede patienter 5

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10 The three fallacies of dopamine in gambling disorder Jakob Linnet Forskningsklinikken for Ludomani, Århus Universitetshospital Nørrebrogade 44, bygning 30 DK 8000 Århus C. Ludomani er en afhængighedstilstand forbundet med dopaminerge dysfunktioner. Foredraget tager udgangspunkt i tre hypoteser om dopaminerge dysfunktioner i ludomani, som forekommer at være fejlslutninger. Den første hypotese antager, at personer med ludomani har lavere baseline bindingspotentiale, hvilket ofte ses ved stofmisbrug; den anden hypotese antager, at spilleaktivitet er forbundet med højere dopaminfrigivelse ved ludomani; den tredje hypotese antager, at gevinster er forbundet med højere dopaminfrigivelse ved ludomani. Det har ikke været muligt at finde belæg for disse hypoteser i positron emissions tomografi (PET) undersøgelser af dopaminfrigivelse ved ludomani. I stedet ser det ud til at dopaminerg kodning af usikkerhed bedre kan redegørelse for de dopaminerge dysfunktioner ved ludomani. Personer med ludomani lider muligvis af en "dobbelt belastningstilstand", hvor dopaminfrigivelse er forbundet med øget spænding, men dårligere problemløsningsadfærd. 9

11 Health anxiety in preadolescence concurrent health problems and longitudinal pathways in childhood Charlotte Ulrikka Rask 1,2, Anja Munkholm 3, Lars Clemmensen 3, Martin K. Rimvall 3, Eva Ørnbøl 1, Pia Jeppesen 3,4, Anne Mette Skovgaard 5 1 The Research Clinic for Functional Disorders and Psychosomatics, AUH 2 Child and Adolescent Psychiatric Center Risskov, AUH 3 Child and Adolescent Mental Health Center, Mental Health Services, Glostrup 4 Faculty of Health Science, University of Copenhagen 5 Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, Denmark. Objective Epidemiological data on the distribution, persistence and clinical correlates of health anxiety (HA) in childhood are scarce. This study investigated HAA symptoms and associated mental and somatic health problems and use of health services in primary care in a general population birth cohort. Method HA symptoms were examined in year old children (N=1886) from the Copenhagen Child Cohort by the Childhood Illness Attitude Scales (CIAS), together with socio demographic information, the child s medical and mental status and health care utilisation. Regression analyses were used to compare groups with low (N=184), intermediate (N=1539) and high (N=161) HA symptom scores. The association between former assessed HA symptoms at age 5 7 years and current HA symptoms at age years was examined by Stuart Maxwell test. Results HA symptoms were significantly associated with emotional disorders and unspecific somatic complaints (p values<.001) but not chronic medical conditions. In regression analyses controlling for gender and physical comorbidity children with the highest HA symptom score had the highest medical costs in primary care (p=0.027) where they used almost twice more health care than children with the lowest score during the two year period preceding inclusion. HA symptoms at age 5 7 years significantly predicted high levels of HA symptoms at age years (p<.001). Conclusions Symptoms of HA including hypochondriacal fears and beliefs were non trivial in preadolescents as they showed continuity from early childhood and association with emotional disorders, unspecific physical complaints and increased health care costs. Further research of the clinical significance of HA in children is required. 10

12 Cognitive assessment of depressed rats; ipads for rodents Thao Phuong Tran, Helle Lyng Christensen, Freja Bertelsen, Arne Møller and Ove Wiborg Translational Neuropsychiatry Unit, Dept of Clinical Medicine, Aarhus University Major depressive disorder (MDD) is a disabling disease associated with significant mortality and health cost. Some of the main symptoms of MDD are anhedonia (loss of general interest) and devastating cognitive impairments or distortions. To identify new therapeutic targets, the focus is on cognitive dysfunctions like: 1) a cognitive bias or selective preference for negative inputs 2) cognitive deficits, which include impairments in attention, short term memory and executive functioning. This project focuses on cognitive impairments associated with Chronic Mild Stress (CMS) induced anhedonia. After chronically exposure of rats to unpredictable stressors some of them will, like humans, become anhedonic, while others are able at coping and termed resilient. To assess the cognitive performance of the rats we use the Touch Screen Operant Platform which is highly similar to the human cognitive tests. One of the main tasks is Pairwise Discrimination (PD) learning and reversal. During the PD task, the rats are scored for their ability to acquire new associations (picture A=reward, picture B=punishment), functions known to depend upon the orbitofrontal region of prefrontal cortex and interconnected subcortical areas. After the task has been acquired, the rats have to do reversed learning (picture B=reward, picture A=punishment), addressing cognitive flexibility. With this project, we aim at getting new insights into cognitive impairments associated with stress induced depression. 11

13 Evaluating 10 years of pre graduate research in medicine and psychiatry Niels Okkels 1,2,3, Marlene Skovgaard 3,4, Mette Krogh Christensen 5, Niklas Telinius 6,7, Ellen Margrethe Hauge 8 1 Department of Organic Psychiatric Disorders and Emergency Ward (Dept. M), Aarhus University Hospital, Risskov, Denmark. 2 Psychiatric Hospital Augustenborg, Hospital of Southern Jutland, Denmark. 3 Society for Medical Student Research, Aarhus University, Denmark. 4 Graduate School of Health, Faculty of Medicine, Aarhus University, Denmark. 5 Center for Medical Education, Aarhus University, Denmark. 6 Department of Biomedicine, Aarhus University, Denmark. 7 Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby, Denmark. 8 Department of Rheumathology, Aarhus University Hospital, Denmark. Introduction In Denmark, medical students can apply for an optional, one year, pre graduate research programme. The programme has existed for 25 years. However, little is known about the main quantitative outcomes; namely scientific publications and continuation to a PhD. programme. Also, little is known about the distribution of students between the medical specialties, including psychiatry. Method We included all medical students enrolled in the pre graduate research programme (n=687) from at Aarhus University, Denmark. We made a systematic literature search on the publications of a sub group of the students (n=227). Students were characterized in terms of age, sex, and years of medical school completed at the time of embarking the programme. Students affiliated with psychiatric departments (n=12) were characterized and compared with their peers. Results All together the 227 students published 224 papers. Of these, 90% were original articles and 43% had a student as first author. Fifty two percent published 1 papers. Twelve out of 687 students (2%) were enrolled at a psychiatric department. Of these, 1 student published 1 paper as second author and none continued in a PhD. Overall, publication was associated with (i) fast completion of the programme, (ii) having a male main supervisor and (iii) continuing to a PhD. Conclusion Scientific publishing and PhD. recruitment was associated with fast completion and early enrolment in the pre graduate research programme. A relatively low proportion of students were affiliated with psychiatric departments. 12

14 De sociale og personlige omkostninger af ubehandlet ADHD hos voksne Anne Mette Lange Aarhus University Hospital, Research Department, Centre for Child & Adolescent Psychiatry Oplæget er baseret på undersøgelsen: The Private and Social Costs of ADHD: COST ANALYSIS By CASA Cost Analysis Study group for ADHD : David Daley, Rasmus Højbjerg Jacobsen, Anne Mette Lange, Anders Sørensen, and Jeanette Walldorf. The Rockwool Foundation Research Unit Study Paper No. 69: 2014 Introduktion De samlede sociale og personlige økonomiske konsekvenser af ADHD har ikke hidtil været belyst. Tidligere undersøgelser har haft en række metodologiske begrænsninger, og været baseret på forsikringsdatabaser, og typisk taget udgangspunkt i omkostninger i forhold til sundhedsydelser. Ved brug af de danske registre er dette studie et forsøg på at opnå et estimat af de sociale og personlige omkostninger af ADHD hos voksne ved at sammenligne gruppen med en matched kontrol gruppe. Metode En gruppe af 1431 individer diagnosticeret med ADHD, uden anden ko morbiditet blev identificeret ud fra de danske registre. Gruppen blev sammenlignet på en række outcomes med en gruppe af søskende uden ADHD og komorbiditet. Resultater ADHD medførte signifikant større personlige omkostninger (lønindtægt og uddannelsesstatus) og sociale omkostninger (overførselsindkomster, manglende skatteindtægter, kriminalitet, trafikulykker, anbringelser, og sundhedsydelser) for gruppen af individer med ADHD sammenlignet med gruppen af søskende uden ADHD. Diskussion Resultaterne fremhæver den betydelige indvirkning, som ubehandlet ADHD har for voksne, både personligt og samfundsmæssigt. Konsekvenserne ved ubehandlet ADHD drøftes og konkrete tiltag for at nedbringe de høje omkostninger fremlægges. 13

15 Depression and the risk of autoimmune disease: A nationally representative, prospective longitudinal study Niklas W. Andersson Afdeling M, AUH Risskov Background Depression has been associated with various inflammatory related physical conditions, such cardiovascular and neurodegenerative diseases. Yet, little is known about the association between depression and autoimmune diseases (ADs). Objectives This study examined the association between depression and risk of AD, investigating the temporal and dose response nature of these relationships. Methods A prospective study including approximately 1.1 million people was conducted using linked Danish registries. 145,217 participants with depression were identified between 1995 and Survival analyses were used to estimate the relative risk of AD among those with, compared to without, depression. Analyses were adjusted for gender, age, and mental disorders. Results Depression was associated with increased risk of a wide range of ADs. One depressive episode was associated with 40% increased risk of any AD (IRR=1.40, 95% CI= ), while having 4 or more depressive episodes showed a 112% increase in risk (IRR=2.12, 95% CI= ) suggesting a dose response relationship. Results indicated a general increased risk of AD following the emergence of depression (during first year, IRR=1.29, 95% CI= , and persisting after 11 years or more IRR=1.53, 95% CI= ). Conclusion Depression appears to be associated with increased risk of the onset of a range of ADs. The pattern of these associations is suggestive of a dose response relationship and the increased risk of ADs was not confined to a specific time period following the onset of depression. Depression may play a role in the etiology of certain autoimmune conditions. Further research is needed to validate and clarify present findings. 14

16 Clinical and Psychometric Validation of the Psychotic Depression Assessment Scale Østergaard SD, Pedersen CH, Uggerby P, Munk Jørgensen P, Rothschild AJ, Larsen JI, Gøtzsche C, Søndergaard MG, Bille AG, Bolwig TG, Larsen JK, Bech P Aarhus Universitetshospital, Risskov. Afdeling P. Background/Objectives Recent studies have indicated that the 11 item Psychotic Depression Assessment Scale (PDAS), consisting of the 6 item melancholia subscale (HAM D6) of the Hamilton Depression Rating Scale and 5 psychosis items from the Brief Psychiatric Rating Scale (BPRS), is a clinically valid, scalable (unidimensional), and responsive measure for the severity of unipolar psychotic depression (UPD). The aim of this study was to subject the PDAS, and its depression (HAM D6) and psychosis (BPRS5) subscales to further clinical and psychometric validation. Methods Patients with clinical diagnoses of UPD assigned at Danish psychiatric hospitals participated in semi structured interviews. Video recordings of these interviews were assessed by two experienced psychiatrists (global severity rating of psychotic depression, depressive symptoms and psychotic symptoms) and by two young physicians (rating on 27 symptom items, including the 11 PDAS items). The clinical validity of the PDAS and its subscales was investigated by Spearman correlation analysis of the global severity ratings and the PDAS, HAM D6, and BPRS5 total scores. The scalability of the scales was tested by Mokken analysis. Results Ratings from 39 subjects with unipolar psychotic depression and nine patients with bipolar psychotic depression were included in the analysis. The Spearman correlation analysis versus global severity ratings indicated that the PDAS, HAM D6 and BPRS5 were clinically valid measures of both UPD and BPD. According to the Mokken analysis, the scales demonstrated acceptable scalability. Conclusions The clinical validity and scalability of the PDAS and its subscales, the HAM D6 and BPRS5, was confirmed in an independent sample. 15

17 Modelling chronic inflammation in rats: behaviour and whole body adaptations Christina W Fischer, Betina Elfving, Sten Lund and Gregers Wegener Translational Neuropsychiatry Unit, AU Background Inflammation is the body s first defence system against infections, but exaggerated inflammatory processes may be involved in chronic diseases, ranging from depression to diabetes. Chronic inflammation affects the whole body, from brain function and behavioural adaptations to energy regulation. Objective In order to understand the underlying mechanisms, the aim of this study was to develop a model of chronic inflammation in rats. Specifically, we assessed: 1) behavioural changes, 2) cytokine levels in the brain and in blood, and 3) peripheral adaptations. Methods Sprague Dawley rats (n=60) were randomized to receive a single (20h) or chronic (eight weeks) treatment with either lipopolysaccharide (LPS, 600μg/kg, i.p.) or saline. Behavioural tests included: locomotor activity in an open field, and depressive like behaviour in the forced swim test. 24 cytokines were investigated using a multiplexing technology (Luminex xmap) and the Bio Plex 200 platform (Bio Rad Laboratories, USA) in serum, frontal cortex, and hypothalamus. Results and discussion Interestingly, chronic LPS treated rats displayed similar sickness behaviour (decreased appetite, low activity level and depressive like behaviour) as acute LPS treated rats. However, distinct chronic inflammatory responses were detected; elevated pro inflammatory cytokines (IL 1β and IFN γ) in the brain, induced local tissue responses (hepatomegaly and decreased fat mass), and hyperglycemia. Surprisingly, no cytokine changes were observed in serum following chronic LPS treatment, indicating compartment specific responses. Conclusion Taken together, chronic LPS administration induced multiple local inflammatory responses and behavioural adaptions. A model of chronic inflammatory sequelae could elucidate molecular mechanism behind psychiatric symptoms and therefore aid in targeting treatment options. 16

18 Prosodi hos deprimerede patienter Nicolai Ladegaard Afdeling Q Afdeling for Depression og Angst, AUH Risskov Affektive lidelser er en af tidens største sundhedsmæssige udfordringer. Forekomsten af affektive lidelser er høj og stigende. Diagnostik og monitorering af psykiske lidelser baseres på kvalitative vurdering af sundhedsfaglige professionelle. Nærværende forskningsprojekt arbejder hen imod at udvikle et elektronisk værktøj, der på baggrund af patienters talemønstre skal understøtte klinikerens vurdering af patientens status. Psykiske lidelser manifesterer sig typisk ved distinkte talemønstre. Optagelser at patienters stemmer behandles via stateof the art metoder inden for signalbehandling. Vha. maskinindlæringsteknikker vurderes symptomer og diagnoser automatisk baseret på små anomalier i talemønsteret (fx den tidslige struktur af tonelejet, pauser og talehastighed). Dette muliggør støtte til klinisk praksis (bl.a. tilbagefaldsforebyggelse) og klinisk forskning i de underliggende mekanismer ved psykiske lidelser. 17

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26 POSTER NR. 1 Probiotic treatment has anti depressant effect independent of diet Anders Abildgaard 1,2, Gregers Wegener 1,Marianne Hokland 3 & Sten Lund 2 1 Translational Neuropsychiatry Unit, Aarhus University (Risskov) 2 Medical Dept. MEA, Aarhus University Hospital (Nørrebrogade) 3 Dept. of Biomedicine, Aarhus University Background The literature suggests a bi directional association between metabolic disorders (type 2 diabetes, metabolic syndrome) and depressive disorder. The gut microbiota may play an important role in both disease entities, and diet is known to alter the gut microbiota composition. Aim Considering the likely existence of a gut brain axis, does probiotic treatment affect glucose metabolism, depressive like behaviour or memory in healthy rats? May probiotic treatment protect against the adverse effects of a high fat diet? Methods 40 male Sprague Dawley rats were fed a high fat or control diet for 10 weeks. Additionally, a probiotic mix (8 lactobacillus/bifidobacteria species) or placebo were administered daily during the last 5 weeks. The animals were subjected to behavioural as well as metabolic tests. Furthermore, cytokine production from anti CD3/28 stimulated blood lymphocytes was measured. Results Independent of diet, probiotic treatment was associated with a marked reduction in depressive like behaviour, but it did not affect memory. Consumption of high fat diet led to increased body weight as well as increased glucose and insulin levels during an oral glucose tolerance test, but probiotic treatment did not affect these measures. Final analyses are still ongoing. Discussion Our findings add perspective to the potentially important role of the gut brain axis and clearly supports the novel concept of psychobiotics. Indeed, the probiotics used in this study should also be validated in a depression model. Nevertheless, our study lends inspiration to further studies into the involved pathophysiological mechanisms. 25

27 POSTER NR. 2 Betydningen af moderens vægt for forekomsten af ADHD og autisme hos børn Christina Hebsgaard Andersen Børne og Ungdomspsykiatrisk Center, Risskov. Attention deficit hyperactivity disorder (ADHD) og autisme spektrum forstyrrelser (autisme) er neuropsykiatriske lidelser, som viser sig i barndommen med alvorlige følger for de ramte børn og deres forældre. Årsagerne til ADHD og autisme er ikke klarlagt, men der menes at være en væsentlig genetisk komponent i lidelserne sandsynligvis i kombination med miljøpåvirkninger. Blandt de miljøpåvirkninger, som er blevet diskuteret, er moderens vægt og vægtstigning. Der er muligvis en sammenhæng mellem moderens vægt i forbindelse med graviditeten og udviklingen af ADHD og autisme hos børnene. Der foreligger en række studier, som viser forskellige resultater, og der er fremsat teorier om årsagssammenhænge i relation til hormonforstyrrelser. I Danmark findes en af de største fødselskohorter i verden med ca deltagere, Bedre Sundhed for Mor og Barn, hvor bl.a. oplysninger om moderens vægt i forbindelse med graviditeten er indsamlet. Børnene i kohorten er i dag mellem 11 og 16 år, og via de danske registre er det muligt at identificere de børn, som er blevet diagnosticeret med ADHD eller autisme. En undersøgelse i kohorten af sammenhængene mellem moderens vægt i forbindelse med graviditeten og senere ADHD eller autisme hos barnet, vil være et unikt studie pga. størrelsen og kvaliteten af de indsamlede data, og det vil kunne tilføre afgørende nyt til den internationale søgen efter årsager til ADHD og autisme. 26

28 POSTER NR. 3 Depression and the risk of severe infections: prospective analyses on a nationwide representative sample. Niklas W. Andersson Afdeling M, AUH Risskov Objective Depression is linked with physical health. Preliminary research suggests an association between depression and subsequent increased risk of infections, yet little is known on this topic. This study investigated the association between depression and risk of various types of infections, including dose response and temporal relations. Methods A historical prospective population based study including 976,398 participants, of whom 142,169 had a history of depression between 1995 and 2012, was conducted using linked Danish registries. Survival analyses were used to estimate the relative risk of infections among those with, compared to those without, depression while adjusting for gender and age. Results Depression was associated with increased risk of a wide range of infections (IRR=1.61, 95% CI= , for any infection). In dose response analysis: the risk of infection was IRR=1.57, 95% CI= at a single depressive episode and IRR=1.97, 95% CI= if having experienced 4 or more depressive episodes. However, only few cases contributed to the analysis on more than 2 depressive episodes and results did not indicate a perfect linear association. There was little evidence of a specific temporal effect but rather a general increased risk of infection subsequent to the onset of depression. Conclusion Present findings suggest the presence of depression may confer increased risk of infection, and that this increased susceptibility is not confined to a discrete time period following the onset of depression. A dose response relationship may be present but further research is needed to further examine and to support the herein presented additional physical health consequences of depression. 27

29 POSTER NR. 4 Ketamine and Neuronal Plasticity of Hippocampus Maryam Ardalan 1,2, Gregers Wegener 2,3, Torsten M. Madsen 4, Jens R. Nyengaard 1 1. Stereology and Electron Microscopy Laboratory, Aarhus University Hospital, Aarhus, Denmark 2. Translational Neuropsychiatry Unit, Aarhus University Hospital, Risskov, Denmark 3. Pharmaceutical Research Center of Excellence, School of Pharmacy (Pharmacology), North West University, Potchefstroom, South Africa 4. Lundbeck A/S, International Clinical Research, Valby, Denmark Background & Aim Depressive disorders are common, serious and associated with enormous morbidity. In this study, design unbiased stereological methods are used to test the neuronal plasticity hypothesis in rat brain hippocampus as one of the main underlying mechanisms for anti depressive effects of the drug Ketamine. The neuronal plasticity hypothesis describes structural and functional plasticity and cellular resilience. This includes the promotion of dendritic growth, axonal sprouting, increased neurogenesis, synaptic remodeling, and new synaptic connections within specific brain regions. Material & method After ketamine injection and perfusion fixation of the rat brains, hippocampus is isolated, straightened out and embedded in 5% agar. The straightened hippocampus is sectioned perpendicular to its longest axis at 65 μm thickness on a vibratome. Two sets of sections are chosen based on a systematic sampling principle and a section sampling fraction of 1/12. There are 8 9 sections in each of the two sets. For examining synaptogenesis in stratum radiatum of CA1 subregion of hippocampus, the length of CA1 stratum pyramidale is measured along the CA2 subicular (CA2 SUB) axis at light microscopy and used as a 1D sampling guide. By use of the physical disector and electron microscopy the numerical density of synapses is estimated. We will divide asymmetric synapses in two spine and shaft synapses. The volume of different subfields of hippocampus is estimated by point counting using the Cavalieri estimator at light microscopy. 28

30 POSTER NR. 5 Toxoplasma gondii seropositvity is positively associated with anxiety and burnout syndrome Cecilie Bay Richter Translational Neuropsychiatry Unit, AU Toxoplasma gondii (TOX) is a common parasite affecting approximately one third of the human population, primarily targeting neurons and causing neuroinflammation. An increasing number of studies are providing evidence that the disease is associated with behavioural changes and psychiatric disease. The objective of this study is to examine TOX seropositivity in a large human population in relation to psychiatric symptoms. A population of 548 participants was initially included and the participants went through a semi structured diagnostic interview (SCAN interview) followed by blood sampling. From this population, a control group (n=158) with no diagnosis of psychiatric disorders was extracted as well as a group consisting of subjects showing symptoms of anxiety (n=106) and burnout syndrome (n=51). Blood serum was examined for IgG antibodies to TOX using ELISA assays. Data were analysed using logistic regression models and show that seropositivity of TOX is positively associated with anxiety (adjusted odds ratio [OR]=2.05; 95% CI, ; p=0.016). In addition, we find an association between seropositivity and burnout syndrome (OR=3.43; 95% CI, ; p<0.001). These data supports the notion that TOX is associated with psychiatric disorders. Our results are consistent with previous reports on an association between TOX and anxiety. Furthermore, we show a positive association between TOX seropositivity and the stress related syndrome, burnout syndrome. 29

31 POSTER NR. 6 Psychopharmacological treatment patterns of bipolar disorder in Denmark Louise Bjørklund Forskningsenhed P, Aarhus Universitetshospital, Risskov The pharmacological treatment of bipolar disorder is complex and often a lifelong effort. This is due to the fact that the treatment depends on the state of the patient (mania, depression, mixed episode) and also because around 90 % of the patients need co prescribing. Antidepressants are used in the treatment of more than half of the Danish patients with bipolar disorder, but not always in conjunction with an antimanic agent, as recommended. It involves a risk of clinical worsening. The aim of the study is to investigate the psychopharmacological treatment patterns of bipolar disorder in Denmark in order to compare treatment patterns with Danish and International guidelines, and to document the consequences of antidepressant use in bipolar disorder with and without concomitant mood stabilizer. Some of the possible consequences to investigate are the risk of affective switching (switch from depression to mania), the risk of suicide and the risk of development of mixed states. The study population consists of all Danish residents treated for bipolar disorder, outpatient or during hospitalization, between 1995 and These people are identified by the Danish Psychiatric Central Research Register where they are registered with an ICD 8/ICD 10 diagnosis of bipolar disorder. The prescription database provides information about the pharmacological use. Potentially, the study will results in better pharmacological treatment of bipolar disorder in Denmark by supporting guidelines with concrete knowledge within the area. 30

32 POSTER NR. 7 Chronic mild stress exposure induces the depression like symptoms in rats and attenuates EDHF like component of endothelium dependent relaxation Elena Bouzinova Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Cardiovascular diseases have high co morbidity with major depression. In the chronic mild stress (CMS) model of depression rats are exposed to chronic unpredictable mild stressors. However, only some rats develop depression like symptoms (including anhedonia which is measured as a reduction in sucrose intake), while others are stress resistant ( resilient ). In the current study, anhedonic rats reduced their sucrose intake after 8 weeks of CMS by 55±7% while the resilient rats did not change their sucrose consumption compared with the baseline ntake. We analyzed endotheliumdependent relaxation of isolated mesenteric small arteries from non stressed, anhedonic, and resilient rats under isometric conditions. There was no difference in acetylcholine induced relaxation of noradrenaline pre constricted arteries from different groups under control (inhibitors free) conditions. L NAME treatment revealed an elevated NOdependent relaxation in arteries from anhedonic rats. Accordingly, enos expression was increased in anhedonic group. Selective inhibition of COX 1 with SC560 revealed similar COX 1 dependent contraction in the three groups. NS398, a selective COX 2 inhibitor, suppressed relaxation stronger in arteries from anhedonic rats. No difference in the expression of COX1 and COX2 was found. Finally, endothelium dependent hyperpolarization (EDH) component of relaxation, sensitive to inhibition by apamin and TRAM, was significantly reduced in anhedonic rats. This was associated with a significant reduction in the expression of intermittent conduction K+ channels. Conclusions Our findings demonstrate that depression like symptoms are associated with reduced EDH like relaxation and elevated significance of NO and COX 2 dependent signals in rat mesenteric arteries. These changes in endothelial function could affect peripheral resistance and organ perfusion in major depression. 31

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