Vienna Study on Genetics of Suicidal Behaviour in Affective Disorders

The proposed "Vienna Study on Genetics of Suicidal Behaviour in Affective Disorders" study is to our knowledge the first genetic study designed to investigate suicidal behaviour in affective disorder patients as the primary phenotype prospectively. In order to explore the aetiology of suicidal behaviour and identify potential diagnostic biomarkers, we will apply a combined genetic, epigenetic and gene expression approach to provide us a unique integrative framework for the investigation of the multifactorial aetiology of suicidal behaviour. We plan to collect detailed phenotypic information (including three validated suicidality questionnaires), blood samples (for genetic, epigenetic and gene expression analyses), as well as serum samples (to investigate protein levels) of 840 affective disorder patients suffering from either major depressive disorder (MDD, approximately 420 patients) or bipolar affective disorder (BPD, approximately 420 patients). Sample collection will be performed at the "Department of Psychiatry and Psychotherapy" of the Medical University Vienna and at the "Landesklinikum Donauregion Tulln" in lower Austria. While some prior investigations on suicidal behaviour compared suicide attempters with healthy comparison subjects, we elected instead to contrast suicidal behaviour with non-suicidal behaviour among affective disorder patients, which will allow us to distinguish genes conferring suicide risk beyond that conferred by the affective disorders itself. Since we don`t have statistical power for hypothesis-free genome-wide association, we will investigate a selection of serotonergic, neurotrophic, noradrenergic and HPA-axis candidate genes, identified based upon previous reports on association with suicidal behaviour. Nevertheless, the sample will be provided for future large-scale association studies (including genome-wide association and next-generation sequencing studies) investigating suicidal behaviour genetics and epigenetics in the context of national and international collaborations. In a second stage (not part of the current proposal), we aim to follow-up individuals included in the current study by annual telephone interviews within the next 10 years, obtaining updated information on mental health and suicidal behaviour. Since part of the patients might have committed suicide when establishing contacts at a later point, the proposed study will possibly allow powerful research into genetics of completed suicide.

The Vienna Study on Genetics of Suicidal Behaviour in Affective Disorders (VieSAD) was designed to investigate suicidal behaviour in affective disorder patients. Thus, while previous studies were not primarily designed to address suicidality, the detailed definition of suicidal behaviour is the major strength of the study. Besides, among other information, data on life events and childhood trauma were collected, allowing to investigate their influence on suicidal behaviour depending on the individuals genotype. We collected blood samples and extensive diagnostic information of 846 patients suffering from affective disorders (unipolar depression and bipolar affective disorder). Approximately two thirds of the patients included (65.6%) were females, 34.4% were males. Using six different questionnaires, we assessed both actual suicidal risk and lifetime suicidality, and created six suicidality categories, allowing both dimensional (extent of suicide risk) and categorical (e.g. suicide attempt yes/no, suicide risk yes/no) analyses. We investigated, among others, the impact of childhood trauma on suicide attempts in affective disorder patients (Bernegger et al. 2015), finding that female suicide attempters showed significantly higher (p<0.001) childhood trauma scores in comparison to non-suicidal controls. In addition, females with a history of self-harming behaviour had significantly higher (p<0.001) childhood trauma scores. In contrast, these associations were not found in males. The COMT (catecholamine-O-methyltransferase) gene has been known to contribute to the aetiology of neuropsychiatric disorders such as depression. We found a significant association with suicide attempt (p=0.003) (Bernegger et al. 2017), and extent of suicide risk (Schosser et al, in preparation). We further found that COMT gene expression was significantly decreased in females, whereas increased oxytocin gene expression was observed in females with suicidal ideations (Kienesberger et al., in preparation). Since hypothalamus-pituitary-adrenal-axis (HPA-axis) is closely involved in the development of affective disorders, we investigated, among others, the CRHR1 (corticotropin-releasing hormone receptor 1) gene, finding no association with previous suicide attempts in affective disorder patients. However, we found an association of CRHR1 polymorphisms with suicide attempt in those that had experienced childhood trauma (Ludwig et al. 2018).