Genetics of aggression-related traits as risk factors for suicidal behavior

The risk of suicide-related behavior is supposed to be determined by a complex interplay of sociocultural factors, psychiatric history, personality traits, and genetic vulnerability. This view is supported by adoption and family studies indicating that suicidal acts have a genetic contribution that is independent of the heritability of Axis I and II psychopathology. Neurobiological studies have shown that serotonergic dysfunction is implicated in suicidal behaviors. Additionally aggression-related traits are mediated by the serotonergic system. Since both, aggression related traits and serotonergic activity are partially heritable and correlate inversely, variations in genes of the serotonergic system might then, to some extent, account for variations in aggression-related behavior. For that reasons we have initiated a large scale case control genetic association study which comprises of 250 suicide attempters and 1900 healthy volunteers and investigated the role of a comprehensive set of serotonergic candidate genes. Additionally we conducted a large-scale gene expression analysis using cDNA-microarrays to identify new candidate-genes for suicide. We found several genes to be differentially expressed in the orbitofrontal cortex of suicide completers. Cross-validation experiments using quantitative RT-PCR validated 9 genes so far. These genes have been genotyped in our patients and controls and associations with suicidal behavior and intermediate phenotypes will be presented.