S30.01 - Genetic findings in the HPA-axis in suicide attempters

Abstract

According to a stress-vulnerability model, genetic set-up, as well as environmental exposure to psychological stress, contributes to a person's predisposition for suicidality, as well as to Major Depression (MD). The main neurochemical findings on suicidality have suggested alterations in neurosytems which are usually implicated in MD; a lowered serotonergic (5HT) activity, depletion of the noradrenergic (NA) system and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Whereas the genes of e.g. the 5HT system and of the key NA-biosynthesis enzyme, tyrosine hydroxylase, have been studied extensively in this context the genes in the HPA axis have only begun to be investigated recently.

Our group was the first to study the genetic variation in the CRHR1 gene in connection to depression and stress among suicidal individuals. We reported also findings that genetic variation in a transcription factor of the POMC gene, TBX 19, which is regulated by CRH, showed association and linkage to the anger/hostility personality trait and suicidality. Those results suggest that genetic variation in the CRH-mediated regulation of the HPA axis is a factor of importance in suicidality and, as other have shown as well, for major depression.

During symposiums the results obtained from the replication analyses of single nucleotide polymorphisms (SNPs) in candidate genes, in 1000 family trios with suicide attempter offspring, by using the transmission disequilibrium test both in a two-stages screening/replication sample design and in detailed reanalysis in the entire sample, will be discussed.