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Genes Brain Behav. 2008 Feb;7(1):14-9. Epub 2007 Mar 21.

The CRHR1 gene: a marker for suicidality in depressed males exposed to low stress.

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The National and the Stockholm County Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), the Department of Public Health Sciences, Karolinska Institute (KI), Stockholm, Sweden.


The risk of suicide, which causes about 1 million deaths each year, is considered to augment as the levels of stress increase. Dysregulation in the stress response of the hypothalamic-pituitary-adrenocortical (HPA) axis, involving the corticotrophin-releasing hormone (CRH) and its main receptor (CRHR1), is associated with depression, frequent among suicidal males. Here we have analyzed single nucleotide polymorphisms (SNPs) in these genes, in family trios with suicide attempter offspring (n = 542), by using the transmission disequilibrium test both in a two-staged screening/replication sample design and in detailed reanalysis in the entire sample. Stratification based on the levels of lifetime stress showed reproducible association and linkage of an SNP in the CRHR1 gene (rs4792887) to suicide attempters exposed to low levels of stress (P = 0.002), among whom most males were depressed (P = 0.001). The identified allele may represent a part of the genetic susceptibility for suicidality by increasing HPA axis activity upon exposure to low levels of stress.

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