Genetic Investigation of Suicide Attempt and Suicide

Genetic investigation of suicide attempt and suicideA number of studies suggest that there are heritable components of both suicidal behaviour and suicide-related mental-illnesses such as anxiety disorders, depression, alcohol and drug abuse. The GISS research project (Genetic Investigation of Suicide Attempt and Suicide) conducted at NASP aims at shedding light on these aspects of suicide, using a unique database of 660 nuclear families with suicide attempter children (so-called trios), as well as a control-sample of 519 non-suicidal, healthy volunteers. The dataset includes both DNA and psychometric data for all members, and the family-based structure permit association analyses which are robust to confounding by populations stratification.

Our main findings up to date relate to single-nucleotide polymorphisms in several candidate genes, genes which are of importance for the normal structure and function of the human brain. One of the aims of GISS is to investigate how environmental stress may cause acute or chronic dysregulation of biological stress-responsive systems, and subsequently affect the suicidality of certain subjects (but not others). We showed that the different parts of the CRHR1 gene, which is a key regulator of the major stress-responsive system, the hypothalamic-pituitary-adrenal (HPA) axis driving the secretion of stress-hormone cortisol, associated with suicide attempts through a rather complex pattern of gene-environment interactions (GxEs) in our sample, involving e.g. childhood/adolescence physical assaults or cumulative exposure to stressful life events throughout life. Interestingly, the HPA axis has also been shown by others to be dysregulated prior to suicides as well as in suicide-related psychopathologies. In line with the polygenetic diathesis of complex outcomes such as suicidal behaviors, other genes observed to associate in our sample included e.g. the axonal guidance gene SLIT2 and the glutamatergic receptor GRIN2B. We are in the process of analyzing results from a genome-wide scan, which will give more insights into the overall polygenetic etiology of suicidality, including the role of GxEs in this context.

These and other findings emanating from GISS increase our understanding about interplay between fundamental neurobiological mechanisms with environmental factors regarding suicidal behaviors and related psychopatologies, pinpointing combinations of genes and environments of importance in certain suicidal subjects. Such knowledge could in the future be used to e.g. enhance the specificity of biomarkers being yet only partially predictive of suicidal behaviors (e.g. cortisol response), or to better define an underlying probability distribution for suicidal behaviors in general. This has potential to become a useful complement to guiding suicide prevention and intervention efforts, either in the clinical settings or in public health.

Related publications:

Gene-environment interactions between CRHR1 variants and physical assaultphysical assault in suicide attempts
Genetics of HPA-axis, depression and suicidality
The 2009 Nobel conference on the role of genetics in promoting suicide prevention and the mental health of the population
Association of polymorphisms in the SLIT2 axonal guidance gene with anger in suicide attempters
Depression in suicidal males: genetic risk variants in the CRHR1 gene.
Nature and nurture in suicidal behavior, the role of genetics: some novel findings concerning personality traits and neural ...
The CRHR1 gene: a marker for suicidality in depressed males exposed to low stress
Association of the serotonin transporter promotor polymorphism with suicide attempters with a high medical damage.
Genetic variation in the hypothalamic-pituitary-adrenocortical axis regulatory factor, T-box 19, and the angry/hostility ...
The serotonin 1A receptor C(-1019)G polymorphism in relation to suicide attempt.

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Marcus Sokolowski