Stress and Genes Linked to Suicide Attempts

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stress-and-genes-linked-to-suicide-attempts_medium_smallThe Question
Do genes related to stress contribute to suicide attempts, and are some people more prone to stress-related suicidal behavior?

Background
Stressful life events can trigger suicidal behavior in some people and not others. The stress response known as fight-or-flight is driven by the stress hormone cortisol, which is regulated by a part of the neuroendocrine system called the hypothalamic-pituitary-adrenal (HPA) axis.

The Study
672 family trios (two parents, one child with a severe suicide attempt) provided blood samples and personal information about their history and emotions. Dr. Wasserman studied a variety of genes associated with the HPA axis to see if they tell us anything about the roles of stress and genes in suicide. The specific genes of interest were compared with 519 healthy individuals with no history of a suicide attempt. Wasserman studied stress-related genes and their interaction with stressful environmental factors, such as history of physical assault before or after age 19, and level of lifetime stress. She also included measures of mental health conditions, depressive symptoms, anger, and aggression.

Results

  • The HPA gene CRHR1, which is related to the regulation of stress, was linked to suicidal behavior independent of any specific mental health condition.
  • Different gene-environment interaction (GxE) risk profiles were identified. The gene’s association with suicidal behavior depended on factors such as depressive symptoms, history of physical assault, and lifetime level of stressful life events.
  • The serotonergic gene HTR2A, as well as genes from other neurotransmitter systems (GRIN2B and ODC1), were not strongly linked to suicidal behavior.
  • SAT1, a gene found to be related to death by suicide, was also found to be linked to suicide attempts.
  • The gene AVPR1B was associated with suicidal behavior in people with moderate levels of depressive symptoms, though not with major depressive disorder or anxiety disorder.
  • Gender played a role in some GxE associations, but not all.

Takeaway
As we learn more, we hope to identify genetic profiles for suicide risk that we could measure with a blood test and would indicate a person’s risk of suicidal behavior. We could also use these biomarkers to develop interventions — like gene or talk therapies — to reduce that risk. Personalized interventions would be possible taking factors like gender and personal history into account.

Publications from AFSP grant

  • Ben-Efraim YJ, Wasserman D, Wasserman J, Sokolowski M.  Gene-environment interactions between CRHR1 variants and physical assault in suicide attempts. Genes Brain Behav. 2011 Aug;10(6):663-72. doi: 10.1111/j.1601-183X.2011.00703.x. Epub 2011 Jun 9. PMID: 21605337http://onlinelibrary.wiley.com/doi/10.1111/j.1601-183X.2011.00703.x/pdf
  • Ben-Efraim YJ, Wasserman D, Wasserman J, Sokolowski M. Family-based study of HTR2A in suicide attempts: observed gene, gene × environment and parent-of-origin associations. Mol Psychiatry. 2013 Jul;18(7):758-66. doi: 10.1038/mp.2012.86. Epub 2012 Jul 3. PMID: 22751492http://www.ncbi.nlm.nih.gov/pubmed/22751492
  • Sokolowski M, Ben-Efraim YJ, Wasserman J, Wasserman D. Glutamatergic GRIN2B and polyaminergic ODC1 genes in suicide attempts: associations and gene-environment interactions with childhood/adolescent physical assault. Mol Psychiatry. 2013 Sep;18(9):985-92. doi: 10.1038/mp.2012.112. Epub 2012 Jul 31. PMID: 22850629.
  • Ben-Efraim YJ, Wasserman D, Wasserman J, Sokolowski M. Family-based study of AVPR1B association and interaction with stressful life events on depression and anxiety in suicide. attempts. Neuropsychopharmacology, 2013 Jul; Vol. 38 (8), pp. 1504-11.  doi: 10.1038/npp.2013.49. Epub 2013 Feb 19. PMID: 23422793

Danuta Wasserman, M.D., Ph.D. is the Professor of Psychiatry and Suicidology, Karolinska Institute, Sweden; Head and Founder of National Centre for Suicide Research and Prevention of Mental lll-Health (NASP); and Director for WHO Collaborating Centre for Research, Methods Development and Training in Suicide Prevention.

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