Gene Mutations Associated With Suicide Risk Among Depression Patients

/ Author:  / Reviewed by: Joseph V. Madia, MD

Single mutations in genes involved with nerve cell formation and growth appear to be associated with the risk of suicide among individuals with depression, according to a report to appear in the April issue of Archives of General Psychiatry.
An estimated 10 to 20 million suicides are attempted each year around the world, and 1 million are completed. Patients with psychiatric disorders are more likely to attempt suicide, and those patients with depression or other mood disorders are at higher risk. "Twin and family studies suggest that suicide and suicide attempts are heritable traits and likely part of the same phenotype, with completed suicide and suicide attempts clustering in the same families," the authors write. "The genetic risk factors for suicide appear to be independent from the underlying psychiatric disorder."

Martin A. Kohli, Ph.D., of the John P. Hussman Institute for Human Genomics in Miami, and colleagues investigated genetic variants among 394 depressed patients, including 113 who had attempted suicide, and 366 matched healthy control participants. The authors then replicated their results in 744 German patients with major depressive disorder (152 of whom had attempted suicide) and 921 African American non-psychiatric clinic patients (119 of whom had attempted suicide).

The researchers investigated single-nucleotide polymorphisms (SNPs), or variants in a single base pair along a strand of DNA, in two genes associated with the neurotrophic system, which produces proteins involved in nerve cell growth. Five SNPs appeared significantly more common among individuals with a history of suicide attempts. Carriers of the three most significant markers had a 4.5-fold higher risk of attempting suicide than those participants who carried none of the three mutations.

"The facts that the genetic associations with suicide attempts were stronger when comparing depressed patients with suicide attempts versus depressed patients without suicide attempts than with healthy control subjects and that these SNPs were not associated with major depressive disorder suggest that these associations are specific to suicide attempts," the authors write, and not linked to depression in general.

"This supports the large body of evidence that dysfunctional neurotrophic signaling might be involved in the pathophysiology of suicidal behavior," they conclude.

This study is supported by a grant from the Exzellenz-Stiftung of the Max Planck Society and by a grant from the National Genome Research Network, Federal Ministry of Education and Research.

Jann Ingmire

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Review Date: 
September 21, 2010