Suicide Gene Identified




Suicidal behavior is a leading cause of death and disability in the United States. Suicide is influenced by a variety of factors, including psychological, social, moral, political, and economic influences. Heredity has also been linked to suicidal thoughts and actions. Now, new evidence suggests that suicide attempt is linked to a specific gene.

In 2007, the most recent year with available data, suicide was the 11th leading cause of death in the United States, claiming nearly 35,000 lives (Europe has it worse). The total cost of suicidal behavior (fatal and nonfatal outcomes) was approximately $33 billion in 2000. The suicide rate for males is roughly four times higher than it is for females. Beginning in adolescence, suicide rates rise steadily with increasing age and peak among the 40- to 54-year-old age group. Suicide rates decline in older populations.

No one cause is linked to suicide, but self-directed harm has been associated with environmental and genetic influences. In particular, substance abuse disorders, depressive disorders, and bipolar disorder are linked to inherited conditions and associated with an increased risk of suicide. The present study, published in Molecular Psychiatry, reports an association between attempted suicide and a gene on chromosome 2, substantiating the heritable component of suicidal behavior.

The study evaluated the entire genomes of patients with bipolar disorder who had attempted suicide (n=1201) and those who had not (n=1497). In total, there were more than 2500 regions located on various chromosomes that showed significant associations with suicidal behavior. The strongest association was with a region on chromosome 2 containing the ACP1 gene. This gene encodes for a signaling protein (tyrosine phosphatase) produced in the brain. Alterations in this gene promote the up-regulation of signaling proteins that influence cell survival and synaptic plasticity; it is also linked to immune system function and carcinogenesis. Tyrosine phosphatase also decreases the activation of a signaling pathway that is activated by lithium. (Lithium is used to treat bipolar disorder and has antisuicidal properties.) In people who have attempted or completed suicide, expression of this gene is high.

Most suicide prevention efforts focus on counseling, education, and clinical intervention of disorders known to increase suicidal behavior. Identifying specific genes that increase susceptibility to suicide could lead to the development of novel, gene-targeted therapies for suicide prevention. Larger samples sizes including different populations are needed to confirm these findings and direct therapies toward individuals predisposed to suicide.

References

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Cui H, Supriyanto I, Sasada T, Shiroiwa K, Fukutake M, Shirakawa O, Asano M, Ueno Y, Nagasaki Y, & Hishimoto A (2011). Association study of EP1 gene polymorphisms with suicide completers in the Japanese population. Progress in neuro-psychopharmacology & biological psychiatry PMID: 21447366

Mahon PB, Stütz AM, Seifuddin F, Huo Y, Goes FS, Jancic D, Judy JT, Depaulo JR Jr, Gershon ES, McMahon FJ, Zandi PP, Potash JB, & Willour VL (2010). Case-control association study of TGOLN2 in attempted suicide. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 153B (5), 1016-23 PMID: 20468057

Perlis RH, Huang J, Purcell S, Fava M, Rush AJ, Sullivan PF, Hamilton SP, McMahon FJ, Schulze TG, Potash JB, Zandi PP, Willour VL, Penninx BW, Boomsma DI, Vogelzangs N, Middeldorp CM, Rietschel M, Nöthen M, Cichon S, Gurling H, Bass N, McQuillin A, Hamshere M, Wellcome Trust Case Control Consortium Bipolar Disorder Group, Craddock N, Sklar P, & Smoller JW (2010). Genome-wide association study of suicide attempts in mood disorder patients. The American journal of psychiatry, 167 (12), 1499-507 PMID: 21041247

Serafini G, Pompili M, Innamorati M, Giordano G, Tatarelli R, Lester D, Girardi P, & Dwivedi Y (2011). Glycosides, depression and suicidal behaviour: the role of glycoside-linked proteins. Molecules (Basel, Switzerland), 16 (3), 2688-713 PMID: 21441870

Willour VL, Seifuddin F, Mahon PB, Jancic D, Pirooznia M, Steele J, Schweizer B, Goes FS, Mondimore FM, Mackinnon DF, The Bipolar Genome Study (BiGS) Consortium, Perlis RH, Lee PH, Huang J, Kelsoe JR, Shilling PD, Rietschel M, Nöthen M, Cichon S, Gurling H, Purcell S, Smoller JW, Craddock N, Depaulo JR Jr, Schulze TG, McMahon FJ, Zandi PP, & Potash JB (2011). A genome-wide association study of attempted suicide. Molecular psychiatry PMID: 21423239

Willour VL, Zandi PP, Badner JA, Steele J, Miao K, Lopez V, MacKinnon DF, Mondimore FM, Schweizer B, McInnis MG, Miller EB, Depaulo JR Jr, Gershon ES, McMahon FJ, & Potash JB (2007). Attempted suicide in bipolar disorder pedigrees: evidence for linkage to 2p12. Biological psychiatry, 61 (5), 725-7 PMID: 17046723

Jennifer Gibson, PharmD

Jennifer Gibson, PharmD, is a practicing clinical pharmacist and medical writer/editor with experience in researching and preparing scientific publications, developing public relations materials, creating educational resources and presentations, and editing technical manuscripts. She is the owner of Excalibur Scientific, LLC.
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