Suspected Link Found Between Suicide, Gene Alteration

Life experiences and environmental factors can alter genes in animals and people, the provocative new scientific field of epigenetics is finding (Psychiatric News, March 5).

Moreover, the gene alterations appear often to take place via the biochemical process of methylation, in which a methyl group latches onto a gene and alters its expression.

Methylation of a specific gene—the one that codes for brain-derived neurotrophic factor (BDNF)—has now been found to be significantly more plentiful in the brains of 44 people who committed suicide than in the brains of 33 people who died from other causes.

The finding appeared in the March Archives of General Psychiatry. The study's lead investigator was Lorenzo Chiariotti, M.D., Ph.D., a professor of general pathology at the University of Naples in Italy.

But what could such a link between BDNF gene methylation and suicide mean? Since the degree of methylation of the gene corresponded with lower levels of its messenger RNA, methylation might have disrupted expression of the gene. And such a disrupted expression in turn might have damaged BDNF functions in subjects' brains and thereby made them more vulnerable to suicide. Indeed, other researchers have reported decreased levels of BDNF in the prefrontal cortex of suicide victims.

Further, suicidal behavior has been linked with early traumatic experiences. So it's plausible, Chiariotti told Psychiatric News, that such experiences might lead to BDNF gene methylation, which in turn leads to disrupted BDNF gene expression. Then disrupted BDNF gene expression contributes to BDNF abnormalities, thereby increasing an individual's suicide susceptibility later in life.

The good news about gene methylation, however, is that it is potentially reversible. So if a drug were found that reverses BDNF gene methylation, it might be given to patients at high risk of suicide and might help keep them from committing suicide, Chiariotti suggested, but “at present, drugs able to selectively demethylate specific genes have not been discovered.”

Nonetheless, he noted, “the possible use of unspecific ‘epigenetic drugs’ is currently under evaluation for treatment of different psychiatric conditions associated with specific genes' hypermethylation.”

Epigenetic research is also leading to treatment advances in medical fields other than psychiatry. In 2004, the Food and Drug Administration approved a cancer drug based on epigenetic principles. It is called Vidaza and is made by the Pharmion Corporation. It exerts its effects by removing marks of methylation from genes that counter tumor development.

The study was funded by Regione Campania (the Italian government region in which Naples is located) and by the Italian Ministry of University and Research.

An abstract of “Increased BDNF Promoter Methylation in the Wernicke Area of Suicide Subjects” is posted at <http://archpsyc.ama-assn.org/cgi/content/abstract/67/3/258>.