Exposure to childhood maltreatment increases the risk for most psychiatric disorders as well as many negative consequences of these conditions. This new study, by Dr. Gustavo Turecki and colleagues at McGill University, Canada, provides important insight into one of the most extreme outcomes, suicide.
“In this study, we expanded our previous work on the epigenetic regulation of the glucocorticoid receptor gene by investigating the impact of severe early-life adversity on DNA methylation,” explained Dr. Turecki. The glucocorticoid receptor is important because it is a brain target for the stress hormone cortisol.
The researchers studied brain tissue from people who had committed suicide, some of whom had a history of childhood maltreatment, and compared that tissue to people who had died from other causes. They found that particular variants of the glucocorticoid receptor were less likely to be present in the limbic system, or emotion circuit, of the brain in people who had committed suicide and were maltreated as children compared to the other two groups.
This study also advances the understanding of how the altered pattern of glucocorticoid receptor regulation developed in the maltreated suicide completers. The authors found that the pattern of methylation of the gene coding for the glucocorticoid receptors was altered in the suicide completers with a history of abuse. These DNA methylation differences were associated with distinct gene expression patterns.
Since methylation is one way that genes are switched on or off for long periods of time, it appears that childhood adversity can produce long-lasting changes in the regulation of a key stress response system that may be associated with increased risk for suicide.
“Preventing suicide is a critical challenge for psychiatry. This study provides important new information about brain changes that may increase the risk of suicide,” said Dr. John Krystal, Editor of Biological Psychiatry. “It is striking that early life maltreatment can produce these long-lasting changes in the control of specific genes in the brain. It is also troubling that the consequences of this process can be so dire. Thus, it is important that we continue to study these epigenetic processes that seem to underlie aspects of the lasting consequences of childhood adversity.”
The article is “Differential Glucocorticoid Receptor Exon 1B, 1C, and 1H Expression and Methylation in Suicide Completers with a History of Childhood Abuse” by Benoit Labonte, Volodymyr Yerko, Jeffrey Gross, Naguib Mechawar, Michael J. Meaney, Moshe Szyf, and Gustavo Turecki (doi: 10.1016/j.biopsych.2012.01.034). The article appears in Biological Psychiatry, Volume 72, Issue 1 (July 1, 2012), published by Elsevier.
The authors’ affiliations, and disclosures of financial and conflicts of interests are available in the article.
John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.