How Adversity Changes the Brain—and Its Genes

The genetics of experience: how adversity sets the stage for suicide

Posted Oct 27, 2008

How does adversity translate into depression? In particular, how does life experience make a person suicidal? This month, scientists opened a new window on mood disorder in the brain, using the tools of a discipline we have been tracking on this blog, epigenetics. The study shows causation in a direction that is only just becoming familiar: harmful experiences can give rise to harmful genetics.

Michael O. Poulter, of Carleton University in Ottawa, along with Canadian and Hungarian colleagues, looked at the brains of depressed patients who had committed suicide and contrasted them with brains of patients who had died suddenly of other causes. The postmortem tissue differed in terms of the ways genes had been altered during life. In the suicides, the brain tissue from the pre-frontal cortex showed a methylation of DNA related to parts of neurons that handle GABA, a neurotransmitter important in mood regulation. The study actually looked directly at the related messenger RNA; the RNA changes correlated with deficits in the enzymes and receptors downstream - that is to say that the methylation impaired brain structure and functioning.

Readers of this blog may recall that in the face of adversity, certain genes in the brain will be methylated, effectively shutting them down. Once they occur, these changes are difficult to reverse, creating stable disabilities, perhaps for the remainder of a life. Bad experience gives mammals a different genetics and different brains.

What remains unknown is when the alteration occurred in the brains Poulter examined. In this column, we have discussed research on rodents in which stress during pregnancy caused in changes in the epigenetics of offspring. A recent postmortem study of suicidal men and women who had been abused in childhood found changes in RNA, via methylation of DNA, in the hippocampus. But research on a GABA receptor (in this case, in the temporal lobe) similar to the one Poulter looked at has found "progressive DNA methylation increases across the full lifespan." The editorial writer in Biological Psychiatry, where the latest article appeared, links these changes with similar ones in suicide victims that affect RNA coding for serotonin receptors, changes opposed by the administration of serotonergic antidepressants; the suggestion is that an integrated view of DNA and RNA editing—that is to say epigenetics—may create a new understanding of mood disorder and its potential treatment.

This line of research is in its infancy. And though the two states can overlap, suicidality is not the same as mood disorder. But for now, it looks as if harmful experiences at any stage of life can cause long-lasting impairments in genes and gene expression in the very parts of the brain—prefrontal cortex, hippocampus, temporal lobe—implicated in depression.

As with other evidence we have discussed here, this new line of findings suggests that depression caused by stress simply is depression—indeed, that trauma can create the genetics of depression in people who were not born with them. This research undercuts the notion that "caused" depressions should be classed as mere sadness, as well as the idea that depression triggered by specific sorts of harm, such as loss of a loved one, should be placed in a separate category. However you get there, once you have the genetics of mood disorder or suicidality, you are at grave risk.

About the Author

Peter D. Kramer is a psychiatrist and author. His books include Against Depression and Listening to Prozac. His new book, Ordinarily Well, will be published by Farrar, Straus and Giroux in June.

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