The Oct 15 edition of Biological Psychiatry published two articles on the epigenetics of suicide. Typically, suicide in the young and old is blamed on childhood abuse, maltreatment and related “environmental” stressors. It’s believed that suicidal tendencies stem from the frontal cortex and hippocampus. Obviously, everything leads back to a gene or two at some point, making, as my PI would say, “this hypothesis somewhat lacking in explanatory power.”
Two recent studies show evidence in the depressed suicidal brain of what the authors like to call “epigenetic” mechanisms, defined here as “a chemical modification of the DNA and/or the histone proteins associated with it.” In this case, the authors believe a small but vital stretch of DNA which regulates codons, or DNA sequences that code for proteins, is being both under and over expressed in the brains of depressed suicide victims. This region regulates the production of a neurotransmitter protein, GABA-A a1, known for its calming affect–think Prozac. The confusion lies not at the level of the gene, or even the protein, but at higher levels: divisions and subdivision of the prefrontal cortex where these expression levels are collated and the possible conflation of depression with suicide.
Another confounding factor is the timing of expression levels for this regulatory region. If the autopsied frontal lobe of adult suicide victims is chemically different than what it was preceding the suicidal state, then the expression levels could be a result of the suicidal state and not the cause. However, if expression levels were previously altered–brought on by an early childhood psychological trauma that led to a mood disorder for example–then the scientists would be on to something. In other words, do these expression levels act as a genetic suicide note? There is some evidence that this the case, since a similar region regulating similar genes in the frontal cortex is under constant epigenetic alteration throughout the brain’s development. A commentary in Biological Psychiatry on the two papers:
Therefore, one might speculate that alterations in DNA methylation and other types of chromatin modifications eventually could emerge as key events in a pathophysiological cascade originally triggered by adverse events and various stressors in childhood and adolescence, then impairing GABAergic and other neurotransmission and significantly increasing the risk for suicidal behaviors in the context of mood disorders or schizophrenia and other psychiatric disease.
Of course, the larger issue at hand is the brain itself, a three-dimensional, highly intricate and interconnected wet-works of microscopic data processors encased in a hard shell, and how to get at it. Unlike most behavioral research, this one is unique in that it takes a direct approach to the brain–as opposed to those dime-a-dozen MRI studies–by grinding up bits of the newly dead parts.
All in all, the argument for epigenetics seems kind of lazy since the authors haven’t shown heritability in chromatin modification in the gene they’re studying.