The Epigenetics of Mental Illness

Mental disorders like depression will likely affect 1/6 of Americans at some point in their life. That probability might be higher if you’re a Cleveland sports fan, but seriously, with mental illnesses affecting hundreds of millions of people globally each year, we’re glad to see an increasing focus on the epigenetics of these disorders. In a nice review article in the Journal of Proteome Research, Mariana Plazas-Mayorca and Kent Vrana at the Penn State College of Medicine highlight recent evidence illustrating the epigenetic changes in…


DNMT3b is often upregulated in the frontopolar cortex of suicide victims which might explain the hypermethylation in gamma-aminobutyric acid type A (GABA-A) receptor’s promoter. GABA-A is often under-expressed in depressed patients.



Brain mRNA expression levels of reelin, a protein pinned in schizophrenia, are reduced and inversely correlate with DNMT1 in diagnosed patients possibly indicating DNMT1 is responsible for reelin promoter hypermethylation. HDAC treatment increased the promoter methylation suggesting histone acetylation may be in on the act too.

Drug Addiction

Even small doses of cocaine (or “chewing gum” for the Paris Hilton supporters out there) have been found to drive significant changes to the tails of several histones including a boost in histone H4 acetylation which activates genes involved in cocaine-related behaviors.

Embrace the Proteome

Because causes of neuropsychiatric disorders is currently poorly understood, Plazas-Mayorca and Vrana use the rest of the review to make the case for including proteomic characterizations in genetic investigations to capture the dynamic interplay between genes and the environment. “Proteomic technologies have greatly facilitated the study of epigenetic mechanisms,” says Plazas-Mayorca. “The study of neuropsychiatric disorders is just starting to benefit from the applications of such technologies.”

There’s a lot covered in this one so when you’re ready to brush up on the epigenetics in mental illness or mull over the proteomic options to incorporate into your next experiment, check out Journal of Proteome Research, August 2010