Epigenetics Might Provide Clues for Mood Disorders

A fascinating study from McGill University in Montreal suggests the answer could be yes. Researchers showed that in rats, differential maternal behavior towards pups influences their stress sensitivity in adulthood. Pups of better rat mothers showed differences in DNA methylation and histone marks compared to those of less attentive moms at the site of a key stress system gene. Treatment with a drug that changed the epigenetic marks abolished the maternal effect on stress sensitivity, supporting a causal role for epigenetics.

Another study, from the University of Texas Southwestern Medical Center, provides evidence that epigenetic changes can be induced by stress in adulthood. Adult mice exposed to highly aggressive neighbors become socially avoidant, defeated, and subordinate, in some ways mimicking human depression. Researchers showed that these mice developed histone changes in a depression-related gene, and that these changes were reversed by the antidepressant imipramine.

There is evidence that other antidepressants — Parnate and Prozac — can also alter histone marks. And giving mice a histone-altering chemical produces an antidepressant-like effect. One of the leading bipolar disorder medications, valproic acid, influences histones as well.

Defeating the Black Dog

At the Johns Hopkins Epigenetics Center, we are investigating epigenetic variations that might play a role in stress, depression, and bipolar disorder. One of our tools is a microarray, sometimes called a chip, which is about the size of your hand, and has 2.1 million microscopic pieces of DNA on it.

When DNA from a person or a mouse is placed on it, the chip can detect methylation across nearly every gene in the mix, all at the same time. The lead developer of this tool, center director Andrew Feinberg, named it CHARM, an acronym, because Baltimore, where Johns Hopkins is located, has been optimistically dubbed "Charm City."

There is ample reason to be optimistic that advances in our understanding of the epigenetics of mood disorders will ultimately lead to better treatments. As Winston Churchill, who suffered from depression himself, said: "For myself I am an optimist — it does not seem to be much use being anything else."

Dr. James Potash is an associate professor of psychiatry and co-director of the Mood Disorders Program at the Johns Hopkins School of Medicine in Baltimore, Maryland. If you have questions or comments, please email at moods@jhu.edu. To participate in our genetic and clinical studies, call 1-877-MOODS-JH.

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