Genetics Shaped by the Environment and Linked to Mental Illness: Heritable and Reversible?

Bechara J. Saab, Ph.D., Expert on mental health research
Bechara J. Saab, Ph.D.

A 2012 NARSAD Young Investigator, Bechara J. Saab, Ph.D., of Brain Research Institute at the University of Zurich, Switzerland, along with several colleagues, have published a fascinating review of evidence showing how environmental influences can lead to the development of mental illnesses. In a review article published in the journal Biological Psychiatry in February, 2013, Dr. Saab and colleagues focus on the ways in which environmental insults―not only things like a mother’s stress or a father’s low self-esteem but also exposure to toxic chemicals in food, air and water, as well as drugs of abuse―translate into chemical changes that affect the way our genes are expressed. The field is referred to as "epigenetics." Other NARSAD Grantees, including Kenneth Kendler, M.D. of Virginia Commonwealth University and Eric Nestler, M.D., Ph.D. of the Icahn School of Medicine at Mount Sinai, have performed pioneering experiments over the past decade demonstrating how the environment affects the “expression” of our genes without altering the actual DNA sequence.

The Zurich team, including Dr. Saab, explain that environmental insults can chemically tag DNA with molecules of methyl, for instance. These changes not only can perturb the way genes in brain cells are expressed, they "propagate across generations.” This has only recently been demonstrated. The Biological Psychiatry paper charts the ways in which these epigenetic responses to the environment can be represented in the sex cells of rodents and humans, such that they increase the risk for behavioral dysfunction not only in the current generation, but for several subsequent generations as well.  

“A transgenerational dimension to how environmental factors may influence epigenetic processes in brain cells and sperm and egg cells adds an important layer of complexity” to the challenge of treating brain disorders, the team reports. But this can actually be good news. Unlike genetic mutations that promote illness, epigenetic changes are reversible. This avoids the need to resort to unproven gene therapy. There are medications now under development, and several already on the market, that can reverse certain epigenetic “marks” that disrupt normal biological function. This work “is still in its infancy,” but indicates a very promising new horizon for the development of effective treatments for psychiatric disorders, they say.