Gene Variants Protect Against Depression Triggered by Childhood Stress

Certain variations in a gene that helps regulate our response to stress may protect adults who were abused in childhood from developing depression, a new study has found.

Almost 15 million U.S. adults have major depression. Scientists believe that a combination of gene variations and life experiences contribute to the disorder. However, the specific genetic factors that contribute to depression have been unclear. Dr. Kerry J. Ressler of Emory University and Dr. Rebekah G. Bradley of the Atlanta VA Medical Center led a team exploring the role of a stress hormone, corticotropin-releasing hormone, that's been tied to depression.

The team focused on a corticotropin-releasing hormone receptor called CRHR1. Receptors act as binding sites, in or on cells, for chemical messengers like hormones that affect cell function. The research was funded by NIH's National Institute of Mental Health (NIMH), National Center for Research Resources (NCRR) and National Institute on Drug Abuse (NIDA), among others.

The scientists first interviewed 422 adults, 97.4% of them African American, with high rates of lifetime trauma and asked them questions about depression and childhood trauma. They also collected their saliva in mouthwash and isolated their DNA. The researchers then examined the variations in their CRHR1 genes.

The results were published in the February 2008 issue of the Archives of General Psychiatry. The team found significant links between several genetic variants in CRHR1 and the effects of childhood abuse. About one-third of the participants had variations in the CRHR1 gene that appear to be somewhat protective against early-life stress. Of the people in the study with a history of child abuse, those with certain variations had only about half the symptoms of moderate to severe depression as others.

The finding was strengthened when the researchers repeated the study in 199 white adults and came up with similar results.

CRH and its receptor are part of a larger hormone system that regulates the response to stress, in part by helping to regulate neurotransmission—the chemical messages through which brain cells communicate with each other. Extreme stress in childhood, caused by factors such as abuse, can hyperactivate this system and have developmental effects that raise the risk of depression when those children grow into adults.

“People's biological variations set the stage for how they respond to different environmental factors, like stress, that can lead to depression,” said NIMH Director Dr. Thomas R. Insel. “Knowing what those variations are eventually could help clinicians individualize care for their patients by predicting who may be at risk or suggesting more precise avenues for treatment.”