|Gene Variants Protect Against Adult Depression
Triggered by Childhood Stress
Finding could one day help identify people at risk
Certain variations in a gene that helps regulate response to stress
tend to protect adults who were abused in childhood from developing
depression, according to new research funded by the National Institute
of Mental Health (NIMH), part of the National Institutes of Health.
Adults who had been abused but didn't have the variations in the
gene had twice the symptoms of moderate to severe depression, compared
to those with the protective variations.
"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 Thomas R. Insel, M.D. "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."
Almost 15 million U.S. adults have major depression. The new report
adds to evidence that a combination of gene variations and life
experiences promote the disorder or protect people from it. Variations
in many genes are thought to be involved, but few of them have
Results of the study were published in the February 4 issue of
the Archives of General Psychiatry by Kerry J. Ressler,
M.D., Ph.D., of Emory University, Rebekah G. Bradley, of the Atlanta
VA Medical Center, and others.
The study also supports previous evidence that a stress hormone,
corticotropin-releasing hormone (CRH), plays a role in depression.
The variations are in a gene that makes a receptor for the hormone.
Receptors are proteins that act as binding sites, in or on cells,
for chemical messengers that affect cell function. The receptor
for CRH is called CRHR1.
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 the system, increasing
risk of depression in adulthood.
"Our results suggest that genetic differences in CRH-mediated
neurotransmission may change the developmental effects that childhood
abuse can have on the stress hormone system — developmental
effects that can raise the risk of depression in adults," said
To conduct their research, scientists interviewed 422 adults,
mostly African American, and tested their DNA. About one-third
of them had the variations in the CRHR1 gene that appear to be
somewhat protective if early-life stress has occurred. Of the people
in the study who had a history of child abuse, those with certain
variations had only about half the symptoms of moderate to severe
depression as those who had more common variations in the same
The finding was strengthened when the researchers repeated the
study in 199 white adults and came up with similar results. In
addition to racial differences, the two groups differed socioeconomically.
The combined findings suggest that the gene variations are protective
across the ethnic groups and socioeconomic levels.
"We know that childhood abuse and early life stress are among
the strongest contributors to adult depression, and this study
again brings to light the importance of preventing them," Ressler
said. "But when these tragic events do occur, studies like
this one ultimately can help us learn how we might be able to better
intervene against the pathology that often follows."
Additional research funding from the National Institutes of Health
was provided by the National Center for Research Resources and
the National Institute on Drug Abuse. Emory University, the Emory
and Grady Memorial Hospital General Clinical Research Center, and
the Burroughs Wellcome Fund also contributed.
For more information about depression, visit the NIMH website
The National Institute of Mental Health (NIMH) mission is to reduce
the burden of mental and behavioral disorders through research
on mind, brain, and behavior. More information is available at
on the NIMH website at http://www.nimh.nih.gov/.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.