Some Adults Abused As Children Carry Gene Which
Protects Them From Depression
February 5, 2008
Some forms of a gene that controls the body's response to stress hormones appear
to protect adults who were abused in childhood from depression, psychiatrists
have found.
People who had been abused as children and who carried the most protective forms
of the gene, called corticotropin-releasing hormone receptor one (CRHR1), had
markedly lower measures of depression, compared with people with less protective
forms, the researchers found in a recent study.
The findings could guide doctors in finding new ways to treat depression in
people who were abused as children, says senior author Kerry Ressler, MD, PhD,
assistant professor of psychiatry and behavioral sciences at Emory University
School of Medicine.
"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," Dr. Ressler says. "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."
The results of the study, performed on two separate racially and economically
distinct groups from the Atlanta area, were published in the February 4 issue of
the Archives of General Psychiatry.
The first and second authors of the study are Rebekah Bradley, PhD, at the
Atlanta Veterans Affairs Medical Center and Elisabeth Binder, MD, PhD, at Emory
University and the Max Planck Institute for Psychiatry in Munich, Germany. Dr.
Ressler, who also is a scientist at Emory's Yerkes National Primate Research
Center and a member of the Center for Behavioral Neuroscience, and Joseph
Cubells, MD, PhD, associate professor of human genetics at Emory University
School of Medicine, are co-senior authors.
The team's research illustrates how life events and genetic influences can
combine in complex ways, leading to depression or protection from it. Almost 15
million U.S. adults have major depression, according to the National Institute
of Mental Health.
The study also supports previous evidence that corticotropin-releasing hormone (CRH)
and related hormones play a role in depression. Other studies have found
increased levels of CRH and altered levels of its receptor in the brains of
patients with depression.
Some pharmaceutical firms are testing compounds that block CRHR1 as potential
medications for depression.
The receptor for a hormone acts like a receiver or radar dish for messages sent
between cells. CRH stimulates the pituitary gland to release another hormone,
adrenocorticotropin, which in turn induces the release of cortisol from the
adrenal cortex.
Extreme stress in childhood can over-activate this cascade of hormones,
increasing the risk of depression in adulthood, Dr. Ressler says.
"Our results suggest that genetic differences in signals mediated by CRH
may amplify or soften the developmental effects that childhood abuse can have --
effects that can raise the risk of depression in adults," he says.
In the study, scientists began by interviewing more than 470 adults and testing
their DNA, looking for alternative spellings or SNPs (single nucleotide
polymorphisms) in several parts of the CRHR1 gene.
This first group was mostly black and a majority had a monthly income less than
$1,000. The researchers measured their symptoms of depression and had them
answer questionnaires about childhood trauma. Their responses were categorized
as low, mild, moderate and severe.
Overall, people with a history of moderate or severe child abuse had depression
symptoms that averaged about double the level of those with low or mild child
abuse scores.
Roughly 30 percent of the group had variations in the CRHR1 gene that together
appeared to be protective if moderate to severe abuse had occurred. People who
had inherited two copies of the most protective forms of the gene, or "haplotypes,"
had average depression symptoms that were about half those of people who had not
inherited those haplotypes. A haplotype comprises several SNPs that frequently
appear together.
These differences in depression symptoms were only seen in people with histories
of moderate to severe abuse; depression levels were not significantly different
in people with low to mild abuse.
The most significant SNPs appear in the part of the gene preceding the region
that encodes the receptor protein, suggesting that the variations may affect its
regulation rather than the composition of the protein, the authors say.
The findings were strengthened when the researchers repeated the study in 199
white, middle-income adults and came up with similar results, suggesting that
the genetic variations act in a way that is independent of ethnic background or
economic status.
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Article adapted by Medical News Today from original press release.
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Research funding came from the National Institute of Mental Health, the National
Centers for Research Resources and the National Institute of Drug Abuse. Emory
University's Women's Mental Health Program, the Emory and Grady Memorial
Hospital General Clinical Research Center, and the Burroughs Wellcome Fund also
contributed.
Source: Kathi Baker
Emory
University
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