|Gene Variant Increases Risk for Alcoholism Following
Girls who suffered childhood sexual abuse are more likely to develop
alcoholism later in life if they possess a particular variant of
a gene involved in the body’s response to stress, according to
a new study led by researchers at the National Institute on Alcohol
Abuse and Alcoholism (NIAAA), part of the National Institutes of
Health (NIH). The new finding could help explain why some individuals
are more resilient to profound childhood trauma than others.
“With this study we see yet again that nature and nurture often
work together, not independently, to influence our overall health
and well-being,” says NIH Director Elias A. Zerhouni, M.D.
“This finding underscores the central role that gene-environment
interactions play in the pathogenesis of complex diseases such
as alcoholism,” adds NIAAA Director Ting-Kai Li, M.D. A report
of the study appears in the June 26, 2007 advance online publication
of Molecular Psychiatry.
Previous studies have shown that childhood sexual abuse increases
the risk for numerous mental health problems in adulthood. However
not all abused children develop such problems, a likely indication
that genetic factors also play a role. Recent studies have linked
the monoamine oxidase A (MAOA) gene with adverse behavioral outcomes
stemming from childhood mistreatment.
“MAOA is an enzyme that metabolizes various neurotransmitters
that regulate the body’s response to stress,” explains first author
Francesca Ducci, M.D., a visiting fellow in NIAAA’s Laboratory
of Neurogenetics in Bethesda, Maryland. DNA variations occur within
a regulatory area — the MAOA-linked polymorphic region (MAOA-LPR) — of
the MAOA gene. Two such MAOA-LPR variants occur
most frequently and result in high or low MAOA enzyme activity.
In a recent study, researchers found that maltreated boys who possessed
the low activity MAOA-LPR variant were more likely to
develop behavior problems than boys with the high activity variant.
“Our aim was to test whether this low activity variant influences
the impact of childhood sexual abuse on alcoholism and antisocial
personality disorder (ASPD) in women,” says Dr. Ducci.
She and her colleagues analyzed DNA samples from a group of American
Indian women living in a community in which rates of alcoholism
and ASPD are about six times higher than the average rates among
all U.S. women. Childhood sexual abuse is also prevalent in this
population, reported by about half of the women in the community,
compared with a U.S. average of 13 percent.
“The high rates of sexual abuse and alcoholism in this population
make it particularly suitable for studying the interaction of genes
and stressful environmental exposures,” explains senior author
David Goldman, M.D., chief of the NIAAA Laboratory of Neurogenetics.
Analyses of MAOA-LPR genotypes in this study revealed
that women who had been sexually abused in childhood were much
more likely to develop alcoholism and antisocial behavior if they
had the low activity variant whereas the high activity variant
was protective. In contrast, there was no relationship between
alcoholism, antisocial behavior and MAOA-LPR genotype
among non-abused women.
“Our findings show that MAOA seems to moderate the impact
of childhood trauma on adult psychopathology in females in the
same way as previously shown among males,” says Dr. Ducci. “The MAOA-LPR low
activity allele appears to confer increased vulnerability to the
adverse psychosocial consequences of childhood sexual abuse.”
Dr. Ducci and her colleagues suggest that the effect of MAOA on
the hippocampus, a brain region which is involved in the processing
of emotional experience, may underlie the interaction between MAOA and
childhood trauma. They note that previous research showed that
people with the low activity variant at the MAOA-LPR locus
have hyperactivation of the hippocampus when retrieving negative
Other co-authors of the study include Mary-Anne Enoch, M.D., Colin
Hodgkinson, Ph.D. and Ke Xu, MD, Ph.D., of the NIAAA Laboratory
of Neurogenetics, Mario Catena, MD, of the Department of Psychiatry,
University of Pisa, Italy, and Robert W. Robin, Ph.D., of the Center
for the Prevention and Resolution of Violence in Tucson, Arizona.
The National Institute on Alcohol Abuse and Alcoholism, part of
the National Institutes of Health, is the primary U.S. agency for
conducting and supporting research on the causes, consequences,
prevention, and treatment of alcohol abuse, alcoholism, and alcohol
problems and disseminates research findings to general, professional,
and academic audiences. Additional alcohol research information
and publications are available at www.niaaa.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.