|Past Child Abuse Plus Variations in Gene Result
in Potent PTSD Risk for Adults|
Combined factors may change biology of stress-response system
as it develops
A traumatic event is much more likely to result in posttraumatic
stress disorder (PTSD) in adults who experienced trauma in childhood — but
certain gene variations raise the risk considerably if the childhood
trauma involved physical or sexual abuse, scientists have found.
The research was conducted with funding from the National Institute
of Mental Health, which is part of the National Institutes of Health,
"Untangling complex interactions between genetic variations
and environmental factors can help us learn how to predict more
accurately who's at risk of disorders like PTSD. It can help us
learn which prevention and treatment strategies are likely to work
best for each person," said NIMH Director Thomas R. Insel,
Results of the study were reported on March 19 in a special issue
of the Journal of the American Medical Association devoted
to the influence of genes on health and disease, by Elisabeth Binder,
M.D., Ph.D., Kerry J. Ressler, M.D., Ph.D., and colleagues from
Emory University and other facilities.
"These results are early and will need to be replicated,
but they support the hypothesis that combinations of genes and
environmental factors affect the risk for stress-related disorders
like PTSD," Ressler said. "Understanding how gene-environment
interactions affect mental health can help us understand the neurobiology
of these illnesses."
The gene in question is active in the biochemical make-up of the
body's stress-response system. Results of the study suggest that
early-life abuse can result in particularly potent changes to this
system as it develops — depending partly on whether or not
the variations are present in the gene.
Inherited variations in multiple genes, which have yet to be identified,
are estimated to account for 30 to 40 percent of the risk of developing
PTSD. The gene identified in this study is one likely candidate,
although others are almost certain to emerge.
To conduct their study, the researchers surveyed 900 primarily
African-American people 18 to 81 years old, from poor, urban neighborhoods.
As is common in impoverished environments, many of the people in
this study had experienced severe traumatic experiences in childhood
and had later experienced other kinds of trauma as adults. The
researchers also examined the genetic make-up of 765 of the participants.
They found that having a history of child abuse — which
was the case for almost 30 percent of the people in this study — led
to more than twice the number of PTSD symptoms in adults who had
later undergone other traumas, compared to traumatized adults who
weren't abused in childhood. But the history of child abuse wasn't
enough, by itself, to lead to the increase in symptoms; the increase
appeared to depend on whether or not certain variations in the
stress-related gene also were present.
Likewise, the gene variations by themselves didn't appear to affect
the risk. The combination of the gene variations and past child
abuse were the key ingredients for the doubled PTSD symptoms when
a subsequent trauma occurred.
The scientists also detected protective variations in the same
gene. People who had these resiliency variations didn't have a
substantial increase in PTSD symptoms after a trauma in adulthood,
even if they had been abused in childhood.
The gene is called FKBP5, and the protein it produces
helps regulate the amount of binding that takes place between stress
hormones and their receptors on cells. Binding between the hormones
and the receptors leads to cell functions that help regulate response
to stress, a process that may be altered by variations in the gene.
The researchers showed that this process was changed in ways that
led to excess stress-hormone reactivity in study participants who
had both the risk version of the gene and PTSD symptoms.
"This finding helps us understand the neurobiology of PTSD.
It's equally important to understand how to decrease the high rates
of childhood and adult trauma that inner-city populations suffer," Ressler
said. "PTSD rates in U.S. inner cities are as high as among
In addition to NIMH, the National Institute on Drug Abuse and
the National Center for Research Resources, also of the National
Institutes of Health, provided funding for the study. Other contributors
included the Emory and Grady Memorial General Clinical Research
Center and the Burroughs Wellcome Fund.
For more information about posttraumatic stress disorder, visit
the NIMH web site at http://www.nimh.nih.gov/health/topics/post-traumatic-stress-disorder-ptsd/index.shtml
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 web site 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 the NIH
web site at http://www.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.
Binder EB, Bradley RG, Wei L, Epstein MP, Deveau TC, Mercer KB, Tang
Y, Gillespie CF, Heim CM, Nemeroff CB, Schwartz AC, Cubells JF, Ressler
KJ. Association of FKBP5 Polymorphisms and Childhood Abuse With Risk
of Posttraumatic Stress Disorder Symptoms in Adults. Journal
of the American Medical Association, 299 (11): 1291-1305. March