|Scientists Find Genetic Factor in Stress Response
Inherited variations in the amount of an innate anxiety-reducing
molecule help explain why some people can withstand stress better
than others, 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).
"Stress response is an important variable in vulnerability
to alcohol dependence and other addictions, as well as other psychiatric
disorders," noted NIAAA Director Ting-Kai Li, M.D. "This
finding could help us understand individuals' initial vulnerability
to these disorders."
Scientists led by David Goldman, M. D., chief of the NIAAA Laboratory
of Neurogenetics, identified gene variants that affect the expression
of a signaling molecule called neuropeptide Y (NPY). Found in brain
and many other tissues, NPY regulates diverse functions, including
appetite, weight, and emotional responses.
"NPY is induced by stress and its release reduces anxiety," said
Dr. Goldman. "Previous studies have shown that genetic factors
play an important role in mood and anxiety disorders. In this study,
we sought to determine if genetic variants of NPY might contribute
to the maladaptive stress responses that often underlie these disorders." A
report of the findings appears online today in Nature.
Analyses of human tissue samples led by researchers at NIAAA identified
several NPY gene variants. Collaborations with NIH-supported scientists
at the University of Michigan, University of Pittsburgh, University
of Helsinki, University of Miami, University of Maryland, the University
of California at San Diego, and Yale University, showed that these
variants result in a range of different effects including altered
levels of NPY in brain and other tissues, and differences in emotion
and emotion-induced responses of the brain.
The researchers evaluated the NPY gene variants' effects on brain
responses to stress and emotion. Using functional brain imaging,
they found that individuals with the variant that yielded the lowest
level of NPY reacted with heightened emotionality to images of
threatening facial expressions. "Metabolic activity in brain
regions involved in emotional processing increased when these individuals
were presented with the threatening images," explained Dr.
In another brain imaging experiment, people with the low level
NPY variant were found to have a diminished ability to tolerate
moderate levels of sustained muscular pain. Previous studies had
shown that NPY's behavioral effects are mediated through interactions
with opioid compounds produced by the body to help suppress pain,
stress, and anxiety. "As shown by brain imaging of opioid
function, these individuals released less opioid neurotransmitter
in response to muscle discomfort than did individuals with higher
levels of NPY," said Dr. Goldman. "Their emotional response
to pain was also higher, showing the close tie between emotionality
and resilience to pain and other negative stimuli."
In a preliminary finding, the low level NPY gene variant was found
to be more common than other variants among a small sample of individuals
with anxiety disorders. The researchers also found that low level
NPY expression was linked to high levels of trait anxiety. "Trait
anxiety is an indication of an individual's level of emotionality
or worry under ordinary circumstances," explained Dr. Goldman.
The researchers conclude that these converging findings are consistent
with NPY's role as an anxiety-reducing peptide and help explain
inter-individual variation in resiliency to stress. "This
inherited functional variation could also open up new avenues of
research for other human characteristics, such as appetite and
metabolism, which are also modulated by NPY," said Dr. Goldman.
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.