Post traumatic stress disorder (PTSD) develops in some people who have experienced a shocking, scary or dangerous event.
Low estrogen levels may make women more susceptible to the
development of post traumatic stress disorder at some points in
their menstrual cycles or lifetimes, while high estrogen levels may be
‘HDAC4 gene, critical for learning and memory, is activated in the amygdala while the mice undergo fear learning, but only when estrogen levels are low.’
New research from Emory University School of Medicine and Harvard
Medical School provides insight into how estrogen changes gene activity
in the brain to achieve its protective effects.
The findings, published in Molecular Psychiatry
, could inform the design of preventive treatments aimed at reducing the risk of PTSD after someone is traumatized.
The scientists examined blood samples from 278 women from the Grady
Trauma Project, a study of low-income Atlanta residents with high levels
of exposure to violence and abuse. They analyzed maps of DNA
methylation, a modification of DNA that is usually a sign of genes that
are turned off.
The group included adult women of child-bearing age, in which
estrogen rises and falls with the menstrual cycle, and women that had
gone through menopause and had much lower estrogen levels.
"We knew that estrogen affects the activity of many genes throughout
the genome," says Alicia Smith, associate professor and vice chair
of research in the Department of Gynecology and Obstetrics at Emory
University School of Medicine. "But if you look at the
estrogen-modulated sites that are also associated with PTSD, just one
That site is located in a gene called HDAC4, known to be critical
for learning and memory in mice. Genetic variation in HDAC4 among the
women was linked to a lower level of HDAC4 gene activity and differences
in their ability to respond to and recover from fear, and also
differences in "resting state" brain imaging. Women with the same
variation also showed stronger connections in activation between the
amygdala and the cingulate cortex, two regions of the brain involved in
On top of that, experiments with female mice showed that the HDAC4
gene was activated in the amygdala while the mice were undergoing fear
learning, but only when estrogen levels in the mice were low.
Smith says these results could lead to estrogen being used as a
preventive treatment to lower the risk of PTSD after trauma. More
information about how estrogen exerts its effects is coming to light;
the authors note that in addition to modulating fear learning, estrogen
has also been proposed to alter pain perception.
In this paper, estrogen's effects in males were not studied; other
scientists have found that in males, testosterone is converted into
estrogen in the brain, where it plays a key role in development.