Women are twice as likely to suffer post-traumatic stress disorder (PTSD) than men, and new research shows that low estrogen levels in some women may be a significant factor.
Researchers from Emory University School of Medicine and Harvard Medical School expanded on a growing body of research linking estrogen to stress, studying how 278 women coped with traumatic episodes during different times of their menstrual cycle, when estrogen levels naturally ebb or increase.
Informed by previous research on the impact of estrogen on brain circuitry, the researchers mapped DNA modifications of the women using blood samples taken during specific periods of the month.
Their analysis pinpointed one specific gene – HDAC4 – that appears to be linked to a person’s ability to react to and overcome fear.
“We knew that estrogen affects the activity of many genes throughout the genome,” said Dr. 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 pops out.”
Women with lower levels of HDAC4 activity had a different reaction to traumatic events and altered “resting imaging” of the brain, and they were less likely to suffer from PTSD than women with increased expression of their HDAC4 gene.
Also, tests in mice showed that fear training increased the activity of the HDAC4 gene only in rodents with low estrogen levels. No effect was noted during fear training in mice with high estrogen levels.
“The results of this study suggest that estrogen status may increase risk for PTSD in some women, in part through its regulation of HDAC4. To the best of our knowledge, this is the first report of which we are aware to take an unbiased approach towards revealing alterations in DNA methylation that are associated with PTSD diagnosis in women,” state the researchers in Molecular Psychiatry.
The Importance of Estrogen
The current study adds a new layer of understanding to the impact of estrogen on human functioning. “The physiological effects of estrogen are widespread,” describe the researchers, adding that varying levels of estrogen are “linked to differences in the hypothalamic-pituitary-adrenal axis response to stress and variation in multiple neurotransmitter systems.”
Previous studies have found clear differences in the impact of trauma on women depending on the timing of their menstrual cycle. “Women who had recently experienced trauma reported more trauma-related flashbacks if they were in the mid-luteal phase of their cycle at the time of either the trauma or the assessment,” write the researchers.
Additionally, estrogen is critical to memory formation, including memories that would be better forgotten. “Emerging evidence suggests that estrogen may have an impact on the degree to which memories, especially fear-related memories, are formed or retrieved,” they write.
About 7 percent of people will experience PTSD in their lifetime, according to the National Institutes of Health, and about one in nine women will develop the severe anxiety disorder, according to PTSD United.
“PTSD is characterized by an inability to regulate emotional responses that are associated with trauma and has been associated with increased amygdala activity and alterations in precortical regions known to mediate and modulate fear memories,” notes the study.
The researchers suggest that estrogen may potentially be used as a treatment to ease the chances of PTSD after a trauma.