Two studies have found that men and women”s immune systems respond differently to chronic post-traumatic stress disorder.
The studies by researchers at the San Francisco VA Medical Center and the University of California, San Francisco, found that while men showed no response, women on the other hand showed a strong response.
While a robust immune response protects the body from foreign invaders, such as bacteria and viruses, an over-activated response causes inflammation, which can lead to such conditions as cardiovascular disease and arthritis.
The authors took blood samples from 49 men (24 with PTSD and 25 controls) and 18 women (10 with PTSD and 8 controls).
They then used gene microarray technology to determine which genes were activated in the subjects” monocytes, which are immune cells that regularly cross the barrier between the bloodstream and the brain, and thus give a broad picture of immune reaction in both the body and brain.
“We were looking for evidence of inflammation caused by immune activation,” lead author Thomas Neylan, MD, director of the PTSD program at SFVAMC and a professor in residence of psychiatry at UCSF, explained.
“We know that people with PTSD have higher rates of cardiovascular disease and arthritis, which are diseases associated chronic inflammation.
“We also hoped that seeing which genes were expressed in PTSD might show us potential therapeutic approaches that we hadn”t thought of,” he said.
The researchers found no evidence of increased immune activation among the men with PTSD compared to those without PTSD. In contrast, the women with PTSD showed significant evidence of immune activation compared to women without PTSD.
“Previous gene microarray studies on PTSD grouped men and women together, which gave inconclusive results,” senior investigator Lynn Pulliam, MS, PhD, chief of microbiology at SFVAMC and professor of laboratory medicine and medicine at UCSF, said.
“This is the first time that it”s been shown that men and women respond differently to PTSD on a very basic biological level,” she said.
Neylan characterized the finding as “unexpected”, and said the researchers do not know why there seems to be such a marked difference between men and women.
However, in another study, they analysed data collected from the same subjects to explore one possible explanation: gender differences in cell signalling pathways.
“We know that gene expression patterns are determined by hormones and proteins that are circulating in the body, and we know that some of those hormones and proteins are produced in response to signals from the brain or central nervous system,” explained lead author Aoife O”Donovan, PhD, a researcher in psychiatry at SFVAMC and UCSF.
“These signalling pathways are used by the brain and central nervous system to communicate with the immune system and tell immune cells what to do,” O”Donovan said.
The researchers used sophisticated bioinformatics software to look at three different signalling pathways associated with inflammation: NF-kappa B, glucocorticoid receptor (GR), and CREB/ATF.
In the NF-kappa B and GR pathways in both men and women with PTSD, they found evidence of signalling that could promote inflammation.
In the CREB/ATF pathway, however, they found what O”Donovan called “totally contrasting” effects: men with PTSD had increased signalling, which in turn could possibly lead to less inflammation, while women with PTSD had decreased signalling, which could lead to more inflammation.
“This particular pathway might be a clue to the gender difference in monocyte gene expression in PTSD,” Pulliam said.
O”Donovan cautioned: “It”s still very early, but these bioinformatics results are telling us something about how PTSD could increase the risk for autoimmune disorders like arthritis as well as cardiovascular disease, cancer, and other diseases of aging.”
“They also point us in the direction of some potential treatment targets, telling us where future investigative energy might be well spent,” O”Donovan said.
Neylan emphasized that because of the small sample size, particularly among the women, the results of the two studies are suggestive rather than conclusive.
“The next step is to look at larger groups of men and women, and we are working on that,” he stated.
The studies have been published in the January 2011 issue (posted in April 2011) of the journal Disease Markers and March 2011 issue of Brain, Behaviour, and Immunity.