From The Quarterly, Spring 2011

Kerry J. Ressler, M.D., Ph.D., member of the Brain & Behavior Research Foundation Scientific Council, led recent research that may demonstrate one reason why women are generally more vulnerable to post-traumatic stress disorder (PTSD) than men and pinpointed a genetic anomaly that could account for the disparity.



In an initial study of 64 subjects with a history of significant trauma, Dr. Ressler and his team found that a high blood level of a hormone called PACAP (pituitary adenylate cyclaseactivating polypeptide) in women but not in men was associated with women’s higher incidence of PTSD. In addition to the differences observed between the sexes, the research also showed that women with above-average PACAP levels had PTSD symptom scores five times higher than women with lower PACAP levels.



To explore the basis of these findings, the team conducted genetic studies in more than 1,200 traumatized subjects, examining 44 single nucleotide polymorphisms, or SNPS, of genes associated with the PACAP system. (SNPs, pronounced “snips,” are variations in the DNA sequence in a gene.) They found that a variation in the gene for the PACAP receptor, which appears to change how that gene responds to the primary female hormone estrogen, was linked to PTSD risk in women.



However, despite comparable levels of trauma, women in the study with the more protective PACAP receptor gene variation had lower rates of PTSD than men, as opposed to those women with the risk gene variation.



PACAP has long been known to be a stress-response hormone, but its specific role in PTSD has been unclear. The study’s findings, which were reported in the Feb. 24 issue of the journal Nature, suggest strongly to Dr. Ressler and his colleagues that PACAP and its receptor system may be integrally involved in regulating the psychological and physiological responses to traumatic stress. The research also seems to indicate that men and women who have been traumatized may arrive at PTSD by different bio-logical pathways, and that now researchers have a clue as to how that works – the genetic data that points to changes in the ability to respond to estrogen.



Pointing to these results as opening a new window into the biology of PTSD, Dr. Ressler expresses the hope that the identification of PACAP as an indicator of PTSD may lead to new diagnostic tools and eventually to new, more precisely targeted treatments for anxiety disorders.



Dr. Ressler is a Howard Hughes Medical Institute Investigator and an associate professor in the department of psychiatry and behavioral sciences in the Emory University School of Medicine, and a researcher with the Yerkes National Primate Research Center in Atlanta. Dr. Ressler received 2002 and 2005 NARSAD Young Investigator Grants and was honored with a 2009 NARSAD Freedman Award recognizing his significant findings as a Young Investigator grantee.