Why do some people who experience traumatizing events develop Post-Traumatic Stress Disorder while others don't? Scientists know that, in general, the more traumatic events a person experiences the higher their likelihood of developing PTSD, but even under extreme stress not all individuals develop the disorder. Now, researchers writing in Biological Psychiatry say that survivors of the 1994 Rwandan Genocide may help explain how genetic factors influence this relationship.

Researchers studied 424 Rwandan Genocide survivors, some with and some without PTSD. As expected, they found that those survivors with higher traumatic load had a higher prevalence of lifetime PTSD, a dose-response relationship. But importantly, they also found that the Val158Met polymorphism of the gene encoding the enzyme catechol-O-methyltransferase (COMT) plays a role in this relationship.

Individuals homozygous for the Met allele of this COMT polymorphism have substantially lower activity of this enzyme. Lower COMT activity would be expected to produce higher levels of norepinephrine and dopamine, neurotransmitters that are released during stress. Rwandan survivors with at least one Val allele in this gene showed the typical dose-response relationship between trauma severity and PTSD risk, but those homozygous for the Met allele exhibited a high risk for PTSD independently of the severity of traumatic load.

In other words, people who, due to their genotype, were more likely to inactivate the stress neurotransmitters were somewhat protected from developing stress-related problems relative to people who were less able to metabolize the transmitters.

"We hope that molecular genetics will help us to identify those who are most resilient so that we can learn about ways that people cope with stress at a psychological, behavioral, and biological level. We also would like a biological test to help us to identify people who are most vulnerable to the negative effects of stress so that we could target supportive services to these people," said Dr. John Krystal, Editor of Biological Psychiatry.

Dr. Iris-Tatjana Kolassa cautions that many technical and clinical questions remain open in attempting to develop molecular genetic tests that predict patterns of stress response. But she acknowledged that human genetics could someday play a role in the prevention and treatment of PTSD.



Citation: Iris-Tatjana Kolassa et al., 'The Risk of Posttraumatic Stress Disorder After Trauma Depends on Traumatic Load and the Catechol-O-Methyltransferase Val158Met Polymorphism' Biological Psychiatry, 2010, 67(4): 304 doi: 10.1016/j.biopsych.2009.10.009