A Genetic Susceptibility to PTSD?

Post-traumatic stress disorder (PTSD) has been in the news a lot lately, primarily due to the prevalence of PTSD in Iraq war veterans. PTSD can occur following any severely stressful event, and recent research has shown that some individuals are genetically “at-risk” for its development.

A study of adult victims of childhood trauma compared the occurrence of PTSD and genetic variations in the FKBP5 gene, which is related to stress response. Not surprisingly, the study found that both abusive and nonabusive childhood traumatic events were linked to the development of PTSD. In addition, four specific variations of the FKBP5 gene significantly increased the risk of PTSD in child abuse victims. This effect was still present after controlling for depression severity, age, sex, and the occurrence of other kinds of trauma.

These genetic variants did not increase the risk of PTSD in those who experienced childhood trauma other than abuse. The FKBP5 gene encodes a protein that modulates the glucocorticoid receptor. Glucocorticoids, such as cortisol, are one of the body’s basic stress hormones, released in response to a variety of physical and psychological stressors. Variants of the gene produce proteins with more or less activity, which in theory would affect the ability of the glucocorticoid receptor to bind and transmit intracellular signals from circulating glucocorticoids.

The physical effects of cortisol excess are easy to detect — high blood sugar, weight gain, hypertension, and dementia all occur with extremely high levels of cortisol that result from exogenous administration or tumor production of the hormone. Its effects on mental function at lower levels seen with psychological stress are harder to pinpoint. Cortisol levels are frequently abnormal in patients with mood disorders, suggesting that it does affect, or is affected by, one’s mental state.

Identification of genetic variants that place individuals at increased risk of PTSD is still a long way from clinical utility. However, with further research, genetic testing may be used to identify people who need close follow-up after traumatic events, allowing for early detection and implementation of therapy.

Reference

Binder, E.B. et al. (2008). Association of FKBP5 Polymorphisms and Childhood Abuse With Risk of Posttraumatic Stress Disorder Symptoms in Adults. JAMA, 299(11), 1291-1305.