Serotonin Transporter Polymorphisms Are Linked to Posttraumatic Stress Disorder Susceptibility

Posttraumatic stress disorder (PTSD) is a psychiatric condition that results in severe anxiety after the exposure to an acute traumatic event.  PTSD is characterized by flashbacks or nightmares, avoidance of stimuli associated with the trauma, and increased sensory arousal.  In addition, the DSM-IV requires that symptoms are present for one month and cause significant social, personal, and occupational dysfunction.  PTSD has been known to occur in veterans of war, and prior studies of Vietnam War twin veterans have suggested that there is a genetic and familial predisposition for the condition.  The treatment of choice for PTSD is the selective serotonin reuptake inhibitors (SSRIs), which block the presynaptic uptake of serotonin in the synaptic cleft.  Previous genetic studies have implicated a role for the serotonin transporter protein in the pathogenesis of PTSD, which provides evidence as to why SSRIs are effective in the treatment of the condition.  Researchers, lead by Dr. Kerry Ressler, have shown that the rs25531 polymorphism of the serotonin transporter gene and the 5-HTTLPR multimarker genotype are associated with significantly increased risk for the development of PTSD.  The results of their research were published online in the journal Archives of General Psychiatry.  The researchers conducted an ongoing longitudinal study of female students exposed to an acute traumatic event on the campus of the Northern Illinois University.  On February, 14, 2008 a gunman shot and killed 5 people and injured 21 people on the campus of the university.  Female students already enrolled in a study of traumatic events that had been exposed to the shooting incident were selected to volunteer to participate in the current study.  The 204 female participants were interviewed prior to the shooting, completed post event trauma related measures of PTSD, and had DNA specimens collected via salivary samples.  The investigators found that the STin2 variant and the 5-HTTLPR variant alone of the serotonin transporter did not associate with increased PTSD symptoms.  The 5-HTTLPR multimarker genotype (combined 5-HTTLPR and rs25531) and the rs25531 polymorphism variant were associated with significantly increased risk of developing PTSD symptoms after the shooting incident.  The authors wrote, “These data suggest that differential function of the serotonin transporter may mediate differential response to a severe trauma. When examined in a relatively homogenous sample with shared trauma and known prior levels of child and adult trauma, the 5-HTTLPR multimarker genotype may serve as a useful predictor of risk for PTSD-related symptoms in the weeks and months following the trauma”.  This study establishes a foundation for future investigation into the genetic susceptibility for the development of PTSD, and may help identify those individuals with increase risk.  In addition, these results may help identify which PTSD patients will benefit the most from treatment with SSRIs versus other psychiatric medication regimens that do not target the serotonin transporter.

Reference:

Kristina B. Mercer et al. “Acute and Posttraumatic Stress Symptoms in a Prospective Gene X Environment Study of a University Campus Shooting” Arch Gen Psychiatry. published online September 5, 2011. doi:10.1001/archgenpsychiatry.2011.109

Tagged as: 5-HTTLPR multimarker genotype, Dr. Kerry Ressler, DSM-IV, posttraumatic stress disorder, PTSD, rs25531 polymorphism, selective serotonin reuptake inhibitors, serotonin transporter, serotonin transporter gene, SSRIs, STin2 variant