Preliminary Evidence of the Short Allele of the Serotonin Transporter Gene Predicting Poor Response to Cognitive Behavior Therapy in Posttraumatic Stress Disorder

Objective: This study was intended to assess the extent to which the low-expression alleles of the serotonin transporter gene promoter predict poor response to cognitive behavior therapy in patients with posttraumatic stress disorder (PTSD). Method: Forty-five patients with PTSD underwent an 8-week exposure-based cognitive behavior therapy program and provided mouth swabs or saliva samples to extract genomic DNA and classify individuals according to four allelic forms (S(A), S(G), L(A), L(G)) of the 5-HTT-linked polymorphic region (5-HTTLPR). We determined whether the 5-HTTLPR genotype predicted change in PTSD severity following treatment (n = 45) and 6 months later (n = 42). Results: After controlling for pretreatment PTSD severity and number of treatment sessions, the 5-HTTLPR low-expression genotype group (S or L, allele carriers) displayed more severe PTSD 6 months following treatment relative to other patients. Conclusions: This study suggests a genetic contribution to treatment outcome following cognitive behavior therapy and implicates the serotonergic system in response to exposure-based treatments in PTSD.