Therapygenetics: Serotonin transporter gene polymorphism (5-HTTLPR) is associated with behavioral treatment response to virtual exposure therapy in patients with spider phobia.

Identifying biomarkers predicting therapy outcomes before treatment holds great promise for advancing precision medicine. Genetic variants such as the serotonin transporter gene linked polymorphic region (5-HTTLPR) may be associated with response to cognitive behavioral therapy in anxiety disorders, albeit results so far are controversial. Contributing to the ongoing debate, we investigated whether treatment response to a highly standardized one-session virtual reality exposure therapy (VRET) was predicted by 5-HTTLPR genotype. N = 194 patients with arachnophobia (spider phobia) were genotyped for 5-HTTLPR and the functionally related single nucleotide polymorphism rs25531 and grouped into high- (LA/LA), and low-expression (S/S, S/LG, LG/LG, S/LA, LG/LA) genotype. At baseline, after VRET, and at a 6-month follow-up, participants underwent a standardized behavioral avoidance task (BAT) and the spider phobia questionnaire (SPQ) to assess symptom severity. Chi-square tests revealed a significant association between 5-HTTLPR/rs25531 and behavioral treatment outcome, that remained significant at the 6-month follow-up. No association was found between genotype and self-reported symptom severity measured with the SPQ. Our results support the idea that while LA/LA genotype carriers might benefit from highly standardized treatment, lower 5-HTT expression may convey risk to poorer treatment response, likely necessitating more tailored psychotherapeutic interventions to promote sufficient response.