• Open Access

Sex dependent influence of a functional polymorphism in steroid 5-α-reductase type 2 (SRD5A2) on post-traumatic stress symptoms§


  • How to Cite this Article: Gillespie CF, Almli LM, Smith AK, Bradley B, Kerley K, Crain DF, Mercer KB, Weiss T, Phifer J, Tang Y, Cubells JF, Binder EB, Conneely KN, Ressler KJ. 2013. Sex Dependent Influence of a Functional Polymorphism in Steroid 5-α-Reductase Type 2 (SRD5A2) on Post-Traumatic Stress Symptoms. Am J Med Genet Part B 162B:283–292.

  • Financial Disclosure Statement: There were no commercial sponsors or commercial relationships related to the current work. All additional financial ties of the investigators within the last 3 years are disclosed herein: Dr. Gillespie has received funding from APIRE/Wyeth, NARSAD, NIDA, NCCAM, and NIMH. Dr. Bradley has received funding from AFSP. Dr. Binder receives funding from NIMH, the Behrens-Weise foundation and PharmaNeuroBoost. Dr. Ressler has received awards and/or funding support related to other studies from Burroughs Wellcome Foundation, NARSAD, NIMH, NIDA, and is a cofounder of Extinction Pharmaceuticals for use of NMDA-based therapeutics with Psychotherapy.

  • §

    Charles F. Gillespie and Lynn M. Almli equally contributed to this work.


A non-synonymous, single nucleotide polymorphism (SNP) in the gene coding for steroid 5-α-reductase type 2 (SRD5A2) is associated with reduced conversion of testosterone to dihydrotestosterone (DHT). Because SRD5A2 participates in the regulation of testosterone and cortisol metabolism, hormones shown to be dysregulated in patients with PTSD, we examined whether the V89L variant (rs523349) influences risk for post-traumatic stress disorder (PTSD). Study participants (N = 1,443) were traumatized African-American patients of low socioeconomic status with high rates of lifetime trauma exposure recruited from the primary care clinics of a large, urban hospital. PTSD symptoms were measured with the post-traumatic stress symptom scale (PSS). Subjects were genotyped for the V89L variant (rs523349) of SRD5A2. We initially found a significant sex-dependent effect of genotype in male but not female subjects on symptoms. Associations with PTSD symptoms were confirmed using a separate internal replication sample with identical methods of data analysis, followed by pooled analysis of the combined samples (N = 1,443, sex × genotype interaction P < 0.002; males: n = 536, P < 0.001). These data support the hypothesis that functional variation within SRD5A2 influences, in a sex-specific way, the severity of post-traumatic stress symptoms and risk for diagnosis of PTSD. © 2013 Wiley Periodicals, Inc.