The “S” allele of the serotonin transporter is not associated with major depression in a sample of veterans.

The results of some studies suggest that the serotonin transporter-linked polymorphic region (5-HTTLPR) short (S) allele, relative to the long (L) allele, is associated with risk for Major Depressive Disorder (MDD), and thus serves as a biomarker for MDD, while results from other studies do not support that conclusion. Persons with an S allele demonstrate a 2- to 2.5 fold decrease in serotonin transcription rate compared to the L-allele, which may increase their risk for MDD. Differences in study populations may help explain the differences in findings between those meta-analyses. To date, there have been no published reports which have addressed the possible association between the S allele and MDD among military veterans.

This study, funded in part by NIDA’s National Drug Abuse Treatment Clinical Trials Network (CTN), assessed the possible association of the S allele with MDD among a study population of veterans in treatment for substance use disorder. It was hypothesized that the S allele would be associated with MDD in the study sample. Subjects signing informed consent were 101 veterans recruited from VA behavioral health and substance use treatment clinics in the VA Pittsburgh Healthcare System, and 91 of those subjects were genotyped for 5-HTTLPR polymorphisms. The study sample from whom genetic material was collected included 82 males and 9 females, of whom 53 were white, 38 were black, and one was “other.” Fifty-four members of the study sample (59%) met DSM-IV criteria for an MDD on the SCID. Forty-five of the subjects demonstrated one or two S alleles, while 46 did not do so.

Conclusions: The presence of the S allele of the serotonin transporter was not found to be significantly associated with the diagnosis of MDD in the sample. This finding, in combination with other recent negative findings from other researchers involving non-veteran populations raises questions regarding the clinical utility of using genetics tests involving the assessment of the alleles of the serotonin transporter as a possible biomarker for Major Depressive Disorder.