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Kristina B. Mercer, MPH; Holly K. Orcutt, PhD; Jeffrey F. Quinn, BS; Caitlin A. Fitzgerald, BS; Karen N. Conneely, PhD; Richard T. Barfield, BA; Charles F. Gillespie, MD, PhD; Kerry J. Ressler, MD, PhD

Arch Gen Psychiatry. 2012;69(1):89-97. doi:10.1001/archgenpsychiatry.2011.109

Context  The serotonin transporter (SLC6A4) has been associated with several stress-related syndromes including posttraumatic stress disorder (PTSD). The ability to detect meaningful associations is largely dependent on reliable measures of preexisting trauma.

Objective  To study the association of genetic variants within SLC6A4 with acute and posttraumatic stress symptoms in a civilian cohort with known levels of preexisting trauma and PTSD symptoms collected prior to a shared index traumatic event.

Design  Ongoing longitudinal study.

Setting  On February 14, 2008, a lone gunman shot multiple people on the campus of Northern Illinois University in DeKalb, Illinois, killing 5 and wounding 21. As part of an ongoing longitudinal study on that campus, a cohort of female undergraduate students, interviewed prior to the shooting, completed follow-up trauma-related measures including PTSD symptom severity (follow-up survey was launched 17 days postshooting; n = 691). To obtain DNA, salivary samples were collected from a subset of the original study population based on willingness to participate (n = 276).

Participants  Two hundred four undergraduate women.

Main Outcome Measures  SLC6A4 polymorphisms STin2, 5-HTTLPR, and rs25531 were genotyped in 235 individuals.

Results  We found that although the STin2 variant and 5-HTTLPR alone did not associate with increased PTSD symptoms, rs25531 and the 5-HTTLPR multimarker genotype (combined 5-HTTLPR and rs25531) were associated with significantly increased acute stress disorder symptoms at 2 to 4 weeks postshooting (n = 161; P < .05). This association remained significant when controlling for race and for level of shooting exposure (n = 123; P < .007). The association was most robust with the 5-HTTLPR multimarker genotype and avoidance symptoms (P = .003).

Conclusion  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.

Author Affiliations: School of Medicine (Mss Mercer, Quinn, and Fitzgerald and Drs Conneely, Gillespie, and Ressler) and Rollins School of Public Health (Mr Barfield), Emory University, Atlanta, Georgia; Howard Hughes Medical Institute, Bethesda, Maryland (Ms Mercer and Dr Ressler); and Northern Illinois University, DeKalb (Dr Orcutt).

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