Association of 5-HTTLPR With Post-Traumatic Stress Disorder in US Service Members

Xian-Zhang Hu; Robert J Ursano; David Benedek; Xiaoxia Li; Biomarker Study Group; Lei Zhang

doi:10.1177/24705470241245497

Association of 5-HTTLPR With Post-Traumatic Stress Disorder in US Service Members

Chronic Stress (Thousand Oaks). 2024 Apr 26:8:24705470241245497. doi: 10.1177/24705470241245497. eCollection 2024 Jan-Dec.

Authors

Xian-Zhang Hu^{1

2}, Robert J Ursano¹, David Benedek¹, Xiaoxia Li^{1

2}; Biomarker Study Group; Lei Zhang¹

Affiliations

¹ Center for the Study of Traumatic Stress, Department of Psychiatry, USUHS, Bethesda, MD, USA.
² Henry M Jackson Foundation for the Advancement of Military Medicine.

Abstract

Objective: Post-traumatic stress disorder (PTSD) is a mental disorder that manifests after exposure to a stressful traumatic event, such as combat experience. Accumulated evidence indicates an important genetic influence in the development of PTSD. The serotonin transporter (5-HTT) gene has been identified as a candidate for PTSD and a polymorphism of the serotonin transporter-linked promoter region (5-HTTLPR) is associated with the disorder in the general population. However, whether it is associated with PTSD in active military service members has not been investigated. This study aimed to investigate the relationship between 5-HTTLPR and PTSD in service members.

Methods: Leucocyte genomic DNA was extracted from service members, including those with PTSD (n = 134) or without PTSD (n = 639). The 5-HTTLPR polymorphism was detected by means of 2 stages of TaqMan fluorescent PCR assay. PTSD symptoms and symptom severity were assessed using the PTSD Checklist (PCL), a 17-item, DSM-based, self-report questionnaire with well-established validity and reliability. PTSD was determined based on endorsement of DSM-IV criteria and a PCL total score ≥ 44.

Results: Significant differences in biallele distribution were observed between PTSD and controls (χ2 = 7.497, P = .024). The frequency of SS, SL, and LL genotypes in the PTSD group was 0.17, 0.56, and 0.27 respectively, compared to the frequencies of 0.27, 0.43, and 0.29 in non-PTSD controls. Carriers of the L allele had higher scores for reexperiencing and arousal symptoms on the PCL, compared to SS homozygote carriers (P < .05). The triallele genotypes showed no significant differences in distribution between the PTSD and control groups (P > .05) and no relationship with PTSD symptom severity. The interaction of triallelic genotypes of 5-HTTLPR and traumatic life events was associated with re-experiencing, avoidance, and arousal (P < .05 for all). Multiple regression analysis revealed significant correlations between both biallelic and triallelic genotypes of 5-HTTLPR, the interaction of the number of stressful lifetime events, and 5-HTTLPR genotypes with PCL total score (P < .001).

Conclusion: Our findings suggested that 5-HTT might play a minor role in PTSD, and the interaction between 5-HTTLPR and the environment had effects on PCL score, complementing and emphasizing 5-HTT for PTSD, especially in the military population.

Keywords: 5-HTTLPR; PTSD; PTSD Checklist; association analysis; serotonin transporter.