Abstract
Exposure to stress predicts the occurrence of posttraumatic stress disorder (PTSD) in individuals harboring the serotonin transporter promoter variant 5-HTTLPR. We carried out a meta-analysis of studies investigating the interaction between 5-HTTLPR, stress, and PTSD to clarify the interrelatedness of these factors. We reviewed all relevant studies published in English before May 2016. The Lipták–Stouffer z-score method for meta-analysis was applied to combined data. The z score was separately calculated for the stressful life events, childhood adversity, bi- and triallelic loci, and cross-sectional and longitudinal studies subgroups. A total of 14 studies with 15,883 subjects met our inclusion criteria. We found strong evidence that the presence of 5-HTTLPR influenced the relationship between stress and PTSD (P = 0.00003), with the strongest effects observed in the cross-sectional and longitudinal groups (P = 0.01 and 2.0 × 10−6, respectively). Stressful life events and childhood adversity separately interacted with 5-HTTLPR in PTSD (P = 2.0 × 10−8 and 0.003, respectively). When the studies were stratified by locus classification, the evidence was stronger for the triallelic (P = 4.0 × 10−8) than for the biallelic (P = 0.054) locus subgroup. There was strong evidence that 5-HTTLPR influences the relationship between stress and PTSD.
Highlights
Exposure to stress predicts the occurrence of posttraumatic stress disorder (PTSD) in individuals harboring the serotonin transporter promoter variant 5-HTTLPR
Twelve studies were pooled for a total of 8771 study subjects; the results revealed a significant interaction between stressful life events and 5-HTTLPR polymorphism (P = 2.0 × 10−8) (Fig. 2)
Seven studies were pooled with a total of 8023 study subjects; the results revealed a trend towards a significant interaction between a biallelic 5-HTTLPR locus, life stress, and PTSD (P = 0.054) (Fig. 2)
Summary
Exposure to stress predicts the occurrence of posttraumatic stress disorder (PTSD) in individuals harboring the serotonin transporter promoter variant 5-HTTLPR. We carried out a meta-analysis of studies investigating the interaction between 5-HTTLPR, stress, and PTSD to clarify the interrelatedness of these factors. The z score was separately calculated for the stressful life events, childhood adversity, bi- and triallelic loci, and cross-sectional and longitudinal studies subgroups. We found strong evidence that the presence of 5-HTTLPR influenced the relationship between stress and PTSD (P = 0.00003), with the strongest effects observed in the cross-sectional and longitudinal groups (P = 0.01 and 2.0 × 10−6, respectively). Stressful life events and childhood adversity separately interacted with 5-HTTLPR in PTSD (P = 2.0 × 10−8 and 0.003, respectively). Numerous studies have demonstrated that childhood adversity is associated with a range of metal disorders including major depression[14], antisocial disorder, substance abuse[15], and PTSD16. Several gene loci associated with PTSD have been www.nature.com/scientificreports/
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