Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations.
BACKGROUND
The 5-HTTLPR polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) has been found to moderate several categories of emotional response after stressful life events. Previous studies generally focused on its effect on depressive symptoms; little is known about its moderation of the development of posttraumatic stress disorder (PTSD).


OBJECTIVE
To examine the effects of childhood adversity, adult traumatic events, 5-HTTLPR genotypes, and gene x environment interactions on the etiology of PTSD.


METHODS
A cross-sectional study in which participants in several studies investigating the genetics of substance dependence were also screened for lifetime PTSD. The triallelic system of 5-HTTLPR was genotyped. Logistic regression modeling was used in the analyses.


METHODS
General community.


METHODS
Five hundred eighty-two European American and 670 African American individuals who reported experiences of childhood adversity, adult traumatic events, or both. Main Outcome Measure Diagnosis of PTSD, defined by DSM-IV diagnostic criteria and assessed through the Semi-Structured Assessment for Drug Dependence and Alcoholism interview.


RESULTS
Childhood adversity and adult traumatic events both predicted PTSD. Although the 5-HTTLPR genotype alone did not predict the onset of PTSD, it interacted with adult traumatic events and childhood adversity to increase the risk for PTSD, especially for those with high rates of both types of trauma exposure (European American: odds ratio [OR], 2.86; 95% confidence interval [CI], 1.50-5.45; P = .002; African American: OR, 1.88; 95% CI, 1.04-3.40; P = .04; pooled: OR, 2.31; 95% CI, 1.50-3.56; P < .001).


CONCLUSIONS
Participants who had both childhood adversity and adult traumatic events were more likely to develop lifetime PTSD compared with those who experienced either type of adverse event. The risk was increased in individuals with 1 or 2 copies of the S' (S) allele compared with the L' (L) homozygotes. Our study provides additional direct evidence that PTSD is influenced by the interactive effect of environmental and genetic factors.
Xie
Pingxing
P
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Kranzler
Henry R
HR
Poling
James
J
Stein
Murray B
MB
Anton
Raymond F
RF
Brady
Kathleen
K
Weiss
Roger D
RD
Farrer
Lindsay
L
Gelernter
Joel
J
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D002648:Child; D002649:Child Abuse / Q000523:psychology; D003430:Cross-Sectional Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012931:Social Environment; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis* / Q000235:genetics*; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000235:genetics; D044465:White People / Q000235:genetics
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins