Research report Association of TPH1, TPH2, and 5HTTLPR with PTSD and depressive symptoms Armen K. Goenjian a, b, e, ⁎, Julia N. Bailey c, d , David P. Walling b , Alan M. Steinberg a , Devon Schmidt b , Uma Dandekar d , Ernest P. Noble e a UCLA/Duke University National Center for Child Traumatic Stress, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles (UCLA), United States b Collaborative Neuroscience Network, Garden Grove, CA 92845, United States c Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA, United States d Epilepsy Genetics/Genomics Laboratories, VA GLAHS, Los Angeles, CA, United States e Alcohol Research Center, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, United States article info abstract Article history: Received 29 January 2012 Accepted 5 February 2012 Available online 6 April 2012 Objective: To examine the potential contribution of the tryptophan hydroxylase (TPH1and TPH2) genes, and the serotonin transporter promoter polymorphism (5HTTLPR) to the unique and pleiotropic risk of PTSD symptoms and depressive symptoms. Methods: Participants included 200 adults exposed to the 1988 Spitak earthquake from 12 multigenerational families (3 to 5 generations). Severity of trauma exposure, PTSD, and de- pressive symptoms were assessed using standard psychometric instruments. Pedigree-based variance component analysis was used to assess the association between select genes and the phenotypes. Results: After adjusting for age, sex, exposure and environmental variables, there was a signif- icant association of PTSD symptoms with the ‘t’ allele of TPH1 SNP rs2108977 (p b 0.004), explaining 3% of the phenotypic variance. This allele also showed a non-significant trend for an association with depressive symptoms (p = 0.08). Also, there was a significant association of PTSD symptoms and the ‘t’ allele of TPH2 SNP rs11178997 (p = 0.03), explaining 4% of the variance. Depressive symptoms were significantly associated with the ‘s’ allele of 5HTTLPR (p = 0.03), explaining 4% of the variance. Limitations: Retrospective rating of exposure may have been subject to memory failure leading to misestimation of symptom severities. Second, findings may not be generalizable to other ethnic/racial populations. Conclusion: To our knowledge, this is the first published report showing that variants in TPH1 and TPH2 genes constitute risk factors for PTSD symptoms. Additionally, the TPH1 gene may be associated pleiotropically with PTSD and depressive symptoms. The association of the ‘s’ allele of 5HTTLPR polymorphism with depression adds to similar findings from case/case–control studies. © 2012 Elsevier B.V. All rights reserved. Keywords: Genetics PTSD Depression Tryptophan hydroxylase Serotonin transporter 1. Introduction 1.1. Comorbidity of PTSD and depression Comorbidity of PTSD and depression has been documented in numerous psychiatric epidemiologic studies (for example, see Breslau et al., 1991; Kessler et al., 1995). In the National Journal of Affective Disorders 140 (2012) 244–252 ⁎ Corresponding author at: Alcohol Research Center, Rm. 58-242, UCLA Neuropsychiatric Institute, 760 Westwood, CA 90024, United States. Tel.: +1 310 523 4200; fax: +1 310 373 4039. E-mail address: agoenjia@aol.com (A.K. Goenjian). 0165-0327/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2012.02.015 Contents lists available at SciVerse ScienceDirect Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad