title: Association of TPH1, TPH2, and 5HTTLPR with PTSD and depressive symptoms.
abstract: OBJECTIVE
  To examine the potential contribution of the serotonin hydroxylase (TPH1 and 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 depressive 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 significant association of PTSD symptoms with the 't' allele of TPH1 SNP rs2108977 (p<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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: UCLA/Duke University National Center for Child Traumatic Stress, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles (UCLA), USA. agoenjia@aol.com
authors.forename: Armen K
authors.initials: AK
authors.lastname: Goenjian
authors.forename: Julia N
authors.initials: JN
authors.lastname: Bailey
authors.forename: David P
authors.initials: DP
authors.lastname: Walling
authors.forename: Alan M
authors.initials: AM
authors.lastname: Steinberg
authors.forename: Devon
authors.initials: D
authors.lastname: Schmidt
authors.forename: Uma
authors.initials: U
authors.lastname: Dandekar
authors.forename: Ernest P
authors.initials: EP
authors.lastname: Noble
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015897:Comorbidity; D003863:Depression / Q000453:epidemiology / Q000235:genetics*; D055866:Earthquakes; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013313:Stress Disorders, Post-Traumatic / Q000453:epidemiology / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C497467:TPH1 protein, human; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase