title: Association of COMT and TPH-2 genes with DSM-5 based PTSD symptoms.
abstract: BACKGROUND
  Dopaminergic and serotonergic systems have been implicated in PTSD. The present study evaluated the association of four catechol-O-methyltransferase (COMT) gene loci, and the joint effect of COMT and tryptophan hydroxylase 2 (TPH2) genes on PTSD symptoms.
  
  
  METHODS
  Subjects included 200 Caucasian Armenian adults exposed to the 1988 Spitak earthquake from 12 multigenerational (3-5 generations) families. Instruments used included the UCLA PTSD Reaction Index based on DSM-5 criteria, and the Beck Depression Inventory.
  
  
  RESULTS
  The adjusted heritabilitiy of vulnerability to DSM-5 based PTSD symptoms was 0.60 (p<10(-4)). There was a significant association of the COMT allele rs4633C with total PTSD (p<0.03), and D category (p<0.04) (negative alterations in cognitions and mood) severity scores, but not with C category (avoidance) scores. There was no genetic correlation between C and D category severity scores. COMT allele rs4633C and the TPH-2 allele rs11178997T together accounted for 7% of the variance in PTSD severity scores (p<0.001). None of the COMT alleles were associated with depression.
  
  
  CONCLUSIONS
  The ratings of earthquake exposure and prior trauma may have been subject to recall bias. The findings may not be generalizable to other ethnic/racial populations.
  
  
  CONCLUSIONS
  COMT allele rs4633C may be causally related and/or is in linkage disequilibrium with gene(s) that are causally related to PTSD symptoms. Carriers of these COMT and the TPH-2 alleles may be at increased risk for PTSD. The findings provide biological support for dividing DSM-IV category C symptoms into DSM-5 categories C and D.
authors.affiliation: UCLA/Duke University National Center for Child Traumatic Stress, Department of Psychiatry, Geffen School of Medicine, University of California, Los Angeles (UCLA), CA, USA; Collaborative Neuroscience Network, Garden Grove, CA, USA. Electronic address: agoenjia@ucla.edu.
authors.forename: Armen K
authors.initials: AK
authors.lastname: Goenjian
authors.affiliation: Alcohol Research Center, Department of Psychiatry, Geffen School of Medicine, UCLA, CA, USA.
authors.forename: Ernest P
authors.initials: EP
authors.lastname: Noble
authors.affiliation: UCLA/Duke University National Center for Child Traumatic Stress, Department of Psychiatry, Geffen School of Medicine, University of California, Los Angeles (UCLA), CA, USA.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Steinberg
authors.affiliation: Collaborative Neuroscience Network, Garden Grove, CA, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Walling
authors.affiliation: Department of Psychology, University of California at Riverside, CA, USA.
authors.forename: Sofia T
authors.initials: ST
authors.lastname: Stepanyan
authors.affiliation: Sequencing & Genotyping Core, Department of Human Genetics, UCLA, CA, USA.
authors.forename: Sugandha
authors.initials: S
authors.lastname: Dandekar
authors.affiliation: Department of Epidemiology, UCLA Fielding School of Public Health; Epilepsy Genetics/Genomics Laboratories, VA GLAHS, Los Angeles, CA, USA.
authors.forename: Julia N
authors.initials: JN
authors.lastname: Bailey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001136:Armenia; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D003863:Depression / Q000235:genetics; D039721:Diagnostic and Statistical Manual of Mental Disorders; D055866:Earthquakes; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Catechol-O-methyltransferase (COMT); Genetics; PTSD; Trauma; Tryptophan hydroxylase 2 (TPH 2)