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J Affect Disord. 2015 Feb 1;172:472-8. doi: 10.1016/j.jad.2014.10.034. Epub 2014 Oct 22.

Association of COMT and TPH-2 genes with DSM-5 based PTSD symptoms.

Author information

1
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.
2
Alcohol Research Center, Department of Psychiatry, Geffen School of Medicine, UCLA, CA, USA.
3
UCLA/Duke University National Center for Child Traumatic Stress, Department of Psychiatry, Geffen School of Medicine, University of California, Los Angeles (UCLA), CA, USA.
4
Collaborative Neuroscience Network, Garden Grove, CA, USA.
5
Department of Psychology, University of California at Riverside, CA, USA.
6
Sequencing & Genotyping Core, Department of Human Genetics, UCLA, CA, USA.
7
Department of Epidemiology, UCLA Fielding School of Public Health; Epilepsy Genetics/Genomics Laboratories, VA GLAHS, Los Angeles, CA, USA.

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.

LIMITATIONS:

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.

CONCLUSION:

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.

KEYWORDS:

Catechol-O-methyltransferase (COMT); Genetics; PTSD; Trauma; Tryptophan hydroxylase 2 (TPH 2)

PMID:
25451452
DOI:
10.1016/j.jad.2014.10.034
[Indexed for MEDLINE]

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