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).
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