Genetic pathways to posttraumatic stress disorder and depression in children: Investigation of catechol-O-methyltransferase (COMT) Val158Met using different PTSD diagnostic models

Abstract

The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been linked to PTSD, although findings have been inconsistent. Recently, different diagnostic criteria for PTSD have been introduced by ICD-11 and DSM-5, including separate criteria for adults and for young children (i.e., the preschool criteria). The preschool criteria may be applicable to older children as well. This study is the first to examine COMT associations with depression and PTSD, using new diagnostic models, in school-age children (7–11 years) exposed to a natural disaster. Children (n = 115) provided saliva samples for genotyping and completed measures assessing disaster exposure, posttraumatic stress, and depressive symptoms. COMT Met allele carriers were at risk for PTSD, but only when using ICD-11 (OR = 6.99) or the preschool criteria (OR = 4.77); there was a trend for DSM-IV and no association for DSM-5 (adult criteria). However, all children agreed upon as having PTSD by both DSM-5 and ICD-11 were Met allele carriers. The genetic association between the COMT Met allele and PTSD seemed primarily driven by arousal symptoms, as a significant relationship emerged only for the PTSD arousal symptom cluster. In contrast, COMT Val allele homozygosity was associated with depression (OR = 4.34). Thus, findings suggest that opposing COMT genotypes increased vulnerability to depressive versus arousal-based clinical presentations following trauma exposure. As a result, the heterogeneity of the DSM-5 PTSD criteria and its inclusion of depressive symptoms may mask COMT associations with DSM-5 PTSD. Future research should consider how the use of different diagnostic models of PTSD may influence genetic findings.