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

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.