Interplay between COMT Val158Met, childhood adversities and sex in predicting panic pathology: Findings from a general population sample

Abstract Background The single nucleotide polymorphism rs4680 of the catechol-O-methyltransferase ( COMT ) gene has been implicated to be involved in the etiopathogenesis of panic. However, it remains unresolved whether rs4680 modifies the risk-association between early life stress and subsequent development of panic pathology. Methods The genotype of rs4680 was determined for n = 2242 adults with European ancestry from the Study of Health in Pomerania (SHIP, a regional longitudinal cohort study from northeastern Germany). Lifetime fearful spells, panic attacks and panic disorder were assessed according to DSM-IV in 2007–2010 (when participants were aged 29–89) using the Munich Composite International Diagnostic Interview (DIA-X/M-CIDI). Childhood adversities were assessed with the Childhood Trauma Questionnaire (CTQ). Results Logistic regressions with interaction terms (adjusted for sex and age) revealed that rs4680 interacted with total childhood adversity, emotional abuse and physical abuse in predicting panic disorder: Respective childhood adversities predicted panic disorder in carriers of the Val/Met or Met/Met genotype, but not Val/Val genotype. Moreover, a 3-way interaction was found between rs4680, emotional abuse and sex in predicting panic attacks: Emotional abuse predicted panic attacks among male carriers of the Val/Val genotype and female carriers of the Val/Met or Met/Met genotype, but not among male carriers of the Val/Met or Met/Met genotype or female carriers of the Val/Val genotype. Limitations Genotype data were derived by imputation. Childhood adversities and panic were assessed retrospectively. Conclusions Especially (female) carriers of the Val/Met or Met/Met genotype of rs4680 might profit from targeted early interventions to prevent the onset of panic after childhood adversities.