Our integrative neuroscience model of emotion processing proposes that the effects of genetic polymorphisms on emotional function and risk for disorders of negative affect may vary with gender. The COMT Met allele has been related to anxiety traits (in women), while MAO-A genotypes have been linked to anxiety and phobic disorders (in women) and increased aggression (in men). Using a facial emotion perception task, we examined the role of neuroimaging endophenotypes in the association between COMT, MAO-A and negative mood, and the moderating effects of gender.
About 273 healthy subjects from the Brain Resource International Database provided data from cheek swabs (for genotyping). We assessed mood and temperament (using DASS and NEO), and emotion-related brain function (using event-related potential recording).
COMT heterozygotes (V/M) were associated with higher neuroticism, and reduced and delayed neural responses to emotion in women. By contrast, while the MAO-A genotype showed no direct effects on negative mood, the high-activity alleles were associated with faster and greater responses to emotion in men.
The gender-related dissociation in the impact of COMT and MAO-A on emotion processing and negative mood suggests that these variants contribute to the differential expression of mood disorders in men and women. Integrative genotype-endophenotype makers may offer promise as a tool to aid in early identification of vulnerability to mood disorder and the selection of optimal treatments.