Genetically based reduced MAOA and COMT functioning is associated with the cortisol stress response - a replication study

In 2007, Molecular Psychiatry published a unique study by Jabbi and colleagues, in which they showed that the combination of genetic variance in the MAOA and COMT gene was associated with increased responses of the HPA axis to stress. This finding was replicated in the TRAILS study and published as Letter to the Editor in Molecular Psychiatry. Our letter addresses the combined influence of the MAOA length polymorphism and the COMT val158met SNP on saliva cortisol responses towards a standardized social stress test in a large (n = 452) sample of adolescents (mean age 16.01 yrs, 38.5% girls, no oral contraceptive users). Jabbi et al. (1) showed that the COMT met/met genotype in combination with low MAOA, present in males predominantly, was associated with increased ACTH responses. We replicated this association in adolescent boys. The effect of COMT in the low MAOA group was different between boys and girls. The highest cortisol levels and most pronounced responses were observed in met/met boys while in val/val girls. This gender difference is in concordance with the hypothesized differential effects of high and low COMT functioning in the development of mental disorders in men and women. Our finding should be interpreted with caution; although our overall sample size was large, the low MAOA genotype group consisted of only 29 girls (relative to 100 boys).