Associations between the COMT Val/Met polymorphism, early life stress, and personality among healthy adults

Karin F Hoth¹, Robert H Paul¹, Leanne M Williams², Carol Dobson-Stone³, Elizabeth Todd³, Peter R Schofield^3,4, John Gunstad¹, Ronald A Cohen¹, Evian Gordon⁵

¹Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA; ²Brain Dynamics Centre and Discipline of Psychological Medicine, University of Sydney, Westmead Hospital, Westmead, Sydney, Australia; ³Garvan Institute of Medical Research, Sydney, Australia; ⁴Prince of Wales Medical Research Institute and University of New South Wales, Sydney, Australia; ⁵Brain Resource Company & Brain Resource International Database, Sydney, Australia

Abstract: Efforts to identify genetic factors that confer an increased risk for the expression of psychiatric symptoms have focused on polymorphisms in variety of candidate genes, including the catechol-O-methyltransferase (COMT) gene. Results from previous studies that have examined associations between the functional COMT polymorphism (Val158Met) and mental health have been mixed. In the present study, we examined the relationships between COMT, early life stress, and personality in a healthy adult sample. Consistent with previous studies, we hypothesized that individuals with the low-activity genotype would have higher neuroticism and lower extraversion and that this effect would be more pronounced in females. In addition, we extended the previous literature by investigating the potential influence of early life stress. A total of 486 healthy adults underwent genetic testing and personality assessment. Results revealed that individuals homozygous for the COMT low enzyme activity allele had lower extraversion on the NEO-FFI and demonstrated a trend toward greater neuroticism. These relationships were not influenced by sex or the presence of reported early life stress. The finding that COMT genotype was associated with extraversion, and more weakly with neuroticism, is consistent with previous studies. Future research to clarify the influence of sex and gene–environmental interactions is warranted.

Keywords: anxiety; depression; gene-environment interaction, early life stress