O R I G I N A L R E S E A R C H 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 Schofield3,4 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 Correspondence: Karin Hoth Centers for Behavioral and Preventive Medicine, One Hoppin Street, Coro West, 3rd Floor, Providence, RI 02903, USA Tel +1 401 793 8788 Fax +1 401 793 8287 Email Karin_Hoth@Brown.edu 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 Introduction Recent genetic linkage and epidemiological studies have focused on the identification of genetic polymorphisms thought to confer an increased risk for psychiatric symptoms, including anxiety and depression. The catechol-O-methyltransferase (COMT) gene has been implicated in the expression of anxiety and depression secondary to its role in the enzymatic degradation of adrenaline, noradrenaline, and dopamine (Lannfelt et al 1992; Akil et al 2003). A functional polymorphism characterized by a substitution of methionine (Met) in place of valine (Val) at codon 158 results in a 2- to 4-fold decrease in the activity of the COMT enzyme. Functional effects of the polymorphism for neurotransmission in the brain have been documented (Akil et al 2003; Bray et al 2003) and it has been suggested that the low enzyme activity allele (Met) increases susceptibility to a range of psychiatric symptoms (Shifman et al 2004). Findings from studies examining the association between the COMT polymorphism and the expression of affective symptoms in clinical populations are mixed. Although some authors have observed an association between the Met allele and affective disorders (Li et al 1997; Kirov et al 1998; Mynett-Johnson et al 1998; Papolos et al 1998), others have found no association (Ohara et al 1998b; Frisch et al Neuropsychiatric Disease and Treatment 2006:2(2) 219–225 © 2006 Dove Medical Press Limited. All rights reserved 219