Catechol-O-methyltransferase Val158Met genotype in healthy and personality disorder individuals: Preliminary results from an examination of cognitive tests hypothetically differentially sensitive to dopamine functions

Winnie W Leung¹, Margaret M McClure¹, Larry J Siever^1,2, Deanna M Barch³, Philip D Harvey^1,2

¹Department of Veterans Affairs, VISN 3 Mental Illness Research, Education, and Clinical Center (MIRECC), Bronx, NY, USA; ²Department of Psychiatry, Mt. Sinai School of Medicine, New York, NY, USA; ³Departments of Psychology and Psychiatry, Washington University, St. Louis, MO, USA

Abstract: A functional polymorphism of the gene coding for Catechol-O-methyltrasferase (COMT), an enzyme responsible for the degradation of the catecholamine dopamine (DA), epinephrine, and norepinephrine, is associated with cognitive deficits. However, previous studies have not examined the effects of COMT on context processing, as measured by the AX-CPT, a task hypothesized to be maximally relevant to DA function. 32 individuals who were either healthy, with schizotypal personality disorder, or non-cluster A, personality disorder (OPD) were genotyped at the COMT Val158Met locus. Met/Met (n = 6), Val/Met (n = 10), Val/Val (n = 16) individuals were administered a neuropsychological battery, including the AX-CPT and the N-back working memory test. For the AX-CPT, Met/Met demonstrated more AY errors (reflecting good maintenance of context) than the other genotypes, who showed equivalent error rates. Val/Val demonstrated disproportionately greater deterioration with increased task difficulty from 0-back to 1-back working memory demands as compared to Met/Met, while Val/Met did not differ from either genotypes. No differences were found on processing speed or verbal working memory. Both context processing and working memory appear related to COMT genotype and the AX-CPT and N-back may be most sensitive to the effects of COMT variation.

Keywords: COMT, dopamine, context processing, working memory, schizotypal personality disorder