COMT genotype and response to cognitive remediation in schizophrenia

Background: A functional polymorphism of the catechol-. O-methyltransferase (. COMT) gene (Val158Met) partially appears to influence cognitive performance in schizophrenia subjects and healthy controls by modulating prefrontal dopaminergic activity. This study evaluated the association of the COMT Val108/158 Met genotype with response to computerized neurocognitive remediation (CRT). Method: 145 subjects with DSM-IV-TR schizophrenia or schizoaffective disorder were genotyped via saliva sampling. Subjects were evaluated on neurocognitive assessments (MATRICS) and clinical symptoms (PANSS) at baseline and endpoint after 12. weeks of CRT. "Improvement" was defined as ≥. 67% of cognitive domains (≥. 4) showing performance increases. If ≤. 67% (≤. 2) of domains improved, the change was defined as "minimal improvement." A general linear model was conducted for change of each cognitive domain. Results: Of 145 subjects, data from 138 subjects were usable. Distribution of COMT genotype: Met/Met: 28 (20.29%), Val/Met: 61 (44.20%), and Val/Val: 49 (35.51%). No significant differences were seen among genotype groups at baseline or across genotype group for "Improvement" vs. "Minimal Improvement." GLM analysis showed significant differences in Verbal Learning (p= 0.003), Visual Learning (p= 0.014) and Attention/Vigilance (p= 0.011) favoring Met/Met and Val/Met groups. Conclusions: The low activity Met allele (Met/Met; Val/Met) was associated with significantly greater improvements in the MATRICS domains of Verbal Learning, Visual Learning and Attention/Vigilance after CRT.