COMT genotype associated with differential cognitive responses to treatment in patients with schizophrenia

Lindenmayer, Khan, et al report in the October issue of Schizophrenia Research that a functional polymorphism of the catechol-O-methyltransferase (COMT) gene (Val158Met) affects cognitive performance in schizophrenia subjects and healthy controls by modulating prefrontal dopaminergic activity. They evaluated 145 genotyped subjects with schizophrenia or schizoaffective disorder using the MATRICS and PANSS at baseline and then again after 12 weeks of computer-guided behavioral intervention (CRT). While no differences were seen among genotype groups at baseline, significant differences favoring Met/Met and Val/Met groups were demonstrated in Verbal Learning (p=0.003), Visual Learning (p=0.014) and Attention/Vigilance (p=0.011). They conclude that subjects carrying the low activity Met allele (Met/Met; Val/Met) are likely to show significantly greater improvements in the MATRICS domains of Verbal Learning, Visual Learning and Attention/Vigilance after CRT.

This important study provides further evidence for the heterogeneity of treatment response in schizophrenia, but also points to the need for more etiologically-informed and biomarker-informed outcomes. 

For further information:

https://www.ncbi.nlm.nih.gov/pubmed/26255563