Morphological changes in gray matter volume correlate with catechol-O-methyl transferase gene Val158Met polymorphism in first-episode treatment-naïve patients with schizophrenia.

The catechol-O-methyltransferase (COMT) gene is a schizophrenia susceptibility gene. A common functional polymorphism of this gene, Val158/158Met, has been proposed to influence gray matter volume (GMV). However, the effects of this polymorphism on cortical thickness/surface area in schizophrenic patients are less clear. In this study, we explored the relationship between the Val158Met polymorphism of the COMT gene and the GMV/cortical thickness/cortical surface area in 150 first-episode treatment-naïve patients with schizophrenia and 100 healthy controls. Main effects of diagnosis were found for GMV in the cerebellum and the visual, medial temporal, parietal, and middle frontal cortex. Patients with schizophrenia showed reduced GMVs in these regions. And main effects of genotype were detected for GMV in the left superior frontal gyrus. Moreover, a diagnosis × genotype interaction was found for the GMV of the left precuneus, and the effect of the COMT gene on GMV was due mainly to cortical thickness rather than cortical surface area. In addition, a pattern of increased GMV in the precuneus with increasing Met dose found in healthy controls was lost in patients with schizophrenia. These findings suggest that the COMTMet variant is associated with the disruption of dopaminergic influence on gray matter in schizophrenia, and the effect of the COMT gene on GMV in schizophrenia is mainly due to changes in cortical thickness rather than in cortical surface area.