COMT influences on prefrontal and striatal blood oxygenation level-dependent responses during working memory among individuals with schizophrenia, their siblings, and healthy controls

Abstract

Introduction. Recent theories have suggested that corticostriatal interactions may play an important part in mediating working memory demands and may impact clinical symptomology of schizophrenia. These effects are thought to occur through changes in dopamine signalling from the midbrain and via feedback from the frontal cortex. The catechol-O-methyltransferase (COMT) Val158Met polymorphism may prove useful for studying these effects in vivo. Methods. In this study, patients with schizophrenia, their well siblings, and healthy controls were genotyped and scanned using functional magnetic resonance imaging (fMRI) while they performed a working memory task. Results. We found that patients and their siblings, but not controls, who were Val homozygotes displayed greater activity of the DLPFC, striatum, and the cerebellum during the task than respective Met carriers. We also found a relationship between striatal activity and negative symptoms for the Val homozygote group. Conclusions. Our findings support and extend previous studies of COMT effects on cognition and neural activity, and suggest that changes in dopamine availability may differentially impact corticostriatal functioning of individuals at risk for schizophrenia from those who are not. We also found some evidence supporting the proposed role of striatal dopamine signalling and clinical symptoms associated with anhedonia and apathy.