Current understanding of the interplay between catechol-O-methyltransferase genetic variants, sleep, brain development and cognitive performance in schizophrenia

Abnormal sleep is an endophenotype of schizophrenia. Here we provide an overview of the genetic mechanisms that link specific sleep physiological processes to schizophrenia-related cognitive defects. In particular, we will review the possible relationships between catechol-O-methyltransferase (COMT), sleep regulation and schizophrenia development. Recent studies validate the hypothesis that COMT mutations may trigger disturbances during adolescence that affect sleep and cortical development. Anomalies in cortical development during this critical developmental phase may increase the susceptibility for schizophrenia. In conclusion, in view of therapeutic efficacy, we can envisage indications for future investigations into the role of COMT for sleep regulation, cognitive performance and sleep-related cognitive deficits.