Interrogating the Relationship Between Schizotypy, the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism, and Neuronal Oscillatory Activity.

The COMT Val158Met polymorphism affects the availability of synaptic dopamine in the prefrontal cortex and has been widely studied as a genetic risk factor for psychosis. Schizotypy is associated with an increased risk of psychosis, with some studies implicating similar neurobiological mechanisms to schizophrenia. The present study sought to interrogate the link between the COMT Val158Met polymorphism and schizotypy using electroencephalogram (EEG) to identify neurophysiological mechanisms underpinning psychosis risk. Neurotypical (N = 91) adults were genotyped for the COMT Val158Met polymorphism, completed the Schizotypal Personality Questionnaire (SPQ), and had eyes open resting-state EEG recorded for 4 min. SPQ suspiciousness subscale scores were higher for individuals homozygous for Val/Val and Met/Met versus Val/Met genotypes. Delta, theta, alpha-2, beta-1, and beta-2 amplitudes were lower for Val/Val than Met/Met individuals. Lower theta amplitudes were correlated with higher total SPQ scores (P = 0.050), and multiple regression revealed that higher delta, and lower theta and beta-2 amplitudes (but not COMT genotype) best predicted total SPQ scores (P = 0.014). This study demonstrates the importance of COMT genotype in determining trait suspiciousness and EEG oscillatory activity. It also highlights relationships between dopaminergic alterations, EEG and schizotypy that are dissimilar to those observed in schizophrenia.