ORIGINAL ARTICLE Interrogating the Relationship Between Schizotypy, the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism, and Neuronal Oscillatory Activity Genevieve Z. Steiner 1,2 , Francesca M. Fernandez 3,4,5 , Madilyn Coles 1 , Diana Karamacoska 1,2 , Emma Barkus 5 , Samantha J. Broyd 5 , Nadia Solowij 5 , Owen T. Watson 6 , Christine L. Chiu 6 , Joanne M. Lind 6,7 and Robert J. Barry 2 1 NICM Health Research Institute and Translational Health Research Institute (THRI), Western Sydney University, Penrith NSW 2751, Australia, 2 Brain & Behavior Research Institute and School of Psychology, University of Wollongong, Wollongong NSW 2522, Australia, 3 Faculty of Science, Medicine and Health, University of Wollongong, Wollongong NSW 2522, Australia, 4 School of Science, Australian Catholic University, Brisbane QLD 4014, Australia, 5 School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong NSW 2522, Australia, 6 Faculty of Medicine and Health Sciences, Macquarie University, Macquarie Park NSW 2190, Australia and 7 School of Medicine,Western Sydney University, Penrith NSW 2751, Australia Address correspondence to Genevieve Z. Steiner, Western Sydney University, Locked Bag 1797, Penrith NSW 2751, Australia, email: G.Steiner@ westernsydney.edu.au orcid.org/0000-0002-8708-6104 Abstract 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. Key words: COMT Val158Met polymorphism (rs4680), electroencephalograph (EEG), eLORETA, Schizotypy © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com Cerebral Cortex, July 2019; 3048–3058 doi: 10.1093/cercor/bhy171 Advance Access Publication Date: 31 July 2018 Original Article Downloaded from https://academic.oup.com/cercor/article/29/7/3048/5062355 by guest on 08 December 2022