Executive control in schizophrenia: a preliminary study on the moderating role of COMT Val158Met for comorbid alcohol and substance use disorders

Abstract

Background: A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val158Met) appears to influence cognition in people with alcohol/substance use disorders (AUD/SUD) and in those with psychosis.

Methods: To explore the potential moderating effect of these factors, a cross-sectional study was conducted, randomly recruiting subjects with DSM-IV diagnosis of schizophrenia. AUD/SUD was rigorously assessed, as well as COMT Val158Met polymorphism. Executive control functioning was measured using the Intra-Extra Dimensional Set Shift (IED). The effect of a possible interaction between comorbid AUD/SUD and COMT Val158Met polymorphism on IED scores was explored.

Results: Subjects with schizophrenia, comorbid AUD/SUD, and MetMet carriers for SNP rs4680 of the COMT gene showed worse performance on IED completed stages scores, as compared with individuals with ValVal genotype. However, among subjects without AUD/SUD, those with the MetMet variant performed better than people carrying ValVal genotype.

Conclusions: This study is the first to date examining the impact of COMT on cognition in a highly representative sample of people with schizophrenia and comorbid AUD/SUD. Differential moderating effects of COMT Val/Met genotype variations may similarly influence executive functions in people with schizophrenia and comorbid AUD/SUD.

Keywords:

• Dopamine
• genetic polymorphism
• neuropsychology
• schizophrenia
• substance dependence

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Notes on contributors

Giuseppe Carrà, MD, MSc, PhD, is a Researcher at the Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy.

Gabriella Nicolini, PhD, is a Researcher at the Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy.

Cristina Crocamo, PhD, is a Post-doctoral researcher at the Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy.

Annamaria Lax, MD, is a psychiatrist at the Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy.

Francesca Amidani, MD, is a psychiatrist at the Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy.

Francesco Bartoli, MD, got his PhD in Neurosciences, and is now completing specialist training at the Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy.

Filippo Castellano, MD, PhD, is a psychiatrist at the Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy.

Alessia Chiorazzi, PhD, is a Post-doctoral researcher at the Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy.

Giulia Gamba, MD, is undergoing specialist training in Psychiatry at the Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy.

Costanza Papagno, MD, PhD, is a Full Professor of Psychology at the Department of Psychology, University of Milano Bicocca, Milano, Italy.

Massimo Clerici, MD, PhD is an Associate Professor of Psychiatry at the Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy.