Table_1_COMT, 5-HTR2A, and SLC6A4 mRNA Expressions in First-Episode Antipsychotic-Naïve Schizophrenia and Association With Treatment Outcomes.xlsx

Background: Dopaminergic and serotonergic systems play crucial roles in the pathophysiology of schizophrenia and modulate response to antipsychotic treatment. However, previous studies of dopaminergic and serotonergic genes expression are sparse, and their results have been inconsistent. In this longitudinal study, we aim to investigate the expressions of Catechol-O-methyltransferase (COMT), serotonin 2A receptor (5-HTR2A), and serotonin transporter gene (SLC6A4) mRNA in first-episode antipsychotic-naïve schizophrenia and to test if these mRNA expressions are associated with cognitive deficits and treatment outcomes or not.

Method: We measured COMT, 5-HTR2A, and SLC6A4 mRNA expressions in 45 drug-naive first-episode schizophrenia patients and 38 health controls at baseline, and repeated mRNA measurements in all patients at the 8-week follow up. Furthermore, we also assessed antipsychotic response and cognitive improvement after 8 weeks of risperidone monotherapy.

Results: Patients were divided into responders (N = 20) and non-responders groups (N = 25) according to the Remission criteria of the Schizophrenia Working Group. Both patient groups have significantly higher COMT mRNA expression and lower SLC6A4 mRNA expression when compared with healthy controls. Interestingly, responder patients have significantly higher levels of COMT and 5-HTR2A mRNA expressions than non-responder patients at baseline. However, antipsychotic treatment has no significant effect on the expressions of COMT, 5-HTR2A, and SLC6A4 mRNA over 8-week follow up.

Conclusion: Our findings suggest that dysregulated COMT and SLC6A4 mRNA expressions may implicate in the pathophysiology of schizophrenia, and that COMT and 5-HTR2A mRNA may be potential biomarkers to predict antipsychotic response.