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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.

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