Dopaminergic influence of antipsychotic treatment outcomes in schizophrenia

Purpose: Schizophrenia is a challenging health condition characterized by a wide range of symptoms and varying responses to treatment. Studies on how genes affect drug responses have been promising. In particular, genes involved in the dopamine system of the brain, such as dopamine receptor D1 (<i>DRD1</i>), dopamine receptor D2 (<i>DRD2</i>), dopamine receptor D3 (<i>DRD3</i>), and catechol-O-methyltransferase (<i>COMT</i>) appear to play key roles in the response of patients to antipsychotic medications. This review examined studies on specific genes involved in the dopaminergic system, which plays a key role in how antipsychotic drugs work.Methods: The PubMed, Scopus, Web of Science, and Google Scholar databases were searched, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the protocol was registered with PROSPERO (CRD420251168294). Eligible studies included patients diagnosed with schizophrenia who were treated with antipsychotics and had dopaminergic gene variant data.Results: Of 73 screened articles, 26 met the inclusion criteria. Among the gene variants studied, <i>COMT</i> rs4680 and <i>DRD2</i> rs1800497 showed consistent links to treatment responses, particularly in reducing symptom severity as measured by the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scores. The relationship between genetic variants and clinical outcomes was statistically significant (P=0.007), whereas the study design showed no such association (P=0.416). Forest plots revealed varied effect sizes across gene families, with <i>COMT</i> and <i>DRD2</i> generally showing odds ratios >1.0, indicating a favorable impact on treatment.Conclusion: Our findings suggest that certain dopaminergic gene variants, especially <i>COMT</i> rs4680 and <i>DRD2</i> rs1800497, may serve as valuable markers for predicting the response of patients with schizophrenia to antipsychotic therapy.