ArticleInternational journal of molecular sciences2026
Steroidomic Differences Among Clozapine, Olanzapine, and Risperidone in Male Patients with First-Episode Psychosis, Including a Treatment-Resistant Schizophrenia Subgroup.
Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Clozapine (Clo) is the most effective antipsychotic for treatment-resistant schizophrenia (TRS), yet the mechanisms underlying its unique clinical profile remain insufficiently understood. Neuroactive steroids (NASs) influence neuronal excitability, neuroplasticity, inflammation, and stress responses-domains disrupted in schizophrenia-and may contribute to antipsychotic pharmacodynamics. This pilot study examined whether Clo exhibits a distinctive steroidomic pattern compared with olanzapine (Ola) and risperidone (Ris) in male patients with first-episode psychosis, including a clinically defined TRS subgroup receiving Clo. Serum collected after group-specific treatment durations (Clo: 17.7 ± 12.4; Ola: 13.9 ± 1.9; Ris: 12.9 ± 1.3 months) was analyzed by GC-MS/MS, with steroidogenic enzyme activities inferred from precursor-product molar ratios as proxies of metabolic balance. Statistical evaluation included age-adjusted ANCOVA, OPLS, multiple regression, and trend-based analysis of coordinated pathway-level shifts. Although Ola increased several steroid concentrations, its overall and unconjugated trends did not differ significantly from Clo (
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