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Although dopaminergic dysfunction remains central to current disease models and treatment, dopamine-centered frameworks alone cannot fully explain cognitive deficits, treatment resistance, or marked variability in therapeutic response. Emerging evidence supports a broader view in which genetic susceptibility and environmental exposures converge on multiple interacting biological systems, including dopaminergic and glutamatergic neurotransmission, neuroimmune and glial dysfunction, kynurenine pathway metabolism, large-scale brain network dysconnectivity, and gut\u2013brain communication. In this review, we integrate these mechanisms within a systems-level framework and discuss how their interactions may contribute to symptom heterogeneity and disease progression. We further examine the limitations of conventional dopamine D2-based antipsychotics, emerging non-dopaminergic pharmacological strategies, and adjunctive interventions targeting cognition and functional recovery. Finally, we highlight major translational barriers, including treatment resistance, medication non-adherence, adverse-effect burden, and the lack of clinically actionable biomarkers. An integrated understanding of converging neurobiological mechanisms may provide a stronger foundation for mechanism-informed patient stratification and precision treatment in schizophrenia.<\/jats:p>","DOI":"10.3390\/biom16091283","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T16:07:32Z","timestamp":1788538052000},"page":"1283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Schizophrenia: Converging Neurobiological Mechanisms and Emerging Therapeutic Strategies"],"prefix":"10.3390","volume":"16","author":[{"given":"Chun-Mei","family":"Gong","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Basic Medical Sciences, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China"},{"name":"Key Laboratory of Brain Science Research Transformation in Tropical Environment of Hainan Province, School of Basic Medical Sciences, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China"},{"name":"Department of Human Anatomy, School of Basic Medical Sciences, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Ze","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Basic Medical Sciences, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China"},{"name":"Key Laboratory of Brain Science Research Transformation in Tropical Environment of Hainan Province, School of Basic Medical Sciences, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine 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