Schizophrenia: Converging Neurobiological Mechanisms and Emerging Therapeutic Strategies

Schizophrenia is a highly heterogeneous neuropsychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive impairment, with substantial long-term functional consequences. 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–brain 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.