Mazandaran Association of Emergency Medicine Humanistic Studies and Social Researches 3092-6467 2 1 2025 12 21 The Neurobiological Basis of Schizophrenia: An Integrative Review 236750 10.22034/hssr.2025.236750 EN Salayeva Navbahor Department of Pedagogy and Psychology, Urgench State University, Urgench, Uzbekistan. Sadullayeva Sevara Department of Psychological Sciences, Mamun University, Khiva, Uzbekistan Ollaberganov Zayniddin Umarbekovich Department of Medicine, Urgench Mamun University, Urgench, Uzbekistan. Khajiqurbonova Niginabonu Department of Clinical Subjects, Tashkent State Medical University, Tashkent, Uzbekistan. Sultanov Muhammad Department of Psychology, Mamun University, Khiva, Uzbekistan. Saginova Aygerim Sisenbayevna Department of Medicine, Urgench Mamun University, Urgench, Uzbekistan. Journal Article Background: Schizophrenia is a severe psychiatric disorder characterized by a complex, multifactorial origin. While dopaminergic theories have been predominant, contemporary perspectives highlight an integrated dysfunction across genetic, molecular, and neural circuit levels, rooted in neurodevelopmental abnormalities. Objectives: This review synthesizes recent evidence from genetics, neuroimaging, and molecular psychiatry to present an updated model of schizophrenia pathophysiology. It focuses on the interplay between synaptic pruning, interneuron dysfunction, and brain network dysconnectivity. Methods: We conducted a narrative, integrative review. Searches in PubMed, Scopus, and Web of Science (2014-2025) utilized terms like "schizophrenia neurobiology," "dysconnectivity," "NMDA receptor hypofunction," "parvalbumin interneurons," and "genetic risk." Evidence was thematically synthesized to construct a coherent pathophysiological model. Results: Findings outline a pathway from genetic risk (e.g., complement C4 loci) to excessive adolescent synaptic pruning, leading to impairment of parvalbumin-positive GABAergic interneurons. This results in N-methyl-D-aspartate receptor (NMDAR) hypofunction, a disrupted cortical excitation/inhibition balance, and aberrant neural oscillations. These local deficits manifest as large-scale dysconnectivity within cortico-striato-thalamo-cortical (CSTC) circuits, underpinning positive, negative, and cognitive symptoms. Dopaminergic dysregulation is positioned downstream of primary glutamatergic/GABAergic pathology. Conclusion: Schizophrenia is best conceptualized as a neurodevelopmental disorder of synaptic connectivity. Future therapeutics should target earlier pathological stages, such as immune-mediated pruning and glutamatergic signalling, offering potential for novel treatments and preventative strategies.

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