Schizophrenia: Current Advances in Neurobiology, Genomics, Diagnostic Strategies, and Novel Therapeutic Interventions

Abstract

Schizophrenia is a severe, chronic, and highly heterogeneous neuropsychiatric disorder that affects approximately 1% of the global population. It is one of the leading causes of disability among young adults and imposes a substantial clinical, social, and economic burden worldwide. The disorder is characterized by positive and negative symptoms, cognitive impairment, and social dysfunction, all of which markedly reduce patients' quality of life. Despite decades of intensive research, the underlying mechanisms of schizophrenia remain incompletely understood. Current evidence indicates that its pathogenesis arises from complex interactions among genetic susceptibility, neurodevelopmental abnormalities, environmental risk factors, immune dysregulation, and dysfunction of multiple neurotransmitter systems. Recent advances in molecular genetics, epigenetics, neuroimaging, and systems neuroscience have fundamentally reshaped our understanding of the disease. Schizophrenia is now recognized as a disorder of disrupted neural circuitry, impaired synaptic plasticity, and abnormal brain connectivity rather than a consequence of a single neurotransmitter imbalance. This review provides a comprehensive and up-to-date overview of schizophrenia, covering its epidemiology, clinical manifestations, major risk factors, molecular pathophysiology, diagnostic advances, and emerging therapeutic strategies. Particular emphasis is placed on the interactions among dopaminergic, glutamatergic, γ-aminobutyric acid (GABA)-ergic, serotonergic, cholinergic, and neuroinflammatory pathways and their contributions to cortical circuit dysfunction, cognitive decline, and psychotic symptoms. Finally, the review integrates current molecular, genetic, neurodevelopmental, and clinical evidence to highlight recent advances in schizophrenia research and their implications for precision diagnosis, personalized medicine, and the development of mechanism-based therapeutic interventions.