Abstract

Schizophrenia is a chronic, severe, and disabling neuropsychiatric disorder that affects approximately 20 to 24 million people globally. Characterized by a wide spectrum of positive, negative, cognitive, and affective symptoms, its etiology and pathophysiology remain multifaceted and influenced by multiple interacting factors. Advances in brain science and neurological research have shifted the traditional dopamine-centric model to incorporate glutamatergic and GABAergic dysfunctions, neurodevelopmental disruptions, immune dysregulation, and oxidative stress. Genetic and epigenetic factors further contribute to disease vulnerability, interacting dynamically with environmental risk factors such as perinatal complications, psychosocial stress, and substance use. Modern diagnostic approaches now explore molecular, imaging, genetic, and proteomic biomarkers alongside emerging tools like digital phenotyping and artificial intelligence (AI) based analysis to improve early detection and individualized care. Neuroimaging studies consistently reveal gray matter loss, altered connectivity, and ventricular enlargement, while Electroencephalograph and event-related potentials have identified potential endophenotypes. Despite the availability of first- and second-generation antipsychotics, approximately 20% to 30% of patients experience treatment-resistant schizophrenia (TRS), for which clozapine remains the most effective option. Emerging pharmacotherapies targeting glutamate, gamma-aminobutyric acid (GABA), and inflammatory pathways are under investigation to address cognitive and negative symptoms more effectively. Nonpharmacological interventions, such as cognitive behavioral therapy (CBT), family-based psychosocial programs, digital therapeutics, and virtual reality (VR)-based treatments, are being increasingly integrated into comprehensive care plans. These approaches aim to enhance coping, reduce the likelihood of relapse, and improve overall quality of life. While significant challenges persist, including stigma, unequal access to care, and translational gaps between research and practice, the future of schizophrenia management lies in precision psychiatry and the development of personalized, integrative treatment strategies. This review highlights the current neurological and pathophysiological insights into schizophrenia, explores novel diagnostic and therapeutic innovations, and underscores the urgent need to bridge research with real-world clinical practice for improved patient outcomes.

Keywords

neurotransmitters, neurochemical signaling, prefrontal cortex, dopamine hypothesis, gabaergic systems, clozapine, virtual reality, artificial intelligence