Blood-Brain Barrier Disruption in Schizophrenia: Insights, Mechanisms, and Future Directions

The blood-brain barrier (BBB) plays a crucial role in maintaining the homeostasis of the central nervous system by regulating solute transport and preventing neurotoxic substances from infiltrating brain tissue. In schizophrenia, emerging evidence identifies BBB dysfunction as a key pathophysiological factor associated with neuroinflammation, tight junction abnormalities, and endothelial dysfunction. Recent advancements in neuroimaging techniques, such as arterial spin labeling (ASL), have provided valuable tools for investigating BBB permeability and its role in disease progression. This review synthesizes findings from postmortem studies, serum and cerebrospinal fluid biomarker analyses, and advanced neuroimaging research to elucidate BBB alterations in schizophrenia. It highlights the mechanistic roles of tight junction protein dysregulation, neurovascular unit dysfunction, and immune responses in disrupting BBB integrity. Furthermore, the review examines the bidirectional effects of antipsychotic medications on BBB, addressing both therapeutic opportunities and potential challenges. By emphasizing the pivotal role of BBB dysfunction in schizophrenia pathogenesis, this review underscores its translational potential. Through the integration of multidisciplinary evidence, it lays the foundation for innovative diagnostic approaches and therapeutic strategies, enhancing our understanding of schizophrenia's complex pathophysiology.