Schizophrenia as a Disorder of Biological Barriers: A Narrative Review and Potential Interventions

TL;DR

This paper explores how biological barriers may be involved in schizophrenia and suggests potential interventions to maintain these barriers.

Contribution

The paper introduces a novel perspective on schizophrenia as a disorder of biological barriers and proposes new intervention strategies.

Findings

Schizophrenia may involve premature aging of neurons and glial cells, leading to cognitive symptoms.

Aryl hydrocarbon receptor may regulate gut and blood-brain barriers, influencing microorganism translocation.

Interventions targeting barrier function could prevent central nervous system pathology in schizophrenia.

Abstract

Severe mental illnesses, including schizophrenia and schizophrenia-like disorders, have been associated with premature neuronal and glial senescence, microglial activation, and gray matter volume reduction. These changes may drive clinical symptoms of schizophrenia, including cognitive impairment. Aryl hydrocarbon receptor, abundantly expressed in the intestinal and blood–brain barrier, is the master regulator of both tight junctions and cellular senescence. Under pathological circumstances, this receptor may promote premature gut aging, enabling the translocation of bacteria or their components from the gastrointestinal tract into systemic circulation and from there into the central nervous system. In this review article, we discuss a potential mechanism of schizophrenia–microorganismal migration, microglial activation, and gray matter volume reduction. We also focus on potential interventions for maintaining barrier function. These approaches include natural and synthetic modulators of the aryl hydrocarbon receptor as well as biophysical strategies to preserve barrier integrity and prevent central nervous system pathology.

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