Schizophrenia Pathophysiology a Product of NMDA Receptor and GABA Interneuron Dysregulation in the Prefrontal Cortex and Hippocampus

Abstract

Schizophrenia is noted for its complexity, owing to its heterogeneous expression and encompassment of symptoms that are seemingly opposite in nature. The current therapeutic efficacy against schizophrenia is limited, necessitating the translation of more descriptive biochemical mechanisms into the clinical scene. One converging mechanism, which implicates the dysregulation of excitatory N-methyl-D-aspartate (NMDA) receptors and inhibitory γ-Aminobutyric acid (GABA) interneurons, provides a complete biochemical mechanism that accounts for the diverse symptomatology of schizophrenia. Specifically, the dysfunction of NMDA receptors on GABA interneurons alters inhibitory and excitatory activity differentially in the prefrontal cortex (PFC) and hippocampus, giving rise to divergent abnormalities. Evidence from various studies suggests that NMDA-GABA interneuron dysfunction serves as a one of the primary contributors of schizophrenic pathophysiology and is possibly implicated in its pathogenesis, indicating the mechanism\u27s significant clinical potential