Distribution of Microtubule-Associated Protein MAP2-Immunoreactive Interstitial Neurons in the Parahippocampal White Matter in Subjects With Schizophrenia

Abstract

OBJECTIVE: Evidence suggests that schizophrenia is a neurodevelopmental disorder that may involve abnormal connectivity between various cortical and subcortical brain areas. The parahippocampal gyrus is an area important for higher cognition in which a variety of cytoarchitectural, neuronal morphometric, and innervation abnormalities in schizophrenia have been reported. Previous studies have reported abnormal distributions of interstitial white matter neurons in prefrontal, parietal, and temporal neocortices, which suggests that schizophrenia may be related to prenatal disturbances in the cortical subplate, a transitory structure involved in the formation of connections in the developing cortex from which the interstitial white matter neurons derive. Abnormalities in the distribution of interstitial white matter neurons in the parahippocampal gyrus in schizophrenia may indicate an alteration in the migration of subplate neurons or in the pattern of programmed cell death that could lead to defective cortical circuitry and impaired cognition. METHOD: The authors used a monoclonal antibody against the microtubule-associated protein MAP2 to label interstitial white matter neurons in the anterior region of the parahippocampal gyrus from 41 individuals with schizophrenia and 15 comparison subjects. The distribution of MAP2-labeled neurons in relation to the gray matter/white matter boundary was determined by computer-assisted microscopy. RESULTS: The number of interstitial white matter neurons decreased with increasing white matter depth in both groups, but significantly more slowly in the schizophrenia group, with interstitial white matter neurons located deeper in white matter in schizophrenia subjects. CONCLUSIONS: These findings indicate there is an abnormality in the residua of the cortical subplate in the anterior region of the adult parahippocampal gyrus in schizophrenia subjects.