Density of small dendritic spines and microtubule-associated-protein-2 immunoreactivity in the primary auditory cortex of subjects with schizophrenia

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 44; no. 6; pp. 1055 - 1061
• Main Authors: McKinney, Brandon C., MacDonald, Matthew L., Newman, Jason T., Shelton, Micah A., DeGiosio, Rebecca A., Kelly, Ryan M., Fish, Kenneth N., Sampson, Allan R., Lewis, David A., Sweet, Robert A.
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.05.2019; Springer International Publishing
• Subjects: Adult; Auditory Cortex - cytology; Auditory Cortex - diagnostic imaging; Auditory Cortex - pathology; Autopsy; Case-Control Studies; Cell Count; Cohort Studies; Confocal microscopy; Cortex (auditory); Dendritic spines; Dendritic Spines - pathology; Dendritic Spines - ultrastructure; Female; Humans; Immunohistochemistry; Male; Mental disorders; Microscopy, Confocal; Microtubule-Associated Proteins; Middle Aged; Phenotypes; Psychotic Disorders - diagnostic imaging; Psychotic Disorders - pathology; Pyramidal Cells - pathology; Pyramidal Cells - ultrastructure; Schizophrenia; Schizophrenia - diagnostic imaging; Schizophrenia - pathology
• ISSN: 0893-133X; 1740-634X; 1740-634X
• DOI: 10.1038/s41386-019-0350-7

Previously, we demonstrated that dendritic spine density (DSD) in deep layer 3 of the primary auditory cortex (A1) is lower, due to having fewer small spines, in subjects with schizophrenia (SZ) than non-psychiatric control (NPC) subjects. We also previously demonstrated that microtubule-associated-protein-2 immunoreactivity (MAP2-IR) in A1 deep layer 3 is lower, and positively correlated with DSD, in SZ subjects. Here, we first sought to confirm these findings in an independent cohort of 25 SZ-NPC subject pairs (cohort 1). We used immunohistochemistry and confocal microscopy to measure DSD and MAP2-IR in A1 deep layer 3. Consistent with previous studies, both DSD and MAP2-IR were lower in SZ subjects. We then tested the hypothesis that MAP2-IR mediates the effect of SZ on DSD in a cohort of 45 SZ-NPC subject pairs (combined cohort) that included all subjects from cohort 1 and two previously studied cohorts. Based on the distribution of MAP2-IR values in NPC subjects, we categorized each SZ subject as having either low MAP2-IR (SZ MAP2-IR(low)) or normal MAP2-IR (SZ MAP2-IR(normal)). Among SZ MAP-IR(low) subjects, mean DSD was significantly lower than in NPC subjects. However, mean DSD did not differ between SZ MAP2-IR(normal) and NPC subjects. Moreover, MAP2-IR statistically mediated small spine differences, with lower MAP2-IR values associated with fewer small spines. Our findings confirm that low density of small spines and low MAP2-IR are robust SZ phenotypes and suggest that MAP2-IR mediates the effect of SZ on DSD.