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

Neuropsychopharmacology. 2019 May;44(6):1055-1061. doi: 10.1038/s41386-019-0350-7. Epub 2019 Feb 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Auditory Cortex / cytology
  • Auditory Cortex / diagnostic imaging
  • Auditory Cortex / pathology*
  • Autopsy
  • Case-Control Studies
  • Cell Count
  • Cohort Studies
  • Dendritic Spines / pathology*
  • Dendritic Spines / ultrastructure
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Microscopy, Confocal
  • Microtubule-Associated Proteins*
  • Middle Aged
  • Psychotic Disorders / diagnostic imaging
  • Psychotic Disorders / pathology*
  • Pyramidal Cells / pathology*
  • Pyramidal Cells / ultrastructure
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / pathology*


  • MAP2 protein, human
  • Microtubule-Associated Proteins