The neuropathology of schizophrenia: A selective review of past studies and emerging themes in brain structure and cytoarchitecture

Neuroscience. 2015 Sep 10;303:82-102. doi: 10.1016/j.neuroscience.2015.06.028. Epub 2015 Jun 23.


Schizophrenia is a devastating mental illness. Although its etiology is still largely unknown, strides have been taken throughout the last several decades to elucidate the nature of the neuropathology behind this disorder. The advent of neuroimaging technologies such as computerized axial tomography and magnetic resonance imaging have progressed knowledge about the macroscopic brain changes that occur in schizophrenia, including the characteristic enlarged ventricle size and reductions in gray matter volume, whole-brain volume, and white matter anisotropy. Although this review presents a broad outline of current and historical neuropathological research, the focus is primarily on the quantitative neuropathology of the cerebral cortex in schizophrenia, which may underlie many of the larger scale changes observed. The reduced neuropil hypothesis has been suggested as a microanatomical explanation to account for these macroscopic changes, although the present review finds that evidence does not always support this. A quantitative meta-analytic summary of these studies, focused on neuron density, provides support for the finding of increased neuron density in schizophrenia, with variation dependent on age. This is consistent with neuroimaging data and implicates an altered aging trajectory as a factor in the pathogenesis of schizophrenia. Combined with evidence from other neuroanatomical studies reviewed here, as well as studies in childhood-onset schizophrenia, the evidence converges on a progressive neurodevelopmental model of schizophrenia related to altered neuroplasticity. The evidence also supports a particular vulnerability of inhibitory cortical circuits with markers of interneurons showing some of the more consistent reductions in schizophrenia.

Keywords: aging; inhibition; neuron; neuropathology; neuroplasticity; schizophrenia.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / pathology*
  • Cell Count
  • Cerebral Cortex / pathology
  • Encephalitis / complications
  • Encephalitis / pathology
  • Humans
  • Microglia / pathology
  • Neurons / pathology
  • Schizophrenia / etiology
  • Schizophrenia / pathology*