Review of pathological hallmarks of schizophrenia: comparison of genetic models with patients and nongenetic models

Schizophr Bull. 2010 Mar;36(2):301-13. doi: 10.1093/schbul/sbp133. Epub 2009 Nov 10.


Schizophrenia is a condition that impairs higher brain functions, some of which are specific to humans. After identification of susceptibility genes for schizophrenia, many efforts have been made to generate genetics-based models for the disease. It is under debate whether behavioral deficits observed in rodents are sufficient to characterize these models. Alternatively, anatomical and neuropathological changes identified in brains of patients with schizophrenia may be utilized as translatable characteristics between humans and rodents, which are important for validation of the models. Here, we overview such anatomical and neuropathological changes in humans: enlarged ventricles, dendritic changes in the pyramidal neurons, and alteration of specific subtypes of interneurons. In this review, we will overview such morphological changes in brains from patients with schizophrenia. Then, we will describe that some of these alterations are already recapitulated even in classic nongenetic models for schizophrenia. Finally, in comparison with the changes in patients and nongenetic models, we will discuss the anatomical and neuropathological manifestation in genetic models for schizophrenia.

Publication types

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

MeSH terms

  • Animals
  • Brain / pathology*
  • Diffusion Magnetic Resonance Imaging
  • Disease Models, Animal*
  • Dominance, Cerebral / genetics
  • Dominance, Cerebral / physiology
  • Genetic Association Studies*
  • Genetic Predisposition to Disease / genetics*
  • Hippocampus / pathology
  • Humans
  • Image Processing, Computer-Assisted
  • Imaging, Three-Dimensional
  • Lateral Ventricles / pathology
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Inbred C57BL
  • Models, Genetic*
  • Nerve Tissue Proteins / genetics
  • Rats
  • Schizophrenia / genetics*
  • Schizophrenia / pathology*
  • Social Environment
  • Temporal Lobe / pathology


  • DISC1 protein, human
  • Disc1 protein, mouse
  • Nerve Tissue Proteins