Cell biology of the hippocampal formation in schizophrenia

Biol Psychiatry. 1999 Feb 15;45(4):395-402. doi: 10.1016/s0006-3223(98)00331-x.


The hippocampal formation (HF) has been a centerpiece of neuropathologic investigations of schizophrenia. Numerous MRI studies have demonstrated a slight bilateral reduction in HF volume. Reports of reduced N-acetyl aspartate measured with in vivo proton spectroscopy suggest that neuronal pathology exists. However, morphometric data from postmortem studies have not revealed a clear change in HF size, and recent studies of neuronal number and of cytoarchitecture have been largely negative. Evidence of glial proliferation is consistently absent. The most reproducible positive anatomic finding in postmortem HF has been reduced size of neuronal cell bodies. Studies of gene transcription have provided replicable evidence of decreased expression of mRNAs for synaptophysin, GAP-43, cholecystokinin, and non-NMDA glutamate receptor subunits (GLU R 1 and 2), particularly in CA 3-4. These data about the cellular and molecular biology of the HF in schizophrenia are different from that found in a number of conditions associated with hippocampal damage, including excitotoxicity, epilepsy, alcoholism, Alzheimer's disease, steroid neurotoxicity, and normal aging. Notwithstanding the real possibility that the data are epiphenomena of chronic illness, the findings may implicate a unique cellular defect in schizophrenia--a genetic variation affecting the plasticity of HF circuitry and connectivity. Directions for further research are proposed.

Publication types

  • Review

MeSH terms

  • Hippocampus / metabolism
  • Hippocampus / pathology*
  • Humans
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Pathways / pathology
  • Neural Pathways / physiopathology
  • Neuronal Plasticity / physiology
  • Neurons / metabolism
  • Neurons / pathology*
  • Phenotype
  • Schizophrenia / genetics
  • Schizophrenia / metabolism
  • Schizophrenia / pathology*
  • Transcription, Genetic


  • Nerve Tissue Proteins