Recent advances in postmortem pathology and neurochemistry in schizophrenia

Curr Opin Psychiatry. 2009 Mar;22(2):154-60. doi: 10.1097/YCO.0b013e328323d52e.

Abstract

Purpose of review: This is a review examining recent data from the study of the postmortem central nervous system (CNS) of patients with schizophrenia.

Recent findings: Studies on the human CNS transcriptome suggest changes in pro-inflammatory pathways and myelination in schizophrenia, whereas changes in the proteome suggest that pathways involved in energy and metabolism may be particularly stressed. There appear to be complex changes in the expression of proposed candidate genes for schizophrenia such as NRG1, DISC1, RGS4 and DTNB1, and there are continued reports of alterations in central gamma-aminobutyric acidergic, dopaminergic, glutamatergic and cholinergic pathways in patients with the disorder. Data on epigenetic mechanisms and transcriptome regulation suggest that at least some changes in gene expression may be due to changes in levels of gene promoter methylation or microRNAs in the CNS of patients with schizophrenia.

Summary: Postmortem CNS studies have begun to unravel changes in the epigenetic regulation of gene expression that may be central to how gene-environment interactions contribute to the onset of schizophrenia. In addition, a recent study indicates that it is possible to use biomarkers to segregate the syndrome of schizophrenia into more biologically homogeneous populations, which should decrease the biological complexity observed within that group within the schizophrenia syndrome.

Publication types

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

MeSH terms

  • Brain / pathology*
  • Brain / physiopathology*
  • DNA Methylation / genetics
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology
  • Epigenesis, Genetic / genetics
  • Gene Expression / genetics
  • Gene Expression Profiling
  • Genetic Markers / genetics
  • Humans
  • MicroRNAs / genetics
  • Neural Pathways / pathology
  • Neural Pathways / physiopathology
  • Neurotransmitter Agents / genetics
  • Neurotransmitter Agents / physiology*
  • Promoter Regions, Genetic / genetics
  • Proteome / genetics
  • Risk Factors
  • Schizophrenia / genetics
  • Schizophrenia / pathology*
  • Schizophrenia / physiopathology*
  • Social Environment

Substances

  • Genetic Markers
  • MicroRNAs
  • Neurotransmitter Agents
  • Proteome