Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene

Am J Hum Genet. 2006 Sep;79(3):586-92. doi: 10.1086/507566. Epub 2006 Jul 31.

Abstract

Oxidative stress could be involved in the pathophysiology of schizophrenia, a major psychiatric disorder. Glutathione (GSH), a redox regulator, is decreased in patients' cerebrospinal fluid and prefrontal cortex. The gene of the key GSH-synthesizing enzyme, glutamate cysteine ligase modifier (GCLM) subunit, is strongly associated with schizophrenia in two case-control studies and in one family study. GCLM gene expression is decreased in patients' fibroblasts. Thus, GSH metabolism dysfunction is proposed as one of the vulnerability factors for schizophrenia.

Publication types

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

MeSH terms

  • Case-Control Studies
  • Down-Regulation
  • Fibroblasts / enzymology
  • Fibroblasts / metabolism
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Glutamate-Cysteine Ligase / genetics*
  • Glutathione / metabolism
  • Humans
  • Oxidative Stress / genetics*
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / analysis
  • Schizophrenia / enzymology
  • Schizophrenia / genetics*

Substances

  • RNA, Messenger
  • Glutamate-Cysteine Ligase
  • Glutathione