Schizophrenia and Oxidative Stress: Glutamate Cysteine Ligase Modifier as a Susceptibility Gene

• Published in: American journal of human genetics Vol. 79; no. 3; pp. 586 - 592
• Main Authors: Tosic, Mirjana, Ott, Jurg, Barral, Sandra, Bovet, Pierre, Deppen, Patricia, Gheorghita, Fulvia, Matthey, Marie-Louise, Parnas, Josef, Preisig, Martin, Saraga, Michael, Solida, Alessandra, Timm, Sally, Wang, August G., Werge, Thomas, Cuénod, Michel, Quang Do, Kim
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.09.2006; University of Chicago Press; The American Society of Human Genetics
• Subjects: Biological and medical sciences; Case-Control Studies; Down-Regulation; Fibroblasts - enzymology; Fibroblasts - metabolism; Gene Frequency; General aspects. Genetic counseling; Genetic Predisposition to Disease - genetics; Glutamate-Cysteine Ligase - genetics; Glutathione - metabolism; Humans; Medical genetics; Medical sciences; Oxidative Stress - genetics; Polymorphism, Single Nucleotide; RNA, Messenger - analysis; Schizophrenia - enzymology; Schizophrenia - genetics; Glutamate-cysteine ligase; Human; Oxidative stress; Carbon-nitrogen ligases; Enzyme; Schizophrenia; Modifier gene; Genetic determinism; Psychosis; Sensitivity; Ligases; Predisposition; Genetics
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/507566

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.