Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene.
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.
Tosic
Mirjana
M
Center for Psychiatric Neuroscience, Lausanne University Hospital, Lausanne, Switzerland. Mirjana.Tosic@chuv.ch
Ott
Jurg
J
Barral
Sandra
S
Bovet
Pierre
P
Deppen
Patricia
P
Gheorghita
Fulvia
F
Matthey
Marie-Louise
ML
Parnas
Josef
J
Preisig
Martin
M
Saraga
Michael
M
Solida
Alessandra
A
Timm
Sally
S
Wang
August G
AG
Werge
Thomas
T
Cuénod
Michel
M
Do
Kim Quang
KQ
D016022:Case-Control Studies; D015536:Down-Regulation; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005721:Glutamate-Cysteine Ligase / Q000235:genetics*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000032:analysis; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics*
D012333:RNA, Messenger; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione