ArticleProceedings of the National Academy of Sciences of the United States of America2007
Impaired glutathione synthesis in schizophrenia: convergent genetic and functional evidence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 147 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Investigating the Effect of Diroximel Fumarate on Glutathione in Schizophrenia
Combination Therapy of Deferiprone and N-Acetylcysteine for Treating Negative Symptoms in Schizophrenia
Who cites it
147 citing papers in PubMed, 2 syntheses or guidelines pooled it, 304 citations in OpenAlex.
- Meta-analysis of oxidative stress in schizophrenia.Biological psychiatry · 2013Pooled it
- Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia.CNS drugs · 2011Pooled it
- N-Acetylcysteine (NAC) in Schizophrenia Resistant to Clozapine: A Double-Blind, Randomized, Placebo-Controlled Trial Targeting Negative Symptoms.Schizophrenia bulletin · 2022Trial
- N-acetylcysteine add-on treatment leads to an improvement of fornix white matter integrity in early psychosis: a double-blind randomized placebo-controlled trial.Translational psychiatry · 2018Trial
- N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis.Schizophrenia bulletin · 2018Trial
- Trial
- From Damage to Dysregulation: Reframing Oxidative Stress and Redox Homeostasis in Central Nervous System Disease.International journal of molecular sciences · 2026Review
- Redox Homeostasis and Oxidative Stress in Schizophrenia: Glutathione-NMDA-Neuroimmune Convergence and a Hypothesis-Generating Iron-Lipid Redox Extension.International journal of molecular sciences · 2026Review
- Review
- From brain bioenergetics to hypothalamic glucoregulation: A shared-systems hypothesis for intrinsic dysglycemia in schizophrenia.Reviews in endocrine & metabolic disorders · 2026Review
- Glutathione deficiency in the early postnatal developmental period as a neurodevelopmental animal model of schizophrenia.Pharmacological reports : PR · 2026Review
- Psychosis as a multisystem disorder of aberrant aging.npj aging · 2026Review
- From Micro Molecular to Functional Levels Through Macro Structures: Mediation of Structural Brain Changes on the Relationship Between Oxidative Stress and Cognition in Early Onset Psychosis.Schizophrenia bulletin open · 2026Article
- A comprehensive review on schizophrenia: epidemiology, pathogenesis, diagnosis, conventional treatments, and proposed natural compounds used for management.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- CENPT prevents renal cell carcinoma against ferroptosis by enhancing the synthesis of glutathione.Cell death & disease · 2025Article
- Lifelong Glutathione Deficiency in Mice Increased Lifespan and Delayed Age-Related Motor Declines.Aging and disease · 2024Article
- The effect of phencyclidine-mediated blockade of NMDA receptors in the early postnatal period on glutathione and sulfur amino acid levels in the rat brain as a potential causative factor of schizophrenia-like behavior in adulthood.Pharmacological reports : PR · 2024Article
- microRNA and the Post-Transcriptional Response to Oxidative Stress during Neuronal Differentiation: Implications for Neurodevelopmental and Psychiatric Disorders.Life (Basel, Switzerland) · 2024Article
- Article
- Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Schizophrenia is a complex multifactorial brain disorder with a genetic component. Convergent evidence has implicated oxidative stress and glutathione (GSH) deficits in the pathogenesis of this disease. The aim of the present study was to test whether schizophrenia is associated with a deficit of GSH synthesis. Cultured skin fibroblasts from schizophrenia patients and control subjects were challenged with oxidative stress, and parameters of the rate-limiting enzyme for the GSH synthesis, the glutamate cysteine ligase (GCL), were measured. Stressed cells of patients had a 26% (P = 0.002) decreased GCL activity as compared with controls. This reduction correlated with a 29% (P < 0.001) decreased protein expression of the catalytic GCL subunit (GCLC). Genetic analysis of a trinucleotide repeat (TNR) polymorphism in the GCLC gene showed a significant association with schizophrenia in two independent case-control studies. The most common TNR genotype 7/7 was more frequent in controls [odds ratio (OR) = 0.6, P = 0.003], whereas the rarest TNR genotype 8/8 was three times more frequent in patients (OR = 3.0, P = 0.007). Moreover, subjects with disease-associated genotypes had lower GCLC protein expression (P = 0.017), GCL activity (P = 0.037), and GSH contents (P = 0.004) than subjects with genotypes that were more frequent in controls. Taken together, the study provides genetic and functional evidence that an impaired capacity to synthesize GSH under conditions of oxidative stress is a vulnerability factor for schizophrenia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.