Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?

Version 1 : Received: 21 September 2021 / Approved: 27 September 2021 / Online: 27 September 2021 (12:47:39 CEST)

How to cite: Palaniyappan, L.; Park, M.T.M.; Jeon, P.; Limongi, R.; Yang, K.; Sawa, A.; Théberge, J. Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?. Preprints 2021, 2021090449 (doi: 10.20944/preprints202109.0449.v1). Palaniyappan, L.; Park, M.T.M.; Jeon, P.; Limongi, R.; Yang, K.; Sawa, A.; Théberge, J. Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?. Preprints 2021, 2021090449 (doi: 10.20944/preprints202109.0449.v1).

Abstract

Schizophrenia continues to be an illness with poor outcome. Most mechanistic changes occur many years before the first episode of schizophrenia; these are not reversible after the illness onset. A developmental mechanism that is still modifiable in adult life may center on intracortical glutathione (GSH). A large body of pre-clinical data has suggested the possibility of notable GSH-deficit in a subgroup of patients with schizophrenia. Nevertheless, studies of intracortical GSH are not conclusive in this regard. In this review, we highlight the recent ultra-high field magnetic resonance spectroscopic studies linking GSH to critical outcome measures across various stages of schizophrenia. We discuss the methodological steps required to conclusively establish or refute the persistence of GSH-deficit subtype and clarify the role of the central antioxidant system in disrupting the brain structure and connectivity in the early stages of schizophrenia. We propose in-vivo GSH quantification for patient selection in forthcoming antioxidant trials in psychosis. This review offers directions for a promising non-dopaminergic early intervention approach in schizophrenia.

Keywords

glutathione; glutamate; psychosis; schizophrenia; redox; antioxidant; oxidative stress; myelin; spectroscopy

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