Potential Role of Glutathione Antioxidant Pathways in the Pathophysiology and Adjunct Treatment of Psychiatric Disorders

Oxidative stress is defined as the imbalance between the production of free radicals and their removal by antioxidants, leading to accumulation and subsequent organ and tissue damage. Antioxidant status and its role in the accumulation of free radicals has been observed in a number of psychological disorders. Glutathione is commonly referred to as the principal antioxidant of the brain and, therefore, plays a critical role in maintaining redox homeostasis. Reduced levels of glutathione in the brain increase its vulnerability to oxidative stress, and may be associated with the development and progression of several psychiatric disorders. Within this review, we focus on analyzing potential associations between the glutathione antioxidant pathway and psychiatric disorders: major depressive disorder, schizophrenia, bipolar disorder, and generalized anxiety disorder. Our research suggests that studies regarding these four disorders have shown decreased levels of GSH in association with diseased states; however, conflicting results note no significant variance in glutathione pathway enzymes and/or metabolites based on diseased state. In studying the potential of NAC administration as an adjunct therapy, various studies have shown NAC to augment therapy and/or aid in symptomatic management for psychiatric disorders, while contrasting results exist within the literature. Based on the conflicting findings throughout this review, there is room for study regarding the potential role of glutathione in the development and progression of psychiatric disorders. Our findings further suggest a need to study such pathways with consideration of the interactions with first-line pharmacotherapy, and the potential use of antioxidants as supplemental therapy.

Automated summary

Oxidative stress refers to the imbalance between free radical production and antioxidant removal, leading to accumulation and tissue damage. Glutathione, as the brain's main antioxidant, plays a crucial role in maintaining redox homeostasis and its reduced levels are associated with the development and progression of psychiatric disorders. This review focuses on analyzing the potential associations between the glutathione antioxidant pathway and major depressive disorder, schizophrenia, bipolar disorder, and generalized anxiety disorder.