Exploring the role of glutathione therapy in schizophrenia: a case report

Rana Pehlivan; Marco Antonio Batisti Pasquali; Parinda Parikh

doi:10.18203/2394-6040.ijcmph20251400

Authors

Rana Pehlivan Department of Medicine, Istanbul University, Cerrahpaşa, Istanbul, Turkey
Marco Antonio Batisti Pasquali Department of Medicine, Universidade do Sul de Santa Catarina (UNISUL), Tubarão, Santa Catarina, Brazil https://orcid.org/0000-0003-4836-5095
Parinda Parikh Department of Psychiatry, Weill-Cornell Medical College, White Plains, New York, USA https://orcid.org/0009-0009-7552-4515

DOI:

https://doi.org/10.18203/2394-6040.ijcmph20251400

Keywords:

Schizophrenia, Glutathione, Oxidative stress

Abstract

Schizophrenia is a psychiatric disorder consisting of debilitating symptoms. Accumulating evidence suggests that oxidative stress is one of the main mechanisms of pathogenesis, and patients with schizophrenia have lower levels of glutathione, a crucial antioxidant. In this case, we present a 23-year-old male with severe schizophrenia who was undergoing treatment with multiple antipsychotics but showed minimal improvement in general psychopathology on the Positive and Negative Syndrome Scale (PANSS). Given that the patient was on numerous medications, we introduced glutathione as a novel approach. We hypothesize that glutathione is an antioxidant that reduces oxidative stress and enhances the overall functioning of schizophrenia patients. We administered weekly glutathione treatment for 10 weeks. Our findings suggest that glutathione as an adjunct therapy significantly improves symptoms in patients with schizophrenia. No important adverse effects occurred during follow-up.

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References

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association; 2013, p. 87-90. DOI: https://doi.org/10.1176/appi.books.9780890425596

McCutcheon RA, Reis Marques T, Howes OD. Schizophrenia—An Overview. JAMA Psychiatry. 2020;77(2):201. DOI: https://doi.org/10.1001/jamapsychiatry.2019.3360

Howes OD, Onwordi EC. The synaptic hypothesis of schizophrenia version III: a master mechanism. Mol Psychiatry. 2023;28(5):1843–56. DOI: https://doi.org/10.1038/s41380-023-02043-w

Howes OD, McCutcheon R, Owen MJ, Murray RM. The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia. Biol Psychiatry. 2017;81(1):9–20. DOI: https://doi.org/10.1016/j.biopsych.2016.07.014

Müller N. Inflammation in Schizophrenia: Pathogenetic Aspects and Therapeutic Considerations. Schizophr Bull. 2018;44(5):973–82. DOI: https://doi.org/10.1093/schbul/sby024

Fatemi SH, Folsom TD. The Neurodevelopmental Hypothesis of Schizophrenia, Revisited. Schizophr Bull. 2009;35(3):528–48. DOI: https://doi.org/10.1093/schbul/sbn187

Ermakov EA, Dmitrieva EM, Parshukova DA, Kazantseva DV, Vasilieva AR, Smirnova LP. Oxidative Stress‐Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives. Oxid Med Cell Longev. 2021;2021(1). DOI: https://doi.org/10.1155/2021/8881770

Leza JC, García-Bueno B, Bioque M, Arango C, Parellada M, Do K, et al. Inflammation in schizophrenia: A question of balance. Neurosci Biobehav Rev. 2015;55:612–26. DOI: https://doi.org/10.1016/j.neubiorev.2015.05.014

Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: Evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008;11(6):851–876. DOI: https://doi.org/10.1017/S1461145707008401

Berk M, Ng F, Dean O, Dodd S, Bush AI. Glutathione: A novel treatment target in psychiatry. Trends Pharmacological Sci. 2008;29(7):346–51. DOI: https://doi.org/10.1016/j.tips.2008.05.001

Jomova K, Raptova R, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol. 2023;97(10):2499–574. DOI: https://doi.org/10.1007/s00204-023-03562-9

Carletti B, Banaj N, Piras F, Bossù P. Schizophrenia and Glutathione: A Challenging Story. J Pers Med. 2023;13(11):1526. DOI: https://doi.org/10.3390/jpm13111526

Perkins DO, Jeffries CD, Do KQ. Potential Roles of Redox Dysregulation in the Development of Schizophrenia. Biol Psychiatry. 2020;88(4):326–36. DOI: https://doi.org/10.1016/j.biopsych.2020.03.016

Hardingham GE, Do KQ. Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis. Nat Rev Neurosci. 2016;17(2):125–34. DOI: https://doi.org/10.1038/nrn.2015.19

Chang Y, Xie Y, Weiss DS. Positive allosteric modulation by ultraviolet irradiation on GABA A, but not GABA C, receptors expressed in Xenopus oocytes. J Physiol. 2001;536(2):471–8. DOI: https://doi.org/10.1111/j.1469-7793.2001.0471c.xd

Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, et al. Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci. 2008;31(5):234–42. DOI: https://doi.org/10.1016/j.tins.2008.02.005

Dean O, den Buuse M, Bush AI, Copolov DL, Ng F, Dodd S, et al. A Role for Glutathione in the Pathophysiology of Bipolar Disorder and Schizophrenia? Animal Models and Relevance to Clinical Practice. Curr Med Chem. 2009;16(23):2965–76. DOI: https://doi.org/10.2174/092986709788803060

Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, et al. N-Acetyl Cysteine as a Glutathione Precursor for Schizophrenia—A Double-Blind, Randomized, Placebo-Controlled Trial. Biol Psychiatry. 2008;64(5):361–8. DOI: https://doi.org/10.1016/j.biopsych.2008.03.004