Antioxidant defense in schizophrenia and bipolar disorder: A meta-analysis of MRS studies of anterior cingulate glutathione

Tushar Kanti Das; Alborz Javadzadeh; Avyarthana Dey; Priyadharshini Sabesan; Jean Théberge; Joaquim Radua; Lena Palaniyappan

doi:10.1016/j.pnpbp.2018.08.006

Antioxidant defense in schizophrenia and bipolar disorder: A meta-analysis of MRS studies of anterior cingulate glutathione

Prog Neuropsychopharmacol Biol Psychiatry. 2019 Apr 20:91:94-102. doi: 10.1016/j.pnpbp.2018.08.006. Epub 2018 Aug 17.

Authors

Tushar Kanti Das¹, Alborz Javadzadeh², Avyarthana Dey³, Priyadharshini Sabesan², Jean Théberge⁴, Joaquim Radua⁵, Lena Palaniyappan⁶

Affiliations

¹ Department of Psychiatry, University of Western Ontario, London, ON, Canada; Robarts Research Institute, London, ON. Canada; Lawson Health Research Institute, London, ON. Canada.
² Department of Psychiatry, University of Western Ontario, London, ON, Canada.
³ Department of Psychiatry, University of Western Ontario, London, ON, Canada; Robarts Research Institute, London, ON. Canada.
⁴ Lawson Health Research Institute, London, ON. Canada; Department of Medical Biophysics, University of Western Ontario, London, ON, Canada; Department of Diagnostic Imaging, St. Joseph's Health Care London, ON, Canada.
⁵ FIDMAG Germanes Hospitalàries, CIBERSAM, Sant Boi de Llobregat, Spain; Institute of Psychiatry, King's College London, De Crespigny Park, London,UK; Centre for Psychiatric Research and Education, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Psychiatry, University of Western Ontario, London, ON, Canada; Robarts Research Institute, London, ON. Canada; Lawson Health Research Institute, London, ON. Canada; Department of Medical Biophysics, University of Western Ontario, London, ON, Canada. Electronic address: lpalaniy@uwo.ca.

PMID: 30125624
DOI: 10.1016/j.pnpbp.2018.08.006

Abstract

Background: Glutathione [GSH] is a major intracellular antioxidant that disposes peroxides and protects neurons and glial cells from oxidative stress. In both schizophrenia and bipolar disorder, atypical levels of GSH have been demonstrated, particularly in the anterior cingulate cortex (ACC), though no consistent results have emerged due to limitations in sample size. Our objective was to evaluate if GSH levels in the ACC are abnormal in these 2 disorder, when compared to healthy controls.

Methods: We reviewed all 1H-MRS studies reporting GSH values for patients satisfying DSM or ICD based criteria for (1) the psychotic disorders - schizophrenia or schizoaffective disorder or (2) bipolar disorder in comparison to a healthy controls (HC) group in the Anterior Cingulate Cortex (ACC) published until June 2018. A random-effects model was used to calculate the pooled effect size. A meta-regression analysis of moderator variables was also undertaken.

Results: The literature search identified 18 studies with a total sample size of 581 controls, 578 patients with schizophrenia or bipolar disorder. There is a small but significant reduction in ACC GSH in patients with schizophrenia compared to HC (N = 13; RFX SMD =0.26; 95% CI [0.07 to 0.44]; p = 0.008; heterogeneity p = 0.11). There is a significant increase in the ACC GSH concentration in bipolar disorder compared to HC (N = 6; RFX SMD = -0.28, 95% CI [-0.09 to -0.47]; p = 0.003; heterogeneity p = 0.95).

Conclusions: We report a small, but significant reduction in GSH concentration in the ACC in schizophrenia, and a similar sized increase in bipolar disorder. A notable limitation is the lack of sufficient data to examine the moderating effect of the symptom profile. Schizophrenia and bipolar disorder have notably different patterns of redox abnormalities in the ACC. Reduced ACC GSH may confer a schizophrenia-like clinical phenotype, while an excess favouring a bipolar disorder-like profile.

Keywords: Antioxidant; Bipolar disorder; Glutathione; Schizophrenia; Spectroscopy.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review

MeSH terms

Antioxidants / metabolism*
Biomarkers / metabolism
Bipolar Disorder / diagnostic imaging
Bipolar Disorder / metabolism*
Cross-Sectional Studies
Glutathione / metabolism*
Gyrus Cinguli / diagnostic imaging
Gyrus Cinguli / metabolism*
Humans
Magnetic Resonance Spectroscopy / methods*
Schizophrenia / diagnostic imaging
Schizophrenia / metabolism*

Substances

Antioxidants
Biomarkers
Glutathione

Grants and funding

375104/Canadian Institute of Health Research /International