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

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.

Putative Astroglial Dysfunction in Schizophrenia: A Meta-Analysis of 1H-MRS Studies of Medial Prefrontal Myo-Inositol.

Background: Several lines of evidence support a role for astroglial pathology in schizophrenia. Myo-inositol is particularly abundant in astroglia. Many small sized studies have reported on myo-inositol concentration in schizophrenia, but to date these have not been pooled to estimate a collective effect size. Methods: We reviewed all proton magnetic resonance spectroscopy (1H-MRS) studies reporting myo-inositol values for patients satisfying DSM or ICD based criteria for schizophrenia in comparison to a healthy controls group in the medial prefrontal cortex published until February 2018. A random-effects model was used to calculate the pooled effect size using metafor package. A meta-regression analysis of moderator variables was also undertaken. Results: The literature search identified 19 studies published with a total sample size of 585 controls, 561 patients with schizophrenia. Patients with schizophrenia had significantly reduced medial prefrontal myo-inositol compared to controls (RFX standardized mean difference = 0.19, 95% CI [0.05-0.32], z = 2.72, p = 0.0067; heterogeneity p = 0.09). Studies with more female patients reported more notable schizophrenia-related reduction in myo-inositol (z = 2.53, p = 0.011). Discussion: We report a small, but significant reduction in myo-inositol concentration in the medial prefrontal cortex in schizophrenia. The size of the reported effect indicates that the biological pathways affecting the astroglia are likely to operate only in a subset of patients with schizophrenia. MRS myo-inositol could be a useful tool to stratify and investigate such patients.