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

Abstract

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.

Glutamatergic hypo-function in the left superior and middle temporal gyri in early schizophrenia: a data-driven three-dimensional proton spectroscopic imaging study

“…We speculate that increased t-Cho only in treated patients suggests an adaptive glial response to antipsychotics in the left medial frontal cortex. Investigations on inositol in schizophrenia have been sparse but a recent meta-analysis reported reductions in medial frontal regions in predominantly treated patients [ 39 ]. However, cerebellar or other regions were not examined.…”

Longitudinal changes in brain metabolites in healthy subjects and patients with first episode psychosis (FEP): a 7-Tesla MRS study

“…It is highly enriched in astrocytes and has been used as a marker of astrocyte activity (38). A meta-analysis reported a small, but significant, reduction in mI concentration in the medial frontal cortex in SZ (39).…”

Lowered Antioxidant Defenses and Increased Oxidative Toxicity Are Hallmarks of Deficit Schizophrenia: Neurocognitive and Symptom Correlates

“…In chronic schizophrenia, no significant changes could be observed in LOOH, PON1 activity, nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP) and advanced oxidation protein products (AOPP) [23]. Recent meta-analyses showed increased signs of oxidative stress, including increased MDA and NO, and a lowered total antioxidant status including lowered levels of specific antioxidants including the glutathione in plasma and brain although not all studies could detect such differences [24][25][26][27][28][29]. Such differences may be explained by sample characteristics such as clinical features and staging of illness.…”