Glutamate in Dorsolateral Prefrontal Cortex in Patients With Schizophrenia: A Meta-Analysis of 1-HMRS Studies

Abstract

Abstract Background To date, there is no systematic overview of glutamate in dorsolateral prefrontal cortex (DLPFC) of schizophrenia patients. We here meta-analyzed case-control studies of high-field magnetic resonance spectroscopy (1H-MRS) investigating glutamate in DLPFC. Additionally, we estimated variance ratios, to investigate homo-/heterogeneity. Methods Preregistration of the study was performed on September 20th 2019 (osf.io/5uyr6). Predefined literature search on PubMed comprised articles with search terms: (Magnetic Resonance Spectroscopy OR MRS) AND (Glutamate OR Glut* OR GLX) AND (schizophrenia OR psychosis OR schizophren*). Meta-analyses with a fixed and random-effects model with inverse variance method, DerSimonian-Laird estimator for τ2, and Cohen's d were calculated. For differences in variability, we calculated a random-effects model for measures of variance ratios. The primary study outcome was the difference in glutamate in DLPFC in cases vs. controls. Secondary outcomes were differences in variability. Results The quantitative analysis comprised n=429 patients and n=365 controls. Overall, we found no group difference (d=0.03[-0.20; 0.26],z=0.28,p=0.78). Sensitivity analysis revealed an effect for medication status (Q=8.35,p=0.039) i.e. increased glutamate in antipsychotic naive patients (d=0.46[0.08; 0.84],z=2.37,p=0.018). Concerning variance ratios, we found an effect of medication status (Q=16.95, p Conclusion We carefully interpret the higher levels and lower variability in cortical glutamate in antipsychotic naive patients as a possible key factor due to a putative allostatic mechanism. We conclude that care has to be taken when evaluating metabolite levels in clinical samples where medication might confound findings.