Abstract
Background
Glutamate especially in frontal cortical areas was proposed to be altered in patients with schizophrenia. In the dorsolateral prefrontal cortex (DLPFC), glutamate levels might serve as functional markers of schizophrenia since this region is involved in working memory function which is impaired in schizophrenia patients. To date, there is no systematic overview on glutamate in dorsolateral prefrontal cortex at high-field intensities. We here meta-analyze magnetic resonance spectroscopy (1-HMRS) studies comprising measurement in dorsolateral prefrontal cortex (DLPFC).
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*). We screened for case-control studies comprising glutamate levels as measured by 1-HMRS in DLPFC. Meta-analysis with a fixed and random effects model with inverse variance method, DerSimonian-Laird estimator for tau2 and Cohen’s d were estimated.
Results
329 studies were initially screened. 13 Studies were included into quantitative analysis comprising n=436 patients and n=365 controls. The random effects model revealed no difference between patients and controls (d=0.033 [-0.19; 0.26], z=0.29, p=0.77). The test for heterogeneity shows a moderate amount of heterogeneity (tau2=0.096, I2=57.4%). Subsequent sensitivity analysis reveals significant between group effect for medication status (Q=7.94, p=0.0473) i.e. an increased glutamate level in antipsychotic naïve patients (d=0.46 [0.08; 0.84], z=2.37, p=0.018).
Discussion
We conclude that care has to be taken when evaluating metabolite levels in such a heterogeneous group and interpret that increase cortical glutamate in antipsychotic naïve patients with schizophrenia might be due to possible allostatic mechanisms.
Lower Choline-Containing Metabolites/Creatine (Cr) Rise and Failure to Sustain NAA/Cr Levels in the Dorsolateral Prefrontal Cortex Are Associated with Depressive Episode Recurrence under Maintenance Therapy: A Proton Magnetic Resonance Spectroscopy Retrospective Cohort Study