Neurometabolite levels in antipsychotic-naïve/free patients with schizophrenia: A systematic review and meta-analysis of 1H-MRS studies

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Background:Studies using proton magnetic resonance spectroscopy (1H-MRS) have reported altered neurometabolite levels in patients with schizophrenia. However, results are possibly confounded by the influence of antipsychotic (AP). Thus, this meta-analysis aimed to examine neurometabolite levels in AP-naïve/free patients with schizophrenia.Methods:A literature search was conducted using Embase, Medline, and PsycINFO to identify studies that compared neurometabolite levels in AP-naïve/free patients with schizophrenia to healthy controls (HCs). Eight neurometabolites (glutamate, glutamine, glutamate + glutamine, N-acetylaspartate [NAA], choline, creatine, myo-inositol, and γ-Aminobutyric acid [GABA]) and seven regions of interest (ROI; medial prefrontal cortex, dorsolateral prefrontal cortex, frontal white matter, occipital lobe, basal ganglia, hippocampus/medial temporal lobe, and thalamus) were examined.Results:Twenty-one studies (N = 1281) were included in the analysis. The results showed lower thalamic NAA levels (3 studies, n = 174, effect size = −0.56, P = 0.0005) in the patient group. No group differences were identified for other neurometabolites.Conclusions:Our findings suggest that impaired neuronal integrity in the thalamus may be a potential trait maker in the early stages of schizophrenia.HighlightsAntipsychotics may be a confounding factor of 1H-MRS studies.This is the meta-analysis of 1H-MRS studies focusing on unmedicated schizophrenia.This study replicated the finding of lower NAA levels in the Thalamus.Impaired thalamic neuronal integrity may be a trait maker in early schizophrenia.

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