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

Prog Neuropsychopharmacol Biol Psychiatry. 2018 Aug 30;86:340-352. doi: 10.1016/j.pnpbp.2018.03.016. Epub 2018 Mar 23.


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.

Keywords: Antipsychotic-naïve; Proton magnetic resonance spectroscopy; Schizophrenia; Untreated.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Humans
  • Proton Magnetic Resonance Spectroscopy
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / metabolism*


  • Aspartic Acid
  • N-acetylaspartate