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

Yusuke Iwata, Shinichiro Nakajima, Eric Plitman, Yukiko Mihashi, Fernando Caravaggio, Jun Ku Chung, Julia Kim, Philip Gerretsen, Masaru Mimura, Gary Remington, Ariel Graff-Guerrero

Research output: Contribution to journalReview article

18 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)340-352
Number of pages13
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Publication statusPublished - 2018 Aug 30



  • Antipsychotic-naïve
  • Proton magnetic resonance spectroscopy
  • Schizophrenia
  • Untreated

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

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