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  Glutamate in the dorsolateral prefrontal cortex in patients with schizophrenia: A meta-analysis of 1H-magnetic resonance spectroscopy studies

Kaminski, J., Mascarell-Maricic, L., Fukuda, Y., Katthagen, T., Heinz, A., & Schlagenhauf, F. (2021). Glutamate in the dorsolateral prefrontal cortex in patients with schizophrenia: A meta-analysis of 1H-magnetic resonance spectroscopy studies. Biological Psychiatry, 89(3), P270-P277. doi:10.1016/j.biopsych.2020.09.001.

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Kaminski, Jakob1, 2, 3, 4, Author
Mascarell-Maricic, Lea1, 2, 3, 4, Author
Fukuda, Yu1, 2, 3, 4, Author
Katthagen, Teresa1, 2, 3, 4, Author
Heinz, Andreas1, 2, 3, 5, Author
Schlagenhauf, Florian1, 2, 3, 4, 5, 6, Author           
1Charité University Medicine Berlin, Germany, ou_persistent22              
2FU Berlin, Germany, ou_persistent22              
3Humboldt University Berlin, Germany, ou_persistent22              
4Berlin Institute of Health (BIH), Germany, ou_persistent22              
5Bernstein Center for Computational Neuroscience, Berlin, Germany, ou_persistent22              
6Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              


Free keywords: (1)H-MRS; Antipsychotic medication; Dorsolateral prefrontal cortex; Glutamate; Psychosis; Schizophrenia
 Abstract: Background: To date, there is no systematic overview of glutamate in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia. Here, we meta-analyzed case-control studies of high-field proton 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 20, 2019. The 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 the DLPFC in cases versus controls. Secondary outcomes were differences in variability.

Results: The quantitative analysis comprised 429 cases and 365 controls. Overall, we found no group difference (d = 0.03 [95% confidence interval (CI), -0.20 to 0.26], z = 0.28, p = .78). Sensitivity analysis revealed an effect for medication status (Q = 8.35, p = .039), i.e., increased glutamate in antipsychotic-naïve patients (d = 0.46 [95% CI, 0.08 to 0.84], z = 2.37, p = .018). Concerning variance ratios, we found an effect of medication status (Q = 16.95, p < .001) due to lower coefficient of variation ratio (CVR) in medication-naïve patients (logCVR = -0.49 [95% CI, -0.78 to -0.20], z = -3.33, p < .001). In studies with medicated patients, we found higher CVR (logCVR = 0.22 [95% CI, 0.06 to 0.39], z = 2.67; p = .008).

Conclusions: We carefully interpret the higher levels and lower variability in cortical glutamate in antipsychotic-naïve patients as a possible key factor resulting from a putative allostatic mechanism. We conclude that care has to be taken when evaluating metabolite levels in clinical samples in which medication might confound findings.


Language(s): eng - English
 Dates: 2020-08-282020-04-112020-09-012020-09-082021-02-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.biopsych.2020.09.001
Other: epub 2020
PMID: 33129486
 Degree: -



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Title: Biological Psychiatry
  Other : Biol. Psychiatry
Source Genre: Journal
Publ. Info: New York : Elsevier
Pages: - Volume / Issue: 89 (3) Sequence Number: - Start / End Page: P270 - P277 Identifier: ISSN: 0006-3223
CoNE: https://pure.mpg.de/cone/journals/resource/954925384111