Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_92E4F0AE47DF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.
Journal
Molecular psychiatry
Author(s)
Merritt K., McCutcheon R.A., Aleman A., Ashley S., Beck K., Block W., Bloemen OJN, Borgan F., Boules C., Bustillo J.R., Capizzano A.A., Coughlin J.M., David A., de la Fuente-Sandoval C., Demjaha A., Dempster K., Do K.Q., Du F., Falkai P., Galińska-Skok B., Gallinat J., Gasparovic C., Ginestet C.E., Goto N., Graff-Guerrero A., Ho B.C., Howes O., Jauhar S., Jeon P., Kato T., Kaufmann C.A., Kegeles L.S., Keshavan M.S., Kim S.Y., King B., Kunugi H., Lauriello J., León-Ortiz P., Liemburg E., Mcilwain M.E., Modinos G., Mouchlianitis E., Nakamura J., Nenadic I., Öngür D., Ota M., Palaniyappan L., Pantelis C., Patel T., Plitman E., Posporelis S., Purdon S.E., Reichenbach J.R., Renshaw P.F., Reyes-Madrigal F., Russell B.R., Sawa A., Schaefer M., Shungu D.C., Smesny S., Stanley J.A., Stone J., Szulc A., Taylor R., Thakkar K.N., Théberge J., Tibbo P.G., van Amelsvoort T., Walecki J., Williamson P.C., Wood S.J., Xin L., Yamasue H., McGuire P., Egerton A.
Working group(s)
1H-MRS in Schizophrenia Investigators
Contributor(s)
de la Fuente-Sandoval C., van Amelsvoort T., McGuire P.K.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Publication state
Published
Issued date
05/2023
Peer-reviewed
Oui
Volume
28
Number
5
Pages
2039-2048
Language
english
Notes
Publication types: Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p < 0.001; glutamine: CVR = 0.15, p = 0.003; Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05; Glx: CVR = 0.25, p < 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008; Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = -0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = -0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = -0.15, p = 0.03), higher thalamic glutamine (g = 0.53, p < 0.001) and higher BG Glx in patients relative to controls (g = 0.28, p < 0.001). Proportion of males was negatively associated with MFC glutamate (z = -0.02, p < 0.001) and frontal white matter Glx (z = -0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01, p = 0.01) and temporal lobe (z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies.
Keywords
Male, Humans, Glutamic Acid/metabolism, Schizophrenia/metabolism, Glutamine/metabolism, Brain/metabolism, Proton Magnetic Resonance Spectroscopy
Pubmed
Web of science
Open Access
Yes
Create date
28/02/2023 14:36
Last modification date
08/08/2024 6:37
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