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Brain glucose metabolism in schizophrenia: a systematic review and meta-analysis of 18FDG-PET studies in schizophrenia

Lookup NU author(s): Dr Leigh TownsendORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Background: Impaired brain metabolism may be central to schizophrenia pathophysiology, but the magnitude and consistency of metabolic dysfunction is unknown. Methods: We searched MEDLINE, PsychINFO and EMBASE between 01/01/1980 and 13/05/2021 for studies comparing regional brain glucose metabolism using 18FDG-PET, in schizophrenia/first-episode psychosis v. controls. Effect sizes (Hedges g) were pooled using a random-effects model. Primary measures were regional absolute and relative CMRGlu in frontal, temporal, parietal and occipital lobes, basal ganglia and thalamus. Results: Thirty-six studies (1335 subjects) were included. Frontal absolute glucose metabolism (Hedge's g = -0.74 ± 0.54, p = 0.01; I2 = 67%) and metabolism relative to whole brain (g = -0.44 ± 0.34, p = 0.01; I2 = 55%) were lower in schizophrenia v. controls with moderate heterogeneity. Absolute frontal metabolism was lower in chronic (g = -1.18 ± 0.73) v. first-episode patients (g = -0.09 ± 0.88) and controls. Medicated patients showed frontal hypometabolism relative to controls (-1.04 ± 0.26) while metabolism in drug-free patients did not differ significantly from controls. There were no differences in parietal, temporal or occipital lobe or thalamic metabolism in schizophrenia v. controls. Excluding outliers, absolute basal ganglia metabolism was lower in schizophrenia v. controls (-0.25 ± 0.24, p = 0.049; I2 = 5%). Studies identified reporting voxel-based morphometry measures of absolute 18FDG uptake (eight studies) were also analysed using signed differential mapping analysis, finding lower 18FDG uptake in the left anterior cingulate gyrus (Z = -4.143; p = 0.007) and the left inferior orbital frontal gyrus (Z = -4.239; p = 0.02) in schizophrenia. Conclusions: We report evidence for hypometabolism with large effect sizes in the frontal cortex in schizophrenia without consistent evidence for alterations in other brain regions. Our findings support the hypothesis of hypofrontality in schizophrenia.


Publication metadata

Author(s): Townsend L, Pillinger T, Selvaggi P, Veronese M, Turkheimer F, Howes O

Publication type: Article

Publication status: Published

Journal: Psychological Medicine

Year: 2023

Volume: 53

Issue: 11

Pages: 4880-4897

Print publication date: 01/08/2023

Online publication date: 22/06/2022

Acceptance date: 23/03/2022

Date deposited: 20/06/2023

ISSN (print): 0033-2917

ISSN (electronic): 1469-8978

Publisher: Cambridge University Press

URL: https://doi.org/10.1017/S003329172200174X

DOI: 10.1017/S003329172200174X


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Funding

Funder referenceFunder name
094849/Z/10/Z
666
King’s College London
Maudsley Charity
Maudsley NHS Foundation Trust
MC-A656-5QD30
National Institute for Health Research (NIHR) Biomedical Research Centre at South London
MRC
Wellcome Trust

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