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Psychological Medicine Aug 2023Impaired brain metabolism may be central to schizophrenia pathophysiology, but the magnitude and consistency of metabolic dysfunction is unknown. (Meta-Analysis)
Meta-Analysis
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 FDG-PET, in schizophrenia/first-episode psychosis controls. Effect sizes (Hedges ) 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 = -0.74 ± 0.54, = 0.01; = 67%) and metabolism relative to whole brain ( = -0.44 ± 0.34, = 0.01; = 55%) were lower in schizophrenia controls with moderate heterogeneity. Absolute frontal metabolism was lower in chronic ( = -1.18 ± 0.73) first-episode patients ( = -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 controls. Excluding outliers, absolute basal ganglia metabolism was lower in schizophrenia controls (-0.25 ± 0.24, = 0.049; = 5%). Studies identified reporting voxel-based morphometry measures of absolute FDG uptake (eight studies) were also analysed using signed differential mapping analysis, finding lower FDG uptake in the left anterior cingulate gyrus ( = -4.143; = 0.007) and the left inferior orbital frontal gyrus ( = -4.239; = 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.
Topics: Humans; Glucose; Schizophrenia; Fluorodeoxyglucose F18; Brain; Positron-Emission Tomography
PubMed: 35730361
DOI: 10.1017/S003329172200174X