Brain glucose metabolism in schizophrenia: a systematic review and meta-analysis of 18 FDG-PET studies in schizophrenia.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational case-control neuroimaging studies
PubMed 35730361 · doi:10.1017/S003329172200174X
What was done
The authors searched MEDLINE, PsychINFO, and EMBASE from 1980 through May 2021 for studies using 18F-FDG PET to compare regional brain glucose metabolism (absolute and relative CMRGlu) between patients with schizophrenia or first-episode psychosis and healthy controls. Effect sizes (Hedges' g) across the frontal, temporal, parietal, and occipital lobes, basal ganglia, and thalamus were pooled using random-effects meta-analysis. A subset of eight studies reporting voxel-based morphometry measures of FDG uptake was evaluated via signed differential mapping analysis.
What was found
Thirty-six studies with 1,335 subjects were included. Schizophrenia patients showed significantly lower absolute frontal glucose metabolism (Hedges' g = -0.74 ± 0.54, p = 0.01; I² = 67%) and relative frontal metabolism (g = -0.44 ± 0.34, p = 0.01; I² = 55%) compared to controls. Absolute frontal hypometabolism was pronounced in chronic patients (g = -1.18 ± 0.73) and medicated patients (g = -1.04 ± 0.26), but not statistically significant in first-episode (g = -0.09 ± 0.88) or drug-free patients. No metabolic differences were found in parietal, temporal, or occipital lobes, or the thalamus. Excluding outliers showed lower absolute basal ganglia metabolism in schizophrenia (g = -0.25 ± 0.24, p = 0.049; I² = 5%). Voxel-based analyses revealed lower uptake in the left anterior cingulate gyrus (Z = -4.143, p = 0.007) and left inferior orbital frontal gyrus (Z = -4.239, p = 0.02).
Why it matters
This review provides quantitative evidence supporting the hypofrontality hypothesis in schizophrenia, demonstrating that metabolic dysfunction is localized to frontal regions rather than generalized across the whole brain.
Limits
Moderate heterogeneity was observed in frontal metabolic analyses (I² = 55–67%). Differences were primarily evident in chronic and medicated cohorts, confounding disease pathology with antipsychotic exposure and illness duration. Voxel-based analysis was restricted to only eight studies.
Cited by
- contradicts Cerebral glucose hypometabolism is a central characteristic of neurodegenerative conditions and is present in schizophrenia and bipolar disorder before the diagnosis of psychosis or administration of medications.