Cerebral glucose metabolism: the potential missing link in autism research-a literature review and meta-analytic...

The global prevalence of Autism Spectrum Condition (ASC) is increasing, yet effective supportive interventions remain largely unidentified, highlighting the urgent need to clarify the underlying neuropathophysiology. Neuroimaging offers a pathway toward this understanding; however, most studies rely on indirect measures of neurophysiology, whereas direct approaches such as [¹⁸F]Fluorodeoxyglucose positron emission tomography (FDG-PET) remain underutilized and lack systematic synthesis in the literature. This review and meta-analysis evaluated FDG-PET research in ASC. A systematic search identified 2,725 records, of which 21 studies compared FDG-PET findings between autistic and neurotypical individuals. Nine met the inclusion criteria for the review, and eight were included in the meta-analysis. The review revealed inconsistent findings, reporting both increased and decreased glucose metabolism in ASC, likely reflecting methodological heterogeneity. The meta-analysis found no statistically significant differences, but indicated a weak non-significant trend toward elevated glucose metabolism in the striatum in autistic compared to neurotypicals individuals (standardized mean difference [SMD] = 0.416; 95% CI - 0.200 to 1.032; p = 0.186). Despite 40 years of FDG-PET research in ASC, the number of studies remains limited, and several exhibit methodological shortcomings. Evidence from FDG-PET studies in other psychiatric and neurological disorders underscores the technique's potential value in ASC research. The findings of this study further emphasize the urgent need for rigorously designed investigations to clarify the relationship between cerebral glucose metabolism and autism, with the ultimate goal of advancing our understanding of the autistic brain.