Subcortical dopamine D₂ receptor availability and glucose metabolism in autism: a dual-tracer PET/MR study.

Abstract

Dopaminergic signalling and glucose metabolism have been implicated in autism spectrum disorder (ASD), yet in vivo evidence in the human brain remains largely unexplored. This study examined subcortical dopamine D₂ receptor availability and glucose metabolism in ASD to assess their clinical relevance. In this dual-tracer PET/MR case-control study, 30 autistic and 30 neurotypical adults (age-, sex-, body mass index-, and IQ-matched) underwent [¹¹C]raclopride PET to assess dopamine D₂ receptor availability, [¹⁸F]FDG PET to measure glucose metabolism and resting-state fMRI to evaluate functional connectivity. Autistic individuals demonstrated increased D₂ receptor availability in the thalamus, with additional increases in the nucleus accumbens and putamen among autistic males compared to neurotypical males. Glucose metabolism was elevated in the thalamus and globus pallidus in ASD relative to NT, and this pattern persisted within both autistic males and autistic females in sex‑stratified comparisons. Globus pallidus and thalamic glucose metabolism correlated positively with social and communication difficulties. Resting-state fMRI analyses revealed diagnosis- and sex-dependent correlations between thalamic D₂ receptor availability and functional connectivity. This study provides in vivo evidence of elevated subcortical D₂R availability and glucose metabolism in autistic adults, a pattern observed across sexes. We also show that D₂R availability is tightly linked to glucose metabolism and that D₂R-functional connectivity coupling is altered in ASD, both relative to neurotypical adults and between autistic males and females. These findings highlight dopaminergic mechanisms as potential biomarkers and therapeutic targets in ASD.