Brain Dopamine D1 Receptor Binding in Young Adults with Autism Spectrum Disorder

Background:  Autism spectrum disorder (ASD) is characterized by repetitive and/or obsessive interests and behavior and by deficits in sociability and communication. Previous neuroimaging studies using positron emission tomography (PET) found the dopaminergic dysregulation in the orbitofrontal cortex and microglial activation in more diverse brain regions in adults with ASD, although the relationship between the two phenomena remains unclear.

Objectives:  To determine a possible association between the dopamine D1 receptor availability and microglial activation in living subjects with ASD.

Methods:  We measured the binding of dopamine D1-like receptors with the radio-ligand ¹¹C-SCH23390 in the brain of subjects with ASD (n=20) and age- and sex-matched control subjects (n=20). The binding of radio-ligand ¹¹C-PK11195 was also measured as a representative index of microglial activation. Whole-brain voxel-based analyses as well as regions of interest-based methods were used for between-subjects analysis and within-subjects correlation analysis with respect to clinical variables.

Results:  We found significantly higher ¹¹C-SCH23390 binding potentials in the orbitofrontal cortex and midbrain of subjects with ASD compared to control (corrected P<.05). A previous finding of elevated ¹¹C-PK11195 binding in the brain of ASD was confirmed. The levels of ¹¹C-SCH23390 binding in the orbitofrontal cortex was positively correlated with ¹¹C-PK11195 binding in the midbrain, but not the orbitofrontal cortex per se. There was no significant correlation between PET data and clinical valuables evaluated.

Conclusions: The results suggest that the availability of D1 receptor at the resting state is elevated in the orbitofrontal cortex of subjects with ASD. The increased availability of D1 receptor may reflect a possible pathophysiological aspect intrinsic to the ASD brain with extensive microglial activation.