Microglial Activation in Young Adults With Autism Spectrum Disorder

Context  A growing body of evidence suggests that aberrant immunologic systems underlie the pathophysiologic characteristics of autism spectrum disorder (ASD). However, to our knowledge, no information is available on the patterns of distribution of microglial activation in the brain in ASD.

Objectives  To identify brain regions associated with excessively activated microglia in the whole brain, and to examine similarities in the pattern of distribution of activated microglia in subjects with ASD and control subjects.

Design  Case-control study using positron emission tomography and a radiotracer for microglia—[¹¹C](R)-(1-[2-chrorophynyl]- N-methyl- N-[1-methylpropyl]-3 isoquinoline carboxamide) ([¹¹C](R)-PK11195).

Setting  Subjects recruited from the community.

Participants  Twenty men with ASD (age range, 18-31 years; mean [SD] IQ, 95.9 [16.7]) and 20 age- and IQ-matched healthy men as controls. Diagnosis of ASD was made in accordance with the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview–Revised.

Main Outcome Measures  Regional brain [¹¹C](R)-PK11195 binding potential as a representative measure of microglial activation.

Results  The [¹¹C](R)-PK11195 binding potential values were significantly higher in multiple brain regions in young adults with ASD compared with those of controls (P < .05, corrected). Brain regions with increased binding potentials included the cerebellum, midbrain, pons, fusiform gyri, and the anterior cingulate and orbitofrontal cortices. The most prominent increase was observed in the cerebellum. The pattern of distribution of [¹¹C](R)-PK11195 binding potential values in these brain regions of ASD and control subjects was similar, whereas the magnitude of the [¹¹C](R)-PK11195 binding potential in the ASD group was greater than that of controls in all regions.

Conclusions  Our results indicate excessive microglial activation in multiple brain regions in young adult subjects with ASD. The similar distribution pattern of regional microglial activity in the ASD and control groups may indicate augmented but not altered microglial activation in the brain in the subjects with ASD.