Older Adults with Autism: So Much for the Gray Matter?

Background: The anatomical signature of autism spectrum disorder (ASD) is marked by age-specific changes in children and adolescents, showing different rates in different brain regions during different life phases. However, there’s a paucity of studies examining brain anatomy in middle and late adulthood in ASD, making it unknown whether ASD in adults is characterized by differences in brain anatomy.

Objectives: To use structural neuroimaging to characterize disorder-related and age-related changes of gray matter morphology in adults and elderly with ASD and controls.

Methods: We performed a cross-sectional structural 3T MRI study of 51 individuals with clinical ASD (35 Males) and 49 age- and sex-matched controls (32 Males) between the ages 30-74 years (Mean age ASD=51.5 (12.6); Mean age Controls=50.1 (11.9)). Inclusion criteria for ASD participants: 1) a formal clinical diagnosis of ASD prior to inclusion; 2) confirmation of the clinical diagnosis: 33 individuals had a score above the cutoff of the ADOS (>7; Autism Diagnostic Observation Schedule module 4) and those not scoring above this cutoff did score above the AQ cutoff (>26; Autism-Spectrum Quotient, 50-item list). All participants had an estimated IQ above 80, lack of history of neurological disorders or chronic illness, learning disabilities and schizophrenia. For the control group, an additional exclusion criterion was a first or second-degree family member with ASD.

Our main outcome measures included: Surface-based and lobar measures of cortical volume, cortical thickness, surface area and local gyrification index, and volumes of subcortical structures. In addition, we examined laterality indices reflecting the magnitude of left > right asymmetry of these morphological properties. Exploratory analyses were performed to examine group-by-age interactions for the various morphometric measures.

Results: Surface-based and lobar measures, and subcortical volumes did not differ significantly between ASD and controls. Irrespective of group, significant age-related volume loss and cortical thinning was found, but no age-related differences in surface area or local gyrification indices were found. No group differences were found in lateralization indices after correction for multiple comparisons. Taking a conservative approach, all between-group analyses were also performed with the ADOS-only group (i.e. those individuals with ADOS-scores above cutoff (>7), but this did not result in any significant findings.

Conclusions: The lack of significant anatomical differences between individuals with ASD and controls suggests that clinical ASD in middle and late adulthood is not related to or explained by gray matter morphology. These results extent prior findings of suggestive gray matter normalization in late adolescence and early adulthood, and may suggest that ASD is not characterized by continuous distinct developmental gray matter trajectories.