Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental condition with multiple causes, co-morbid conditions, and a wide range of symptoms and symptom severity. This makes the neuroanatomy of ASD inherently difficult to describe. Although several autistic ‘core’ structures have repeatedly been highlighted in the literature, reports of region-specific differences in ASD are highly variable. Such variable findings may simply be explained by confounds such as clinical heterogeneity between studies, or analytical techniques. Alternatively, variability in findings may indicate that differences in brain anatomy in ASD are relatively subtle and spatially distributed. Hence, very large sample sizes of well-characterized individuals are required to yield to reliable results. So far, however, most neuroimaging studies on ASD are limited by small sample sizes.
The aim of this study was therefore to investigate (1) the feasibility of multi-centre structural MRI acquisition, and (2) to examine brain anatomy in ASD in a very large sample of well characterised male adults with ASD and matched controls.
Overall, 178 participants were recruited and scanned at three participating centres - (1) Institute of Psychiatry, London, (2) Autism Research Centre, Cambridge, (3) Autism Research Group, Oxford. The total sample included 89 adults diagnosed with ASD, and 89 healthy controls (matched for age and FSIQ), with approximately equal numbers of people with ASD and controls recruited at each site. All participants with ASD were diagnosed using the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). Quantitative imaging (relaxometry) was used to acquire multi-centre compatible structural Magnetic Resonance Images (MRI). A conventional non-parametric voxel-based approach employing the GLM was used to examine differences in grey and white matter volume between groups.
There were no significant group differences in total brain volume, total grey and white matter, and total CSF. However, significant grey matter volume differences were observed in three large clusters including temporal, frontal and occipital regions. Differences in white matter were observed throughout the brain and were dominated by regional deficits in the ASD group relative to controls. There were significant relationships between differences in brain anatomy and behaviour.
This study is one of the first to demonstrate the feasibility of multi-centre MRI acquisition of brain anatomy in ASD, and to investigate neuroanatomical differences in a large and well-characterized sample of adults. Our results confirm the hypothesis that adult ASD is accompanied by localized anatomical abnormalities that are related to variation in specific behaviours, rather than global differences.