A Comparison of Global Brain Volume, Regional Grey Matter and White Matter in Autism Spectrum Disorder and Its Relationship with Symptom Severity in Children and Adolescents: A Voxel-Based Morphometry Study

Background:  It has been widely reported that there are neuroanatomical differences in ASD. However, little consensus exists with regards to the regions implicated, in part due to the non-replication of findings. This may be because prior studies included individuals with co-morbid physical health problems and / or intellectual disability. As such, the exact neurobiological foundations of the highly variable behavioural phenotype of ASD are little understood.

Objectives: This study therefore aimed to investigate (a) if there are differences in global brain volumes between otherwise healthy children and adolescents with ASD and healthy controls of normal overall intelligence who did not significantly differ in gender, age and IQ; and (b) if volumetric differences are associated with clinical variation as measured by the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule-Generic (ADOS-G).

Methods:  Using non-invasive Magnetic Resonance Imaging (MRI) techniques, eighteen right-handed child and adolescent males with ASD (mean age = 12.5 (SD = 2.7); mean IQ = 105 (SD = 17.2)) and eighteen healthy controls (mean age = 13.9 (SD = 2.7; mean IQ = 108 (SD = 11.3)), who did not differ significantly in mean age and full scale IQ, were scanned at the Centre for Neuroimaging Sciences, Institute of Psychiatry, King’s College London using GE 3 Tesla (T) MR system (General-Electric, Milwaukee, WI, USA). Voxel Based Morphometry (VBM) analysis was utilised to investigate the between group differences in neuroanatomy and to assess their relationship with ASD symptomatology as measured by the various domains in the ADI-R and ADOS-G using Pearson’s product-moment correlation coefficient.

Results: Children and adolescents with ASD did not differ significantly from healthy controls in mean global brain volume, grey matter volume and white matter volume. There were however, significant volumetric differences in regional white matter between the two groups. White matter was predominantly reduced bilaterally in the internal capsule, and unilaterally in the left corpus callosum. Further, correlation analysis of regional differences indicated that white matter deficits in the internal capsule were correlated with severity of social and communication impairments.

Conclusions:  Not all children and adolescents with ASD have macrocephaly. This may particularly apply to otherwise healthy individuals. Nevertheless, within this population differences in white matter development are associated with clinical variation.