Psychological Medicine

Original Articles

Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study

F. Toala1a2 c1, E. M. Dalya2, L. Pagea2, Q. Deeleya2, B. Hallahana1a2, O. Bloemena2, W. J. Cuttera2, M. J. Brammera3, S. Currana2, D. Robertsona2, C. Murphya2, K. C. Murphya1 and D. G. M. Murphya2

a1 Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland

a2 Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK

a3 Section of Image Analysis, Centre for Neuroimaging Science, Institute of Psychiatry, King's College, London, UK


Background Autistic spectrum disorder (ASD) is characterized by stereotyped/obsessional behaviours and social and communicative deficits. However, there is significant variability in the clinical phenotype; for example, people with autism exhibit language delay whereas those with Asperger syndrome do not. It remains unclear whether localized differences in brain anatomy are associated with variation in the clinical phenotype.

Method We used voxel-based morphometry (VBM) to investigate brain anatomy in adults with ASD. We included 65 adults diagnosed with ASD (39 with Asperger syndrome and 26 with autism) and 33 controls who did not differ significantly in age or gender.

Results VBM revealed that subjects with ASD had a significant reduction in grey-matter volume of medial temporal, fusiform and cerebellar regions, and in white matter of the brainstem and cerebellar regions. Furthermore, within the subjects with ASD, brain anatomy varied with clinical phenotype. Those with autism demonstrated an increase in grey matter in frontal and temporal lobe regions that was not present in those with Asperger syndrome.

Conclusions Adults with ASD have significant differences from controls in the anatomy of brain regions implicated in behaviours characterizing the disorder, and this differs according to clinical subtype.

(Received April 16 2009)

(Revised August 19 2009)

(Accepted September 15 2009)

(Online publication November 06 2009)


c1 Address for correspondence: Dr F. Toal, MRCPsych, Institute of Forensic Mental Health, Thomas Embling Hospital, Yarra Bend Road, Melbourne, Australia. (Email: