Meta-analysis of gray matter abnormalities in autism spectrum disorder: should Asperger disorder be subsumed under a broader umbrella of autistic spectrum disorder?

Arch Gen Psychiatry. 2011 Apr;68(4):409-18. doi: 10.1001/archgenpsychiatry.2011.27.


Context: Studies investigating abnormalities of regional gray matter volume in autism spectrum disorder (ASD) have yielded contradictory results. It is unclear whether the current subtyping of ASD into autistic disorder and Asperger disorder is neurobiologically valid.

Objectives: To conduct a quantitative meta-analysis of voxel-based morphometry studies exploring gray matter volume abnormalities in ASD, to examine potential neurobiological differences among ASD subtypes, and to create an online database to facilitate replication and further analyses by other researchers.

Data sources: We retrieved studies from PubMed, ScienceDirect, Scopus, and Web of Knowledge databases between June 3, 1999, the date of the first voxel-based morphometry study in ASD, and October 31, 2010. Studies were also retrieved from reference lists and review articles. We contacted authors soliciting additional data.

Study selection: Twenty-four data sets met inclusion criteria, comprising 496 participants with ASD and 471 healthy control individuals.

Data extraction: Peak coordinates of clusters of regional gray matter differences between participants with ASD and controls, as well as demographic, clinical, and methodologic variables, were extracted from each study or obtained from the authors.

Data synthesis: No differences in overall gray matter volume were found between participants with ASD and healthy controls. Participants with ASD were found to have robust decreases of gray matter volume in the bilateral amygdala-hippocampus complex and the bilateral precuneus. A small increase of gray matter volume in the middle-inferior frontal gyrus was also found. No significant differences in overall or regional gray matter volumes were found between autistic disorder and Asperger disorder. Decreases of gray matter volume in the right precuneus were statistically higher in adults than in adolescents with ASD.

Conclusions: These results confirm the crucial involvement of structures linked to social cognition in ASD. The absence of significant differences between ASD subtypes may have important nosologic implications for the DSM-5. The publically available database will be a useful resource for future research.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Asperger Syndrome / diagnosis*
  • Asperger Syndrome / pathology*
  • Atrophy / pathology
  • Brain / pathology*
  • Brain Mapping / methods
  • Child
  • Child Development Disorders, Pervasive / diagnosis*
  • Child Development Disorders, Pervasive / pathology*
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Nerve Fibers, Unmyelinated / pathology*