title: Meta-analysis of gray matter abnormalities in autism spectrum disorder: should Asperger disorder be subsumed under a broader umbrella of autistic spectrum disorder?
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Twenty-four data sets met inclusion criteria, comprising 496 participants with ASD and 471 healthy control individuals.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, England.
authors.forename: Esther
authors.initials: E
authors.lastname: Via
authors.forename: Joaquim
authors.initials: J
authors.lastname: Radua
authors.forename: Narcis
authors.initials: N
authors.lastname: Cardoner
authors.forename: Francesca
authors.initials: F
authors.lastname: Happé
authors.forename: David
authors.initials: D
authors.lastname: Mataix-Cols
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D020817:Asperger Syndrome / Q000175:diagnosis* / Q000473:pathology*; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping / Q000379:methods; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis* / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology*