title: Regional brain volume differences between males with and without autism spectrum disorder are highly age-dependent.
abstract: BACKGROUND
  Neuroanatomical differences between individuals with and without autism spectrum disorder (ASD) were inconsistent in the literature. Such heterogeneity may substantially originate from age-differential effects.
  
  
  METHODS
  Voxel-based morphometry was applied in 86 males with ASD and 90 typically developing control (TDC) males (aged 7 to 29 years). Three steps of statistical modeling (model 1, multiple regression with age as a covariate; model 2, multiple regression further considering diagnosis-by-age interaction; model 3, age-stratified analyses) were performed to dissect the moderating effects of age on diagnostic group differences in neuroanatomy.
  
  
  RESULTS
  Across ages, males with and without ASD did not differ significantly in total gray matter (GM) or white matter (WM) volumes. For both groups, total GM volumes decreased and WM volumes increased with age. For regional volume, comparing with the model only held the age constant (model 1), the main effect of group altered when diagnosis-by-age interaction effects were considered (model 2). Here, participants with ASD had significantly greater relative regional GM volumes than TDC in the right inferior orbitofrontal cortex and bilateral thalamus; for WM, participants with ASD were larger than TDC in the bilateral splenium of corpus callosum and right anterior corona radiata. Importantly, significant diagnosis-by-age interactions were identified at the bilateral anterior prefrontal cortex, bilateral cuneus, bilateral caudate, and the left cerebellum Crus I for GM and left forceps minor for WM. Finally, age-stratified analyses (model 3) showed distinct patterns in GM and WM volumetric alterations in ASD among subsamples of children, adolescents, and adults.
  
  
  CONCLUSIONS
  Our findings suggest that the heterogeneous reports on the atypical neuroanatomy of ASD may substantially originate from age variation in the study samples. Age variation and its methodological and biological implications have to be carefully delineated in future studies of the neurobiology of ASD.
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei, 10002 Taiwan.
authors.forename: Hsiang-Yuan
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, No. 1, Jen-Ai Road Section 1, Taipei, 10051 Taiwan.|Department of Child Psychiatry, Chang Gung Memorial Hospital at Linkou, No. 5 Fu-Hsing St., Taoyuan, 33305 Taiwan.
authors.forename: Hsing-Chang
authors.initials: HC
authors.lastname: Ni
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei, 10002 Taiwan.|Autism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge, CB2 8AH UK.|Centre for Addiction and Mental Health, Hospital for Sick Children, and Department of Psychiatry, University of Toronto, 250 College St., Toronto, M5T 1R8 Canada.
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Lai
authors.affiliation: Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, No. 1, Jen-Ai Road Section 1, Taipei, 10051 Taiwan.|Center for Optoelectronic Medicine, National Taiwan University College of Medicine, No. 1, Jen-Ai Road Section 1, Taipei, 10051 Taiwan.
authors.forename: Wen-Yih Isaac
authors.initials: WI
authors.lastname: Tseng
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei, 10002 Taiwan.|Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, No. 1, Jen-Ai Road Section 1, Taipei, 10051 Taiwan.|Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, No. 1, Jen-Ai Road Section 1, Taipei, 10051 Taiwan.
authors.forename: Susan Shur-Fen
authors.initials: SS
authors.lastname: Gau
keywords: Age; Autism spectrum disorder; Development; Regional brain volume; Structural MRI; Voxel-based morphometry