title: Atypical development of white matter microstructure of the corpus callosum in males with autism: a longitudinal investigation.
abstract: BACKGROUND
  The corpus callosum is the largest white matter structure in the brain, and it is the most consistently reported to be atypical in diffusion tensor imaging studies of autism spectrum disorder. In individuals with typical development, the corpus callosum is known to undergo a protracted development from childhood through young adulthood. However, no study has longitudinally examined the developmental trajectory of corpus callosum in autism past early childhood.
  
  
  METHODS
  The present study used a cohort sequential design over 9 years to examine age-related changes of the corpus callosum in 100 males with autism and 56 age-matched males with typical development from early childhood (when autism can first be reliably diagnosed) to mid-adulthood (after development of the corpus callosum has been completed) (3 to 41 years of age).
  
  
  RESULTS
  The group with autism demonstrated a different developmental trajectory of white matter microstructure in the anterior corpus callosum's (genu and body) fractional anisotropy, which suggests atypical brain maturation in these regions in autism. When analyses were broken down by age group, atypical developmental trajectories were present only in the youngest participants (10 years of age and younger). Significant main effects for group were found in terms of decreased fractional anisotropy across all three subregions of the corpus callosum (genu, body, and splenium) and increased mean diffusivity, radial diffusivity, and axial diffusivity in the posterior corpus callosum.
  
  
  CONCLUSIONS
  These longitudinal results suggest atypical early childhood development of the corpus callosum microstructure in autism that transitions into sustained group differences in adolescence and adulthood. This pattern of results provides longitudinal evidence consistent with a growing number of published studies and hypotheses regarding abnormal brain connectivity across the life span in autism.
authors.affiliation: Occupational Therapy Program, Department of Kinesiology, University of Wisconsin-Madison, Madison, WI USA ; Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705 USA.
authors.forename: Brittany G
authors.initials: BG
authors.lastname: Travers
authors.affiliation: Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705 USA ; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI USA.
authors.forename: Do P M
authors.initials: do PM
authors.lastname: Tromp
authors.affiliation: Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705 USA.
authors.forename: Nagesh
authors.initials: N
authors.lastname: Adluru
authors.affiliation: Department of Psychiatry, Harvard School of Medicine, Boston, MA USA ; Neurostatistics Laboratory, McLean Hospital, Belmont, MA USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lange
authors.affiliation: Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705 USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Destiche
authors.affiliation: Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705 USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Ennis
authors.affiliation: Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT USA.
authors.forename: Jared A
authors.initials: JA
authors.lastname: Nielsen
authors.affiliation: Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT USA.
authors.forename: Alyson L
authors.initials: AL
authors.lastname: Froehlich
authors.affiliation: Department of Radiology, University of Utah, Salt Lake City, UT USA ; Department of Pediatrics, University of Utah and Primary Children's Medical Center, Salt Lake City, UT USA.
authors.forename: Molly B D
authors.initials: MB
authors.lastname: Prigge
authors.affiliation: Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT USA ; School of Computing, University of Utah, Salt Lake City, UT USA.
authors.forename: P Thomas
authors.initials: PT
authors.lastname: Fletcher
authors.affiliation: Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT USA ; Department of Radiology, University of Utah, Salt Lake City, UT USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Anderson
authors.affiliation: Department of Pediatrics, University of Utah and Primary Children's Medical Center, Salt Lake City, UT USA ; Department of Neurology, University of Utah, Salt Lake City, UT USA.
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Zielinski
authors.affiliation: Department of Psychology, Brigham Young University, Provo, UT USA ; Neuroscience Center, Brigham Young University, Provo, UT 84602 USA.
authors.forename: Erin D
authors.initials: ED
authors.lastname: Bigler
authors.affiliation: Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705 USA ; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI USA.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Lainhart
authors.affiliation: Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705 USA ; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Alexander
keywords: Adolescence; Adulthood; Brain development; Childhood; Developmental disorders; Diffusion tensor imaging