title: Longitudinal changes in cortical thickness in autism and typical development.
abstract: The natural history of brain growth in autism spectrum disorders remains unclear. Cross-sectional studies have identified regional abnormalities in brain volume and cortical thickness in autism, although substantial discrepancies have been reported. Preliminary longitudinal studies using two time points and small samples have identified specific regional differences in cortical thickness in the disorder. To clarify age-related trajectories of cortical development, we examined longitudinal changes in cortical thickness within a large mixed cross-sectional and longitudinal sample of autistic subjects and age- and gender-matched typically developing controls. Three hundred and forty-five magnetic resonance imaging scans were examined from 97 males with autism (mean age = 16.8 years; range 3-36 years) and 60 males with typical development (mean age = 18 years; range 4-39 years), with an average interscan interval of 2.6 years. FreeSurfer image analysis software was used to parcellate the cortex into 34 regions of interest per hemisphere and to calculate mean cortical thickness for each region. Longitudinal linear mixed effects models were used to further characterize these findings and identify regions with between-group differences in longitudinal age-related trajectories. Using mean age at time of first scan as a reference (15 years), differences were observed in bilateral inferior frontal gyrus, pars opercularis and pars triangularis, right caudal middle frontal and left rostral middle frontal regions, and left frontal pole. However, group differences in cortical thickness varied by developmental stage, and were influenced by IQ. Differences in age-related trajectories emerged in bilateral parietal and occipital regions (postcentral gyrus, cuneus, lingual gyrus, pericalcarine cortex), left frontal regions (pars opercularis, rostral middle frontal and frontal pole), left supramarginal gyrus, and right transverse temporal gyrus, superior parietal lobule, and paracentral, lateral orbitofrontal, and lateral occipital regions. We suggest that abnormal cortical development in autism spectrum disorders undergoes three distinct phases: accelerated expansion in early childhood, accelerated thinning in later childhood and adolescence, and decelerated thinning in early adulthood. Moreover, cortical thickness abnormalities in autism spectrum disorders are region-specific, vary with age, and may remain dynamic well into adulthood.
authors.affiliation: 1 Department of Pediatrics, University of Utah, Salt Lake City, UT, USA2 Department of Neurology, University of Utah, Salt Lake City, UT, USA3 Primary Children's Medical Centre, Salt Lake City, UT, USA brandon.zielinski@hsc.utah.edu.
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Zielinski
authors.affiliation: 1 Department of Pediatrics, University of Utah, Salt Lake City, UT, USA4 Department of Radiology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Molly B D
authors.initials: MB
authors.lastname: Prigge
authors.affiliation: 4 Department of Radiology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Jared A
authors.initials: JA
authors.lastname: Nielsen
authors.affiliation: 5 Department of Psychology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Alyson L
authors.initials: AL
authors.lastname: Froehlich
authors.affiliation: 6 Neuroscience Centre, Brigham Young University, Provo, UT, USA.
authors.forename: Tracy J
authors.initials: TJ
authors.lastname: Abildskov
authors.affiliation: 4 Department of Radiology, University of Utah, Salt Lake City, UT, USA7 Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Anderson
authors.affiliation: 8 Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USA9 School of Computing, University of Utah, Salt Lake City, UT, USA.
authors.forename: P Thomas
authors.initials: PT
authors.lastname: Fletcher
authors.affiliation: 8 Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Zygmunt
authors.affiliation: 10 Waisman Laboratory for Brain Imaging and Behaviour, University of Wisconsin, Madison, WI, USA.
authors.forename: Brittany G
authors.initials: BG
authors.lastname: Travers
authors.affiliation: 11 Department of Psychiatry, Harvard Medical School, Boston, MA, USA12 Department of Biostatistics, Harvard Medical School, Boston, MA, USA13 Neurostatistics Laboratory, McLean Hospital, Belmont, MA, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lange
authors.affiliation: 10 Waisman Laboratory for Brain Imaging and Behaviour, University of Wisconsin, Madison, WI, USA14 Department of Medical Physics, University of Wisconsin, Madison, WI, USA15 Department of Psychiatry, University of Wisconsin, Madison, WI, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Alexander
authors.affiliation: 6 Neuroscience Centre, Brigham Young University, Provo, UT, USA16 Department of Psychology, Brigham Young University, Provo, UT, USA.
authors.forename: Erin D
authors.initials: ED
authors.lastname: Bigler
authors.affiliation: 10 Waisman Laboratory for Brain Imaging and Behaviour, University of Wisconsin, Madison, WI, USA15 Department of Psychiatry, University of Wisconsin, Madison, WI, USA.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Lainhart
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000473:pathology*; D001931:Brain Mapping / Q000379:methods; D002540:Cerebral Cortex / Q000254:growth & development* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D007361:Intelligence Tests; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D055815:Young Adult
keywords: MRI; autism; brain development; developmental neuroimaging; human brain mapping
references.citation: J Autism Dev Disord. 2000 Jun;30(3):205-23
references.pmid: 11055457
references.citation: J Am Acad Child Adolesc Psychiatry. 1997 Feb;36(2):282-90
references.pmid: 9031582
references.citation: Neuroimage. 2012 Jul 16;61(4):1402-18
references.pmid: 22430496
references.citation: Brain Res. 2011 Mar 22;1380:138-45
references.pmid: 20920490
references.citation: Neuroimage. 2011 Sep 15;58(2):391-400
references.pmid: 21749926
references.citation: Dev Med Child Neurol. 2002 Jan;44(1):4-16
references.pmid: 11811649
references.citation: Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18191-6
references.pmid: 20921389
references.citation: Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):17089-94
references.pmid: 24082094
references.citation: Am J Psychiatry. 2004 Mar;161(3):539-46
references.pmid: 14992981
references.citation: PLoS One. 2012;7(11):e49172
references.pmid: 23185305
references.citation: Hum Brain Mapp. 2010 Apr;31(4):556-66
references.pmid: 19790171
references.citation: Cereb Cortex. 2009 Nov;19(11):2728-35
references.pmid: 19299253
references.citation: Arch Gen Psychiatry. 2010 Apr;67(4):397-405
references.pmid: 20368515
references.citation: Arch Gen Psychiatry. 2011 May;68(5):467-76
references.pmid: 21536976
references.citation: Neuroimage. 2002 Aug;16(4):1038-51
references.pmid: 12202091
references.citation: JAMA. 2003 Jul 16;290(3):393-4
references.pmid: 12865381
references.citation: Arch Gen Psychiatry. 2005 Dec;62(12):1366-76
references.pmid: 16330725
references.citation: Brain. 2010 Dec;133(Pt 12):3745-54
references.pmid: 20926367
references.citation: JAMA. 2003 Jul 16;290(3):337-44
references.pmid: 12865374
references.citation: Hum Brain Mapp. 2013 Feb;34(2):425-36
references.pmid: 22021093
references.citation: Neuroimage. 2012 Apr 15;60(3):1890-901
references.pmid: 22326986
references.citation: Am J Med Genet A. 2006 Nov 1;140(21):2257-74
references.pmid: 17022081
references.citation: Curr Opin Neurol. 2004 Aug;17(4):489-96
references.pmid: 15247547
references.citation: Neurology. 2002 Jul 23;59(2):175-83
references.pmid: 12136053
references.citation: Cereb Cortex. 1996 Sep-Oct;6(5):726-36
references.pmid: 8921207
references.citation: Neuroimage. 2007 Jan 1;34(1):61-73
references.pmid: 17023185
references.citation: J Autism Dev Disord. 2006 Oct;36(7):849-61
references.pmid: 16845581
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11050-5
references.pmid: 10984517
references.citation: J Neurosci. 2012 Apr 4;32(14):4856-60
references.pmid: 22492041
references.citation: Ann N Y Acad Sci. 2004 Jun;1021:77-85
references.pmid: 15251877
references.citation: Neuroimage. 2006 Jul 1;31(3):968-80
references.pmid: 16530430
references.citation: Neuroimage. 2006 Jul 1;31(3):993-1003
references.pmid: 16624590
references.citation: Nature. 2006 Mar 30;440(7084):676-9
references.pmid: 16572172
references.citation: Neuroimage. 2010 Nov 15;53(3):1135-46
references.pmid: 20006715
references.citation: Neuroimage. 2010 Apr 1;50(2):589-99
references.pmid: 20026220
references.citation: Cereb Cortex. 2004 Jan;14(1):11-22
references.pmid: 14654453
references.citation: Am J Psychiatry. 2000 Feb;157(2):163-71
references.pmid: 10671382
references.citation: Neuroimage. 2005 May 1;25(4):1256-65
references.pmid: 15850743
references.citation: Autism Res. 2013 Apr;6(2):78-90
references.pmid: 23436773
references.citation: J Autism Dev Disord. 2012 Mar;42(3):419-27
references.pmid: 21556969
references.citation: J Neurosci. 2010 Mar 24;30(12):4419-27
references.pmid: 20335478
references.citation: Biol Psychiatry. 2009 Aug 15;66(4):320-6
references.pmid: 19520362
references.citation: Neuropsychologia. 1971 Mar;9(1):97-113
references.pmid: 5146491
references.citation: J Autism Dev Disord. 1994 Oct;24(5):659-85
references.pmid: 7814313
references.citation: Brain. 2003 May;126(Pt 5):1182-92
references.pmid: 12690057
references.citation: JAMA Psychiatry. 2013 Jan;70(1):59-70
references.pmid: 23404046
references.citation: Neuroimage. 2010 Dec;53(4):1181-96
references.pmid: 20637289
references.citation: Cereb Cortex. 2006 Sep;16(9):1276-82
references.pmid: 16306324
references.citation: J Child Neurol. 2001 Jun;16(6):421-4
references.pmid: 11417608
references.citation: Neurology. 2001 Jul 24;57(2):245-54
references.pmid: 11468308
references.citation: Neuron. 2002 Jan 31;33(3):341-55
references.pmid: 11832223
references.citation: Am J Psychiatry. 2006 Jul;163(7):1290-2
references.pmid: 16816240
references.citation: Cereb Cortex. 2010 Jun;20(6):1332-40
references.pmid: 19819933
references.citation: J Psychiatr Res. 2013 Apr;47(4):453-9
references.pmid: 23260170