title: The effect of age, diagnosis, and their interaction on vertex-based measures of cortical thickness and surface area in autism spectrum disorder.
abstract: Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is accompanied by an atypical development of brain maturation. So far, brain development has mainly been studied during early childhood in ASD, and using measures of total or lobular brain volume. However, cortical volumetric measures are a product of two distinct biological neuroanatomical features, cortical thickness, and surface area, which most likely also have different neurodevelopmental trajectories in ASD. Here, we therefore examined age-related differences in cortical thickness and surface area in a cross-sectional sample of 77 male individuals with ASD ranging from 7 to 25 years of age, and 77 male neurotypical controls matched for age and FSIQ. Surface-based measures were analyzed using a general linear model (GLM) including linear, quadratic, and cubic age terms, as well as their interactions with the main effect of group. When controlling for the effects of age, individuals with ASD had spatially distributed reductions in cortical thickness relative to controls, particularly in fronto-temporal regions, and also showed significantly reduced surface area in the prefrontal cortex and the anterior temporal lobe. We also observed significant group × age interactions for both measures. However, while cortical thickness was best predicted by a quadratic age term, the neurodevelopmental trajectory for measures of surface area was mostly linear. Our findings suggest that ASD is accompanied by age-related and region-specific reductions in cortical thickness and surface area during childhood and early adulthood. Thus, differences in the neurodevelopmental trajectory of maturation for both measures need to be taken into account when interpreting between-group differences overall.
authors.affiliation: Department of Forensic and Neurodevelopmental Sciences, and the Sackler Institute for Translational Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, SE5 8AF, UK, christine.ecker@kcl.ac.uk.
authors.forename: C
authors.initials: C
authors.lastname: Ecker
authors.forename: A
authors.initials: A
authors.lastname: Shahidiani
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: E
authors.initials: E
authors.lastname: Daly
authors.forename: C
authors.initials: C
authors.lastname: Murphy
authors.forename: V
authors.initials: V
authors.lastname: D'Almeida
authors.forename: S
authors.initials: S
authors.lastname: Deoni
authors.forename: S C
authors.initials: SC
authors.lastname: Williams
authors.forename: N
authors.initials: N
authors.lastname: Gillan
authors.forename: M
authors.initials: M
authors.lastname: Gudbrandsen
authors.forename: R
authors.initials: R
authors.lastname: Wichers
authors.forename: D
authors.initials: D
authors.lastname: Andrews
authors.forename: L
authors.initials: L
authors.lastname: Van Hemert
authors.forename: D G M
authors.initials: DG
authors.lastname: Murphy
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging; D002540:Cerebral Cortex / Q000254:growth & development* / Q000473:pathology*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000473:pathology*; D003430:Cross-Sectional Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009483:Neuropsychological Tests; D009929:Organ Size; D055815:Young Adult
references.citation: Brain. 2013 Jun;136(Pt 6):1956-67
references.pmid: 23715094
references.citation: Hum Brain Mapp. 2010 Apr;31(4):556-66
references.pmid: 19790171
references.citation: JAMA. 2011 Nov 9;306(18):2001-10
references.pmid: 22068992
references.citation: Arch Gen Psychiatry. 2011 May;68(5):467-76
references.pmid: 21536976
references.citation: Biol Psychiatry. 2007 Aug 1;62(3):262-6
references.pmid: 17224135
references.citation: Nat Rev Neurosci. 2007 Dec;8(12):976-87
references.pmid: 18026167
references.citation: J Autism Dev Disord. 1989 Jun;19(2):185-212
references.pmid: 2745388
references.citation: Development. 2004 Jul;131(13):3133-45
references.pmid: 15175243
references.citation: J Child Neurol. 2013 Jun;28(6):732-9
references.pmid: 22832774
references.citation: Biol Psychiatry. 2009 Nov 15;66(10):942-9
references.pmid: 19726029
references.citation: J Neurosci. 2011 May 11;31(19):7174-7
references.pmid: 21562281
references.citation: Neuroimage. 2004 Jul;22(3):1060-75
references.pmid: 15219578
references.citation: Cortex. 2012 Feb;48(2):183-93
references.pmid: 21718979
references.citation: Arch Gen Psychiatry. 2006 May;63(5):540-9
references.pmid: 16651511
references.citation: Cereb Cortex. 2009 Nov;19(11):2728-35
references.pmid: 19299253
references.citation: J Comp Neurol. 1997 Oct 20;387(2):167-78
references.pmid: 9336221
references.citation: Nat Rev Neurosci. 2008 Apr;9(4):267-77
references.pmid: 18354399
references.citation: Brain. 2002 Aug;125(Pt 8):1839-49
references.pmid: 12135974
references.citation: Neuroimage. 2012 Jul 16;61(4):1428-43
references.pmid: 22446492
references.citation: Biol Psychiatry. 2005 Jan 15;57(2):126-33
references.pmid: 15652870
references.citation: Biol Psychiatry. 2008 Oct 1;64(7):589-98
references.pmid: 18672231
references.citation: Hum Brain Mapp. 1999;8(2-3):98-101
references.pmid: 10524599
references.citation: Nat Rev Neurosci. 2008 Feb;9(2):148-58
references.pmid: 18209732
references.citation: Brain. 2010 Dec;133(Pt 12):3745-54
references.pmid: 20926367
references.citation: Trends Neurosci. 1995 Sep;18(9):383-8
references.pmid: 7482803
references.citation: Hum Brain Mapp. 1999;8(4):272-84
references.pmid: 10619420
references.citation: Nat Neurosci. 1999 Oct;2(10):861-3
references.pmid: 10491603
references.citation: Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):13222-7
references.pmid: 23878213
references.citation: Autism. 2010 Sep;14(5):408-29
references.pmid: 20926457
references.citation: Neuroimage. 2004 Jun;22(2):619-25
references.pmid: 15193590
references.citation: Lancet. 1997 Dec 13;350(9093):1761-6
references.pmid: 9413479
references.citation: PLoS One. 2007 Sep 12;2(9):e883
references.pmid: 17849012
references.citation: Neuroimage. 1999 Feb;9(2):179-94
references.pmid: 9931268
references.citation: Nat Neurosci. 2004 Feb;7(2):136-44
references.pmid: 14703572
references.citation: Neuroimage. 2011 Sep 15;58(2):391-400
references.pmid: 21749926
references.citation: Acta Neuropathol. 2006 Sep;112(3):287-303
references.pmid: 16819561
references.citation: Nature. 2009 May 28;459(7246):528-33
references.pmid: 19404256
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: Brain. 2005 Feb;128(Pt 2):268-76
references.pmid: 15548557
references.citation: J Autism Dev Disord. 1994 Oct;24(5):659-85
references.pmid: 7814313
references.citation: Arch Gen Psychiatry. 2012 Feb;69(2):195-209
references.pmid: 22310506
references.citation: JAMA Psychiatry. 2013 Jan;70(1):59-70
references.pmid: 23404046
references.citation: Int J Dev Neurosci. 2005 Apr-May;23(2-3):153-70
references.pmid: 15749242
references.citation: Am J Psychiatry. 2006 Jul;163(7):1290-2
references.pmid: 16816240
references.citation: Trends Neurosci. 2008 Mar;31(3):137-45
references.pmid: 18258309
references.citation: Neuropsychologia. 2007 Apr 9;45(8):1672-84
references.pmid: 17336346
references.citation: Curr Opin Neurobiol. 2007 Feb;17(1):103-11
references.pmid: 17275283
references.citation: Soc Neurosci. 2008;3(2):97-112
references.pmid: 18633852
references.citation: Brain. 2010 Feb;133(Pt 2):611-24
references.pmid: 20008375
references.citation: Trends Cogn Sci. 2005 Feb;9(2):60-8
references.pmid: 15668098
references.citation: Cereb Cortex. 2010 Jun;20(6):1332-40
references.pmid: 19819933
references.citation: Dev Neurosci. 2008;30(1-3):24-32
references.pmid: 18075251
references.citation: Arch Gen Psychiatry. 2012 Jan;69(1):53-61
references.pmid: 22213789
references.citation: Neuroimage. 1999 Feb;9(2):195-207
references.pmid: 9931269