Uncovering neurodevelopmental paths to autism spectrum disorder through an integrated analysis of developmental measures and neural sensitivity to faces.
Journal
Journal of psychiatry & neuroscience : JPN
ISSN: 1488-2434
Titre abrégé: J Psychiatry Neurosci
Pays: Canada
ID NLM: 9107859
Informations de publication
Date de publication:
04 01 2021
04 01 2021
Historique:
entrez:
3
10
2020
pubmed:
4
10
2020
medline:
29
10
2021
Statut:
epublish
Résumé
Autism spectrum disorder (ASD) is highly heterogeneous in its etiology and manifestation. The neurobiological processes underlying ASD development are reflected in multiple features, from behaviour and cognition to brain functioning. An integrated analysis of these features may optimize the identification of these processes. We examined cognitive and adaptive functioning and ASD symptoms between 8 and 36 months in 161 infants at familial high risk for ASD and 71 low-risk controls; we also examined neural sensitivity to eye gaze at 8 months in a subsample of 140 high-risk and 61 low-risk infants. We used linked independent component analysis to extract patterns of variation across domains and development, and we selected the patterns significantly associated with clinical classification at 36 months. An early process at 8 months, indicating high levels of functioning and low levels of symptoms linked to higher attention to gaze shifts, was reduced in infants who developed ASD. A longitudinal process of increasing functioning and low levels of symptoms was reduced in infants who developed ASD, and another process suggesting a stagnation in cognitive functioning at 24 months was increased in infants who developed ASD. Although the results showed a clear significant trend relating to clinical classification, we found substantial overlap between groups. We uncovered underlying processes that acted together early in development and were associated with clinical outcomes. Our results highlighted the complexity of emerging ASD, which goes beyond the borders of clinical categories. Future work should integrate genetic data to investigate the specific genetic risks linked to these processes.
Sections du résumé
BACKGROUND
Autism spectrum disorder (ASD) is highly heterogeneous in its etiology and manifestation. The neurobiological processes underlying ASD development are reflected in multiple features, from behaviour and cognition to brain functioning. An integrated analysis of these features may optimize the identification of these processes.
METHODS
We examined cognitive and adaptive functioning and ASD symptoms between 8 and 36 months in 161 infants at familial high risk for ASD and 71 low-risk controls; we also examined neural sensitivity to eye gaze at 8 months in a subsample of 140 high-risk and 61 low-risk infants. We used linked independent component analysis to extract patterns of variation across domains and development, and we selected the patterns significantly associated with clinical classification at 36 months.
RESULTS
An early process at 8 months, indicating high levels of functioning and low levels of symptoms linked to higher attention to gaze shifts, was reduced in infants who developed ASD. A longitudinal process of increasing functioning and low levels of symptoms was reduced in infants who developed ASD, and another process suggesting a stagnation in cognitive functioning at 24 months was increased in infants who developed ASD.
LIMITATIONS
Although the results showed a clear significant trend relating to clinical classification, we found substantial overlap between groups.
CONCLUSION
We uncovered underlying processes that acted together early in development and were associated with clinical outcomes. Our results highlighted the complexity of emerging ASD, which goes beyond the borders of clinical categories. Future work should integrate genetic data to investigate the specific genetic risks linked to these processes.
Identifiants
pubmed: 33009904
pii: 10.1503/jpn.190148
doi: 10.1503/jpn.190148
pmc: PMC7955837
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
E34-E43Subventions
Organisme : Medical Research Council
ID : MR/T003057/1
Pays : United Kingdom
Informations de copyright
© 2021 Joule Inc. or its licensors
Déclaration de conflit d'intérêts
G. Bussu reports a grant from the European Community’s Horizon 2020 Program (Brainview) during the conduct of this study. E. Jones reports grants from the European Community’s Horizon 2020 Program (Brainview and EU AIMS) and the UK Medical Research Council during the conduct of this study. T. Charman reports grants from the UK Medical Research Council and the Innovative Medicines Initiative during the conduct of the study, as well as personal fees from Hoffmann-La Roche Ltd, Sage Publications and Guilford Publications, outside the submitted work. C. Beckmann is the co-founder, director and shareholder of SBGneuro Ltd. No other competing interests were declared.
Références
Elife. 2019 Jul 03;8:
pubmed: 31268418
Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):17648-53
pubmed: 25422429
Lancet. 2014 Mar 8;383(9920):896-910
pubmed: 24074734
J Autism Dev Disord. 2018 Jul;48(7):2418-2433
pubmed: 29453709
Neuroimage Clin. 2016 Mar 04;11:357-367
pubmed: 27298764
J Child Psychol Psychiatry. 2010 Mar;51(3):259-76
pubmed: 19912448
Biol Psychiatry. 2017 Aug 1;82(3):186-193
pubmed: 28392081
Biol Psychiatry. 2013 Aug 1;74(3):195-203
pubmed: 23313640
J Am Acad Child Adolesc Psychiatry. 2016 Mar;55(3):179-87
pubmed: 26903251
Neuropsychologia. 2019 Mar 18;126:20-26
pubmed: 28389367
Mol Psychiatry. 2017 Oct;22(10):1385-1394
pubmed: 28937691
Curr Biol. 2012 Feb 21;22(4):338-42
pubmed: 22285033
J Neurodev Disord. 2015;7(1):24
pubmed: 26203305
Brain. 2013 Sep;136(Pt 9):2825-35
pubmed: 23838695
J Autism Dev Disord. 1994 Jun;24(3):247-57
pubmed: 8050980
Autism Res. 2017 Jan;10(1):169-178
pubmed: 27417857
Dev Psychopathol. 2005 Summer;17(3):599-619
pubmed: 16262984
Curr Dir Psychol Sci. 2007 Oct 1;16(5):269-274
pubmed: 19343102
Am J Psychiatry. 2010 Jul;167(7):748-51
pubmed: 20595427
Biol Psychiatry. 2013 Aug 1;74(3):189-94
pubmed: 23374640
Dialogues Clin Neurosci. 2017 Dec;19(4):325-333
pubmed: 29398928
J Autism Dev Disord. 2013 Jul;43(7):1527-38
pubmed: 23114567
J Am Acad Child Adolesc Psychiatry. 2002 Oct;41(10):1239-45
pubmed: 12364846
Am J Occup Ther. 2012 Sep-Oct;66(5):577-85
pubmed: 22917124
Mol Autism. 2017 Jun 23;8:24
pubmed: 28649312
Autism. 2008 Sep;12(5):433-56
pubmed: 18805941
Neurosci Biobehav Rev. 2014 Feb;39:1-33
pubmed: 24361967
Biol Psychiatry. 2014 Feb 1;75(3):231-7
pubmed: 23954107
Nature. 2017 Feb 15;542(7641):348-351
pubmed: 28202961
Dev Psychopathol. 2018 May;30(2):553-569
pubmed: 28803559
Dev Neuropsychol. 2012;37(3):187-209
pubmed: 22545658
Sci Transl Med. 2017 Jun 7;9(393):
pubmed: 28592562
J Neurodev Disord. 2016 Mar 15;8:7
pubmed: 26981158
J Child Psychol Psychiatry. 2015 Sep;56(9):988-98
pubmed: 25921776
Am J Psychiatry. 2013 Aug;170(8):899-908
pubmed: 23511344
Nature. 2013 Dec 19;504(7480):427-31
pubmed: 24196715
Neuroimage. 2011 Feb 1;54(3):2198-217
pubmed: 20932919
J Autism Dev Disord. 2013 Apr;43(4):817-28
pubmed: 22855372
Neuroimage. 2004;23 Suppl 1:S208-19
pubmed: 15501092
Neurosci Biobehav Rev. 2019 Jul;102:24-55
pubmed: 30917924
J Neurodev Disord. 2018 Jan 29;10(1):3
pubmed: 29378525
Nat Rev Neurol. 2014 Feb;10(2):74-81
pubmed: 24468882
Neurosci Biobehav Rev. 2019 May;100:296-304
pubmed: 30885812
J Psychiatry Neurosci. 2017 Nov;42(6):386-394
pubmed: 28832320