Deconstructing autism: from unitary syndrome to contributory developmental endophenotypes

International Review of Psychiatry
John N Constantino

Abstract

A recent generation of family studies has revealed that autism can be predicted from an array of neurobehavioural susceptibilities that are appreciable before the syndrome is diagnosed, and that each may be traceable to partially-independent sets of genetic variation. Some of these liabilities are not necessarily specific to ASD-those that are non-specific could account for a significant share of the 'missing heritability' of autism, would (by definition) contribute to pleiotropy, and relate to so-called 'co-morbidities', which are inappropriately named if they actually contribute to (or exacerbate) the severity of autism itself. Linking genetic variants to these underlying traits rather than to a diagnosis of 'autism' may be more productive in devising personalized approaches to developmental intervention, especially if autism represents an epiphenomenon of earlier-interacting susceptibilities. In this article, the implications of conceptualizing autism as a syndrome of neurobehavioural degeneration is considered, predicated on the notion that it can arise from a critical co-aggregation of earlier-interacting neuropsychiatric liabilities, the phenotypic expression of which-importantly-can be moderated by sex.

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Citations

Jan 11, 2019·Autism Research : Official Journal of the International Society for Autism Research·Shuang QiuYawen Liu
Jan 19, 2019·Brain Sciences·Lauren M SchmittCraig Erickson
Sep 20, 2019·Journal of Autism and Developmental Disorders·Zoë HawksNatasha Marrus
Feb 7, 2020·Journal of Neurodevelopmental Disorders·Jessica B GiraultUNKNOWN IBIS Network
Jun 1, 2018·Cerebral Cortex·Lauren E LiberoChristine Wu Nordahl
Oct 22, 2020·Molecular Autism·Ilaria Minio-PaluelloSimon Baron-Cohen
Jan 13, 2021·Journal of Child Psychology and Psychiatry, and Allied Disciplines·Mark H JohnsonEmily J H Jones
Jan 26, 2021·Journal of Autism and Developmental Disorders·Giacomo Vivanti, Daniel S Messinger
Jan 12, 2021·Journal of Neurodevelopmental Disorders·Robin SifreJed T Elison
Nov 12, 2018·Comprehensive Psychiatry·Theodore P BeauchaineElizabeth P Hayden
Jul 3, 2021·Journal of Personalized Medicine·María Luján Ferreira, Nicolás Loyacono
Jul 12, 2021·Molecular Autism·Kathryn E UnruhMatthew W Mosconi
Aug 4, 2021·Annals of the New York Academy of Sciences·Jennifer CableJennifer G Mulle
Sep 10, 2021·Psychiatry Investigation·Jeeyoung ChunHee Jeong Yoo

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