Can the "female protective effect" liability threshold model explain sex differences in autism spectrum disorder?
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
19 10 2022
19 10 2022
Historique:
received:
19
01
2022
revised:
09
05
2022
accepted:
24
06
2022
pubmed:
23
7
2022
medline:
25
10
2022
entrez:
22
7
2022
Statut:
ppublish
Résumé
Male sex is a strong risk factor for autism spectrum disorder (ASD). The leading theory for a "female protective effect" (FPE) envisions males and females have "differing thresholds" under a "liability threshold model" (DT-LTM). Specifically, this model posits that females require either a greater number or larger magnitude of risk factors (i.e., greater liability) to manifest ASD, which is supported by the finding that a greater proportion of females with ASD have highly penetrant genetic mutations. Herein, we derive testable hypotheses from the DT-LTM for ASD, investigating heritability, familial recurrence, correlation between ASD penetrance and sex ratio, population traits, clinical features, the stability of the sex ratio across diagnostic changes, and highlight other key prerequisites. Our findings reveal that several key predictions of the DT-LTM are not supported by current data, requiring us to establish a different conceptual framework for evaluating alternate models that explain sex differences in ASD.
Identifiants
pubmed: 35868305
pii: S0896-6273(22)00589-X
doi: 10.1016/j.neuron.2022.06.020
pmc: PMC9588569
mid: NIHMS1821152
pii:
doi:
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3243-3262Subventions
Organisme : NINDS NIH HHS
ID : R01 NS114551
Pays : United States
Organisme : NINDS NIH HHS
ID : R56 NS114551
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH116999
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097211
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH114924
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103525
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests J.N.C. receives royalties from Western Psychological Services for the commercial distribution of the social responsiveness scale, a quantitative measure of autistic traits implemented in some of the studies cited in this article.
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