Etude de jumeaux sur l'heritabilite alteree de la substance blanche chez des jeunes atteints de trouble du spectre de l'autisme

Titre original en anglais : A Twin Study of Altered White Matter Heritability in Youth With Autism Spectrum Disorder

Cette publication est incluse dans le projet « Contributions académiques de personnes autistes sur l’autisme ». un auteur·ice de cette publication est identifié·e comme autiste dans le projet.

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Hegarty, J. P., Monterrey, J. C., Tian, Q., Cleveland, S. C., Gong, X., Phillips, J. M., Wolke, O. N., McNab, J. A., Hallmayer, J. F., Reiss, A. L., Hardan, A. Y., & Lazzeroni, L. C. (2023). A Twin Study of Altered White Matter Heritability in Youth With Autism Spectrum Disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 63(1), 65-79. https://doi.org/10.1016/j.jaac.2023.05.030

Date de publication: 03/07/2023 Ajout dans AutiHub: 05/10/2026 Type: Article Langue de l’article: Anglais
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Auteurs

Auteur·ices des publications
12
Auteur·ices de la publication identifié·es comme autistes
1 / 12 (8,3 %)
  1. John P. Hegarty *
  2. Julio C Monterrey
  3. Qiyuan Tian
  4. Sue C. Cleveland
  1. Xinyi Gong
  2. Jennifer M. Phillips
  3. Olga N. Wolke
  4. Jennifer A. McNab
  1. Joachim F. Hallmayer
  2. Allan L. Reiss
  3. Antonio Y. Hardan
  4. Laura C. Lazzeroni

Résumé

OBJECTIF : Des alterations de la substance blanche sont frequemment rapportees dans le trouble du spectre de l'autisme (TSA), mais leur etiologie est actuellement inconnue. L'objectif de cette investigation etait d'examiner, pour la premiere fois, l'impact des facteurs genetiques et environnementaux sur la microstructure de la substance blanche chez des jumeaux atteints de TSA, par comparaison avec des jumeaux temoins sans TSA. METHODE : Des IRM ponderees en diffusion ont ete obtenues chez des paires de jumeaux de meme sexe (ages de 6 a 15 ans), dans lesquelles au moins 1 jumeau avait recu un diagnostic de TSA, ou aucun des jumeaux ne presentait d'antecedents de troubles neurologiques ou psychiatriques. L'anisotropie fractionnelle (AF) et la diffusivite moyenne (DM) ont ete examinees dans differents faisceaux de substance blanche du cerveau, et des analyses statistiques ainsi qu'une modelisation des jumeaux ont ete realisees afin d'evaluer la proportion de variation associee aux facteurs genetiques additifs (A) et aux facteurs environnementaux communs/partages (C) ou uniques (E). Nous avons egalement developpe une nouvelle methode d'analyse du score de difference entre paires de jumeaux, qui produit des estimations quantitatives des contributions genetiques et environnementales a la covariance partagee entre differents traits cerebraux et comportementaux. RESULTATS : Des donnees de bonne qualite etaient disponibles pour 84 paires de jumeaux : 50 paires TSA (32 concordantes pour le TSA [16 monozygotes ; 16 dizygotes], 16 discordantes pour le TSA [3 monozygotes ; 13 dizygotes], et 2 paires dans lesquelles 1 jumeau avait un TSA et l'autre presentait certains symptomes infraliminaires [1 monozygote ; 1 dizygote]) et 34 paires temoins (20 monozygotes ; 14 dizygotes). Les valeurs moyennes d'AF et de DM dans l'ensemble du cerveau, respectivement, etaient principalement mediees genetiquement tant chez les jumeaux temoins (A = 0.80, IC a 95 % [0.57, 1.02] ; A = 0.80 [0.55, 1.04]) que chez les jumeaux concordants pour un TSA (A = 0.71 [0.33, 1.09] ; A = 0.84 [0.32,1.36]). Cependant, il existait egalement des differences significatives entre les groupes, specifiques a certains faisceaux. Par exemple, les effets genetiques sur les fibres commissurales etaient principalement associes a des differences dans les capacites cognitives generales et peut-etre a certaines differences diagnostiques relatives au TSA, car l'analyse du score de difference entre paires de jumeaux a indique que les facteurs genetiques pourraient avoir contribue a environ 40 % a 50 % de la covariation entre les scores de QI et l'AF du corps calleux. Inversement, l'impact accru des facteurs environnementaux sur certaines fibres de projection et d'association etait principalement associe a des differences de severite des symptomes chez les jumeaux atteints de TSA ; par exemple, nos analyses suggeraient que des facteurs environnementaux uniques pourraient avoir contribue a environ 10 % a 20 % de la covariation entre la severite des symptomes lies a l'autisme et l'AF des pedoncules cerebelleux et de la capsule externe. CONCLUSION : Les alterations de la substance blanche chez les jeunes atteints de TSA sont associees a la fois a des contributions genetiques et a une vulnerabilite ou une reactivite potentiellement accrue aux influences environnementales. DECLARATION SUR LA DIVERSITE ET L'INCLUSION : Nous avons veille a assurer un equilibre entre les sexes et les genres lors du recrutement des participants humains. Nous avons veille a assurer la diversite raciale, ethnique et/ou d'autres types de diversite lors du recrutement des participants humains. Nous avons veille a ce que les questionnaires de l'etude soient prepares de maniere inclusive. Un ou plusieurs auteurs de cet article s'identifient comme membres d'un ou de plusieurs groupes raciaux et/ou ethniques historiquement sous-representes dans les sciences. Un ou plusieurs auteurs de cet article s'identifient comme membres d'un ou de plusieurs groupes sexuels et/ou de genre historiquement sous-representes dans les sciences. Un ou plusieurs auteurs de cet article s'identifient comme vivant avec un handicap. La liste des auteurs de cet article comprend des contributeurs issus du lieu et/ou de la communaute ou la recherche a ete menee, et ils ont participe a la collecte des donnees, a la conception, a l'analyse et/ou a l'interpretation du travail.

OBJECTIVE: White matter alterations are frequently reported in autism spectrum disorder (ASD), yet the etiology is currently unknown. The objective of this investigation was to examine, for the first time, the impact of genetic and environmental factors on white matter microstructure in twins with ASD compared to control twins without ASD. METHOD: Diffusion-weighted MRIs were obtained from same-sex twin pairs (6-15 years of age) in which at least 1 twin was diagnosed with ASD or neither twin exhibited a history of neurological or psychiatric disorders. Fractional anisotropy (FA) and mean diffusivity (MD) were examined across different white matter tracts in the brain, and statistical and twin modeling were completed to assess the proportion of variation associated with additive genetic (A) and common/shared (C) or unique (E) environmental factors. We also developed a novel Twin-Pair Difference Score analysis method that produces quantitative estimates of the genetic and environmental contributions to shared covariance between different brain and behavioral traits. RESULTS: Good-quality data were available from 84 twin pairs, 50 ASD pairs (32 concordant for ASD [16 monozygotic; 16 dizygotic], 16 discordant for ASD [3 monozygotic; 13 dizygotic], and 2 pairs in which 1 twin had ASD and the other exhibited some subthreshold symptoms [1 monozygotic; 1 dizygotic]) and 34 control pairs (20 monozygotic; 14 dizygotic). Average FA and MD across the brain, respectively, were primarily genetically mediated in both control twins (A = 0.80, 95% CI [0.57, 1.02]; A = 0.80 [0.55, 1.04]) and twins concordant for having ASD (A = 0.71 [0.33, 1.09]; A = 0.84 [0.32,1.36]). However, there were also significant tract-specific differences between groups. For instance, genetic effects on commissural fibers were primarily associated with differences in general cognitive abilities and perhaps some diagnostic differences for ASD because Twin-Pair Difference-Score analysis indicated that genetic factors may have contributed to ∼40% to 50% of the covariation between IQ scores and FA of the corpus callosum. Conversely, the increased impact of environmental factors on some projection and association fibers were primarily associated with differences in symptom severity in twins with ASD; for example, our analyses suggested that unique environmental factors may have contributed to ∼10% to 20% of the covariation between autism-related symptom severity and FA of the cerebellar peduncles and external capsule. CONCLUSION: White matter alterations in youth with ASD are associated with both genetic contributions and potentially increased vulnerability or responsivity to environmental influences. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. The author list of this paper includes contributors from the location and/or community where the research was conducted and they participated in the data collection, design, analysis, and/or interpretation of the work.

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Références citées
65
Avec un DOI
60
Sans DOI, à partir du texte brut de la bibliographie
5
4 / 65 (6,2 %) références citées comprennent au moins une personne identifiée comme autiste.
Références avec données à compléter
3 / 65 (4,6 %)
Références avec noms d’auteurices détectés
62 / 65 (95,4 %)
Sans nom d’auteurice détecté
3
Sans titre structuré
1
Sans identifiant stable
5
Références avec noms bruts d’auteurices restant à vérifier
1
Références avec problème de récupération des métadonnées externes
0
Ces indicateurs portent sur les références citées affichées sur cette page, après fusion des doublons techniques. Une référence sans DOI peut quand même soutenir les statistiques d’auteurices lorsqu’un titre et des noms d’auteurices sont disponibles.
Noms d’auteurices détectés dans la bibliographie citée
435
À partir du DOI ou de métadonnées externes
435
À partir du texte brut validé de la bibliographie
0
Noms bruts déjà validés
0
Noms bruts restant à vérifier
1
88 / 435 (20,2 %) noms sont associés à un·e auteurice déjà présent·e dans AutiHub. 347 / 435 (79,8 %) noms ne sont pas encore associés.
Noms associés à une personne identifiée comme autiste
4 / 435 (0,9 %)
Calculé sur l’ensemble des noms d’auteurices détectés dans la bibliographie citée. Parmi les noms associés à un·e auteurice déjà présent·e dans AutiHub : 4 / 88 (4,5 %). Personnes distinctes identifiées comme autistes : 1 / 343 (0,3 %).
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