Genetic correlates of phenotypic heterogeneity in autism

Warrier, Varun; Zhang, Xinhe; Reed, Patrick M.; Havdahl, Alexandra; Moore, Tyler M.; Cliquet, Freddy; Leblond, Claire S.; Rolland, Thomas; Rosengren, Anders; Cáceres, Antonia San José; Hayward, Hannah; Crawley, Daisy; Faulkner, Jessica; Sabet, Jessica; Ellis, Claire; Oakley, Bethany; Loth, Eva; Charman, Tony; Murphy, Declan; Holt, Rosemary; Waldman, Jack; Upadhyay, Jessica; Gunby, Nicola; Lai, Meng‐Chuan; Renouf, Gwilym; Ruigrok, Amber N. V.; Taylor, Emily; Ziauddeen, Hisham; Deakin, Julia; Bruttopilo, Sara Ambrosino di; Dijk, Sarai van; Rijks, Yvonne; Koops, Tabitha; Douma, Miriam; Spaan, Alyssia; Selten, Iris; Steffers, Maarten; Themaat, Anna Ver Loren van; Bast, Nico; Baumeister, Sarah; O’Dwyer, Larry; Bours, Carsten; Rausch, Annika; Rhein, Daniel von; Cornelissen, Ineke; Bruin, Yvette de; Graauwmans, Maartje; Kostrzewa, Elzbieta; Cauvet, Élodie; Tammimies, Kristiina; Sitnikow, Rouslan; Dumas, Guillaume; Kim, Yang-Min; Hougaard, David M.; Bybjerg‐Grauholm, Jonas; Werge, Thomas; Mortensen, Preben Bo; Mors, Ole; Nordentoft, Merete; Adhya, Dwaipayan; Alamanza, Armandina; Allison, Carrie; Garvey, Isabelle; Parsons, Tracey; Smith, Paula; Tsompanidis, Alex; Burton, Graham J.; Heazell, Alexander E P; Gabis, Lidia V.; Biron‐Shental, Tal; Lancaster, Madeline A.; Srivastava, Deepak; Mill, Jonathan; Rowitch, David H.; Hurles, Matthew; Geschwind, Daniel H.; Børglum, Anders D.; Robinson, Elise; Grove, Jakob; Martin, Hilary C.; Bourgeron, Thomas; Baron‐Cohen, Simon

doi:10.1038/s41588-022-01072-5

Cited by 84 publications

(79 citation statements)

References 91 publications

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“…For instance, future studies including more participants with comorbid conditions such as epilepsy should investigate whether they represent moderator of outcome. Furthermore, they could determine whether the additive effect of various genetic mutations may moderate the outcome ( 71 ). In our sample, four participants had a reported genetic finding with a potential causal effect in ASD.…”

Section: Discussionmentioning

confidence: 99%

Distinct Patterns of Cognitive Outcome in Young Children With Autism Spectrum Disorder Receiving the Early Start Denver Model

et al. 2022

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Evidence-based, early intervention significantly improves developmental outcome in young children with autism. Nonetheless, there is high interindividual heterogeneity in developmental trajectories during the therapy. It is established that starting intervention as early as possible results in better developmental outcomes. But except for younger age at start, there is no clear consensus about behavioral characteristics that could provide a reliable individual prediction of a child's developmental outcome after receiving an early intervention. In this study, we analyze developmental trajectories of preschoolers with autism who received 2 years of intervention using the Early Start Denver Model (ESDM) approach in Geneva, Switzerland in an individual setting (n = 55, aged 28.7 ± 5.1 months with a range of 15–42). Our aim was to identify early predictors of response to intervention. We applied a cluster analysis to distinguish between 3 groups based on their cognitive level at intake, and rates of cognitive change over the course of intervention. The first group of children only had a mild cognitive delay at intake and nearly no cognitive delay by the end of intervention (Higher Cognitive at baseline: HC). The children in the two other groups all presented with severe cognitive delay at baseline. However, they had two very different patterns of response to intervention. The majority significantly improved developmental scores over the course of intervention (Optimal Responders: OptR) whereas a minority of children showed only modest improvement (Minimal Responders: MinR). Further analyses showed that children who ended up having an optimal 2-year intervention outcome (OptR) were characterized by higher adaptive functioning at baseline combined with rapid developmental improvement during the first 6 months of intervention. Inversely, less significant progress by the sixth month of intervention was associated with a less optimal response to treatment (MinR).

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Section: Discussionmentioning

confidence: 99%

Distinct Patterns of Cognitive Outcome in Young Children With Autism Spectrum Disorder Receiving the Early Start Denver Model

et al. 2022

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“…For instance, future studies including more participants with comorbid conditions such as epilepsy should investigate whether they represent moderator of outcome. Furthermore, they could determine whether the additive effect of various genetic mutations may moderate the outcome (Warrier et al, 2020). In our sample, four participants had a reported genetic finding with a potential causal effect in ASD.…”

Section: Discussionmentioning

confidence: 99%

Distinct patterns of cognitive outcome in young children with autism spectrum disorder receiving the Early Start Denver Model

Godel

Robain

Kojovic

et al. 2021

Preprint

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Evidence-based early intervention approaches have been shown to significantly improve many areas of development in young children with autism. Despite having an overall positive impact for most children, there is high inter-individual heterogeneity of response to treatment, and it is currently not possible to predict which child will benefit from which specific intervention. In this study, we analyze developmental trajectories of young children with autism who received two-years of Early Start Denver Model intervention in Geneva, Switzerland (n=47). Using cluster analyses, we distinguish between 3 subgroups based on cognitive level at baseline and rates of change over time. The first subgroup of children had cognitive scores at baseline only slightly below what would be expected for their age and were found to have nearly no cognitive delay by the end of treatment (High at Baseline: HB). The children in the two other subgroups all presented with severe cognitive delay at baseline, with the second group′s cognitive scores improving significantly in the first year of intervention, along with increased communication and daily living skills (High Responders: HR). The third subgroup showed little to no cognitive level change over the course of treatment (Minimal Responders: MR). Furthermore, the rates of change in cognition and adaptative behavior in the HR subgroup were already significantly higher compared to the MR subgroup within the first 6 months of intervention. A rapid and early response to intervention might thus represent a predictor of optimal outcome. Inversely, slower progress by the sixth month of intervention may predict that the child will have a slower response to the treatment overall and may need alternative supports to reach their learning objectives quickly.

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“…repetitive behavior scale [RBS]) (Antaki et al, 2022), or SCQ and RBS (Warrier et al, 2022). Together, the overall evidence that genetic liability scales with severity is weak, as it would be expected for all sources of genetic liability (i.e., de novo and PRS).…”

Section: A B Cmentioning

confidence: 99%

Can the “female protective effect” liability threshold model explain sex differences in autism spectrum disorder?

Dougherty

Marrus

Maloney

et al. 2022

Neuron

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Genetic correlates of phenotypic heterogeneity in autism

Cited by 84 publications

References 91 publications

Distinct Patterns of Cognitive Outcome in Young Children With Autism Spectrum Disorder Receiving the Early Start Denver Model

Distinct Patterns of Cognitive Outcome in Young Children With Autism Spectrum Disorder Receiving the Early Start Denver Model

Distinct patterns of cognitive outcome in young children with autism spectrum disorder receiving the Early Start Denver Model

Can the “female protective effect” liability threshold model explain sex differences in autism spectrum disorder?

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