Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 May;28(5):2158-2169.
doi: 10.1038/s41380-023-02016-z. Epub 2023 Mar 29.

Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism

Charlotte M Pretzsch  1 , Dorothea L Floris  2   3 , Tim Schäfer  4 , Anke Bletsch  4 , Caroline Gurr  4 , Michael V Lombardo  5 , Chris H Chatham  6 , Julian Tillmann  6 , Tony Charman  7 , Martina Arenella  8   9 , Emily Jones  10 , Sara Ambrosino  11 , Thomas Bourgeron  12 , Guillaume Dumas  13 , Freddy Cliquet  12 , Claire S Leblond  12 , Eva Loth  8 , Bethany Oakley  8 , Jan K Buitelaar  3 , Simon Baron-Cohen  14 , Christian F Beckmann  3 , Antonio M Persico  15 , Tobias Banaschewski  16 , Sarah Durston  11 , Christine M Freitag  4 ; EU-AIMS/AIMS-2-TRIALS Consortium; Declan G M Murphy #  8 , Christine Ecker #  4
Collaborators, Affiliations

Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism

Charlotte M Pretzsch et al. Mol Psychiatry. 2023 May.

Abstract

Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals' adaptive skills naturally improve or remain stable, while others' decrease. To pave the way for 'precision-medicine' approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6-30 years), with two assessment time points separated by ~12-24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful "Increasers", "No-changers", and "Decreasers" in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup's neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences' potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes.

PubMed Disclaimer

Conflict of interest statement

CHC is a full-time employee of F. Hoffmann-La Roche, Ltd. JT is a consultant to F. Hoffmann-La Roche Ltd. TC has served as a paid consultant to F. Hoffmann-La Roche Ltd and Servier. He has received royalties from Sage Publications and Guilford Publications. JB has been in the past three years a consultant to/member of advisory board of/ and/or speaker for Takeda/Shire, Roche, Medice, Angelini, Janssen, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. AMP receives royalties from Hogrefe and SEU, and has received support and/or been a speaker for Servier and Sanofi. TBa served in an advisory or consultancy role for eye level, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmBH, Roche, and Takeda. He received conference support or speaker’s fee by Janssen, Medice, and Takeda. He received royalties from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press. The present work is unrelated to these relationships. CMF receives royalties for books on ASD, ADHD, and MDD. DGMM has served as a paid consultant to F. Hoffmann-La Roche Ltd and Servier. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Neuroanatomical differences between neurotypicals and those individuals whose adaptive behavioural scores increased.
The figure displays between-group differences in (a) neuroanatomy at baseline (T1), (b) neuroanatomical development between T1 and T2, and (c) neuroanatomy at follow-up (T2). Each row displays random-field theory (RFT)-corrected t-values. L left, R right.
Fig. 2
Fig. 2. Neuroanatomical differences between neurotypicals and those individuals whose adaptive behavioural scores did not change.
The figure displays between-group differences in (a) neuroanatomy at baseline (T1), (b) neuroanatomical development between T1 and T2, and (c) neuroanatomy at follow-up (T2). Each row displays random-field theory (RFT)-corrected t-values. L left, R right.
Fig. 3
Fig. 3. Neuroanatomical differences between neurotypicals and those individuals whose adaptive behavioural scores decreased.
The figure displays between-group differences in (a) neuroanatomy at baseline (T1), (b) neuroanatomical development between T1 and T2, and (c) neuroanatomy at follow-up (T2). Each row displays random-field theory (RFT)-corrected t-values. L left, R right.
Fig. 4
Fig. 4. Genetic correlates of neuroanatomical variability: enrichment analyses for cortical phenotypes (y-axis, rows) by autism-associated gene lists (x-axis, columns).
Tile colours indicate FDR q-values. Tile labels indicate enrichment odds ratios. CT cortical thickness, ∆ change between T1 and T2, DG Decreasers, IG Increasers, NCG No-changers, NT Neurotypicals, SA surface area, T1 timepoint 1, T2 timepoint 2.
See this image and copyright information in PMC

References

    1. Knopf A. Autism prevalence increases from 1 in 60 to 1 in 54: CDC. Brown Univ Child Adolesc Behav Lett. 2020;36:4.
    1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. DSM-5, 5th edn. In: American Psychiatric Association, editor. Washington, DC: American Psychiatric Association; 2013.
    1. Sparrow SS, Balla DA, Cicche HV. Vineland Adaptive Behavior Scales-Interview Edition Survey Form Manual. Circle Pines: American Guidance Service; 1984.
    1. Mouga S, Almeida J, Cafe C, Duque F, Oliveira G. Adaptive profiles in autism and other neurodevelopmental disorders. J Autism Dev Disord. 2015;45:1001–12. doi: 10.1007/s10803-014-2256-x. - DOI - PubMed
    1. Tomanik SS, Pearson DA, Loveland KA, Lane DM, Bryant, Shaw J. Improving the reliability of autism diagnoses: examining the utility of adaptive behavior. J Autism Dev Disord. 2007;37:921–8. doi: 10.1007/s10803-006-0227-6. - DOI - PubMed

Publication types