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

Charlotte Pretzsch, Dorothea Floris, Tim Schäfer, Anke Bletsch, Caroline Gurr, Michael V. Lombardo, Christopher H. Chatham, Julian Tillmann, Tony Charman, Martina Arenella, Emily Jones, Sara Ambrosino, Thomas Bourgeron, Guillaume Dumas, Freddy Cliquet, Claire S. Leblond, Eva Loth, Beth Oakley, Jan Buitelaar, Simon Baron-CohenChristian F. Beckmann, Antonio M. Persico, Tobias Banaschewski, Sarah Durston, Christine Freitag, Declan Murphy, Christine Ecker

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
93 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)2158-2169
Number of pages12
JournalMolecular Psychiatry
Volume28
Issue number5
Early online date29 Mar 2023
DOIs
Publication statusPublished - May 2023

Fingerprint

Dive into the research topics of 'Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism'. Together they form a unique fingerprint.

Cite this