Gray matter covariations and core symptoms of autism: the EU-AIMS Longitudinal European Autism Project
Creators
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Mei, Ting1
- Llera, Alberto1
- Floris, Dorothea L.1
- Forde, Natalie J.1
- Tillmann, Julian2
- Durston, Sarah3
- Moessnang, Carolin4
- Banaschewski, Tobias5
- Holt, Rosemary J.6
- Baron-Cohen, Simon6
- Rausch, Annika1
- Loth, Eva7
- Dell'Acqua, Flavio7
- Charman, Tony2
- Murphy, Declan G. M.7
- Ecker, Christine7
- Beckmann, Christian F.1
- Buitelaar, Jan K.1
- the EU-AIMS LEAP group
- 1. Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
- 2. Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
- 3. Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
- 4. Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
- 5. Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
- 6. Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK
- 7. Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Description
Background: Voxel-based morphometry (VBM) studies in autism spectrum disorder (autism) have yielded diverging results. This might partly be attributed to structural alterations being associating with the combined influence of several regions rather than with a single region. Further, these structural covariation differences may relate to continuous measures of autism rather than with categorical case–control contrasts. The current study aimed to identify structural covariation alterations in autism, and assessed canonical correlations between brain covariation patterns and core autism symptoms.
Methods: We studied 347 individuals with autism and 252 typically developing individuals, aged between 6 and 30 years, who have been deeply phenotyped in the Longitudinal European Autism Project. All participants' VBM maps were decomposed into spatially independent components using independent component analysis. A generalized linear model (GLM) was used to examine case–control differences. Next, canonical correlation analysis (CCA) was performed to separately explore the integrated effects between all the brain sources of gray matter variation and two sets of core autism symptoms.
Results: GLM analyses showed significant case–control differences for two independent components. The first component was primarily associated with decreased density of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and increased density of caudate nucleus in the autism group relative to typically developing individuals. The second component was related to decreased densities of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to typically developing individuals. The CCA results showed significant correlations between components that involved variation of thalamus, putamen, precentral gyrus, frontal, parietal, and occipital lobes, and the cerebellum, and repetitive, rigid and stereotyped behaviors and abnormal sensory behaviors in autism individuals.
Limitations: Only 55.9% of the participants with autism had complete questionnaire data on continuous parent-reported symptom measures.
Conclusions: Covaried areas associated with autism diagnosis and/or symptoms are scattered across the whole brain and include the limbic system, basal ganglia, thalamus, cerebellum, precentral gyrus, and parts of the frontal, parietal, and occipital lobes. Some of these areas potentially subserve social-communicative behavior, whereas others may underpin sensory processing and integration, and motor behavior.
Files
13229_2020_389_MOESM1_ESM.pdf
Additional details
Funding
- MATRICS – Multidisciplinary Approaches to Translational Research In Conduct Syndromes 603016
- European Commission
- AGGRESSOTYPE – Aggression subtyping for improved insight and treatment innovation in psychiatric disorders 602805
- European Commission
- TACTICS – Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes 278948
- European Commission