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Mol Psychiatry. 2019 Apr 26. doi: 10.1038/s41380-019-0420-6. [Epub ahead of print]

Large-scale analyses of the relationship between sex, age and intelligence quotient heterogeneity and cortical morphometry in autism spectrum disorder.

Author information

1
Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada. saashi.bedford@mail.mcgill.ca.
2
Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada. saashi.bedford@mail.mcgill.ca.
3
Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada.
4
Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
5
Department of Psychiatry, McGill University, Montreal, QC, Canada.
6
Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada.
7
Department of Biological and Biomedical Engineering, McGill University, Montreal, QC, Canada.
8
Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.
9
Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
10
Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, UK.
11
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
12
National Autism Unit, Bethlem Royal Hospital, London, UK.
13
Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Goethe University, Frankfurt am Main, Germany.
14
Hassenfeld Children's Hospital at NYU Langone Department of Child and Adolescent Psychiatry, Child Study Center, New York City, NY, USA.
15
Department of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
16
Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada.
17
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
18
Department of Psychology, University of Cyprus, Nicosia, Cyprus.
19
Developmental Neurogenomics Unit, Human Genetics Branch, National Institute of Mental Health, Bethesda, MD, USA.
20
Section on Behavioral Pediatrics, National Institute of Mental Health, Bethesda, MD, USA.
21
Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON, Canada.
22
The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
23
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
24
Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
25
Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada. mallar@cobralab.ca.
26
Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada. mallar@cobralab.ca.
27
Department of Psychiatry, McGill University, Montreal, QC, Canada. mallar@cobralab.ca.
28
Department of Biological and Biomedical Engineering, McGill University, Montreal, QC, Canada. mallar@cobralab.ca.

Abstract

Significant heterogeneity across aetiologies, neurobiology and clinical phenotypes have been observed in individuals with autism spectrum disorder (ASD). Neuroimaging-based neuroanatomical studies of ASD have often reported inconsistent findings which may, in part, be attributable to an insufficient understanding of the relationship between factors influencing clinical heterogeneity and their relationship to brain anatomy. To this end, we performed a large-scale examination of cortical morphometry in ASD, with a specific focus on the impact of three potential sources of heterogeneity: sex, age and full-scale intelligence (FIQ). To examine these potentially subtle relationships, we amassed a large multi-site dataset that was carefully quality controlled (yielding a final sample of 1327 from the initial dataset of 3145 magnetic resonance images; 491 individuals with ASD). Using a meta-analytic technique to account for inter-site differences, we identified greater cortical thickness in individuals with ASD relative to controls, in regions previously implicated in ASD, including the superior temporal gyrus and inferior frontal sulcus. Greater cortical thickness was observed in sex specific regions; further, cortical thickness differences were observed to be greater in younger individuals and in those with lower FIQ, and to be related to overall clinical severity. This work serves as an important step towards parsing factors that influence neuroanatomical heterogeneity in ASD and is a potential step towards establishing individual-specific biomarkers.

PMID:
31028290
DOI:
10.1038/s41380-019-0420-6

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