Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology

Saashi A Bedford; Meng-Chuan Lai; Michael V Lombardo; Bhismadev Chakrabarti; Amber Ruigrok; John Suckling; Evdokia Anagnostou; Jason P Lerch; Margot Taylor; Rob Nicolson; Georgiades Stelios; Jennifer Crosbie; Russell Schachar; Elizabeth Kelley; Jessica Jones; Paul D Arnold; Eric Courchesne; Karen Pierce; Lisa T Eyler; Kathleen Campbell; Cynthia Carter Barnes; Jakob Seidlitz; Aaron F Alexander-Bloch; Edward T Bullmore; Simon Baron-Cohen; Richard A I Bethlehem; MRC AIMS Consortium and Lifespan Brain Chart Consortium

doi:10.1101/2023.12.06.23299587

Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology

medRxiv [Preprint]. 2023 Dec 7:2023.12.06.23299587. doi: 10.1101/2023.12.06.23299587.

Authors

Saashi A Bedford^{1

2}, Meng-Chuan Lai^{1

3

4

5

6}, Michael V Lombardo⁷, Bhismadev Chakrabarti^{1

8}, Amber Ruigrok^{1

9}, John Suckling², Evdokia Anagnostou^{10

11}, Jason P Lerch^{12

13

14}, Margot Taylor^{12

15}, Rob Nicolson¹⁶, Georgiades Stelios¹⁷, Jennifer Crosbie^{5

12

18}, Russell Schachar^{5

12

18}, Elizabeth Kelley^{19

20

21}, Jessica Jones^{19

20

21}, Paul D Arnold^{22

23}, Eric Courchesne²⁴, Karen Pierce²⁴, Lisa T Eyler²⁵, Kathleen Campbell²⁴, Cynthia Carter Barnes²⁴, Jakob Seidlitz^{26

27

28}, Aaron F Alexander-Bloch^{26

27

28}, Edward T Bullmore², Simon Baron-Cohen^{1

29}, Richard A I Bethlehem^{1

2

30}; MRC AIMS Consortium and Lifespan Brain Chart Consortium

Affiliations

¹ Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, CB2 8AH, UK.
² Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, CB2 0SZ, UK.
³ The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health and Azrieli Adult Neurodevelopmental Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M6J 1H4, Canada.
⁴ Department of Psychiatry, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
⁵ Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5T 1R8, Canada.
⁶ Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei 100229, Taiwan.
⁷ Laboratory for Autism and Neurodevelopmental Disorders, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, Italy.
⁸ Centre for Autism, School of Psychology and Clinical Language Sciences, University of Reading, Reading RG6 6ES, UK.
⁹ Division of Psychology and Mental Health, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester.
¹⁰ Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada.
¹¹ Department of Pediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
¹² Program in Neurosciences and Mental Health, Research Institute, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
¹³ Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
¹⁴ Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
¹⁵ Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
¹⁶ Department of Psychiatry, University of Western Ontario, London, Ontario, Canada.
¹⁷ McMaster University, Hamilton, Ontario, Canada.
¹⁸ Genetics & Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
¹⁹ Department of Psychology, Queen's University, Kingston, ON K7L 3N6 Canada.
²⁰ Centre for Neuroscience Studies, Queen's University, Kingston, ON K7L 3N6 Canada.
²¹ Department of Psychiatry, Queen's University, Kingston, ON K7L 3N6 Canada.
²² The Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
²³ Departments of Psychiatry and Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
²⁴ Department of Neurosciences, University of California San Diego, La Jolla, California, USA.
²⁵ Department of Psychiatry, University of California San Diego, La Jolla, California, USA.
²⁶ Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
²⁷ Department of Child and Adolescent Psychiatry and Behavioral Science, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
²⁸ Lifespan Brain Institute, The Children's Hospital of Philadelphia and Penn Medicine, Philadelphia, PA 19104, USA.
²⁹ Cambridge Lifetime Autism Spectrum Service (CLASS), Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
³⁰ Department of Psychology, University of Cambridge, Cambridge, UK.

Abstract

Background: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Normative modelling provides a unified framework for studying age-specific and sex-specific divergences in neurodivergent brain development.

Methods: Here we use normative modelling and a large, multi-site neuroimaging dataset to characterise cortical anatomy associated with autism and ADHD, benchmarked against models of typical brain development based on a sample of over 75,000 individuals. We also examined sex and age differences, relationship with autistic traits, and explored the co-occurrence of autism and ADHD (autism+ADHD).

Results: We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume localised to the superior temporal cortex, whereas individuals with ADHD showed more global effects of cortical thickness increases but lower cortical volume and surface area across much of the cortex. The autism+ADHD group displayed a unique pattern of widespread increases in cortical thickness, and certain decreases in surface area. We also found evidence that sex modulates the neuroanatomy of autism but not ADHD, and an age-by-diagnosis interaction for ADHD only.

Conclusions: These results indicate distinct cortical differences in autism and ADHD that are differentially impacted by age, sex, and potentially unique patterns related to their co-occurrence.

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Abstract

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