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Altered structural brain asymmetry in autism spectrum disorder: large-scale analysis via the ENIGMA Consortium
By
Merel C. Postema,
Daan van Rooij,
Evdokia Anagnostou,
Celso Arango,
Guillaume Auzias,
Marlene Behrmann,
Geraldo Busatto Filho,
Sara Calderoni,
Rossa Calvo,
Eileen Daly,
Christine Deruelle,
Adriana Di Martino,
Ilan Dinstein,
Fabio Luis S. Duran,
Sarah Durston,
Christine Ecker,
Stefan Ehrlich,
Damien Fair,
Jennifer Fedor,
Xin Feng,
Jackie Fitzgerald,
Dorothea L. Floris,
Christine M. Freitag,
Louise Gallagher,
David C. Glahn,
Ilaria Gori,
Shlomi Haar,
Liesbeth Hoekstra,
Neda Jahanshad,
Maria Jalbrzikowski,
Joost Janssen,
Joseph A. King,
Luisa L. Zaro,
Jason P. Lerch,
Beatriz Luna,
Mauricio M. Martinho,
Jane McGrath,
Sarah E. Medland,
Filippo Muratori,
Clodagh M. Murphy,
Declan G.M. Murphy,
Kirsten O’Hearn,
Bob Oranje,
Mara Parellada,
Olga Puig,
Alessandra Retico,
Pedro Rosa,
Katya Rubia,
Devon Shook,
Margot Taylor,
Michela Tosetti,
Gregory L. Wallace,
Fengfeng Zhou,
Paul Thompson,
Simon E. Fisher,
Jan K. Buitelaar,
Clyde Francks
Posted 09 Mar 2019
bioRxiv DOI: 10.1101/570655
Background: Left-right asymmetry is an important organizing feature of the healthy brain. Various studies have reported altered structural brain asymmetry in autism spectrum disorder (ASD). However, findings have been inconsistent, likely due to limited sample sizes and low statistical power. Methods: We investigated 1,774 subjects with ASD and 1,809 controls, from 54 datasets, for differences in the asymmetry of thickness and surface area of 34 cerebral cortical regions. We also examined global hemispheric measures of cortical thickness and area asymmetry, and volumetric asymmetries of subcortical structures. Data were obtained via the ASD Working Group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas. Results: ASD was significantly associated with reduced leftward asymmetry of total hemispheric average cortical thickness, compared to controls. Eight regional thickness asymmetries, distributed over the cortex, also showed significant associations with diagnosis after correction for multiple comparisons, for which asymmetry was again generally lower in ASD versus controls. In addition, the medial orbitofrontal surface area was less rightward asymmetric in ASD than controls, and the putamen volume was more leftward asymmetric in ASD than controls. The largest effect size had Cohen's d = 0.15. Most effects did not depend on age, sex, IQ, or disorder severity. Conclusion: Altered lateralized neurodevelopment is suggested in ASD, affecting widespread cortical regions with diverse functions. Large-scale analysis was necessary to reliably detect, and accurately describe, subtle alterations of structural brain asymmetry in this disorder.
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