Daan van Rooij1, Evdokia Anagnostou1, Celso Arango1, Guillaume Auzias1, Marlene Behrmann1, Geraldo F Busatto1, Sara Calderoni1, Eileen Daly1, Christine Deruelle1, Adriana Di Martino1, Ilan Dinstein1, Fabio Luis Souza Duran1, Sarah Durston1, Christine Ecker1, Damien Fair1, Jennifer Fedor1, Jackie Fitzgerald1, Christine M Freitag1, Louise Gallagher1, Ilaria Gori1, Shlomi Haar1, Liesbeth Hoekstra1, Neda Jahanshad1, Maria Jalbrzikowski1, Joost Janssen1, Jason Lerch1, Beatriz Luna1, Mauricio Moller Martinho1, Jane McGrath1, Filippo Muratori1, Clodagh M Murphy1, Declan G M Murphy1, Kirsten O'Hearn1, Bob Oranje1, Mara Parellada1, Alessandra Retico1, Pedro Rosa1, Katya Rubia1, Devon Shook1, Margot Taylor1, Paul M Thompson1, Michela Tosetti1, Gregory L Wallace1, Fengfeng Zhou1, Jan K Buitelaar1. 1. From the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behavior, Donders Center for Cognitive Neuroimaging, Radboud University Medical Center, Nijmegen, the Netherlands; the Karakter Child and Adolescent Psychiatry University Center, Nijmegen; the Bloorview Research Institute, University of Toronto, Toronto; the Child and Adolescent Psychiatry Department, Gregorio Marañón General University Hospital, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid; Institut de Neurosciences de la Timone, Aix Marseille Université, CNRS, Marseille, France; the Department of Psychology, Carnegie Mellon University, Pittsburgh; the IRCCS Stella Maris Foundation, Pisa, Italy; the Department of Forensic and Neurodevelopmental Sciences and the Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology, and Neuroscience, King's College London; the Institute for Pediatric Neuroscience, Child Study Center, NYU Langone Health, New York; the Department of Psychology and Department of Brain and Cognitive Sciences, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva, Israel; Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, the Netherlands; the Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, University Hospital, Goethe University Frankfurt am Main, Frankfurt, Germany; the Department of Behavioral Neuroscience, Oregon Health and Science University, Portland; the Department of Psychiatry, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, School of Medicine, and the Trinity College Institute of Neuroscience, Trinity College, Dublin; the National Institute for Nuclear Physics, Pisa Division, Pisa, Italy; the Mouse Imaging Centre and the Department of Diagnostic Imaging, Hospital for Sick Children, University of Toronto, Toronto; the Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; the Behavioural Genetics Clinic, Adult Autism Service, Behavioural and Developmental Psychiatry Clinical Academic Group, South London and Maudsley Foundation NHS Trust, London; the Laboratory of Neuroimaging, University of São Paulo Medical School, São Paulo, Brazil; the Imaging Genetics Center, Mark and Mary Stevens Institution for Neuroimaging and Informatics, University of Southern California, Marina del Rey; the Department of Speech, Language, and Hearing Sciences, George Washington University, Washington, D.C.; the College of Computer Science and Technology and the Key Laboratory of Symbolic Computation and Knowledge Engineering of the Ministry of Education, Jilin University, Changchun, Jilin, China.
Abstract
OBJECTIVE: Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. METHOD: The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. RESULTS: The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. CONCLUSIONS: The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.
OBJECTIVE: Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. METHOD: The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. RESULTS: The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. CONCLUSIONS: The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASDpatients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.
Authors: Eric Courchesne; Karen Pierce; Cynthia M Schumann; Elizabeth Redcay; Joseph A Buckwalter; Daniel P Kennedy; John Morgan Journal: Neuron Date: 2007-10-25 Impact factor: 17.173
Authors: E Courchesne; C M Karns; H R Davis; R Ziccardi; R A Carper; Z D Tigue; H J Chisum; P Moses; K Pierce; C Lord; A J Lincoln; S Pizzo; L Schreibman; R H Haas; N A Akshoomoff; R Y Courchesne Journal: Neurology Date: 2001-07-24 Impact factor: 9.910
Authors: S Baron-Cohen; H A Ring; E T Bullmore; S Wheelwright; C Ashwin; S C Williams Journal: Neurosci Biobehav Rev Date: 2000-05 Impact factor: 8.989
Authors: Cynthia Mills Schumann; Julia Hamstra; Beth L Goodlin-Jones; Linda J Lotspeich; Hower Kwon; Michael H Buonocore; Cathy R Lammers; Allan L Reiss; David G Amaral Journal: J Neurosci Date: 2004-07-14 Impact factor: 6.167
Authors: Andrew C Stanfield; Andrew M McIntosh; Michael D Spencer; Ruth Philip; Sonia Gaur; Stephen M Lawrie Journal: Eur Psychiatry Date: 2007-08-31 Impact factor: 5.361
Authors: Xiang-Zhen Kong; Premika S W Boedhoe; Yoshinari Abe; Pino Alonso; Stephanie H Ameis; Paul D Arnold; Francesca Assogna; Justin T Baker; Marcelo C Batistuzzo; Francesco Benedetti; Jan C Beucke; Irene Bollettini; Anushree Bose; Silvia Brem; Brian P Brennan; Jan Buitelaar; Rosa Calvo; Yuqi Cheng; Kang Ik K Cho; Sara Dallaspezia; Damiaan Denys; Benjamin A Ely; Jamie Feusner; Kate D Fitzgerald; Jean-Paul Fouche; Egill A Fridgeirsson; David C Glahn; Patricia Gruner; Deniz A Gürsel; Tobias U Hauser; Yoshiyuki Hirano; Marcelo Q Hoexter; Hao Hu; Chaim Huyser; Anthony James; Fern Jaspers-Fayer; Norbert Kathmann; Christian Kaufmann; Kathrin Koch; Masaru Kuno; Gerd Kvale; Jun Soo Kwon; Luisa Lazaro; Yanni Liu; Christine Lochner; Paulo Marques; Rachel Marsh; Ignacio Martínez-Zalacaín; David Mataix-Cols; Sarah E Medland; José M Menchón; Luciano Minuzzi; Pedro S Moreira; Astrid Morer; Pedro Morgado; Akiko Nakagawa; Takashi Nakamae; Tomohiro Nakao; Janardhanan C Narayanaswamy; Erika L Nurmi; Joseph O'Neill; Jose C Pariente; Chris Perriello; John Piacentini; Fabrizio Piras; Federica Piras; Christopher Pittenger; Y C Janardhan Reddy; Oana Georgiana Rus-Oswald; Yuki Sakai; Joao R Sato; Lianne Schmaal; H Blair Simpson; Noam Soreni; Carles Soriano-Mas; Gianfranco Spalletta; Emily R Stern; Michael C Stevens; S Evelyn Stewart; Philip R Szeszko; David F Tolin; Aki Tsuchiyagaito; Daan van Rooij; Guido A van Wingen; Ganesan Venkatasubramanian; Zhen Wang; Je-Yeon Yun; Paul M Thompson; Dan J Stein; Odile A van den Heuvel; Clyde Francks Journal: Biol Psychiatry Date: 2019-04-30 Impact factor: 13.382
Authors: Saashi A Bedford; Min Tae M Park; Gabriel A Devenyi; Stephanie Tullo; Jurgen Germann; Raihaan Patel; Evdokia Anagnostou; Simon Baron-Cohen; Edward T Bullmore; Lindsay R Chura; Michael C Craig; Christine Ecker; Dorothea L Floris; Rosemary J Holt; Rhoshel Lenroot; Jason P Lerch; Michael V Lombardo; Declan G M Murphy; Armin Raznahan; Amber N V Ruigrok; Elizabeth Smith; Michael D Spencer; John Suckling; Margot J Taylor; Audrey Thurm; Meng-Chuan Lai; M Mallar Chakravarty Journal: Mol Psychiatry Date: 2019-04-26 Impact factor: 15.992
Authors: Maria Jalbrzikowski; David Freedman; Catherine E Hegarty; Eva Mennigen; Katherine H Karlsgodt; Loes M Olde Loohuis; Roel A Ophoff; Raquel E Gur; Carrie E Bearden Journal: J Am Acad Child Adolesc Psychiatry Date: 2019-01-18 Impact factor: 8.829
Authors: Dina R Dajani; Catherine A Burrows; Mary Beth Nebel; Stewart H Mostofsky; Kathleen M Gates; Lucina Q Uddin Journal: Brain Connect Date: 2019-11
Authors: John H Gilmore; Benjamin Langworthy; Jessica B Girault; Jason Fine; Shaili C Jha; Sun Hyung Kim; Emil Cornea; Martin Styner Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2020-06-09