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. 2021 Feb 1;11(1):82.
doi: 10.1038/s41398-021-01201-4.

Evidence for similar structural brain anomalies in youth and adult attention-deficit/hyperactivity disorder: a machine learning analysis

Yanli Zhang-James  1 , Emily C Helminen  2 , Jinru Liu  3 ; ENIGMA-ADHD Working Group; Barbara Franke  4   5   6 , Martine Hoogman  4   5 , Stephen V Faraone  7   8
Collaborators, Affiliations

Evidence for similar structural brain anomalies in youth and adult attention-deficit/hyperactivity disorder: a machine learning analysis

Yanli Zhang-James et al. Transl Psychiatry. .

Abstract

Attention-deficit/hyperactivity disorder (ADHD) affects 5% of children world-wide. Of these, two-thirds continue to have impairing symptoms of ADHD into adulthood. Although a large literature implicates structural brain differences of the disorder, it is not clear if adults with ADHD have similar neuroanatomical differences as those seen in children with recent reports from the large ENIGMA-ADHD consortium finding structural differences for children but not for adults. This paper uses deep learning neural network classification models to determine if there are neuroanatomical changes in the brains of children with ADHD that are also observed for adult ADHD, and vice versa. We found that structural MRI data can significantly separate ADHD from control participants for both children and adults. Consistent with the prior reports from ENIGMA-ADHD, prediction performance and effect sizes were better for the child than the adult samples. The model trained on adult samples significantly predicted ADHD in the child sample, suggesting that our model learned anatomical features that are common to ADHD in childhood and adulthood. These results support the continuity of ADHD's brain differences from childhood to adulthood. In addition, our work demonstrates a novel use of neural network classification models to test hypotheses about developmental continuity.

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Conflict of interest statement

Dr. Barbara Franke has received educational speaking fees from Shire and Medice. Dr. Stephen V Faraone received income, potential income, travel expenses continuing education support and/or research support from Takeda, OnDosis, Tris, Otsuka, Arbor, Ironshore, Rhodes, Akili Interactive Labs, Enzymotec, Sunovion, Supernus, and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child’s Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is Program Director of www.adhdinadults.com. Dr. Asherson has served as a consultant and as a speaker at sponsored events for Eli Lilly, Novartis, and Shire, and he has received educational/research awards from Eli Lilly, GW Pharma, Novartis, QbTech, Shire, and Vifor Pharma. Dr. Banaschewski has served in an advisory or consultancy role for Actelion, Eli Lilly, Hexal Pharma, Lundbeck, Medice, Neurim Pharmaceuticals, Novartis, Oberberg GmbH, and Shire; he has received conference support or speaking fees from Eli Lilly, Medice, Novartis, and Shire; he has been involved in clinical trials conducted by Shire and Viforpharma; and he has received royalties from CIP Medien, Hogrefe, Kohlhammer, and Oxford University Press. Dr. Bellgrove has received speaking fees and travel support from Shire. Dr. Biederman has received research support from AACAP, Alcobra, the Feinstein Institute for Medical Research, the Forest Research Institute, Genentech, Headspace, Ironshore, Lundbeck AS, Magceutics, Merck, Neurocentria, NIDA, NIH, PamLab, Pfizer, Roche TCRC, Shire, SPRITES, Sunovion, the U.S. Department of Defense, the U.S. Food and Drug Administration, and Vaya Pharma/Enzymotec; he has served as a consultant or on scientific advisory boards for Aevi Genomics, Akili, Alcobra, Arbor Pharmaceuticals, Guidepoint, Ironshore, Jazz Pharma, Medgenics, Piper Jaffray, and Shire; he has received honoraria from Alcobra, the American Professional Society of ADHD and Related Disorders, and the MGH Psychiatry Academy for tuition-funded CME courses; he has a financial interest in Avekshan, a company that develops treatments for ADHD; he has a U.S. patent application pending (Provisional Number #61/233,686) through MGH corporate licensing, on a method to prevent stimulant abuse; and his program has received royalties from a copyrighted rating scale used for ADHD diagnoses, paid to the Department of Psychiatry at Massachusetts General Hospital by Ingenix, Prophase, Shire, Bracket Global, Sunovion, and Theravance. Dr. Brandeis has served as an unpaid scientific consultant for an EU-funded neurofeedback trial. Dr. Buitelaar has served as a consultant, advisory board member, and/or speaker for Eli Lilly, Janssen-Cilag, Medice, Roche, Shire, and Servier. Dr. Coghill has served in an advisory or consultancy role for Eli Lilly, Medice, Novartis, Oxford Outcomes, Shire, and Viforpharma; he has received conference support or speaking fees from Eli Lilly, Janssen McNeil, Medice, Novartis, Shire, and Sunovion; and he has been involved in clinical trials conducted by Eli Lilly and Shire. Dr. Dale is a founder of and holds equity in CorTechs Labs, Inc., and has served on the scientific advisory boards of CorTechs Labs and Human Longevity, Inc., and he receives funding through research grants with GE Healthcare. Mr. Earl is co-inventor of the Oregon Health and Science University Technology #2198 (co-owned with Washington University in St. Louis), FIRMM: Real time monitoring and prediction of motion in MRI scans, exclusively licensed to Nous, Inc., and any related research. Any potential conflict of interest has been reviewed and managed by OHSU. Dr. Fair is a founder of Nous Imaging, Inc.; any potential conflicts of interest are being reviewed and managed by OHSU. Dr. Haavik has received speaking fees from Biocodex, Eli Lilly, HB Pharma, Janssen-Cilag, Medice, Novartis, and Shire. Dr. Hoekstra has received a research grant from and served on the advisory board for Shire. Dr. Karkashadze has received payment for article authorship and speaking fees from Sanofi and from Pikfarma. Dr. Konrad has received speaking fees from Eli Lilly, Medice, and Shire. Dr. Kuntsi has received speaking honoraria and advisory panel payments for participation at educational events sponsored by Medice; all funds are received by King’s College London and used for studies of ADHD. Dr. Lesch has served as a speaker for Eli Lilly and has received research support from Medice and travel support from Shire. Dr. Mattos has served on speakers’ bureau and/or as a consultant for Janssen-Cilag, Novartis, and Shire and has received travel awards from those companies to participate in scientific meetings; the ADHD outpatient program (Grupo de Estudos do Déficit de Atenção/Institute of Psychiatry) chaired by Dr. Mattos also received research support from Novartis and Shire. Dr. Mehta has received research funding from Lundbeck, Shire, and Takeda and has served on advisory boards for Lundbeck and Autifony. Dr. Ramos-Quiroga has served on the speakers bureaus and/or as a consultant for Almirall, Braingaze, Eli Lilly, Janssen-Cilag, Lundbeck, Medice, Novartis, Shire, Sincrolab, and Rubió; he has received travel awards for taking part in psychiatric meetings from Eli Lilly, Janssen-Cilag, Medice, Rubió, and Shire; and the Department of Psychiatry chaired by him has received unrestricted educational and research support from Actelion, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, Oryzon, Psious, Roche, Rubió, and Shire. Dr. Reif has received honoraria for serving as speaking or on advisory boards for Janssen, Medice, Neuraxpharm, Servier, and Shire. Dr. Rubia has received speaking fees form Shire and Medice and a grant from Eli Lilly. Dr. Thompson has received funding support from Biogen. Dr. Van Erp has served as consultant for Roche Pharmaceuticals and has a contract with Otsuka Pharmaceutical, Ltd. Dr. Walitza has received lecture honoraria from Eli Lilly and Opopharma, support from the Hartmann Müller, Olga Mayenfisch, and Gertrud Thalmann foundations, and royalties from Beltz, Hogrefe, Kohlhammer, Springer, and Thieme. Dr. Yanli Zhang-James is supported by the European Union’s Seventh Framework Programme for research, technological development, and demonstration under grant agreement no. 602805 and the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 667302. Emily C Helminen, Jinru Liu, Dr. Martine Hoogman, and other contributing members of the ENIGMA-ADHD Working Group declare no conflict of interest.

Figures

Fig. 1
Fig. 1. Area under the receiver operating characteristic curve for the test results.
Area under the receiver operating characteristic curve (AUC) accuracy statistics for the held-out test results were plotted (as dots) with their 95% confidence intervals (as horizontal lines). The vertical line at an AUC of 0.5 indicates a chance level of diagnostic accuracy. If the 95%CI does not overlap with the 0.5 vertical line, it indicates significant predictive accuracy. A AUC comparison of the models using only MRI features. A AUC comparison of the models using MRI features plus age and sex. In both A and B, the Top portion shows the base models, where models were trained and validated in child or adult samples and tested on their corresponding age groups; Bottom portion tests the hypotheses that if model trained/validated on child samples can also predict adult ADHD and vice versa. Note that test sample consists of combined training, validation, and test sets from the other age group because they are not used in the model optimization and training.
See this image and copyright information in PMC

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