Evidence map›Paper›PMID 28219628›Full record

SynthesisThe lancet. Psychiatry2017

Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis.

Martine Hoogman, Janita Bralten, Derrek P Hibar, Maarten Mennes, Marcel P Zwiers, Lizanne S J Schweren, Kimm J E van Hulzen, Sarah E Medland, Elena Shumskaya, Neda Jahanshad and 72 more

Erratum issuedAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The lancet. Psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 410 papers, 16 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
410citing papers in PubMed, 16 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

410 citing papers in PubMed, 16 syntheses or guidelines pooled it.

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  16. Adult-Onset ADHD: A Critical Analysis and Alternative Explanations.Child psychiatry and human development · 2022
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350 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

82 authors.

Martine HoogmanDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands. Electronic address: martine.hoogman@radboudumc.nl.
Janita BraltenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands.
Derrek P HibarImaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, University of Southern California, Marina del Rey, CA, USA.
Maarten MennesDonders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands.
Marcel P ZwiersDonders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands.
Lizanne S J SchwerenDepartment of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Kimm J E van HulzenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands.
Sarah E MedlandQIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Elena ShumskayaDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands.
Neda JahanshadImaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, University of Southern California, Marina del Rey, CA, USA.
Patrick de ZeeuwNICHE-lab, Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, Netherlands.
Eszter SzekelyNeurobehavioral Clinical Research Section, National Human Genome Research Institute, Bethesda, MD, USA.
Gustavo SudreNeurobehavioral Clinical Research Section, National Human Genome Research Institute, Bethesda, MD, USA.
Thomas WolfersDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands.
Alberdingk M H OnninkDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands.
Janneke T DammersDepartment of Psychiatry, Radboud University Medical Center, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands.
Jeanette C MostertDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands.
Yolanda Vives-GilabertAsociación para la Innovación en Análisis, Gestión y Procesamiento de Datos Científicos y Tecnológicos, Barcelona, Spain.
Gregor KohlsChild Neuropsychology Section, University Hospital Aachen, Aachen, Germany.
Eileen OberwellandChild Neuropsychology Section, University Hospital Aachen, Aachen, Germany; JARA Translational Brain Medicine, Research Center Juelich, Aachen, Germany.
Jochen SeitzDepartment of Child and Adolescent Psychiatry, University Hospital Aachen, Aachen, Germany.
Martin Schulte-RütherChild Neuropsychology Section, University Hospital Aachen, Aachen, Germany; JARA Translational Brain Medicine, Research Center Juelich, Aachen, Germany.
Sara AmbrosinoNICHE-lab, Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, Netherlands.
Alysa E DoyleDepartment of Psychiatry and Center for Human Genetics Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research at the Broad Institute, Cambridge, MA, USA.
Marie F HøvikDepartment of Clinical Medicine, University of Bergen, Bergen, Norway.
Margaretha DramsdahlPsychiatry, Region Zealand, Denmark.
Leanne TammDepartment of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Theo G M van ErpDepartment of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
Anders DaleDepartments of Neurosciences and Radiology, University of California, San Diego, San Diego, CA, USA; UCSD Center for Translational Imaging and Precision Medicine, San Diego, CA, USA.
Andrew SchorkDepartment of Cognitive Science, UC San Diego, La Jolla, CA, USA.
Annette ConzelmannDepartment of Child and Adolescent Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany; Department of Psychology, University of Würzburg, Würzburg, Germany.
Kathrin ZierhutDepartment of Medical Psychology and Psychotherapy, Medical Sociology and Rehabilitation Sciences, University of Würzburg, Würzburg, Germany; Department of Psychology, University of Würzburg, Würzburg, Germany.
Ramona BaurDepartment of Psychology, University of Würzburg, Würzburg, Germany.
Hazel McCarthyDepartment of Psychiatry, University of Dublin, Trinity College Dublin, Dublin, Ireland.
Yuliya N YonchevaThe Child Study Center at NYU Langone Medical Center, New York, NY, USA.
Ana CubilloDepartment of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Kaylita ChantilukeDepartment of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Mitul A MehtaDepartment of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Yannis PaloyelisDepartment of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Sarah HohmannDepartment of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Sarah BaumeisterDepartment of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Ivanei BramatiD'Or Institute for Research and Education, Rio de Janeiro, Brazil.
Paulo MattosD'Or Institute for Research and Education, Rio de Janeiro, Brazil; Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Fernanda Tovar-MollD'Or Institute for Research and Education, Rio de Janeiro, Brazil; Morphological Sciences Program, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Pamela DouglasDepartment of Psychiatry, University of California, Los Angeles, CA, USA.
Tobias BanaschewskiDepartment of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Daniel BrandeisDepartment of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Child and Adolescent Psychiatry, Psychiatric Hospital, University of Zurich, Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; Neuroscience Centre Zurich, University of Zurich, Zurich, Switzerland; ETH Zurich, Zurich, Switzerland.
Jonna KuntsiSocial Genetic and Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Philip AshersonSocial Genetic and Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Katya RubiaDepartment of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Clare KellyDepartment of Psychiatry, University of Dublin, Trinity College Dublin, Dublin, Ireland; The Child Study Center at NYU Langone Medical Center, New York, NY, USA; Trinity College Institute of Neuroscience, Dublin, Ireland.
Adriana Di MartinoThe Child Study Center at NYU Langone Medical Center, New York, NY, USA.
Michael P MilhamCenter for the Developing Brain, Child Mind Institute, New York, NY, USA; Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
Francisco X CastellanosThe Child Study Center at NYU Langone Medical Center, New York, NY, USA; Division of Child and Adolescent Psychiatric Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
Thomas FrodlDepartment of Psychiatry, University of Dublin, Trinity College Dublin, Dublin, Ireland; Department of Psychiatry and Psychotherapy, University Hospital, Otto-von-Guericke-University, Magdeburg, Germany.
Mariam ZentisDepartment of Psychiatry and Psychotherapy, University Hospital, Otto-von-Guericke-University, Magdeburg, Germany.
Klaus-Peter LeschDivision of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany; Department of Translational Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
Andreas ReifDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
Paul PauliDepartment of Psychology, University of Würzburg, Würzburg, Germany.
Terry L JerniganDepartments of Cognitive Science, Psychiatry, Radiology, and Center for Human Development, University of California, San Diego, CA, USA.
Jan HaavikKG Jebsen Centre for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway; Department of Psychiatry, Haukeland University Hospital, Bergen, Norway.
Kerstin J PlessenChild and Adolescent Mental Health Center, Capital Region, Denmark.
Astri J LundervoldDepartment of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
Kenneth HugdahlDepartment of Psychiatry, Haukeland University Hospital, Bergen, Norway; Department of Radiology, Haukeland University Hospital, Bergen, Norway; Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
Larry J SeidmanDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA.
Joseph BiedermanDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA; Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA.
Nanda RommelseDepartment of Psychiatry, Radboud University Medical Center, Nijmegen, Netherlands; Karakter Child and Adolescent Psychiatry, Nijmegen, Netherlands.
Dirk J HeslenfeldDepartment of Cognitive Psychology, VU University Amsterdam, Amsterdam, Netherlands; Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, Netherlands.
Catharina A HartmanDepartment of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Pieter J HoekstraDepartment of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Jaap OosterlaanDepartment of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, Netherlands.
Georg von PolierChild Neuropsychology Section, University Hospital Aachen, Aachen, Germany.
Kerstin KonradChild Neuropsychology Section, University Hospital Aachen, Aachen, Germany.
Oscar VilarroyaDepartment of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Fundació IMIM, Barcelona, Spain.
Josep Antoni Ramos-QuirogaDepartment of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Psychiatry, Hospital Universitari Vall d'Hebron, CIBERSAM, Barcelona, Spain.
Joan Carles SolivaDepartment of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Sarah DurstonNICHE-lab, Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, Netherlands.
Jan K BuitelaarDepartment of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Karakter Child and Adolescent Psychiatry, Nijmegen, Netherlands.
Stephen V FaraoneKG Jebsen Centre for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway; Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA.
Philip ShawNeurobehavioral Clinical Research Section, National Human Genome Research Institute, Bethesda, MD, USA; National Institute of Mental Health, Bethesda, MD, USA.
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, University of Southern California, Marina del Rey, CA, USA.
Barbara FrankeDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands; Department of Psychiatry, Radboud University Medical Center, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands.

Funding

The neurobehavioral, environmental and genetic factors impacting ADHD.ZIAHG200378 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI SHAW, PHILIP · 2012 to 2025
$17.7M
TR&D3: Intrinsic Surface MappingP41EB015922 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2012 to 2022
$14.1M
Training U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1M
International Multi-Center ADHD Genetics ProjectR01MH062873 · NIMH · UPSTATE MEDICAL UNIVERSITY · PI FARAONE, STEPHEN V · 2002 to 2007
$7.2M
Longitudinal Discovery of Brain Developmental TrajectoriesU01MH099059 · NIMH · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI MILHAM, MICHAEL PETER · 2013 to 2017
$3.7M
Research Training in Translational Developmental NeuroscienceT32MH067763 · NIMH · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CASTELLANOS, FRANCISCO XAVIER · 2003 to 2013
$2.9M
Discovery Science of Human Brain Function Across the LifespanR01MH094639 · NIMH · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI MILHAM, MICHAEL PETER · 2011 to 2014
$2.7M
Neuroanatomy of Adult ADHD: An MRI Morphometric StudyR01MH062152 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI SEIDMAN, LARRY J · 2002 to 2006
$2.1M
Functional and Structural Connectivity in Adult Attention Deficit Hyperactivity DR01MH083246 · NIMH · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CASTELLANOS, FRANCISCO XAVIER · 2009 to 2011
$1.7M
Translational Developmental Neuroscience of AutismK23MH087770 · NIMH · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DI MARTINO, ADRIANA · 2010 to 2013
$644k
Structural and Functional Biomarkers of Attention-Deficit/Hyperactivity DisorderK01MH110645 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DOUGLAS, PK · 2017 to 2020
$632k
Genetic Imaging of Working Memory and Interference Control in ADHDR21MH091461 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI DOYLE, ALYSA E, SEIDMAN, LARRY J · 2011 to 2012
$480k
Medical Research Council G0300189NIBIB NIH HHS P41 EB015922NIBIB NIH HHS U54 EB020403NIMH NIH HHS K01 MH110645NIMH NIH HHS K23 MH087770NIMH NIH HHS R01 MH062152NIMH NIH HHS R01 MH062873NIMH NIH HHS R01 MH081803NIMH NIH HHS R01 MH083246NIMH NIH HHS R01 MH094639NIMH NIH HHS R21 MH091461NIMH NIH HHS T32 MH067763NIMH NIH HHS U01 MH099059
6 · The paper itself

Abstract

backgroundNeuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis.

methodsIn this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156.

findingsOur sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years): in the accumbens (Cohen's d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5).

interpretationWith the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes.

fundingNational Institutes of Health.

Indexed as

Magnetic Resonance ImagingAdolescentAdultAttention Deficit Disorder with HyperactivityBrainCase-Control StudiesChildChild, PreschoolCross-Sectional StudiesFemaleHumansLinear ModelsLongitudinal StudiesMaleMiddle AgedNeuroimaging

Identifiers

PMID28219628
PMCPMC5933934

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.