Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Unbalanced risk-benefit analysis of ADHD drugs

    Research output: Contribution to journalLetterResearchpeer-review

  2. Traumatic brain injury and dementia

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Traumatic brain injury and dementia - Authors' reply

    Research output: Contribution to journalComment/debateResearchpeer-review

  • 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
  • Patrick de Zeeuw
  • Eszter Szekely
  • Gustavo Sudre
  • Thomas Wolfers
  • Alberdingk M H Onnink
  • Janneke T Dammers
  • Jeanette C Mostert
  • Yolanda Vives-Gilabert
  • Gregor Kohls
  • Eileen Oberwelland
  • Jochen Seitz
  • Martin Schulte-Rüther
  • Sara Ambrosino
  • Alysa E Doyle
  • Marie Farstad Høvik
  • Margaretha Dramsdahl
  • Leanne Tamm
  • Theo G M van Erp
  • Anders Dale
  • Andrew J Schork
  • Annette Conzelmann
  • Kathrin Zierhut
  • Ramona Baur
  • Hazel McCarthy
  • Yuliya N Yoncheva
  • Ana Cubillo
  • Kaylita Chantiluke
  • Mitul A Mehta
  • Yannis Paloyelis
  • Sarah Hohmann
  • Sarah Baumeister
  • Ivanei Bramati
  • Paulo Mattos
  • Fernanda Tovar-Moll
  • Pamela S Douglas
  • Tobias Banaschewski
  • Daniel Brandeis
  • Jonna Kuntsi
  • Philip Asherson
  • Katya Rubia
  • Clare Kelly
  • Adriana Di Martino
  • Michael P Milham
  • Francisco X Castellanos
  • Thomas Frodl
  • Mariam Zentis
  • Klaus-Peter Lesch
  • Andreas Reif
  • Paul Pauli
  • Terry L Jernigan
  • Jan Haavik
  • Kerstin J Plessen
  • Astri J Lundervold
  • Kenneth Hugdahl
  • Larry J Seidman
  • Joseph Biederman
  • Nanda Rommelse
  • Dirk J Heslenfeld
  • Catharina A Hartman
  • Pieter J Hoekstra
  • Jaap Oosterlaan
  • Georg von Polier
  • Kerstin Konrad
  • Oscar Vilarroya
  • Josep Antoni Ramos-Quiroga
  • Joan Carles Soliva
  • Sarah Durston
  • Jan K Buitelaar
  • Stephen V Faraone
  • Philip Shaw
  • Paul M Thompson
  • Barbara Franke
View graph of relations

BACKGROUND: Neuroimaging 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.

METHODS: In 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.

FINDINGS: Our 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).

INTERPRETATION: With 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.

FUNDING: National Institutes of Health.

Original languageEnglish
JournalThe Lancet Psychiatry
Volume4
Issue number4
Pages (from-to)310-319
Number of pages10
ISSN2215-0366
DOIs
Publication statusPublished - Jun 2017

    Research areas

  • Journal Article

ID: 50052336