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<p>Clinical heterogeneity in the symptom trajectories of attention deficit hyperactivity disorder (ADHD) is well documented, but their neurodevelopmental mechanisms remain unclear. We used a longitudinal cohort of adolescents (ABCD; <i>n</i> = 7,436) to show that persistent, remitting and emergent ADHD symptom trajectories correlated with persistent, improving and worsening behavioral changes, respectively. Each trajectory had distinct brain signatures: faster cortical thinning (persistence), slower thinning (emergence) and faster subcortical expansion (remission). Slower cortical thinning in the right posterior cingulate was associated with inattention symptom increase, whereas faster hippocampal expansion was associated with inattention symptom decrease. These signatures enhance ADHD symptom prediction at age 13 and generalize to young adults (age 23) in the IMAGEN cohort. The hippocampal signature for remitting symptoms was replicated in IMAGEN and two clinical cohorts (ADHD-200 and ADHD-1000). Given that baseline ADHD medication use was not significantly associated with the remitting trajectory, our findings suggest that current treatments may not facilitate sustained remission, highlighting the potential for new interventions.</p>

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Cortical thinning and hippocampal expansion as brain signatures of attention deficit hyperactivity disorder symptom trajectories

  • 期刊论文

  • 发表日期：

    2026年2月10日

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  • Wenjie Hou,
  • Daqian Zhu,
  • Barbara J. Sahakian,
  • Samuele Cortese,
  • Christelle Langley,
  • Lizhu Luo,
  • Qingyang Li,
  • Zixin Gu,
  • Luolong Cao,
  • Gareth J. Barker,
  • Arun L. W. Bokde,
  • Rüdiger Brühl,
  • Sylvane Desrivières,
  • Herta Flor,
  • Hugh Garavan,
  • Penny Gowland,
  • Antoine Grigis,
  • Andreas Heinz,
  • Jean-Luc Martinot,
  • Marie-Laure Paillère Martinot,
  • Eric Artiges,
  • Frauke Nees,
  • Dimitri Papadopoulos Orfanos,
  • Luise Poustka,
  • Michael N. Smolka,
  • Sarah Hohmann,
  • Nathalie Holz,
  • Nilakshi Vaidya,
  • Henrik Walter,
  • Robert Whelan,
  • Gunter Schumann,
  • Li Yang,
  • Tobias Banaschewski,
  • Qiang Luo

摘要

Clinical heterogeneity in the symptom trajectories of attention deficit hyperactivity disorder (ADHD) is well documented, but their neurodevelopmental mechanisms remain unclear. We used a longitudinal cohort of adolescents (ABCD; n = 7,436) to show that persistent, remitting and emergent ADHD symptom trajectories correlated with persistent, improving and worsening behavioral changes, respectively. Each trajectory had distinct brain signatures: faster cortical thinning (persistence), slower thinning (emergence) and faster subcortical expansion (remission). Slower cortical thinning in the right posterior cingulate was associated with inattention symptom increase, whereas faster hippocampal expansion was associated with inattention symptom decrease. These signatures enhance ADHD symptom prediction at age 13 and generalize to young adults (age 23) in the IMAGEN cohort. The hippocampal signature for remitting symptoms was replicated in IMAGEN and two clinical cohorts (ADHD-200 and ADHD-1000). Given that baseline ADHD medication use was not significantly associated with the remitting trajectory, our findings suggest that current treatments may not facilitate sustained remission, highlighting the potential for new interventions.