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<p>Mounting evidence suggests that hierarchical psychopathology factors underlie psychiatric comorbidity. However, the exact neurobiological characterizations of these multilevel factors remain elusive. Here, leveraging the brain-behavior predictive framework with a 10-year longitudinal imaging-genetic cohort (IMAGEN, ages 14, 19 and 23, <i>N</i> = 1,750), we constructed 2 neural factors underlying externalizing and internalizing symptoms, which were reproducible across 6 clinical and population-based datasets (ABCD, STRATIFY/ESTRA, ABIDE II, ADHD-200 and XiNan, from age 10 to age 36, <i>N</i> = 3,765). These two neural factors exhibit distinct neural configurations: hyperconnectivity in impulsivity-related circuits for the externalizing symptoms and hypoconnectivity in goal-directed circuits for the internalizing symptoms. Both factors also differ in their cognitive-behavior relevance, genetic substrates and developmental profiles. Together with previous findings, we propose a hierarchical neurocognitive model of comorbid psychopathology (NeuroHiP) from preadolescence to adulthood, comprising a general neuropsychopathological factor (manifested as inefficient executive control) and two stratified factors of externalizing (deficient inhibition control) and internalizing (impaired goal-directed function) symptoms, respectively. These holistic insights are crucial for the development of stratified therapeutic interventions for mental disorders.</p>

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Hierarchical neurocognitive model of externalizing and internalizing comorbidity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月13日

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  • Chao Xie,
  • Shitong Xiang,
  • Yueyuan Zheng,
  • Chun Shen,
  • Yuzhu Li,
  • Wei Cheng,
  • Nilakshi Vaidya,
  • Zuo Zhang,
  • Lauren Robinson,
  • Jeanne Winterer,
  • Yuning Zhang,
  • Sinead King,
  • Gareth J. Barker,
  • Arun L. Bokde,
  • Rüdiger Brühl,
  • Hedi Kebir,
  • Dongtao Wei,
  • Eric Artiges,
  • Marina Bobou,
  • M. John Broulidakis,
  • Tobias Banaschewski,
  • Andreas Becker,
  • Christian Büchel,
  • Patricia Conrod,
  • Tahmine Fadai,
  • Herta Flor,
  • Antoine Grigis,
  • Yvonne Grimmer,
  • Hugh Garavan,
  • Penny Gowland,
  • Andreas Heinz,
  • Corinna Insensee,
  • Viola Kappel,
  • Hervé Lemaître,
  • Jean-Luc Martinot,
  • Marie-Laure Paillère Martinot,
  • Betteke Maria van Noort,
  • Frauke Nees,
  • Dimitri Papadopoulos Orfanos,
  • Jani Penttilä,
  • Luise Poustka,
  • Juliane H. Fröhner,
  • Ulrike Schmidt,
  • Julia Sinclair,
  • Michael N. Smolka,
  • Argyris Stringaris,
  • Maren Struve,
  • Henrik Walter,
  • Robert Whelan,
  • Jiang Qiu,
  • Peng Xie,
  • Barbara J. Sahakian,
  • Trevor W. Robbins,
  • Sylvane Desrivières,
  • Gunter Schumann,
  • Jianfeng Feng,
  • Tianye Jia,
  • Betteke Maria van Noort,
  • Gunter Schumann

摘要

Mounting evidence suggests that hierarchical psychopathology factors underlie psychiatric comorbidity. However, the exact neurobiological characterizations of these multilevel factors remain elusive. Here, leveraging the brain-behavior predictive framework with a 10-year longitudinal imaging-genetic cohort (IMAGEN, ages 14, 19 and 23, N = 1,750), we constructed 2 neural factors underlying externalizing and internalizing symptoms, which were reproducible across 6 clinical and population-based datasets (ABCD, STRATIFY/ESTRA, ABIDE II, ADHD-200 and XiNan, from age 10 to age 36, N = 3,765). These two neural factors exhibit distinct neural configurations: hyperconnectivity in impulsivity-related circuits for the externalizing symptoms and hypoconnectivity in goal-directed circuits for the internalizing symptoms. Both factors also differ in their cognitive-behavior relevance, genetic substrates and developmental profiles. Together with previous findings, we propose a hierarchical neurocognitive model of comorbid psychopathology (NeuroHiP) from preadolescence to adulthood, comprising a general neuropsychopathological factor (manifested as inefficient executive control) and two stratified factors of externalizing (deficient inhibition control) and internalizing (impaired goal-directed function) symptoms, respectively. These holistic insights are crucial for the development of stratified therapeutic interventions for mental disorders.