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Shared and Distinct Alterations in Brain Structure of Youth With Internalizing or Externalizing Disorders: Findings From the ENIGMA Antisocial Behavior, ADHD, Major Depressive Disorder, and Anxiety Working Groups

2025· article· en· W4413139760 on OpenAlexaff
Sophie Townend, Marlene Staginnus, Yidian Gao, Nina Alexander, Volker Arolt, Tobias Banaschewski, Mark A. Bellgrove, Vivek Benegal, James Blair, Laura Blanco‐Hinojo, Ole Jonas Boeken, Joscha Böhnlein, Sven Bölte, Linda M. Bonnekoh, Daniel Brandeis, Rodrigo A. Bressan, Fabian Breuer, Willem B. Bruin, Jan K. Buitelaar, Katie L. Burkhouse, Monica E. Calkins, Marta Cano, Narcı́s Cardoner, Hui Chen, Xianliang Chen, David Coghill, Olivier F. Colins, Colm G. Connolly, Michael Craig, Kathryn R. Cullen, Udo Dannlowski, Christopher G. Davey, Andrea Dietrich, Daifeng Dong, Christine M. Freitag, Thomas Frodl, Liesbet Goossens, Dominik Grotegerd, Raquel E. Gur, Ruben C Gur, Jan Haavik, Cindy C. Hagan, Tim Hahn, Alfons O. Hamm, Ben J. Harrison, Catharina A. Hartman, Martin J. Herrmann, Tiffany C. Ho, Pieter J. Hoekstra, Bharath Holla, Karim Ibrahim, Andrea Parolin Jackowski, Hamidreza Jamalabadi, Yali Jiang, Tilo Kircher, Kerstin Konrad, Anna Kraus, Jonna Kuntsi, Till Langhammer, Luisa Lázaro, Elisabeth J. Leehr, Ulrike Lueken, Ren Ma, Frank P. MacMaster, Gisele Gus Manfro, Anne Martinelli, Hannah Meinert, Susanne Meinert, Jarosław M. Michałowski, Qingsen Ming, Robert Moeck, Lilianne R. Mujica‐Parodi, Benson Mwangi, Janina Neufeld, Joel T. Nigg, Ruth Tuura, Hyuntaek Oh, Jaap Oosterlaan, Yannis Paloyelis, Pedro Mário Pan, Luca Passamonti, Wenceslao Peñate, K. Luan Phan, Kerstin Jessica Plessen, Jesús Pujol, Karl Lundin Remnélius, Francisco Rivero, Katya Rubia, Ramiro Salas, Giovanni Abrahão Salum, Theodore D Satterthwaite, Anne Schienle, Elisabeth Schrammen, Koen Schruers, Günter Schumann, Arjun Sethi, Timothy J. Silk, Norbert Skokauskas, Jordan W. Smoller, Jair C. Soares, Lin Sørensen, Christina Stadler, Michael C. Stevens, Benjamín Straube, Thomas Straube, Andreas Ströhle, Gustavo Sudre, Denis G. Sukhodolsky, Kate Sully, Xiaoqiang Sun, Chad M. Sylvester, Nicola Toschi, Steven J.A. van der Werff, Alasdair Vance, Robert Vermeiren, Albert Wabnegger, Xiaoping Wang, Julia Wendt, Sarah Whittle, Julian Wiemer, Anderson M. Winkler, Hans‐Ulrich Wïttchen, Mon‐Ju Wu, Qiong Wu, Yunbo Yang, Shuqiao Yao, Jibiao Zhang, Jiansong Zhou, André Zugman, Giovana Zunta‐Soares, Peter Zwanzger, Sophia I. Thomopoulos, Neda Jahanshad, Paul M. Thompson, Kevin Hilbert, Arielle Baskin–Sommers, Charlotte A. M. Cecil, Moji Aghajani, Daniel S. Pine, Nic J.A. van der Wee, Dan J. Stein, Nynke A. Groenewold, Janna Marie Bas‐Hoogendam, Laura K. M. Han, Elena Pozzi, Lianne Schmaal, Barbara Franke, Martine Hoogman, Esther Walton, Stéphane A. De Brito, Graeme Fairchild

Bibliographic record

VenueBiological Psychiatry · 2025
Typearticle
Languageen
FieldMedicine
TopicAttention Deficit Hyperactivity Disorder
Canadian institutionsNova Scotia Health AuthorityDalhousie University
FundersNIH Clinical CenterNational Institute of Mental HealthDet Sundhedsvidenskabelige Fakultet, Københavns UniversitetInstituto de Salud Carlos IIIEconomic and Social Research CouncilAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General HospitalH. Lundbeck A/SMedical Research CouncilServierFaculty of Health and Medical Sciences, University of Western AustraliaJulius-Maximilians-Universität WürzburgMassachusetts General HospitalUniversity of Cape TownXiangya Hospital, Central South UniversityRadboud Universitair Medisch CentrumCentre d'Imagerie BioMédicaleLeids Universitair Medisch CentrumUniversitetet i BergenTaylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine in St. LouisWestfälische Wilhelms-Universität MünsterUniversität PotsdamFudan UniversityUniversity of PennsylvaniaPhilipps-Universität MarburgTechnische Universität DresdenGentofte HospitalCentral South UniversityUniversität BielefeldWashington University in St. LouisUniversiteit MaastrichtRadboud UniversiteitMonash UniversityDeakin UniversityInstitute of Psychiatry, Psychology and Neuroscience, King’s College LondonMinisterio de Economía y CompetitividadRijksuniversiteit GroningenNational Institute of Mental Health and NeurosciencesUniversiteit LeidenUniversity of Southern CaliforniaUniversity of SouthamptonCalifornia Institute of TechnologySanofiNorges Teknisk-Naturvitenskapelige UniversitetPerelman School of Medicine, University of PennsylvaniaTakeda Pharmaceutical CompanyUniversity of California, Los AngelesUniversity of Texas Rio Grande ValleyCurtin University of TechnologySouth African Medical Research CouncilUniversitair Medisch Centrum GroningenUniversity of MinnesotaUniversität GreifswaldBiogenFlorida State UniversityVistagen TherapeuticsHaukeland UniversitetssjukehusUniversiteit GentAccareUniversity of BathPennsylvania State UniversityYale UniversityKarolinska InstitutetKing's College LondonChildren's Hospital of PhiladelphiaL'Oreal USA
KeywordsPsychologyAnxietyAmygdalaClinical psychologyDepression (economics)Major depressive disorderConduct disorderInsulaEntorhinal cortexAttention deficit hyperactivity disorderBrain sizeSpecific phobiaPsychiatryGeneralized anxiety disorderNeuroscienceHippocampusMedicineMagnetic resonance imaging

Abstract

fetched live from OpenAlex

BACKGROUND: Externalizing and internalizing disorders are common in youth but are often studied separately, preventing researchers from identifying shared (i.e., transdiagnostic) alterations in brain structure. Using data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium, we conducted a mega-analysis to identify shared and distinct cortical and subcortical brain alterations across internalizing (anxiety disorders and depression) and externalizing (attention-deficit/hyperactivity disorder [ADHD] and conduct disorder [CD]) disorders in youth. METHODS: 3D T1-weighted magnetic resonance imaging data from youths (age range 4-21 years) with anxiety disorders (n = 1044), depression (n = 504), ADHD (n = 1317), and CD (n = 1172) along with healthy control participants (n = 4743) were analyzed. We assessed group differences in regional cortical thickness, surface area (SA), and subcortical volume using linear models, adjusted for site, age, and sex, as well as total intracranial volume in the SA and subcortical volume models. RESULTS: We observed transdiagnostic associations, with both internalizing and externalizing disorders characterized by lower SA in the insula, entorhinal cortex, and middle temporal gyrus and lower amygdala volume (Cohen's ds = -0.07 to -0.24) as well as total SA and intracranial volume (ds = -0.11 to -0.25). Externalizing-specific reductions in SA were observed in frontoparietal regions (ds = -0.08 to -0.13), but no internalizing-specific associations were identified. Disorder-specific alterations were identified for ADHD, CD, and anxiety disorders but not depression. CONCLUSIONS: Both common and disorder-specific alterations were identified, with regions involved in salience attribution and emotion processing implicated across internalizing and externalizing disorders. These novel findings can guide future research targeting common biological processes across youth psychiatric disorders as well as features unique to individual disorders.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.004
metaresearch head score (Gemma)0.008
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.024

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.008
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.003
Bibliometrics0.0020.002
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.034
GPT teacher head0.312
Teacher spread0.279 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations3
Published2025
Admission routes1
Has abstractyes

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