TY - JOUR
T1 - Shared and distinct alterations in brain structure of youth with internalizing or externalizing disorders
T2 - Findings from the ENIGMA Antisocial Behavior, ADHD, MDD, and Anxiety Working Groups
AU - Townend, Sophie
AU - Staginnus, Marlene
AU - Gao, Yidian
AU - Alexander, Nina
AU - Arolt, Volker
AU - Banaschewski, Tobias
AU - Bellgrove, Mark A
AU - Benegal, Vivek
AU - Blair, Robert J
AU - Blanco-Hinojo, Laura
AU - Boeken, Ole Jonas
AU - Böhnlein, Joscha
AU - Bölte, Sven
AU - Bonnekoh, Linda M
AU - Brandeis, Daniel
AU - Bressan, Rodrigo A
AU - Breuer, Fabian
AU - Bruin, Willem B
AU - Buitelaar, Jan K
AU - Burkhouse, Katie L
AU - Calkins, Monica E
AU - Cano, Marta
AU - Cardoner, Narcis
AU - Chen, Hui
AU - Chen, Xianliang
AU - Coghill, David R
AU - Colins, Olivier F
AU - Connolly, Colm G
AU - Craig, Michael C
AU - Cullen, Kathryn R
AU - Dannlowski, Udo
AU - Davey, Christopher G
AU - Dietrich, Andrea
AU - Dong, Daifeng
AU - Freitag, Christine M
AU - Frodl, Thomas
AU - Goossens, Liesbet
AU - Grotegerd, Dominik
AU - Gur, Raquel E
AU - Gur, Ruben C
AU - Haavik, Jan
AU - Hagan, Cindy C
AU - Hahn, Tim
AU - Hamm, Alfons O
AU - Harrison, Ben J
AU - Hartman, Catharina A
AU - Herrmann, Martin J
AU - Ho, Tiffany C
AU - Hoekstra, Pieter J
AU - Holla, Bharath
AU - ENIGMA Antisocial Behavior, Anxiety, ADHD, and MDD Working Groups
AU - Schruers, Koen
PY - 2025/8/12
Y1 - 2025/8/12
N2 - 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 Consortium, we conducted a mega-analysis to identify shared and distinct cortical and subcortical brain alterations across internalizing (anxiety disorders and depression) and externalizing disorders (attention-deficit/hyperactivity disorder [ADHD] and conduct disorder [CD]) in youth. METHODS: 3D T1-weighted MRI data from youth (aged 4-21 years) with anxiety disorders (n=1,044), depression (n=504), ADHD (n=1,317), and CD (n=1,172), along with healthy controls (n=4,743) were analyzed. We assessed group differences in regional cortical thickness, surface area, and subcortical volume using linear models, adjusted for site, age, and sex, and total intracranial volume in the surface area and subcortical volume models. RESULTS: We observed transdiagnostic associations, with both internalizing and externalizing disorders characterized by lower surface area 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 surface area and intracranial volume (ds=-0.11 to -0.25). Externalizing-specific reductions in surface area were observed in fronto-parietal 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 findings can guide future research targeting common biological processes across youth psychiatric disorders as well as features unique to individual disorders.
AB - 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 Consortium, we conducted a mega-analysis to identify shared and distinct cortical and subcortical brain alterations across internalizing (anxiety disorders and depression) and externalizing disorders (attention-deficit/hyperactivity disorder [ADHD] and conduct disorder [CD]) in youth. METHODS: 3D T1-weighted MRI data from youth (aged 4-21 years) with anxiety disorders (n=1,044), depression (n=504), ADHD (n=1,317), and CD (n=1,172), along with healthy controls (n=4,743) were analyzed. We assessed group differences in regional cortical thickness, surface area, and subcortical volume using linear models, adjusted for site, age, and sex, and total intracranial volume in the surface area and subcortical volume models. RESULTS: We observed transdiagnostic associations, with both internalizing and externalizing disorders characterized by lower surface area 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 surface area and intracranial volume (ds=-0.11 to -0.25). Externalizing-specific reductions in surface area were observed in fronto-parietal 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 findings can guide future research targeting common biological processes across youth psychiatric disorders as well as features unique to individual disorders.
KW - Child and adolescent psychiatry
KW - ENIGMA
KW - Meta-analysis
KW - Structural MRI
KW - Transdiagnostic
KW - Youth
U2 - 10.1016/j.biopsych.2025.08.003
DO - 10.1016/j.biopsych.2025.08.003
M3 - Article
SN - 0006-3223
JO - Biological Psychiatry
JF - Biological Psychiatry
ER -