Cortical structure and subcortical volumes in conduct disorder: a coordinated analysis of 15 international cohorts from the ENIGMA-Antisocial Behavior Working Group

ENIGMA-Antisocial Behavior Working Group

doi:10.1016/S2215-0366(24)00187-1

Cortical structure and subcortical volumes in conduct disorder: a coordinated analysis of 15 international cohorts from the ENIGMA-Antisocial Behavior Working Group

ENIGMA-Antisocial Behavior Working Group

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Background: Conduct disorder is associated with the highest burden of any mental disorder in childhood, yet its neurobiology remains unclear. Inconsistent findings limit our understanding of the role of brain structure alterations in conduct disorder. This study aims to identify the most robust and replicable brain structural correlates of conduct disorder. Methods: The ENIGMA-Antisocial Behavior Working Group performed a coordinated analysis of structural MRI data from 15 international cohorts. Eligibility criteria were a mean sample age of 18 years or less, with data available on sex, age, and diagnosis of conduct disorder, and at least ten participants with conduct disorder and ten typically developing participants. 3D T1-weighted MRI brain scans of all participants were pre-processed using ENIGMA-standardised protocols. We assessed group differences in cortical thickness, surface area, and subcortical volumes using general linear models, adjusting for age, sex, and total intracranial volume. Group-by-sex and group-by-age interactions, and DSM-subtype comparisons (childhood-onset vs adolescent-onset, and low vs high levels of callous-unemotional traits) were investigated. People with lived experience of conduct disorder were not involved in this study. Findings: We collated individual participant data from 1185 young people with conduct disorder (339 [28·6%] female and 846 [71·4%] male) and 1253 typically developing young people (446 [35·6%] female and 807 [64·4%] male), with a mean age of 13·5 years (SD 3·0; range 7–21). Information on race and ethnicity was not available. Relative to typically developing young people, the conduct disorder group had lower surface area in 26 cortical regions and lower total surface area (Cohen's d 0·09–0·26). Cortical thickness differed in the caudal anterior cingulate cortex (d 0·16) and the banks of the superior temporal sulcus (d –0·13). The conduct disorder group also had smaller amygdala (d 0·13), nucleus accumbens (d 0·11), thalamus (d 0·14), and hippocampus (d 0·12) volumes. Most differences remained significant after adjusting for ADHD comorbidity or intelligence quotient. No group-by-sex or group-by-age interactions were detected. Few differences were found between DSM-defined conduct disorder subtypes. However, individuals with high callous-unemotional traits showed more widespread differences compared with controls than those with low callous-unemotional traits. Interpretation: Our findings provide robust evidence of subtle yet widespread brain structural alterations in conduct disorder across subtypes and sexes, mostly in surface area. These findings provide further evidence that brain alterations might contribute to conduct disorder. Greater consideration of this under-recognised disorder is needed in research and clinical practice. Funding: Academy of Medical Sciences and Economic and Social Research Council.

Original language	English
Pages (from-to)	620-632
Number of pages	13
Journal	The Lancet Psychiatry
Volume	11
Issue number	8
Early online date	16 Jul 2024
DOIs	https://doi.org/10.1016/S2215-0366(24)00187-1
Publication status	Published - Aug 2024

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10.1016/S2215-0366(24)00187-1

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@article{0f81edd6d2a640078aab3d9ca10e62c9,

title = "Cortical structure and subcortical volumes in conduct disorder: a coordinated analysis of 15 international cohorts from the ENIGMA-Antisocial Behavior Working Group",

abstract = "Background: Conduct disorder is associated with the highest burden of any mental disorder in childhood, yet its neurobiology remains unclear. Inconsistent findings limit our understanding of the role of brain structure alterations in conduct disorder. This study aims to identify the most robust and replicable brain structural correlates of conduct disorder. Methods: The ENIGMA-Antisocial Behavior Working Group performed a coordinated analysis of structural MRI data from 15 international cohorts. Eligibility criteria were a mean sample age of 18 years or less, with data available on sex, age, and diagnosis of conduct disorder, and at least ten participants with conduct disorder and ten typically developing participants. 3D T1-weighted MRI brain scans of all participants were pre-processed using ENIGMA-standardised protocols. We assessed group differences in cortical thickness, surface area, and subcortical volumes using general linear models, adjusting for age, sex, and total intracranial volume. Group-by-sex and group-by-age interactions, and DSM-subtype comparisons (childhood-onset vs adolescent-onset, and low vs high levels of callous-unemotional traits) were investigated. People with lived experience of conduct disorder were not involved in this study. Findings: We collated individual participant data from 1185 young people with conduct disorder (339 [28·6%] female and 846 [71·4%] male) and 1253 typically developing young people (446 [35·6%] female and 807 [64·4%] male), with a mean age of 13·5 years (SD 3·0; range 7–21). Information on race and ethnicity was not available. Relative to typically developing young people, the conduct disorder group had lower surface area in 26 cortical regions and lower total surface area (Cohen's d 0·09–0·26). Cortical thickness differed in the caudal anterior cingulate cortex (d 0·16) and the banks of the superior temporal sulcus (d –0·13). The conduct disorder group also had smaller amygdala (d 0·13), nucleus accumbens (d 0·11), thalamus (d 0·14), and hippocampus (d 0·12) volumes. Most differences remained significant after adjusting for ADHD comorbidity or intelligence quotient. No group-by-sex or group-by-age interactions were detected. Few differences were found between DSM-defined conduct disorder subtypes. However, individuals with high callous-unemotional traits showed more widespread differences compared with controls than those with low callous-unemotional traits. Interpretation: Our findings provide robust evidence of subtle yet widespread brain structural alterations in conduct disorder across subtypes and sexes, mostly in surface area. These findings provide further evidence that brain alterations might contribute to conduct disorder. Greater consideration of this under-recognised disorder is needed in research and clinical practice. Funding: Academy of Medical Sciences and Economic and Social Research Council.",

author = "{ENIGMA-Antisocial Behavior Working Group} and Yidian Gao and Marlene Staginnus and Sophie Townend and Celso Arango and Sahil Bajaj and Tobias Banaschewski and Barker, {Edward D.} and Vivek Benegal and Kathryn Berluti and Anka Bernhard and Blair, {Robert J.R.} and Boateng, {Charlotte P.S.} and Bokde, {Arun L.W.} and Daniel Brandeis and Buitelaar, {Jan K.} and Burt, {S. Alexandra} and Cardinale, {Elise M.} and Josefina Castro-Fornieles and Hui Chen and Xianliang Chen and Chester, {Sally C.} and Colins, {Olivier F.} and Harriet Cornwell and Michael Craig and Cubillo, {Ana I.} and Sylvane Desrivieres and D{\'i}az, {Dana E.} and Andrea Dietrich and Daifeng Dong and Dykstra, {Anouk H.} and Barbara Franke and Freitag, {Christine M.} and Glennon, {Jeffrey C.} and Karen Gonzalez-Madruga and Hagan, {Cindy C.} and Hoekstra, {Pieter J.} and Bharath Holla and Hyde, {Luke W.} and Karim Ibrahim and Nimrah Jabeen and Declan Murphy and Ruth Roberts and Ilyas Sagar-Ouriaghli and Gunter Schumann and Arjun Sethi and Sonuga-Barke, {Edmund J.S.} and Essi Viding and Cecil, {Charlotte A.M.} and Esther Walton and {De Brito}, {Stephane A.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license",

year = "2024",

month = aug,

doi = "10.1016/S2215-0366(24)00187-1",

language = "English",

volume = "11",

pages = "620--632",

journal = "The Lancet Psychiatry",

issn = "2215-0366",

publisher = "Elsevier",

number = "8",

}

TY - JOUR

T1 - Cortical structure and subcortical volumes in conduct disorder

T2 - a coordinated analysis of 15 international cohorts from the ENIGMA-Antisocial Behavior Working Group

AU - ENIGMA-Antisocial Behavior Working Group

AU - Gao, Yidian

AU - Staginnus, Marlene

AU - Townend, Sophie

AU - Arango, Celso

AU - Bajaj, Sahil

AU - Banaschewski, Tobias

AU - Barker, Edward D.

AU - Benegal, Vivek

AU - Berluti, Kathryn

AU - Bernhard, Anka

AU - Blair, Robert J.R.

AU - Boateng, Charlotte P.S.

AU - Bokde, Arun L.W.

AU - Brandeis, Daniel

AU - Buitelaar, Jan K.

AU - Burt, S. Alexandra

AU - Cardinale, Elise M.

AU - Castro-Fornieles, Josefina

AU - Chen, Hui

AU - Chen, Xianliang

AU - Chester, Sally C.

AU - Colins, Olivier F.

AU - Cornwell, Harriet

AU - Craig, Michael

AU - Cubillo, Ana I.

AU - Desrivieres, Sylvane

AU - Díaz, Dana E.

AU - Dietrich, Andrea

AU - Dong, Daifeng

AU - Dykstra, Anouk H.

AU - Franke, Barbara

AU - Freitag, Christine M.

AU - Glennon, Jeffrey C.

AU - Gonzalez-Madruga, Karen

AU - Hagan, Cindy C.

AU - Hoekstra, Pieter J.

AU - Holla, Bharath

AU - Hyde, Luke W.

AU - Ibrahim, Karim

AU - Jabeen, Nimrah

AU - Murphy, Declan

AU - Roberts, Ruth

AU - Sagar-Ouriaghli, Ilyas

AU - Schumann, Gunter

AU - Sethi, Arjun

AU - Sonuga-Barke, Edmund J.S.

AU - Viding, Essi

AU - Cecil, Charlotte A.M.

AU - Walton, Esther

AU - De Brito, Stephane A.

PY - 2024/8

Y1 - 2024/8

N2 - Background: Conduct disorder is associated with the highest burden of any mental disorder in childhood, yet its neurobiology remains unclear. Inconsistent findings limit our understanding of the role of brain structure alterations in conduct disorder. This study aims to identify the most robust and replicable brain structural correlates of conduct disorder. Methods: The ENIGMA-Antisocial Behavior Working Group performed a coordinated analysis of structural MRI data from 15 international cohorts. Eligibility criteria were a mean sample age of 18 years or less, with data available on sex, age, and diagnosis of conduct disorder, and at least ten participants with conduct disorder and ten typically developing participants. 3D T1-weighted MRI brain scans of all participants were pre-processed using ENIGMA-standardised protocols. We assessed group differences in cortical thickness, surface area, and subcortical volumes using general linear models, adjusting for age, sex, and total intracranial volume. Group-by-sex and group-by-age interactions, and DSM-subtype comparisons (childhood-onset vs adolescent-onset, and low vs high levels of callous-unemotional traits) were investigated. People with lived experience of conduct disorder were not involved in this study. Findings: We collated individual participant data from 1185 young people with conduct disorder (339 [28·6%] female and 846 [71·4%] male) and 1253 typically developing young people (446 [35·6%] female and 807 [64·4%] male), with a mean age of 13·5 years (SD 3·0; range 7–21). Information on race and ethnicity was not available. Relative to typically developing young people, the conduct disorder group had lower surface area in 26 cortical regions and lower total surface area (Cohen's d 0·09–0·26). Cortical thickness differed in the caudal anterior cingulate cortex (d 0·16) and the banks of the superior temporal sulcus (d –0·13). The conduct disorder group also had smaller amygdala (d 0·13), nucleus accumbens (d 0·11), thalamus (d 0·14), and hippocampus (d 0·12) volumes. Most differences remained significant after adjusting for ADHD comorbidity or intelligence quotient. No group-by-sex or group-by-age interactions were detected. Few differences were found between DSM-defined conduct disorder subtypes. However, individuals with high callous-unemotional traits showed more widespread differences compared with controls than those with low callous-unemotional traits. Interpretation: Our findings provide robust evidence of subtle yet widespread brain structural alterations in conduct disorder across subtypes and sexes, mostly in surface area. These findings provide further evidence that brain alterations might contribute to conduct disorder. Greater consideration of this under-recognised disorder is needed in research and clinical practice. Funding: Academy of Medical Sciences and Economic and Social Research Council.

AB - Background: Conduct disorder is associated with the highest burden of any mental disorder in childhood, yet its neurobiology remains unclear. Inconsistent findings limit our understanding of the role of brain structure alterations in conduct disorder. This study aims to identify the most robust and replicable brain structural correlates of conduct disorder. Methods: The ENIGMA-Antisocial Behavior Working Group performed a coordinated analysis of structural MRI data from 15 international cohorts. Eligibility criteria were a mean sample age of 18 years or less, with data available on sex, age, and diagnosis of conduct disorder, and at least ten participants with conduct disorder and ten typically developing participants. 3D T1-weighted MRI brain scans of all participants were pre-processed using ENIGMA-standardised protocols. We assessed group differences in cortical thickness, surface area, and subcortical volumes using general linear models, adjusting for age, sex, and total intracranial volume. Group-by-sex and group-by-age interactions, and DSM-subtype comparisons (childhood-onset vs adolescent-onset, and low vs high levels of callous-unemotional traits) were investigated. People with lived experience of conduct disorder were not involved in this study. Findings: We collated individual participant data from 1185 young people with conduct disorder (339 [28·6%] female and 846 [71·4%] male) and 1253 typically developing young people (446 [35·6%] female and 807 [64·4%] male), with a mean age of 13·5 years (SD 3·0; range 7–21). Information on race and ethnicity was not available. Relative to typically developing young people, the conduct disorder group had lower surface area in 26 cortical regions and lower total surface area (Cohen's d 0·09–0·26). Cortical thickness differed in the caudal anterior cingulate cortex (d 0·16) and the banks of the superior temporal sulcus (d –0·13). The conduct disorder group also had smaller amygdala (d 0·13), nucleus accumbens (d 0·11), thalamus (d 0·14), and hippocampus (d 0·12) volumes. Most differences remained significant after adjusting for ADHD comorbidity or intelligence quotient. No group-by-sex or group-by-age interactions were detected. Few differences were found between DSM-defined conduct disorder subtypes. However, individuals with high callous-unemotional traits showed more widespread differences compared with controls than those with low callous-unemotional traits. Interpretation: Our findings provide robust evidence of subtle yet widespread brain structural alterations in conduct disorder across subtypes and sexes, mostly in surface area. These findings provide further evidence that brain alterations might contribute to conduct disorder. Greater consideration of this under-recognised disorder is needed in research and clinical practice. Funding: Academy of Medical Sciences and Economic and Social Research Council.

UR - http://www.scopus.com/inward/record.url?scp=85198588569&partnerID=8YFLogxK

U2 - 10.1016/S2215-0366(24)00187-1

DO - 10.1016/S2215-0366(24)00187-1

M3 - Article

C2 - 39025633

AN - SCOPUS:85198588569

SN - 2215-0366

VL - 11

SP - 620

EP - 632

JO - The Lancet Psychiatry

JF - The Lancet Psychiatry

IS - 8

ER -

Cortical structure and subcortical volumes in conduct disorder: a coordinated analysis of 15 international cohorts from the ENIGMA-Antisocial Behavior Working Group

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