Cortical structure and subcortical volumes in conduct disorder: A coordinated analysis of 15 international cohorts from the ENIGMA Antisocial Behavior working group

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. Therefore, 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 mean sample age ≤18 years, data available on sex, age and research or clinical diagnoses of conduct disorder, and at least 10 conduct disorder and 10 typically-developing participants. 3D T1-weighted MRI scans of youth with conduct disorder and typically-developing youth 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, group-by-age interactions, and DSM-subtype comparisons (childhood-onset versus adolescent-onset, low versus high levels of callous-unemotional traits were investigated. People with lived experience of conduct disorder were not involved.

Findings: We collated individual participant data from 1,185 youth with conduct disorder (339 female, 28·6%) and 1,253 typically-developing youth (446 female, 35·6%), with a mean age of 13·38 years (SD 3.01; range 7-21). Informa[on on race and ethnicity was not available. Relative to typically-developing youth, the conduct disorder group had lower surface area in 26 cortical regions and lower total surface area (Cohen’s ds=0·09-0·26). There were cortical thickness differences in two regions (ds=0·13-0·16). The conduct disorder group also had smaller amygdala, accumbens, thalamus, and hippocampus volumes (ds=0·11-0·14). Most differences survived adjusting for attention-deficit/hyperactivity disorder comorbidity or IQ. No group-by-sex or group-by-age interactions were detected. Limited differences were found between conduct disorder subtypes, whereas all subtypes displayed shared alterations compared to controls. However, those with high callous-unemotional traits showed more widespread differences compared to controls.

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 may contribute to conduct disorder and highlight the need for greater consideration of this under-recognised disorder.