NIH-funded conduct disorder study identifies new brain regions associated with the disorder, offering future directions for research efforts and clinical practice
• Press release
A neuroimaging study of young people who exhibit a persistent pattern of disruptive, aggressive and antisocial behavior, known as conduct disorder, has revealed extensive changes in brain structure. The most pronounced difference was a smaller region of the brain’s outer layer, known as the cerebral cortex, which is critical for many aspects of behavior, cognition and emotion. The study, co-authored by researchers at the National Institutes of Health (NIH), is published in The Lancet Psychiatry.
“Conduct disorder has one of the highest burdens of any mental disorder in youth. However, it remains understudied and undertreated. “Understanding the brain differences associated with the disorder brings us one step closer to developing more effective approaches to diagnosis and treatment, with the ultimate goal of improving long-term outcomes for children and their families,” said co- author Daniel Pine, MD, Chief of the Division of Developmental and Emotional Neuroscience at NIH’s National Institute of Mental Health. “The critical next steps are to follow the children over time to determine whether the differences in brain structure seen in this study are a cause of the conduct disorder or a long-term consequence of the disorder.”
A collaborative team of researchers reviewed standardized MRI data from youth ages 7 to 21 who had participated in 15 studies from around the world. The analyzes compared the surface area and thickness of the cerebral cortex and the volume of deeper subcortical areas of the brain between 1,185 youth diagnosed with conduct disorder and 1,253 youth without the disorder. Additional analyzes compared cortical and subcortical brain measures between boys and girls, age of symptom onset (childhood vs. adolescence), and level of empathy and other prosocial traits (high vs. low).
Youth with conduct disorder had lower total area along the cortex in 26 of 34 individual regions, two of which showed significant changes in cortical thickness. Youth with conduct disorder also had lower volume in several subcortical brain regions, including the amygdala, hippocampus, and thalamus, which play a central role in regulating behaviors that are often challenging for those with the disorder. Although some of these brain regions, such as the prefrontal cortex and amygdala, had been linked to conduct disorder in previous studies, other regions were implicated in the disorder for the first time.
Correlations with brain structure did not differ between boys and girls and were observed in conduct disorder subgroups based on age of onset and level of prosocial characteristics. Young people who showed signs of a more severe form of the disorder, indicated by low levels of empathy, guilt and remorse, showed the greatest number of brain changes.
These findings from the largest, most diverse, and most powerful study of conduct disorder to date are consistent with a growing body of evidence that the disorder is related to brain structure. The study also provides new evidence that brain changes are more widespread than previously shown, covering all four lobes and cortical and subcortical regions. These findings offer new avenues for investigating potential causal links between differences in brain structure and conduct disorder symptoms and for targeting brain regions as part of clinical efforts to improve diagnosis and treatment.
Yidian Gao, Ph.D., at the University of Birmingham and Marlene Staginnus, Ph.D., at the University of Bath co-led the study, which was conducted by the international Enhancing Genetic Neuroimaging through Meta-Analysis (ENIGMA) – Antisocial Behavior Working Group. The ENIGMA consortium received funding from several NIH institutes through a cross-NIH funding alliance Big Data to Knowledge Centers of Excellence .
Report:
Gao, Y., Staginnus, M., & the ENIGMA-Antisocial Behavior Working Group. (2024). Cortical structure and subcortical volumes in conduct disorder: A coordinated analysis of 15 international cohorts from the ENIGMA Antisocial Behavior Working Group. The Lancet Psychiatry, 11, 620-632. https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(24)00187-1/fulltext
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