• Carl Delfin, Peter Andiné, Märta Wallinius, and Malin Björnsdotter.
• Centre for Ethics, Law and Mental Health, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Research Department, Regional Forensic Psychiatric Clinic, Växjö, Sweden. Electronic address: carl.delfin@gu.se.
• Neuroscience. 2021 May 21; 463: 1-13.

AbstractThe externalizing spectrum, including traits and behaviors such as aggression, reduced inhibitiory control and substance abuse, is associated with altered prefrontal brain morphology. However, the degree to which different manifestations of the externalizing spectrum are associated with distinct or overlapping variations in individual brain morphology is unclear. Here, we therefore used structural magnetic resonance imaging, self-report assessment, and a response inhibition task in a sample of 59 young adults to examine how cortical thickness in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex (DLPFC) relate to four different manifestations of the externalizing spectrum: disinhibition, callous aggression, substance abuse, and behavioral inhibitory control. Using Bayesian linear regression models controlling for age, gender, and years of education, we found that the different manifestations of the externalizing spectrum were associated with both distinct and overlapping morphology variations. Specifically, both callous aggression and inhibitory control was associated with increased cortical thickness of the OFC, a region involved in reward processing, decision-making, and regulation of anxiety and fear. Both disinhibition and substance abuse were associated with DLPFC thickness, although with opposite association patterns, possibly reflecting processes related to inhibitory control, working memory and attention. Moreover, disinhibition, but not callous aggression or substance abuse, was associated with behavioral inhibitory control. Our results provide further support for the link between externalizing behaviors and prefrontal brain morphology, while identifying distinct prefrontal areas associated with different clinically relevant manifestations. These findings may help guide further research aimed at developing novel treatment and intervention strategies for externalizing behaviors and disorders.Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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