Sex matters: association between callous-unemotional traits and uncinate fasciculus microstructure in youths with conduct disorder

Thomas Villemonteix, Jack C Rogers, Ophélie Courbet, Karen Gonzalez-Madruga, Gregor Kohls, Nora M Raschle, Christina Stadler, Kerstin Konrad, Christine M Freitag, Graeme Fairchild, Stéphane A De Brito

Research output: Contribution to journalArticlepeer-review


Among youths with conduct disorder, those with callous-unemotional traits are at increased risk for persistent antisocial behaviour. Although callous-unemotional traits have been found to be associated with white-matter brain abnormalities, previous diffusion imaging studies were conducted in small samples, preventing examination of potential sex by callous-unemotional traits interaction effects on white matter. Here, we used tract-based spatial statistics at a whole-brain level and within regions of interest to compare the white matter correlates of callous-unemotional traits in female vs. male youths with conduct disorder, in a sample (n = 124) recruited through a multi-site protocol. A sex-specific association between callous-unemotional traits and white matter was found in the left uncinate fasciculus, where callous-unemotional traits were positively associated with axial diffusivity in males, while an opposite pattern was found in females. These findings are in line with previous studies suggesting that the uncinate fasciculus is a key tract implicated in the development of psychopathy, but also add to recent evidence showing that sexual dimorphism needs to be taken into account when examining the structural correlates of mental disorders in general, and callous-unemotional traits in conduct disorder in particular.

Original languageEnglish
JournalBrain imaging and behavior
Early online date23 Aug 2021
Publication statusE-pub ahead of print - 23 Aug 2021

Bibliographical note

Funding Information:
This study was funded by the European Union’s Seventh Framework Programme for research, technological development and demonstration (FP7/2007-2013) under Grant Agreement no° 602407 (FemNAT-CD; coordinator: Christine M. Freitag). During the writing-up of the manuscript, Stephane A. De Brito was supported by a short-term Invitational Fellowship from the Japanese Society for the Promotion of Science (JSPS - S19103) and an International Academic Fellowship from the Leverhulme Trust (IAF-2019-032).The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Dr. Raschle has received grant support as a Jacobs Foundation Early Career Fellow 2017-2019 (grant no. 2016 1217 13). Prof. Stadler has received royalties for a book on aggression. Prof. Konrad has received speaker fees from Shire Pharmaceuticals and Medice. Prof. Freitag has received royalties for books on Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder. She has served as consultant to Desitin and Roche. Dr. De Brito has received speaker fees from the Child Mental Health Centre and the Centre for Integrated Molecular Brain Imaging. Drs. Gonzalez-Madruga, Rogers, Kohls, Fairchild, Villemonteix and Ms. Courbet report no biomedical financial interests or potential conflicts of interest.


  • Callous-unemotional traits
  • Conduct disorder
  • Diffusion tensor imaging (DTI)
  • FemNAT-CD
  • Sex differences
  • Uncinate fasciculus

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Behavioral Neuroscience


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