White matter microstructure of the extended limbic system in male and female youth with conduct disorder

Karen Gonzalez-Madruga, Jack Rogers, Nicola Toschi, Roberta Riccelli, Areti Smaragdi, Ignazio Puzzo, Roberta Clanton, Jesper Anderson, Sarah Baumann, Gregor Kohls, Nora Maria Raschle, Lynn Valérie Fehlbaum, Willeke Martine Menks, Christina Stadler, Kerstin Konrad, Christine M. Freitag, Stephane De Brito, Edmund Sonuga-Barke, Graeme Fairchild

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Background: Previous studies of conduct disorder (CD) have reported structural and functional alterations in the limbic system. However, the white matter tracts that connect limbic regions have not been comprehensively studied. The uncinate fasciculus (UF), a tract connecting limbic to prefrontal regions, has been implicated in CD. However, CD-related alterations in other limbic tracts, such as the cingulum and the fornix, have not been investigated. Furthermore, few studies have examined the influence of sex and none have been adequately powered to test whether the relationship between CD and structural connectivity differs by sex. We examined whether adolescent males and females with CD exhibit differences in structural connectivity compared to typically-developing controls.

Methods: We acquired diffusion-weighted MRI data from 101 adolescents with CD (52 females) and 99 controls (50 females). Data were processed for deterministic spherical deconvolution tractography. Virtual dissections of the UF, the three subdivisions of the cingulum (retrosplenial, parahippocampal and subgenual cingulum), and the fornix were performed and measures of fractional anisotropy (FA) and hindrance-modulated orientational anisotropy (HMOA) were analysed.

Results: The CD group had lower FA and HMOA in the right retrosplenial cingulum tract relative to controls. Importantly, these effects were moderated by sex - males with CD significantly lower FA compared to male controls, whereas CD and control females did not differ.

Conclusions: Our results highlight the importance of considering sex when studying the neurobiological basis of CD. Sex differences in retrosplenial cingulum connectivity may contribute to sex differences in the clinical presentation of CD.
Original languageEnglish
Pages (from-to)58-67
JournalPsychological Medicine
Issue number1
Early online date30 Jan 2019
Publication statusPublished - Jan 2020


  • ADHD
  • callous-unemotional traits
  • conduct disorder
  • diffusion tensor imaging
  • sex differences
  • spehrical deconvolution
  • tractography
  • white matter


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