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

Gonzalez-Madruga, K., Rogers, J., Toschi, N. , Riccelli, R., Smaragdi, A., Puzzo, I. ORCID: 0000-0002-4480-5519, Clanton, R., Andersson, J., Baumann, S., Kohls, G., Raschle, N., Fehlbaum, L. V., Menks, W. M., Stadler, C., Konrad, K., Freitag, C. M., De Brito, S. A., Sonuga-Barke, E. J. S. & Fairchild, G. (2019). White matter microstructure of the extended limbic system in male and female youth with conduct disorder. Psychological Medicine, 50(1), pp. 58-67. doi: 10.1017/s0033291718003951


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 with typically developing controls.

We acquired diffusion-weighted magnetic resonance imaging 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 cingulum (RSC), parahippocampal and subgenual cingulum], and the fornix were performed and measures of fractional anisotropy (FA) and hindrance-modulated orientational anisotropy (HMOA) were analysed.

The CD group had lower FA and HMOA in the right RSC 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.

Our results highlight the importance of considering sex when studying the neurobiological basis of CD. Sex differences in RSC connectivity may contribute to sex differences in the clinical presentation of CD.

Publication Type: Article
Additional Information: This article has been published in a revised form in Psychological Medicine This version is free to view and download for private research and study only. Not for re-distribution, re-sale or use in derivative works. © Cambridge University Press 2019.
Publisher Keywords: Conduct disorder, callous-unemotional traits, spherical deconvolution, tractography, ADHD, white matter, diffusion tensor imaging (DTI), sex differences
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Departments: School of Health & Psychological Sciences > Psychology
SWORD Depositor:
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