Abstract
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.
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 language | English |
|---|---|
| Pages (from-to) | 58-67 |
| Number of pages | 10 |
| Journal | Psychological Medicine |
| Volume | 50 |
| Issue number | 1 |
| Early online date | 30 Jan 2019 |
| DOIs | |
| Publication status | Published - 1 Jan 2020 |
Bibliographical note
Funding Information:for taking part in this study. We also thank Dr Flavio Dell’Acqua for his guidance and advice in this study, and Dr Etta Howells for providing training in white matter tract dissection. Karen Gonzalez-Madruga was partly funded by a Ph.D. studentship from the National Council of Science and Technology (CONACYT), Mexico.
Funding Information:
Financial support. This study was funded by the European Commission’s Seventh Framework Programme for research, technological development and demonstration (FP7/ 2007–2013) under Grant Agreement no. 602407 (FemNAT-CD; coordinator: Professor Christine Freitag, Goethe University).
Funding Information:
Conflict of interest. Professor Freitag receives royalties for books on attention-deficit/hyperactivity disorder and autism spectrum disorder. She has served as consultant to Desitin and Roche. Professor Sonuga-Barke has received speaker fees, consultancy, research funding and conference support from Shire Pharma. Speaker fees from Janssen Cilag, consultancy from Neurotech solutions, Aarhus University, Copenhagen University and Berhanderling, Skolerne, Copenhagen, KU Leuven. Book royalties from OUP and Jessica Kingsle. Edmund Sonuga-Barke has been awarded grants from the MRC, ESRC, Wellcome Trust, Solent NHS Trust, European Commission, Child Health Research Foundation New Zealand, NIHR, Nuffield Foundation, Fonds Wetenschappelijk Onderzoek-Vlan-deren (FWO) and MQ – Transforming Mental Health. Dr Fairchild has received funding from the European Commission, the UK Medical Research Council, the National Council for Science and Technology (CONACYT), the UK Economic and Social Research Council and Kids’ Company. Professor Konrad has received speaker fees from Shire Pharmaceuticals and Medice. Professor Stadler receives royalties for a book on aggression. Dr De Brito has received speaker fees from the Child Mental Health Centre and the Centre for Integrated Molecular Brain Imaging. All other co-authors declare no potential conflicts of interest.
Publisher Copyright:
Copyright © Cambridge University Press 2019.