Karen González-Madruga1, Jack Rogers2, Nicola Toschi3, Roberta Riccelli1, Areti Smaragdi4, Ignazio Puzzo5, Roberta Clanton2, Jesper Andersson6, Sarah Baumann7, Gregor Kohls7, Nora Raschle8, Lynn Fehlbaum8, Willeke Menks8, Christina Stadler8, Kerstin Konrad7, Christine M Freitag9, Stephane A De Brito2, Edmund Sonuga-Barke10, Graeme Fairchild11. 1. Department of Psychology, University of Southampton, Southampton, UK. 2. School of Psychology and Birmingham University Imaging Centre, University of Birmingham, Birmingham, UK. 3. Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome, Italy. 4. Centre for Addiction and Mental Health, Toronto, Canada. 5. West London Mental Health Trust, Broadmoor High Secure Hospital, London, UK. 6. FMRIB, John Radcliffe Hospital, University of Oxford, Oxford, UK. 7. Department of Child and Adolescent Psychiatry, Child Neuropsychology Section, Psychosomatics and Psychotherapy, University Hospital RWTH Aachen, Aachen, Germany. 8. Department of Child and Adolescent Psychiatry, Psychiatric University Clinics and University of Basel, Basel, Switzerland. 9. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany. 10. Child and Adolescent Psychiatry Department, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK. 11. Department of Psychology, University of Bath, Bath, UK.
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 with typically developing controls. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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 with typically developing controls. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Entities:
Keywords:
ADHD; callous-unemotional traits; conduct disorder; diffusion tensor imaging; sex differences; spherical deconvolution; tractography; white matter