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

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

BackgroundPrevious 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.MethodsWe 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.ResultsThe 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.ConclusionsOur 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.

ADHD, callous-unemotional traits, conduct disorder, diffusion tensor imaging, sex differences, spherical deconvolution, tractography, white matter
0033-2917
González-Madruga, Karen
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Rogers, Jack
8844ca15-f92f-4005-9e72-fea8423f7561
Toschi, Nicola
6d782adc-5749-422b-a98e-4f5fd9121152
Riccelli, Roberta
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Smaragdi, Areti
b090586a-a5c3-4ec0-b05e-167a5a0f4543
Puzzo, Ignazio
8d08d90f-23a2-4377-9c1f-984dade361b1
Clanton, Roberta
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Andersson, Jesper
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Baumann, Sarah
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Kohls, Gregor
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Raschle, Nora
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Fehlbaum, Lynn
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Menks, Willeke
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Stadler, Christina
ee3bd6ab-e3fe-436b-987d-266764f4acde
Konrad, Kerstin
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Freitag, Christine M.
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De Brito, Stephane A.
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Sonuga-Barke, Edmund
bc80bf95-6cf9-4c76-a09d-eaaf0b717635
Fairchild, Graeme
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González-Madruga, Karen
3e194679-da6d-4392-9668-440541e4952f
Rogers, Jack
8844ca15-f92f-4005-9e72-fea8423f7561
Toschi, Nicola
6d782adc-5749-422b-a98e-4f5fd9121152
Riccelli, Roberta
17dc2394-bc7c-4480-9cdf-e21a7a503061
Smaragdi, Areti
b090586a-a5c3-4ec0-b05e-167a5a0f4543
Puzzo, Ignazio
8d08d90f-23a2-4377-9c1f-984dade361b1
Clanton, Roberta
25d1a52d-40e4-4fbb-8630-eec8642ad7d7
Andersson, Jesper
2568e234-7b39-40a0-a8bd-6c2f8329190b
Baumann, Sarah
2f5c1fd6-6176-49ea-9033-470e057e0fa6
Kohls, Gregor
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Raschle, Nora
b35b8bf8-f5a9-453e-b326-f4a267493be0
Fehlbaum, Lynn
85ff234a-161e-4fec-8f7e-0304600fbec1
Menks, Willeke
19cd53c6-2336-4b1e-ba61-7100baf8f5c0
Stadler, Christina
ee3bd6ab-e3fe-436b-987d-266764f4acde
Konrad, Kerstin
327d1cf7-6ccd-4f2a-8391-6bbf9e4f6905
Freitag, Christine M.
05f89bf2-49e2-4803-8c7e-3f4d25bf79d8
De Brito, Stephane A.
6dec1536-9ab4-4c4e-afbc-dd02d510bd98
Sonuga-Barke, Edmund
bc80bf95-6cf9-4c76-a09d-eaaf0b717635
Fairchild, Graeme
f99bc911-978e-48c2-9754-c6460666a95f

González-Madruga, Karen, Rogers, Jack, Toschi, Nicola, Riccelli, Roberta, Smaragdi, Areti, Puzzo, Ignazio, Clanton, Roberta, Andersson, Jesper, Baumann, Sarah, Kohls, Gregor, Raschle, Nora, Fehlbaum, Lynn, Menks, Willeke, Stadler, Christina, Konrad, Kerstin, Freitag, Christine M., De Brito, Stephane A., Sonuga-Barke, Edmund and Fairchild, Graeme (2019) White matter microstructure of the extended limbic system in male and female youth with conduct disorder. Psychological Medicine. (doi:10.1017/S0033291718003951).

Record type: Article

Abstract

BackgroundPrevious 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.MethodsWe 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.ResultsThe 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.ConclusionsOur 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.

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More information

Accepted/In Press date: 4 December 2018
e-pub ahead of print date: 30 January 2019
Keywords: ADHD, callous-unemotional traits, conduct disorder, diffusion tensor imaging, sex differences, spherical deconvolution, tractography, white matter

Identifiers

Local EPrints ID: 430590
URI: http://eprints.soton.ac.uk/id/eprint/430590
ISSN: 0033-2917
PURE UUID: b7ca1857-182a-45ef-aa5f-57448932ecc0
ORCID for Graeme Fairchild: ORCID iD orcid.org/0000-0001-7814-9938

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Date deposited: 03 May 2019 16:30
Last modified: 07 Oct 2020 00:15

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Contributors

Author: Karen González-Madruga
Author: Jack Rogers
Author: Nicola Toschi
Author: Roberta Riccelli
Author: Areti Smaragdi
Author: Ignazio Puzzo
Author: Roberta Clanton
Author: Jesper Andersson
Author: Sarah Baumann
Author: Gregor Kohls
Author: Nora Raschle
Author: Lynn Fehlbaum
Author: Willeke Menks
Author: Christina Stadler
Author: Kerstin Konrad
Author: Christine M. Freitag
Author: Stephane A. De Brito
Author: Edmund Sonuga-Barke
Author: Graeme Fairchild ORCID iD

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