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

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

doi:10.1017/S0033291718003951

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

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

^*Corresponding author for this work

Child & Adolescent Psychiatry

Research output: Contribution to journal › Article › peer-review

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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.

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	https://doi.org/10.1017/S0033291718003951
Publication status	Published - 6 Jan 2020

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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White matter microstructure of the extended limbic_SONUGA-BARKE_Publishedonline30January2019_GREEN AAMAccepted author manuscript, 1.55 MB

https://openaccess.city.ac.uk/id/eprint/21418/

Cite this

González-Madruga, K., Rogers, J., Toschi, N., Riccelli, R., Smaragdi, A., Puzzo, I., Clanton, R., Andersson, J., Baumann, S., Kohls, G., Raschle, N., Fehlbaum, L., Menks, W., Stadler, C., Konrad, K., Freitag, C. M., De Brito, S. A., Sonuga-Barke, E., & Fairchild, G. (2020). White matter microstructure of the extended limbic system in male and female youth with conduct disorder. Psychological Medicine, 50(1), 58-67. https://doi.org/10.1017/S0033291718003951

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

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.",

keywords = "ADHD, callous-unemotional traits, conduct disorder, diffusion tensor imaging, sex differences, spherical deconvolution, tractography, white matter",

author = "Karen Gonz{\'a}lez-Madruga and Jack Rogers and Nicola Toschi and Roberta Riccelli and Areti Smaragdi and Ignazio Puzzo and Roberta Clanton and Jesper Andersson and Sarah Baumann and Gregor Kohls and Nora Raschle and Lynn Fehlbaum and Willeke Menks and Christina Stadler and Kerstin Konrad and Freitag, {Christine M.} and {De Brito}, {Stephane A.} and Edmund Sonuga-Barke and Graeme Fairchild",

year = "2020",

month = jan,

day = "6",

doi = "10.1017/S0033291718003951",

language = "English",

volume = "50",

pages = "58--67",

journal = "Psychological Medicine",

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González-Madruga, K, Rogers, J, Toschi, N, Riccelli, R, Smaragdi, A, Puzzo, I, Clanton, R, Andersson, J, Baumann, S, Kohls, G, Raschle, N, Fehlbaum, L, Menks, W, Stadler, C, Konrad, K, Freitag, CM, De Brito, SA, Sonuga-Barke, E & Fairchild, G 2020, 'White matter microstructure of the extended limbic system in male and female youth with conduct disorder', Psychological Medicine, vol. 50, no. 1, pp. 58-67. https://doi.org/10.1017/S0033291718003951

TY - JOUR

T1 - White matter microstructure of the extended limbic system in male and female youth with conduct disorder

AU - González-Madruga, Karen

AU - Rogers, Jack

AU - Toschi, Nicola

AU - Riccelli, Roberta

AU - Smaragdi, Areti

AU - Puzzo, Ignazio

AU - Clanton, Roberta

AU - Andersson, Jesper

AU - Baumann, Sarah

AU - Kohls, Gregor

AU - Raschle, Nora

AU - Fehlbaum, Lynn

AU - Menks, Willeke

AU - Stadler, Christina

AU - Konrad, Kerstin

AU - Freitag, Christine M.

AU - De Brito, Stephane A.

AU - Sonuga-Barke, Edmund

AU - Fairchild, Graeme

PY - 2020/1/6

Y1 - 2020/1/6

N2 - 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.

AB - 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.

KW - ADHD

KW - callous-unemotional traits

KW - conduct disorder

KW - diffusion tensor imaging

KW - sex differences

KW - spherical deconvolution

KW - tractography

KW - white matter

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U2 - 10.1017/S0033291718003951

DO - 10.1017/S0033291718003951

M3 - Article

AN - SCOPUS:85060802699

SN - 0033-2917

VL - 50

SP - 58

EP - 67

JO - Psychological Medicine

JF - Psychological Medicine

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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