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

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

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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 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.

Original language	English
Pages (from-to)	58-67
Journal	Psychological Medicine
Volume	50
Issue number	1
Early online date	30 Jan 2019
DOIs	https://doi.org/10.1017/S0033291718003951
Publication status	Published - Jan 2020

Keywords

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

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Checked for eligibility: 20/12/2018 This paper has been accepted for publication and will appear in a revised form in Psychological Medicine (See: https://www.cambridge.org/core/journals/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
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Cite this

Gonzalez-Madruga, K., Rogers, J., Toschi, N., Riccelli, R., Smaragdi, A., Puzzo, I., Clanton, R., Anderson, J., Baumann, S., Kohls, G., Raschle, N. M., Fehlbaum, L. V., Menks, W. M., Stadler, C., Konrad, K., Freitag, C. M., De Brito, S., 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. Advance online publication. 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 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.",

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

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

year = "2020",

month = jan,

doi = "10.1017/S0033291718003951",

language = "English",

volume = "50",

pages = "58--67",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

number = "1",

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Gonzalez-Madruga, K, Rogers, J, Toschi, N, Riccelli, R, Smaragdi, A, Puzzo, I, Clanton, R, Anderson, J, Baumann, S, Kohls, G, Raschle, NM, Fehlbaum, LV, Menks, WM, Stadler, C, Konrad, K, Freitag, CM, De Brito, S, 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 - Gonzalez-Madruga, Karen

AU - Rogers, Jack

AU - Toschi, Nicola

AU - Riccelli, Roberta

AU - Smaragdi, Areti

AU - Puzzo, Ignazio

AU - Clanton, Roberta

AU - Anderson, Jesper

AU - Baumann, Sarah

AU - Kohls, Gregor

AU - Raschle, Nora Maria

AU - Fehlbaum, Lynn Valérie

AU - Menks, Willeke Martine

AU - Stadler, Christina

AU - Konrad, Kerstin

AU - Freitag, Christine M.

AU - De Brito, Stephane

AU - Sonuga-Barke, Edmund

AU - Fairchild, Graeme

PY - 2020/1

Y1 - 2020/1

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 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.

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 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.

KW - ADHD

KW - callous-unemotional traits

KW - conduct disorder

KW - diffusion tensor imaging

KW - sex differences

KW - spehrical deconvolution

KW - tractography

KW - white matter

UR - http://www.scopus.com/inward/record.url?scp=85060802699&partnerID=8YFLogxK

U2 - 10.1017/S0033291718003951

DO - 10.1017/S0033291718003951

M3 - Article

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

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