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Investigating the fronto-limbic and hypothalamic-pituitary-adrena axis systems in conduct disorder

Investigating the fronto-limbic and hypothalamic-pituitary-adrena axis systems in conduct disorder
Investigating the fronto-limbic and hypothalamic-pituitary-adrena axis systems in conduct disorder
In this thesis, I report studies investigating the neurobiology of conduct disorder (CD) – a disorder diagnosed in children and adolescents who display a persistent pattern of disruptive and aggressive behaviour. My particular focus is on the role of frontal, limbic and hypothalamic-pituitary-adrenal (HPA) axis systems, and especially whether CD-related alterations in these systems differ between males and females. A range of different imaging techniques were applied to data from the Neurobiological and Treatment of Adolescent Female Conduct Disorder study (Fem-NAT-CD). In study 1 (Chapter 4), we employed surface-based morphometry techniques to assess frontal and limbic (cortical and subcortical) brain structures. Similar patterns of CD-related related reductions in cortical volume, thickness, and surface area in the superior frontal gyrus were seen in both sexes. The second study (Chapter 5) assessed the shape of subcortical limbic structures. Youths with CD exhibited shape deformations (i.e., inward) in the shell of the nucleus accumbens compared to controls, independent of sex. The third study (Chapter 6) used spherical deconvolution basedtractography and virtually dissected key fronto-limbic white matter tracts, namely: the uncinate fasciculus, fornix, and the subgenual, retrosplenial and parahippocampal bundles of the cingulum. We observed reduced fractional anisotropy in the retrosplenial cingulum in the CD group relative to healthy controls. However, this result was moderated by sex: males with CD showed reduced, while females with CD showed increased fractional anisotropy compared to sex-matched healthy controls. Finally, we investigated sex differences in HPA axis function (Chapter 7) by measuring cortisol response during the Trier Social Stress Test for Children. Both males and females with CD showed blunted cortisol response to stress, and such effects were not explained by low levels of self-rated fear or anxiety. In a small, proof of concept analysis we observed a positive correlation between cortical volume of the superior frontal gyrus and cortisol reactivity. I conclude that the neurobiological basis of CD is relatively similar in males and females. Thus, previous findings in males with CD may also apply for females with CD. Suggestions for future research are presented and clinical implications are discussed.
University of Southampton
González-Madruga, Karen Denise
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González-Madruga, Karen Denise
3e194679-da6d-4392-9668-440541e4952f
Fairchild, Graeme
f99bc911-978e-48c2-9754-c6460666a95f
Sonuga-barke, Edmund J
bc80bf95-6cf9-4c76-a09d-eaaf0b717635

González-Madruga, Karen Denise (2018) Investigating the fronto-limbic and hypothalamic-pituitary-adrena axis systems in conduct disorder. University of Southampton, Doctoral Thesis, 355pp.

Record type: Thesis (Doctoral)

Abstract

In this thesis, I report studies investigating the neurobiology of conduct disorder (CD) – a disorder diagnosed in children and adolescents who display a persistent pattern of disruptive and aggressive behaviour. My particular focus is on the role of frontal, limbic and hypothalamic-pituitary-adrenal (HPA) axis systems, and especially whether CD-related alterations in these systems differ between males and females. A range of different imaging techniques were applied to data from the Neurobiological and Treatment of Adolescent Female Conduct Disorder study (Fem-NAT-CD). In study 1 (Chapter 4), we employed surface-based morphometry techniques to assess frontal and limbic (cortical and subcortical) brain structures. Similar patterns of CD-related related reductions in cortical volume, thickness, and surface area in the superior frontal gyrus were seen in both sexes. The second study (Chapter 5) assessed the shape of subcortical limbic structures. Youths with CD exhibited shape deformations (i.e., inward) in the shell of the nucleus accumbens compared to controls, independent of sex. The third study (Chapter 6) used spherical deconvolution basedtractography and virtually dissected key fronto-limbic white matter tracts, namely: the uncinate fasciculus, fornix, and the subgenual, retrosplenial and parahippocampal bundles of the cingulum. We observed reduced fractional anisotropy in the retrosplenial cingulum in the CD group relative to healthy controls. However, this result was moderated by sex: males with CD showed reduced, while females with CD showed increased fractional anisotropy compared to sex-matched healthy controls. Finally, we investigated sex differences in HPA axis function (Chapter 7) by measuring cortisol response during the Trier Social Stress Test for Children. Both males and females with CD showed blunted cortisol response to stress, and such effects were not explained by low levels of self-rated fear or anxiety. In a small, proof of concept analysis we observed a positive correlation between cortical volume of the superior frontal gyrus and cortisol reactivity. I conclude that the neurobiological basis of CD is relatively similar in males and females. Thus, previous findings in males with CD may also apply for females with CD. Suggestions for future research are presented and clinical implications are discussed.

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Investigating the Fronto-limbic and Hypothalamic-Pituitary-Adrena; Axis Systems in Conduct Disorder - Version of Record
Available under License University of Southampton Thesis Licence.
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Published date: March 2018

Identifiers

Local EPrints ID: 422469
URI: http://eprints.soton.ac.uk/id/eprint/422469
PURE UUID: f0e5b323-b1d6-49e3-87cd-1289750bb7e0
ORCID for Graeme Fairchild: ORCID iD orcid.org/0000-0001-7814-9938

Catalogue record

Date deposited: 24 Jul 2018 16:30
Last modified: 14 Mar 2019 05:04

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