Neuropsychiatry and white matter microstructure in Huntington's Disease

Journal article


Gregory, Sarah L., Scahill, Rachael I., Seunarine, Kiran K., Stopford, Cheryl, Zhang, Hui, Zhang, Jiaying, Orth, Michael, Dürr, Alexandra, Roos, Raymund A. C., Langbehn, Douglas R., Long, Jeffrey D., Johnson, Hans, Rees, Geraint, Tabrizi, Sarah J., Craufurd, David I. O., Campbell, C., Campbell, Melissa, Labuschagne, Izelle, Milchman, C., ... Campbell, Colin. (2015) Neuropsychiatry and white matter microstructure in Huntington's Disease. Journal of Huntington's Disease. 4(3), pp. 239 - 249. https://doi.org/10.3233/JHD-150160
AuthorsGregory, Sarah L., Scahill, Rachael I., Seunarine, Kiran K., Stopford, Cheryl, Zhang, Hui, Zhang, Jiaying, Orth, Michael, Dürr, Alexandra, Roos, Raymund A. C., Langbehn, Douglas R., Long, Jeffrey D., Johnson, Hans, Rees, Geraint, Tabrizi, Sarah J., Craufurd, David I. O., Campbell, C., Campbell, Melissa, Labuschagne, Izelle, Milchman, C., Coleman, Allison J., Dar Santos, Rachelle C., Decolongon, J., Sturrock, A., Jauffret, Céline, Justo, Damian, Lehericy, Stephane, Marelli, Cecilia, Nigaud, Kevin, Valabrègue, Romain, Bechtel, Natalie, Bohlen, Stefan, van den Bogaard, Simon, Dumas, Eve M., Van der Grond, Jeroen, 't Hart, E. P., Arran, N., Callaghan, Jenny, Stopford, Cheryl, Cash, David, Crawford, H., Fox, Nick, Hobbs, Nicola Z., Lahiri, Nayana, Malone, Ian, Read, Joy, Say, Miranda Julia, Whitehead, Dean, Wild, E., Jones, R., Axelson, Eric, Queller, Sarah and Campbell, Colin
Abstract

Background: Neuropsychiatric symptoms in Huntington’s disease (HD) are often evident prior to clinical diagnosis. Apathy is highly correlated with disease progression, while depression and irritability occur at different stages of the disease, both before and after clinical onset. Little is understood about the neural bases of these neuropsychiatric symptoms and to what extent those neural bases are analogous to neuropsychiatric disorders in the general population.

Objective: We used Diffusion Tensor Imaging (DTI) to investigate structural connectivity between brain regions and any putative microstructural changes associated with depression, apathy and irritability in HD.

Methods: DTI data were collected from 39 premanifest and 45 early-HD participants in the Track-HD study and analysed using whole-brain Tract-Based Spatial Statistics. We used regression analyses to identify white matter tracts whose structural integrity (as measured by fractional anisotropy, FA) was correlated with HADS-depression, PBA-apathy or PBA-irritability scores in gene-carriers and related to cumulative probability to onset (CPO).

Results: For those with the highest CPO, we found significant correlations between depression scores and reduced FA in the splenium of the corpus callosum. In contrast, those with lowest CPO demonstrated significant correlations between irritability scores and widespread FA reductions. There was no significant relationship between apathy and FA throughout the whole brain.

Conclusions: We demonstrate that white matter changes associated with both depression and irritability in HD occur at different stages of disease progression concomitant with their clinical presentation.

KeywordsHuntington’s disease; diffusion tensor imaging; depression; irritability; apathy
Year2015
JournalJournal of Huntington's Disease
Journal citation4 (3), pp. 239 - 249
PublisherIOS Press
ISSN1879-6397
Digital Object Identifier (DOI)https://doi.org/10.3233/JHD-150160
Scopus EID2-s2.0-84961695910
Open accessOpen access
Page range239 - 249
Research GroupSchool of Philosophy
Publisher's version
Additional information

© 2015 – IOS Press and the authors. All rights reserved. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution License (CC-BY).

Place of publicationNetherlands
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