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
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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A comparison of executive function in Body Dysmorphic Disorder (BDD) and Obsessive-Compulsive Disorder (OCD)
Labuschagne, Izelle, Rossell, Susan, Dunai, Judith, Castle, David and Kyrios, Michael. (2013). A comparison of executive function in Body Dysmorphic Disorder (BDD) and Obsessive-Compulsive Disorder (OCD). Journal of Obsessive-Compulsive and Related Disorders. 2(3), pp. 257 - 262. https://doi.org/10.1016/j.jocrd.2013.05.003
Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex
Sripada, Chandra, Phan, Kinhluan, Labuschagne, Izelle, Welsh, Robert, Nathan, Pradeep and Wood, Amanda. (2013). Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex. International Journal of Neuropsychopharmacology (print). 16(2), pp. 255 - 260. https://doi.org/10.1017/S1461145712000533
Emotional face recognition deficits and medication effects in pre-manifest through stage-II Huntington's disease
Labuschagne, Izelle, Jones, Rebecca, Callaghan, Jenny, Whitehead, Daisy, Dumas, Eve, Say, Miranda, Hart, Ellen, Justo, Damian, Coleman, Allison, Dar Santos, Rachelle, Frost, Chris, Craufurd, David, Trabrizi, Sarah and Stout, Julie. (2013). Emotional face recognition deficits and medication effects in pre-manifest through stage-II Huntington's disease. Psychiatry Research. 207(1-2), pp. 118 - 126. https://doi.org/10.1016/j.psychres.2012.09.022
Emotional face recognition deficits and medication effects in pre-manifest through stage-II Huntington's disease
Labuschagne, Izelle, Jones, Rebecca, Callaghan, Jenny, Whitehead, Daisy, Dumas, Eve, Say, Miranda, Hart, Ellen, Justo, Damian, Coleman, Allison, Dar Santos, Rachelle, Frost, Chris, Craufurd, David, Tabrizi, Sarah and Stout, Julie. (2013). Emotional face recognition deficits and medication effects in pre-manifest through stage-II Huntington's disease. Psychiatry Research. 207(1-2), pp. 118 - 126. https://doi.org/10.1016/j.psychres.2012.09.022
Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex
Sripada, Chandra, Phan, Kinhluan, Labuschagne, Izelle, Welsh, Robert, Nathan, Pradeep and Wood, Amanda. (2013). Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex. International Journal of Neuropsychopharmacology. 16(2), pp. 255 - 260. https://doi.org/10.1017/S1461145712000533
Visual working memory impairment in premanifest gene-carriers and early Huntington's Disease
Dumas, Eve M., Say, Miranda Julia, Jones, Rebecca D., Labuschagne, Izelle, O'Regan, Alison M., Hart, Ellen P., van den Bogaard, Simon J. A., Queller, Sarah, Justo, Damian, Coleman, Allison J., dar Santos, Rachelle C., Durr, Alexandra, Leavitt, Blair R., Tabrizi, Sarah J., Roos, Raymund A. C. and Stout, Julie C.. (2012). Visual working memory impairment in premanifest gene-carriers and early Huntington's Disease. Journal of Huntington's Disease. 1(1), pp. 97 - 106. https://doi.org/10.3233/JHD-2012-120010
Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease
Stout, Julie, Jones, Rebecca, Labuschagne, Izelle, O'Regan, Alison, Say, Miranda, Dumas, Eve, Queller, Sarah, Justo, Damian, Dar Santos, Rachelle, Coleman, Allison, Hart, Ellen, Durr, Alexandra, Leavitt, Blair, Roos, Raymund, Langbehn, Doug, Tabrizi, Sarah J. and Frost, Chris. (2012). Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease. Journal of Neurology, Neurosurgery and Psychiatry. 83(7), pp. 687 - 694. https://doi.org/10.1136/jnnp-2011-301940
Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin
Labuschagne, Izelle, Phan, K. Luan, Wood, Amanda, Angstadt, Mike, Chua, Phyllis, Heinrichs, Markus, Stout, Julie C., Nathan, Pradeep J. and Pradeep,. (2012). Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin. International Journal of Neuropsychopharmacology (print). 15(7), pp. 883 - 896. https://doi.org/10.1017/S1461145711001489
Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease
Stout, Julie, Jones, Rebecca, Labuschagne, Izelle, O'Regan, Alison, Say, Miranda, Dumas, Eve, Queller, Sarah, Justo, Damian, Dar Santos, Rachelle, Coleman, Allison, Hart, Ellen, Durr, Alexandra, Leavitt, Blair, Roos, Raymund, Langbehn, Douglas, Tabrizi, Sarah J. and Frost, Chris. (2012). Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease. Journal of Neurology, Neurosurgery and Psychiatry. 83(7), pp. 687 - 694. https://doi.org/10.1136/jnnp-2011-301940
What the cognitive deficits in body dysmorphic disorder tell us about the underlying neurobiology: An investigation of three cases
Labuschagne, Izelle, Castle, David and Rossell, Susan L.. (2011). What the cognitive deficits in body dysmorphic disorder tell us about the underlying neurobiology: An investigation of three cases. International Journal of Cognitive Therapy. 4(1), pp. 21 - 33. https://doi.org/10.1521/ijct.2011.4.1.21
Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder
Labuschagne, Izelle, Phan, K. Luan, Wood, Amanda G., Angstadt, Mike, Chua, Phyllis, Heinrichs, Markus, Stout, Julie C. and Nathan, Pradeep. (2010). Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology. 35(12), pp. 2403 - 2413. https://doi.org/10.1038/npp.2010.123
Augmenting serotonin neurotransmission with citalopram modulates emotional expression decoding but not structural encoding of moderate intensity sad facial emotional stimuli: An event-related potential (ERP) investigation
Labuschagne, Izelle, Croft, Rodney, Phan, K. Luan and Nathan, Pradeep. (2010). Augmenting serotonin neurotransmission with citalopram modulates emotional expression decoding but not structural encoding of moderate intensity sad facial emotional stimuli: An event-related potential (ERP) investigation. Journal of Psychopharmacology. 24(8), pp. 1153 - 1164. https://doi.org/10.1177/0269881108097878
Executive function in body dysmorphic disorder
Dunai, Judith, Labuschagne, Izelle, Castle, David J., Kyrios, Michael and Rossell, Susan. (2010). Executive function in body dysmorphic disorder. Psychological Medicine. 40(9), pp. 1541 - 1548. https://doi.org/10.1017/S003329170999198X
An examination of delusional thinking and cognitive styles in body dysmorphic disorder
Labuschagne, Izelle, Castle, David J., Dunai, Judith, Kyrios, Michael and Rossell, Susan. (2010). An examination of delusional thinking and cognitive styles in body dysmorphic disorder. Australian and New Zealand Journal of Psychiatry. 44(8), pp. 706 - 712. https://doi.org/10.3109/00048671003671007
Evidence for modulation of facial emotional processing bias during emotional expression decoding by serotonergic and noradrenergic antidepressants: An event-related potential (ERP) study
Kerestes, Rebecca, Labuschagne, Izelle, Croft, Rodney, O'Neill, Barry, Bhagwagar, Zubin M., Phan, K Luan and Nathan, Pradeep. (2009). Evidence for modulation of facial emotional processing bias during emotional expression decoding by serotonergic and noradrenergic antidepressants: An event-related potential (ERP) study. Psychopharmacology. 202(4), pp. 621 - 634. https://doi.org/10.1007/s00213-008-1340-3