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J Huntingtons Dis. 2015;4(3):239-49. doi: 10.3233/JHD-150160.

Neuropsychiatry and White Matter Microstructure in Huntington's Disease.

Author information

1
Wellcome Trust Centre for Neuroimaging, UCL, London, UK.
2
Institute of Cognitive Neuroscience, University College London, UK.
3
Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
4
Developmental Imaging and Biophysics Section, UCL Institute of Child Health, London, UK.
5
Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester and Manchester Academic Health Science Centre, Manchester, UK.
6
Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
7
Department of Computer Science and Centre for Medical Image Computing, UCL, London, UK.
8
Department of Neurology, University of Ulm, Ulm, Germany.
9
APHP Department of Genetics, Groupe Hospitalier Pitié-Salpêtrière, and Institut du Cerveau et de la Moelle, INSERM U1127, CNRS UMR7225, Sorbonne Universités - UPMC Université Paris VI UMR_S1127, Paris, France.
10
Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
11
Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
12
Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.
13
Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA.
14
National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.

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.

KEYWORDS:

Huntington’s disease; apathy; depression; diffusion tensor imaging; irritability

PMID:
26443926
PMCID:
PMC4684097
DOI:
10.3233/JHD-150160
[Indexed for MEDLINE]
Free PMC Article

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