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.
