The neuroanatomy of subthreshold depressive symptoms in Huntington's disease: a combined diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) study

BACKGROUND: Depressivesymptoms are prominent psychopathological features of Huntington's disease(HD), making a negative impact on social functioning and well-being. METHOD: We compared the frequencies of a historyof depression, previous suicide attemptsand current subthreshold depressionbetween 61 early-stage HD participants and 40 matched controls. The HD group was then split based on the overall HD group's median Hospital Anxietyand Depression Scale- depressionscore into a group of 30 non- depressedparticipants (mean 0.8, s.d. = 0.7) and a group of 31 participants with subthreshold depressivesymptoms (mean 7.3, s.d. = 3.5) to explore the neuroanatomyunderlying subthreshold depressivesymptoms in HD using voxel-based morphometry(VBM) and diffusion tensor imaging (DTI). RESULTS: Frequencies of historyof depression, previous suicide attemptsor current subthreshold depressivesymptoms were higher in HD than in controls. The severity of current depressivesymptoms was also higher in HD, but not associated with the severity of HD motor signs or disease burden. Compared with the non- depressedHD group DTI revealed lower fractional anisotropy(FA) values in the frontal cortex, anterior cingulate cortex, insulaand cerebellum of the HD group with subthreshold depressivesymptoms. In contrast, VBM measures were similar in both HD groups. A historyof depression, the severity of HD motor signs or disease burdendid not correlate with FA values of these regions. CONCLUSIONS: Current subthreshold depressivesymptoms in early HD are associated with microstructural changes - without concomitant brain volume loss - in brain regions known to be involved in major depressivedisorder, but not those typically associated with HD pathology