Background Neuropsychiatric symptoms are a common feature of Huntington’s disease (HD). Despite are identifiable years before motor-based disease onset, little is known about the prevalence and significance of neuropsychiatric symptoms in pre-manifested (preHD) individuals.
Objectives To determine the prevalence and significance of a wide range of neuropsychiatric features in positive gene carriers far and near disease onset and how they compare to early symptomatic and healthy controls.
Methods Neurological, medication, cognitive and behavioural data were obtained from n = 129 gene positive and n = 101 healthy controls from the Spanish cohort of the Registry study. Participants were classified as preHD far (preHD-A; n = 34) and near (PreHD-B; n = 24) to disease onset, early-HD (n = 70) and healthy controls (n = 101). Frequency and severity of neuropsychiatric symptoms were addressed through the Problems Behaviour Assessment Scale in its short form (PBA-s).
Results Clinically meaningful depressive symptoms are present in in all the groups showing no significance differences. Apathy appeared in up to 32% of preHD-A linearly increasing in frequency and severity up to 62% in Early-HD. Meaningful symptoms of irritability and executive dysfunction appeared in both preHD-B and Early-HD groups. The probability for presenting clinically meaningful apathetic symptoms appeared 15 to 88 times higher in preHD-A and preHD-B respectively compared to healthy controls. More than half of the preHD-B also presented significant symptoms of irritability and executive dysfunction.
Discussion A wide range of neuropsychiatric symptoms are observable along the pre-manifested and early stage of HD. The frequency, severity and probability to develop meaningful apathetic symptoms linearly increases along disease stages. High prevalence of depressive symptoms in healthy controls should respond to the influence HD as a misrecognized environmental stressor. Longitudinal studies are needed to clarify the meaning of neuropsychiatric features in the earliest disease stages and the potential usefulness of apathy scores as early markers of disease progression.
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