F060 Characterisation of neuropsychiatric features in young adult gene expansion carriers: insights from the Huntington’s disease young adult study (HD-YAS)

<h3>Background</h3> Neuropsychiatric symptoms are prevalent and commonly appear early in Huntington’s disease (HD). The HD Young Adult Study aims to characterise the HD phenotype ~24 years from predicted disease onset, in a unique cohort of gene expansion carriers (GECs) longitudinally evaluated at two visits (V1 and V2) ~4.5 years apart. <h3>Aims</h3> To assess the earliest changes in neuropsychiatric domains in GECs, compared to controls. <h3>Methods</h3> 154 participants were recruited over V1 and V2. V1 data collection (2017–2019) involved 131 participants (64 GECs, 67 controls), with an additional 23 participants (9 GECs, 14 controls) recruited during V2 (2022–2024); 103 participants had longitudinal data. Participants completed self-report neuropsychiatric questionnaires assessing depression, anxiety, apathy, impulsivity, sleep hygiene, obsessive-compulsive behaviour, frontal systems behaviours, and general health status. General least-square linear models were employed to evaluate group differences both cross-sectionally and longitudinally, with possible age and CAG-length-driven effects analysed within the GEC group. <h3>Results</h3> Cross-sectionally, GECs perceived a worse general health status compared to controls (FDR=0.096). Longitudinally, no significant differences between GECs and controls were observed (FDR&gt;0.35). However, within the GEC group, a decrease in subjective measures of obsessive-compulsive behaviours (FDR=0.107) and disinhibition over time (FDR=0.107) was evident when considering predicted years to disease onset. <h3>Conclusions</h3> GECs tended to perceive a worse general health status compared to controls. Reduced subjective self-report impulsivity scores might be attributed to brain maturation typical of younger cohorts, or an intentional portrayal by GECs. However, there is no significant decline in neuropsychiatric features over 4.5 years in this far-from-onset cohort.