A systematic review and meta-analysis of depression and apathy frequency in adult-onset Huntington’s disease

Depression and apathy are associated with decreased functional capacity in Huntington's disease (HD) but frequency of depression and apathy in HD is largely unknown. Systematic literature searching was conducted across 21 databases until 30 June 2021. Inclusion criteria was limited to clinician-rated assessments of depression and apathy and adult-onset HD. Inverse-variance heterogeneity meta-analyses were conducted exploring depression and apathy frequency within individuals from families affected by HD, and within individuals with confirmed HD gene-positive status. Screening identified 289 articles for full-text review; nine remained for meta-analysis. Depression frequency in the lifetime in adults affected by or at-risk for HD was 38%, I2 = 99%. Apathy frequency in the lifetime in adults affected by or at-risk for HD was 40%, I2 = 96%. The robustness of the findings improved when limiting the analysis to gene-positive individuals only where apathy was found to be slightly more common than depression, 48% and 43% respectively. Future studies may consider reporting results from juvenile-onset HD and adult-onset HD cohorts separately to further explore phenotypic profiles.