BackgroundHuntington's disease (HD) is a hereditary neurodegenerative disease characterized by a combination of motor, cognitive, and mental health issues, with depression being the most common. Despite its importance, the relationship between depression and disease progression is still debatable.ObjectiveThe primary objective of this study was to examine the frequency of depression across different disease stages in individuals with HD. We also explored the associations between depression and other HD-related factors.MethodsThis systematic review comprehensively searched MEDLINE, APA PsycINFO, and Embase databases for studies on depression in individuals with HD. Pooled depression frequencies were calculated for premanifest and manifest HD. Depression was analyzed based on HD functional stages and diagnostic tools, alongside reviewing its association with various HD factors.ResultsWe assessed 6523 records and included 104 studies. Our meta-analyses revealed that the overall frequency of depression was higher in manifest HD compared to premanifest HD (0.38 vs. 0.23). However, the progression of depression did not follow a consistent pattern, with peaks occurring in earlier rather than later stages. Additionally, the frequency of depression was lower in studies using diagnostic criteria compared to those using clinical scales (0.25 vs. 0.42).ConclusionsOur findings showed that the rate of depression is high in HD and varies depending on the disease stage and the criteria used. This emphasizes the necessity for tailored and unified diagnostic criteria for depression in HD.