This study focuses on neurodegenerative diseases inherited in an autosomal dominant manner for which offspring are 50% at-risk of disease. Being at-risk of a genetic neurodegenerative disease has...Show moreThis study focuses on neurodegenerative diseases inherited in an autosomal dominant manner for which offspring are 50% at-risk of disease. Being at-risk of a genetic neurodegenerative disease has been shown to impact psychological well-being as some studies have reported significant levels of anxiety and depression in mutation carriers. Other studies have found no significant psychological impact in mutation carriers. In addition to conflicting results, few studies have examined the psychological impact in those atrisk before predictive-testing. The aim of this study was to examine the effect of being 50% at risk of an autosomal dominant neurodegenerative disease, defined by having a positive family history, on depression and anxiety as compared to healthy controls with no family history of dominant neurodegenerative disease. Additionally, we aimed to examine levels of depression and anxiety in different at-risk awareness groups (mutation carrier, mutation non-carrier or unaware) and different types of disease (Huntington’s disease and “Other”, e.g., familial Alzheimer’s disease and frontotemporal dementia) compared to healthy controls. Seventy-two articles were included in the systematic review, 10 articles were included in the depression meta-analysis and seven articles were included for the anxiety meta-analysis. The systematic review showed that some studies reported significantly higher levels of anxiety and depression in at-risk individuals, particularly mutation carriers, compared to controls while other studies reported no significant difference. The systematic review also showed that; a) mutation non-carriers and partners of those at-risk were used as healthy controls; b) studies used similar instruments to measure depression and anxiety; and c) most studies were on Huntington’s disease. The meta-analysis for depression showed that those at-risk do experience significantly higher levels of depression compared to healthy controls (p = .05). The anxiety meta-analysis was non-significant. This study highlights the psychological needs for individuals at-risk and suggests future research to have; a) healthy controls that do not include non-mutation carriers and partners of those at-risk; b) better instruments to measure anxiety and depression in those at-risk; and c) to examine other neurodegenerative diseases in addition to Huntington’s disease.Show less