Substance abuse may be a risk factor for earlier onset of Huntington disease

Environmental factors may contribute as much as one-third of the variance in Huntington disease (HD) age of onset. Substance abuse is a risk factor for other neurodegenerative disorders; however, whether substance abuse influences HD age of onset is not well established. This study investigated the relationships between alcohol, drug, and tobacco abuse and HD age of onset in 136 participants with symptomatic HD. CAG repeat length was used as a covariate in all analyses, as it represents the most significant determinant of HD age of onset. The relationship between substance abuse, HD age of onset, and sex was also examined, as women may experience greater medical harm from substance abuse. Lifetime alcohol abuse and lifetime drug abuse were associated with earlier age of HD onset; a similar trend was seen for current tobacco abuse. For women, lifetime alcohol abuse was associated with earlier onset of HD, with a similar trend for lifetime drug abuse. However, alcohol, drug, and tobacco abuse were not significantly associated with age of onset in men. Further work is needed to determine whether substance abuse is a causative risk factor for earlier onset of HD, and why the environmental factors associated with age of onset vary by sex.