Associations of Blood Inflammatory Cytokines and Hair Cortisol with Depression Symptoms and Cognitive Functioning in Huntington’s Disease

Abstract

AbstractBackgroundHuntington’s disease (HD) is an inherited neurodegenerative disease involving progressive motor abnormalities, cognitive decline, and psychiatric disturbances. Depression and cognitive difficulties are among the most impactful symptoms of HD, yet the pathogenesis of these symptoms is not fully understood. HD involves low-level chronic inflammation and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which are linked to depression and cognitive impairment in non-HD populations. However, previous research on the relationships of these pathologies with depression and cognition in HD is limited and inconsistent.MethodsFifty-three adults with the HD gene expansion (30 pre-manifest, 23 manifest) completed measures of depression and cognitive functioning. Forty-eight out of 53 participants provided hair samples for quantification of cortisol, and 34 participants provided blood samples for quantification of peripheral inflammatory cytokines. We examined the associations of four cytokines (interleukin (IL)-6, IL-10, IL-1β, and tumour necrosis factor (TNF)-α) and cortisol levels with depression and cognitive scores.ResultsIn unadjusted models, higher levels of plasma IL-6, IL-10, and TNF-α correlated with higher depression scores, and higher levels of IL-10 and TNF-α correlated with poorer cognitive performance. After controlling for age, sex, and body mass index, only the correlations of IL-10 with depression and cognitive performance remained significant. No correlations were evident with hair cortisol.ConclusionsPeripheral inflammation is associated with depression symptoms and cognitive impairment in HD. Our findings suggest that interactions between the immune and nervous systems are important in HD, and that inflammatory cytokines may be suitable as therapeutic targets for future clinical trials in HD.