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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\u2010level chronic inflammation and dysregulation of the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis, which are linked to depression and cognitive impairment in non\u2010HD populations. However, previous research on the relationships of these pathologies with depression and cognition in HD is limited and inconsistent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifty\u2010three adults with the HD gene expansion (30 premanifest and 23 manifest) completed measures of depression and cognitive functioning. Forty\u2010eight 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]\u20106, IL\u201010, IL\u20101\u03b2, and tumor necrosis factor [TNF]\u2010\u03b1) and cortisol levels with depression and cognitive scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In unadjusted models, higher levels of plasma IL\u20106, IL\u201010, and TNF\u2010\u03b1 correlated with higher depression scores, and higher levels of IL\u201010 and TNF\u2010\u03b1 correlated with poorer cognitive performance. After controlling for age, sex, and body mass index, only the correlations of IL\u201010 with depression and cognitive performance remained significant. No correlations were evident with hair cortisol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretations<\/jats:title><jats:p>Peripheral 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 highlight the potential of chronic inflammation as a therapeutic target in early stages of HD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52016","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T04:25:14Z","timestamp":1707971114000},"page":"989-999","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Associations of inflammatory cytokines and cortisol with nonmotor features of Huntington's disease"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2458-865X","authenticated-orcid":false,"given":"Hiba","family":"Bilal","sequence":"first","affiliation":[{"name":"School of Psychological Sciences, and Turner Institute for Brain and Mental Health Monash University  Clayton Victoria 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