Plasma Cytokine Levels in Relation to Neuropsychiatric Symptoms and Cognitive Dysfunction in Huntington's disease.

BACKGROUND: In Huntington's disease (HD) the innate immune system is activated, as reflected by increased plasma levels of different cytokines. OBJECTIVE: To explore whether increased cytokine levels are associated with neuropsychiatric symptoms and cognitive dysfunction in HD mutation carriers. METHOD: Plasma cytokine levels of TNF-alpha, interleukin (IL)-1ra, IL-1ß, IL-5, IL-6, IL-8 and Il-10 were assessed in 124 HD mutation carriers at two time points 2 years apart (totalling 214 observations). Using multilevel regression analysis, cytokines were analysed in relation to neuropsychiatric symptoms and cognitive dysfunction. Depressed mood was assessed with the depression subscale of the Problem Behaviours Assessment (PBA), apathy with the Apathy Scale, and irritability with the Irritability Scale. Cognitive functioning was assessed using the Mini-Mental State Examination (MMSE) and a battery of executive cognitive functioning tests, aggregated into an executive cognitive functioning (ExCog) score. RESULTS: Inverse associations were found in adjusted models between IL-6 and ExCog score (ß= -0.114; p = 0.01) and between IL-1ra and ExCog score (ß= -0.110; p = 0.02). No associations between cytokine levels and any of the other neuropsychiatric symptom scores remained statistically significant in adjusted models. CONCLUSION: Higher plasma levels of IL-6 and IL-1ra are weakly associated with cognitive dysfunction in HD, but not with other neuropsychiatric symptoms.

Irritability in Huntington's disease.

Irritability is a frequent neuropsychiatric symptom in patients with Huntington's disease (HD). The Irritability Scale (IS) and the irritability factor of the Problem Behaviours Assessment (PBA) was used to assess irritability among 130 HD mutation carriers and 43 verified non-carriers. The IS was tested using receiver operating characteristic analysis against different cut-offs of the PBA irritability factor. A robust IS cut-off score of ≥14 points was found indicating that 45 (35%) of the 130 mutation carriers were irritable vs. 4 (9%) of the 43 non-carriers (P=0.001). The level of agreement between self-report and informant-report IS was of moderate strength (intraclass correlation=0.61). Using univariate and multivariate regression analyses, independent correlates of irritability were being married/living together (P=0.02), CAG repeat length (P=0.01), and use of benzodiazepines (P=0.008). Using the same model with the informant's irritability score, use of benzodiazepines was the only significant independent correlate of irritability (P=0.005). Irritability is a prominent symptom of HD and can be reliably assessed with the IS using a cut-off score ≥14 points. Although it is unclear whether benzodiazepine use causes irritability, or irritability leads to the prescription of benzodiazepines, clinical evaluation with respect to the use of benzodiazepines in HD warrants attention.