Activation of the innate immune system has been postulated in the pathogenesis of Huntington's disease (HD). We studied serum concentrations of C-reactive protein (CRP) and low albumin as positive... Show moreActivation of the innate immune system has been postulated in the pathogenesis of Huntington's disease (HD). We studied serum concentrations of C-reactive protein (CRP) and low albumin as positive and negative acute-phase proteins in HD. Multivariate linear and logistic regression was used to study the association between acute-phase protein levels in relation to clinical, neuropsychiatric, cognitive, and psychotropic use characteristics in a cohort consisting of 122 HD mutation carriers and 42 controls at first biomarker measurement, and 85 HD mutation carriers and 32 controls at second biomarker measurement. Significant associations were found between acute-phase protein levels and Total Functioning Capacity (TFC) score, severity of apathy, cognitive impairment, and the use of antipsychotics. Interestingly, all significant results with neuropsychiatric symptoms disappeared after additional adjusting for antipsychotic use. High sensitivity CRP levels were highest and albumin levels were lowest in mutation carriers who continuously used antipsychotics during follow-up versus those that had never used antipsychotics (mean difference for CRP 1.4 SE mg/L; P=0.04; mean difference for albumin 3 SE g/L; P<0.001). The associations found between acute-phase proteins and TFC score, apathy, and cognitive impairment could mainly be attributed to the use of antipsychotics. This study provides evidence that HD mutation carriers who use antipsychotics are prone to develop an acute-phase response. Show less
Bouwens, J.A.; Hubers, A.A.M.; Duijn, E. van; Cobbaert, C.M.; Roos, R.A.C.; Mast, R.C. van der; Giltay, E.J. 2014
Activation of the innate immune system has been postulated in the pathogenesis of Huntington׳s disease (HD). We studied serum concentrations of C-reactive protein (CRP) and low albumin as positive... Show moreActivation of the innate immune system has been postulated in the pathogenesis of Huntington׳s disease (HD). We studied serum concentrations of C-reactive protein (CRP) and low albumin as positive and negative acute-phase proteins in HD. Multivariate linear and logistic regression was used to study the association between acute-phase protein levels in relation to clinical, neuropsychiatric, cognitive, and psychotropic use characteristics in a cohort consisting of 122 HD mutation carriers and 42 controls at first biomarker measurement, and 85 HD mutation carriers and 32 controls at second biomarker measurement. Significant associations were found between acute-phase protein levels and Total Functioning Capacity (TFC) score, severity of apathy, cognitive impairment, and the use of antipsychotics. Interestingly, all significant results with neuropsychiatric symptoms disappeared after additional adjusting for antipsychotic use. High sensitivity CRP levels were highest and albumin levels were lowest in mutation carriers who continuously used antipsychotics during follow-up versus those that had never used antipsychotics (mean difference for CRP 1.4 SE mg/L; P=0.04; mean difference for albumin 3 SE g/L; P<0.001). The associations found between acute-phase proteins and TFC score, apathy, and cognitive impairment could mainly be attributed to the use of antipsychotics. This study provides evidence that HD mutation carriers who use antipsychotics are prone to develop an acute-phase response. Show less
Hubers, A.A.M.; Duijn, E. van; Roos, R.A.C.; Craufurd, D.; Rickards, H.; Landwehrmeyer, G.B.; ... ; REGISTRY Investigators European Hu 2013
BACKGROUND: In Huntington's disease (HD) the risk of suicide is increased. Since suicidality may precede suicide, this study investigates prevalence, clinical associations and predictors of... Show moreBACKGROUND: In Huntington's disease (HD) the risk of suicide is increased. Since suicidality may precede suicide, this study investigates prevalence, clinical associations and predictors of suicidality in HD. METHODS: Suicidality was investigated in 152 mutation carriers and 56 non-carriers, and was considered present if the score on the item 'suicidal ideation' of the Problem Behaviours Assessment (PBA) was >1 point. After 2years, 100 mutation carriers who were free of suicidality at baseline were re-assessed. Associations and predictors of suicidality were analyzed using multivariate logistic regression analysis. RESULTS: Eleven (20%) pre-motor and 20 (20%) motor symptomatic mutation carriers were considered suicidal compared to none of the non-carriers. Cross-sectionally, suicidal mutation carriers were more likely to use antidepressants (odds ratio=5.3), were more often apathetic (OR=2.8), more often had a depressed mood according to the PBA (OR=5.9), and were more often diagnosed with a DSM-IV depression diagnosis (OR=4.7). Independent associations were more frequent use of antidepressants (OR=4.0) and presence of a depressed mood (OR=4.2). Longitudinally, depressed mood (OR=10.6) at baseline was the only independent predictor of suicidality at follow-up. LIMITATIONS: Selection bias might have occurred which could have affected the suicidality rate. CONCLUSION: It is important to screen both pre-motor and motor symptomatic HD mutation carriers for suicidality. The presence of a depressed mood is both associated with and predictive of suicidality in HD and assessment of depressed mood can help to identify individuals with increased risk for suicide. Show less
