The Clinical Picture of Psychosis in Manifest Huntington's Disease: A Comprehensive Analysis of the Enroll-HD Database

Background: Psychotic symptoms have been under-investigated in Huntington's disease (HD) and research is needed in order to elucidate the characteristics linked to the unique phenotype of HD patients presenting with psychosis.Objective: To evaluate the frequency and factors associated with psychosis in HD.Methods: Cross-sectional study including manifest individuals with HD from the Enroll-HD database. Both conventional statistical analysis (Stepwise Binary Logistic Regression) and five machine learning algorithms [Least Absolute Shrinkage and Selection Operator (LASSO); Elastic Net; Support Vector Machines (SVM); Random Forest; and class-weighted SVM] were used to describe factors associated with psychosis in manifest HD patients.Results: Approximately 11% of patients with HD presented history of psychosis. Logistic regression analysis indicated that younger age at HD clinical diagnosis, lower number of CAG repeats, history of [alcohol use disorders, depression, violent/aggressive behavior and perseverative/obsessive behavior], lower total functional capacity score, and longer time to complete trail making test-B were associated with psychosis. All machine learning algorithms were significant (chi-square p < 0.05) and capable of distinguishing individual HD patients with history of psychosis from those without a history of psychosis with prediction accuracy around 71–73%. The most relevant variables were similar to those found in the conventional analyses.Conclusions: Psychiatric and behavioral symptoms as well as poorer cognitive performance were related to psychosis in HD. In addition, psychosis was associated with lower number of CAG repeats and younger age at clinical diagnosis of HD, suggesting that these patients may represent a unique phenotype in the HD spectrum

Patient-Reported Value of a Standardized Welcome Letter for Huntington Disease Clinic

Communication is an essential component of patient satisfaction, which can be especially challenging in patients with neurobehavioral symptoms. As an effective form of communication, Patient Welcome Letter (PWL) should be designed in a way to cover a wide range of literacy. We designed a PWL for our Huntington Disease (HD) clinic using readability and suitability measures. Of the 80 patients that received the PWL, 47 filled out the survey. A majority of patients (\u3e90%) found the PWL clear, understandable, and well-organized. The PWL was deemed valuable overall by 91.4% of participants

Neuroimmunology of Huntington’s Disease: Revisiting Evidence from Human Studies

Huntington’s disease (HD) is a neurodegenerative disorder characterized by selective loss of neurons in the striatum and cortex, which leads to progressive motor dysfunction, cognitive decline, and psychiatric disorders. Although the cause of HD is well described—HD is a genetic disorder caused by a trinucleotide (CAG) repeat expansion in the gene encoding for huntingtin (HTT) on chromosome 4p16.3—the ultimate cause of neuronal death is still uncertain. Apart from impairment in systems for handling abnormal proteins, other metabolic pathways and mechanisms might contribute to neurodegeneration and progression of HD. Among these, inflammation seems to play a role in HD pathogenesis. The current review summarizes the available evidence about immune and/or inflammatory changes in HD. HD is associated with increased inflammatory mediators in both the central nervous system and periphery. Accordingly, there have been some attempts to slow HD progression targeting the immune system

Neuroimmunology of Huntington's Disease: Revisiting Evidence from Human Studies

Huntington's disease (HD) is a neurodegenerative disorder characterized by selective loss of neurons in the striatum and cortex, which leads to progressive motor dysfunction, cognitive decline, and psychiatric disorders. Although the cause of HD is well described-HD is a genetic disorder caused by a trinucleotide (CAG) repeat expansion in the gene encoding for huntingtin (HTT) on chromosome 4p16.3-the ultimate cause of neuronal death is still uncertain. Apart from impairment in systems for handling abnormal proteins, other metabolic pathways and mechanisms might contribute to neurodegeneration and progression of HD. Among these, inflammation seems to play a role in HD pathogenesis. The current review summarizes the available evidence about immune and/or inflammatory changes in HD. HD is associated with increased inflammatory mediators in both the central nervous system and periphery. Accordingly, there have been some attempts to slow HD progression targeting the immune system

Gene Expression Profiling in Huntington’s Disease: Does Comorbidity with Depressive Symptoms Matter?

Huntington’s disease (HD) is an inherited neurodegenerative disease. Besides the well-characterized motor symptoms, HD is marked by cognitive impairment and behavioral changes. In this study, we analyzed the blood of HD gene carries using RNA-sequencing techniques. We evaluated samples from HD gene carriers with (n = 8) and without clinically meaningful depressive symptoms (n = 8) compared with healthy controls (n = 8). Groups were age- and sex-matched. Preprocessing of data and between-group comparisons were calculated using DESeq2. The Wald test was used to generate p-values and log2 fold changes. We found 60 genes differently expressed in HD and healthy controls, of which 21 were upregulated and 39 downregulated. Within HD group, nineteen genes were differently expressed between patients with and without depression, being 6 upregulated and 13 downregulated. Several of the top differentially expressed genes are involved in nervous system development. Although preliminary, our findings corroborate the emerging view that in addition to neurodegenerative mechanisms, HD has a neurodevelopmental component. Importantly, the emergence of depression in HD might be related to these mechanisms

Promises and pitfalls of immune-based strategies for Huntington's disease

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disease characterized by the selective loss of neurons in the striatum and cortex, leading to progressive motor dysfunction, cognitive decline and behavioral symptoms. HD is caused by a trinucleotide (CAG) repeat expansion in the gene encoding for huntingtin. Several studies have suggested that inflammation is an important feature of HD and it is already observed in the early stages of the disease. Recently, new molecules presenting anti-inflammatory and/or immunomodulatory have been investigated for HD. The objective of this review is to discuss the data obtained so far on the immune-based therapeutic strategies for HD

Revisiting the neuropsychiatry of Huntington's disease

ABSTRACT Huntington's disease (HD) is an autosomal dominant neurodegenerative disease classified under the choreas. Besides motor symptoms, HD is marked by cognitive and behavioral symptoms, impacting patients' functional capacity. The progression of cognitive impairment and neuropsychiatric symptoms occur in parallel with neurodegeneration. The nature of these symptoms is very dynamic, and the major clinical challenges include executive dysfunction, apathy, depression and irritability. Herein, we provide a focused updated review on the cognitive and psychiatric features of HD