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

2020 ◽  
Vol 21 (22) ◽  
pp. 8474
Author(s):  
Gabriela Delevati Colpo ◽  
Natalia Pessoa Rocha ◽  
Erin Furr Stimming ◽  
Antonio Lucio Teixeira
Keyword(s):  
Depressive Symptoms ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
System Development ◽  
Wald Test ◽  
Nervous System Development ◽  
Behavioral Changes ◽  
Healthy Controls ◽  
Gene Carriers ◽  
Hd Gene

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.

Assessing Impairment of Executive Function and Psychomotor Speed in Premanifest and Manifest Huntington’s Disease Gene-expansion Carriers

2015 ◽  
Vol 21 (3) ◽  
pp. 193-202 ◽  
Author(s):  
Ida Unmack Larsen ◽  
Tua Vinther-Jensen ◽  
Anders Gade ◽  
Jørgen Erik Nielsen ◽  
Asmus Vogel
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuropsychological Testing ◽  
Distinct Group ◽  
Healthy Controls ◽  
Psychomotor Speed ◽  
Gene Expansion ◽  
Individual Scores ◽  
Hd Gene ◽  
Group Comparisons

AbstractExecutive functions (EF) and psychomotor speed (PMS) has been widely studied in Huntington’s disease (HD). Most studies have focused on finding markers of disease progression by comparing group means at different disease stages. Our aim was to investigate performances on nine measures of EF and PMS in a group of premanifest and manifest HD-gene expansion carriers and to investigate which measures were most sensitive for assessment of individual patients by analyzing frequencies of impaired performances relative to healthy controls. We recruited HD gene-expansion carriers, 48 manifest and 50 premanifest and as controls 39 healthy gene-expansion negative individuals. All participants underwent neurological examination and neuropsychological testing with nine cognitive measures. The frequency of impairment was investigated using cutoff scores. In group comparisons the manifest HD gene-expansion carriers scored significantly worse than controls on all tests and in classification of individual scores the majority of scores were classified as probably impaired (10th percentile) or impaired (5th percentile) with Symbol Digit Modalities Test (SDMT) being the most frequently impaired. Group comparisons of premanifest HD gene-expansion carriers and healthy controls showed significant differences on SDMT and Alternating fluency tests. Nevertheless the frequencies of probably impaired and impaired scores on individual tests were markedly higher for Alternating and Lexical fluency tests than for SDMT. We found distinct group differences in frequency of impairment on measures of EF and PMS in manifest and premanifest HD gene-expansion carriers. Our results indicate to what degree these measures can be expected to be clinically impaired. (JINS, 2015, 21, 1–10)

Predictors of Working Capacity Changes Related to Huntington’s Disease: A Longitudinal Study

2021 ◽  
pp. 1-8
Author(s):  
Kasper F. van der Zwaan ◽  
Milou Jacobs ◽  
Erik W. van Zwet ◽  
Raymund A.C. Roos ◽  
Susanne T. de Bot
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Psychiatric Symptoms ◽  
Motor Dysfunction ◽  
Healthy Controls ◽  
Working Capacity ◽  
Predictive Values ◽  
Gene Carriers ◽  
The Impact

Background: Huntington’s disease (HD) is an inherited neurodegenerative disorder that is characterized by motor, cognitive, and psychiatric symptoms. Although 65%of HD expanded gene carriers report changes in employment as the first functional loss, little is known about the predictors leading to changes of working capacity. Given the impact on quality of life, understanding of these factors is of great clinical value. Objective: This study evaluates disease specific characteristics and their predictive value in loss of working capacity in HD. Methods: Longitudinal data was collected through the worldwide observational study (Enroll-HD), with 15,301 participants in total and 2,791 HD and healthy control participants meeting the inclusion criteria. Changes in working capacity were analyzed by means of a survival analysis. Predictive values of demographic factors and clinical characteristics were assessed for premanifest and manifest HD through Cox regressions. Results: HD expanded gene carriers, manifest and premanifest combined, had a 31%chance of experiencing changes in employment after three years, compared to 4%in healthy controls. Apathy was found to be the most crucial determinant of working capacity changes in premanifest HD, while executive and motor dysfunction play an important role in manifest HD. Conclusion: HD expanded gene carriers are more likely to lose working capacity compared to healthy controls. Disease progression, altered motor function, cognitive decline, and in an early stage of the disease apathetic symptoms are indicative of negative changes in working capacity. Clinicians should recognize that early disease related changes, especially apathy, can affect working capacity.

scholarly journals 9 Aberrant striatal value representation in Huntington’s disease gene carriers 25 years before onset

2020 ◽  
Vol 91 (8) ◽  
pp. e4.1-e4
Author(s):  
Akshay Nair ◽  
Eileanoir B Johnson ◽  
Sarah Gregory ◽  
Katherine Osborne-Crowley ◽  
Paul Zeun ◽  
...  
Keyword(s):  
Reinforcement Learning ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Functional Imaging ◽  
Learning Task ◽  
Therapeutic Window ◽  
Group Differences ◽  
Gene Carriers ◽  
Hd Gene ◽  
Motor Onset

AimsHuntington’s disease (HD) is a devastating genetic neurodegenerative condition typically manifesting clinically in the fourth or fifth decade. With the advent of genetic therapies there is increased need to identify the earliest changes associated with carrying the HD gene. In this study we sought to determine the earliest functional imaging differences between HD gene carriers and matched controls. Based on previous work, we hypothesised that as compared to controls, HD gene carriers decades from onset would show a neural ‘reward bias’ – an exaggerated striatal response to gains as compared to losses.MethodsWe recruited 35 HD gene carriers, estimated to be on average 26 years from motor onset, and 35 controls. Groups were well matched for age, gender and education level.Participants completed a reinforcement learning task in a fMRI scanner using a sequence optimised for orbitofrontal and striatal signal. In this task participants were required to learn to choose between stimuli with the aim of maximise rewards and avoiding losses. Task behaviour was modelled using a computational model and computational variables from the best fitting model was used to probe fMRI data.ResultsAs hypothesised, we found that, in comparison to matched controls, gene carriers over 25 years from motor onset showed exaggerated striatal responses to gain as compared to loss predicting stimuli (p=0.003) in a reinforcement learning task. Using computational analysis, we also found group differences in striatal representation of stimulus value (p=0.0007).ConclusionThese represent the earliest functional imaging differences between HD gene carriers and controls. Behaviourally gene carriers, 9 years from predicted onset, have shown enhanced learning from gains as compared to losses. Importantly, we found no group differences in behaviour, or caudate volumes. Our data suggests a therapeutic window exists whereby HD- related functional neural changes are detectable 25 years before predicted onset.

scholarly journals Longitudinal resting state fMRI analysis in healthy controls and premanifest Huntington's disease gene carriers: A three-year follow-up study

2014 ◽  
Vol 36 (1) ◽  
pp. 110-119 ◽  
Author(s):  
Omar F.F. Odish ◽  
Annette A. van den Berg-Huysmans ◽  
Simon J.A. van den Bogaard ◽  
Eve M. Dumas ◽  
Ellen P. Hart ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Resting State ◽  
Disease Gene ◽  
Resting State Fmri ◽  
Healthy Controls ◽  
Follow Up Study ◽  
Gene Carriers ◽  
Fmri Analysis

scholarly journals Visual Working Memory Impairment in Premanifest Gene-Carriers and Early Huntington's Disease

2012 ◽  
Vol 1 (1) ◽  
pp. 97-106 ◽  
Author(s):  
Eve M. Dumas ◽  
Miranda J. Say ◽  
Rebecca Jones ◽  
Izelle Labuschagne ◽  
Alison M. O'Regan ◽  
...  
Keyword(s):  
Working Memory ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Visual Working Memory ◽  
Memory Impairment ◽  
Gene Carriers

scholarly journals Loss of extra-striatal phosphodiesterase 10A expression in early premanifest Huntington's disease gene carriers

2016 ◽  
Vol 368 ◽  
pp. 243-248 ◽  
Author(s):  
Heather Wilson ◽  
Flavia Niccolini ◽  
Salman Haider ◽  
Tiago Reis Marques ◽  
Gennaro Pagano ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Gene ◽  
Gene Carriers ◽  
Phosphodiesterase 10A

Psychopathology in Verified Huntington’s Disease Gene Carriers

2007 ◽  
Vol 19 (4) ◽  
pp. 441-448 ◽  
Author(s):  
E. van Duijn ◽  
E.M. Kingma ◽  
R.C. van der Mast
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Gene ◽  
Gene Carriers

scholarly journals Structural and functional brain network correlates of depressive symptoms in premanifest Huntington's disease

2017 ◽  
Vol 38 (6) ◽  
pp. 2819-2829 ◽  
Author(s):  
Peter McColgan ◽  
Adeel Razi ◽  
Sarah Gregory ◽  
Kiran K. Seunarine ◽  
Alexandra Durr ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Brain Network ◽  
Functional Brain ◽  
Functional Brain Network

scholarly journals Cognitive and Motor Norms for Huntington’s Disease

2020 ◽  
Vol 35 (6) ◽  
pp. 671-682
Author(s):  
James A Mills ◽  
Jeffrey D Long ◽  
Amrita Mohan ◽  
Jennifer J Ware ◽  
Cristina Sampaio
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rating Scale ◽  
Word Reading ◽  
Natural Aging ◽  
Color Naming ◽  
Stroop Interference ◽  
Healthy Controls ◽  
Aging Effects ◽  
Motor Score

Abstract Background The progression of Huntington’s disease (HD) for gene-expanded carriers is well-studied. Natural aging effects, however, are not often considered in the evaluation of HD progression. Objective To examine the effects of natural aging for healthy controls and to develop normative curves by age, sex, and education from the distribution of observed scores for the Symbol Digit Modalities Test, Stroop Word Reading Test, Stroop Color Naming Test, Stroop Interference Test, Total Motor Score, and Total Functional Capacity (TFC) from the Unified Huntington’s Disease Rating Scale (UHDRS) along with a composite score. Methods After combining longitudinal REGISTRY and Enroll-HD data, we used quantile regression and natural cubic splines for age to fit models for healthy controls (N = 3,394; N observations = 8,619). Normative curves were estimated for the 0.05, 0.25, 0.50, 0.75, and 0.95 quantiles. Two types of reference curves were considered: unconditional curves were dependent on age alone, whereas conditional curves were dependent on age and other covariates, namely sex and education. Results Conditioning on education was necessary for the Symbol Digit, Stroop Word, Stroop Color, Stroop Interference, and composite UHDRS. Unconditional curves were sufficient for the Total Motor Score. TFC was unique in that the curve was constant over age with its intercept at the maximum score (TFC = 13). For all measures, sex effects were minimal, so conditioning on sex was unwarranted. Conclusions Extreme quantile estimates for each measure can be considered as boundaries for natural aging and scores falling beyond these thresholds are likely the result of disease progression. Normative curves and tables are developed and can serve as references for clinical characterization in HD.

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