David Craufurd

Institute for Human Development, New Dilli, NCT, India

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Publications (109)659.77 Total impact

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    ABSTRACT: Insufficient evidence exists to guide the long-term pharmacological management of Huntington’s disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such “inverse” associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.
    No preview · Article · Jan 2016 · PLoS Currents
  • George McNally · Hugh Rickards · Mike Horton · David Craufurd
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    ABSTRACT: Background: The short version of the Problem Behaviours Assessment (PBA-s) is the recommended outcome measure for behavioural symptoms in Huntington's disease. Rasch analysis was used to further investigate the measurement limitations of the PBA-s. Objectives: 1) To assess the psychometric properties of the 11 severity and frequency items within the PBA-s and 2) to determine the construct validity of using a total PBA-s score as a clinical outcome measure. Methods: PBA-s data for 517 participants from Enroll-HD were included in the Rasch analysis. Separate analyses were conducted for the severity and frequency items of the PBA-s, using RUMM2030 software. Achieving fit to the model provides supporting evidence that all items contribute to a single underlying latent trait. This property is defined as internal construct validity. Results: The total PBA-s severity score demonstrated several important limitations, including disordered response categories for all 11 severity items, local dependency and poor targeting. However, modifying the original five-point scoring system to a four-point system resulted in ordered response categories for seven of the severity items and achieved a good overall fit to the Rasch model. For the total PBA-s frequency score, fit to the model was not achieved even after amendments to the scoring system. Conclusions: This study suggests that with reduction to a four-point scoring system, the total PBA-s severity score may be considered a valid clinical outcome measure. This study also suggests limitations in the use of a total PBA-s frequency score.
    No preview · Article · Dec 2015 · Journal of Huntington's disease
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    ABSTRACT: Weight loss is an important complication of Huntington's disease (HD), however the mechanism for weight loss in HD is not entirely understood. Mutant huntingtin is expressed in the gastrointestinal (GI) tract and, in HD mice, mutant huntingtin inclusions are found within the enteric nervous system along the GI tract. A reduction of neuropeptides, decreased mucosal thickness and villus length, as well as gut motility impairment, have also been shown in HD mice. We therefore set out to study gastric mucosa of patients with HD, looking for abnormalities of mucosal cells using immunohistochemistry. In order to investigate possible histological differences related to gastric acid production, we evaluated the cell density of acid producing parietal cells, as well as gastrin producing cells (the endocrine cell controlling parietal cell function). In addition, we looked at chief cells and somatostatin-containing cells. In gastric mucosa from HD subjects, compared to control subject biopsies, a reduced expression of gastrin (a marker of G cells) was found. This is in line with previous HD mouse studies showing reduction of GI tract neuropeptides.
    No preview · Article · Nov 2015 · PLoS Currents
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    ABSTRACT: Objective: Psychiatric symptoms are a significant aspect of Huntington's disease, an inherited neurodegenerative illness. The presentation of these symptoms is highly variable, and their course does not fully correlate with motor or cognitive disease progression. The authors sought to better understand the development and longitudinal course of psychiatric manifestations in individuals who carry the Huntington's disease mutation, starting from the prodromal period prior to motor diagnosis. Method: Longitudinal measures for up to 10 years of psychiatric symptoms from the Symptom Checklist-90-Revised were obtained from 1,305 participants (1,007 carrying the Huntington's disease mutation and 298 without [classified as controls]) and 1,235 companions enrolled in the Neurobiological Predictors of Huntington's Disease (PREDICT-HD) study. Participants with the mutation were stratified into three groups according to probability of motor diagnosis within 5 years. Using linear mixed-effects regression models, differences in psychiatric symptoms at baseline and over time between the mutation-positive groups and the controls were compared, as well as between ratings by mutation-positive participants and their companions. Results: Nineteen of 24 psychiatric measures (12 participant ratings and 12 companion ratings) were significantly higher at baseline and showed significant increases longitudinally in the individuals with the Huntington's disease mutation compared with controls. The differences were greatest in comparisons of symptom reports from companions compared with self-reports, especially in participants who were closest to motor diagnosis. Conclusions: The results indicate that psychiatric manifestations develop more often than previously thought in the Huntington's disease prodrome. Symptoms also increase with progression of disease severity. Greater symptom ratings by companions than by mutation-positive participants suggest decreasing awareness in those affected.
    No preview · Article · Oct 2015 · American Journal of Psychiatry
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    ABSTRACT: Background: Neuropsychiatric symptoms in Huntington's disease (HD) are often evident prior to clinical diagnosis. Apathy is highly correlated with disease progression, while depression and irritability occur at different stages of the disease, both before and after clinical onset. Little is understood about the neural bases of these neuropsychiatric symptoms and to what extent those neural bases are analogous to neuropsychiatric disorders in the general population. Objective: We used Diffusion Tensor Imaging (DTI) to investigate structural connectivity between brain regions and any putative microstructural changes associated with depression, apathy and irritability in HD. Methods: DTI data were collected from 39 premanifest and 45 early-HD participants in the TrackHD study and analysed using whole-brain Tract-Based Spatial Statistics. We used regression analyses to identify white matter tracts whose structural integrity (as measured by fractional anisotropy, FA) was correlated with HADS-depression, PBA-apathy or PBA-irritability scores in gene-carriers and related to cumulative probability to onset (CPO). Results: For those with the highest CPO, we found significant correlations between depression scores and reduced FA in the splenium of the corpus callosum. In contrast, those with lowest CPO demonstrated significant correlations between irritability scores and widespread FA reductions. There was no significant relationship between apathy and FA throughout the whole brain. Conclusions: We demonstrate that white matter changes associated with both depression and irritability in HD occur at different stages of disease progression concomitant with their clinical presentation.
    Full-text · Article · Sep 2015 · Journal of Huntington's disease
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    ABSTRACT: It has been suggested that treatment with ethyl-eicosapentaenoic acid (EPA) may improve motor function in patients with Huntington's disease (HD) with cytosine-adenine-guanine repeat numbers of <45. This multicenter, randomized, double-blind, placebo-controlled 6-month trial compared the effects of ethyl-EPA versus placebo on 290 subjects with mild-to-moderate HD. The primary endpoint was the change from baseline to 6 months in the Total Motor Score 4 (TMS-4) component of the Unified Huntington's Disease Rating Scale (UHDRS). Secondary endpoints included change from baseline in UHDRS subscores and Clinical Global Impression (CGI). No significant differences in TMS-4 scores were noted between treatment groups. Similarly, there were no significant differences between groups on any of the UHDRS subscores or CGI scores. Ethyl-EPA was not beneficial in patients with HD during 6 months of placebo-controlled evaluation. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Full-text · Article · Jul 2015 · Movement Disorders
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    ABSTRACT: The authors report the inter-rater reliability and factor structure of the Short Problem Behaviors Assessment (PBA-s), a semistructured interview to measure severity and frequency of behavioral problems in Huntington's disease. Video recordings of 410 PBA-s interviews were rescored by an independent rater, and Cohen's kappa calculated to assess inter-rater reliability. The mean kappa was 0.74 for severity and 0.76 for frequency scores, whereas weighted kappa (allowing scores to differ by 1 point) was 0.94 for severity and 0.92 for frequency scores. The results of factor analysis were consistent with previous studies using other measures. The authors conclude that the PBA-s is a reliable measure.
    No preview · Article · Feb 2015 · The Journal of Neuropsychiatry and Clinical Neurosciences
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    ABSTRACT: Background The Enroll-HD project aims to recruit one third of the manifest HD patients living in areas served by study sites. We conducted an audit of REGISTRY study participants at two sites (Manchester and Liverpool) to assess the feasibility of this, and to investigate the effect of geographical and socioeconomic factors on equality of access to the service. Aims To determine the number of REGISTRY participants per 100,000 of the population in different areas of North West England, and the relationship of this to distance from study sites and indicators of economic deprivation. Methods The total number of living REGISTRY participants and the number of currently active study participants were calculated for each county and borough in north west England. Postcodes were used to assign subjects to census areas (Lower-layer Super Output Areas; LSOAs) and the distribution of LSOAs containing at least one REGISTRY participant was compared to the overall distribution using the Index of Multiple Deprivations (IMD) of the UK Office of National Statistics. Results Rates of current REGISTRY participation varied greatly from borough to borough, but was approximately 4/100,000 across most of the region, rising to 6/100,000 when inactive participants were included. The borough with the highest rate of participation was the one most geographically distant (about 3 h travel) from the study sites. LSOAs containing a REGISTRY participant were significantly more likely to have a higher IMD score (more deprived). Conclusion If the prevalence of HD is 12/100,000, our findings suggest that the goal of recruiting one third of the available subjects is achievable. Distance from the study site does not appear to be a barrier to access in our region. Given that the primary cause of HD is genetic, the significant relationship with indices of deprivation suggests that HD has a detrimental effect on the socioeconomic status of families, as well as the health of affected individuals.
    No preview · Article · Jan 2015 · Neurotherapeutics
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    ABSTRACT: AimsSelisistat, a selective SirT1 inhibitor is being developed as a potentially disease-modifying therapeutic for Huntington's disease (HD). This was the first study of selisistat in HD patients and was primarily aimed at development of pharmacodynamic biomarkers.Methods This was a randomized, double-blind, placebo-controlled, multicentre exploratory study. Fifty-five male and female patients in early stage HD were randomized to receive 10 mg or 100 mg of selisistat or placebo once daily for 14 days. Blood sampling, clinical and safety assessments were conducted throughout the study. Candidate pharmacodynamic markers included circulating soluble huntingtin and innate immune markers.ResultsSelisistat was found to be safe and well tolerated, and systemic exposure parameters showed that the average steady-state plasma concentration achieved at the 10 mg dose level (125 nm) was comparable with the IC50 for SirT1 inhibition. No adverse effects on motor, cognitive or functional readouts were recorded. While circulating levels of soluble huntingtin were not affected by selisistat in this study, the biological samples collected have allowed development of assay technology for use in future studies. No effects on innate immune markers were seen.Conclusions Selisistat was found to be safe and well tolerated in early stage HD patients at plasma concentrations within the anticipated therapeutic concentration range.
    No preview · Article · Sep 2014 · British Journal of Clinical Pharmacology

  • No preview · Article · Sep 2014 · Journal of Neurology Neurosurgery & Psychiatry
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    ABSTRACT: Background Huntington’s disease (HD) is commonly associated with psychiatric disturbance. Often evident in premanifest gene-carriers, little is understood about the neural bases underlying these HD symptoms. While structural imaging has so far failed to provide any major insight, Diffusion Tensor Imaging (DTI) can be used to investigate connectivity between brain regions and any putative microstructural changes that may occur in HD. Aims To examine structural connectivity associated with depression, apathy and irritability in HD gene-carriers. Methods DTI data was collected from 39 premanifest and 45 early-HD participants, as part of the TrackHD study and was analysed using whole-brain Tract-Based Spatial Statistics to extract fractional anisotropy (FA) values – a surrogate marker for tract integrity and efficacy of communication between brain regions. Regression analyses were performed on all gene-carriers using HADS depression and PBA apathy and irritability scores. Results High disease load (measured by CPO) was associated with highly significant, whole-brain corrected correlations between depression scores and reduced FA in the bilateral splenium of the corpus callosum. There were significant widespread negative associations between irritability scores and FA. Interestingly, low disease load participants demonstrated significant correlations between irritability scores and FA reduction. There were no significant associations between apathy and FA. Conclusions Both depression and irritability are associated with reductions in white matter integrity in HD. The opposite relationships between FA and measures of depression and irritability as a function of disease progression suggest that diverse mechanisms associated with both the onset and progression of psychiatric disturbance in HD.
    No preview · Article · Sep 2014 · Journal of Neurology Neurosurgery & Psychiatry
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    ABSTRACT: Background Huntington Disease (HD) is an autosomal dominant neurodegenerative disease that typically manifests with motor, cogniti1ve and psychiatric symptoms. The majority of research emphasises the motor and cognitive phenotype of HD. Cross-sectional research consistently shows increased psychiatric and behavioural impairments in HD although few studies have examined longitudinal changes in psychiatric symptoms. Aims Here we report longitudinal behavioural data with up to ten years of follow-up to identify behavioural changes that occur in premanifest HD up to and through motor conversion. Methods Using the Symptom Check List-90-Revised (SCL90), a 90-item self-report scale of psychological symptomatology, we analysed data from 1305 participants (cases and controls) with 6112 observations and their 1235 companions with 5365 observations. Individuals with CAG repeat expansion (CAG≥36) served as cases while people who tested negative for the expansion (CAG <36) were controls. Participant and companion ratings were analysed separately using linear mixed effects regression (LMER). The time metric was duration, defined as time since study entry in years. Results Of the 24 psychiatric outcome variables examined, 19 showed significant baseline and longitudinal differences between cases and controls. Further, when analyses were conducted to examine ratings between cases and companions, findings showed inconsistency between the raters that is interpreted in terms of unawareness associated with HD progression. Conclusions In cases near motor onset, companion ratings appear to be more valid than patient-report. Our findings indicate that unawareness increases in concert with disease progression during premanifest stages. Psychiatric disturbances demonstrate worsening over time in concert with disease progression in HD.
    No preview · Article · Sep 2014 · Journal of Neurology Neurosurgery & Psychiatry
  • J. Scaria · D. Rogers · M. Jones · C. Daly · D. Craufurd
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    ABSTRACT: Background Huntington’s disease (HD) is characterised by a triad of motor, cognitive and psychiatric symptoms. Depression is common, but experience suggests that the clinical features of depression in patients with HD may differ from those in the general population, depression in HD being more variable from day to day, and more susceptible to changes in environmental factors and mental stimulation. Aim To compare the clinical features of depression in Huntington’s disease with depression in the general population. Methods The subjects were 15 HD patients with depression and 15 depressed patients from an out-patient psychiatry clinic. Recruitment was based on inclusion criteria designed to select patients with moderate depression. The non-HD comparison group was matched for age, sex and Visual Analogue Mood Scores. Both groups completed the Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory, Test for Anhedonia questionnaire and a modified version of the Montgomery Asberg Depression Rating Scale with 3 questions added about environmental susceptibility of low mood. Results There was no significant difference in the total score of all the questionnaires used. The anhedonia (‘lack of enjoyment’) item of the HADS was significantly lower in depressed patients with HD, but we did not find a similar difference for anhedonia items in other scales. Concentration difficulties and susceptibility of mood to environmental stimulation were greater in HD patients, but this difference did not attain statistical significance. Conclusion The clinical features of depression in patients with HD were similar to those from the general population. However, this pilot study was statistically under-powered, and there was a clear trend for the depressed HD patients to report more improvement in mood with favourable environmental changes. We plan a further study to replicate this in a larger sample and to explore the temporal pervasiveness of low mood in the two groups.
    No preview · Article · Sep 2014 · Journal of Neurology Neurosurgery & Psychiatry
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    ABSTRACT: Background Predictive testing based on CAG repeat length measurement has been available since 1993. Data on numbers of tests conducted at 23 genetic centres were available through a UK Huntington’s Prediction Consortium. Aims To determine the cumulative uptake of predictive tests for those at 50% risk in the UK. Methods The numerator was the cumulative number of tests undertaken between 1993 and 2012. The denominator was the cumulative population at 50% risk. This was estimated from HD prevalence and ratio of number at risk to number affected using the method of Tassicker et al2009. Prevalence estimates vary, so we analysed the data using 3 different values: 8, 10 and 12 × 10–5. We used two values for the ratio of affected cases to those at risk: 1:5 and 1:4.2. We used Tassicker et al’s estimate of 18.8 years for illness duration. Although minimal, missing data for 1994 to 2012 were imputed using standard techniques; data were not imputed for 1993 because of uncertainties about when centres started to offer predictive testing. Results We produced a range of cumulative uptake percentages based on the different scenarios. If the prevalence is 10 × 10–5then the cumulative uptake of predictive tests after 20 years is approximately 18% based on a ratio of affected cases to those at risk of 1:5, and 21% based on a ratio of 1: 4.2. A prevalence of 12 × 10–5and ratio of 5 gave a cumulative uptake of approximately 15% whereas a prevalence of 8 × 10–5and ratio of 4.2 gave a cumulative uptake of approximately 26%. Conclusion This complete analysis of all predictive tests conducted in the UK over a 20-year period confirms that uptake of predictive testing among those at high risk of HD is no more than approximately 15–26%.
    No preview · Article · Sep 2014 · Journal of Neurology Neurosurgery & Psychiatry

  • No preview · Article · Aug 2014 · Practical Neurology
  • Joby Scaria · David Craufurd
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    ABSTRACT: Objective Huntington's Disease (HD) is an inherited progressive neurodegenerative disorder, characterised by a triad of motor, cognitive and psychiatric symptoms. Depression is common in patients with HD, but does not correlate well with motor or cognitive measures of disease progression, suggesting that different neuropathological process may be involved. However clinical experience suggests that depressive symptoms in HD are variable and tend to fluctuate from day to day and in response to environmental factors and mental stimulation, suggesting that HD related cognitive changes and impaired motivation might contribute to the aetiology of depressive symptoms. The aim of the present exploratory pilot study was therefore to compare the clinical features of depression in HD with depression in general population. Method A cross sectional comparison study was completed with 15 depressed Huntington's Disease patients and 15 depressed patients from general population. Recruitment of the participants was based on specific inclusion and exclusion criteria and selected patients with moderate depression. The comparison group was matched for age, sex and Visual Analogue Mood Scores. All subjects in both groups completed the Hospital Anxiety and Depression Scale, Beck Depression Inventory, Test for Anhedonia questionnaire and Montgomery Asberg Depression Rating Scale; the latter was modified for this study with 3 extra questions about environmental susceptibility of low mood. Results The results of the study indicate that there was no significant difference between groups in the clinical features of depression, based on the total score of all the questionnaires used. Depressed patients without HD had significantly higher scorers on the lack of enjoyment (anhedonia) item from the Hospital Anxiety and Depression Scale; however, this was the only significant difference between the groups, and this finding did not survive Bonferroni Correction. There was a trend for concentration difficulties and improvement in mood based on changes in environmental factors to be more pronounced in HD patients, but this difference was not statistically significant based on p values and confidence intervals. Conclusion We conclude that there is no significant difference in the clinical features of depression in Huntington's disease compared to depressed patients from general population. The overall effect size for the whole study was low to medium and based on the calculations more significant results could be obtained with more than 100 participants in each group in future studies. We plan a further study looking at the pervasiveness of low mood over time in the two groups.
    No preview · Article · Aug 2014 · Journal of Neurology Neurosurgery & Psychiatry
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    ABSTRACT: People with Huntington's disease (HD) may show reduced awareness of physical and mental changes in themselves. This article reviews the evidence for loss of awareness (anosognosia) in an attempt to elucidate its characteristics and possible underlying mechanisms. It is shown that defective awareness occurs across domains. People with HD may under-report the presence or severity of involuntary movements, under-estimate cognitive impairment and deny behavioural change. Nevertheless, awareness is not all or none. Moreover, it may be affected differentially for different symptom domains and emerge at different stages of disease, raising the possibility of distinct contributory mechanisms. Findings of an inverse relationship between insight and severity of disease suggest that cognitive impairment, in particular executive dysfunction, may be an important contributory factor. Evidence has accrued to support this argument. However, cognitive impairment cannot fully account for patients' lack of awareness of involuntary movements. Findings that patients accurately report consequences but not the experience of involuntary movements, and better acknowledge their presence when watching videotapes of themselves suggests that physiological factors play an important role. The putative role of denial as a coping mechanism is discussed. Recognition by clinicians of deficient self-awareness is crucial because of its implications for diagnosis and optimal clinical management of HD.
    No preview · Article · Jul 2014 · Journal of Huntington's disease
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    ABSTRACT: The majority of Huntington's disease (HD) mutation carriers experience some psychopathology during their lifetime, varying from irritability to psychosis, but prevalences of particular symptoms vary widely due to diverse study populations in different stages of HD and the use of different assessment methods. The study population consisted of 1993 HD mutation carriers from 15 European countries, all participating in the observational REGISTRY study. The behavioural section of the Unified HD Rating Scale was used to examine the prevalence and correlates of five neuropsychiatric features: depression, irritability/aggression, obsessive/compulsive behaviours, apathy and psychosis. Twenty-seven per cent of the participants did not have any neuropsychiatric symptom in the last month. Moderate to severe apathy occurred in 28.1% of the participants, whereas moderate to severe depression was found in 12.7%. Irritable/aggressive symptoms were present in 13.9% of the participants, and 13.2% showed obsessive/compulsive behaviours. Moderate to severe psychotic symptoms were found in only 1.2%. Only 54.9% of all participants with moderate to severe depression used antidepressants, suggesting undertreatment of depression. Obsessive/compulsive behaviours and irritability/aggression were inversely correlated with the Total Functional Capacity score, but with apathy showing the strongest inverse association. A variety of neuropsychiatric symptoms are highly prevalent in different stages of HD in this European HD population, with apathy as the most frequent symptom. Depression, irritability/aggression and OCBs are prevalent in all stages of HD. Apathy was the key neuropsychiatric symptom occurring most often in advanced HD stages. Due to possible selection of relatively healthy participants, prevalences reported in this study might be an underestimation of prevalence in the entire HD population.
    No preview · Article · May 2014 · Journal of neurology, neurosurgery, and psychiatry
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    ABSTRACT: Background Previous studies indicate increased prevalences of suicidal ideation, suicide attempts, and completed suicide in Huntington's disease (HD) compared with the general population. This study investigates correlates and predictors of suicidal ideation in HD. Methods The study cohort consisted of 2106 HD mutation carriers, all participating in the REGISTRY study of the European Huntington's Disease Network. Of the 1937 participants without suicidal ideation at baseline, 945 had one or more follow-up measurements. Participants were assessed for suicidal ideation by the behavioural subscale of the Unified Huntington's Disease Rating Scale (UHDRS). Correlates of suicidal ideation were analyzed using logistic regression analysis and predictors were analyzed using Cox regression analysis. Results At baseline, 169 (8.0%) mutation carriers endorsed suicidal ideation. Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]: 0.9–1.0), anxiety (OR=2.14; 95%CI: 1.4–3.3), aggression (OR=2.41; 95%CI: 1.5–3.8), a previous suicide attempt (OR=3.95; 95%CI: 2.4–6.6), and a depressed mood (OR=13.71; 95%CI: 6.7–28.0) were independently correlated to suicidal ideation at baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%. Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI: 1.1–4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2–5.0) at baseline were independent predictors of incident suicidal ideation, whereas a previous suicide attempt was not predictive. Limitations As suicidal ideation was assessed by only one item, and participants were a selection of all HD mutation carriers, the prevalence of suicidal ideation was likely underestimated. Conclusions Suicidal ideation in HD frequently occurs. Assessment of suicidal ideation is a priority in mutation carriers with a depressed mood and in those using benzodiazepines.
    Full-text · Article · Oct 2013 · Journal of Affective Disorders
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    ABSTRACT: Neuropathological studies in Huntington disease (HD) have demonstrated neuronal loss in the striatum, as well as in other brain regions including the cortex. With diffusion tensor MRI we evaluated the hypothesis that the clinical dysfunction in HD is related to regionally specific lesions of circuit-specific cortico-basal ganglia networks rather than to the striatum only. We included 27 HD and 24 controls from the TRACK-HD Paris cohort. The following assessments were used: self-paced tapping tasks, trail B making test (TMT), University of Pennsylvania smell identification test (UPSIT), and apathy scores from the problem behaviors assessment. Group comparisons of fractional anisotropy and mean diffusivity and correlations were performed using voxel-based analysis. In the cortex, HD patients showed significant correlations between: (i) self paced tapping and mean diffusivity in the parietal lobe at 1.8 Hz and prefrontal areas at 3 Hz, (ii) UPSIT and mean diffusivity in the parietal, and median temporal lobes, the cingulum and the insula, and fractional anisotropy in the insula and the external capsule, (iii) TMT B and mean diffusivity in the white matter of the superior frontal, orbital, temporal, superior parietal and post central areas, and (iv) apathy and fractional anisotropy in the white matter of the rectus gyrus. In the basal ganglia, we found correlations between the self paced tapping, UPSIT, TMT tests, and mean diffusivity in the anterior part of the putamen and the caudate nucleus. In conclusion, disruption of motor, associative and limbic cortico-striatal circuits differentially contribute to the clinical signs of the disease. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    Full-text · Article · Sep 2013 · Human Brain Mapping

Publication Stats

6k Citations
659.77 Total Impact Points


  • 2015
    • Institute for Human Development
      New Dilli, NCT, India
  • 1989-2015
    • The University of Manchester
      • • Centre for Genetic Medicine
      • • Respiratory Medicine Research Group
      Manchester, England, United Kingdom
  • 2014
    • North Western Deanery
      Manchester, England, United Kingdom
  • 2010-2014
    • Central Manchester University Hospitals NHS Foundation Trust
      Manchester, England, United Kingdom
  • 1989-2010
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 2009
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
  • 2004-2009
    • Saint Mary's Hospital Center
      Montréal, Quebec, Canada
  • 2002
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 1999
    • University of British Columbia - Vancouver
      • Department of Medical Genetics
      Vancouver, British Columbia, Canada
  • 1992
    • University of Wales
      • College of Medicine
      Cardiff, Wales, United Kingdom