David Craufurd

Institute for Human Development, New Dilli, NCT, India

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Publications (97)602.97 Total impact

  • [Show abstract] [Hide abstract]
    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.
    PLoS Currents 11/2015; 7. DOI:10.1371/10.1371/currents.hd.858b4cc7f235df068387e9c20c436a79
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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.
    American Journal of Psychiatry 10/2015; DOI:10.1176/appi.ajp.2015.14121551 · 12.30 Impact Factor
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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.
    Journal of Huntington's disease 09/2015; 4(3):239-249. DOI:10.3233/JHD-150160
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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.
    Movement Disorders 07/2015; 30(10). DOI:10.1002/mds.26308 · 5.68 Impact Factor
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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.
    The Journal of Neuropsychiatry and Clinical Neurosciences 02/2015; 27(1):59-64. DOI:10.1176/appi.neuropsych.13070169 · 2.82 Impact Factor
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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.
    Neurotherapeutics 01/2015; 12(1):267-267. DOI:10.1136/jnnp-2014-309032.257 · 5.05 Impact Factor
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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.
    British Journal of Clinical Pharmacology 09/2014; 79(3). DOI:10.1111/bcp.12512 · 3.88 Impact Factor

  • Practical Neurology 08/2014; 15(1). DOI:10.1136/practneurol-2013-000790
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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.
    Journal of Huntington's disease 07/2014; 3(2):125-135. DOI:10.3233/JHD-140109
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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.
    Journal of neurology, neurosurgery, and psychiatry 05/2014; 85(12). DOI:10.1136/jnnp-2013-307343 · 6.81 Impact Factor
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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.
    Journal of Affective Disorders 10/2013; 151(1). DOI:10.1016/j.jad.2013.06.001 · 3.38 Impact Factor
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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.
    Human Brain Mapping 09/2013; 34(9). DOI:10.1002/hbm.22055 · 5.97 Impact Factor

  • 07/2013; 15(1-2). DOI:10.3109/21678421.2013.817586
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    ABSTRACT: Background TRACK-HD is a multinational prospective observational study of Huntington's disease (HD) that examines clinical and biological findings of disease progression in individuals with premanifest HD (preHD) and early-stage HD. We aimed to describe phenotypic changes in these participants over 36 months and identify baseline predictors of progression. Methods Individuals without HD but carrying the mutant huntingtin gene (classed as preHD-A if >= 10.8 years and preHD-B if <10.8 years from predicted onset), participants with early HD (classed as HD1 if they had a total functional capacity score of 11-13 and HD2 if they had a score of 7-10), and healthy control individuals were assessed at four study sites in the Netherlands, the UK, France, and Canada. We measured 36-month change for 3T Mill, clinical, cognitive, quantitative motor, and neuropsychiatric assessments and examined their prognostic value. We also assessed the relation between disease progression and the combined effect of CAG repeat length and age. All participants were analysed according to their baseline subgroups. Longitudinal results were analysed using a combination of repeated-measure weighted least squares models and, when examining risk of new diagnosis, survival analysis. Findings At baseline, 366 participants were enrolled between Jan 17, and Aug 26,2008, and of these 298 completed 36-month follow-up: 97 controls, 58 participants with preHD-A, 46 with preHD-B, 66 with HD1, and 31 with HD2. In the preHD-B group, several quantitative motor and cognitive tasks showed significantly increased rates of decline at 36 months, compared with controls, whereas few had at 24 months. Of the cognitive measures, the symbol digit modality test was especially sensitive (adjusted mean loss 4.11 points [95% CI 1.49-6-73] greater than controls; p=0.003). Among psychiatric indicators, apathy ratings specifically showed significant increases (0.34 points [95% CI 0.02-0.66] greater than controls; p=0-038). There was little evidence of reliable change in non-imaging measures in the preHD-A group, with the exception of the speeded tapping inter-tap interval (0-01 s [95% CI 0.01-0.02] longer than controls; p=0-0001). Several baseline imaging, quantitative motor, and cognitive measures had prognostic value, independent of age and CAG repeat length, for predicting subsequent clinical diagnosis in preHD. Of these, grey-matter volume and inter-tap interval were particularly sensitive (p=0.013 and 0.002, respectively). Longitudinal change in these two measures was also greater in participants with preHD who received a diagnosis of HD during the study compared with those who did not, after controlling for CAG repeat length and age-related risk (p=0.006 and 0.0003, respectively). In early HD, imaging, quantitative motor, and cognitive measures were predictive of decline in total functional capacity and tracked longitudinal change; also, neuropsychiatric changes consistent with frontostriatal pathological abnormalities were associated with this loss of functional capacity (problem behaviours assessment composite behaviour score p<0.0001). Age and CAG repeat length explained variance in longitudinal change of multimodal measures, with the effect more prominent in preHD. Interpretation We have shown changes in several outcome measures in individuals with preHD over 36 months. These findings further our understanding of HD progression and have implications for clinical trial design.
    The Lancet Neurology 07/2013; 12(7):637. DOI:10.1016/S1474-4422(13)70088-7 · 21.90 Impact Factor
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    ABSTRACT: The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis.
    PLoS ONE 07/2013; 8(7):68951-. DOI:10.1371/journal.pone.0068951 · 3.23 Impact Factor
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    ABSTRACT: Background Understanding the relation between predominantly choreatic and hypokinetic-rigid motor subtypes and cognitive and general functioning may contribute to knowledge about different motor phenotypes in Huntington's disease.Methods In the European Huntington's Disease Network Registry study, 1882 subjects were classified as being predominantly choreatic (n = 528) or hypokinetic-rigid (n = 432), according to their scores on items of the total motor score a priori labeled as choreatic or hypokinetic-rigid; the other 922 patients were of a mixed type. The relationship between motor type and cognitive (verbal fluency, symbol digit modalities, Stroop color, word and interference tests) and functional (total functional capacity) capacity was investigated using multiple linear regression.ResultsMotor subtype contributed significantly to the total functional capacity score (partial r2: 7.8%; P < .001) and to the 5 cognitive scores (partial r2 ranged from 2.0% to 8.4%; all P < .001).Conclusions Patients with a predominantly choreatic motor phenotype performing better in all areas than patients with a hypokinetic-rigid motor phenotype. © 2013 Movement Disorder Society
    Movement Disorders 07/2013; 28(8). DOI:10.1002/mds.25422 · 5.68 Impact Factor
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    PLoS ONE 07/2013; · 3.23 Impact Factor
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    ABSTRACT: Depression causes significant morbidity and mortality, and this also occurs in Huntington Disease (HD), an inherited neurodegenerative illness with motor, cognitive, and psychiatric symptoms. The presentation of depression in this population remains poorly understood, particularly in the prodromal period before development of significant motor symptoms. In this study, we assessed depressive symptoms in a sample of 803 individuals with the HD mutation in the prodromal stage and 223 mutation-negative participants at the time of entry in the Neurobiological Predictors of HD (PREDICT-HD) study. Clinical and biological HD variables potentially related to severity of depression were analyzed. A factor analysis was conducted to characterize the symptom domains of depression in a subset (n=168) with clinically significant depressive symptoms. Depressive symptoms were found to be more prevalent in HD mutation carriers but did not increase with proximity to HD diagnosis and were not associated with length of the HD mutation. Increased depressive symptoms were significantly associated with female gender, self-report of past history of depression, and a slight decrease in functioning, but not with time since genetic testing. The factor analysis identified symptom domains similar to prior studies in other populations. These results show that individuals with the HD mutation are at increased risk to develop depressive symptoms at any time during the HD prodrome. The clinical presentation appears to be similar to other populations. Severity and progression are not related to the HD mutation.
    Journal of Psychiatric Research 06/2013; 47(10). DOI:10.1016/j.jpsychires.2013.05.026 · 3.96 Impact Factor
  • Natalie Arran · David Craufurd · Jane Simpson ·
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    ABSTRACT: Individuals with a diagnosis of Huntington's disease (HD) have been shown to experience various emotional, behavioural and psychosocial consequences. The current study employs Leventhal's self-regulation model to explore the biopsychosocial factors related to psychological distress in people with HD, and further examine the relationship between illness perceptions, coping and psychological distress. Eighty-seven people diagnosed with HD completed the Illness Perceptions Questionnaire-Revised adapted for the population. Participants also completed self-report measures of coping and psychological distress. Data were also collected on clinical and demographic variables previously found to be associated with psychological distress. Hierarchical multiple regression analyses demonstrated that illness perceptions of identity, treatment control and timeline cyclical were predictors of anxiety while illness perceptions of identity and perceiving the cause to be related to chance were found to be significant positive predictors of depression. The coping strategy of seeking instrumental support also contributed to scores of depression, and self-report clinical variables of pain and role functioning related to physical difficulties predicted anxiety and depression, respectively. The findings suggest that illness perceptions play a significant role in psychological distress experienced by people with HD. Consequently, a focus on interventions which might change illness perceptions, and perhaps then reduce psychological distress, would be useful for future research.
    Psychology Health and Medicine 06/2013; 19(2). DOI:10.1080/13548506.2013.802355 · 1.26 Impact Factor
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    ABSTRACT: Background: Volumetric MRI studies have highlighted the pronounced loss of white matter in premanifest and early Huntington's Disease (HD). The current study focussed on the corpus callosum (CC) since it provides interhemispheric connections to vulnerable cortical areas. Objectives: To investigate cross-sectional and longitudinal group differences in CC volume and hypothesis-driven associations with three cognitive tasks. Methods: Baseline and 24-month 3T MRI were analysed from 106 premanifest (PreHD), (59 preHD-A ≥10.8 and 47 preHD-B <10.8 years from predicted onset), 84 early HD (53 Stage 1 (HD1) and 31 Stage 2 (HD2)) and 101 control subjects from the TRACK-HD study, using a semi-automated technique for CC delineation. Between-group differences in volume and 24-month atrophy rates, and correlations with cognitive performance were investigated using regression models, adjusting for potential confounders. Results: PreHD-B, HD1 and HD2 had statistically significantly smaller baseline CC volumes (p < 0.001) and all groups had elevated 24-month atrophy rates compared with controls (p < 0.001). Smaller baseline CC volume was associated with impaired performance in the Circle Tracing Indirect task in early HD (p < 0.05). Positive, non-statistically significant relationships with Stroop Word Reading were shown in both gene-positive groups. There was no evidence of an association with the Trail Making B task. Conclusions: We found reduced CC volume and elevated 24-month atrophy rates, even in individuals far from disease onset. Structural degeneration of interhemispheric connections may contribute to cognitive deficits, such as performance in the Circle Tracing Indirect task in HD. Examination of different image acquisitions may provide more specific information about underlying CC degeneration.
    Journal of Huntington's disease 01/2013; 2(4):517-526. DOI:10.3233/JHD-130077

Publication Stats

5k Citations
602.97 Total Impact Points


  • 2015
    • Institute for Human Development
      New Dilli, NCT, India
  • 2010-2014
    • Central Manchester University Hospitals NHS Foundation Trust
      Manchester, England, United Kingdom
  • 1989-2014
    • The University of Manchester
      • • Centre for Genetic Medicine
      • • Respiratory Medicine Research Group
      Manchester, England, United Kingdom
    • St. Mary Medical Center
      Long Beach, California, United States
  • 2009
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
  • 2004-2009
    • Saint Mary's Hospital Center
      Montréal, Quebec, Canada
  • 1990-2003
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 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