Perceived stress in prodromal Huntington disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Downing N
PROVIDER: S-EPMC3165107 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Perceived stress in prodromal Huntington disease.
Downing Nancy N Smith Megan M MM Beglinger Leigh J LJ Mills James J Duff Kevin K Rowe Kelly C KC Epping Eric E Paulsen Jane S JS
Psychology & health 20110621 2
This study examines perceived stress and its relationship to depressive symptoms, life changes and functional capacity in a large sample of individuals who are positive for the Huntington disease (HD) gene expansion but not yet diagnosed. Participants were classified by estimated proximity to HD diagnosis (far, mid, near) and compared with a non-gene-expanded comparison group. Persons in the mid group had the highest stress scores. A significant interaction between age and time since HD genetic ...[more]
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Project description:OBJECTIVE:Assessment of daily functions affected by cognitive loss in prodromal Huntington's disease (HD) is necessary in practice and clinical trials. We evaluated baseline and longitudinal sensitivity of the Everyday Cognition (ECog) scales in prodromal HD and compared self- and companion-ratings. METHOD:Everyday cognition was self-assessed by 850 participants with prodromal HD and 768 companions. We examined internal structure using confirmatory factor analysis (CFA) on baseline data. For longitudinal analysis, we stratified participants into Low, Medium, and High disease progression groups. We examined ECog scores for group differences and participant-and-companion differences using linear mixed effects regression (LMER). Comparison with the Total Functional Capacity (TFC) scale was made. RESULTS:CFA revealed good fit of a 5-factor model having a global factor (total score), and subfactors (subscales) of memory, language, visuospatial perception, and executive function. At study entry, participants and companions in the Medium and High groups reported significantly worsened everyday cognition as well as significant functional decline over time. Losses became more pronounced and participant and companion ratings diverged as individuals progressed. TFC showed significant functional loss over time in the High group but not in the Medium group. CONCLUSIONS:Disease progression is associated with reduced self- and companion-reported everyday cognition in prodromal HD participants who are less than 13 years to estimated motor onset. Our findings suggest companion ratings are more sensitive than participants' for detecting longitudinal change in daily cognitive function. ECog appears more sensitive to specific functional changes in the prodrome of HD than the TFC.
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Project description:Antidepressant usage in prodromal Huntington Disease (HD) remains uncharacterized, despite its relevance in designing experiments, studying outcomes of HD, and evaluating the efficacy of therapeutic interventions. We searched baseline medication logs of 787 prodromal HD and 215 healthy comparison (HC) participants for antidepressant use. Descriptive and mixed-effects logistic regression modeling characterized usage across participants. At baseline, approximately one in five prodromal HD participants took antidepressants. Of those, the vast majority took serotonergic antidepressants (selective serotonin reuptake inhibitor (SSRI) or serotonin/norepinephrine reuptake inhibitor (SNRI)). Significantly more prodromal HD participants used serotonergic antidepressants than their HC counterparts. Because of the prevalence of these medications, further analyses focused on this group alone. Mixed-effects logistic regression modeling revealed significant relationships of both closer proximity to diagnosis and female sex with greater likelihood to be prescribed a serotonergic antidepressant. More prodromal HD participants took antidepressants in general and specifically the subclass of serotonergic antidepressants than their at-risk counterparts, particularly when they were closer to predicted time of conversion to manifest HD. These propensities must be considered in studies of prodromal HD participants.
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Project description:Cognitive changes in the prodromal phase of Huntington disease (prHD) are found in multiple domains, yet their neural bases are not well understood. One component process that supports cognition is inhibitory control. In the present fMRI study, we examined brain circuits involved in response inhibition in 65 prHD participants and 36 gene-negative (NEG) controls using the stop signal task (SST). PrHD participants were subdivided into three groups (LOW, MEDIUM, HIGH) based on their CAG-Age Product (CAP) score, an index of genetic exposure and a proxy for expected time to diagnosis. Poorer response inhibition (stop signal duration) correlated with CAP scores. When response inhibition was successful, activation of the classic frontal inhibitory-network was normal in prHD, yet stepwise reductions in activation with proximity to diagnosis were found in the posterior ventral attention network (inferior parietal and temporal cortices). Failures in response inhibition in prHD were related to changes in inhibition centers (supplementary motor area (SMA)/anterior cingulate and inferior frontal cortex/insula) and ventral attention networks, where activation decreased with proximity to diagnosis. The LOW group showed evidence of early compensatory activation (hyperactivation) of right-hemisphere inhibition and attention reorienting centers, despite an absence of cortical atrophy or deficits on tests of executive functioning. Moreover, greater activation for failed than successful inhibitions in an ipsilateral motor-control network was found in the control group, whereas such differences were markedly attenuated in all prHD groups. The results were not related to changes in cortical volume and thickness, which did not differ among the groups. However, greater hypoactivation of classic right-hemisphere inhibition centers [inferior frontal gyrus (IFG)/insula, SMA/anterior cingulate cortex (ACC)] during inhibition failures correlated with greater globus pallidus atrophy. These results are the first to demonstrate that response inhibition in prHD is associated with altered functioning in brain networks that govern inhibition, attention, and motor control.
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Project description:Analysis of microRNA (miRNA) expression in CSF from prodromal Huntington disease patients.
2020-05-10 | GSE150174 | GEO
Project description:As therapeutics are being developed to target the underlying neuropathology of Huntington disease, interest is increasing in methodologies for conducting clinical trials in the prodromal phase. This study was designed to examine the potential utility of structural MRI measures as outcome measures for such trials.Data are presented from 211 prodromal individuals and 60 controls, scanned both at baseline and at the 2-year follow-up. Prodromal participants were divided into groups based on proximity to estimated onset of diagnosable clinical disease: far (>15 years from estimated onset), mid (9-15 years) and near (<9 years). Volumetric measurements of caudate, putamen, total striatum, globus pallidus, thalamus, total grey and white matter and cerebrospinal fluid were performed.All prodromal groups showed a faster rate of atrophy than controls in striatum, total brain and cerebral white matter (especially in the frontal lobe). Neither prodromal participants nor controls showed any significant longitudinal change in cortex (either total cortical grey or within individual lobes). When normal age-related atrophy (ie, change observed in the control group) was taken into account, there was more statistically significant disease-related atrophy in white matter than in striatum.Measures of volume change in striatum and white-matter volume, particularly in the frontal lobe, may serve as excellent outcome measures for future clinical trials in prodromal Huntington disease. Clinical trials using white matter or striatal volume change as an outcome measure will be most efficient if the sample is restricted to individuals who are within 15 years of estimated onset of diagnosable disease.
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