Zonisamide effects on sleep problems and depressive symptoms in Parkinson's disease.
Ontology highlight
ABSTRACT: Background
We aimed to evaluate the effect of zonisamide (ZNS) on motor symptoms and nonmotor symptoms such as depressive symptoms and sleep problems in Parkinson's disease (PD) patients with or without tremor.Methods
We conducted a 3-month, open-label study to assess the effects of ZNS on motor symptoms, depressive symptoms and sleep problems. Twenty levodopa-treated PD patients with motor fluctuation completed the study. Patients received 25-50 mg/day of ZNS and were assessed for the Japanese version of the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts I, III, and IV, PD Sleep Scale (PDSS)-2, Beck depression inventory-2 (BDI-II), and PD Questionnaire (PDQ-8) at baseline and after 1, 2 and 3 months of treatment. Patients were categorized into the tremor group and nontremor group to assess changes in clinical parameters.Results
At 3 months, the scores on the MDS-UPDRS parts I, III and IV significantly improved and off-time reduced compared to baseline. Additionally, the PDSS-2 total score significantly decreased at 3 months. Although there were no significant differences in changes in UPDRS part I, III, or IV between the groups after ZNS treatment, the tremor group had significant improvements in PDSS-2 at 3 months and BDI-II at 1, 2 and 3 months compared with the nontremor group.Conclusion
We showed the beneficial effects of ZNS on motor symptoms and sleep problems in levodopa-treated PD patients with motor fluctuation. ZNS may be more effective for several nonmotor symptoms in PD patients with tremor compared with those without tremor.
SUBMITTER: Suzuki K
PROVIDER: S-EPMC7994695 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:AimTo assess prevalence and characteristics of vasomotor symptoms in community-dwelling Japanese women.MethodsThese were cross-sectional analyses using data from the National Institute for Longevity Sciences-Longitudinal Study of Aging. The main outcome measures were prevalence and severity of hot flashes and sweating. Associations between hot flashes/sweating (slight, moderate, or severe vs none) and sleep problems were explored using logistic regression, with and without adjustment for age, daily physical activity, and number of urinations/night. Associations between hot flashes/sweating and sleep problems, depressive symptoms, and dietary variables were explored in logistic regression models or general linear models.ResultsA total of 1152 women between 40 and 91 years of age were enrolled. Hot flashes were reported by 24.5% of participants; with prevalence and severity highest in those 50-54 years or 2-5 years postmenopause. Sleep problems were reported 15 percentage points more frequently by women who reported hot flashes than by those without hot flashes. Adjusted odds ratios [95% CI] for difficulty in falling asleep and difficulty in sleeping through were 2.09 [1.565-2.796] and 2.07 [1.549-2.763]), respectively. Also, hot flashes were associated with higher risk of depressive symptoms (adjusted odds ratio [95% CI]: 2.99 [2.07-4.32]) and lower life satisfaction, self-esteem, and self-rated health status. A similar pattern was observed in women with and without sweating. No associations were found between hot flashes and dietary factors.ConclusionsClear associations were found between hot flashes and sleeping problems, even after adjusting for potential confounding factors. Women who reported hot flashes also reported worse mental and physical health than those who did not report hot flashes.
| S-EPMC9291044 | biostudies-literature
Project description:BackgroundNon-motor symptoms, including sleep disorders and depression, are common in Parkinson's disease (PD). The purpose of our study is to explore the effect of sleep disorders, including the probable rapid eye movement (REM) sleep behavior disorder (pRBD) and the daytime sleepiness, on depressive symptoms in patients with early and prodromal PD.MethodsA total of 683 participants who obtained from the Parkinson Progression Markers Initiative (PPMI) were included, consisting of 423 individuals with early PD, 64 individuals with prodromal PD, and 196 healthy controls (HCs), who were followed up to 5 years from baseline. Multiple linear regression models and linear mixed-effects models were conducted to explore the relationship between sleep disorders and depression at baseline and longitudinally, respectively. Multiple linear regression models were used to further investigate the association between the change rates of daytime sleepiness score and depression-related score. Mediation analyses were also performed.ResultsAt baseline analysis, individuals with early and prodromal PD, who had higher RBD screening questionnaire (RBDSQ) score, or who were considered as pRBD, or who manifested specific behaviors of RBD (things falling down when sleep or disturbance of sleep), showed significantly the higher score of depression-related questionnaires. Our 5-year follow-up study showed that sleep disorders, including pRBD and daytime sleepiness, were associated with the increased depressive-related score in individuals with early and prodromal PD. Interestingly, we also found that the increased possibilities of daytime sleepiness were associated with depressive-related score. Finally, mediation analysis demonstrated that the relationship between RBD and depressive symptoms was partially mediated by autonomic symptoms, such as postural hypertension, salivation, dysphagia, and constipation.ConclusionOur study shows that sleep disorders, including pRBD and daytime sleepiness, are associated with depression at baseline and longitudinally, which is partially mediated by the autonomic dysfunction in early and prodromal PD, with an implication that sleep management is of great value for disease surveillance.
| S-EPMC9226450 | biostudies-literature
Project description:The diagnosis of Parkinson's disease (PD) is currently anchored on clinical motor symptoms, which appear more than 20 years after initiation of the neurotoxicity. Extra-nigral involvement in the onset of PD with probable nonmotor manifestations before the development of motor signs, lead us to the preclinical (asymptomatic) or prodromal stages of the disease (various nonmotor or subtle motor signs). REM sleep behavior disorder (RBD) and depression are established prodromal clinical markers of PD and predict worse motor and cognitive outcomes. Nevertheless, taken by themselves, these markers are not yet claimed to be practical in identifying high-risk individuals. Combining promising markers may be helpful in a reliable diagnosis of early PD. Therefore, we aimed to detect neural correlates of RBD and depression in 93 treatment-naïve and non-demented early PD by means of diffusion MRI connectometry. Comparing four groups of PD patients with or without comorbid RBD and/or depressive symptoms with each other and with 31 healthy controls, we found that these two non-motor symptoms are associated with lower connectivity in several white matter tracts including the cerebellar peduncles, corpus callosum and long association fibers such as cingulum, fornix, and inferior longitudinal fasciculus. For the first time, we were able to detect the involvement of short association fibers (U-fibers) in PD neurodegenerative process. Longitudinal studies on larger sample groups are needed to further investigate the reported associations.
| S-EPMC6028696 | biostudies-other
Project description:Sleep disturbances are common non-motor symptoms in Parkinson's disease (PD). Experimental studies suggest involvement of the serotonergic system in the regulation of sleep and arousal. Using [11C]DASB positron emission tomography, a marker of serotonin transporter availability, we investigated whether sleep dysfunction is associated with serotonergic dysfunction in PD.We studied 14 PD patients with sleep dysfunction, 14 PD without sleep dysfunction, and 12 healthy controls. Groups were matched for age, disease duration, severity of motor symptoms, daily intake of levodopa equivalent units, body-mass-index, depression and fatigue. [11C]DASB non-displaceable binding potential (BPND) was calculated for regions with a role in the regulation of sleep and arousal.[11C]DASB BPND was reduced by 32-49% in PD patients with sleep dysfunction, and 14-25% in PD without sleep dysfunction, compared to healthy controls. PD patients with sleep dysfunction had lower [11C]DASB BPND in caudate (P?<?0.01), putamen (P?<?0.001), ventral striatum (P?<?0.001), thalamus (P?<?0.05), hypothalamus (P?<?0.001) and raphe nuclei (P?<?0.01), compared to PD without sleep dysfunction. Higher severity of sleep symptoms (assessed with Parkinson Disease Sleep Scale) correlated with lower [11C]DASB binding in caudate (r?=?0.77; P?<?0.001), putamen (r?=?0.84; P?<?0.001), ventral striatum (r?=?0.86; P?<?0.001), thalamus (r?=?0.79; P?<?0.001), hypothalamus (r?=?0.90; P?<?0.001) and raphe nuclei (r?=?0.83; P?<?0.001).Our findings demonstrate that sleep dysfunction in PD is associated with reduced serotonergic function in the midbrain raphe, basal ganglia and hypothalamus. Strategies to increase serotonin levels in the brain could be a promising approach to treat sleep dysfunction in PD, and may also have relevance in other neurodegenerative disorders.
| S-EPMC5964830 | biostudies-other
Project description:BackgroundSleep problems are associated with increased risk of physical and mental illness. Identifying risk factors is an important method of reducing public health impact. We examined the association between maternal postnatal depression (PND) and offspring adolescent sleep problems.MethodThe sample was derived from Avon Longitudinal Study of Parents and Children (ALSPAC) participants. A sample with complete data across all variables was used, with four outcome variables. A sensitivity analysis imputing for missing data was conducted (n = 9633).ResultsPND was associated with increased risk of sleep problems in offspring at ages 16 and 18 years. The most robust effects were sleep problems at 18 years [adjusted odds ratio (OR) for a 1 s.d. increase in PND, 1.26, 95% confidence interval (CI) 1.15-1.39, p < 0.001] and waking more often (adjusted OR 1.14, 95% CI 1.05-1.25, p = 0.003). This remained after controlling for confounding variables including antenatal depression and early sleep problems in infancy.ConclusionsPND is associated with adolescent offspring sleep problems. Maternal interventions should consider the child's increased risk. Early sleep screening and interventions could be introduced within this group.
| S-EPMC5244447 | biostudies-literature
Project description:ObjectivesExperiences of racial discrimination are common for Black Americans and have been associated with depression and sleep disturbance, factors likely involved in the insidious development of health disparities. The current study replicates these associations and examines longitudinal linkages.MethodBlack American couples (men: N = 248, Mage = 40, SD = 9; women: N = 277, Mage = 37, SD = 7) and their children, aged 9 to 14 (N = 276, Mage = 11, SD = 1), completed measures of experiences of racial discrimination, depressive symptoms, and sleep problems at baseline and 8-month follow-up. In separate analyses for men, women, and youth, we examined concurrent and prospective associations of racial discrimination with depressive symptoms and sleep problems, then used longitudinal indirect effect models to examine whether depressive symptoms in response to racial discrimination led to increased sleep problems, or vice versa.ResultsRacial discrimination was associated concurrently with depressive symptoms and sleep problems for all family members. Prospective associations were also found with depressive symptoms and sleep problems in fathers and youth, and sleep problems in mothers. Longitudinal models showed significant indirect effects of racial discrimination on change in sleep problems through depressive symptoms for fathers and mothers, and a similar, but nonsignificant, pattern in youth. There were no indirect effects on change in depressive symptoms through sleep problems.ConclusionsPersistent associations of racial discrimination with depressive symptoms and sleep problems reflect a lasting impact of racial discrimination. Because discrimination's effects on depression may contribute to increased sleep problems over time, interventions that buffer the effects of discrimination on depressive symptoms may also reduce sleep problems. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
| S-EPMC7876626 | biostudies-literature
Project description:Although many experimental studies have shown the favorable effects of zonisamide on mitochondria using models of Parkinson's disease (PD), the influence of zonisamide on metabolism in PD patients remains unclear. To assess metabolic status under zonisamide treatment in PD, we performed a pilot study using a comprehensive metabolome analysis. Plasma samples were collected for at least one year from 30 patients with PD: 10 without zonisamide medication and 20 with zonisamide medication. We performed comprehensive metabolome analyses of plasma with capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography time-of-flight mass spectrometry. We also measured disease severity using Hoehn and Yahr (H&Y) staging and the Unified Parkinson's Disease Rating Scale (UPDRS) motor section, and analyzed blood chemistry. In PD with zonisamide treatment, 15 long-chain acylcarnitines (LCACs) tended to be increased, of which four (AC(12:0), AC(12:1)-1, AC(16:1), and AC(16:2)) showed statistical significance. Of these, two LCACs (AC(16:1) and AC(16:2)) were also identified by partial least squares analysis. There was no association of any LCAC with age, disease severity, levodopa daily dose, or levodopa equivalent dose. Because an upregulation of LCACs implies improvement of mitochondrial β-oxidation, zonisamide might be beneficial for mitochondrial β-oxidation, which is suppressed in PD.
| S-EPMC6356654 | biostudies-literature
Project description:Depression is one of the most common non-motor symptoms in Parkinson's disease (PD). A thorough understanding of factors associated with depressive symptomatology may facilitate early detection and guide future intervention strategies. The objective of the study was to determine associated and predictive factors of depression in patients with PD. Analyses were performed in data of the SCOPA-PROPARK cohort, a 5-year hospital-based longitudinal cohort of over 400 PD patients who have been examined annually. Linear mixed models using data of all patients were used to identify factors associated with longitudinal changes in Beck Depression Inventory (BDI) scores. A survival analysis using data of patients without depression at baseline was performed to identify risk factors for future depression (i.e. BDI ≥ 15). The proportion of patients with depression was approximately 20 % and remained stable during follow-up, with approximately half of cases showing a persistent course. Female gender, more severe disability, more severe motor fluctuations, autonomic and cognitive dysfunction, poorer nighttime sleep and daytime sleepiness were independently associated with higher BDI scores over time. Higher baseline BDI score, daytime sleepiness and a higher levodopa dosage were risk factors for future depression. Depression is common in PD, where it may follow a persistent or non-persistent course. Apart from motor fluctuations and levodopa dose, depressive symptoms in PD are mainly associated with factors of non-dopaminergic origin. This suggests that depression in PD is an inherent consequence of the progressive pathobiology of the disease, which may render its treatment with currently available treatment options difficult.
| S-EPMC4893359 | biostudies-literature
Project description:Depression and its related mood disorders are a major global health issue that disproportionately affects young adults. A number of factors that influence depressive symptoms are particularly relevant to the young adult developmental stage, including sleep loss, poor sleep quality, and the tendency toward eveningness in circadian preferences. However, relatively few studies have examined the relationship between sleep and circadian phenotypes, and their respective influences on mood, or considered potential molecular mechanisms driving these associations. Here, we use a multi-year, cross-sectional study of 806 primarily undergraduates to examine the relationships between sleep-wake chronotype, sleep disturbance, depression and genotypes associated with the PER3 variable number of tandom repeats (VNTR) polymorphism-circadian gene variants associated with both chronotype and sleep homeostatic drive. In addition, we use objective, Fitbit-generated sleep structure data on a subset of these participants (n = 67) to examine the relationships between chronotype, depression scores, actual measures of sleep duration, social jetlag, and the percent of deep and rapid eye movement (REM) sleep per night. In this population, chronotype is weakly associated with depressive symptoms and moderately correlated with self-reported sleep disturbance. Sleep disturbance is significantly associated with depression scores, but objective sleep parameters are not directly correlated with Beck Depression Inventory (BDI-II) scores, with the exceptions of a moderate correlation between social jetlag and depression scores in females and a marginal correlation between sleep duration and depression scores. Multiple regression and path analyses reveal that chronotype effects on depressive symptoms in this population are mediated largely by sleep disturbance. The PER3 VNTR genotype significantly predicts depressive symptoms in a model with objective sleep parameters, but it does not significantly predict depressive symptoms in a model with chronotype or subjective sleep disturbance. Interestingly, PER35,5 genotypes, in males only, are independently related to chronotype and depression scores. Our results support hypotheses linking subjective sleep quality and chronotype and provide a first step in understanding how objective sleep structure may be linked to chronotype and depressive symptoms. Our results also suggest that circadian gene variants may show sex-specific effects linking sleep duration and sleep structure to depression.
| S-EPMC7479229 | biostudies-literature
Project description:BackgroundAdolescent electronic cigarette (e-cigarette) use remains high. Elucidating contributing factors may enhance prevention strategies. Neurobiologically, amygdala-insula resting-state functional connectivity (rsFC) has been linked with aspects of sleep, affect, and substance use (SU). As such, we hypothesized that amygdala's rsFC with the insula would be associated with e-cigarette use via sleep problems and/or depression levels.MethodsAn adolescent sample (N = 146) completed a rs-fMRI scan at time 1 and self-reports at time 2 (∼15 months later). Given consistent associations between mental health outcomes and the rsFC of the laterobasal amygdala (lbAMY) with the anterior insula, we utilized a seed region (lbAMY) to region of interest (ROI) analysis approach to characterize brain-behavior relationships. Two serial mediation models tested the interrelations between amygdala's rsFC with distinct anterior insula subregions (i.e., ventral insula [vI], dorsal insula [dI]), sleep problems, depression levels, and days of e-cigarette use.ResultsAn indirect effect was observed when considering the lbAMY's rsFC with the vI. Greater rsFC predicted more sleep problems, more sleep problems were linked with greater depressive symptoms, and greater depressive symptoms were associated with more e-cigarette use (indirect effect = 0.08, CI [0.01,0.21]). Indicative of a neurobiological dissociation, a similar indirect effect linking these variables was not observed when considering the lbAMY's rsFC with the dI (indirect effect = 0.03, CI [-0.001,0.10]).ConclusionsThese outcomes highlight functional interactions between the amygdala and insula as a neurobiological contributor to sleep problems, depressive symptoms, and ultimately SU thereby suggesting potential intervention points to reduce teen e-cigarette use.
| S-EPMC9730909 | biostudies-literature