Classical complement pathway factor alterations in narcolepsy

2022 ◽  
pp. 1-8
Author(s):  
Hande Yüceer ◽  
Duygu Gezen Ak ◽  
Gülçin Benbir Şenel ◽  
Erdinç Dursun ◽  
Vuslat Yılmaz ◽  
...  

Abstract Objective: Narcolepsy is a chronic sleep disorder long hypothesised to be an autoimmune disease. Complement-mediated immune mechanisms have not been investigated in detail in narcolepsy. Our aim was to establish the significance of classical pathway activation in narcolepsy. Methods: Sera of 42 narcolepsy patients and 26 healthy controls were screened with ELISA to determine the levels of C1q, C3a, C4d and complement component 4 binding protein (C4BP). A home-made ELISA method was developed to detect antibodies to C4BP-alpha (anti-C4BPA). The correlation between complement levels and clinical findings was examined. Results: C1q levels were significantly higher in narcolepsy patients while C4d and C4BP levels were significantly lower compared to healthy controls. C3a levels were comparable among patients and controls. Eleven narcolepsy patients showed serum anti-C4BPA levels. Total rapid eye movements (REM) time, sleep onset latency, REM sleep latency, sleep activity, percentage of wakefulness after sleep onset and Epworth sleepiness scale scores were correlated with levels of different complement factors. Conclusion: Complement-mediated immune mechanisms might partake in narcolepsy pathogenesis. The precise role of autoantibodies on complement level alterations needs to be investigated. Levels of complement factors and degradation products may potentially be utilised as biomarkers to predict the clinical severity of narcolepsy.

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A303-A303
Author(s):  
Cagri Yuksel ◽  
Xi Chen ◽  
Lauren Watford ◽  
Margaret Gardner ◽  
Kathryn Lewandowski ◽  
...  

Abstract Introduction Recent studies show that sleep favors oligodendrocyte proliferation and myelination, and sleep loss is associated with alterations in white matter structure and decreased myelination. Psychotic disorders are characterized by disrupted white matter integrity, and abnormal axon and myelin structure. Despite common sleep disturbances in these disorders, little is known about the relationship between sleep quality and white matter findings. A novel in vivo neuroimaging technique that combines diffusion tensor spectroscopy (DTS) and magnetization transfer ratio (MTR) allows separately examining the axon structure and glial function, and myelin content, respectively. Using this method, we examined the association of sleep quality with white matter biology in a sample of patients with psychotic disorders and matched healthy controls. Methods Participants included patients diagnosed with bipolar disorder with psychotic features (euthymic or depressed, n=12) and schizophrenia spectrum disorders (n=9), and age and sex matched healthy controls (n=20). DTS and MTR data was collected from the right prefrontal white matter at 4T. DTS measures included apparent diffusion coefficients of water, NAA, creatine and choline. Sleep quality was measured using Pittsburgh Sleep Quality Index (PSQI). Results PSQI total score was significantly higher in patients. and patient sample included a higher percentage of poor sleepers (PSQI total score>5). In patients, total PSQI score and sleep onset latency were significantly and negatively associated with MTR (F=6.9, p=0.02 and F=9.7, p=0.007, respectively). There was no difference in any DTS measures between groups. Conclusion Our preliminary results show that poor sleep quality is associated with decreased myelin content in the frontal lobe, in patients with psychotic disorders. This finding suggests that sleep loss may be a mediator of white matter alterations in psychosis. Support (if any) This work is supported by National Institute of Mental Health K23MH119322 to Cagri Yuksel


2020 ◽  
Vol 238 (1) ◽  
pp. 83-94
Author(s):  
Lieke W. A. Hermans ◽  
Marta Regis ◽  
Pedro Fonseca ◽  
Sebastiaan Overeem ◽  
Tim R. M. Leufkens ◽  
...  

Abstract Rationale The mechanisms underlying impaired sleep quality in insomnia are not fully known, but an important role for sleep fragmentation has been proposed. Objectives The aim of this study is to explore potential mechanisms of sleep fragmentation influencing alterations of perceived sleep quality. Methods We analyzed polysomnography (PSG) recordings from a double-blind crossover study with zopiclone 7.5 mg and placebo, in elderly participants with insomnia complaints and age-matched healthy controls. We compared survival dynamics of sleep and wake across group and treatment. Subsequently, we used a previously proposed model to estimate the amount of sleep onset latency (SOL) misperception from PSG-defined sleep fragmentation. Self-reported and model-estimated amount of SOL misperception were compared across group and treatment, as well as model prediction errors. Results In the zopiclone night, the average segment length of NREM sleep was increased (group F = 1.16, p = 0.32; treatment F = 8.89, p< 0.01; group x treatment F = 0.44, p = 0.65), while the segment length of wake was decreased (group F = 1.48, p = 0.23; treatment F = 11.49, p< 0.01; group x treatment F = 0.36, p = 0.70). The self-reported and model-estimated amount of SOL misperception were lower during the zopiclone night (self-reported group F = 6.08, p< 0.01, treatment F = 10.8, p< 0.01, group x treatment F = 2.49, p = 0.09; model-estimated F = 1.70, p = 0.19, treatment F = 16.1, p< 0.001, group x treatment F = 0.60, p = 0.55). The prediction error was not altered (group F = 1.62, p = 0.20; treatment F = 0.20, p = 0.65; group x treatment F = 1.01, p = 0.37). Conclusions Impaired subjective sleep quality is associated with decreased NREM stability, together with increased stability of wake. Furthermore, we conclude that zopiclone-induced changes in SOL misperception can be largely attributed to predictable changes of sleep architecture.


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A418-A418
Author(s):  
I Y Chen ◽  
A B Neikrug ◽  
J Adams ◽  
L McMillan ◽  
M A Yassa ◽  
...  

Abstract Introduction Disturbances in sleep and behavioral activity rhythms (BAR) are frequently observed in individuals with depression. However, it remains unclear how activity variability across the 24-hour period is specifically associated with this disorder. The present study aimed to examine actigraphy-measured sleep and BAR in depression. Methods As part of a larger study, fourteen patients with DSM-5 major depressive episode (27.8±7.7 years, 69.2% female) and 13 healthy controls (21.8±1.2 years, 76.5% female) were evaluated with 7-14 days of wrist-actigraphy. Actigraphy-derived sleep parameters included total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE). Minute-by-minute activity counts were aggregated into hour-by-hour bins; hourly mean activity levels were then generated to depict 24-hour activity patterns (i.e., BAR). Factorial (GroupxTime) mixed models were conducted to examine whether BAR differed between patients with MDD and controls. Generalized Additive Models (GAM), by fitting smoothed nonlinear curves to log-transformed aggregated activity, were performed as exploratory analyses to characterize onset (UP slope) and offset (DOWN slope) of BAR. Results Compared to healthy controls, patients with MDD exhibited greater actigraphic TST (p=.026); no other between-group differences were detected for the remaining sleep parameters. Significant between-group differences were observed for mean activity during wakefulness (p&lt;.001). Mixed models assessing hour-by-hour daily activity revealed a significant GroupxTime interaction (p=.001) with significant main effects of group (p=.017) and time (p&lt;.001); patients with MDD had lower activity from 6 to 9 pm (ps&lt;.005). Exploratory GAMs results showed an attenuated DOWN slope in patients with MDD (p=.014), indicating a slower decrease in activity during the evening. Conclusion Altered BAR, characterized by an overall dampened activity pattern that was most prominent during the evening, was associated with depression. Furthermore, patients with MDD took longer to wind down in the evening. Future studies are needed to explore the potential benefits of adjunctive interventions addressing both BAR along with sleep in mitigating symptoms of depression. Support Research supported by National Institutes of Health R01 MH102392.


2021 ◽  
Author(s):  
E.C. Stanyer ◽  
H. Creeney ◽  
A.D. Nesbitt ◽  
P. R. Holland ◽  
J. Hoffmann

AbstractObjectivesSleep disturbance is often associated with migraine. However, there is a paucity of research investigating objective and subjective measures of sleep in migraineurs. This meta-analysis aims to determine whether there are differences in subjective sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI) and objective sleep physiology measured using polysomnography between adult and pediatric migraineurs, and healthy controls.MethodsA systematic search of five databases was conducted to find case-controlled studies which measured polysomnography and/or PSQI in migraineurs. Effect sizes (Hedges’ g) were entered into a random effects model meta-analysis.Results32 separate studies were eligible. Overall, adult migraineurs had higher PSQI scores than healthy controls (g = 0.75, p < .001). This effect was larger in chronic than episodic migraineurs (g = 1.03, p < .001, g = 0.63, p < .001 respectively). For polysomnographic studies, adult and pediatric migraineurs displayed a lower percentage of REM sleep (g = −0.22, p = 0.017, g = −0.71, p = 0.025 respectively) than healthy controls. Pediatric migraineurs also displayed less total sleep time (g = −1.37, p = 0.039), more wake (g = 0.52, p < .001) and shorter sleep onset latency (g = −0.37, p < .001) than healthy controls.ConclusionMigraineurs have significantly poorer subjective sleep quality, and altered sleep compared to healthy individuals – a finding which is particularly evident in children. This has implications for developing appropriate treatments. Further longitudinal empirical studies are required to enhance our understanding of this relationship.


ORL ro ◽  
2016 ◽  
Vol 4 (1) ◽  
pp. 56-59
Author(s):  
Raluca Ioana Teleanu ◽  
Magdalena Sandu ◽  
Eugenia Roza

Melatonin  is a hormone produced by the pineal gland during the night, as a response to the light-darkness variation. The endogenous melatonin levels have a cyclic evolution throughout the entire life. Various roles have been cited such as the in utero developement of the fetus through its action on the placenta, neurons and glial cells, a major role in the regulation of the cyrcadian rhythm, antioxidative, antiinflammatory roles, as well as celullar and umoral immunity modulation. In the European Union, exogenous melatonin has been evaluated by the European Food Safety Authority (EFSA) for reducing sleep onset latency and the conclusion was that it has efficacy studies in this regard.  


2020 ◽  
Vol 4 (2) ◽  
pp. 167-176
Author(s):  
Achim Elfering ◽  
Christin Gerhardt ◽  
Diana Pereira ◽  
Anna Schenker ◽  
Maria U. Kottwitz

Abstract Purpose Accidents are more likely to occur during the morning hours of Mondays (Monday effect). This might be due to a higher level of cognitive failure on Monday morning at work. Methods In a pilot actigraphy study across one working week, we explored this Monday effect and regressed daily self-reported workplace cognitive failure on weekdays (Monday versus other days), background social stressors at work, delayed sleep onset and sleep duration. Diary data were gathered from 40 full-time employees. Results Confirming our assumptions, results revealed work-related cognitive failure and sleep-onset latency on the previous night to be higher on Mondays compared to other workdays. Work-related cognitive failure correlated positively with delayed sleep-onset latency and background social stressors. In multilevel regression analysis, Monday significantly explained variations in workplace cognitive failure. The addition of background social stressors at work and sleep-onset latency to the regression model showed unique contributions to the prediction of workplace cognitive failure. No significant two-way or three-way interactions between working days, sleep-onset latency or sleep duration, and background social stressors were found. Conclusion Peak levels of cognitive failure on Monday morning and the association of cognitive failure with social stressors at work contribute to understanding the mechanisms involved in the increased prevalence of occupational accidents on Monday morning. Occupational safety interventions should address both social stressors at work and individual sleep hygiene.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A78-A78
Author(s):  
Zahra Mousavi ◽  
Jocelyn Lai ◽  
Asal Yunusova ◽  
Alexander Rivera ◽  
Sirui Hu ◽  
...  

Abstract Introduction Sleep disturbance is a transdiagnostic risk factor that is so prevalent among emerging adults it is considered to be a public health epidemic. For emerging adults, who are already at greater risk for psychopathology, the COVID-19 pandemic has disrupted daily routines, potentially changing sleep patterns and heightening risk factors for the emergence of affective dysregulation, and consequently mood-related disturbances. This study aimed to determine whether variability in sleep patterns across a 3-month period was associated with next-day positive and negative affect, and affective dynamics, proximal affective predictors of depressive symptoms among young adults during the pandemic. Methods College student participants (N=20, 65% female, Mage=19.80, SDage=1.0) wore non-invasive wearable devices (the Oura ring https://ouraring.com/) continuously for a period of 3-months, measuring sleep onset latency, sleep efficiency, total sleep, and time spent in different stages of sleep (light, deep and rapid eye movement). Participants reported daily PA and NA using the Positive and Negative Affect Schedule on a 0-100 scale to report on their affective state. Results Multilevel models specifying a within-subject process of the relation between sleep and affect revealed that participants with higher sleep onset latency (b= -2.98, p&lt;.01) and sleep duration on the prior day (b= -.35, p=.01) had lower PA the next day. Participants with longer light sleep duration had lower PA (b= -.28, p=.02), whereas participants with longer deep sleep duration had higher PA (b= .36, p=.02) the next day. On days with higher total sleep, participants experienced lower NA compared to their own average (b= -.01, p=.04). Follow-up exploratory bivariate correlations revealed significant associations between light sleep duration instability and higher instability in both PA and NA, whereas higher deep sleep duration was linked with lower instability in both PA and NA (all ps&lt; .05). In the full-length paper these analyses will be probed using linear regressions controlling for relevant covariates (main effects of sleep, sex/age/ethnicity). Conclusion Sleep, an important transdiagnostic health outcome, may contribute to next-day PA and NA. Sleep patterns predict affect dynamics, which may be proximal predictors of mood disturbances. Affect dynamics may be one potential pathway through which sleep has implications for health disparities. Support (if any):


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A144-A144
Author(s):  
Kathleen O’Hora ◽  
Beatriz Hernandez ◽  
Laura Lazzeroni ◽  
Jamie Zeitzer ◽  
Leah Friedman ◽  
...  

Abstract Introduction The prevalence of insomnia complaints in older adults is 30–48%, compared to 10–15% in the general population. Cognitive Behavioral Therapy for Insomnia (CBT-I) is a first-line, non-pharmacological sleep treatment for Insomnia. However, the relative impact of Behavioral (BT) and Cognitive (CT) components compared to that of CBT-I in older adults is unknown. Methods 128 older adults with insomnia were randomized to receive CBT-I, BT, or CT. Sleep diaries and the Insomnia Severity Index (ISI) were collected pre- and post-treatment and at a 6-month follow-up. We conducted split-plot linear mixed models with age and sex as covariates to assess within and between subject changes to test effects of group, time, and their interaction on ISI, sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), time in bed (TIB), sleep efficiency (SE), and percent of treatment responders (ISI decrease&gt;7) and remitters (ISI&lt;8). Effect size (d) was calculated by dividing the difference between means by the root-mean-squared error of the mixed effects model. Results All treatments lead to a significant improvement across outcome measures at post-treatment (p’s&lt;0.001) and 6-months (p’s&lt;0.01), with the exception of TIB, response, and remission. For TIB, there was a significant Group x Time interaction (p&lt;0.001): while all treatments significantly reduced TIB post-treatment relative to baseline, CBT-I (p&lt;0.001,d=-2.26) and BT (p&lt;0.001,d=-1.59) performed significantly better than CT (p=0.003, d=-0.68). In contrast, at 6-months CBT-I (p&lt;0.001,d=-1.16) performed significantly better at reducing TIB than CT (p=0.195,d=-0.24) or BT (p=0.023,d=-0.61) relative to baseline. There was also a non-significant trend for a Group x Time interaction for remission status (p=0.062). Whereas, the percentage of remitters within all groups post-treatment did not differ from chance (p&gt;0.234), at 6 months, the percentage of remitters was significantly higher than chance in CBT-I (73.63%,p=0.026) and BT (78.08%,p=0.012), but not CT (47.85%,p=0.826). There were no other significant time or interaction effects (all p&gt;0.05). Conclusion CBT-I and its components are effective in improving subjective insomnia symptoms in older adults. Evidence suggests CBT-I may be superior to either CT or BT alone in improving TIB in older adults. Support (if any) NIMHR01MH101468; MIRECC at VAPAHCS


Author(s):  
Frank Faltraco ◽  
Denise Palm ◽  
Adriana Uzoni ◽  
Lena Borchert ◽  
Frederick Simon ◽  
...  

AbstractA link between dopamine levels, circadian gene expression, and attention deficit hyperactivity disorder (ADHD) has already been demonstrated. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after dopamine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different dopamine concentrations in human dermal fibroblast (HDF) cultures, the rhythmicity of circadian gene expression (Clock, Bmal1, Per1-3, Cry1) was analyzed via qRT-PCR. We found no statistical significant effect in the actigraphy of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, wake after sleep onset, and total number of wake bouts. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. Dopamine has no effect on Per3 expression in healthy controls, but produces a significant difference in the ADHD group at ZT24 and ZT28. In the ADHD group, incubation with dopamine, either 1 µM or 10 µM, resulted in an adjustment of Per3 expression to control levels. A similar effect also was found in the expression of Per2. Statistical significant differences in the expression of Per2 (ZT4) in the control group compared to the ADHD group were found, following incubation with dopamine. The present study illustrates that dopamine impacts on circadian function. The results lead to the suggestion that dopamine may improve the sleep quality as well as ADHD symptoms by adjustment of the circadian gene expression, especially for Per2 and Per3.


Author(s):  
Bente Storm Mowatt Haugland ◽  
Mari Hysing ◽  
Asle Hoffart ◽  
Åshild Tellefsen Haaland ◽  
Jon Fauskanger Bjaastad ◽  
...  

AbstractThe potential effect of early intervention for anxiety on sleep outcomes was examined in a sample of adolescents with anxiety (N = 313, mean 14.0 years, SD = 0.84, 84% girls, 95.7% Norwegians). Participants were randomized to one of three conditions: a brief or a standard-length cognitive-behavioral group-intervention (GCBT), or a waitlist control-group (WL). Interventions were delivered at schools, during school hours. Adolescents with elevated anxiety were recruited by school health services. Questionnaires on self-reported anxiety symptoms, depressive symptoms, and sleep characteristics were administered at pre- and post-intervention, post-waitlist, and at 1-year follow-up. Adolescents reported reduced insomnia (odds ratio (OR) = 0.42, p < 0.001) and shorter sleep onset latency (d = 0.27, p <  0.001) from pre- to post-intervention. For insomnia, this effect was maintained at 1-year follow-up (OR = 0.54, p = 0.020). However, no effect of GCBT on sleep outcomes was found when comparing GCBT and WL. Also, no difference was found in sleep outcomes between brief and standard-length interventions. Adolescents defined as responders (i.e., having improved much or very much on anxiety after GCBT), did not differ from non-responders regarding sleep outcomes. Thus, anxiety-focused CBT, delivered in groups, showed no effect on sleep outcomes. Strategies specifically targeting sleep problems in adolescents should be included in GCBT when delivered as early intervention for adolescents with elevated anxiety.Trial registry Clinical trial registration: School Based Low-intensity Cognitive Behavioral Intervention for Anxious Youth (LIST); http://clinicalrials.gov/; NCT02279251, Date: 11.31. 2014


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