Tag: insomnia

Sleep Disorders in Post-COVID Syndrome: A Psychiatric or Neurological Problem?

Abstract:

The coronavirus pandemic that began in 2019 continues. COVID-19 adversely affects human health not only in the acute, but also in the long-term period of the disease: in a large percentage of cases, health is not fully restored after long periods, requires medical intervention, and is often difficult to correct.

Researchers noted during the first wave of the pandemic in 2020 that about 10-20% of patients did not fully recover by three weeks from disease onset and the possible duration of the recovery period remains insufficiently clear, as do the reasons for differences in course during this period. Prolonged recovery after viral infection is not a feature exclusive to COVID-19, which does not facilitate the management of patients with post-COVID syndrome (PCS).

The mental health impact of COVID-19 is significant, with at least 30% of recovered patients likely to have symptoms of anxiety and/or depression after the acute phase has passed. Since the onset of COVID-19, there has been an increase in sleep disorders by 42%, with every third COVID-19 survivor reporting sleep complaints. In PCS, this condition is referred to as coronasomnia.

The success of therapy for this condition depends on identifying and correcting patients’ mental disorders, as anxiety and depression are often accompanied by sleep disorders this results in a bidirectional interaction between mental disorders and sleep quality. This article presents data on the anti-anxiety drugs Noofen and Adaptol, which help to correct the manifestations of PCS with sleep disorders.

Source: Kotova OV, Medvedev VE, Poluektov MG, Belyaev AA, Akarachkova ES. Sleep Disorders in Post-COVID Syndrome: A Psychiatric or Neurological Problem? Neurosci Behav Physiol. 2023;53(1):16-20. doi: 10.1007/s11055-023-01385-w. Epub 2023 Mar 11. PMID: 36969358; PMCID: PMC10006556. https://link.springer.com/article/10.1007/s11055-023-01385-w (Full text available as PDF file)

 

Persistent short nighttime sleep duration is associated with a greater post-COVID risk in fully mRNA-vaccinated individuals

Abstract:

Short nighttime sleep duration impairs the immune response to virus vaccination, and long nighttime sleep duration is associated with poor health status. Thus, we hypothesized that short (<6 h) and long (>9 h) nighttime sleepers have a higher post-COVID risk than normal nighttime sleepers, despite two doses of mRNA vaccine (which has previously been linked to lower odds of long-lasting COVID-19 symptoms). Post-COVID was defined as experiencing at least one core COVID-19 symptom for at least three months (e.g., shortness of breath).

Multivariate logistic regression adjusting for age, sex, BMI, and other factors showed in 9717 respondents (age span 18-99) that two mRNA vaccinations lowered the risk of suffering from post-COVID by about 21% (p < 0.001). When restricting the analysis to double-vaccinated respondents (n = 5918), short and long sleepers exhibited a greater post-COVID risk than normal sleepers (adjusted OR [95%-CI], 1.56 [1.29, 1.88] and 1.87 [1.32, 2.66], respectively). Among respondents with persistent sleep duration patterns during the pandemic compared to before the pandemic, short but not long sleep duration was significantly associated with the post-COVID risk (adjusted OR [95%-CI], 1.59 [1.24, 2.03] and 1.18 [0.70, 1.97], respectively). No significant association between sleep duration and post-COVID symptoms was observed in those reporting positive SARS-CoV-2 test results (n = 538).

Our findings suggest that two mRNA vaccinations against SARS-CoV-2 are associated with a lower post-COVID risk. However, this protection may be less pronounced among those sleeping less than 6 h per night. Our findings warrant replication in cohorts with individuals with confirmed SARS-CoV-2 infection.

Source: Xue P, Merikanto I, Chung F, Morin CM, Espie C, Bjorvatn B, Cedernaes J, Landtblom AM, Penzel T, De Gennaro L, Holzinger B, Matsui K, Hrubos-Strøm H, Korman M, Leger D, Mota-Rolim S, Bolstad CJ, Nadorff M, Plazzi G, Reis C, Chan RNY, Wing YK, Yordanova J, Bjelajac AK, Inoue Y, Partinen M, Dauvilliers Y, Benedict C. Persistent short nighttime sleep duration is associated with a greater post-COVID risk in fully mRNA-vaccinated individuals. Transl Psychiatry. 2023 Feb 1;13(1):32. doi: 10.1038/s41398-023-02334-4. PMID: 36726008; PMCID: PMC9890416. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9890416/ (Full text)

Central hypersomnia and chronic insomnia: expanding the spectrum of sleep disorders in long COVID syndrome – a prospective cohort study

Abstract:

Introduction: Long-onset COVID syndrome has been described in patients with COVID-19 infection with persistence of symptoms or development of sequelae beyond 4 weeks after the onset of acute symptoms, a medium- and long-term consequence of COVID-19. This syndrome can affect up to 32% of affected individuals, with symptoms of fatigue, dyspnea, chest pain, cognitive disorders, insomnia, and psychiatric disorders. The present study aimed to characterize and evaluate the prevalence of sleep symptoms in patients with long COVID syndrome.

Methodology: A total of 207 patients with post-COVID symptoms were evaluated through clinical evaluation with a neurologist and specific exams in the subgroup complaining of excessive sleepiness.

Results: Among 189 patients included in the long COVID sample, 48 (25.3%) had sleep-related symptoms. Insomnia was reported by 42 patients (22.2%), and excessive sleepiness (ES) was reported by 6 patients (3.17%). Four patients with ES were evaluated with polysomnography and test, multiple sleep latencies test, and actigraphic data. Two patients had a diagnosis of central hypersomnia, and one had narcolepsy. A history of steroid use was related to sleep complaints (insomnia and excessive sleepiness), whereas depression was related to excessive sleepiness. We observed a high prevalence of cognitive complaints in these patients.

Conclusion: Complaints related to sleep, such as insomnia and excessive sleepiness, seem to be part of the clinical post-acute syndrome (long COVID syndrome), composing part of its clinical spectrum, relating to some clinical data.

Source: Moura AEF, Oliveira DN, Torres DM, Tavares-Júnior JWL, Nóbrega PR, Braga-Neto P, Sobreira-Neto MA. Central hypersomnia and chronic insomnia: expanding the spectrum of sleep disorders in long COVID syndrome – a prospective cohort study. BMC Neurol. 2022 Nov 9;22(1):417. doi: 10.1186/s12883-022-02940-7. PMID: 36352367; PMCID: PMC9643986. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643986/ (Full text)

Sleep symptoms are essential features of long-COVID – Comparing healthy controls with COVID-19 cases of different severity in the international COVID sleep study (ICOSS-II)

Abstract:

Many people report suffering from post-acute sequelae of COVID-19 or “long-COVID”, but there are still open questions on what actually constitutes long-COVID and how prevalent it is. The current definition of post-acute sequelae of COVID-19 is based on voting using the Delphi-method by the WHO post-COVID-19 working group. It emphasizes long-lasting fatigue, shortness of breath and cognitive dysfunction as the core symptoms of post-acute sequelae of COVID-19.

In this international survey study consisting of 13,628 subjects aged 18-99 years from 16 countries of Asia, Europe, North America and South America (May-Dec 2021), we show that post-acute sequelae of COVID-19 symptoms were more prevalent amongst the more severe COVID-19 cases, i.e. those requiring hospitalisation for COVID-19. We also found that long-lasting sleep symptoms are at the core of post-acute sequelae of COVID-19 and associate with the COVID-19 severity when COVID-19 cases are compared with COVID-negative cases.

Specifically, fatigue (61.3%), insomnia symptoms (49.6%) and excessive daytime sleepiness (35.8%) were highly prevalent amongst respondents reporting long-lasting symptoms after hospitalisation for COVID-19. Understanding the importance of sleep-related symptoms in post-acute sequelae of COVID-19 has a clinical relevance when diagnosing and treating long-COVID.

Source: Merikanto I, Dauvilliers Y, Chung F, Wing YK, de Gennaro L, Holzinger B, Bjorvatn B, Morin CM, Penzel T, Benedict C, Koscec Bjelajac A, Chan NY, Espie CA, Hrubos-Strøm H, Inoue Y, Korman M, Landtblom AM, Léger D, Matsui K, Mota-Rolim S, Nadorff MR, Plazzi G, Reis C, Yordanova J, Partinen M. Sleep symptoms are essential features of long-COVID – Comparing healthy controls with COVID-19 cases of different severity in the international COVID sleep study (ICOSS-II). J Sleep Res. 2022 Oct 8:e13754. doi: 10.1111/jsr.13754. Epub ahead of print. PMID: 36208038. https://onlinelibrary.wiley.com/doi/10.1111/jsr.13754 (Full text)

Study on the active components and mechanism of Suanzaoren decoction in improving cognitive impairment caused by sleep deprivation

Abstract:

Ethnopharmacological relevance: Suanzaoren Decoction (SZRD) is a traditional and classic prescription for the treatment of insomnia, with a history of more than 1,000 years. It replenishes blood components, calms the nerves, reduces fever and irritability. It is commonly used in the clinical treatment of chronic fatigue syndrome, cardiac neurosis, and menopausal syndromes. Modern pharmacological studies have shown that it improves cognitive impairment; however, its mechanism of action remains unclear.

Aim of the study: This study preliminarily investigated the potential bioactive components and mechanism of SZRD in improving cognitive impairment by exploring network pharmacology, molecular docking, and conducting in vivo experiments.

Materials and methods: The components of various Chinese herbs in SZRD and their disease-related targets were identified through network pharmacology and literature. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of intersection targets were performed using the relevant database. Next, the “Components-Targets-Pathways” (C-T-P) and “Protein-Protein interaction” networks were constructed using the enrichment analysis results to further identify potential pathways, bioactive components, and hub genes. At the same time, molecular docking was used to further distinguish the key bioactive components and genes of SZRD responsible for improving cognitive impairment. Finally, the potential mechanism of action was further analysed and verified using in vivo experiments.

Results: A total of 117 potential active components and 138 intersection targets were identified by network pharmacology screening. The key bioactive components, including calycosin, 5-Prenylbutein, licochalcone G, glypallichalcone, and ZINC189892, were identified by analysing the networks and molecular docking results. Hub genes included ACHE, CYP19A1, EGFR, ESR1, and ESR2. The oestrogen signalling pathway was the most important in the enrichment analysis. In vivo experiments further proved that SZRD could improve cognitive impairment by affecting the oestrogen signalling pathway and the expression of ACHE and CYP19A1.

Conclusions: Network pharmacology and in vivo experiments demonstrate that SZRD improves cognitive impairment caused by sleep disturbance through estrogen receptor pathway, which provides a basis for its clinical application.

Source: Cheng L, Wang F, Li ZH, Wen C, Ding L, Zhang SB, You QY. Study on the active components and mechanism of Suanzaoren decoction in improving cognitive impairment caused by sleep deprivation. J Ethnopharmacol. 2022 Jun 28:115502. doi: 10.1016/j.jep.2022.115502. Epub ahead of print. PMID: 35777606. https://www.sciencedirect.com/science/article/abs/pii/S0378874122005414 (Full text)

Systematic Review of Sleep Characteristics in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

(1) Background-Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifaceted illness characterized by profound and persistent fatigue unrelieved by rest along with a range of other debilitating symptoms. Experiences of unrefreshing and disturbed sleep are frequently described by ME/CFS patients. This is the first systematic review assessing sleep characteristics in ME/CFS. The aim of this review is to determine whether there are clinical characteristics of sleep in ME/CFS patients compared to healthy controls using objective measures such as polysomnography and multiple sleep latency testing.

(2) Methods-the following databases-Pubmed, Embase, Medline (EBSCO host) and Web of Science, were systematically searched for journal articles published between January 1994 to 19 February 2021. Articles that referred to polysomnography or multiple sleep latency testing and ME/CFS patients were selected, and further refined through use of specific inclusion and exclusion criteria. Quality and bias were measured using the Joanna Briggs Institute checklist.

(3) Results-twenty observational studies were included in this review. The studies investigated objective measures of sleep quality in ME/CFS. Subjective measures including perceived sleep quality and other quality of life factors were also described.

(4) Conclusions-Many of the parameters measured including slow- wave sleep, apnea- hypopnea index, spectral activity and multiple sleep latency testing were inconsistent across the studies. The available research on sleep quality in ME/CFS was also limited by recruitment decisions, confounding factors, small sample sizes and non-replicated findings. Future well-designed studies are required to understand sleep quality in ME/CFS patients.

Source: Maksoud R, Eaton-Fitch N, Matula M, Cabanas H, Staines D, Marshall-Gradisnik S. Systematic Review of Sleep Characteristics in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare (Basel). 2021 May 11;9(5):568. doi: 10.3390/healthcare9050568. PMID: 34065013. https://pubmed.ncbi.nlm.nih.gov/34065013/

Sleep problems in adolescents with CFS: A case-control study nested within a prospective clinical cohort

Abstract:

Sleep problems have a negative impact on a range of outcomes and are very common in adolescents with chronic fatigue syndrome (CFS). We aimed to (a) establish whether adolescents with CFS have more self-reported sleep problems than illness controls as well as healthy controls, (b) investigate changes in sleep problems and (c) explore the extent to which sleep problems at baseline predict fatigue and functioning at follow-up in adolescents with CFS. The Insomnia Scale was completed by 121 adolescents with CFS, 78 healthy adolescents and 27 adolescents with asthma. Eighty (66%) treatment-naïve adolescents with CFS completed questionnaires approximately 3 months later. Adolescents with CFS reported increased sleep problems compared to healthy controls and adolescents with asthma. In CFS, there was no significant change in sleep problems without treatment over a 3-month follow-up. Sleep problems at baseline predicted a significant proportion of the variance in sleep problems at follow-up. Sleep problems should be targeted in treatment. Regulating the ‘body clock’ via the regulation of sleep could influence outcomes not assessed in this study such as school attainment.

Source: Loades ME, Rimes KA, Chalder T. Sleep problems in adolescents with CFS: A case-control study nested within a prospective clinical cohort [published online ahead of print, 2020 May 22]. Clin Child Psychol Psychiatry. 2020;1359104520918364. doi:10.1177/1359104520918364 https://journals.sagepub.com/doi/abs/10.1177/1359104520918364

Emotional Awareness Correlated With Number of Awakenings From Polysomnography in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-A Pilot Study

Abstract:

INTRODUCTION: Unrefreshing sleep is one of the diagnostic criteria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which could be explained by sleep disorders, for example obstructive sleep apnea, reported in our previous study with polysomnography. Our previous findings also indicate difficulties in emotional regulation when measuring alexithymia by TAS-20 (Toronto Alexithymia Scale) and level of emotional awareness by LEAS (Level of Emotional Awareness Scale) in ME/CFS patients. However, the reasons for this are unknown. The purpose of this study was to investigate correlations between data from subjective emotional regulation and polysomnography.

METHODS: Twenty-three ME/CFS patients (5 men and 18 women) of mean age 43, and 30 matched healthy controls (9 males and 21 women) of mean age 45, filled in TAS-20, LEAS, and Hospital Depression and Anxiety Scale (HADS). A polysomnography was performed on patients but not on healthy controls. Thus, values of normal population were used for sleep evaluation in ME/CFS patients.

RESULT: There were significant differences between patients and controls in several aspects of emotional regulation, for example LEAS-self and LEAS-total. Seventy percent of the patients had increased numbers of awakenings (shifts from any sleep stage to awake), 22% had obstructive sleep apneas, and 27% had periodic limb movements. Correlation analysis showed that number of awakenings significantly correlated with LEAS-self and LEAS-total, p < 0.01, respectively. There were no other significant correlations.

CONCLUSION: This pilot study demonstrated significant correlations between reduced emotional awareness and number of awakenings in polysomnography. Future studies with larger cohorts need to be conducted.

Source: Bileviciute-Ljungar I, Friberg D. Emotional Awareness Correlated With Number of Awakenings From Polysomnography in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-A Pilot Study. Front Psychiatry. 2020 Mar 26;11:222. doi: 10.3389/fpsyt.2020.00222. eCollection 2020. https://www.ncbi.nlm.nih.gov/pubmed/32273857

Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Non-restorative sleep is a hallmark symptom of chronic fatigue syndrome/myalgic encephalomyelitis. However, little is known about self-reported sleep disturbances in these subjects. This study aimed to assess the self-reported sleep quality and its impact on quality of life in a Spanish community-based chronic fatigue syndrome/myalgic encephalomyelitis cohort.

A prospective cross-sectional cohort study was conducted in 1,455 Spanish chronic fatigue syndrome/myalgic encephalomyelitis patients. Sleep quality, fatigue, pain, functional capacity impairment, psychopathological status, anxiety/depression and health-related quality of life were assessed using validated subjective measures. The frequencies of muscular, cognitive, neurological, autonomic and immunological symptom clusters were above 80%.

High scores were recorded for pain, fatigue, psychopathological status, anxiety/depression, and low scores for functional capacity and quality of life, all of which correlated significantly (all p < 0.01) with quality of sleep as measured by the Pittsburgh Sleep Quality Index. Multivariate regression analysis showed that after adjusting for age and gender, the pain intensity (odds ratio, 1.11; p <0.05), psychopathological status (odds ratio, 1.85; p < 0.001), fibromyalgia (odds ratio, 1.39; p < 0.05), severe autonomic dysfunction (odds ratio, 1.72; p < 0.05), poor functional capacity (odds ratio, 0.98; p < 0.05) and quality of life (odds ratio, 0.96; both p < 0.001) were significantly associated with poor sleep quality.

These findings suggest that this large chronic fatigue syndrome/myalgic encephalomyelitis sample presents poor sleep quality, as assessed by the Pittsburgh Sleep Quality Index, and that this poor sleep quality is associated with many aspects of quality of life.

Source: Castro-Marrero J, Zaragozá MC, González-Garcia S, Aliste L, Sáez-Francàs N, Romero O, Ferré A, Fernández de Sevilla T, Alegre J.  Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Sleep Res. 2018 May 16:e12703. doi: 10.1111/jsr.12703. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/29770505

The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis

Abstract:

Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways.

In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation. Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene). Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop.

This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders. We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders.

Source: Morris G, Stubbs B, Köhler CA, Walder K, Slyepchenko A, Berk M, Carvalho AF. The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis. Sleep Med Rev. 2018 Apr 4. pii: S1087-0792(17)30152-1. doi: 10.1016/j.smrv.2018.03.007. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/29759891