[Insomnia: definitions, epidemiology and changes with age]. / Insomnie : définitions, épidémiologie et évolution avec l'âge.

INSOMNIA: DEFINITIONS, EPIDEMIOLOGY AND CHANGES WITH AGE. Chronic insomnia is a disorder defined as a subjective complaint relating to the quality and/or quantity of sleep associated with daytime impact, and which must be present 3 nights per week for a period of at least 3 months. This is a common sleep problem in the general population and represents a significant proportion of reasons for consultation in the general practice. It requires early identification at all ages of life to allow the establishment of adequate care, which will have the benefit of both improving the quality of life of these patients in the short term and preventing the consequences of chronic insomnia.

[Insomnia and the biological clock]. / Insomnie et horloge biologique.

INSOMNIA AND THE BIOLOGICAL CLOCK. Multiple physiological and biological rhythms known as «circadian¼ are generated by the biological clock that controls them within the suprachiasmatic nuclei of the hypothalamus. However, the most emblematic circadian rhythm is that of sleep and awakening. It is therefore crucial to check how the clock may be involved in chronic insomnia. What is the influence of the clock on the time and quality of sleep? What are the typical clock disorders that explain insomnia in adolescents, shift and night workers, the elderly and the blind individuals? What are the tools to recommend in general and specialized medicine in the evaluation of the clock in insomnia? What influence finally of the light on the clock and the light therapy to recommend? So many questions and elements of understanding often-poorly known of chronic insomnia.

INSOMNIE ET HORLOGE BIOLOGIQUE. De multiples rythmes physiologiques et biologiques dits « circadiens ¼ sont influencés par l'horloge biologique qui les contrôle au sein des noyaux suprachiasmatiques de l'hypothalamus. Mais le rythme circadien le plus emblématique est celui du sommeil et de l'éveil. Il est donc indispensable de vérifier comment l'horloge biologique peut être impliquée dans une insomnie chronique : quelle est son influence sur les horaires et la qualité du sommeil ? Quels sont les troubles caractéristiques de l'horloge biologique expliquant l'insomnie des adolescents, des travailleurs postés et de nuit, des personnes âgées et des non-voyants ? Quels outils conseiller en médecine générale et spécialisée pour évaluer l'horloge biologique face à une insomnie ? Quelle influence, enfin, de la lumière sur l'horloge biologique et quels conseils donner vis-à-vis de la lumière ? Autant de questions et d'éléments de compréhension sur l'insomnie chronique éclaircis.

[Pharmacotherapies for insomnia]. / Traitements médicamenteux de l'insomnie.

PHARMACOTHERAPIES FOR INSOMNIA. The first line of treatment in adult chronic insomnia is cognitive behavioral therapy (CBT). However, its difficult accessibility limited its use and medications are still often prescribed. Considering the drugs with marketing authorization, Z-drugs (zolpidem and zopiclone) if taken at the right hour and dosage promote sleep initiation and have less deleterious effects than benzodiazepines, especially the long-acting ones which should be avoided. This class of drugs cannot be prescribed longer than 28 days. Some antihistaminic licensed drugs are authorized as hypnotics, with a low proof of efficacy and a risk of adverse event as sedation and somnolence the next day. Their prescription should be avoided in old subjects. Some clinicians used antidepressant sedative medications, at low dosage, as hypnotic drugs but "off label", outside authorization. Now melatonin, an endogenous synchronizer of biologic rhythms, has obtained the authorization for the treatment of insomniac troubles, in subjects of at least 55 years old, in its slow- release formula, replacing the physiological decline of this hormone with aging. Melatonin is not a hypnotic, but has soporific properties, inducing sleep, improving sleep efficacy, sometimes sleep duration and morning alertness. When discontinued, it induced no withdrawal syndrome. It has shown no risk of abuse potential and no deleterious side-effects, if used at the right dose and in the absence of hepatic interaction with other compounds. Finally, a new class of hypnotics, "the orexin antagonists" has its first representative on the French market: daridorexant. The place of these molecules in the therapeutic strategy for chronic insomnia needs to be clarified.

TRAITEMENTS MÉDICAMENTEUX DE L'INSOMNIE. Le traitement de première intention des adultes atteints d'insomnie chronique est la thérapie cognitivo-comportementale. Toutefois, compte tenu des difficultés d'accès à cette thérapeutique, les prescriptions médicamenteuses restent fréquentes. Considérant les médicaments qui ont une autorisation de mise sur le marché (AMM) dans cette indication, les Z-drugs (zolpidem et zopiclone), prises à bon escient, à la bonne posologie et à la bonne heure, favorisent l'initiation du sommeil et ont moins d'effets indésirables que les benzodiapézines, notamment celles à longue durée d'action, dont la prescription doit être évitée. Cette classe de médicaments est soumise à une réglementation particulière de durée de prescription (28 jours au maximum). Certains antihistaminiques peuvent être utiles comme hypnotiques, avec un faible niveau de preuve d'efficacité et des effets indésirables, notamment sur la vigilance du lendemain ; ils sont à éviter chez les sujets âgés. Certains antidépresseurs sédatifs sont prescrits, à faible dose, hors AMM. Plus récemment, la mélatonine, synchroniseur endogène des rythmes biologiques, a obtenu une AMM dans les troubles du sommeil du sujet âgé de 55 ans ou plus, dans sa formulation à longue durée d'action, suppléant la baisse physiologique de cette hormone avec l'âge. Induisant une somnolence, elle favorise l'endormissement, l'efficacité du sommeil, peut améliorer sa durée et assure un réveil de bonne qualité, sans accoutumance, sans syndrome de sevrage, et sans effet délétère majeur si l'on fait attention à la posologie et aux interactions médicamenteuses. Enfin, une nouvelle classe de médicaments, les anti-orexines, compte un premier représentant commercialisé en France : le daridorexant. La place de ces molécules dans la stratégie thérapeutique de l'insomnie chronique devra être précisée.

Sleep deprivation detected by voice analysis.

Sleep deprivation has an ever-increasing impact on individuals and societies. Yet, to date, there is no quick and objective test for sleep deprivation. Here, we used automated acoustic analyses of the voice to detect sleep deprivation. Building on current machine-learning approaches, we focused on interpretability by introducing two novel ideas: the use of a fully generic auditory representation as input feature space, combined with an interpretation technique based on reverse correlation. The auditory representation consisted of a spectro-temporal modulation analysis derived from neurophysiology. The interpretation method aimed to reveal the regions of the auditory representation that supported the classifiers' decisions. Results showed that generic auditory features could be used to detect sleep deprivation successfully, with an accuracy comparable to state-of-the-art speech features. Furthermore, the interpretation revealed two distinct effects of sleep deprivation on the voice: changes in slow temporal modulations related to prosody and changes in spectral features related to voice quality. Importantly, the relative balance of the two effects varied widely across individuals, even though the amount of sleep deprivation was controlled, thus confirming the need to characterize sleep deprivation at the individual level. Moreover, while the prosody factor correlated with subjective sleepiness reports, the voice quality factor did not, consistent with the presence of both explicit and implicit consequences of sleep deprivation. Overall, the findings show that individual effects of sleep deprivation may be observed in vocal biomarkers. Future investigations correlating such markers with objective physiological measures of sleep deprivation could enable "sleep stethoscopes" for the cost-effective diagnosis of the individual effects of sleep deprivation.

Altered reinforcement learning in Narcolepsy type I and other central disorders of hypersomnolence.

Cognitive impairments are described in central disorders of hypersomnolence (CDH), but studies remain very limited and largely focused on narcolepsy type 1 (NT1). The precise nature and origin of these cognitive impairments is poorly understood. Specifically, impaired decision making under ambiguity has been reported in NT1 and suggested to be caused by dysregulation of the direct projections of hypocretin neurons to the dopamine network. However, the decision-making tasks used previously embed different cognitive functions that are difficult to isolate. This study aims to test reinforcement learning in participants with NT1 and with other (non-hypocretin deficient) CDH in a task known to directly depend on the dopamine system. Participants with NT1 (N = 27), other CDH (N = 34, including narcolepsy type 2 and idiopathic hypersomnia, matched with NT1 participants for sleepiness severity), and healthy participants (N = 34) took part in the study. Results showed that all groups had normal and similar positive reinforcement learning, a pattern not suggestive of dopamine deficiency. However, both participants with NT1 and other CDH had decreased learning abilities to avoid losses. This decreased negative reinforcement learning in participants with CDH was associated with the alteration of vigilance. This study provides new insights into the nature of decision making impairment in people with CDH and suggests that these alterations could be minimized by restoring adequate vigilance.

Neurophysiological explorations across the spectrum of psychosis, autism, and depression, during wakefulness and sleep: protocol of a prospective case-control transdiagnostic multimodal study (DEMETER).

BACKGROUND: Quantitative electroencephalography (EEG) analysis offers the opportunity to study high-level cognitive processes across psychiatric disorders. In particular, EEG microstates translate the temporal dynamics of neuronal networks throughout the brain. Their alteration may reflect transdiagnostic anomalies in neurophysiological functions that are impaired in mood, psychosis, and autism spectrum disorders, such as sensorimotor integration, speech, sleep, and sense of self. The main questions this study aims to answer are as follows: 1) Are EEG microstate anomalies associated with clinical and functional prognosis, both in resting conditions and during sleep, across psychiatric disorders? 2) Are EEG microstate anomalies associated with differences in sensorimotor integration, speech, sense of self, and sleep? 3) Can the dynamic of EEG microstates be modulated by a non-drug intervention such as light hypnosis? METHODS: This prospective cohort will include a population of adolescents and young adults, aged 15 to 30 years old, with ultra-high-risk of psychosis (UHR), first-episode psychosis (FEP), schizophrenia (SCZ), autism spectrum disorder (ASD), and major depressive disorder (MDD), as well as healthy controls (CTRL) (N = 21 × 6), who will be assessed at baseline and after one year of follow-up. Participants will undergo deep phenotyping based on psychopathology, neuropsychological assessments, 64-channel EEG recordings, and biological sampling at the two timepoints. At baseline, the EEG recording will also be coupled to a sensorimotor task and a recording of the characteristics of their speech (prosody and turn-taking), a one-night polysomnography, a self-reference effect task in virtual reality (only in UHR, FEP, and CTRL). An interventional ancillary study will involve only healthy controls, in order to assess whether light hypnosis can modify the EEG microstate architecture in a direction opposite to what is seen in disease. DISCUSSION: This transdiagnostic longitudinal case-control study will provide a multimodal neurophysiological assessment of clinical dimensions (sensorimotor integration, speech, sleep, and sense of self) that are disrupted across mood, psychosis, and autism spectrum disorders. It will further test the relevance of EEG microstates as dimensional functional biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT06045897.

Associations between changes in habitual sleep duration and lower self-rated health among COVID-19 survivors: findings from a survey across 16 countries/regions.

BACKGROUND: Self-rated health (SRH) is widely recognized as a clinically significant predictor of subsequent mortality risk. Although COVID-19 may impair SRH, this relationship has not been extensively examined. The present study aimed to examine the correlation between habitual sleep duration, changes in sleep duration after infection, and SRH in subjects who have experienced SARS-CoV-2 infection. METHODS: Participants from 16 countries participated in the International COVID Sleep Study-II (ICOSS-II) online survey in 2021. A total of 10,794 of these participants were included in the analysis, including 1,509 COVID-19 individuals (who reported that they had tested positive for COVID-19). SRH was evaluated using a 0-100 linear visual analog scale. Habitual sleep durations of < 6 h and > 9 h were defined as short and long habitual sleep duration, respectively. Changes in habitual sleep duration after infection of ≤ -2 h and ≥ 1 h were defined as decreased or increased, respectively. RESULTS: Participants with COVID-19 had lower SRH scores than non-infected participants, and those with more severe COVID-19 had a tendency towards even lower SRH scores. In a multivariate regression analysis of participants who had experienced COVID-19, both decreased and increased habitual sleep duration after infection were significantly associated with lower SRH after controlling for sleep quality (ß = -0.056 and -0.058, respectively, both p < 0.05); however, associations between current short or long habitual sleep duration and SRH were negligible. Multinomial logistic regression analysis showed that decreased habitual sleep duration was significantly related to increased fatigue (odds ratio [OR] = 1.824, p < 0.01), shortness of breath (OR = 1.725, p < 0.05), diarrhea/nausea/vomiting (OR = 2.636, p < 0.01), and hallucinations (OR = 5.091, p < 0.05), while increased habitual sleep duration was significantly related to increased fatigue (OR = 1.900, p < 0.01). CONCLUSIONS: Changes in habitual sleep duration following SARS-CoV-2 infection were associated with lower SRH. Decreased or increased habitual sleep duration might have a bidirectional relation with post-COVID-19 symptoms. Further research is needed to better understand the mechanisms underlying these relationships for in order to improve SRH in individuals with COVID-19.

The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023.

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

The association of insomnia with long COVID: An international collaborative study (ICOSS-II).

OBJECTIVE: There is evidence of a strong association between insomnia and COVID-19, yet few studies have examined the relationship between insomnia and long COVID. This study aimed to investigate whether COVID-19 patients with pre-pandemic insomnia have a greater risk of developing long COVID and whether long COVID is in turn associated with higher incident rates of insomnia symptoms after infection. METHODS: Data were collected cross-sectionally (May-Dec 2021) as part of an international collaborative study involving participants from 16 countries. A total of 2311 participants (18-99 years old) with COVID-19 provided valid responses to a web-based survey about sleep, insomnia, and health-related variables. Log-binomial regression was used to assess bidirectional associations between insomnia and long COVID. Analyses were adjusted for age, sex, and health conditions, including sleep apnea, attention and memory problems, chronic fatigue, depression, and anxiety. RESULTS: COVID-19 patients with pre-pandemic insomnia showed a higher risk of developing long COVID than those without pre-pandemic insomnia (70.8% vs 51.4%; adjusted relative risk [RR]: 1.33, 95% confidence interval [CI]: 1.07-1.65). Among COVID-19 cases without pre-pandemic insomnia, the rates of incident insomnia symptoms after infection were 24.1% for short COVID cases and 60.6% for long COVID cases (p < .001). Compared with short COVID cases, long COVID cases were associated with an increased risk of developing insomnia symptoms (adjusted RR: 2.00; 95% CI: 1.50-2.66). CONCLUSIONS: The findings support a bidirectional relationship between insomnia and long COVID. These findings highlight the importance of addressing sleep and insomnia in the prevention and management of long COVID.

Multifactorial sleep disturbance in Klinefelter syndrome: a case report.

Background: Klinefelter syndrome (KS), which is related to the presence of an additional X chromosome in a man, is associated with a broad variety of physical and psychosocial impairments. While the focus is usually placed on symptoms related to hypogonadism, such as infertility, recent studies have noted evidence of poor sleep in those patients. Case Description: We report on the case of a 44-year-old man with KS who consulted in our Sleep medicine center for excessive daytime sleepiness and delayed sleep with irregular patterns. Polysomnography (PSG) revealed sleep apnea syndrome, with both obstructive and central apnea. Peripheral temperature monitoring revealed patterns indicative of altered melatonin secretion. The present case report suggests that sleep disturbance in patients with KS appears multifactorial with the occurrence of: obstructive sleep apnea (OSA), iatrogenic central apnea due to testosterone therapy, and circadian sleep/wake disorder. Conclusions: While this topic warrants larger studies with control groups, this case report suggests there might be specific sleep impairments, associated with three different mechanisms, in patients with KS. Those sleep disorders can worsen psycho-social and cognitive difficulties in those patients, and should therefore be screened for and treated.

Effects of Acute Caffeine Intake on Insulin-Like Growth Factor-1 Responses to Total Sleep Deprivation: Interactions with COMT Polymorphism - A Randomized, Crossover Study.

INTRODUCTION: Genes encoding catechol-O-methyl-transferase (COMT) and adenosine A2A receptor (ADORA2A) have been shown to influence cognitive performances and responses to caffeine intake during prolonged wakefulness. The rs4680 single-nucleotide polymorphism (SNP) of COMT differentiates on memory score and circulating levels of the neurotrophic factor IGF-1. This study aimed to determine the kinetics of IGF-1, testosterone, and cortisol concentrations during prolonged wakefulness under caffeine or placebo intake in 37 healthy participants, and to analyze whether the responses are dependent on COMT rs4680 or ADORA2A rs5751876 SNPs. METHODS: In caffeine (2.5 mg/kg, twice over 24 h) or placebo-controlled condition, blood sampling was performed at 1 h (08:00, baseline), 11 h, 13 h, 25 h (08:00 next day), 35 h, and 37 h of prolonged wakefulness, and at 08:00 after one night of recovery sleep, to assess hormonal concentrations. Genotyping was performed on blood cells. RESULTS: Results indicated a significant increase in IGF-1 levels after 25, 35, and 37 h of prolonged wakefulness in the placebo condition, in subjects carrying the homozygous COMT A/A genotype only (expressed in absolute values [±SEM]: 118 ± 8, 121 ± 10, and 121 ± 10 vs. 105 ± 7 ng/mL for A/A, 127 ± 11, 128 ± 12, and 129 ± 13 vs. 120 ± 11 ng/mL for G/G, and 106 ± 9, 110 ± 10, and 106 ± 10 vs. 101 ± 8 ng/mL for G/A, after 25, 35, and 37 h of wakefulness versus 1 h; p < 0.05, condition X time X SNP). Acute caffeine intake exerted a COMT genotype-dependent reducing effect on IGF-1 kinetic response (104 ± 26, 107 ± 27, and 106 ± 26 vs. 100 ± 25 ng/mL for A/A genotype, at 25, 35, and 37 h of wakefulness vs. 1 h; p < 0.05 condition X time X SNP), plus on resting levels after overnight recovery (102 ± 5 vs. 113 ± 6 ng/mL) (p < 0.05, condition X SNP). Testosterone and cortisol concentrations decreased during wakefulness, and caffeine alleviated the testosterone reduction, unrelated to the COMT polymorphism. No significant main effect of the ADORA2A SNP was shown regardless of hormonal responses. CONCLUSION: Our results indicated that the COMT polymorphism interaction is important in determining the IGF-1 neurotrophic response to sleep deprivation with caffeine intake (NCT03859882).

Polysomnographic parameters in long-COVID chronic insomnia patients.

INTRODUCTION: While COVID-19 is predominantly considered to be an acute self-remitting disease, it has been pointed out that a variety of symptoms can linger for several months, a phenomenon identified as long-COVID. Insomnia is particularly prevalent in long-COVID. In the present study, we aimed at confirming and characterising insomnia in long-COVID patients through polysomnography and to identify whether its parameters differ from patients with chronic insomnia and no long-COVID history. MATERIALS AND METHODS: We conducted a case-control study, including 17 long-COVID patients with insomnia symptoms (cases), and 34 2:1 matched controls with a diagnostic of chronic insomnia and no history of long-COVID. All underwent a one-night polysomnography (PSG). RESULTS: First, we observed that long-COVID patients with insomnia complaints have altered PSG parameters, in favour of the diagnosis of chronic insomnia. Second, we show that insomnia related to long-COVID PSG parameters was not significantly different from regular chronic insomnia PSG parameters. DISCUSSION: Our results indicate that even though it is one of the most prevalent symptoms of long-COVID, its related insomnia resembles typical chronic insomnia, based on PSG studies. Even though additional studies are warranted, our results suggest that the pathophysiology and therapeutic options should be similar to those recommended for chronic insomnia.

Association between hypersomnolence and the COVID-19 pandemic: The International COVID-19 Sleep Study (ICOSS).

BACKGROUND: The COVID-19 pandemic and related restriction measures have affected our daily life, sleep, and circadian rhythms worldwide. Their effects on hypersomnolence and fatigue remain unclear. METHODS: The International COVID-19 Sleep Study questionnaire which included items on hypersomnolence such as excessive daytime sleepiness (EDS), and excessive quantity of sleep (EQS), as well as sociodemographic factors, sleep patterns, psychological symptoms, and quality of life was distributed in 15 countries across the world from May to September in 2020. RESULTS: Altogether responses from 18,785 survey participants (65% women, median age 39 years) were available for analysis. Only 2.8% reported having had COVID-19. Compared to before the pandemic, the prevalence of EDS, EQS, and fatigue increased from 17.9% to 25.5%, 1.6%-4.9%, and 19.4%-28.3% amid the pandemic, respectively. In univariate logistic regression models, reports of having a COVID-19 were associated with EQS (OR 5.3; 95%-CI 3.6-8.0), EDS (2.6; 2.0-3.4), and fatigue (2.8; 2.1-3.6). In adjusted multivariate logistic regression, sleep duration shorter than desired (3.9; 3.2-4.7), depressive symptoms (3.1; 2.7-3.5), use of hypnotics (2.3; 1.9-2.8), and having reported COVID-19 (1.9; 1.3-2.6) remained strong predictors of EDS. Similar associations emerged for fatigue. In the multivariate model, depressive symptoms (4.1; 3.6-4.6) and reports of having COVID-19 (2.0; 1.4-2.8) remained associated with EQS. CONCLUSIONS: A large increase in EDS, EQS, and fatigue occurred due to the COVID-19 pandemic, and especially in self-reported cases of COVID-19. These findings warrant a thorough understanding of their pathophysiology to target prevention and treatment strategies for long COVID condition.

REM Sleep Impairment May Underlie Sleep-Driven Modulations of Tinnitus in Sleep Intermittent Tinnitus Subjects: A Controlled Study.

(1) Background: Poor sleep and fragmented sleep are associated with several chronic conditions. Tinnitus is an auditory symptom that often negatively combines with poor sleep and has been associated with sleep impairment and sleep apnea. The relationship between tinnitus psychoacoustic characteristics and sleep is still poorly explored, notably for a particular subgroup of patients, for whom the perceived loudness of their tinnitus is highly modulated by sleep. (2) Methods: For this observational prospective study, 30 subjects with tinnitus were recruited, including 15 "sleep intermittent tinnitus" subjects, who had reported significant modulations of tinnitus loudness related to night sleep and naps, and a control group of 15 subjects displaying constant non-sleep-modulated tinnitus. The control group had matching age, gender, self-reported hearing loss grade and tinnitus impact on quality of life with the study group. All patients underwent a polysomnography (PSG) assessment for one complete night and then were asked to fill in a case report form, as well as a report of tinnitus loudness before and after the PSG. (3) Results: "Sleep Intermittent tinnitus" subjects had less Stage 3 sleep (p < 0.01), less Rapid-Eye Movement (REM) Sleep (p < 0.05) and more Stage 2 sleep (p < 0.05) in proportion and duration than subjects from the control group. In addition, in the "sleep Intermittent tinnitus" sample, a correlation was found between REM sleep duration and tinnitus overnight modulation (p < 0.05), as well as tinnitus impact on quality of life (p < 0.05). These correlations were not present in the control group. (4) Conclusions: This study suggests that among the tinnitus population, patients displaying sleep-modulated tinnitus have deteriorated sleep quality. Furthermore, REM sleep characteristics may play a role in overnight tinnitus modulation. Potential pathophysiological explanations accounting for this observation are hypothesized and discussed.