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Physiological Reviews Jul 2021While insomnia is the second most common mental disorder, progress in our understanding of underlying neurobiological mechanisms has been limited. The present review... (Review)
Review
While insomnia is the second most common mental disorder, progress in our understanding of underlying neurobiological mechanisms has been limited. The present review addresses the definition and prevalence of insomnia and explores its subjective and objective characteristics across the 24-hour day. Subsequently, the review extensively addresses how the vulnerability to develop insomnia is affected by genetic variants, early life stress, major life events, and brain structure and function. Further supported by the clear mental health risks conveyed by insomnia, the integrated findings suggest that the vulnerability to develop insomnia could rather be found in brain circuits regulating emotion and arousal than in circuits involved in circadian and homeostatic sleep regulation. Finally, a testable model is presented. The model proposes that in people with a vulnerability to develop insomnia, the locus coeruleus is more sensitive to-or receives more input from-the salience network and related circuits, even during rapid eye movement sleep, when it should normally be sound asleep. This vulnerability may ignite a downward spiral of insufficient overnight adaptation to distress, resulting in accumulating hyperarousal, which, in turn, impedes restful sleep and moreover increases the risk of other mental health adversity. Sensitized brain circuits are likely to be subjectively experienced as "sleeping with one eye open". The proposed model opens up the possibility for novel intervention studies and animal studies, thus accelerating the ignition of a neuroscience of insomnia, which is direly needed for better treatment.
Topics: Animals; Arousal; Brain; Humans; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 32790576
DOI: 10.1152/physrev.00046.2019 -
Neuropsychopharmacology : Official... Jan 2020The principal neurons of the arousal and sleep circuits are comprised by glutamate and GABA neurons, which are distributed within the reticular core of the brain and,... (Review)
Review
The principal neurons of the arousal and sleep circuits are comprised by glutamate and GABA neurons, which are distributed within the reticular core of the brain and, through local and distant projections and interactions, regulate cortical activity and behavior across wake-sleep states. These are in turn modulated by the neuromodulatory systems that are comprised by acetylcholine, noradrenaline, dopamine, serotonin, histamine, orexin (hypocretin), and melanin-concentrating hormone (MCH) neurons. Glutamate and GABA neurons are heterogeneous in their profiles of discharge, forming distinct functional cell types by selective or maximal discharge during (1) waking and paradoxical (REM) sleep, (2) during slow wave sleep, (3) during waking, or (4) during paradoxical (REM) sleep. The neuromodulatory systems are each homogeneous in their profile of discharge, the majority discharging maximally during waking and paradoxical sleep or during waking. Only MCH neurons discharge maximally during sleep. They each exert their modulatory influence upon other neurons through excitatory and inhibitory receptors thus effecting a concerted differential change in the functionally different cell groups. Both arousal and sleep circuit neurons are homeostatically regulated as a function of their activity in part through changes in receptors. The major pharmacological agents used for the treatment of wake and sleep disorders act upon GABA and neuromodulatory transmission.
Topics: Acetylcholine; Animals; Arousal; Brain; Electroencephalography; Humans; Nerve Net; Norepinephrine; Sleep Stages; gamma-Aminobutyric Acid
PubMed: 31216564
DOI: 10.1038/s41386-019-0444-2 -
Current Pediatric Reviews 2020Sleep terrors are common, frightening, but fortunately benign events. Familiarity with this condition is important so that an accurate diagnosis can be made. (Review)
Review
BACKGROUND
Sleep terrors are common, frightening, but fortunately benign events. Familiarity with this condition is important so that an accurate diagnosis can be made.
OBJECTIVE
To familiarize physicians with the clinical manifestations, diagnosis, and management of children with sleep terrors.
METHODS
A PubMed search was completed in Clinical Queries using the key terms "sleep terrors" OR "night terrors". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article.
RESULTS
It is estimated that sleep terrors occur in 1 to 6.5% of children 1 to 12 years of age. Sleep terrors typically occur in children between 4 and 12 years of age, with a peak between 5 and 7 years of age. The exact etiology is not known. Developmental, environmental, organic, psychological, and genetic factors have been identified as a potential cause of sleep terrors. Sleep terrors tend to occur within the first three hours of the major sleep episode, during arousal from stage three or four non-rapid eye movement (NREM) sleep. In a typical attack, the child awakens abruptly from sleep, sits upright in bed or jumps out of bed, screams in terror and intense fear, is panicky, and has a frightened expression. The child is confused and incoherent: verbalization is generally present but disorganized. Autonomic hyperactivity is manifested by tachycardia, tachypnea, diaphoresis, flushed face, dilated pupils, agitation, tremulousness, and increased muscle tone. The child is difficult to arouse and console and may express feelings of anxiety or doom. In the majority of cases, the patient does not awaken fully and settles back to quiet and deep sleep. There is retrograde amnesia for the attack the following morning. Attempts to interrupt a sleep terror episode should be avoided. As sleep deprivation can predispose to sleep terrors, it is important that the child has good sleep hygiene and an appropriate sleeping environment. Medical intervention is usually not necessary, but clonazepam may be considered on a short-term basis at bedtime if sleep terrors are frequent and severe or are associated with functional impairment, such as fatigue, daytime sleepiness, and distress. Anticipatory awakening, performed approximately half an hour before the child is most likely to experience a sleep terror episode, is often effective for the treatment of frequently occurring sleep terrors.
CONCLUSION
Most children outgrow the disorder by late adolescence. In the majority of cases, there is no specific treatment other than reassurance and parental education. Underlying conditions, however, should be treated if possible and precipitating factors should be avoided.
Topics: Child; Child, Preschool; Diagnosis, Differential; Humans; Infant; Night Terrors; Prognosis; Sleep
PubMed: 31612833
DOI: 10.2174/1573396315666191014152136 -
Associations between sleep bruxism and other sleep-related disorders in adults: a systematic review.Sleep Medicine Jan 2022Systematic reviews on sleep bruxism (SB) as a comorbid condition of other sleep-related disorders are lacking. Such reviews would contribute to the insight of sleep... (Review)
Review
OBJECTIVE
Systematic reviews on sleep bruxism (SB) as a comorbid condition of other sleep-related disorders are lacking. Such reviews would contribute to the insight of sleep clinicians into the occurrence of SB in patients with other sleep-related disorders, and into the underlying mechanisms of such comorbid associations. This systematic review aimed: 1. to determine the prevalence of SB in adults with other sleep-related disorders; and 2. to determine the associations between SB and other sleep-related disorders, and to explain the underlying mechanisms of these associations.
METHODS
A systematic search on SB and sleep-related disorders was performed in PubMed, Embase, Cochrane Library, and Web of Science to identify eligible studies published until May 15, 2020. Quality assessment was performed using the Risk of Bias Assessment tool for Non-randomized Studies.
RESULTS
Of the 1539 unique retrieved studies, 37 articles were included in this systematic review. The prevalence of SB in adult patients with obstructive sleep apnea, restless leg syndrome, periodic limb movement during sleep, sleep-related gastroesophageal reflux disease, REM behavior disorder (RBD), and sleep-related epilepsy was higher than that in the general population. The specific mechanisms behind these positive associations could not be identified.
CONCLUSIONS
SB is more prevalent in patients with the previously mentioned disorders than in the general population. Sleep arousal may be a common factor with which all the identified disorders are associated, except RBD and Parkinson's disease. The associations between SB and these identified sleep-related disorders call for more SB screening in patients with the abovementioned sleep-related disorders.
Topics: Adult; Humans; Restless Legs Syndrome; Sleep; Sleep Apnea, Obstructive; Sleep Bruxism; Sleep Wake Disorders
PubMed: 34879286
DOI: 10.1016/j.sleep.2021.11.008 -
Neurotherapeutics : the Journal of the... Jan 2021Parasomnias are abnormal behaviors and/or experiences emanating from or associated with sleep typically manifesting as motor movements of varying semiology. We discuss... (Review)
Review
Parasomnias are abnormal behaviors and/or experiences emanating from or associated with sleep typically manifesting as motor movements of varying semiology. We discuss mainly nonrapid eye movement sleep and related parasomnias in this article. Sleepwalking (SW), sleep terrors (ST), confusional arousals, and related disorders result from an incomplete dissociation of wakefulness from nonrapid eye movement (NREM) sleep. Conditions that provoke repeated cortical arousals, and/or promote sleep inertia, lead to NREM parasomnias by impairing normal arousal mechanisms. Changes in the cyclic alternating pattern, a biomarker of arousal instability in NREM sleep, are noted in sleepwalking disorders. Sleep-related eating disorder (SRED) is characterized by a disruption of the nocturnal fast with episodes of feeding after arousal from sleep. SRED is often associated with the use of sedative-hypnotic medications, in particular the widely prescribed benzodiazepine receptor agonists. Compelling evidence suggests that nocturnal eating may in some cases be another nonmotor manifestation of Restless Legs Syndrome (RLS). Initial management should focus upon decreasing the potential for sleep-related injury followed by treating comorbid sleep disorders and eliminating incriminating drugs. Sexsomnia is a subtype of disorders of arousal, where sexual behavior emerges from partial arousal from nonREM sleep. Overlap parasomnia disorders consist of abnormal sleep-related behavior both in nonREM and REM sleep. Status dissociatus is referred to as a breakdown of the sleep architecture where an admixture of various sleep state markers is seen without any specific demarcation. Benzodiazepine therapy can be effective in controlling SW, ST, and sexsomnia, but not SRED. Paroxetine has been reported to provide benefit in some cases of ST. Topiramate, pramipexole, and sertraline can be effective in SRED. Pharmacotherapy for other parasomnias continues to be less certain, necessitating further investigation. NREM parasomnias may resolve spontaneously but require a review of priming and predisposing factors.
Topics: Humans; Parasomnias; Sleep; Sleep Arousal Disorders
PubMed: 33527254
DOI: 10.1007/s13311-021-01011-y -
Journal of Sleep Research Aug 2022Sleep and epilepsy have a reciprocal relationship, and have been recognized as bedfellows since antiquity. However, research on this topic has made a big step forward... (Review)
Review
Sleep and epilepsy have a reciprocal relationship, and have been recognized as bedfellows since antiquity. However, research on this topic has made a big step forward only in recent years. In this narrative review we summarize the most stimulating discoveries and insights reached by the "European school." In particular, different aspects concerning the sleep-epilepsy interactions are analysed: (a) the effects of sleep on epilepsy; (b) the effects of epilepsy on sleep structure; (c) the relationship between epilepsy, sleep and epileptogenesis; (d) the impact of epileptic activity during sleep on cognition; (e) the relationship between epilepsy and the circadian rhythm; (f) the history and features of sleep hypermotor epilepsy and its differential diagnosis; (g) the relationship between epilepsy and sleep disorders.
Topics: Circadian Rhythm; Electroencephalography; Epilepsy; Humans; Sleep; Sleep Wake Disorders
PubMed: 35487880
DOI: 10.1111/jsr.13622 -
Behavioural Brain Research Aug 2017The reticular activating system (RAS) is not an amorphous region but distinct nuclei with specific membrane properties that dictate their firing during waking and sleep.... (Review)
Review
The reticular activating system (RAS) is not an amorphous region but distinct nuclei with specific membrane properties that dictate their firing during waking and sleep. The locus coeruleus and raphe nucleus fire during waking and slow wave sleep, with the pedunculopontine nucleus (PPN) firing during both waking and REM sleep, the states manifesting arousal-related EEG activity. Two important discoveries in the PPN in the last 10 years are, 1) that some PPN cells are electrically coupled, and 2) every PPN cell manifests high threshold calcium channels that allow them to oscillate at beta/gamma band frequencies. The role of arousal in drug abuse is considered here in terms of the effects of drugs of abuse on these two mechanisms. Drug abuse and the perception of withdrawal/relapse are mediated by neurobiological processes that occur only when we are awake, not when we are asleep. These relationships focus on the potential role of arousal, more specifically of RAS electrical coupling and gamma band activity, in the addictive process as well as the relapse to drug use.
Topics: Animals; Arousal; Humans; Substance-Related Disorders
PubMed: 28729115
DOI: 10.1016/j.bbr.2017.07.013 -
Journal of Internal Medicine May 2022The hypocretins (Hcrts), also known as orexins, are two neuropeptides produced exclusively in the lateral hypothalamus. They act on two specific receptors that are... (Review)
Review
The hypocretins (Hcrts), also known as orexins, are two neuropeptides produced exclusively in the lateral hypothalamus. They act on two specific receptors that are widely distributed across the brain and involved in a myriad of neurophysiological functions that include sleep, arousal, feeding, reward, fear, anxiety and cognition. Hcrt cell loss in humans leads to narcolepsy with cataplexy (narcolepsy type 1), a disorder characterized by intrusions of sleep into wakefulness, demonstrating that the Hcrt system is nonredundant and essential for sleep/wake stability. The causal link between Hcrts and arousal/wakefulness stabilisation has led to the development of a new class of drugs, Hcrt receptor antagonists to treat insomnia, based on the assumption that blocking orexin-induced arousal will facilitate sleep. This has been clinically validated: currently, two Hcrt receptor antagonists are approved to treat insomnia (suvorexant and lemborexant), with a New Drug Application recently submitted to the US Food and Drug Administration for a third drug (daridorexant). Other therapeutic applications under investigation include reduction of cravings in substance-use disorders and prevention of neurodegenerative disorders such as Alzheimer's disease, given the apparent bidirectional relationship between poor sleep and worsening of the disease. Circuit neuroscience findings suggest that the Hcrt system is a hub that integrates diverse inputs modulating arousal (e.g., circadian rhythms, metabolic status, positive and negative emotions) and conveys this information to multiple output regions. This neuronal architecture explains the wealth of physiological functions associated with Hcrts and highlights the potential of the Hcrt system as a therapeutic target for a number of disorders. We discuss present and future possible applications of drugs targeting the Hcrt system for the treatment of circuit-related neuropsychiatric and neurodegenerative conditions.
Topics: Humans; Intracellular Signaling Peptides and Proteins; Narcolepsy; Neuropeptides; Orexins; Sleep Initiation and Maintenance Disorders
PubMed: 35043499
DOI: 10.1111/joim.13406