SLEEP

Zitser, Jennifer; Anatürk, Melis; Zsoldos, Enikő; Mahmood, Abda; Filippini, Nicola; Suri, Sana; Leng, Yue; Yaffe, Kristine; Singh-Manoux, Archana; Kivimaki, Mika; Ebmeier, Klaus; Sexton, Claire

doi: 10.1093/sleep/zsz290pmid: 31904084

Study ObjectivesTo examine the association between sleep duration trajectories over 28 years and measures of cognition, gray matter volume, and white matter microstructure. We hypothesize that consistently meeting sleep guidelines that recommend at least 7 hours of sleep per night will be associated with better cognition, greater gray matter volumes, higher fractional anisotropy, and lower radial diffusivity values.MethodsWe studied 613 participants (age 42.3 ± 5.03 years at baseline) who self-reported sleep duration at five time points between 1985 and 2013, and who had cognitive testing and magnetic resonance imaging administered at a single timepoint between 2012 and 2016. We applied latent class growth analysis to estimate membership into trajectory groups based on self-reported sleep duration over time. Analysis of gray matter volumes was carried out using FSL Voxel-Based-Morphometry and white matter microstructure using Tract Based Spatial Statistics. We assessed group differences in cognitive and MRI outcomes using nonparametric permutation testing.ResultsLatent class growth analysis identified four trajectory groups, with an average sleep duration of 5.4 ± 0.2 hours (5%, N = 29), 6.2 ± 0.3 hours (37%, N = 228), 7.0 ± 0.2 hours (45%, N = 278), and 7.9 ± 0.3 hours (13%, N = 78). No differences in cognition, gray matter, and white matter measures were detected between groups.ConclusionsOur null findings suggest that current sleep guidelines that recommend at least 7 hours of sleep per night may not be supported in relation to an association between sleep patterns and cognitive function or brain structure.

Paunio, Tiina

doi: 10.1093/sleep/zsaa081pmid: 32395763

Major depressive disorder (MDD) is a common disorder and, globally, a major cause of disability [1]. The recurrent nature of MDD raises the possibility that preventive measures could be an effective tool in attempts to decrease its incidence and the global burden, which underlines the importance of identification of independent, modifiable risk factors. In this issue of Sleep, Blanken and colleagues address this problem by examining a longitudinal cohort of adults [2]. They monitored potential risk factors at baseline and studied their association with MDD during a 6-year follow-up period. Unlike most previous studies, which have not comprehensively accounted for the lifetime history of depression and thereby the confounding effect of prior disease episodes, Blanken et al. aimed at identifying de novo risk factors for MDD by excluding individuals with previous disease history. The finding of elevated risk for MMD in connection with symptoms of insomnia is in line with previous studies, which have reported a robust twofold to threefold risk for onset of MDD with insomnia at baseline [3]. A risk of the same magnitude was observed in the present study, in which participants, who scored over the insomnia cutoff of the Insomnia Rating Scale, were over two times more likely to develop first-onset MDD as compared to those without insomnia symptoms. Of the various insomnia complaints, the predictive effect was found to be driven by the item measuring difficulty initiating sleep (DIS), “did you have trouble falling asleep”: individuals experiencing DIS at least three times per week were over two times more likely to develop first-onset MDD. Short sleep duration, on the other hand, did not affect the risk, as those reporting sleeping 6 hours or less per night did not have an increased risk for MDD, nor did short sleep interact with the insomnia severity. This contradicts some previous studies, which have reported the insomnia phenotype with objective short sleep as the biologically most severe one, associated with the most elevated risk of secondary adverse health events [4, 5]. By applying a novel analytical tool, Network Outcome Analysis [6, 7], the authors were able to examine the direct predictive value of individual insomnia and other complaints for incidence of depression, with simultaneous control of other confounding factors. This led to the identification of five subthreshold symptoms that predicted first-onset MDD: energy level (fatigue), concentration/decision making, feeling sad (depressed mood), feeling restless (psychomotor agitation), and difficulty falling asleep (DIS). In addition to first-onset MDD, DIS connected also to concurrent symptoms of depressed mood, psychomotor agitation, and difficulty maintaining sleep in the network analysis. However, as the authors discuss, the observed link between DIS and incident MDD presented a unique relationship between these two variables, irrespective of other observed inter-variable relations. Out of other sleep complaints, difficulty maintaining sleep related to DIS, as well as to early morning awakenings in the network analysis. None of these other complaints predicted, however, directly first-onset MDD. Thus, out of the various sleep symptoms, DIS was the most direct indicator of an underlying vulnerability for depression. Although previous research has demonstrated the abundant sleep-wake transitions in insomnia [8], the authors concluded that the core problem in insomnia may rather be the difficulty in transitioning from wake to sleep at sleep onset or later during the night. While the detailed neurobiological mechanisms of insomnia are not completely understood, they are considered to involve overactivity of arousal systems [9, 10]; for review, see Riemann et al.,[11] which according to experimental models, may comprise simultaneous activation of sleep-inducing and arousal-promoting brain areas during sleep [12]. Cortical arousal has been suggested to lead to enhanced information processing during sleep initiation and to tendency to overestimate sleep latency among individuals with insomnia. There was no objective sleep data in the present study, so the possibility of sleep-onset misperception cannot be ruled out. However, recent data evidences that this tendency to overestimate sleep onset latency is influenced by sleep fragmentation, supporting the view of sleep misperception as an actual problem of impaired sleep quality rather than a mere erroneous perception of wakefulness [13]. DIS may also result from incompatibility between the circadian rhythm and the time to attempted sleep, as e.g. in individuals with evening chronotype, too early bed-time may result in sleep-onset insomnia. In the present study, chronotype was not assessed, so this possibility cannot be entirely ruled out. However, as Blanken and colleagues discuss, it is unlikely that the observed association of DIS with depression would solely reflect late chronotype, as both late chronotype and insomnia have been found to associate independently with an increased risk of emotional problems [14]. Finding a direct predictive value for a specific insomnia complaint has great potential to be used for screening of individuals at-risk for depressive disorder. Self-evidently, screening is useful only if an effective treatment exists—which is the case for insomnia. Cognitive-behavioral therapy for insomnia, CBT-I, is the treatment of choice, with a plentitude of evidence from clinical trials [15, 16]. Recent data evidence for its effectiveness also as a preventive measure for depression. In a study on internet users with insomnia and depression symptoms but without the diagnostic criteria for MDD, treatment using online insomnia program based on CBT-I, as compared to an internet-based placebo program, significantly lowered depression symptoms at follow-up of 6 months [17], and digital CBT-I as compared to online sleep education was found to reduce incidence of MDD at 1 yr follow-up among individuals with insomnia [18]. Furthermore, studies on treatment of comorbid insomnia and depression with CBT-I have given encouraging results in previous clinical trials, evidencing for the superiority of CBT-I added on to escitalopram compared to escitaloprame alone [19], internet-based CBT-I compared to CBT for depression [20], and CBT-I to compared to online sleep education [18]. Thus, whether DIS presents as an isolated symptom (i.e. a genuine potential risk factor for MDD without any concurrent symptoms or signs for depressed mood), a residual symptom of prior episode of depression, or a symptom of clinically manifest depressive disorder, is not crucial from the point of view of treatment, since CBT-I is effective for both insomnia disorder and for comorbid insomnia and depression. While there are treatments with reasonable efficacy for depression, many patients do not remit with a single treatment [21] and, consequently, there is an apparent need to develop more personalized approaches. Identification of DIS as a genuine risk factor for first-onset depression, as discovered in the study by Blanken and colleagues, makes it an eligible target for screening and initiation of a treatment protocol, readily available in health care organizations, distributable via various platforms and with a potential to reach large numbers of individuals via digital technologies [22]. Eventually, finding of effective solutions to prevention and early treatment of the risk factors for MDD would have big impact on general health of the populations, given the high global burden of the disorder. Funding This work is supported by Academy of Finland (441239) and Helsinki University Hospital (TYH2019315). Conflict of interest statement. None declared. References 1. Disease GBD , et al. 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Efficacy of internet-delivered cognitive-behavioral therapy for insomnia—a systematic review and meta-analysis of randomized controlled trials . Sleep Med Rev. 2016 ; 30 : 1 – 10 . Google Scholar Crossref Search ADS PubMed WorldCat © Sleep Research Society 2020. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please email: [email protected] This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Adamantidis, A R; Schmidt, M H; Carter, M E; Burdakov, D; Peyron, C; Scammell, Thomas E

doi: 10.1093/sleep/zsz296pmid: 31919524

The sleep disorder narcolepsy is associated with symptoms related to either boundary state control that include excessive daytime sleepiness and sleep fragmentation, or rapid eye movement (REM) sleep features including cataplexy, sleep paralysis, hallucinations, and sleep-onset REM sleep events (SOREMs). Although the loss of Hypocretin/Orexin (Hcrt/Ox) peptides or their receptors have been associated with the disease, here we propose a circuit perspective of the pathophysiological mechanisms of these narcolepsy symptoms that encompasses brain regions, neuronal circuits, cell types, and transmitters beyond the Hcrt/Ox system. We further discuss future experimental strategies to investigate brain-wide mechanisms of narcolepsy that will be essential for a better understanding and treatment of the disease.

Keenan, Brendan T; Galante, Raymond J; Lian, Jie; Simecek, Petr; Gatti, Daniel M; Zhang, Lin; Lim, Diane C; Svenson, Karen L; Churchill, Gary A; Pack, Allan I

doi: 10.1093/sleep/zsz278pmid: 32074270