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Enlighten your clock: How your body tells time – Italian

OBJECTIVE Perinatal depression (PND) is a severe complication of pregnancy, affecting both mothers and newborns. Bright light therapy (BLT) has only been tested in a few studies for treating either antenatal or postnatal depression. We conducted a pilot trial to investigate the efficacy and safety of BLT for PND occurring at any time across the perinatal period. METHODS A single-blind RCT was carried out in women with an EPDS >12 from the 2nd gestational trimester until 9 months postpartum. Participants received either 30-minutes morning BLT (10'000 lux) or dim red light (DRL, 19 lux) for 6 weeks. RESULTS Twenty-two women were randomised to BLT (n = 11) or DRL (n = 11). Among those receiving BLT, 73% achieved remission (improvement ≥50%, EPDS score ≤ 12), in contrast to 27% in the DRL group (p = 0.04). A significant influence of time on EPDS score and group-time interaction emerged, with a greater reduction in the BLT-group across the follow-up period. No women in either group reported major side effects. CONCLUSION Morning BLT induced a significant remission from PND as compared to DRL and this effect was maintained across the perinatal period. BLT showed an excellent safety profile and was well-tolerated, thus representing a valid therapeutic strategy in this vulnerable perinatal population.

Background Perinatal depression (PND) is a severe mental disorder with disruptive consequences on the health and well-being of mothers, children, and their families. Due to the induced socioeconomic burden, it also represents a major public health problem for society as a whole, and is therefore considered a priority target of health prevention strategies at a global level. There is, in fact, general consensus among experts that PND is still prevalent, underrecognized and undertreated. While research on the pathophysiological mechanisms of PND is contributing to an increased knowledge of the multifactorial causes of this condition, and is likely to provide new biomarkers for medical use in the near future, none of these is currently available for the everyday clinical practice. Conversely, there is an urgent need of easy and universal screening instruments, as well as safe and affordable treatments that all women can have access to. Sleep and circadian rhythm disruption are commonly experienced by women during the perinatal period, but there is limited evidence on the objective changes in sleep parameters occurring during pregnancy and how these relate to health outcomes. Moreover, the role of sleep and circadian factors in the etiology of PND and as potential targets for treatment is still underestimated and underinvestigated. As an example, the influence of different circadian preferences for sleep-wake times (chronotypes) on the development of depressive symptoms across the perinatal period has never been investigated. Likewise, the efficacy and safety of bright light therapy (BLT) for the treatment of PND with onset before and/or after delivery have never been tested. Objectives Manuscript 1: to perform the first systematic review and meta-analysis of polysomnographic studies during pregnancy, in order to identify possible objective markers of sleep disruption in pregnant women. Manuscript 2: to investigate whether chronotype is a risk factor for PND and to explore the association between chronotype, maternal sociodemographic characteristics, and lifestyle habits, in relation to PND. Manuscript 3: to conduct the first randomized controlled trial (RCT) aimed at testing the efficacy and safety of BLT for PND occurring over a 12-month observation period. Methods Manuscript 1: by carefully following the PRISMA guidelines, we conducted the first systematic review of polysomnographic studies during pregnancy available in the literature. In addition, we performed a meta-analysis of the data collected on two sleep variables (TST and SE). This was instead not possible for other sleep parameters, due to the large heterogeneity of the reviewed studies. Manuscript 2: as a part of the “Life-ON” project, a multicenter, prospective, cohort study on sleep and mood changes during the perinatal period, 299 women were followed-up from the first trimester of pregnancy until 6 months postpartum. Chronotype was assessed at baseline using the MEQ, while mood was repeatedly evaluated at several timepoints with depression rating scales (i.e., EPDS, HDRS, and MADRS). The influence of time and chronotype on the different scales was estimated by constructing multilevel linear mixed regression models. A Cox proportional-hazard regression model was built to evaluate the association between chronotype and incidence of depression. Manuscript 3: in the frame of the “Life-ON” project, a RCT was conducted in a subsample of women with an EPDS score >12 at any time point from the second trimester of pregnancy up to 6 months postpartum. Participants received either BLT (10’000 lux) or DRL (19 lux) for 6 weeks, 30 minutes in the morning, within 20 minutes after wake up, and at a distance of 30 cm from the light box. Multilevel linear models were constructed to test for the influence of time and treatment group on EPDS values and log-linear models to test for socioeconomic factors influencing PND remission. Results According to our systematic review, the main changes in objective sleep parameters during pregnancy consists in a reduction of sleep duration and a fragmentation of sleep continuity, with an increased number of awakenings and superficial sleep stages (N1, N2), and a simultaneous decrease of SWS, REM sleep, and SE. The meta-analysis revealed a significant reduction of TST by 26.8 min between the first and third trimester of pregnancy, as well as a decrease of SE by 4% within the same time frame. Pregnant evening chronotypes, as compared to the other chronotypes, are more vulnerable to PND symptoms, especially in the immediate postpartum period. Although the survival analysis did not show a statistically significant influence of chronotype on the overall risk of PND, a trend towards an increased risk for PND in evening chronotypes and a reduced risk in intermediate types, as compared to morning types, was observed. Furthermore, in line with the literature, pregnant women with evening chronotype in the Life-ON study were more likely subject to health problems and negative pregnancy outcomes than the other chronotypes, and presented adverse sociodemographic characteristics and lifestyle attitudes, that are commonly associated with a higher risk for PND. Finally, in a RCT testing 6-week morning BLT (10’000 lux) vs. DRL (19 lux) for treating PND, the active light intervention (BLT) showed a remarkable efficacy in inducing a rapid remission from PND compared to DRL. The multilevel linear model revealed a significant influence of time on EPDS score and a group-time interaction, with a greater and sustained reduction in the BLT-group across the whole follow-up period. Conclusion We found evidence that the subjective experience of sleep deterioration, that many women report during pregnancy, is related to objective alterations in sleep architecture, particularly during late gestation. These can only be appropriately recorded by PSG, which should be therefore considered a valuable and sometimes necessary instrument to correctly diagnose sleep disorders, also during pregnancy, by overcoming under- or overestimation bias due to subjective reports of sleep problems. Interestingly, despite several physiological factors may be involved in the subjective worsening of sleep quality across gestation, is not pregnancy per se, that causes major PSG-assessed sleep disorders in healthy, normal-weight women. Rather, it is likely the combination of predisposing factors, such as obesity, higher maternal age or hypertension, and physiological changes occurring during pregnancy, that may contribute in particular to the development of obstructive sleep apnea (OSA) in at-risk pregnant women. Evening chronotype is associated with a time-dependent, greater severity of PND. Thus, assessing chronotype during pregnancy via the administration of an easy screening questionnaire, may help identify women who are likely to experience more severe perinatal depressive symptoms, especially in the early postpartum, and provide them with psychiatric/psychological support and treatment. BLT can not only induce a rapid and significant remission from PND compared to DRL, but the resulting improvement in mood can be maintained over time after treatment completion. These new findings support the integration of BLT as effective and safe chronotherapeutic tool, based on solid scientific evidence, to the equipment available to clinicians for the treatment of PND, thus responding to the need for affordable, easy-to-use, and accessible therapies for patients.

Study Objectives Nighttime transportation noise elicits awakenings, sleep-stage changes, and electroencephalographic (EEG) arousals. Here, we investigated the potential sleep-protective role of sleep spindles on noise-induced sleep alterations. Methods Twenty-six young (19-33 years, 12 women) and 18 older (52-70 years, 9 women) healthy volunteers underwent a repeated measures polysomnographic 6-day laboratory study. Participants spent one noise-free baseline night, followed by four transportation noise-exposure nights (road traffic or railway noise; continuous or intermittent: average sound levels of 45 dB, maximum sound levels of 50-62 dB), and one noise-free recovery night. Sleep stages were scored manually and fast sleep spindle characteristics were quantified automatically using an individual band-pass filtering approach. Results Nighttime exposure to transportation noise significantly increased sleep EEG arousal indices. Sleep structure and continuity were not differentially affected by noise exposure in individuals with a low versus a high spindle rate. Spindle rates showed an age-related decline along with more noise-induced sleep alterations. All-night spindle rates did not predict EEG arousal or awakening probability from single railway noise events. Spindle characteristics were affected in noise-exposure nights compared to noise-free nights: we observed a reduction of the spindle amplitude in both age groups and of the spindle rate in the older group. Conclusions We have evidence that spindle rate is more likely to represent a trait phenomenon, which does not seem to play a sleep-protective role in nighttime transportation noise-induced sleep disruptions. However, the marked reduction in spindle amplitude is most likely a sensitive index for noise-induced sleep alterations.

Hintergrund: Die Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) ist die am häufigsten diagnostizierte Entwicklungsstörung der Kindheit. Oft bleibt diese aber auch bis ins Erwachsenenalter bestehen und wirkt sich negativ auf die Lebensqualität der Betroffenen aus. Dies liegt nicht nur an den Kardinalsymptomen der Erkrankung, sondern auch an den typischerweise damit verbundenen psychiatrischen Begleiterkrankungen und Schlafstörungen. Es wird berichtet, dass der Schlaf von Patienten mit ADHS in jedem Alter subjektiv gestört ist. Ergebnisse von Studien, die den Schlaf bei ADHS objektiv untersucht haben, sind bei Kindern jedoch inkonsistent, während bei Erwachsenen nur sehr wenige Studien vorliegen. Ziel: Periodische Beinbewegungen im Schlaf (PLMS) treten gehäuft beim Restless-Legs-Syndrom (RLS) auf und können in einer Schlaffragmentierung resultieren. Basierend auf dem klinisch beobachteten Zusammenhang zwischen RLS und ADHS, wurden die Schlafstruktur und insbesondere das Muster der motorischen Aktivität im Schlaf bei Patienten mit ADHS untersucht. Es wurde die Hypothese aufgestellt, dass sowohl RLS als auch die ADHS durch vermehrte PLMS gekennzeichnet sind, was die schlechte Schlafqualität von ADHS-Patienten erklären und sogar eine mögliche gemeinsame Pathophysiologie dieser beiden Erkrankungen nahelegen könnte. Um diese Hypothese zu testen, wurde erstmalig eine detaillierte Analyse der Beinbewegungen (LMs) im Schlaf bei Erwachsenen mit ADHS im Vergleich zu gesunden Kontrollpersonen durchgeführt. Methoden: Fünfzehn ADHS-Patienten und achtzehn alters- und geschlechtsausgeglichenen Kontrollpersonen nahmen an einer polysomnographischen Studie im Schlaflabor teil. Der periodische Charakter der LMs wurde mit neueren Verfahren zur Messung von "Periodizität" (d.h. des Periodizitätsindex, der Intermovement-Intervalle und der nächtlichen Zeitverteilung der LMs) zusätzlich zu Standardparametern wie dem PLMS-Index bewertet. Die subjektive Schlafqualität und das Vorliegen psychiatrischer Symptome wurden anhand von Screening-Fragebogen beurteilt. Ergebnisse: Ein Vergleich der objektiven Schlafparameter ließ lediglich für die Schlaflatenz einen signifikanten Unterschied erkennen. Diese war bei den ADHS-Probanden länger als bei den Kontrollen. Die Analyse der Beinbewegungen im Schlaf ergab eine längere Dauer von PLMS im REM-Schlaf bei ADHS-Probanden, sowie einen höheren PLMS-Index im REM-Schlaf. Daten aus den Schlaf- Fragebogen zeigten eine schlechtere subjektive Schlafqualität bei ADHS-Patienten. Schlussfolgerungen: Wie bereits bei Kindern gezeigt sind LMs bei ADHS-Erwachsenen nicht signifikant häufiger als bei gesunden Kontrollen und weisen keine erhöhte Periodizität auf. Diese Befunde scheinen ADHS von anderen pathophysiologisch verwandten Erkrankungen, wie RLS, zu unterscheiden. Die von ADHSPatienten subjektiv wahrgenommene schlechte Schlafqualität, steht im Gegensatz zu den normalen gemessenen polysomnographischen Parametern. Diese abweichende Einschätzung des Schlafes könnte auf subtilere, durch die traditionelle Schlafauswertung nicht erfassbaren Veränderungen im Schlaf hindeuten, welche sich auch bei detaillierterer Analyse von PLMS nicht erklären lassen., Background: Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurodevelopmental disorder of the childhood, but also frequently persists into adulthood, impairing the quality of life of the affected patients. This is not only due to the cardinal symptoms of the disorder, but also to its typically associated psychiatric comorbidities and sleep disturbances. Sleep is reported to be subjectively disturbed by ADHD patients at any age, but the results of studies objectively assessing sleep in ADHD are not consistent in children and still lacking in adults. Aim: Periodic leg movements during sleep (PLMS) are common in Restless Legs Syndrome (RLS) and may result in sleep fragmentation. Based on the clinically observed association between RLS and ADHD, the sleep structure and the pattern of motor activity during sleep in patients with ADHD were investigated. It has been hypothesized that both RLS and ADHD are characterized by increased PLMS, which may explain the poor sleep quality experienced by ADHD patients and even suggest a possible common pathophysiology of these two disorders. To test this hypothesis, a detailed analysis of leg movements (LMs) during sleep was performed for the first time in adults with ADHD compared to healthy control subjects. Methods: Fifteen ADHD patients and eighteen gender- and age-matched control subjects underwent an in-lab polysomnographic study. The periodic character of LMs was evaluated by newer measures of “periodicity” (i.e. the periodicity index, intermovement intervals, and nocturnal time distribution of LMs), in addition to standard parameters, such as the PLMS-Index. Subjective sleep quality and psychiatric symptoms were assessed by screening questionnaire. Results A comparison of the objective sleep parameters revealed only a significant difference for the sleep latency. This was longer in ADHD subjects than in controls. The analysis of LMs showed a longer duration of PLMS in REM sleep in ADHD subjects, and a higher PLMS index in REM sleep. Data from the sleep questionnaire demonstrated a poorer subjective sleep quality in ADHD patients. Conclusions: As demonstrated in children, LMs are not significantly more common in ADHD adults than in healthy controls and show no increased periodicity. These findings seem to differentiate ADHD from other pathophysiologically related disorders, like RLS. The poor sleep quality perceived by ADHD patients contrasts with the normal polysomnographic parameters. This sleep-state misperception may point to more subtle sleep changes that can not be detected by the traditional sleep scoring, nor be explained by a more detailed analysis of PLMS.

Humans live in a 24-hour environment, in which light and darkness follow a diurnal pattern. Our circadian pacemaker, the suprachiasmatic nuclei (SCN) in the hypothalamus, is entrained to the 24-hour solar day via a pathway from the retina and synchronises our internal biological rhythms. Rhythmic variations in ambient illumination impact behaviours such as rest during sleep and activity during wakefulness as well as their underlying biological processes. Rather recently, the availability of artificial light has substantially changed the light environment, especially during evening and night hours. This may increase the risk of developing circadian rhythm sleepwake disorders (CRSWD), which are often caused by a misalignment of endogenous circadian rhythms and external lightdark cycles. While the exact relationship between the availability of artificial light and CRSWD remains to be established, nocturnal light has been shown to alter circadian rhythms and sleep in humans. On the other hand, light can also be used as an effective and noninvasive therapeutic option with little to no side effects, to improve sleep, mood and general well-being. This article reviews our current state of knowledge regarding the effects of light on circadian rhythms, sleep, and mood. (VLID)4394440