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Chronotherapeutic interventions for bipolar depression and mania are promising interventions associated with rapid response and benign side effect profiles. Filtering of biologically active short wavelength (blue) light by orange tinted eyewear has been shown to induce antimanic and sleep promoting effects in inpatient mania. We here describe a study protocol assessing acute and long-term stabilizing effects of blue blocking (BB) glasses in outpatient treatment of bipolar disorder. A total of 150 outpatients with bipolar disorder and current symptoms of (hypo)-mania will be randomized 1:1 to wear glasses with either high (99%) (intervention group) or low (15%) (control group) filtration of short wavelength light (<500 nm). Following a baseline assessment including ratings of manic and depressive symptoms, sleep questionnaires, pupillometric evaluation and 48-h actigraphy, participants will wear the glasses from 6 PM to 8 AM for 7 consecutive days. The primary outcome is the between group difference in change in Young Mania Rating Scale scores after 7 days of intervention (day 9). Following the initial treatment period, the long-term stabilizing effects on mood and sleep will be explored in a 3-month treatment paradigm, where the period of BB treatment is tailored to the current symptomatology using a 14-h antimanic schedule during (hypo-) manic episodes (BB glasses or dark bedroom from 6 PM to 8 AM) and a 2-h maintenance schedule (BB glasses on two hours prior to bedtime/dark bedroom) during euthymic and depressive states. The assessments will be repeated at follow-up visits after 1 and 3 months. Throughout the 3-month study period, participants will perform continuous daily self-monitoring of mood, sleep and activity in a smartphone-based app. Secondary outcomes include between-group differences in actigraphic sleep parameters on day 9 and in day-to-day instability in mood, sleep and activity, general functioning and objective sleep markers (actigraphy) at weeks 5 and 15. The trial will be registered at prior to initiation and has not yet received a trial reference. The current paper is based on protocol version 1.0_31.07.23. Trial sponsor: Lars Vedel Kessing. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare 24-h motor activity patterns between and within three groups of acutely admitted inpatients with schizophrenia and psychotic disorders (n = 28), bipolar mania (n = 18) and motor-retarded unipolar depression (n = 25) and one group of non-hospitalized healthy individuals (n = 28). Motor activity was measured by wrist actigraphy, and analytical approaches using linear and non-linear variability and irregularity measures were undertaken. In between-group comparisons, the schizophrenia group showed more irregular activity patterns than depression cases and healthy individuals. The schizophrenia and mania cases were clinically similar with respect to high prevalence of psychotic symptoms. Although they could not be separated by a formal statistical test, the schizophrenia cases showed more normal amplitudes in morning to evening mean activity and activity variability. Schizophrenia constituted an independent entity in terms of motor activation that could be distinguished from the other diagnostic groups of psychotic and non-psychotic affective disorders. Despite limitations such as small subgroups, short recordings and confounding effects of medication/hospitalization, these results suggest that detailed temporal analysis of motor activity patterns can identify similarities and differences between prevalent functional psychiatric disorders. For this purpose, irregularity measures seem particularly useful to characterize psychotic symptoms and should be explored in larger samples with longer-term recordings, while searching for underlying mechanisms of motor activity disturbances., (Copyright © 2018. Published by Elsevier B.V.)

Millions of people worldwide are working at times that overlap with the normal time for sleep. Sleep problems related to the work schedule may mediate the well-established relationship between shift work and increased risk for disease, occupational errors and accidents. Yet, our understanding of causality and the underlying mechanisms that explain this relationship is limited. We aimed to assess the consequences of night-shift work for sleep and to examine whether night-shift work-induced sleep disturbances may yield electrophysiological markers of impaired maintenance of the waking brain state. An experimental model developed in rats simulated a 4-day protocol of night-work in humans. Two groups of rats underwent 8-h sessions of enforced ambulation, either at the circadian time when the animal was physiologically primed for wakefulness (active-workers, mimicking day-shift) or for sleep (rest-workers, mimicking night-shift). The 4-day rest-work schedule induced a pronounced redistribution of sleep to the endogenous active phase. Rest-work also led to higher electroencephalogram (EEG) slow-wave (1-4 Hz) energy in quiet wakefulness during work-sessions, suggesting a degraded waking state. After the daily work-sessions, being in their endogenous active phase, rest-workers slept less and had higher gamma (80-90 Hz) activity during wake than active-workers. Finally, rest-work induced an enduring shift in the main sleep period and attenuated the accumulation of slow-wave energy during NREM sleep. A comparison of recovery data from 12:12 LD and constant dark conditions suggests that reduced time in NREM sleep throughout the recorded 7-day recovery phase induced by rest-work may be modulated by circadian factors. Our data in rats show that enforced night-work-like activity during the normal resting phase has pronounced acute and persistent effects on sleep and waking behavior. The study also underscores the potential importance of animal models for future studies on the health consequences of night-shift work and the mechanisms underlying increased risk for diseases.

Objective: Available pharmacological treatment of mania is insufficient. Virtual darkness therapy (blue light-blocking treatment by means of orange-tinted glasses) is a promising new treatment option for mania. The basis for this might be the recently identified blue light-sensitive retinal photoreceptor, which is solely responsible for light stimulus to the circadian master clock. This is the first case report describing the clinical course of a closely monitored, hospitalized patient in a manic episode first receiving clear-lensed, and then blue light-blocking glasses., Methods: A 58-year-old Caucasian man, with bipolar I disorder and three previous manic episodes, was hospitalized during a manic episode. In addition to pharmacological treatment, he was treated with clear-lensed glasses for seven days, then one day without glasses, followed by six days of blue light-blocking glasses. During the entire observational period, he wore an actigraph with internal light sensors., Results: Manic symptoms were unaltered during the first seven days. The transition to the blue-blocking regime was followed by a rapid and sustained decline in manic symptoms accompanied by a reduction in total sleep, a reduction in motor activity during sleep intervals, and markedly increased regularity of sleep intervals. The patient's total length of hospital stay was 20 days shorter than the average time during his previous manic episodes., Conclusions: The unusually rapid decline in symptoms, accompanied by uniform sleep parameter changes toward markedly increased regularity, suggest that blue-blockers might be targeting a central mechanism in the pathophysiology of mania that needs to be explored both in clinical research and in basic science., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)