Blue-blocking glasses as adjunctive treatment for bipolar mania - and exploration of motor activity patterns in serious mental disorders

Background: There is a need for more effective treatments of bipolar mania. Promising reports of the effects of dark therapy on bipolar disorder symptoms and the discovery of a mainly blue-light sensitive daylight-signaling retinal ganglion cells has resulted in the utility of BB glasses to create a virtual darkness condition for the brain. Changes in activation or aberrant motor activity is present in all serious mental disorders. Actigraphy is a non-invasive and simple means of assessing motor activity, but is still mostly used to assess sleep outcomes. Before the utility of actigraphy can be broadened, there is need for further exploration of daily activity pattern characteristics for the diagnostic entities. Aims: By means of the Virtual Darkness as Additive Treatment in Mania (VATMAN) trial, we aimed to test the effectiveness and feasibility of BB glasses as an adjunctive treatment for mania compared to placebo glasses. As part of the Agitation at Admittance to a Psychiatric Acute Department Study, we aimed to characterize the motor activity patterns among a new sample of patients with psychotic disorders, and compare these characteristics to the motor activity patterns of patients with affective disorders and with healthy controls. Methods: Eligible patients for the VATMAN trial (hospitalized with bipolar disorder mania and otherwise fulfilling inclusion criteria) were randomized to receive either BB-glasses or clear-lensed placebo glasses. The glasses were worn as an adjunctive treatment from 6:00 p.m. to 8:00 a.m. for seven consecutive days. Manic symptoms were rated daily using the Young Mania Rating Scale. Motor activity was measured using wrist-worn actigraphs. Feasibility was assessed using a self-report patient experience questionnaire together with the clinical observation of side-effects. Sleep was assessed using actigraphy-derived sleep parameters. In the Agitation at Admittance to a Psychiatric Acute Department study, all hospitalized patients in the acute psychiatric ward in Østmarka Hospital, Trondheim were asked to wear an actigraph for 24 h. The motor activity patterns of patients diagnosed with schizophrenia and other psychotic disorders were compared to those of patients with mania, motor-retarded unipolar depression, and healthy controls. Linear and non-linear analytical methods were used to describe and compare motor activity variability and complexity (irregularity) for a 24 h period as well as in morning and evening sequences. Results: Out of 32 randomized patients in the VATMAN trial, 12 patients in the BB-group and 11 patients in the placebo-group were included in the analyses. After seven days, the Cohen’s d effect size was 1.86. There was a significant group difference in YMRS scores after three days (p = 0.042) and the group difference increased steadily throughout the intervention. Observed side effects included headache in one patient and rapidly reversible depressive symptoms in two patients. Actigraphy-derived sleep outcomes at night five showed significantly higher sleep efficiency, lower motor activity and less minutes of wake after sleep onset in the BB group as compared to the placebo group. Several patients in both groups displayed a 48 h-like rhythm of shorter or disrupted sleep. The schizophrenia spectrum group shared the characteristic of high motor activity variability with the unipolar depressed group, but differed with respect to more irregular (complex) activity pattern in the morning sequence. The schizophrenia spectrum and the mania groups could not be separated using formal statistical analyses, being most similar with regards to high morning activity irregularity. The mania group was the only one to show a blunted morning-to-evening activity fluctuation, while the normal morning-to-evening decline was more preserved in the schizophrenia spectrum group. Conclusions: BB-glasses were found to be both effective and feasible as an adjunctive treatment for mania. The BB-group showed actigraphy-derived sleep parameters reflecting less activated sleep compared with the placebo-group. The use of actigraphy data to characterize diurnal motor activity patterns, by use of the combination of linear and non-linear analytical approaches, seems to have potential for assessment of symptoms and for diagnostic support

A randomized controlled trial on the effects of blue-blocking glasses compared to partial blue-blockers on sleep outcomes in the third trimester of pregnancy

Objective Sleep disturbances are common in pregnancy. Blocking blue light has been shown to improve sleep and may be a suitable intervention for sleep problems during pregnancy. The present study investigated the effects of blue light blocking in the evening and during nocturnal awakenings among pregnant women on primary sleep outcomes in terms of total sleep time, sleep efficiency and mid-point of sleep. Methods In a double-blind randomized controlled trial, 60 healthy nulliparous pregnant women in the beginning of the third trimester were included. They were randomized, using a random number generator, either to a blue-blocking glass intervention (n = 30) or to a control glass condition constituting partial blue-blocking effect (n = 30). Baseline data were recorded for one week and outcomes were recorded in the last of two intervention/control weeks. Sleep was measured by actigraphy, sleep diaries, the Bergen Insomnia Scale, the Karolinska Sleepiness Scale and the Pre-Sleep Arousal Scale. Results The results on the primary outcomes showed no significant mean difference between the groups at posttreatment, neither when assessed with sleep diary; total sleep time (difference = .78[min], 95%CI = -19.7, 21.3), midpoint of sleep (difference = -8.9[min], 95%CI = -23.7, 5.9), sleep efficiency (difference = -.06[%], 95%CI = -1.9, 1.8) and daytime functioning (difference = -.05[score points], 95%CI = -.33, .22), nor by actigraphy; total sleep time (difference = 13.0[min], 95%CI = -9.5, 35.5), midpoint of sleep (difference = 2.1[min], 95%CI = -11.6, 15.8) and sleep efficiency (difference = 1.7[%], 95%CI = -.4, 3.7). On the secondary outcomes, the Bergen Insomnia Scale, the Karolinska Sleepiness Scale and the Pre-Sleep Arousal Scale the blue-blocking glasses no statistically significant difference between the groups were found. Transient side-effects were reported in both groups (n = 3). Conclusions The use of blue-blocking glasses compared to partially blue-blocking glasses in a group of healthy pregnant participants did not show statistically significant effects on sleep outcomes. Research on the effects of blue-blocking glasses for pregnant women with sleep-problems or circadian disturbances is warranted.publishedVersio

Motor activity patterns in acute schizophrenia and other psychotic disorders can be differentiated from bipolar mania and unipolar depression

Under embargo until: 02.10.2019The 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.acceptedVersio

A randomized controlled trial on the effect of blue-blocking glasses compared to partial blue-blockers on melatonin profile among nulliparous women in third trimester of the pregnancy

Objective In pregnancy melatonin regulates circadian rhythms, induce sleep, and has a neuroprotective positive effect on fetal development. Artificial blue light in the evening delays and suppresses melatonin production. Thus, we investigated the effect of blocking blue light on the melatonin profile. Methods A randomized controlled trial (n=30 blue-blocking glasses vs. n=30 control glasses with partial blue-blocking effect) including healthy nulliparous pregnant women in the beginning of the third trimester. Salivary melatonin and subjective sleep were measured before and after two weeks of intervention/control condition. Saliva was sampled at 30-min intervals from 3 h before normal bedtime. Melatonin onset was set at 4.0 pg/ml. Results Due to missing data melatonin onset was estimated for 47 participants. At posttreatment, melatonin onset advanced by 28 min in the blue-blocking group compared with the control condition (p=.019). Melatonin levels were significantly higher, favoring the blue-blocking glass condition, at clock time 20:00, 21:00 and 22:00 h, and for sample number 3 and 4. The phase angle (time interval) between melatonin onset and sleep bedtime and sleep onset time increased within the blue blocking group (+45 min and +41 min, respectively), but did not reach statistical significance compared to control condition (+13 min and +26 min, respectively). Conclusion Blocking blue light in the evening had a positive effect on the circadian system with an earlier onset and rise of melatonin levels in healthy nulliparous pregnant women. This demonstrated the effectiveness and feasibility of a simple non-pharmacological chronobiological intervention during pregnancy.publishedVersio

Blue-blocking glasses as additive treatment for mania: Effects on actigraphy-derived sleep parameters

Improvement of sleep is a central treatment goal for patients in a manic state. Blue‐blocking (BB) glasses as adjunctive treatment hasten overall recovery from mania. This method is an evolvement from dark therapy and builds on the discovery of the blue‐light‐sensitive retinal ganglion cell that signals daytime to the brain. We report effects of adjunctive BB glasses on actigraphy‐derived sleep parameters for manic inpatients as compared to placebo. Hospitalized patients with bipolar disorder in a manic state aged 18–70 years were recruited from five clinics in Norway from February 2012 to February 2015. The participants were randomly allocated to wearing BB glasses or placebo (clear glasses) as an adjunctive treatment from 18:00 to 08:00 hours for seven consecutive nights. Sleep and wake were monitored by actigraphy. From 32 eligible patients, 10 patients in each group qualified for the group analyses. The BB group's mean sleep efficiency was significantly higher at night 5 as compared to the placebo group (92.6% vs. 83.1%, p = .027). The 95% confidence interval (CI) was 89.4%–95.8% in the BB group and 75.9%–90.3% in the placebo group. There were fewer nights of interrupted sleep in the BB group: 29.6% versus 43.8% in the placebo group. The BB group received less‐intensive sleep‐promoting pharmacological treatment and showed significantly higher sleep efficiency and more consolidated sleep as compared to the placebo group. Our findings suggest sleep‐promoting effects through deactivating mechanisms. Adjunctive BB glasses seem to be useful for improving sleep for manic patients in the hospital setting.publishedVersio

Shift in Food Intake and Changes in Metabolic Regulation and Gene Expression during Simulated Night-Shift Work:A Rat Model

Night-shift work is linked to a shift in food intake toward the normal sleeping period, and to metabolic disturbance. We applied a rat model of night-shift work to assess the immediate effects of such a shift in food intake on metabolism. Male Wistar rats were subjected to 8 h of forced activity during their rest (ZT2-10) or active (ZT14-22) phase. Food intake, body weight, and body temperature were monitored across four work days and eight recovery days. Food intake gradually shifted toward rest-work hours, stabilizing on work day three. A subgroup of animals was euthanized after the third work session for analysis of metabolic gene expression in the liver by real-time polymerase chain reaction (PCR). Results show that work in the rest phase shifted food intake to rest-work hours. Moreover, liver genes related to energy storage and insulin metabolism were upregulated, and genes related to energy breakdown were downregulated compared to non-working time-matched controls. Both working groups lost weight during the protocol and regained weight during recovery, but animals that worked in the rest phase did not fully recover, even after eight days of recovery. In conclusion, three to four days of work in the rest phase is sufficient to induce disruption of several metabolic parameters, which requires more than eight days for full recovery.publishedVersio

Diurnal variation of motor activity in adult ADHD patients analyzed with methods from graph theory

Attention-deficit /hyperactivity disorder (ADHD) is a common neurodevelopmental syndrome characterized by age-inappropriate levels of motor activity, impulsivity and attention. The aim of the present study was to study diurnal variation of motor activity in adult ADHD patients, compared to healthy controls and clinical controls with mood and anxiety disorders. Wrist-worn actigraphs were used to record motor activity in a sample of 81 patients and 30 healthy controls. Time series from registrations in the morning and evening were analyzed using measures of variability, complexity and a newly developed method, the similarity algorithm, based on transforming time series into graphs. In healthy controls the evening registrations showed higher variability and lower complexity compared to morning registrations, however this was evident only in the female controls. In the two patient groups the same measures were not significantly different, with one exception, the graph measure bridges. This was the measure that most clearly separated morning and evening registrations and was significantly different both in healthy controls and in patients with a diagnosis of ADHD. These findings suggest that actigraph registrations, combined with mathematical methods based on graph theory, may be used to elucidate the mechanisms responsible for the diurnal regulation of motor activity.publishedVersio

Blue-blocking glasses as adjunctive treatment for bipolar mania - and exploration of motor activity patterns in serious mental disorders

Background: There is a need for more effective treatments of bipolar mania. Promising reports of the effects of dark therapy on bipolar disorder symptoms and the discovery of a mainly blue-light sensitive daylight-signaling retinal ganglion cells has resulted in the utility of BB glasses to create a virtual darkness condition for the brain. Changes in activation or aberrant motor activity is present in all serious mental disorders. Actigraphy is a non-invasive and simple means of assessing motor activity, but is still mostly used to assess sleep outcomes. Before the utility of actigraphy can be broadened, there is need for further exploration of daily activity pattern characteristics for the diagnostic entities. Aims: By means of the Virtual Darkness as Additive Treatment in Mania (VATMAN) trial, we aimed to test the effectiveness and feasibility of BB glasses as an adjunctive treatment for mania compared to placebo glasses. As part of the Agitation at Admittance to a Psychiatric Acute Department Study, we aimed to characterize the motor activity patterns among a new sample of patients with psychotic disorders, and compare these characteristics to the motor activity patterns of patients with affective disorders and with healthy controls. Methods: Eligible patients for the VATMAN trial (hospitalized with bipolar disorder mania and otherwise fulfilling inclusion criteria) were randomized to receive either BB-glasses or clear-lensed placebo glasses. The glasses were worn as an adjunctive treatment from 6:00 p.m. to 8:00 a.m. for seven consecutive days. Manic symptoms were rated daily using the Young Mania Rating Scale. Motor activity was measured using wrist-worn actigraphs. Feasibility was assessed using a self-report patient experience questionnaire together with the clinical observation of side-effects. Sleep was assessed using actigraphy-derived sleep parameters. In the Agitation at Admittance to a Psychiatric Acute Department study, all hospitalized patients in the acute psychiatric ward in Østmarka Hospital, Trondheim were asked to wear an actigraph for 24 h. The motor activity patterns of patients diagnosed with schizophrenia and other psychotic disorders were compared to those of patients with mania, motor-retarded unipolar depression, and healthy controls. Linear and non-linear analytical methods were used to describe and compare motor activity variability and complexity (irregularity) for a 24 h period as well as in morning and evening sequences. Results: Out of 32 randomized patients in the VATMAN trial, 12 patients in the BB-group and 11 patients in the placebo-group were included in the analyses. After seven days, the Cohen’s d effect size was 1.86. There was a significant group difference in YMRS scores after three days (p = 0.042) and the group difference increased steadily throughout the intervention. Observed side effects included headache in one patient and rapidly reversible depressive symptoms in two patients. Actigraphy-derived sleep outcomes at night five showed significantly higher sleep efficiency, lower motor activity and less minutes of wake after sleep onset in the BB group as compared to the placebo group. Several patients in both groups displayed a 48 h-like rhythm of shorter or disrupted sleep. The schizophrenia spectrum group shared the characteristic of high motor activity variability with the unipolar depressed group, but differed with respect to more irregular (complex) activity pattern in the morning sequence. The schizophrenia spectrum and the mania groups could not be separated using formal statistical analyses, being most similar with regards to high morning activity irregularity. The mania group was the only one to show a blunted morning-to-evening activity fluctuation, while the normal morning-to-evening decline was more preserved in the schizophrenia spectrum group. Conclusions: BB-glasses were found to be both effective and feasible as an adjunctive treatment for mania. The BB-group showed actigraphy-derived sleep parameters reflecting less activated sleep compared with the placebo-group. The use of actigraphy data to characterize diurnal motor activity patterns, by use of the combination of linear and non-linear analytical approaches, seems to have potential for assessment of symptoms and for diagnostic support

A randomized controlled trial on the effect of blue-blocking glasses compared to partial blue-blockers on melatonin profile among nulliparous women in third trimester of the pregnancy

Objective In pregnancy melatonin regulates circadian rhythms, induce sleep, and has a neuroprotective positive effect on fetal development. Artificial blue light in the evening delays and suppresses melatonin production. Thus, we investigated the effect of blocking blue light on the melatonin profile. Methods A randomized controlled trial (n=30 blue-blocking glasses vs. n=30 control glasses with partial blue-blocking effect) including healthy nulliparous pregnant women in the beginning of the third trimester. Salivary melatonin and subjective sleep were measured before and after two weeks of intervention/control condition. Saliva was sampled at 30-min intervals from 3 h before normal bedtime. Melatonin onset was set at 4.0 pg/ml. Results Due to missing data melatonin onset was estimated for 47 participants. At posttreatment, melatonin onset advanced by 28 min in the blue-blocking group compared with the control condition (p=.019). Melatonin levels were significantly higher, favoring the blue-blocking glass condition, at clock time 20:00, 21:00 and 22:00 h, and for sample number 3 and 4. The phase angle (time interval) between melatonin onset and sleep bedtime and sleep onset time increased within the blue blocking group (+45 min and +41 min, respectively), but did not reach statistical significance compared to control condition (+13 min and +26 min, respectively). Conclusion Blocking blue light in the evening had a positive effect on the circadian system with an earlier onset and rise of melatonin levels in healthy nulliparous pregnant women. This demonstrated the effectiveness and feasibility of a simple non-pharmacological chronobiological intervention during pregnancy

A randomized controlled trial on the effects of blue-blocking glasses compared to partial blue-blockers on sleep outcomes in the third trimester of pregnancy

Objective Sleep disturbances are common in pregnancy. Blocking blue light has been shown to improve sleep and may be a suitable intervention for sleep problems during pregnancy. The present study investigated the effects of blue light blocking in the evening and during nocturnal awakenings among pregnant women on primary sleep outcomes in terms of total sleep time, sleep efficiency and mid-point of sleep. Methods In a double-blind randomized controlled trial, 60 healthy nulliparous pregnant women in the beginning of the third trimester were included. They were randomized, using a random number generator, either to a blue-blocking glass intervention (n = 30) or to a control glass condition constituting partial blue-blocking effect (n = 30). Baseline data were recorded for one week and outcomes were recorded in the last of two intervention/control weeks. Sleep was measured by actigraphy, sleep diaries, the Bergen Insomnia Scale, the Karolinska Sleepiness Scale and the Pre-Sleep Arousal Scale. Results The results on the primary outcomes showed no significant mean difference between the groups at posttreatment, neither when assessed with sleep diary; total sleep time (difference = .78[min], 95%CI = -19.7, 21.3), midpoint of sleep (difference = -8.9[min], 95%CI = -23.7, 5.9), sleep efficiency (difference = -.06[%], 95%CI = -1.9, 1.8) and daytime functioning (difference = -.05[score points], 95%CI = -.33, .22), nor by actigraphy; total sleep time (difference = 13.0[min], 95%CI = -9.5, 35.5), midpoint of sleep (difference = 2.1[min], 95%CI = -11.6, 15.8) and sleep efficiency (difference = 1.7[%], 95%CI = -.4, 3.7). On the secondary outcomes, the Bergen Insomnia Scale, the Karolinska Sleepiness Scale and the Pre-Sleep Arousal Scale the blue-blocking glasses no statistically significant difference between the groups were found. Transient side-effects were reported in both groups (n = 3). Conclusions The use of blue-blocking glasses compared to partially blue-blocking glasses in a group of healthy pregnant participants did not show statistically significant effects on sleep outcomes. Research on the effects of blue-blocking glasses for pregnant women with sleep-problems or circadian disturbances is warranted. Trial registration The trial is registered at ClinicalTrials.gov (NCT03114072)