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.

Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses.

BACKGROUND: IgE is the least abundant immunoglobulin and tightly regulated, and IgE-producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood. OBJECTIVE: The cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT) were investigated. METHODS: In a randomized double-blind, placebo-controlled, time course SLIT study, PBMCs and nasal biopsy samples were collected from 40 adults with seasonal allergic rhinitis at baseline and at 4, 8, 16, 28, and 52 weeks. RNA was extracted from PBMCs, sorted B cells, and nasal biopsy samples for heavy chain variable gene repertoire sequencing. Moreover, mAbs were derived from single B-cell transcriptomes. RESULTS: Combining heavy chain variable gene repertoire sequencing and single-cell transcriptomics yielded direct evidence of a parallel boost of 2 clonally and functionally related B-cell subsets of short-lived IgE+ plasmablasts and IgG+ memory B cells. Mucosal grass pollen allergen exposure by SLIT resulted in highly diverse IgE and IgGE repertoires. These were extensively mutated and appeared relatively stable as per heavy chain isotype, somatic hypermutations, and clonal composition. Single IgGE+ memory B-cell and IgE+ preplasmablast transcriptomes encoded antibodies that were specific for major grass pollen allergens and able to elicit basophil activation at very low allergen concentrations. CONCLUSION: For the first time, we have shown that on mucosal allergen exposure, human IgE memory resides in allergen-specific IgG+ memory B cells. These cells rapidly switch isotype, expand into short-lived IgE+ plasmablasts, and serve as a potential target for therapeutic intervention.

Blue-blocking glasses as additive treatment for mania: a randomized placebo-controlled trial.

OBJECTIVES: The discovery of the blue lightsensitive retinal photoreceptor responsible for signaling daytime to the brain suggested that light to the circadian system could be inhibited by using blue-blocking orange tinted glasses. Blue-blocking (BB) glasses are a potential treatment option for bipolar mania. We examined the effectiveness of BB glasses in hospitalized patients with bipolar disorder in a manic state. METHODS: In a single-blinded, randomized, placebo-controlled trial (RCT), eligible patients (with bipolar mania; age 18-70 years) were recruited from five clinics in Norway. Patients were assigned to BB glasses or placebo (clear glasses) from 6 p.m. to 8 a.m. for 7 days, in addition to treatment as usual. Symptoms were assessed daily by use of the Young Mania Rating Scale (YMRS). Motor activity was assessed by actigraphy, and compared to data from a healthy control group. Wearing glasses for one evening/night qualified for inclusion in the intention-to-treat analysis. RESULTS: From February 2012 to February 2015, 32 patients were enrolled. Eight patients dropped out and one was excluded, resulting in 12 patients in the BB group and 11 patients in the placebo group. The mean decline in YMRS score was 14.1 [95% confidence interval (CI): 9.7-18.5] in the BB group, and 1.7 (95% CI: -4.0 to 7.4) in the placebo group, yielding an effect size of 1.86 (Cohen's d). In the BB group, one patient reported headache and two patients experienced easily reversible depressive symptoms. CONCLUSIONS: This RCT shows that BB glasses are effective and feasible as add-on treatment for bipolar mania.

Blocking blue light during mania - markedly increased regularity of sleep and rapid improvement of symptoms: a case report.

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.