Images: "Too much heat for my non-24-hour sleep-wake disorder!" A case report.

The non-24-hour sleep-wake disorder (N24SWD) is a rare condition, sometimes associated with blindness or with suprachiasmatic nuclei lesions, resulting in a free-running rhythm or hypernycthemeral syndrome. Synchronizers, such as light, when light perception remains, melatonin, food intakes, physical activity, social interactions, and temperature, play a key role in the treatment of N24SWD. In this report, we describe a case illustrating the impact of outdoor temperature in a 34-year-old man with N24SWD effectively treated through a combination of chronotherapy interventions. During 3 consecutive heat waves, he experienced a recurrence of his natural 25.5-hour free-running rhythm, with a consistent bedtime phase delay caused by temperature, resulting in the discontinuation of chronotherapy. After these heat waves, he was able again to resynchronize his rhythms with the combination of chronotherapeutics. This case report highlights that patients with N24SWD may be particularly at risk of relapse during heat waves, with direct implications for monitoring and reinforcing chronotherapies. CITATION: Garrivet J, d'Ortho M-P, Frija-Masson J, et al. "Too much heat for my non-24-hour sleep-wake disorder!" A case report. J Clin Sleep Med. 2024;20(2):329-333.

Light therapy in insomnia disorder: A systematic review and meta-analysis.

In the management of insomnia, physicians and patients are seeking alternative therapeutics to sleeping pills, in addition to sleep hygiene and cognitive behavioural therapy. Bright light therapy (LT) has proven its efficacy in circadian and mood disorders. We conducted a systematic literature review and meta-analysis according to Cochrane and PRISMA guidelines and using the databases Medline, Cochrane, and Web of Science, with a special focus on light therapy and insomnia. Twenty-two studies with a total of 685 participants were included, five of which with a high level of proof. Meta-analysis was performed with 13 of them: light therapy for insomnia compared with control conditions significantly improved wake after sleep onset (WASO: SMD = -0.61 [-1.11, -0.11]; p = 0.017; weighted difference of 11.2 min ±11.5 based on actigraphy, and SMD = -1.09 [-1.43, -0.74] (p < 0.001) weighted difference of -36.4 min ±15.05) based on sleep diary, but no other sleep measures such as sleep latency, total sleep time (TST), or sleep efficiency. Qualitative analysis of the review showed some improvement mainly in subjective measures. Morning light exposure advanced sleep-wake rhythms and evening exposure led to a delay. No worsening was observed in objective nor subjective measures, except for TST in one study with evening exposure. A light dose-response may exist but the studies' heterogeneity and publication bias limit the interpretation. To conclude, light therapy shows some effectiveness for sleep maintenance in insomnia disorders, but further research is needed to refine the light parameters to be chosen according to the type of insomnia, in the hope of developing personalised therapeutics.

Continuous positive airway pressure as an accurate marker for non-24-hour sleep-wake rhythm disorder.

Non-24-h sleep-wake rhythm disorder is quite rare in sighted patients and frequently associated with psychiatric disorders. We report the case of a 46-year-old man with autism spectrum disorder (ASD) and agoraphobia who had been referred for a suspicion of obstructive sleep apnea syndrome (OSAS). Polysomnography and arterial blood gas confirmed moderate OSAS associated with hypoventilation. Continuous positive airway pressure (CPAP) was started on fixed mode with excellent results. At follow-up, his CPAP report data revealed an irregular sleep-wake rhythm with a progressive offset of sleep schedule and wake time delayed from 1 h from day to day. Melatonin (or agonist) is efficacious and safe for long-term treatment in ASD and circadian rhythm sleep-wake disorder (CRSWD) with light therapy and wakefulness promoting medication. This case underlines the importance to sensitise psychiatrists to sleep and CRSWD, and also that CPAP data offer a possible objective alternative to sleep diary.

Multi-Level Processes and Retina-Brain Pathways of Photic Regulation of Mood.

Light exerts powerful biological effects on mood regulation. Whereas the source of photic information affecting mood is well established at least via intrinsically photosensitive retinal ganglion cells (ipRGCs) secreting the melanopsin photopigment, the precise circuits that mediate the impact of light on depressive behaviors are not well understood. This review proposes two distinct retina-brain pathways of light effects on mood: (i) a suprachiasmatic nucleus (SCN)-dependent pathway with light effect on mood via the synchronization of biological rhythms, and (ii) a SCN-independent pathway with light effects on mood through modulation of the homeostatic process of sleep, alertness and emotion regulation: (1) light directly inhibits brain areas promoting sleep such as the ventrolateral preoptic nucleus (VLPO), and activates numerous brain areas involved in alertness such as, monoaminergic areas, thalamic regions and hypothalamic regions including orexin areas; (2) moreover, light seems to modulate mood through orexin-, serotonin- and dopamine-dependent pathways; (3) in addition, light activates brain emotional processing areas including the amygdala, the nucleus accumbens, the perihabenular nucleus, the left hippocampus and pathways such as the retina-ventral lateral geniculate nucleus and intergeniculate leaflet-lateral habenula pathway. This work synthetizes new insights into the neural basis required for light influence mood.

Validity and Usage of the Seasonal Pattern Assessment Questionnaire (SPAQ) in a French Population of Patients with Depression, Bipolar Disorders and Controls.

The Seasonal Pattern Assessment Questionnaire (SPAQ), by Rosenthal et al. (1984), is by far the most used questionnaire to evaluate seasonal effects on mood and behavior. It includes a general seasonality score (GSS), composed of 6 items, from which cutoffs have been established to screen for seasonal affective disorder (SAD). However, it has never been validated in French and associations with circadian rhythm and symptoms of depression and bipolarity remain unclear. In this study, including 165 subjects (95 controls and 70 patients with depression or bipolar disorder), we confirmed the validity of the French version of the SPAQ, with a two-factor structure (a psychological factor: energy, mood, social activity and sleep length; and a food factor: weight and appetite) and a good fit was observed by all indicators. Mood and social activity dimensions were significantly affected by seasons in the depressed/bipolar group and a stronger global seasonality score (GSS) was associated with more severe phenotypes of depression and mania. Subjects meeting SAD and subsyndromal-SAD criteria also showed a delayed circadian rhythm compared to controls. Simple tools, such as the SPAQ, can aid the identification of significant seasonal changes and have direct implications on therapeutics including the use of bright light therapy in order to enhance personalized treatments, but also to prevent adverse seasonal effects.

Association between coffee, tobacco, and alcohol daily consumption and sleep/wake cycle: an actigraphy study in euthymic patients with bipolar disorders.

Individuals with bipolar disorder (BD) have higher than average rates of coffee, tobacco and alcohol use. These substances may have deleterious effects on sleep quality and quantity, which may destabilize sleep/wake cycles and negatively impact the clinical course and prognosis of BD. The use of these substances may also be perceived as a self-medication attempt, for example, to induce sleep or to increase vigilance during the day. The objective of the current study was to investigate associations between the self-reported daily use of coffee, tobacco, and alcohol, and objective measures of sleep and activity patterns in adult individuals with BD. A sample of 147 euthymic individuals with BD were assessed for daily coffee, tobacco and alcohol consumption and 21 days of actigraphy monitoring. Actigraphic measures of sleep quantity and daytime activity were compared between groups classified as coffee+/coffee-, tobacco+/tobacco- and alcohol+/alcohol-, defined according to their current daily use. Then, we examined potential correlations between sleep/wake cycle parameters and the amount of daily consumption of each substance. Multivariable analyses identified associations between the use of coffee, tobacco, and alcohol and several sleep and activity parameters, such as between coffee, alcohol, and the relative amplitude of activity (respectively, p = .003 and p = .005), between alcohol and M10 onset (onset time of the 10 most active hours during the 24-h cycle) (p = .003), and between coffee and sleep duration (p = .047). This study supports the hypothesis that there is a relationship, whose direction would be bidirectional, between the daily use of these substances and the sleep/wake cycle in euthymic individuals with BD. These preliminary results require replications in other retrospective and prospective samples. They may have a clinical impact on psycho-education strategies to be proposed to individuals with BD.

Bright Light as a Personalized Precision Treatment of Mood Disorders.

Background: The use of light for its antidepressant action dates back to the beginnings of civilization. Three decades ago, the use of bright-light therapy (BLT) for treating Seasonal Affective Disorder (SAD) was officially proposed. Since then, a growing scientific literature reports its antidepressant efficacy in both unipolar and bipolar disorders (BD), with or without seasonal patterns. This review aims to examine the management of BLT as a personalized and precision treatment in SAD, unipolar, and BD. Methods: We conducted a narrative review using Medline and Google Scholar databases up to June 2018. Results: BLT has physiological effects by resynchronizing the biological clock (circadian system), enhancing alertness, increasing sleep pressure (homeostatic system), and acting on serotonin, and other monoaminergic pathways. Effects of BLT on mood depend on several factors such as light intensity, wavelength spectrum, illumination duration, time of the day, and individual circadian rhythms. A growing body of evidence has been generated over the last decade about BLT evolving as an effective depression treatment not only to be used in SAD, but also in non-seasonal depression, with efficiency comparable to fluoxetine, and possibly more robust in patients with BD. The antidepressant action of BLT is fast (within 1-week) and safe, with the need in BD to protect against manic switch with mood stabilizers. Side effects might be nausea, diarrhea, headache, and eye irritation, and are generally mild and rare. This good safety profile may be of particular interest, especially in women during the perinatal period or for the elderly. The management of BLT needs to be clarified across mood disorders and future studies are expected to compare different dose-titration protocols, to validate its use as a maintenance treatment, and also to identify predictive biomarkers of response and tolerability. We propose clinical guidelines for BLT use in SAD, non-seasonal depression, and BD. Conclusions : BLT is an efficient antidepressant strategy in mono- or adjunct-therapy, that should be personalized according the unipolar or bipolar subtype, the presence or absence of seasonal patterns, and also regarding its efficacy and tolerability.

Bright Light Therapy in the Morning or at Mid-Day in the Treatment of Non-Seasonal Bipolar Depressive Episodes (LuBi): Study Protocol for a Dose Research Phase I / II Trial.

Objective This study protocol aims to determine, using a rigorous approach in patients with bipolar disorder (BD) and non-seasonal major depressive episode (MDE), the characteristics of bright light therapy (BLT) administration (duration, escalation, morning and mid-day exposures) depending on the tolerance (hypomanic symptoms). Methods Patients with BD I or II and treated by a mood stabilizer are eligible. After 1 week of placebo, patients are randomized between either morning or mid-day exposure for 10 weeks of active BLT with glasses using a dose escalation at 7.5, 10, 15, 30 and 45 minutes/day. A further follow-up visit is planned 6 months after inclusion. Patients will be included by cohorts of 3, with at least 3 days of delay between them, and 1 week between cohorts. If none meet a dose limiting toxicity (DLT; i.e hypomanic symptoms), the initiation dose of the next cohort will be increased. If one patient meet a DLT, an additionnal cohort will start at the same dose. If 2 or 3 patients meet a DLT, from the same cohort or from two cohorts at the same dose initiation, the maximum tolerated dose is defined. This dose escalation will also take into account DLTs observed during the intra-subject escalation on previous cohorts, with a "Target Ceiling Dose" defined if 2 DLTs occured at a dose. Discussion Using an innovative and more ergonomic device in the form of glasses, this study aims to better codify the use of BLT in BD to ensure a good initiation and tolerance. Trial registrationaaClinicalTrials.gov Identifier: NCT03396744.

A double-blind, randomized controlled trial of the use of a 50:50 mixture of nitrous oxide/oxygen in legal abortions.

BACKGROUND: The study was conducted to evaluate the effectiveness of oxygen/nitrous oxide (O(2)/N(2)O) in elective abortions by vacuum aspiration with paracervical block and intravenous paracetamol. DESIGN: This single-center double-blinded randomized study tested O(2)/N(2)O (n=36) and placebo (air, n=36) for additional analgesia in elective abortions with paracervical block and intravenous paracetamol. We assessed intra- and postoperative pain according to both a visual analogic scale rated from 0 to 10 and postoperative analgesic requirements. RESULTS: Mean (±SD) intraoperative, immediate postoperative and late postoperative pain did not differ significantly for patients with O(2)/N(2)O and with air [3.4±2.6 vs. 3.7±3.05 (p=.75), 1.89±2.4 vs. 1.56±2.03 (p=.78), 0.5±0.8 vs. 0.75±1.2 (p=.45)]. The number of patients with scores for low (0-4), moderate (4-7) and severe (7-10) intraoperative, immediate postoperative and late postoperative pain did not differ significantly between the groups. Total adverse effects were significantly higher in the O(2)/N(2)O group [35/180 (19.4%) vs. 18/180 (10%), p=.01]. CONCLUSION: O(2)/N(2)O did not reduce intraoperative or postoperative pain in elective abortions by vacuum aspiration with paracervical analgesia and intravenous paracetamol, and its adverse effect rate was substantial.