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.

The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023.

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder.

BACKGROUND: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. METHODS: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. RESULTS: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. CONCLUSION: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

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.

Biological rhythms and chronotherapeutics in depression.

Depressive syndromes are frequent and heterogeneous brain conditions with more than 90% of patients suffering from sleep complaints. Better characterizing this "sleep" domain may allow to both better treat acute episodes with existing chronotherapeutics, but also to prevent the manifestation or recurrences of mood disorders. This work aims to i) review theoretical and fundamental data of chronotherapeutics, and ii) provide practical recommendations. Light therapy (LT) can be used as a first-line monotherapy of moderate to severe depression of all subtypes. LT can be also used as a combination with antidepressant to maximize patients' response rates, which has a clear superiority to antidepressant alone. Sleep deprivation (SD) is a rapid and powerful chronotherapeutic with antidepressant responses within hours in 45-60% of patients with unipolar or bipolar depression. Different strategies should be combined to stabilize the SD antidepressant effect, including concomitant medications, repeated SD, combination with sleep phase advance and/or LT (triple chronotherapy). Melatonin treatment is of interest in remitted patients with mood disorder to prevent relapses or recurrences, if a complaint of insomnia, poor sleep quality or phase delay syndrome is associated. During the acute phase, melatonin could be used as an adjuvant treatment for symptoms of insomnia associated with depression. The cognitive behavioral therapy for insomnia (CBT-I) can be recommend to treat insomnia during euthymic phases. The Interpersonal and social rhythm therapy (IPSRT) is indicated for the acute treatment of bipolar depression and for the prevention of mood episodes. Chronotherapeutics should always be associated with behavioral measures for healthy sleep.

Light therapy with boxes or glasses to counteract effects of acute sleep deprivation.

Sleep deprivation, in the context of shift work, is an increasing major public health issue. We aimed to determine whether early light administration can counteract sleep deprivation effects, and to compare LED-glasses with a traditional light therapy box. This cross-over design study included 18 individuals exposed to light therapy for 30 minutes at 5 am after one night of complete sleep deprivation, to mimic the night shift condition. Individuals were randomly exposed to 10,000 Lux light box, 2,000 Lux LED blue-enriched glasses, and control (ambient dim-light at 8 lux). Alertness, cognition and mood were assessed throughout the night and following morning. Five women and 13 men (mean 24.78 year old) presented with a progressive and increasing alteration of alertness, cognition, and mood during each sleep deprivation. A rebound was observed at 8 am resulting from the circadian drive overriding cumulative sleep homeostatic effects. Morning light significantly improved sleepiness and sustained attention from 5 to 7 am. These effects were comparable between devices and significantly different from control. Both devices were overall well and similarly tolerated. Early morning light therapy in the condition of sleep loss may have broad practical applications to improve sleepiness, sustained attention and subsequent risk of accidents.

The chronotherapeutic treatment of bipolar disorders: A systematic review and practice recommendations from the ISBD task force on chronotherapy and chronobiology.

AIMS: To systematically review the literature on the efficacy and tolerability of the major chronotherapeutic treatments of bipolar disorders (BD)-bright light therapy (LT), dark therapy (DT), treatments utilizing sleep deprivation (SD), melatonergic agonists (MA), interpersonal social rhythm therapy (IPSRT), and cognitive behavioral therapy adapted for BD (CBTI-BP)-and propose treatment recommendations based on a synthesis of the evidence. METHODS: PRISMA-based systematic review of the literature. RESULTS: The acute antidepressant (AD) efficacy of LT was supported by several open-label studies, three randomized controlled trials (RCTs), and one pseudorandomized controlled trial. SD showed rapid, acute AD response rates of 43.9%, 59.3%, and 59.4% in eight case series, 11 uncontrolled, studies, and one RCT, respectively. Adjunctive DT obtained significant, rapid anti-manic results in one RCT and one controlled study. The seven studies on MA yielded very limited data on acute antidepressant activity, conflicting evidence of both antimanic and maintenance efficacy, and support from two case series of improved sleep in both acute and euthymic states. IPSRT monotherapy for bipolar II depression had acute response rates of 41%, 67%, and 67.4% in two open studies and one RCT, respectively; as adjunctive therapy for bipolar depression in one RCT, and efficacy in reducing relapse in two RCTs. Among euthymic BD subjects with insomnia, a single RCT found CBTI-BP effective in delaying manic relapse and improving sleep. Chronotherapies were generally safe and well-tolerated. CONCLUSIONS: The outcome literature on the adjunctive use of chronotherapeutic treatments for BP is variable, with evidence bases that differ in size, study quality, level of evidence, and non-standardized treatment protocols. Evidence-informed practice recommendations are offered.

Efficacy of light therapy versus antidepressant drugs, and of the combination versus monotherapy, in major depressive episodes: A systematic review and meta-analysis.

Although light therapy (LT) has been shown to be efficient in the treatment of seasonal and non-seasonal depression, it is underused in clinical settings and antidepressant drugs (AD) remain so far the usual first line treatment. The aim of this systematic review and weighted random effect meta-analysis is to examine the randomized controlled trials that compared directly light therapy and antidepressant drugs, as well as their combination (LT + AD). A total of 397 participants were included, with a moderate to severe major depressive episode, from seven independent populations. The median duration of intervention was 5 wks (range 2-8 wks). The superiority (lower depression score) of LT + Placebo compared to AD + Placebo was non-significant (SMD = 0.19 [-0.08-0.45]; p = 0.17). The combination LT + AD was superior to AD + Placebo (SMD = 0.56 [0.24-0.88]; p < 0.001). This superiority was confirmed in the subgroup of patients with non-seasonal depression (SMD = 0.55 [0.16-0.93]; p = 0.005). Meta-analyses showed no or small heterogeneity between studies (I2 = 0%, 18.41%, and 39.23% respectively). No potential publication biases were observed by statistical tests and visual inspection of the funnel plots. No differences were observed between LT and AD, with a clear superiority of the combination, thus both LT monotherapy and combination may be proposed as a first line treatment in seasonal and non-seasonal depression.