Sleep disturbance in bipolar disorder: therapeutic implications

In this review, the authors detail our current understanding of the crucial role that sleep and its disturbances play in bipolar disorder. Multiple lines of evidence suggest that impaired sleep can induce and predict manic episodes. Similarly, treatment of sleep disturbance may serve as both a target of treatment and a measure of response in mania. The depressive phase of bipolar illness is marked by sleep disturbance that may be amenable to somatic therapies that target sleep and circadian rhythms. Residual insomnia in the euthymic period may represent a vulnerability to affective relapse in susceptible patients. Given the importance of sleep in all phases of bipolar disorder, appropriate evaluation and management of sleep disturbance in patients with bipolar illness is further detailed.     

Daytime sleeping, sleep disturbance, and circadian rhythms in the nursing home.

OBJECTIVE: This study reports the frequency of abnormal daytime sleeping and identifies factors related to daytime sleeping, nighttime sleep disturbance, and circadian rhythm abnormalities among nursing home residents. METHODS: The authors conducted secondary analysis of data collected under usual care conditions within a nonpharmacologic sleep intervention trial. All residents from four Los Angeles nursing homes were screened for daytime sleeping (asleep>or=15% of observations, 9:00 am-5:00 pm). Consenting residents with daytime sleeping had two nights of wrist actigraphy to assess nighttime sleep disturbance (asleep<80%, 10:00 pm-6:00 am). Residents with nighttime sleep disturbance completed an additional 72-hour wrist actigraphy recording to assess circadian activity rhythms and light exposure. RESULTS: Sixty-nine percent of 492 observed residents had daytime sleeping, of whom 60% also had disturbed nighttime sleep. Sleep disturbance and daytime sleeping were rarely documented in medical records. Residents spent one-third of the day in their rooms, typically in bed, and were seldom outdoors or exposed to bright light. More time in bed and less social activity were significant predictors of daytime sleepiness. Ninety-seven percent of residents assessed had abnormal circadian rhythms. More daytime sleeping and less nighttime sleep were associated with weaker circadian activity rhythms. Later circadian rhythm acrophase (peak) was associated with more bright light exposure. CONCLUSION: Daytime sleepiness, nighttime sleep disturbance, and abnormal circadian rhythms were common in nursing home residents. Modifiable factors (e.g., time in bed) are associated with sleep/wake abnormalities. Mental health specialists should consider the complexity of factors causing sleep problems in nursing home residents.     

Melatonin, circadian rhythms, and the clock genes in bipolar disorder

Sleep disturbances and dysregulation of circadian rhythms are core elements of bipolar disorder that might be involved in its pathogenesis. It has been proposed that patients with bipolar disorder have an abnormally shifted or arrhythmic circadian system and that the disturbance of circadian rhythms may be caused by an alteration in the circadian clock machinery. Chronotherapeutic strategies based on controlled exposures to environmental stimuli that act on biological rhythms have shown good efficacy in the treatment of illness episodes, thus confirming ex juvantibus the clinical relevance of internal timing in this illness.     

The characteristics of sleep in patients with manifest bipolar disorder, subjects at high risk of developing the disease and healthy controls

Sleep is highly altered during affective episodes in patients with bipolar disorder. There is accumulating evidence that sleep is also altered in euthymic states. A deficit in sleep regulation may be a vulnerability factor with aetiological relevance in the development of the disease. This study aims to explore the objective, subjective and lifetime sleep characteristics of patients with manifest bipolar disorder and persons with an elevated risk of developing the disease. Twenty-two patients with bipolar I and II disorder, nine persons with an elevated risk of developing the disorder and 28 healthy controls were evaluated with a structured interview to characterize subjective and lifetime sleeping habits. In addition, participants wore an actimeter for six nights. Patients with bipolar disorder had longer sleep latency and duration compared with healthy controls as determined by actigraphy. The subjective and lifetime sleep characteristics of bipolar patients differed significantly from healthy controls. The results of participants with an elevated risk of developing the disorder had subjective and lifetime characteristics that were largely analogous to those of patients with manifest bipolar disorder. In particular, both groups described recurring insomnia and hypersomnia, sensitivity to shifts in circadian rhythm, difficulties awakening and prolonged sleep latency. This study provides further evidence that sleep and circadian timing are profoundly altered in patients with bipolar disorder. It may also tentatively suggest that sleep may be altered prior to the first manic episode in subjects at high risk.     

Sleep, illness course, and concurrent symptoms in inter-episode bipolar disorder

We investigated associations between sleep, illness course, and concurrent symptoms in 21 participants with bipolar disorder who were inter-episode. Sleep was assessed using a week-long diary. Illness course and symptoms were assessed via validated semi-structured interviews. Lower and more variable sleep efficiency and more variable total wake time were associated with more lifetime depressive episodes. Variability in falling asleep time was positively correlated with concurrent depressive symptoms. Sleep efficiency was positively correlated with concurrent manic symptoms. These findings suggest that inter-episode sleep disturbance is associated with illness course and that sleep may be an important intervention target in bipolar disorder.     

Sleep and circadian alterations in people at risk for bipolar disorder: A systematic review

BackgroundSleep and circadian abnormalities have been mostly demonstrated in bipolar patients. However, it is not clear whether these alterations are present in population at high risk for bipolar disorder (BD), indicating a possible risk factor for this condition.ObjectiveThis systematic review aims to define current evidence about sleep and rhythm alterations in people at risk for BD and to evaluate sleep and circadian disorders as risk factor for BD.MethodsThe systematic review included all articles about the topic until February 2016. Two researchers performed an electronic search of PubMed and Cochrane Library. Keywords used were ‘sleep’ or ‘rhythm’ or ‘circadian’ AND ‘bipolar disorder’ or ‘mania’ or ‘bipolar depression’ AND ‘high-risk’ or ‘risk’.ResultsThirty articles were analyzed (7451 participants at risk for BD). Sleep disturbances are frequent in studies using both subjective measures and actigraphy. High-risk individuals reported irregularity of sleep/wake times, poor sleep and circadian rhythm disruption. Poor sleep quality, nighttime awakenings, and inadequate sleep are possible predictive factors for BD. A unique study suggested that irregular rhythms increase risk of conversion. People at risk for BD showed high cortisol levels in different times of day. Studies about anatomopathology, melatonin levels, inflammatory cytokines and oxidative stress were not identified. The most important limitations were differences in sleep and rhythm measures, heterogeneity of study designs, and lack of consistency in the definition of population at risk.ConclusionSleep and circadian disturbances are common in people at risk for BD. However, the pathophysiology of these alterations and the impact on BD onset are still unclear.     

Circadian rhythms, sleep, and substance abuse

Substance abuse is linked to numerous mental and physical health problems, including disturbed sleep. The association between substance use and sleep appears to be bidirectional, in that substance use may directly cause sleep disturbances, and difficulty sleeping may be a risk factor for relapse to substance use. Growing evidence similarly links substance use to disturbances in circadian rhythms, although many gaps in knowledge persist, particularly regarding whether circadian disturbance leads to substance abuse or dependence. Given the integral role circadian rhythms play in regulating sleep, circadian mechanisms may account in part for sleep-substance abuse interactions. Furthermore, a burgeoning research base supports a role for the circadian system in regulating reward processing, indicating that circadian mechanisms may be directly linked to substance abuse independently of sleep pathways. More work in this area is needed, particularly in elucidating how sleep and circadian disturbance may contribute to initiation of, and/or relapse to, substance use. Sleep and circadian-based interventions could play a critical role in the prevention and treatment of substance use disorders.     

Evaluating sleep in bipolar disorder: comparison between actigraphy,polysomnography, and sleep diary

Kaplan KA, Talbot LS, Gruber J, Harvey AG. Evaluating sleep in bipolar disorder: comparison between actigraphy, polysomnography, and sleep diary.
Bipolar Disord 2012: 14: 870–879. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Bipolar disorder is an illness characterized by sleep and circadian disturbance, and monitoring sleep in this population may signal an impending mood change. Actigraphy is an important clinical and research tool for examining sleep, but has not yet been systematically compared to polysomnography or sleep diary in bipolar disorder. The present study compares actigraphy, polysomnography, and sleep diary estimates of five standard sleep parameters in individuals with bipolar disorder and matched controls across two nights of assessment. Methods: Twenty‐seven individuals who met diagnostic criteria for bipolar disorder type I or II and were currently between mood episodes, along with 27 matched controls with no history of psychopathology or sleep disturbance, underwent two nights of research laboratory monitoring. Sleep was estimated via polysomnography, actigraphy, and sleep diary. Results: Over the 108 nights available for comparison, sleep parameter estimates from actigraphy and polysomnography were highly correlated and did not differ between the two groups or across the two nights for sleep onset latency, wake after sleep onset, number of awakenings, total sleep time, or sleep efficiency percentage. The medium wake threshold algorithm in the actigraphy software was the most concordant with polysomnography and diaries across the five sleep parameters. Concordance between actigraphy, polysomnography, and sleep diary was largely independent of insomnia presence and medication use. Conclusions: Actigraphy is a valid tool for estimating sleep length and fragmentation in bipolar disorder.     

Circadian rhythms and sleep in bipolar disorder

Murray G, Harvey A. Circadian rhythms and sleep in bipolar disorder.
Bipolar Disord 2010: 12: 459–472. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objective: Biological rhythm pathways are highlighted in a number of etiological models of bipolar disorder, and the management of circadian instability appears in consensus treatment guidelines. There are, however, significant conceptual and empirical limitations on our understanding of a hypothesised link between circadian, sleep, and emotion regulation processes in bipolar disorder. The aim of this article is to articulate the limits of scientific knowledge in relation to this hypothesis. Methods: A critical evaluation of various literatures was undertaken. The basic science of circadian and sleep processes, their involvement in normal emotion regulation, and the types of evidence suggesting circadian/sleep involvement in bipolar disorder are reviewed. Results: Multiple lines of evidence suggest that circadian and sleep‐wake processes are causally involved in bipolar disorder. These processes demonstrably interact with other neurobiological pathways known to be important in bipolar disorder, but are unique in that they are open to behavioural manipulation. Conclusion: Further research into biological rhythm pathways to bipolar disorder is warranted. Person‐environment feedback loops are fundamental to circadian adaptation, and models of circadian pathogenesis (and treatment) should recognize this complexity.     

Circadian rhythm in bipolar disorder: A review of the literature

Sleep disturbances and circadian rhythm dysfunction have been widely demonstrated in patients with bipolar disorder (BD). Irregularity of the sleep–wake rhythm, eveningness chronotype, abnormality of melatonin secretion, vulnerability of clock genes, and the irregularity of social time cues have also been well‐documented in BD. Circadian rhythm dysfunction is prominent in BD compared with that in major depressive disorders, implying that circadian rhythm dysfunction is a trait marker of BD. In the clinical course of BD, the circadian rhythm dysfunctions may act as predictors for the first onset of BD and the relapse of mood episodes. Treatments focusing on sleep disturbances and circadian rhythm dysfunction in combination with pharmacological, psychosocial, and chronobiological treatments are believed to be useful for relapse prevention. Further studies are therefore warranted to clarify the relation between circadian rhythm dysfunction and the pathophysiology of BD to develop treatment strategies for achieving recovery in BD patients.     

Sleep, recovery, and performance: the new frontier in high-performance athletics

The relationship of sleep to post-exercise recovery (PER) and athletic performance is a topic of great interest because of the growing body of scientific evidence confirming a link between critical sleep factors, cognitive processes, and metabolic function. Sleep restriction (sleep deprivation), sleep disturbance (poor sleep quality), and circadian rhythm disturbance (jet lag) are the key sleep factors that affect the overall restorative quality of the sleep state. This article discusses these theoretic concepts, presents relevant clinical cases, and reviews pilot data exploring the prevalence of sleep disturbance in two groups of high-performance athletes.     

Assessment of sleep quality in bipolar euthymic patients

ObjectiveSleep quality is affected in bipolar disorder even in euthymic episodes. The aim of this study was to assess sleep quality in bipolar euthymic patients, determine related clinical characteristics and evaluate its effects on functionality.MethodsA total of 122 outpatients were included. Scales were used to confirm that patients were euthymic. Mini Mental Test was performed to exclude patients with a diagnosis of dementia. A data form for socio-demographic features and clinical characteristics of bipolar disorder have been completed. SCID-I and SCID II were used. The general features of sleep were investigated by General Sleep Questionnaire. All patients completed Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Bipolar Disorder Functioning Questionnaire.Results56.5% of our sample had poor sleep quality. Patients with poor sleep had a longer time to fall asleep and more frequent waking after sleep onset. Caffeine use and smoking, history of suicide attempts, seasonality, comorbidity of lifetime anxiety, somatoform and impulse control disorders, using antidepressant medication and administration of electroconvulsive therapy were significantly higher; emotional and intellectual functioning, household relations, taking initiative, self-sufficiency and total functionality were lower in bipolar patients with poor sleep quality (p < 0.05). The strongest predictor of sleep quality problem was seasonality, recording an odds ratio of 3.91.ConclusionsSleep quality is closely related with clinical features of bipolar disorder. Sleep quality is affected negatively in euthymic episodes of bipolar disorder and poor sleep quality cause loss in functionality. Assessment of sleep disturbances routinely in psychiatric interviews and dealing with sleep problems regardless mood episodes may improve sleep quality, thereby functionality and quality of life.     

Circadian Polymorphisms in Night Owls,in Bipolars,and in Non-24-Hour Sleep Cycles

People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography. In 45 participants, we resequenced portions of 15 circadian genes to identify unknown polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both larger samples, using Illumina Golden Gate assays. Associations of SNPs with the DSPS phenotype and with the morningness-eveningness parametric phenotype were computed for both samples, then combined for meta-analyses. Delayed sleep and "eveningness" were inversely associated with loci in circadian genes NFIL3 (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was associated with non-24-hour sleep-wake cycles, and less robustly, with delayed sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright light and melatonin can palliate circadian disorders, and genetics may clarify the underlying circadian photoperiodic mechanisms. After further replication and identification of the causal polymorphisms, these findings may point to future treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or depression.     

Clinical significance of mobile health assessed sleep duration and variability in bipolar disorder

ObjectiveSleep disturbances are prevalent, persistent, and impairing features of bipolar disorder. However, the near-term and cumulative impact of the severity and variability of sleep disturbances on symptoms and functioning remains unclear. We examined self-reported daily sleep duration and variability in relation to mood symptoms, medication adherence, cognitive functioning, and concurrent daily affect.MethodsForty-one outpatients diagnosed with bipolar disorder were asked to provide daily reports of sleep duration and affect collected via ecological momentary assessment with smartphones over eleven weeks. Measures of depressive and manic symptoms, medication adherence, and cognitive function were collected at baseline and concurrent assessment of affect were collected daily. Analyses examined whether sleep duration or variability were associated with baseline measures and changes in same-day or next-day affect.ResultsGreater sleep duration variability (but not average sleep duration) was associated with greater depressive and manic symptom severity, and lower medication adherence at baseline, and with lower and more variable ratings of positive affect and higher ratings of negative affect. Sleep durations shorter than 7–8 h were associated with lower same-day ratings of positive and higher same-day ratings of negative affect, however this did not extend to next-day affect.ConclusionsGreater cumulative day-to-day sleep duration variability, but not average sleep duration, was related to more severe mood symptoms, lower self-reported medication adherence and higher levels of negative affect. Bouts of short- or long-duration sleep had transient impact on affect. Day-to-day sleep variability may be important to incorporate into clinical assessment of sleep disturbances in bipolar disorder.     

Characterization and Factors Associated with Sleep Quality in Adolescents with Bipolar I Disorder

Sleep disturbance is an early marker for bipolar disorder (BD) onset in youth. We characterized sleep quality in adolescents experiencing mania within the last 6-12 months. We examined the association between mood and sleep in 27 adolescents with BD and 24 matched healthy controls (HC). Subjects were assessed by parent and teen report of sleep, a semi-structured clinical interview, the Young Mania Rating Scale (YMRS), and the Childhood Depression Rating Scale (CDRS-R). Average BD youth YMRS (mean 20.3 ± 7.3) and CDRS-R (mean 42.4 ± 14.1) scores indicated they were still ill at time of assessment. Compared to HCs, adolescents with BD have distinct patterns of prolonged sleep onset latency, frequent nighttime awakenings, and increased total time awake. Mood symptoms, specifically excessive guilt, self-injurious behavior, and worsening evening mood, interfered with sleep. Further studies are needed to determine whether early regulation of sleep would improve long-term outcome in BD youth.     

Circadian variability of objective sleep measures predicts the relapse of a mood episode in bipolar disorder: findings from the APPLE cohort

Aim

Sleep disturbance, a core feature of bipolar disorder, is closely associated with mood symptoms. We examined the association between actigraphy sleep parameters and mood episode relapses in patients with bipolar disorder.

Methods

This prospective cohort study analyzed 193 outpatients with bipolar disorder who participated in the Association between the Pathology of Bipolar Disorder and Light Exposure in Daily Life (APPLE) cohort study. The participants' sleep was objectively evaluated via actigraphy over seven consecutive days for the baseline assessment and then at the 2-year follow-up appointment for mood episode relapses. The actigraphy sleep parameters were presented using the mean and variability (standard deviation) of each sleep parameter for 7 days.

Results

Of the 193 participants, 110 (57%) experienced mood episodes during follow-up. The participants with higher variability in total sleep time had a significantly shorter mean estimated time to mood episode relapses than those with lower variability (12.5 vs. 16.8 months; P < 0.001). The Cox proportional hazards model, when adjusted for potential confounders, demonstrated that variability in total sleep time was significantly associated with an increase in the mood episode relapses (per hour; hazard ratio [HR], 1.407; 95% confidence interval (CI), 1.057–1.873), mainly in the depressive episodes (per hour; HR, 1.477; 95% CI, 1.088–2.006).

Conclusions

Our findings suggest that consistency in sleep time might be useful, as an adjunct therapy, in preventing the recurrence or relapse of mood episodes in bipolar disorder.     

Syndrome métabolique et troubles bipolaires : le sommeil est-il le chaînon manquant ?

ObjectiveTo examine the pathophysiologic mechanisms that may link circadian disorder and metabolic syndrome in bipolar disorder (BP).MethodA systematic review of the literature was conducted from January 2013 to January 2015, using the Medline and Cochrane databases, using the keywords “metabolic syndrome”, “obesity”, “leptin” and “circadian disorders”, “sleeping disorders” and cross-referencing them with “bipolar disorder”. The following types of publications were candidates for review: (i) clinical trials; (ii) studies involving patients diagnosed with bipolar disorder; (iii) studies involving patients with sleeping disorder; or (iv) data about metabolic syndrome.ResultsForty articles were selected. The prevalence of metabolic syndrome in BP was significantly higher compared to the general population (from 36 to 49% in the USA [Vancampfort, 2013]), and could be explained by several factors including reduced exercise and poor diet, genetic vulnerability, frequent depressive episodes, psychiatric comorbidity and psychotropic treatment. This high frequency of metabolic syndrome worsens the prognosis of these patients, increasing morbidity and mortality. Secondly, patients with BP experienced circadian and sleep disturbance, including modification in melatonin secretion. These perturbations are known to persist in periods of mood stabilization and are found in patients’ relatives. Circadian disturbances are factors of relapse in bipolar patients, and they may also have a role in the metabolic comorbidities of these patients. Recent studies show that in populations of patients with bipolar disorder, a correlation between circadian disturbance and metabolic parameters are found. To identify the pathophysiological pathway connecting both could lead to a better comprehension of the disease and new therapeutics. In the overall population, mechanisms have been identified linking circadian and metabolic disorder involving hormones like leptin and ghrelin. These hormones are keys to regulation of energy balance in the organism, via their action on the hypothalamus, and are also regulated by sleep. We have hypothesized that these pathways could be implicated in the vulnerability of bipolar patients to metabolic syndrome. This hypothesis is supported by several studies showing dysregulation in leptin and ghrelin secretion in multiple psychiatric disorders, including bipolar disorder, as well as genetic variations of leptin and ghrelin genes in these diseases. We also assume that other mechanisms may be at stake to explain this link, such as melatonin dysregulation and inflammation.ConclusionsCircadian and sleeping disorder may have a role in the prevalence of metabolic syndrome in BP. Hormones like leptin and ghrelin could be the link between these perturbations. Prevention and treatment of circadian disorder in BP may greatly reduce the occurrence of MetS in these patients. Being aware of this statement and taking care of these troubles should be a big step forward for treatment of BP.     

Mindfulness-based cognitive therapy for nonremitted patients with bipolar disorder

Introduction: Bipolar disorder is characterized by recurrent episodes of depression and/or mania along with interepisodic mood symptoms that interfere with psychosocial functioning. Despite periods of symptomatic recovery, many individuals with bipolar disorder continue to experience substantial residual mood symptoms that often lead to the recurrence of mood episodes. Aims: This study explored whether a new mindfulness‐based cognitive therapy (MBCT) for bipolar disorder would increase mindfulness, reduce residual mood symptoms, and increase emotion‐regulation abilities, psychological well‐being, positive affect, and psychosocial functioning. Following a baseline clinical assessment, 12 individuals with DSM‐IV bipolar disorder were treated with 12 group sessions of MBCT. Results: At the end of treatment, as well as at the 3 months follow‐up, participants showed increased mindfulness, lower residual depressive mood symptoms, less attentional difficulties, and increased emotion‐regulation abilities, psychological well‐being, positive affect, and psychosocial functioning. Conclusions: These findings suggest that treating residual mood symptoms with MBCT may be another avenue to improving mood, emotion regulation, well‐being, and functioning in individuals with bipolar disorder.     

Comment caractériser et traiter les plaintes de sommeil dans les troubles bipolaires ?

Objectives

Sleep complaints are very common in bipolar disorders (BD) both during acute phases (manic and depressive episodes) and remission (about 80 % of patients with remitted BD have poor sleep quality). Sleep complaints during remission are of particular importance since they are associated with more mood relapses and worse outcomes. In this context, this review discusses the characterization and treatment of sleep complaints in BD.

The association between insomnia-related sleep disruptions and cognitive dysfunction during the inter-episode phase of bipolar disorder

Sleep disturbance and cognitive dysfunction are two domains of impairment during inter-episode bipolar disorder. Despite evidence demonstrating the importance of sleep for cognition in healthy and sleep-disordered samples, this link has been minimally examined in bipolar disorder. The present study tested the association between insomnia-related sleep disruptions and cognitive dysfunction during inter-episode bipolar disorder. Forty-seven participants with bipolar disorder and a comorbid insomnia diagnosis (BD-Insomnia) and 19 participants with bipolar disorder without sleep disturbance in the last six months (BD-Control) participated in the study. Two domains of cognition were assessed: working memory and verbal learning. Insomnia-related sleep disruptions were assessed both categorically (i.e., insomnia diagnosis) and dimensionally (i.e., total wake time, total sleep time, total wake time variability, and total sleep time variability). Hierarchical linear regressions, adjusting for participant age, demonstrated that insomnia diagnosis did not have an independent or interactive effect on cognition. However, regardless of insomnia diagnosis, greater total sleep time variability predicted poorer working memory and verbal learning performance. Further, following sleep treatment, a reduction in total wake time predicted improved working memory performance and a reduction in total sleep time variability predicted improved verbal learning performance. These findings raise the possibility that sleep disturbance may contribute to cognitive dysfunction in bipolar disorder and highlight the importance of treating sleep disturbance in bipolar disorder.