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.     

Correlates and prognostic relevance of sleep irregularity in inter-episode bipolar disorder

ObjectivesSleep–wake disturbances, such as sleep irregularity, are common in bipolar disorder. Early studies suggest that sleep irregularity is associated with mood symptoms in bipolar disorder, but little research has been conducted to identify other correlates of sleep irregularity. We investigated the relationship between sleep irregularity and sleep quality, social rhythms, eveningness, sleep-related cognitions and behaviors, and past and future mood episodes in 84 patients with inter-episode bipolar I or II disorder.MethodsThis is a retrospective and prospective, naturalistic follow-up study. The Expanded Consensus Sleep Diary, Pittsburgh Sleep Quality Index (PSQI), Social Rhythm Metric (SRM-II-5), Composite Scale of Morningness (CSM), Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS-16), and Sleep Hygiene Practice Scale (SHPS) were administered. The Square Successive Difference (SSD), derived from a week-long sleep diary, was used as an index of sleep irregularity. Multilevel modeling analysis, which adjusts for biases in parameter estimates, was used to minimize the impact of missing data. Bonferroni correction was performed to account for multiple testing.ResultsHigher SSD scores of sleep diary variables were significantly associated with higher PSQI, SRM-II-5, DBAS-16, and SHPS scores. Irregularity in total sleep time was related to more depressive episodes in the past 5 years (p = .002), while irregularity in wake after sleep onset predicted the onset of depressive episodes over the next 2 years (p = .002).ConclusionSleep irregularity was associated with poor sleep quality, irregular social rhythms, dysfunctional sleep-related cognitions and behaviors, and greater number of depressive episodes in bipolar disorder.     

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.     

Electroencephalographic sleep of adolescents with major depression and normal controls

Forty-nine, mostly outpatient (86%), nonbipolar adolescents, aged Tanner stage III to 18 years, with a current diagnosis of major depressive disorder and 40 adolescents without current presence or history of psychiatric disorder were studied polysomnographically for three consecutive nights. Sleep latency was significantly longer in the depressive groups. The nonendogenous depressive patients exhibited significantly more awake time and lower sleep efficiency during the sleep period. No significant group differences were found for first rapid eye movement (REM) period latency, REM density, or any other REM sleep measures. Age correlated significantly with REM latency and delta sleep time, especially among depressive patients. No significant correlations between sleep measures and severity of illness were found. It appears that the classic REM sleep findings associated with the adult depressive syndrome are not present among depressive adolescents, indicating a later ontogeny for these abnormalities.     

Sleep and slow-wave activity in depressed adolescent boys: a preliminary study

ObjectiveAdolescence is a vulnerable period of life that is characterized by increasing incidence of depression. Sleep disturbance is one of the diagnostic symptoms of depressive disorder. Adolescence is also characterized by dramatic maturational changes in sleep and its regulation. The goal of this study was to assess sleep macroarchitecture and slow-wave activity (SWA) in depressed adolescent boys.MethodsEight non-medicated adolescent boys meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for depressive disorder and 10 age-matched healthy controls (average age 16.0 years) underwent polysomnography in their home environment for two consecutive nights. Sleep macroarchitecture, SWA, and SWA dissipation were assessed in all subjects.ResultsDepressed boys showed a flattened pattern of SWA dissipation through the night. SWA power was lower during the first non-rapid eye movement (NREM) episode in the frontal derivation and higher during the third NREM episode in the central derivation in the group of depressed boys as compared to healthy boys. The SWA dissipation pattern correlated with the severity of depressive symptoms, and the correlation was strongest in the frontal derivation. In addition, total sleep time was shorter in patients as compared to the control group, but no other differences were found in the macroarchitecture of sleep.ConclusionDepression in adolescent boys is characterized by more evenly distributed SWA through the night as compared to healthy subjects, and we showed for the first time that this pattern of SWA distribution is associated with severity of depressive symptoms. These findings suggest that homeostatic regulation of sleep may be impaired in adolescent depression.     

Nocturnal sleep EEG in patients with HIV infection

Summary Nocturnal sleep was studied in 14 human immunodeficiency virus (HIV)-positive patients without opportunistic infections of the central nervous system. Seven patients had no bodily complaints at the time of the investigation. Patients exhibited an impaired nocturnal sleep with longer sleep onset latency, reduced total sleep time, reduced sleep efficiency, and more time spent awake and in stage 1. Stage 2 sleep was significantly decreased; in 2 cases, sleep spindle density was extremely low. REM latency was reduced and correlated negatively with depressive symptomatology, while the percentages of REM and slow wave sleep were normal. No significant differences in sleep parameters were present among patients in different stages of the illness, or between patients with and without bodily complaints. Ventricular size and sulcal width on computed tomography scans correlated with sleep variables indicating reduced sleep quality, and with REM density. Decreased tryptophan plasma levels were associated with shorter and less efficient sleep, and with reduced stage 2 sleep. The findings demonstrate that sleep EEG investigations can be valuable for detecting and monitoring central nervous system affection in HIV-positive individuals.This study was presented in part at the 10th Congress of the European Sleep Research Society, Strasbourg, France, 20–25 May 1990     

Comorbid sleep disorders and suicide risk among children and adolescents with bipolar disorder

Children and adolescents with bipolar disorder are at increased risk for suicide. Sleep disturbances are common among youth with bipolar disorder and are also independently implicated in suicide risk; thus, comorbid sleep disorders may amplify suicide risk in this clinical population. This study examined the effects of comorbid sleep disorders on suicide risk among youth with bipolar disorder. We conducted secondary analyses of baseline data from the Treatment of Early Age Mania (TEAM) study, a randomized controlled trial of individuals aged 6–15 years (mean ± SD = 10.2 ± 2.7 years) with DSM-IV bipolar I disorder (N = 379). Sleep disorders (i.e., nightmare, sleep terror, and sleepwalking disorders) and suicide risk were assessed via the WASH-U-KSADS and the CDRS-R, respectively. We constructed uncontrolled logistic regression models as well as models controlling for trauma history, a generalized anxiety disorder (GAD) diagnosis, and depression symptoms. Participants with a current comorbid nightmare disorder versus those without were nearly twice as likely to screen positive for suicide risk in an uncontrolled model and models controlling for trauma history, a GAD diagnosis, and depression symptoms. Neither a current comorbid sleep terror disorder nor a sleepwalking disorder was significantly associated with suicide risk. This pattern of findings remained consistent for both current and lifetime sleep disorder diagnoses. Youth with bipolar I disorder and a comorbid nightmare disorder appear to be at heightened suicide risk. Implications for assessment and treatment are discussed.     

Revisiting depressive-prone bipolar disorder: polarity of initial mood episode and disease course among bipolar I systematic treatment enhancement program for bipolar disorder participants.

BACKGROUND: We examined the hypothesis that a first depressive rather than manic episode in bipolar disorder might herald a subsequent course notable for greater burden of depressive symptoms. METHODS: We analyzed retrospective data on the polarity of first mood episode obtained from 704 bipolar I subjects entering the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. Subjects with an initial manic or depressive episode and those in whom both poles occurred within the same year were compared. RESULTS: Depressive-onset bipolar disorder was more common in women and those with earlier onset of illness. Adjusting for these differences, it was significantly associated with more lifetime depressive episodes and a greater proportion of time with depression and anxiety in the year prior to study entry. CONCLUSIONS: Polarity of first mood episode may be useful in distinguishing subsets of bipolar patients at risk for a more chronic course.     

抑郁症患者睡眠障碍与血浆增食欲素A的关系

目的 探讨抑郁症患者睡眠障碍与血浆增食欲素A的关系,以期为抑郁症睡眠障碍的干预提供理论基础.方法 67例抑郁症患者行24项汉密尔顿抑郁量表(HAMD-24)及匹兹堡睡眠质量指数量表(Pittsburgh sleep quality index,PSQI)评定,根据睡眠情况分为睡眠障碍组(研究组,n=37)及非睡眠障碍组(阳性对照组,n =30),多导睡眠图检测睡眠情况,放射免疫法检测血浆增食欲素-A水平,并与26例健康体检者进行对比(阴性对照组).结果 与正常对照组及非睡眠障碍组比较,抑郁症睡眠障碍组患者HAMD抑郁量表评分及血浆Orexin-A水平均明显增加(P＜ 0.05,P＜0.01);总睡眠时间减少,睡眠潜伏期长,觉醒次数及时间增多,睡眠效率及维持率明显下降,浅睡(S1期睡眠)增加而深睡(S3、S4期睡眠)减少(P＜0.05,P＜ 0.01);REM潜伏期缩短,REM睡眠时间增多,REM活动度、强度及密度明显增强(P＜0.05,P＜0.01);相关性分析表明,血浆Orexin-A水平与睡眠潜伏期、觉醒时间、觉醒次数均呈正相关(r分别为0.447、0.591、0.670,P＜0.01),与S3％+S4％呈负相关(r=-0.872).结论 睡眠障碍者抑郁程度较非睡眠障碍者更高,血浆Orexin-A水平升高可能是引起抑郁症睡眠障碍的一项重要因素,其机制可能与其促进觉醒有关.     

Action of clovoxamine on the sleep of depressed patients. "Polygraphic recordings"

This study reports the action of clovoxamine, a non-tricyclic non IMAO antidepressant, on the sleep parameters of five patients suffering from primary depressive illness. Before treatment all subjects presented an EEG syndrome of primary depressive sleep disorder (decreased paradoxical sleep latency). Sleep recordings were made after 1 month and 3 months of monotherapy with clovoxamine. PS latency increased to normal values, sleep efficiency improved and wake time decreased, and, more remarkably, paradoxical sleep was not suppressed by clovoxamine.     

Depressive syndrome in major psychoses: a study on 1351 subjects

The aim of this study was to investigate depressive symptomatology across distinct major psychiatric disorders. A total of 1351 subjects affected by major depressive disorder (MDD = 389), bipolar disorder (BP = 511), delusional disorder (DD = 93) and schizophrenia (SKZ = 358) were included in our study. Subjects were assessed using the Operational Criteria for Psychotic Illness checklist (OPCRIT). The most frequently represented depressive symptoms in MDD were Loss of energy/tiredness, Loss of pleasure, Poor concentration, and Sleep disorders. Compared with MDD, BP had higher occurrences of Agitated activity, Excessive sleep, and Increased appetite and/or Weight gain, as well as lower Loss of pleasure. In our sample, 32.3% and 26.8% of DD and SKZ, respectively, had quite consistent depressive symptomatology, with at least four or more depressive symptoms. The most common depressive symptoms were Sleep disorders, Poor concentration and Loss of energy/Tiredness, followed by Psychomotor symptoms in SKZ only. Excessive self-reproach, Suicidal ideation, and Appetite and/or Weight changes were more specific to mood disorders. Finally, compared with SKZ, DD suffered from more depressive symptoms and had more severe depressive symptomatology. A quite consistent level of depressive symptomatology is therefore present in subpopulations of delusional and schizophrenic subjects other than in affective subjects. We identified some symptoms that are common across all major psychoses and symptoms that are more specific to each group.     

Sleep duration and timing are nonlinearly associated with depressive symptoms among older adults

BackgroundGeriatric depression is a common but preventable psychiatric disorder; however, its association with specific sleep patterns remains unclear. Therefore, we examined the association of self-reported sleep duration and sleep timing with depressive symptoms in the older population.MethodsA total of 1068 older Taiwanese adults (52.7% women; 72.2 ± 5.7 y) responded to a telephone survey during 2019–2020. Self-reported data on sociodemographic characteristics, sleep duration, bedtime, wake-up time (adapted items from Pittsburgh Sleep Quality Index), and depressive symptoms (five-item Center for Epidemiological Studies–Depression scale) were included. Generalized additive models were used to examine the nonlinear associations of sleep duration and midpoint sleep time (ie, the midpoint of bedtime and wake-up time) with depressive symptoms.ResultsThe means of sleep duration and midpoint sleep time in the participants were 6 h per night and 02:13 h, respectively. The results showed marked nonlinear associations of sleep patterns with depressive symptoms. Sleep duration shorter than 4 h per night was associated with a relatively higher level of depressive symptoms, with the highest risk (coefficient = 3.41; 95% confidence interval [CI] = 2.12, 4.70) while sleeping 2.06 h per night. The midpoint sleep time was positively associated with depressive symptom scores after 01:00 h.ConclusionsThe results showed that sleep duration and fitting sleep timing were nonlinearly associated with the risks of depressive symptoms in the general older adult population. These findings have implications for targeting nonpharmacological approaches by tackling modifiable behaviors, such as adequate sleep duration and timing, with decreased risks of depressive symptoms in the older adult population.     

The relation of sleep difficulties to fatigue, mood and disability in chronic fatigue syndrome

The relationship of sleep complaints to mood, fatigue, disability, and lifestyle was examined in 69 chronic fatigue syndrome (CFS) patients without psychiatric disorder, 58 CFS patients with psychiatric disorder, 38 psychiatric out-patients with chronic depressive disorders, and 45 healthy controls. The groups were matched for age and gender. There were few differences between the prevalence or nature of sleep complaints of CFS patients with or without current DSM-IIIR depression, anxiety or somatization disorder. CFS patients reported significantly more naps and waking by pain, a similar prevalence of difficulties in maintaining sleep, and significantly less difficulty getting off to sleep compared to depressed patients. Sleep continuity complaints preceded fatigue in only 20% of CFS patients, but there was a strong association between relapse and sleep disturbance. Certain types of sleep disorder were associated with increased disability or fatigue in CFS patients. Disrupted sleep appears to complicate the course of CFS. For the most part, sleep complaints are either attributable to the lifestyle of CFS patients or seem inherent to the underlying condition of CFS. They are generally unrelated to depression or anxiety in CFS.     

Psychopharmacological aspects on monoaminergic and behavioral perturbations in experimental chronic hepatic encephalopathy

Prior studies have found contradictory results regarding the association between course of illness and quality of life among patients with depressive disorder or bipolar disorder. Questionnaires about quality of life and affective symptoms (the EQ-5D, EQ-5D-VAS, WHO (Five) well-being index and the BDI-42) were mailed to a large population of outpatients with depressive or bipolar disorder representative of patients treated in hospital settings in Denmark. Among the 1005 recipients, 49.9% responded to the letter. Depressive disorder was associated with poorer general health (EQ-5D, EQ-5D-VAS) and well-being (WHO (Five) well-being index) and more depressive and anxiety symptoms compared with bipolar disorder. Similarly, more psychiatric admissions were associated with poorer general health and well-being and more depressive and anxiety symptoms. However, when adjusting for the effect of depressive symptoms, the associations between number of admissions and general health, and between numbers of admissions and well-being, lost significance. Thus, depressive symptoms seem to be the strongest predictor of general health and well-being in both disorders. As the response rate to the questionnaire was relatively low, the findings should be interpreted with caution.     

Effects of clozapine on sleep in bipolar and schizoaffective disorders

OBJECTIVE: Sleep disturbances are strongly associated with mood disorders, although the majority of data have been obtained in patients with major depressive disorder. Studies reporting results in bipolar disorder are few, and results have not been consistent. Clozapine is a prototype of atypical antipsychotics, which is effective in improving symptoms of manic episodes in patients with bipolar disorder, or schizoaffective disorder, bipolar type and has been shown to influence sleep in other psychiatric disorders. The present study evaluated the sleep effects of clozapine in bipolar and schizoaffective disorders. METHODS: Participants were 11 women and 4 men (range:28-53 years of age, mean 40.9+/-8.6 years), all with a history of mania by DSM-IV criteria for either bipolar I disorder or schizoaffective disorder, bipolar type. They participated in a sleep study at baseline and again after 6 months initiation of clozapine add-on therapy. RESULTS: Sleep latency was longer on clozapine and the number of awakenings were increased, whereas time in bed (TIB) and total sleep period (TSP) were increased (range: F=6.2-17.9; df=l,12; p<0.05). Although none of the individual sleep stage showed significant treatment changes, both Stage 2 and slow-wave sleep were increased and Stage 2 decreased on clozapine. Subjective sleep measures improved on clozapine with a small but significant improvement in how rested patients felt upon awakening (t=-2.1; df=26; p<0.05). CONCLUSION: Clozapine prolonged sleep latency, improved restedness, and increased total sleep time. Although lack of a control group limits interpretation of these results, they are in general agreement with studies in other psychiatric populations, and support the view that clozapine is primarily a NREM sleep enhancer. The improvement in restedness may be of positive clinical consequence.     

General health and well-being in outpatients with depressive and bipolar disorders

Prior studies have found contradictory results regarding the association between course of illness and quality of life among patients with depressive disorder or bipolar disorder. Questionnaires about quality of life and affective symptoms (the EQ-5D, EQ-5D-VAS, WHO (Five) well-being index and the BDI-42) were mailed to a large population of outpatients with depressive or bipolar disorder representative of patients treated in hospital settings in Denmark. Among the 1005 recipients, 49.9% responded to the letter. Depressive disorder was associated with poorer general health (EQ-5D, EQ-5D-VAS) and well-being (WHO (Five) well-being index) and more depressive and anxiety symptoms compared with bipolar disorder. Similarly, more psychiatric admissions were associated with poorer general health and well-being and more depressive and anxiety symptoms. However, when adjusting for the effect of depressive symptoms, the associations between number of admissions and general health, and between numbers of admissions and well-being, lost significance. Thus, depressive symptoms seem to be the strongest predictor of general health and well-being in both disorders. As the response rate to the questionnaire was relatively low, the findings should be interpreted with caution.     

Sleep disturbances and depression in the elderly in Japan

The purpose of the present study was to evaluate the relationship between sleep disturbances and depression in the Japanese elderly. Methods: These investigations in the Japanese elderly were carried out with the Geriatric Depression Scale, the Pittsburgh Sleep Quality Index, and questions on restless legs syndrome and nocturnal eating disorder. A total of 2023 people (male: 1008; female: 1015; average age: 74.2 +/- 6.3 years) were analyzed by chi2 test and simple and multiple logistic regression. The prevalence of sleep disturbance was 37.3% and that of depression was 31.3%. Female gender and/or older (> or =75 years) age were significantly associated with depression. Characteristics in depressive elderly were poor sleep efficiency, sleep disturbances due to difficulty of initiating sleep (DIS), breathing discomfort, coldness and pain, poor subjective sleep quality and lack of enthusiasm for activities. Sleep disturbances due to using the bathroom, breathing discomfort and coldness and long sleep latency were associated with depression in younger (65-74 years) men. Sleep disturbance due to DIS was associated with depression in older (> or =75 years) men. Sleep disturbance due to pain was associated with depression in younger and older women. Poor sleep efficiency was associated with depression in older women. Poor subjective sleep quality was associated with depression in younger and older men and younger women. Lack of enthusiasm was associated with depression in younger and older men and older women. Restless legs syndrome was statistically significantly associated with depression in younger men. It is concluded that sleep disturbance and depression among the Japanese elderly are closely related symptoms. The features of sleep disturbance with depression differed with sex and age.     

Sleep electroencephalographic coherence abnormalities in individuals at high risk for depression: a pilot study.

BACKGROUND: Sleep electroencephalographic (EEG) studies of individuals with major depressive disorder have identified several microarchitectural features associated with the illness. These abnormalities are also found in clinically remitted individuals, raising the question of whether they are vulnerability markers of depression. This study evaluated the sleep EEG in high-risk individuals to see if abnormalities are present in the sleep EEG prior to the onset of illness. METHODS: A total of 26 subjects (13 males and 13 females) were recruited for study on the basis of 1) having a parent or grandparent treated for major depressive or bipolar affective disorder and 2) having no history of personal psychiatric illness. Polysomnographic data were collected and compared with gender- and age-matched healthy control subjects with no personal or family history of psychiatric illness. The primary outcome measures were interhemispheric and intrahemispheric coherence. RESULTS: Period analysis of the sleep EEG showed that beta-delta coherence was lower bilaterally in male high-risk subjects. Right-hemispheric theta-delta coherence was also lower in male high-risk subjects, with female high-risk subjects evidencing lower beta coherence. CONCLUSIONS: Sleep-EEG abnormalities associated with major depressive disorder are present in never mentally ill individuals at high risk for the illness. These markers may be useful in the prediction of illness and in family genetic studies of mood disorders.     

Correlates of 1-year prospective outcome in bipolar disorder: results from the Stanley Foundation Bipolar Network

OBJECTIVE: The purpose of the study was to examine potential correlates of outcome in patients treated for bipolar disorder. METHOD: During a 1-year period, 258 patients with DSM-IV bipolar disorder or schizoaffective disorder were rated with the prospective NIMH-Life Chart Method, which characterizes each day in terms of the severity of manic and depressive symptoms on the basis of patients' mood-related impairment in their usual educational, social, or occupational roles. Mean ratings for the severity of mania, depression, and overall bipolar illness and the number of manic, depressive, and overall illness episodes were calculated. Potential risk factors were assessed at the start of the study, and multivariate linear regression analysis was used to determine the correlates of the six 1-year outcome measures. RESULTS: Three of the six outcome measures were largely independent of each other and were used in the analysis. The mean rating for severity of mania was associated with comorbid substance abuse, history of more than 10 prior manic episodes, and poor occupational functioning at study entry. The mean rating for severity of depression was associated with a history of more than 10 prior depressive episodes and poor occupational functioning at study entry. The total number of overall illness episodes was associated with a positive family history of drug abuse, a history of prior rapid cycling, and poor occupational functioning. In addition, the mean rating for severity of mania and the total number of overall illness episodes were both initially associated with a history of childhood abuse, but these relationships were lost with the addition of other illness variables to the analysis. CONCLUSIONS: Clinicians who treat patients with bipolar disorder should consider a family history of drug abuse, a history of childhood abuse, prior course of illness, comorbid substance abuse, and occupational functioning in determining prognosis and setting goals for further treatment.