Health-related quality of life as measured by the child health questionnaire in adolescents with bipolar disorder treated with olanzapine

AimTo examine health-related quality of life (HRQoL) in adolescents with bipolar disorder before and after double-blind treatment with olanzapine or placebo.MethodsParents or legal guardians of 160 adolescents with a manic or mixed episode associated with bipolar I disorder were asked to rate their child's health using the Child Health Questionnaire-Parental Form 50 at baseline, before receiving medication, and then again at the end of participation in a 3-week double-blind placebo-controlled study of olanzapine.ResultsAdolescents in both treatment groups began and ended the study with significantly lower scores than normalized values of healthy peers on several HRQoL subscales (lower ratings indicate more impaired functioning), especially those assessing psychosocial factors. However, participants receiving olanzapine exhibited greater improvement than those in the placebo group across multiple HRQoL subscales, including the Behavior, Family activities, and Mental health subscales. Reduction in manic symptoms was associated with improvement in HRQoL values.ConclusionsAs expected, manic adolescents with bipolar disorder exhibit abnormalities in psychosocial, rather than physical factors associated with HRQoL. Treatment with olanzapine had a greater effect on multiple domains of psychosocial functioning compared with placebo, suggesting that in addition to improving manic symptoms, pharmacologic interventions may lessen some of psychosocial deficits experienced by adolescents with bipolar disorder. However, following 3 weeks of treatment, adolescents with bipolar disorder continued to exhibit deficits in several aspects of psychosocial functioning, indicating that additional pharmacologic and psychosocial interventions may be necessary to further improve functional outcome.     

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.     

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.     

Role of treatment alliance in the clinical management of bipolar disorder: stronger alliances prospectively predict fewer manic symptoms

The strength of the treatment alliance between patients and their clinicians may play a unique role in the management of bipolar disorder. However, few empirical studies have examined the alliance in bipolar disorder or its effects on patient outcomes. This study investigates variables associated with a strong treatment alliance in bipolar disorder, and the prospective effects of treatment alliance on patients' mood symptoms and treatment attitudes. Participants were 58 longitudinally followed individuals with Bipolar I disorder. We found that alliance ratings covaried with depressive symptoms, such that alliance strength increased as depressive symptoms decreased, and stronger alliances were associated with more social support. Tests of temporal association indicated that stronger alliances predicted fewer manic symptoms 6 months later. Stronger alliances also predicted less negative attitudes about medication and less of a sense of stigma about bipolar disorder. Thus, a strong treatment alliance may help to reduce manic symptoms over time. It may be that a strong treatment alliance encourages patients' greater acceptance of bipolar disorder and psychopharmacological interventions, and thus contributes to improved medication adherence and clinical outcomes. Considered in sum, these findings suggest that the treatment alliance is an integral component of the long-term management of bipolar disorder.     

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.     

The relationship between sleep disturbance,symptoms and daytime functioning in psoriasis: a prospective study integrating actigraphy and experience sampling methodology

Objective/backgroundSleep disturbance is common in individuals with psoriasis and appears to be related to both physical and psychological factors. We sought to examine whether psoriasis symptoms, night-time arousal and low mood predicted subsequent objective and self-reported sleep; and whether objective and self-reported sleep predicted next-day psoriasis symptoms and day-time functioning.Participants/MethodsA total of 19 individuals (Female: 11 [57.9%], median age: 39 years) with chronic plaque psoriasis and poor sleep quality (mean Pittsburgh Sleep Quality Index, PSQI = 9.11) participated. Momentary assessments of psoriasis symptoms, mood and daytime functioning were completed at five pseudo-random intervals each day for 15 days using time-stamped digital diary entry. Objective sleep was estimated using wrist-worn actigraphy. Self-reported sleep and night-time arousal were assessed each morning using validated measures.Results and conclusionsTwo-level random intercept models showed that increased night-time arousal was associated with poorer diary-reported sleep. Neither self-reported nor objective sleep parameters were associated with daytime psoriasis symptoms in bi-directional analyses. Diary-reported sleep predicted next-day functioning, specifically sleepiness, concentration, and fatigue. Actigraphy-defined total sleep time predicted next-day fatigue. Night-time arousal is associated with poorer self-reported sleep in people with psoriasis, and sleep predicts next-day functioning. Contrary to our hypothesis, sleep disturbance does not appear to be associated with momentary assessments of psoriasis symptoms.     

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.     

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.     

Treatment adherence among patients with bipolar or manic disorder taking atypical and typical antipsychotics

OBJECTIVE: This retrospective claims-based study evaluated treatment adherence among patients with bipolar or manic disorder treated with atypical and typical antipsychotics. METHOD: Claims data for 18,158 antipsychotic treatment episodes in 15,224 commercially insured patients with bipolar or manic disorder (ICD-9-CM criteria), from January 1999 through August 2003, were evaluated. Overall adherence was measured by adherence intensity (medication possession ratio) and treatment duration (length of treatment episodes). Treatment-related factors that may affect medication adherence were also investigated. Pairwise comparisons of the individual atypicals and a combined group of leading typical antipsychotics were undertaken using multiple regression analysis adjusting for differing patient characteristics. RESULTS: Adherence intensity with quetiapine was 3% greater than with the typicals combined (p=.002) and was greater than with risperidone or olanzapine by 4% (p<.001) and 2% (p=.001), respectively. Olanzapine (2%, p<.001) and ziprasidone (3%, p=.001) showed significantly greater adherence intensity than risperidone. Risperidone (p=.002), olanzapine (p=.055), and the typicals (p=.021) demonstrated negative associations between dose and adherence intensity, while quetiapine showed a nonsignificant trend for a positive association (p=.074). Quetiapine and risperidone had significantly longer treatment durations than the typicals combined (1.05 and 1.00 months, respectively, p<.001) and longer treatment durations than olanzapine (0.75 and 0.79 months, respectively, p<.001) or ziprasidone (0.78 months, p=.002 and 0.69 months, p=.003, respectively). Shorter treatment durations were associated with switching to other antipsychotics or remaining on or switching to other psychotropics (e.g., traditional mood stabilizers) only. All of the atypicals except ziprasidone were associated with a significantly lower likelihood of switching compared with the typicals (p<.05). CONCLUSIONS: The claims-based findings of this study suggest that, for bipolar or manic disorder, quetiapine therapy may be associated with better treatment adherence than typical or some atypical antipsychotics. Estimated differences, however, were relatively small, particularly for adherence intensity.     

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.     

Prodromal symptoms to relapse in bipolar disorder

In a cyclical and recurring illness such as bipolar disorder, prodrome detection is of vital importance. This paper describes manic and depressive prodromal symptoms to relapse, methods used in their detection, problems inherent in their assessment, and patients' coping strategies. A review of the literature on the issue was performed using MEDLINE and EMBASE databases (1965-May 2006). 'Bipolar disorder', 'prodromes', 'early symptoms', 'coping', 'manic' and 'depression' were entered as key words. A hand search was conducted simultaneously and the references of the articles found were used to locate additional articles. The most common depressive prodromes are mood changes, psychomotor symptoms and increased anxiety; the most frequent manic prodromes are sleep disturbances, psychotic symptoms and mood changes. The manic prodromes also last longer. Certain psychological interventions, both at the individual and psychoeducational group level, have proven effective, especially in preventing manic episodes. Bipolar patients are highly capable of detecting prodromal symptoms to relapse, although they do find the depressive ones harder to identify. Learning detection, coping strategies and idiosyncratic prodromes are elements that should be incorporated into daily clinical practice with bipolar patients.     

Treatment adherence and illness insight in veterans with bipolar disorder

Insight into the perceived value of psychotherapy and pharmacological treatment may improve adherence to medication regimens among patients with bipolar disorder, because patients are more likely to take medication they believe will make them better. We conducted a cross-sectional survey of patients recruited into the Continuous Improvement for Veterans in Care-Mood Disorders (CIVIC-MD; July 2004-July 2006), assessing therapeutic insight and 2 measures of medication adherence: the Morisky scale of intrapersonal barriers and missing any doses the previous 4 days. Among 435 patients with bipolar disorder, 27% had poor adherence based on missed dose and 46% had poor adherence based on the Morisky. In multivariable models, greater insight into medication was negatively associated with both measures of poor adherence. Odds of poor adherence increased for women, African Americans, mania, and hazardous drinking. The association of mutable factors-hazardous drinking, manic symptoms, and insight-could represent an opportunity to improve adherence.     

Insomnia as a predictor for symptom worsening following antipsychotic withdrawal in schizophrenia

Sleep disturbances have been associated with schizophrenia, and are an especially prominent feature during the prodrome preceding psychotic relapse. In this study, we examined the changes in sleep quality following withdrawal of antipsychotic treatment, as well as the predictive value of sleep disturbances on symptom exacerbation. One hundred twenty-two patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder underwent a 3-week medication wash-out prior to neuroimaging studies. Sleep quality was rated using items on the Hamilton Rating Scale for Depression (HAM-D), while symptom severity was measured using the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). Sleep quality deteriorated progressively following antipsychotic discontinuation. Total insomnia score prior to antipsychotic withdrawal had a significant effect on the severity of psychotic symptoms at the last weekly assessment, while baseline terminal insomnia had a significant effect on disorganized symptoms at the end of the medication-free period. These findings were independent of baseline symptom severity. Our findings suggest that schizophrenia patients with sleep disturbances are at a greater risk for worsening of positive symptoms after antipsychotic discontinuation. The implications of these findings in research and clinical settings are discussed.     

Adjunctive risperidone treatment and sleep symptoms in combat veterans with chronic PTSD

Sleep disturbances are core symptoms of posttraumatic stress disorder (PTSD) and are often resistant to treatment. One reason for the recent use of atypical antipsychotics in PTSD appears to be their effects on sleep. Study objectives were (1) to evaluate preliminarily the sleep effects of adjunctive risperidone, and (2) to evaluate the use of sleep diaries versus the more standard retrospective sleep assessments. This was a pilot, open-label, 12-week, flexible-dose trial of adjunctive risperidone in male veterans with a primary diagnosis of chronic, combat-related PTSD, partially responsive to current medications. Diagnostic interviews were administered at baseline, and PTSD ratings were obtained at baseline and at 6 and 12 weeks. Self-report sleep measures, including morning logs, were obtained at baseline and 6 weeks. Seventeen patients completed at least 6 weeks of the trial. Global ratings of sleep disturbance improved. Changes in frequency of awakenings and reductions in trauma-related dreams were only evident via morning log assessments. Nighttime awakening frequency derived from the sleep logs but not from the Pittsburgh Sleep Quality Index (PSQI) decreased significantly. There were no changes in the PSQI nightmare item; however, sleep log data indicated a reduced proportion of traumatic dreams at 6 weeks. Preliminary results suggest that adjunctive risperidone may benefit sleep disturbances associated with chronic PTSD. Prospective logs may be more sensitive to change than are retrospective scales.     

Biological and psychological correlates of self-reported and objective sleep measures

ObjectiveObjective and self-reported sleep are only moderately correlated and it is uncertain if these two types of sleep measures are associated with distinct biological and psychological outcomes.MethodsParticipants were 119 healthy women aged 26 years on average. Cortisol and blood pressure assessed over one day were the measures of biological function. Psychological variables included optimism, life satisfaction, positive and negative affect as well as emotional distress. Sleep was assessed with the Pittsburgh Quality Index (PSQI), wrist actigraphy and sleep diaries.ResultsGlobal sleep ratings on the PSQI were unrelated to objective sleep efficiency, duration or latency. Sleep duration derived from sleep diaries was highly correlated with objective duration but was unrelated to the PSQI measure. More disturbed sleep on the PSQI was associated with lower psychological wellbeing, as indicated by reduced levels of optimism, life satisfaction and positive affect as well as greater negative affect and emotional distress. Objective sleep efficiency was reduced among participants with lower positive and higher negative affect but there were no other associations between objective sleep indicators and psychological variables tested in our study. Participants with poorer self-reported sleep had lower cortisol awakening response while those with longer objective sleep latency had higher diastolic blood pressure, independently of covariates.ConclusionOur study reveals that self-reported and objective sleep measures, in particular those regarding sleep quality, are weakly associated but have different psychological and biological correlates. This suggests that findings relating self-reported sleep may not necessarily be corroborated by objective sleep indicators.     

High levels of nocturnal activity in children with attention-deficit hyperactivity disorder: a video analysis

Sleep disturbances can lead to symptoms of attention-deficit hyperactivity disorder (ADHD) in children. In the present study, we compared the sleep patterns of 30 children with ADHD, with those of 19 controls matched for age (5-10 years) and sex. Sleep patterns were recorded during one night, using polysomnography (PSG) and a video system in the sleep laboratory. Both ADHD children and controls were medication free and showed no clinical signs of sleep and alertness problems. An infrared camera was used to record all types of movement, which were scored and analyzed using specific software (Observer(R) 3.0; Noldus International, The Netherlands). No significant differences in sleep variables were found between ADHD children and controls. Polysomnography data showed no significant difference between the two groups. Attention-deficit hyperactivity disorder children moved more often than controls (upper limbs, P < 0.04; lower limbs, P < 0.03; all types, P < 0.003). The duration of movements was significantly longer in ADHD children (upper limbs, P < 0.03; all types, P < 0.02). The results of the video analysis were consistent with previous findings that ADHD children have higher levels of nocturnal activity than controls. This activity concerned mostly upper and lower limb movements. Futher studies are required to determine why noctural activity does not affect sleep continuity in a more significant way and whether it should be treated specifically.     

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.     

Sleep and circadian rhythms in bipolar disorder: seeking synchrony, harmony, and regulation

Despite advances in the treatment of bipolar disorder, a significant proportion of patients experience disabling symptoms between episodes, and relapse rates are high. These circumstances suggest that there is a critical need to achieve a mechanistic understanding of triggers of relapse and to target them with specific, empirically derived treatments. Sleep disturbances are among the most prominent correlates of mood episodes and inadequate recovery, yet sleep has been minimally studied in ways that integrate mechanistic understanding and treatment. In this article, the author seeks to define the limits of current knowledge and to specify preliminary clinical implications. Sleep disturbance is important because it impairs quality of life, contributes to relapse, and has adverse consequences for affective functioning. While sleep disturbance and circadian dysregulation are critical pathophysiological elements in bipolar disorder, many questions about the mechanisms that underpin the association remain. The author presents a model that recognizes a role for genetic vulnerability and suggests that there is a bidirectional relationship between daytime affect regulation and nighttime sleep such that an escalating vicious circle of disturbance in affect regulation during the day interferes with nighttime sleep/circadian functioning, and the effects of sleep deprivation contribute to difficulty in affect regulation the following day.     

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.     

An investigation into an evening intake of a saffron extract (affron®) on sleep quality,cortisol, and melatonin concentrations in adults with poor sleep: a randomised,double-blind,placebo-controlled,multi-dose study

Objective/backgroundTo validate and extend on previous positive findings of the sleep-enhancing effects of saffron supplementation in adults with unsatisfactory sleep.Patients/methodsIn this 28-day, 3-arm, parallel-group, double-blind, randomised controlled trial, 120 adults with unsatisfactory sleep received either a placebo, 14 mg, or 28 mg of a standardised saffron extract (affron®), 1 h before bed. Outcome measures included the Pittsburgh Sleep Diary (with sleep quality ratings as the primary outcome measure), Insomnia Symptom Questionnaire (ISQ), Profile of Mood States, Restorative Sleep Questionnaire, the Functional Outcomes of Sleep Questionnaire, and evening salivary melatonin and cortisol concentrations.ResultsCompared to the placebo, saffron supplementation was associated with greater improvements in sleep quality ratings (primary outcome measure), mood ratings after awakening, the ISQ total score, and ISQ-insomnia classifications. However, there were no significant differences between the saffron and placebo groups in other questionnaire and sleep diary outcome measures. Sleep improvements were similar for the two administered saffron doses. Compared to the placebo, saffron supplementation was associated with increases in evening melatonin concentrations but did not affect evening cortisol. Saffron supplementation was well-tolerated with no reported significant adverse effects.ConclusionsThese results provide further validation of the sleep-enhancing effects of 28-days of saffron supplementation in adults with unsatisfactory sleep. Further research is required to examine the efficacy and safety of saffron supplementation using objective sleep measures, over a longer duration, in people presenting with a diagnosed insomnia disorder and other psychogenic and demographic characteristics, and into its potential sleep-enhancing mechanisms of action.