Which actigraphic variables optimally characterize the sleep-wake cycle of individuals with bipolar disorders?

OBJECTIVE: To examine which combination of objectively measured actigraphy parameters best characterizes the sleep-wake cycle of euthymic individuals with bipolar disorder (BD) compared with healthy controls (HC). METHODS: Sixty-one BD cases and 61 matched HC undertook 21 consecutive days of actigraphy. Groups were compared using discriminant function analyses (DFA) that explored dimensions derived from mean values of sleep parameters (Model 1); variability of sleep parameters (2); daytime activity (3); and combined sleep and activity parameters (4). Exploratory within-group analyses examined characteristics associated with misclassification. RESULTS: After controlling for depressive symptoms, the combined model (4) correctly classified 75% cases, while the sleep models (1 and 2) correctly classified 87% controls. The area under the curve favored the combined model (0.86). Age was significantly associated with misclassification among HC, while a diagnosis of BD-II was associated with an increased risk of misclassifications of cases. CONCLUSION: Including sleep variability and activity parameters alongside measures of sleep quantity improves the characterization of cases of euthymic BD and helps distinguish them from HC. If replicated, the findings indicate that traditional approaches to actigraphy (examining mean values for the standard set of sleep parameters) may represent a suboptimal approach to understanding sleep-wake cycles in BD.

Metabolic syndrome and actigraphy measures of sleep and circadian rhythms in bipolar disorders during remission.

OBJECTIVE: This study explored the correlations between sleep and circadian rhythm measures and the metabolic syndrome (MetS) components in remitted patients with bipolar disorder (BD). METHOD: Euthymic patients with BD (n = 67) were recorded by 3 weeks with actigraphy. We used nonparametric correlations to study the links between the MetS parameters, atherogenic index of plasma (AIP), sleep efficacy, sleep latency, fragmentation index, and phase and amplitude of rhythms. We performed multivariable analyses to take into account potential confounding factors such as sleep apnea risk, antipsychotics use, and smoker status. RESULTS: We found correlations between lower sleep efficiency and higher triglyceride levels (P = 0.002), lower M10 onset (beginning of the 10 most active hours during the 24-h cycle) and higher systolic blood pressure (P = 0.03), higher fragmentation index and higher systolic blood pressure (P = 0.009), lower sleep efficiency, higher fragmentation index, and higher AIP (respectively P = 0.02 and P = 0.04). These correlations mostly remained significant when adjusting for confounders, with the exception of M10 onset and systolic blood pressure. CONCLUSION: Sleep efficiency and fragmentation index might contribute to the cardiovascular risk of patients with BD independently of major confounding factors. Although these associations did not imply causality, proposing interventions on sleep quality and circadian rhythm regularity might contribute to reduce cardiovascular risk in patients with BD.

[Circadian markers and genes in bipolar disorder]. / Biomarqueurs et gènes circadiens dans le trouble bipolaire.

INTRODUCTION: Bipolar disorder is a severe and complex multifactorial disease, characterized by alternance of acute episodes of depression and mania/hypomania, interspaced by euthymic periods. The etiological determinants of bipolar disorder yet, are still poorly understood. For the last 30 years, chronobiology is an important field of investigation to better understand the pathophysiology of bipolar disorder. METHODS: We conducted a review using Medline, ISI Database, EMBase, PsyInfo up to January 2015, using the following keywords combinations: "mood disorder", "bipolar disorder", "depression", "unipolar disorder", "major depressive disorder", "affective disorder", for psychiatric conditions; and "circadian rhythms", "circadian markers", "circadian gene", "clock gene", "melatonin" for circadian rhythms. The search critera was presence of word in any field of the article. RESULTS: Quantitative and qualitative circadian abnormalities are associated with bipolar disorders both during acute episodes and euthymic periods, suggesting that these altered circadian rhythms may represent biological trait markers of the disorder. These circadian dysfunctions were assessed by various validated tools including polysomnography, actigraphy, sleep diaries, chronotype assessments and blood melatonin/cortisol measures. Other altered endogenous circadian activities have also been reported in bipolar patients, such as hormones secretion, core body temperature or fibroblasts activity. Moreover, these markers were also altered in healthy relatives of bipolar patients, suggesting a degree of heritability. Several genetic association studies have also showed associations between multiple circadian genes and bipolar disorder, such as CLOCK, ARTNL1, GSK3ß, PER3, NPAS2, NR1D1, TIMELESS, RORA, RORB, and CSNK1ε. Thus, these circadian gene variants may contribute to the genetic susceptibility of the disease. Furthermore, the study of the clock system may help to better understand some phenotypic aspects like the mechanisms of pharmacological treatments used in bipolar disorder, in particular lithium carbonate. CONCLUSION: Several clinical, physiological and genetic data suggest that circadian rhythms dysregulations are involved in the pathophysiology of bipolar disorder. The circadian model has led to the development of new therapeutic strategies such as chronotherapeutics or Inter Personal Social and Rhythms Therapies. Further studies are needed in this promising research field to keep exploring the relationship between these circadian markers, genes and the clinical aspects of the disease.

Sleep and circadian rhythms as possible trait markers of suicide attempt in bipolar disorders: An actigraphy study.

BACKGROUND: The poor prognostic of Bipolar disorders (BD) is closely linked to deaths by suicide. Sleep and circadian abnormalities are observed during all phases of BD and are also associated with suicide attempt (SA). In this context, this study sought to identify specific sleep and circadian rhythms markers associated with suicidal attempt in euthymic patients with BD. METHODS: The sample (N = 236) comprised 3 groups: 147 patients with BD including 57 with a history of SA and 90 without (NoSA), and 89 healthy controls (HC). All participants were recorded during 21 days with actigraphy. RESULTS: SA was associated with women gender (p = 0.03), familial history of SA (p = 0.03), mixed episodes (p = 0.001), and benzodiazepines (p = 0.019). SA, compared to noSA, had a morning phase preference (p = 0.04), and were more vigorous on the circadian type inventory (p = 0.04), and tended to suffer more from insomnia (45% versus 25% respectively, p = 0.10). SA was also associated with an earlier onset of daily activity assessed with actigraphy (M10 onset: p = 0.01). Backward stepwise linear regression indicated that a combination of four variables (Gender, vigour, insomnia, M10onset) significantly differentiated patients with SA from NoSA (p = 0.03). LIMITATIONS: Cross-sectional design, and no examination of suicidal behaviors' subgroups such as first attempters or repeaters, or violent suicide attempt. CONCLUSIONS: Woman gender, vigorous circadian type, insomnia and an earlier daily activity appeared independently associated with SA in BD. If these biomarkers are confirmed in prospective studies, they should be screened and used to prevent suicide, with the development of personal and targeted chronobiological treatments.

Does childhood experience of attention-deficit hyperactivity disorder symptoms increase sleep/wake cycle disturbances as measured with actigraphy in adult patients with bipolar disorder?

Childhood attention-deficit hyperactivity disorder (ADHD) is a common precursor of adult bipolar disorders (BD). Furthermore, actigraphy studies demonstrate that each disorder may be associated with abnormalities in sleep and activity patterns. This study investigates whether the presence or absence of self-reported childhood experiences of ADHD symptoms is associated with different sleep and activity patterns in adults with BD. A sample of 115 euthymic adult patients with BD was assessed for childhood ADHD symptoms using the Wender Utah Rating Scale (WURS) and then completed 21 days of actigraphy monitoring. Actigraphic measures of sleep quantity and variability and daytime activity were compared between BD groups classified as ADHD+ (n = 24) or ADHD- (n = 91), defined according to established cutoff scores for the WURS; then we examined any associations between sleep-wake cycle parameters and ADHD dimensions (using the continuous score on the WURS). Neither approach revealed any statistically significant associations between actigraphy parameters and childhood ADHD categories or dimensions. We conclude that the sleep and activity patterns of adult patients with BD do not differ according to their self-reported history of ADHD symptoms. We discuss the implications of these findings and suggest how future studies might confirm or refute our findings.