Short communication: Do clinical guidelines for bipolar disorders adequately address sleep, circadian rhythm, activity and lifestyle problems?

International audienceObjectives Clinical practice guidelines (CPGs) for the treatment of bipolar disorder (BD) provide guidance to health care professionals and patients about the management of core aspects of BD. This study evaluated the overall quality of CPGs and examined the quantity, specificity, clarity and utility of recommendations about four key contemporary themes: sleep, circadian rhythms, activity and energy, and healthy lifestyles. Methods English language editions of CPGs for the treatment of BD were identified by a systematic search of the literature from 2007 onwards (i.e. 15 years). Blind independent ratings were combined to give consensus scores for the quality of each CPGs (using the 14-item International Center for Allied Health Evidence guideline checklist). Composite ratings of the quantity, specificity, clarity and utility of recommendations about the key themes were undertaken using a 0-3 scale. Results Twenty-five CPGs were eligible for review. Overall quality was high (median checklist score=10), but only 11 (44%) CPGs included even basic information about circadian rhythm disturbances. Combined scores for composite ratings about sleep and circadian rhythms were significantly correlated with overall quality of the CPG (sleep, r = 0.43; circadian rhythms, r = 0.42) but not with year of publication. Limitations No reliable scale exists for generating composite ratings of the four themes we examined. Conclusions Circadian rhythms and chronobiology represent neglected domains in CPGs. Incorporating this important theme into future editions of CPGs would aid health care professionals to identify, prevent, or intervene with these problems and improve outcomes for a significant proportion of individuals with BD

Do self‐ratings of the Pittsburgh Sleep Quality Index reflect actigraphy recordings of sleep quality or variability? An exploratory study of bipolar disorders versus healthy controls

International audienceSleep disturbances are typical symptoms of acute episodes of bipolar disorder (BD) and differentiate euthymic BD cases from healthy controls (HC). Researchers often employ objective recordings to evaluate sleep patterns, such as actigraphy, whilst clinicians often use subjective ratings, such as the Pittsburgh Sleep Quality Index (PSQI). As evidence suggests the measures may disagree, we decided to compare subjective (PSQI) and objective (3 weeks of actigraphy) sleep profiles in BD cases and HC (n = 154). We examined whether a dimensional approach helps to illustrate different patterns of sleep disturbances and whether the concordance between subjective and objective recordings varies according to clinical status (BD versus HC). Principal component analysis (PCA) extracted two factors from the PSQI, and separate PCAs of actigraphy recordings extracted two factors for mean values of sleep parameters and one factor for intra-individual variability. Correlational and linear regression analyses of PCA-derived dimensions demonstrated that, in both BD and HC, a PSQI "Sleep duration-efficiency" factor was significantly correlated with an actigraphy "Sleep initiation-duration" factor. Furthermore, in BD cases only, the PSQI total score and a PSQI "Sleep Impairments" factor were each significantly correlated with an actigraphy "Sleep Variability" factor. Overall, we found that subjective experiences of sleep may be modulated by different components of objectively recorded sleep in BD compared with HC. Also, the use of PCA enabled us to consider the multi-dimensional nature of subjective sleep, whilst the inclusion of intra-individual sleep variability afforded a more subtle evaluation of objective sleep

Our Economy

International audienc

Which Actigraphy Dimensions Predict Longitudinal Outcomes in Bipolar Disorders?

International audienceBipolar disorder (BD) is characterized by recurrent mood episodes. It is increasingly suggested that disturbances in sleep–wake cycles and/or circadian rhythms could represent valuable predictors of recurrence, but few studies have addressed this question. Euthymic individuals with BD (n = 69) undertook 3 weeks of actigraphy recording and were then followed up for a median duration of 3.5 years. Principal component analyses were used to identify core dimensions of sleep quantity/variability and circadian rhythmicity. Associations between clinical variables and actigraphy dimensions and time to first recurrence were explored using survival analyses, and then using area under the curve (AUC) analyses (early vs. late recurrence). Most participants (64%) experienced a recurrence during follow-up (median survival time: 18 months). After adjusting for potential confounding factors, an actigraphy dimension comprising amplitude and variability/stability of circadian rhythms was a significant predictor of time to recurrence (p = 0.009). The AUC for correct classification of early vs. late recurrence subgroups was only 0.64 for clinical predictors, but combining these variables with objectively measured intra-day variability improved the AUC to 0.82 (p = 0.04). Actigraphy estimates of circadian rhythms, particularly variability/stability and amplitude, may represent valid predictive markers of future BD recurrences and could be putative targets for future psychosocial interventions

Associations between circadian misalignment and telomere length in BD: an actigraphy study

International audienceBackground Life expectancy is significantly decreased in bipolar disorder (BD). This is associated with accelerated cellular aging which can be estimated by telomere length (TL). However, specific determinants of shorter TL in BD are under-explored. This study examines whether circadian misalignment (i.e. mismatch between preferred and actual phase of circadian activity rhythms) is associated with shorter TL in BD. Methods Euthymic individuals with BD (n = 101) undertook 21 consecutive days of actigraphy recording and completed the Composite Scale of Morningness (CSM) to assess phase preference for activities (chronotype). Polymerase chain reaction was used to measure TL in blood. Cluster analysis identified circadian aligned/misaligned subgroups as defined by preferred (CSM score) and actual phases of activity (actigraphically determined onset of active and inactive periods). We tested for any associations between TL and clusters, with adjustments for between-cluster differences in socio-demographic and illness factors. Results We identified three clusters: an "Aligned Morning" cluster (n = 31) with preferred and actual timing of activity in the morning, an "Aligned Evening" cluster (n = 37) with preferred and actual timing of activity in the evening and a "Misaligned" cluster (n = 32) with an evening chronotype, but an earlier objective onset of active periods. After adjustment for confounders, we found that TL was significantly associated with circadian misalignment and older age. Conclusions Circadian misalignment may partly explain shorter TL in BD and could contribute to accelerated aging in these individuals

Gene expression of circadian genes and CIART in bipolar disorder: A preliminary case-control study

International audienceBased on the observed circadian rhythms disruptions and sleep abnormalities in bipolar disorders (BD), a chronobiological model has been proposed suggesting that core clock genes play a central role in the vulnerability to the disorder. In this context, the analysis of circadian genes expression levels is particularly relevant, however studies focused on the whole set of core clock genes are scarce. We compared the levels of expression of 19 circadian genes (including the recently described circadian repressor (CIART)) in 37 euthymic individuals with BD and 20 healthy controls (HC), using data obtained by RNA sequencing of lymphoblastoid cell lines and validated the results using RT-qPCR. RNA sequencing data showed that CIART gene expression was correlated with those of ARNTL, ARNTL2, DBP, PER2 and TIMELESS. Data from RNA sequencing showed that the level of expression of four circadian genes (ARNTL, ARNTL2, BHLHE41 and CIART) discriminated individuals with BD from HC. We replicated this result using RT-qPCR for ARNTL and CIART. This study suggests that an imbalance between activation/repression of the transcription within the circadian system in individuals with BD as compared to HC and as such opens avenues for further research in larger independent samples combining both expression and epigenetic analyses

Misperception of sleep in bipolar disorder: an exploratory study using questionnaire versus actigraphy

Background The concept of misperception of sleep refers to the estimated discrepancy between subjective and objective measures of sleep. This has been assessed only in a few prior studies in individuals with Bipolar Disorder (BD) as compared to Healthy Controls (HC) and with mixed results. Methods We assessed a sample of 133 euthymic individuals with BD and 63 HC for retrospective subjective (Pittsburgh Sleep Quality Index) and objective (21 days of actigraphy recording) measures of total sleep time, sleep latency and sleep efficiency. We first investigated the correlations between these subjective and objective measures in the two groups. We then compared individuals with BD and HC for the absolute values of the differences between subjective and objective sleep parameters, used as a proxy of the magnitude of misperception of sleep. Finally, we undertook regression analyses to assess associations between clinical groups, core demographics, clinical factors and misperception of sleep. Results The correlation coefficients between subjective and objective measures of sleep did not differ between groups (total sleep time: rho = .539 in BD and rho = .584 in HC; sleep latency: rho = .190 in BD and rho = .125 in HC; sleep efficiency: rho = .166 in BD and rho = .222 in HC). Individuals with BD did not differ from HC in the magnitude of misperception of total sleep time, sleep latency nor sleep efficiency. Individuals with BD type 1 misperceived their sleep efficiency significantly more than individuals with BD type 2, with no further difference between BD type 1 and BD type 2 regarding sleep latency and sleep duration misperceptions. Three factors (age, symptoms of obstructive sleep apnea, and mild depressive symptoms), were the main contributors to the magnitude of misperception of sleep. Conclusions Misperception of sleep was not associated with a diagnosis of BD. In this sample, mild depressive symptoms, older age, or symptoms of obstructive sleep apnea may be related to greater sleep misperception. In that case, the reliability of subjective measures may decrease as the misperception of sleep increases. This study may help guide clinicians in selecting the best approach for assessing sleep (objective versus subjective measures) in individuals with BD

ESS MEDIUM BETA CAVITY PROTOTYPES MANUFACTURING

The ESS elliptical superconducting Linac consists of two types of 704.42 MHz cavities, medium and high beta, to accelerate the beam from 216 MeV (spoke cavity Linac) up to the final energy at 2 GeV. The last Linac optimization, called Optimus+, has been carried out taking into account the limitations of SRF cavity performance (field emission). The medium and high-beta parts of the Linac are composed of 36 and 84 elliptical cavities, with geometrical beta values of 0.67 and 0.86 respectively. We describe here the procedures and numerical analysis leading from half-cells to a complete medium cavity assembly, which take into account not only the frequency of the fundamental accelerating mode but also the higher order modes near the machine line. The half-cell selection process to form dumb bells will be described, as well as the reshaping and trimming procedure