•Sleep and circadian rhythms disturbances are associated to history of suicide attempts.•Suicide attempt is associated with women gender and a familial history of suicide.•Mixed episodes and ...benzodiazepines are associated with history of suicide attempt in BD.•Insomnia, earlier onset of activity, woman gender and vigorous circadian type are independent predictors.•The predictive value of these biomarkers must be confirmed in a prospective study.
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.
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.
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).
Cross-sectional design, and no examination of suicidal behaviors’ subgroups such as first attempters or repeaters, or violent suicide attempt.
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.
Abstract Mood spectrum disorders (bipolar disorder, recurrent depressive disorder and seasonal affective disorder) are accompanied by circadian deregulations, which can occur during acute mood ...episodes as well as during euthymic periods, and are particularly common among bipolar patients in remission. This suggests that altered circadian rhythms may be biological markers of these disorders. Rhythm dysfunctions have been observed in mood disorder patients by using actigraphic measures and by assessing social metric rhythms, diurnal preferences and melatonin secretion. Since many of these markers are heritable and therefore driven by clock genes, these genes may represent susceptibility factors for mood spectrum disorders. Indeed, several genetic association studies have suggested that certain circadian gene variants play a role in susceptibility to these disorders. Such connections to circadian genes such as CLOCK, ARNTL1, NPAS2, PER3 and NR1D1 have been repeatedly demonstrated for bipolar disorders, and to a lesser extent for recurrent depressive disorders and seasonal affective disorders. The study of circadian phenotypes and circadian genes in mood spectrum disorders represents a major field of research that may yet reveal the pathophysiological determinants of these disorders.
The coronavirus disease 2019 (COVID-19) pandemic has caused major sanitary crisis worldwide. Half of the world has been placed in quarantine. In France, this large-scale health crisis urgently ...triggered the restructuring and reorganization of health service delivery to support emergency services, medical intensive care units and continuing care units. Health professionals mobilized all their resources to provide emergency aid in a general climate of uncertainty. Concerns about the mental health, psychological adjustment, and recovery of health care workers treating and caring for patients with COVID-19 are now arising. The goal of the present article is to provide up-to-date information on potential mental health risks associated with exposure of health professionals to the COVID-19 pandemic.
Authors performed a narrative review identifying relevant results in the scientific and medical literature considering previous epidemics of 2003 (SARS-CoV-1) and 2009 (H1N1) with the more recent data about the COVID-19 pandemic. We highlighted most relevant data concerning the disease characteristics, the organizational factors and personal factors that may contribute to developing psychological distress and other mental health symptoms.
The disease characteristics of the current COVID-19 pandemic provoked a generalized climate of wariness and uncertainty, particularly among health professionals, due to a range of causes such as the rapid spread of COVID-19, the severity of symptoms it can cause in a segment of infected individuals, the lack of knowledge of the disease, and deaths among health professionals. Stress may also be caused by organizational factors, such as depletion of personal protection equipment, concerns about not being able to provide competent care if deployed to new area, concerns about rapidly changing information, lack of access to up-to-date information and communication, lack of specific drugs, the shortage of ventilators and intensive care unit beds necessary to care for the surge of critically ill patients, and significant change in their daily social and family life. Further risk factors have been identified, including feelings of being inadequately supported, concerns about health of self, fear of taking home infection to family members or others, and not having rapid access to testing through occupational health if needed, being isolated, feelings of uncertainty and social stigmatization, overwhelming workload, or insecure attachment. Additionally, we discussed positive social and organizational factors that contribute to enhance resilience in the face of the pandemic. There is a consensus in all the relevant literature that health care professionals are at an increased risk of high levels of stress, anxiety, depression, burnout, addiction and post-traumatic stress disorder, which could have long-term psychological implications.
In the long run, this tragic health crisis should significantly enhance our understanding of the mental health risk factors among the health care professionals facing the COVID-19 pandemic. Reporting information such as this is essential to plan future prevention strategies. Protecting health care professionals is indeed an important component of public health measures to address large-scale health crisis. Thus, interventions to promote mental well-being in health care professionals exposed to COVID-19 need to be immediately implemented, and to strengthen prevention and response strategies by training health care professionals on mental help and crisis management.
Objective: Duration of untreated illness represents a potentially modifiable component of any diagnosis‐treatment pathway. In bipolar disorder (BD), this concept has rarely been systematically ...defined or not been applied to large clinically representative samples.
Method: In a well‐characterized sample of 501 patients with BD, we estimated the duration of untreated bipolar disorder (DUB: the interval between the first major mood episode and first treatment with a mood stabilizer). Associations between DUB and clinical onset and the temporal sequence of key clinical milestones were examined.
Results: The mean DUB was 9.6 years (SD 9.7; median 6). The median DUB for those with a hypomanic onset (14.5 years) exceeded that for depressive (13 years) and manic onset (8 years). Early onset BD cases have the longest DUB (P < 0.0001). An extended DUB was associated with more mood episodes (P < 0.0001), more suicidal behaviour (P = 0.0003) and a trend towards greater lifetime mood instability (e.g. rapid cycling, possible antidepressant‐induced mania).
Conclusion: Duration of untreated bipolar disorder (DUB) will only be significantly reduced by more aggressive case finding strategies. Reliable diagnosis (especially for BD‐II) and/or instigation of recommended treatments is currently delayed by insufficient awareness of the early, polymorphous presentations of BD, lack of systematic screening and/or failure to follow established guidelines.
Objective
Sleep dysregulation is highly prevalent in bipolar disorders (BDs), with previous actigraphic studies demonstrating sleep abnormalities during depressive, manic, and interepisode periods. ...We undertook a meta‐analysis of published actigraphy studies to identify whether any abnormalities in the reported sleep profiles of remitted BD cases differ from controls.
Method
A systematic review identified independent studies that were eligible for inclusion in a random effects meta‐analysis. Effect sizes for actigraphy parameters were expressed as standardized mean differences (SMD) with 95% confidence intervals (95% CI).
Results
Nine of 248 identified studies met eligibility criteria. Compared with controls (N = 210), remitted BD cases (N = 202) showed significant differences in SMD for sleep latency (0.51 0.28–0.73), sleep duration (0.57 0.30–0.84), wake after sleep onset (WASO) (0.28 0.06–0.50) and sleep efficiency (−0.38 −0.70–0.07). Moderate heterogeneity was identified for sleep duration (I2 = 44%) and sleep efficiency (I2 = 44%). Post hoc meta‐regression analyses demonstrated that larger SMD for sleep duration were identified for studies with a greater age difference between BD cases and controls (β = 0.22; P = 0.03) and non‐significantly lower levels of residual depressive symptoms in BD cases (β = −0.13; P = 0.07).
Conclusion
This meta‐analysis of sleep in remitted bipolar disorder highlights disturbances in several sleep parameters. Future actigraphy studies should pay attention to age matching and levels of residual depressive symptoms.
La dimension thymique est souvent considérée – à juste titre – comme centrale dans les différentes phases observées dans les troubles bipolaires de l’humeur. Mais au-delà, une autre dimension, plus ...psychomotrice, apparaît comme un outil de description sémiologique des états dépressifs, (hypo)manes et mixtes et des phases dites de rémission. La mesure de cette dimension psychomotrice peut faire appel à des questionnaires, des tests neuropsychologiques ou des outils d’utilisation plus récente dans le domaine des troubles bipolaires comme l’actigraphie par exemple. Nous montrerons que ces différents outils permettent de modéliser les différents états de la pathologie comme des défauts d’inhibition/activation avec différents outputs comportementaux ou cognitifs. Ces mesures permettraient par exemple de distinguer les dépressions « pures » anergiques/hypo-actives des dépressions avec composante de mixité, toutes deux observées dans le cours évolutif des troubles bipolaires. Elles permettraient aussi potentiellement d’orienter le diagnostic vers des troubles unipolaires ou d’identifier des dimensions de bipolarité. Enfin, ces dimensions d’inhibition/activation pourraient relancer le débat autour de la place centrale de la dopamine comme ces différents états des troubles bipolaires. Certains modèles récents proposent notamment la notion de « déplétion soudaine » en dopamine pour expliquer les transitions entre divers états des troubles bipolaires, caractérisés pour les uns par le ralentissement psychomoteur et ou les autres par une sur-activation psychomotrice. Nous ouvrirons les perspectives sur les possibles usages des agonistes dopaminergiques dans la prise en charge des dépressions bipolaires, alors que ces traitements ont été jusqu’à récemment considérés comme contre-indiqués du fait des risques d’inversion de l’humeur.
•Genetic and environmental factors play a role in lithium response variability.•Epigenetic mechanisms mediate the interplay between genetic and environmental factors.•Pre-existing or Li-induced ...epigenetic marks may play a role in Li response.•Epigenetic measures could shorten the time to identify lithium response status.
Lithium (Li) remains the first line long-term treatment of bipolar disorders notwithstanding a high inter-individual variability of response. Significant research effort has been undertaken to understand the molecular mechanisms underlying Li cellular and clinical effects in order to identify predictive biomarkers of response. Li response has been shown to be partly heritable, however mechanisms that do not rely on DNA variants could also be involved. In recent years, modulation of epigenetic marks in relation with the level of Li response has appeared increasingly plausible. Recent results in this field of research have provided new insights into the molecular processes involved in Li effects. In this review, we examined the literature investigating the involvement of three epigenetic mechanisms (DNA methylation, noncoding RNAs and histone modifications) in Li clinical efficacy in bipolar disorder.
Introduction
Bipolar I disorder is a mental disorder with the risk of severe clinical outcomes. Bipolar disorder was initially defined based on having a better outcome than schizophrenia. However, ...while recent longer-term findings in schizophrenia do not support neuroprogression, bipolar disorder is increasingly depicted as having neuroprogressive elements. There are, however, remarkably few prospective longitudinal studies of representative bipolar I cohorts followed from the first treatment.
Objectives
To study the clinical development of a representative cohort of bipolar disorder patients recruited at their first treatment.
Methods
Patients with DSM-IV Bipolar I or Bipolar NOS were consecutively recruited from in-and outpatient units in the larger Oslo area during their first treatment year and extensively clinically characterized at baseline. They then participated in personal one- and ten-year follow-ups.
Results
Sixty-nine patients participated in the 10-year follow-up. Age at follow-up was 39.0 (
+
9.6) years, 59% were females. A total of 12% had unipolar mania, 58% had psychotic bipolar disorder, and 20% had experienced rapid cycling. At follow-up, 75% were in full affective remission, 60% had regained full functioning, and 54% were in stable full recovery.
Mood episode relapses clustered around the first episode. Despite occasional relapses, 2/3 were mainly euthymic during the follow-up period. A small sub-group was highly affected from the first 2-3 years of treatment, but there were no apparent signs of kindling effects or indications of neuroprogression
Conclusions
The follow-up of this cohort of first-treatment Bipolar I patients does not support the hypothesis of neuroprogression.
Disclosure of Interest
None Declared
The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has ...generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.
Les déterminants pathophysiologiques des troubles bipolaires (TB) sont multiples, incluant des facteurs de susceptibilité génétique et des facteurs environnementaux. Parmi ces derniers, de nombreuses ...pistes ont été explorées parmi lesquelles la survenue de traumatismes dans l’enfance comme facteurs de prédisposition aux TB. Ces traumatismes sont évaluables rétrospectivement grâce au Childhood Trauma Questionnaire. Nous avons montré que les patients bipolaires étaient plus fréquemment exposés à des traumatismes multiples dans l’enfance que les témoins (63 % vs 33 %) et que seuls les abus émotionnels (et non les abus physiques ou sexuels) étaient associés aux TB 2. Nous avons ensuite étudié l’influence des traumatismes subis sur l’expression clinique de la maladie chez 587 patients bipolaires et ainsi montré que les abus émotionnels et sexuels étaient associés à un profil clinique plus sévère caractérisé par un âge de survenue plus précoce, la présence de tentatives de suicide, de cycles rapides et de mésusage de cannabis 3,4. Cette association entre les traumatismes affectifs et la sévérité des TB pourrait être en lien avec une impulsivité/réactivité émotionnelle plus marquée. En effet, nous avons montré que différents registres d’impulsivité (motrice ou cognitive) étaient associés à un profil de sévérité notamment en termes de conduites suicidaires (quoique discuté) et de mésusage de toxiques 3,4. Par ailleurs, il existe une corrélation entre le niveau de traumatismes dans l’enfance et celui d’impulsivité/réactivité émotionnelle à l’âge adulte 1. Les traumatismes dans l’enfance sont fréquents chez les patients bipolaires, aggravent l’expression clinique des troubles et sont associés à un profil psychopathologique caractérisé par une impulsivité/hyperréactivité émotionnelle accrue. Le repérage de ces traumatismes et des caractéristiques cliniques et dimensionnelles associées sont particulièrement pertinents à intégrer dans l’évaluation clinique du patient pour guider la prise en charge.
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