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.
Abnormalities in circadian rhythms play an important role in the pathogenesis of bipolar disorders (BD). Previous genetic studies have reported discrepant results regarding associations between ...circadian genes and susceptibility to BD. Furthermore, plausible behavioral consequences of at-risk variants remain unclear since there is a paucity of correlates with phenotypic biomarkers such as chronotypes. Here, we combined association studies with a genotype/phenotype correlation in order to determine which circadian genes variants may be associated with the circadian phenotypes observed in patients with BD. First, we compared the allele frequencies of 353 single nucleotide polymorphisms spanning 21 circadian genes in two independent samples of patients with BD and controls. The meta-analysis combining both samples showed a significant association between rs774045 in TIMELESS (OR = 1.49 95%CI1.18-1.88; p = 0.0008) and rs782931 in RORA (OR = 1.31 95%CI1.12-1.54; p = 0.0006) and BD. Then we used a "reverse phenotyping approach" to look for association between these two polymorphisms and circadian phenotypes in a subsample of patients and controls. We found that rs774045 was associated with eveningness (p = 0.04) and languid circadian type (p = 0.01), whereas rs782931 was associated with rigid circadian type (p = 0.01). Altogether, these findings suggest that these variants in the TIMELESS and RORA genes may confer susceptibility to BD and impact on circadian phenotypes in carriers who thus had lower ability to properly adapt to external cues.
Circadian rhythm disturbances have been associated with bipolar disorder (BD) during both the mood episodes and the periods of remission. Circadian phase preferences for the evening have been ...reported for remitted patients, whereas the amplitude and stability of their rhythms have never been assessed using questionnaires. The primary aim of our study was the validation of a French version of the Circadian Type Inventory (CTI), whereas its secondary aim was the comparison between remitted patients with BD and healthy controls for rhythm stability and amplitude and for phase preference. For this purpose, we used the CTI and the Composite Scale of Morningness (CSM) that assesses phase preference ("morning" or "evening" type). First, we report here on the validation of the French version of the 11-item Circadian Type Inventory in a sample of 140 remitted patients with BD and 156 healthy controls. Principal components analysis revealed a two-factor structure (FR: flexibility/rigidity scale corresponding to rhythm stability; LV: languid/vigorous scale corresponding to rhythm amplitude) explaining 52% of the variance in the control group and 47% in the bipolar group. Cronbach's alpha was 0.75 for FR and 0.73 for LV. The test-retest reliability was 0.74 for FR and 0.86 for LV (3 wks) and 0.62 for FR and 0.72 for LV (6 mos). LV and FR scores correlated with the Composite Scale of Morningness score (p < 0.00001 and p = 0.0002, respectively). Second, as compared with controls, patients with BD were more languid (p < 0.00001) and showed an evening preference (p = 0.0003), but they did not differ from the controls with regard to flexibility/rigidity. The French version of the CTI appeared to have satisfactory psychometrics characteristics. Bipolar patients exhibited not only abnormalities in phase preference but also in amplitude as measured by languidity. Since circadian rhythm dysfunction has been shown to predict poor functioning and mood relapses in interepisodic patients with BD, this tool would appear to be a promising, easy-to-use, measure of the amplitude and flexibility of circadian rhythms that could enrich the arsenal of assessments used in clinical settings.
Lifetime prevalence of child and adolescent bipolar 1 disorder (BD1) is nearly 0.1 %. Even though it is not a frequent disorder in young people, there is an increased interest for this disorder at ...this age, because of the poor outcome, the severe functional impairments and the major risk of suicide. Diagnosis is complex in view of the more frequent comorbidities, the variability with an age-dependant clinical presentation, and the overlap in symptom presentation with other psychiatric disorders (e.g. disruptive disorders in prepubertal the child and schizophrenia in the adolescent). The presentation in adolescents is very similar to that in adults and in prepubertal children chronic persistent irritability and rapid mood oscillation are often at the foreground. For a while, such presentations were considered as BD-not otherwise specified (BD-NOS), which can explain the outburst of the prevalence of bipolar disorder in children in the US. Longitudinal studies that look for the outcome of such emotional dysregulations have not revealed an affiliation with bipolar disorder spectrum, but with depressive disorders in adulthood. The diagnosis of Disruptive Mood Dysregulation Disorder was proposed in the DSM-5 to identify these children and to prevent confusion with bipolar disorder. The goals of the pharmacological and psychosocial treatments are to control or ameliorate the symptoms, to avoid new episodes or recurrences, to improve psychosocial functioning and well-being, and to prevent suicide. In the US, lithium and four atypical antipsychotics have been approved by the FDA for 10 to 13-year-olds (risperidone, olanzapine, aripiprazole and quetiapine). In France, only lithium salts (after the age of 16) and aripiprazole (after the age of 13) are recommended. Psychosocial treatments, such as a familial or individual approach are developing.
Santé physique et troubles bipolaires Zaghbib, K.; Milhiet, V.; Jamain, S. ...
Annales médico psychologiques,
February 2012, Letnik:
170, Številka:
1
Journal Article
Recenzirano
Les patients bipolaires ont un risque très augmenté de morbidité et de mortalité par rapport à la population générale. Cet aspect de la maladie est un sujet d’intérêt récent et un enjeu pronostique ...majeur. L’espérance de vie des patients bipolaires est réduite de huit à dix ans, en rapport notamment avec des événements cardiovasculaires deux à trois fois plus fréquents et survenant plus précocement. Les facteurs de risques cardiovasculaires sont aussi plus fréquents : syndrome métabolique (30 % à 79 %), surpoids et obésité (32 % à 74 %), dyslipidémie (41 %), hypertension artérielle (39 %), diabète (8 % à 26 %)… D’autres problèmes somatiques sont plus fréquents chez les patients bipolaires : la contamination par les virus VIH (virus de l’immunodéficience humaine), VHC (virus hépatite C), les cancers, les troubles du cycle veille-sommeil et des rythmes circadiens, les migraines, la sclérose en plaques… sans que les mécanismes de ces diverses associations soient complètement élucidés. Les thymorégulateurs utilisés dans les troubles bipolaires peuvent également être source de problèmes physiques et nécessitent une surveillance soignée. Des recommandations simples doivent être connues des professionnels de santé, voire des patients. Il paraît actuellement évident que la prise en charge des patients bipolaires nécessite des soins somatiques avec des points de surveillance spécifiques, cela sous la vigilance d’un partenariat psychiatre/médecin généraliste et dans une logique de prévention.
Bipolar patients have a highly increased risk of physical morbidity and mortality compared to the general population. This aspect is of major importance for the clinical management of bipolar patients. The life expectancy of bipolar patients is reduced by 8 to 10 years, particularly in relation with cardiovascular events (two to three times more common). Cardiovascular risk factors are more common: the metabolic syndrome (30% to 79%), overweight and obesity (32% to 74%), dyslipidemia (41%), hypertension (39%), diabetes (8% to 26%). Other somatic problems are associated with bipolar disorders: the contamination by HIV and HCV virus, cancers, sleep-wake cycle disorders and abnormal circadian rhythms, migraines, multiple sclerosis… The mechanism of these various associations is incomplete. Mood stabilizers used in bipolar disorders can also favor physical problems and requires careful monitoring. Physical care with specific monitoring is a part of the treatment of bipolar disorders. In that regard, a partnership between the psychiatrist and the general practitioner is a major stake for the general outcome.
Le trouble de dysrégulation émotionnelle et comportementale sévère est un nouveau diagnostic relativement peu connu. Il est intégré dans la classification du DSM 5 sous le terme de disruptive mood ...dysregulation disorder pour DMDD. Cette entité a été isolée à partir des travaux anglo-saxons sur les troubles bipolaires de l’enfant pré-pubère. Ces enfants souffrent de symptômes thymiques d’allure hypomaniaque ou dysphorique accompagnés de réactions de colères explosives ayant un retentissement important sur leur environnement familial et scolaire. Ce trouble apparaît précocement et évolue de façon chronique et non épisodique. On retrouve un mauvais contrôle émotionnel, ainsi qu’une incapacité à accéder à l’euthymie et à un attachement sécure chez ces enfants. L’objet de cet article est de rappeler les controverses qui ont conduit à l’élaboration de cette entité en particulier les travaux sur les troubles bipolaires pédiatriques. Nous avons examiné les arguments scientifiques qui plaident en faveur de son individualisation. Nous avons aussi étudié les liens avec d’autres troubles psychiatriques comorbides, dont le trouble déficitaire de l’attention avec hyperactivité. Notre discussion est illustrée par deux vignettes cliniques.
Severe mood dysregulation is a relatively new diagnosis in the field of mental health. It is included into the DSM5 classification under the term DMDD for disruptive mood dysregulation disorder. Disruptive mood dysregulation disorder has been isolated in American and British studies on children's bipolar disorders. Afflicted children typically suffer from chronic irritability i.e. dysphoric or hypomanic-like symptoms, accompanied by an explosive outburst that interferes with their ability to function at home, in school, or with their friend. These disorders appear early and have chronic, non episodic evolution. These children are also characterized by a lack of emotional control and some behavioral dysregulation, preventing them to achieve secure attachment and euthymia. This article presents an overview of diagnostic criteria, the reasons which have supported the creation of the disruptive mood dysregulation disorder, and available research on this disorder. We emphasize the controversies in literature regarding so called “peadiatric bipolar disorder”. The relations with other psychiatric comorbidities including attention deficit-hyperactivity disorder are also discussed. This review is illustrated with two case reports.
Many transmembrane receptors have a desensitized state, in which they are unable to respond to external stimuli. The family of microbial rhodopsin proteins includes one such group of receptors, whose ...inactive or dark-adapted (DA) state is established in the prolonged absence of light. Here, we present high-resolution crystal structures of the ground (light-adapted) and DA states of Archaerhodopsin-3 (AR3), solved to 1.1 Å and 1.3 Å resolution respectively. We observe significant differences between the two states in the dynamics of water molecules that are coupled via H-bonds to the retinal Schiff Base. Supporting QM/MM calculations reveal how the DA state permits a thermodynamic equilibrium between retinal isomers to be established, and how this same change is prevented in the ground state in the absence of light. We suggest that the different arrangement of internal water networks in AR3 is responsible for the faster photocycle kinetics compared to homologs.
Elastic properties of biological membranes are involved in a large number of membrane functionalities and activities. Conventionally characterized in terms of Young's modulus, bending stiffness and ...stretching modulus, membrane mechanics can be assessed at high lateral resolution by means of atomic force microscopy (AFM). Here we show that the mechanical response of biomimetic model systems such as supported lipid bilayers (SLBs) is highly affected by the size of the AFM tip employed as a membrane indenter. Our study is focused on phase-separated fluid-gel lipid membranes at room temperature. In a small tip radius regime (≈ 2 nm) and in the case of fluid phase membranes, we show that the tip can penetrate through the membrane minimizing molecular vertical compression and in absence of molecular membrane rupture. In this case, AFM indentation experiments cannot assess the vertical membrane Young's modulus. In agreement with the data reported in the literature, in the case of larger indenters (>2 nm) SLBs can be compressed leading to an evaluation of Young's modulus and membrane maximal withstanding force before rupture. We show that such force increases with the indenter in agreement with the existing theoretical frame. Finally, we demonstrate that the latter has no influence on the number of molecules involved in the rupture process that is observed to be constant and rather dependent on the indenter chemical composition.
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