Phénotypes circadiens dans les troubles bipolaires (rythmes veille-sommeil et activité motrice diurne mesurés par actigraphie)

La présente thèse s inscrit à la jonction des modèles physiopathologiques génétiques et circadiens des troubles bipolaires. Elle s intéresse plus particulièrement à la caractérisation phénotypique des rythmes veilles-sommeil et de l activité motrice diurne par actigraphie. Au préalable, nous définissons les rythmes circadiens et décrivons l horloge endogène principale. Nous procédons ensuite au démantèlement génotypique et phénotypique des caractéristiques circadiennes dans les troubles bipolaires. Nous nous focalisons sur la mesure des phénotypes circadiens par actigraphie. Puis nous présentons une étude méthodologique caractérisant cinq techniques de dépouillement du signal actigraphique dans les troubles bipolaires. Un intérêt particulier a porté sur le temps dédié au dépouillement et le degré de subjectivité inhérent à chaque méthode. La seconde étude compare des paramètres actigraphiques entre des patients bipolaires euthymiques (n=23), et des patients insomniaques (n=21), dans une démarche de caractérisation de la dimension sommeil. Les relations dans le groupe bipolaire entre mesures actigraphiques, thymie, qualité du sommeil subjectif et qualité de vie ont été explorées, l activité diurne apparaissant significativement corrélée à la qualité subjective du sommeil. Ce résultat laisse concevoir l activité motrice diurne comme une cible thérapeutique pertinente de l amélioration du sommeil dans les troubles bipolaires.Enfin, nous faisons part des différentes thérapeutiques qui découlent d une approche chronobiologique des troubles bipolaires et proposons des pistes de recherches futures.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Espoirs et créations de la psychiatrie de secteur

Dans un entretien filmé accordé à de jeunes collègues, Jacques Fortineau retrace ici quelques unes des grandes lignes qui ont imprimé la traversée de plus de quarante années de pratique psychiatrique. Il restitue le contexte qui a vu naître sa vocation psychiatrique et les filiations qui l’ont porté. Au fil du discours, il dépeint le paysage du secteur psychiatrique en construction, où se font écho petite et grande histoire. Se dessinent alors les frontières annonçant la scission entre neurologie et psychiatrie. Au travers de cette trajectoire se définit une mise en perspective historique de la psychiatrie les années 1960 à nos jours, qui vient alimenter les débats actuels entre politique et psychiatrie, entre psychanalyse et neurobiologie

Sleep in remitted bipolar disorder: a naturalistic case-control study using actigraphy.

International audienceINTRODUCTION: Findings from actigraphic studies suggesting that sleep and circadian rhythms are disrupted in bipolar disorder (BD) patients have been undermined by methodological heterogeneity and the failure to adequately address potential confounders. METHOD: Twenty-six euthymic BD cases and 29 healthy controls (HC), recruited from University Paris-Est and matched for age and gender, were compared on subjective (Pittsburgh Sleep Questionnaire Inventory; PQSI) and objective (mean scores and variability in actigraphy) measures of sleep as recorded by over 21 consecutive days. RESULTS: Multivariate generalized linear modelling (GLM) revealed significant differences between BD cases and HC for five PSQI items (total score and four subscales), four actigraphy variables (mean scores) and five actigraphy variability measures. Backward stepwise linear regression (BSLR) indicated that a combination of four variables (mean sleep duration, mean sleep latency, variability of the fragmentation index over 21 days, and mean score on PSQI daytime dysfunction sub-scale) correctly classified 89% of study participants as cases or controls (Chi-square=39.81; df=6; p=0.001). LIMITATIONS: The sample size (although larger than most actigraphy studies) and incomplete matching of cases and controls may have influenced our findings. It was not possible to control for potential effects of psychotropic medication or differences in employment status between groups. CONCLUSIONS: When potential confounders of sleep and circadian profiles are adequately taken into account (particularly age, gender, daytime sleepiness, mood symptoms, body mass index, and risk of sleep apnoea), a selected subset of quantitative (mean scores) and qualitative (variability) features differentiated euthymic BD cases from HC

An ASMT variant associated with bipolar disorder influences sleep and circadian rhythms: a pilot study.

International audiencePatients with bipolar disorder (BD) experience persistent circadian rhythm and sleep abnormalities during periods of remission, and biological studies have shown that these patients have abnormal melatonin secretion profiles or reactivity to light. We previously reported the association with BD of a common polymorphism (rs4446909) of the promoter of the acetylserotonin O-methyltransferase (ASMT) gene, encoding one of the two enzymes involved in melatonin biosynthesis. This variant was associated with weaker transcription and lower levels of ASMT activity in lymphoblastoid cell lines. Actigraphy, based on the use of a mobile portable device for the analysis of sleep/wake cycles in natural conditions, may be useful for studies of carriers of the at-risk allele. We studied the association between the ASMT rs4446909 variant and sleep/activity, as assessed with the Pittsburgh Sleep Quality Index (PSQI) and by actigraphy, in 53 subjects (25 patients with BD in remission and 28 healthy controls). The two groups were similar for age, sex ratio, current mood symptoms, body mass index and risk of sleep apnea syndrome. In the total sample, the GG at-risk genotype was associated with longer sleep duration (P = 0.03), greater activity in active periods of sleep (P = 0.015) and greater interday stability (P = 0.003). These associations remained significant when disease status was included in the model. Only the association with interday stability remained significant after correction for multiple testing. This pilot study thus shows that a BD-associated functional variant involved in the melatonin synthesis pathway influences sleep and circadian rhythms in bipolar patients in remission and controls

Bipolar disorder with seasonal pattern: clinical characteristics and gender influences.: Bipolar patients with seasonal pattern

International audienceBipolar disorder (BD) has a multifactorial etiology with heterogeneous clinical presentations. Around 25% of BD patients may present with a depressive seasonal pattern (SP). However, there are limited scientific data on the prevalence of SP, its clinical manifestations, and any gender influence. Four hundred and fifty-two BD I and II cases (62% female), recruited from three French university-affiliated psychiatric departments, were assessed for SP. Clinical, treatment, and sociodemographic variables were obtained from structured interviews. One hundred and two (23%) cases met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for SP, with similar frequency according to gender. Multivariate analysis showed a significant association between SP and BD II (odds ratio [OR] = 1.99, p = 0.01), lifetime history of rapid cycling (OR = 2.05, p = 0.02), eating disorders (OR = 2.94, p = 0.003), and total number of depressive episodes (OR = 1.13, p = 0.002). Seventy-one percent of cases were correctly classified by this analysis. However, when stratifying the analyses by gender, SP was associated with BD II subtype (OR = 2.89, p = 0.017) and total number of depressive episodes (OR = 1.21, p = 0.0018) in males but with rapid cycling (OR = 3.02, p = 0.0027) and eating disorders (OR = 2.60, p = 0.016) in females. This is the first study to identify different associations between SP and clinical characteristics of BD according to gender. The authors suggest that SP represents a potentially important specifier of BD. These findings indicate that seasonality may reflect increased severity or complexity of disorder