Search

International audience; Background: The FACE-BD cohort is an observational cohort of individuals with bipolar disorders (BD) who benefited from a systematic evaluation with evidence-based treatment recommendations and who were followed-up every year for 3 years in France. The objectives were to describe the lifetime course of BD, associated psychiatric and somatic comorbidities, and cognition profile. This cohort aims to identify clinical/biological signatures of outcomes, trajectories of functioning and transition between clinical stages. This article summarizes 10 years of findings of the FACE-BD cohort.Method & results: We included 4422 individuals, all having a baseline assessment, among which 61.2% had at least one follow-up visit at either one, two or three years. A subsample of 1200 individuals had at least one biological sample (serum, plasma, DNA). Assessments include family history of psychiatric disorders, psychiatric diagnosis, current mood symptoms, functioning, hospitalizations, suicidal attempts, physical health, routine blood tests, treatment history, psychological dimensions, medico-economic data and a cognitive assessment. Studies from this cohort illustrate that individuals with BD display multiple coexistent psychiatric associated conditions including sleep disturbances, anxiety disorders, substance use disorders and suicide attempts as well as a high prevalence of metabolic syndrome. During follow-up, we observed a 55% reduction of the number of days of hospitalization and a significant improvement in functioning.Conclusions: The FACE-BD cohort provides a strong research infrastructure for clinical research in BD and has a unique position among international cohorts because of its comprehensive clinical assessment and sustainable funding from the French Ministry of Health.

International audience; Objective: To examine which characteristics predict the time to a first mood recurrence at three years in Bipolar Disorder type I (BD-I) and type II (BD-II). Methods: Individuals with BD were followed up to 3 years. Turbull's extension of the Kaplan-Meier analysis for interval-censored data was used to estimate the cumulative probability of recurrence over time. Separate models were performed according to BD subtype to determine which baseline factors were predictive of recurrences and were adjusted for age, gender and educational level. Results: We included 630 individuals with BD-I and 505 with BD-II. The first recurrence of any polarity occurred earlier in BD-II (p = 0.03). The first depressive recurrence occurred earlier in BD-II (p < 0.0001), whereas the first (hypo)manic recurrence occurred earlier in BD-I (p = 0.0003). In BD-I, the clinical variables that were associated to the time to a first mood recurrence were depressive symptoms, lifetime rapid cycling, global activation and the number of psychotropic medications at baseline. In BD-II, the time to a first recurrence was associated with a younger age at onset of BD and a higher number of lifetime mood episodes. The Areas Under the Curve for both models were moderate. Conclusion: Predictors of recurrences showed few specificities to BD-I or BD-II. The ability to predict recurrences in BD based on socio-demographic and clinical variables remained too moderate for a transfer in daily practice. This study highlights the need for further studies that would include other types of predictors, such as molecular, cognitive or neuro-imaging ones, to achieve an accurate level of prediction of recurrences in BD.

International audience; Objective: In addition to heredity, exposure to early-life adversity is an important predisposing risk factor of suicidal behaviour. Although the association between Childhood Trauma (CT) and suicide risk is well documented, interactions between CT and suicidal behaviour in Treatment-Resistant Depression (TRD) populations have received little coverage. This study aimed to evaluate i) association between CT and suicidal behaviour in a TRD population, and ii) the role of personality traits and impulsiveness as potential factors of mediation in these associations.Methods: Patients were recruited from a cohort of the French network of TRD expert centers. Depressive symptom severity, CT, suicidal behaviour, personality traits, and impulsiveness were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), the Childhood Trauma Questionnaire (CTQ), the Columbia Suicide Severity Rating Scale (CSSRS), the Structured Clinical Interview for DSM-IV, the Big Five Inventory, and the Barratt Impulsivness Scale (BIS) respectively.Results: Among the 256 patients with a baseline CTQ, in relation to suicide risk for the current depressive episode, we found an association with the total CTQ scores mediated by the intensity of the current episode in a model adjusted for age and sex (total effect: β = 0.171; p = 0.011, direct effect: β = 0.135; p = 0.043; indirect effect: β = 0.036; p = 0.048). Focusing on CT subtypes, we detected an association between suicide risk and physical neglect in a model adjusted for age and sex (β = 0.301; p = 0.002), without any mediation by the intensity of the current episode. There was no mediation effect from personality traits nor impulsiveness. With regards to CSSRS to assess suicidal ideation, we did not find any association with the total CTQ score and CT subtype scores.Conclusion: We report a strong association between suicidal behaviour and CT (in particular childhood physical neglect) in a TRD population.

International audience; Background: Epidermal necrolysis is a rare and severe cutaneous adverse reaction to drugs with long-term somatic consequences and potentially underrecognized psychological complications.Objectives: To assess the prevalence and risk factors of post-traumatic stress disorder (PTSD) in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a population of adults undergoing psychiatric evaluation.Methods: In this prospective study, we included adult patients admitted at the acute phase of SJS/TEN to our dermatology department from June 2009 to February 2013. The main objective was to assess the prevalence of PTSD at 6 months after the acute disease phase, defined by a PTSD Checklist score > 44. Secondary objectives were to investigate risk factors of PTSD in the medical history of patients and characteristics of the disease at the acute phase by the Peritraumatic Dissociative Experience Questionnaire (PDEQ) and Peritraumatic Distress Inventory (PDI) and the degree of impairment on the Sheehan Disability Scale.Results: We initially included 32 of 80 patients admitted during the study period. At 6 months, seven of 30 still followed up had a PTSD Checklist score > 44, suggesting a PTSD prevalence of 23%; 23 (77%) patients had a hydroxyzine prescription at the acute phase. The main risk factors associated with PTSD at 6 months were psychological results at the acute phase.Conclusions: Despite frequent prescription of hydroxyzine at the acute phase, almost one-quarter of patients with SJS/TEN had PTSD at 6 months. A systematic psychiatric evaluation should be offered regularly for at least 1 year after the acute disease phase.

Introduction La nephrotoxicite precoce des sels de lithium au cours du trouble bipolaire reste hypothetique. L’objectif de cette etude etait d’identifier les determinants du debit de filtration glomerulaire mesure (DFGm) et la valeur diagnostique de l’IRM renale dans la detection precoce de la nephrotoxicite. Description 217 patients adultes consecutifs traites par lithium ont ete systematiquement evalues avec une mesure de DFG. Methodes Une IRM renale etait realisee chez 99 patients avec sequences type echo de spin demi Fourier et echo de spin a train d’echos. Resultats L’âge median etait de 51 [27-62] ans, et la duree mediane de traitement par lithium etait de 5 [2-14] ans. 52 % des patients presentaient une MRC stade 2. En analyse multivariee, les determinants d’un DFGm plus bas etaient une duree de traitement plus longue (β −0,8 [−1 ; −0,6] ml/min/1,73m2 pour chaque annee de traitement), un âge plus eleve (β −0,4 [−0,6 ; −0,3] ml/min/1,73m2 pour chaque annee), l’albuminurie (β −3,97 [−6,6 ;−1,3], p = 0,003), l’hypertension (β −6,85 [−12,6 ;−1,1], p = 0,02) et l’hypothyroidie (β −7,1 [−11,7 ;−2,5], p = 0,003). La lithemie n’etait pas associee au DFGm. En IRM, des microkystes renaux etaient detectes chez 51 % des patients, des un an de traitement. Le DFGm et la duree de traitement par lithium etaient fortement correles chez les patients ayant des microkystes (r = −0,64, p Fig. 1 ). Conclusion Outre les facteurs de risque connus de MRC, la duree de traitement par lithium impactait fortement le DFG independamment de l’âge, particulierement en presence de microkystes. L’hypothyroidie etait aussi independamment associee a la fonction renale. L’IRM renale pourrait donc detecter la nephrotoxicite precoce et irreversible du lithium et aider quant aux strategies preventives.

Background Postpartum period is associated with an increased risk of bipolar disorder diagnosis and relapse, mainly major depressive episode. Onset during this period might be associated with specific characteristics. Aim To compare the socio-demographic and clinical characteristics of parous women presenting with bipolar disorder and an index depressive episode occurring during or outside the postpartum period. Methods Using the multicenter cohort FACE-BD (FondaMental Academic Centers of Expertise for Bipolar Disorders), we considered all women who started their BD with a major depressive episode and have at least one child. We compared two groups depending on the onset: in or outside the postpartum period. Results Among the 759 women who started BD with a major depressive episode, 93 (12.2%) had a postpartum onset, and 666 (87.8%) had not. Women who started BD in the postpartum period with a major depressive episode have a more stable family life, more children, an older age at onset, more Bipolar 2 disorder, less history of suicide attempts, less depressive episodes and more mood stabilizer treatments as compared to those who started with a major depressive episode outside the postpartum period. The multivariable logistic regression showed that women with an onset in the postpartum period had significantly more children, less lifetime depressive episodes and a lower rate of history of suicide attempts as compared to women with an onset outside the postpartum period. Discussion Our results suggest that women starting their BD with postpartum depression have a more favorable course of BD, especially less history of suicide attempt and less lifetime depressive episodes.

Tolerance profile of the antidepressants. (DOCX 147 kb)

organisation, expert panel, questionnaire development and data analysis. (DOCX 21 kb)

Questionnaire. (DOCX 1090 kb)

Definitions (According to the American College of Neuropsychopharmacology) [47]. (DOCX 14 kb)

Antidepressant treatments classified according to the pharmacological profile. (DOCX 14 kb)

Cannabis use, as well as the prevalence of cannabis use disorder, are not known among the population attending general practices in France. We wanted to describe the characteristics of current cannabis users, estimate cannabis use disorder and self-rating of cannabis dependence, and describe medical conditions associated with cannabis use in a general practice in Paris.An anonymous questionnaire was proposed to every patient aged 18-65 in a general practice during three months from June to August 2014. Cannabis use in the last six months was recorded and cannabis use disorder was assessed according to three different means: answering yes to the question: do you feel like you are dependent on cannabis? or answering yes to the question: do you smoke cannabis in the first 5minutes after awakening? or CUDIT score≥8 points.Two hundred and fifty-eight questionnaires were analyzed. Cannabis use in the past six months was found in 54 subjects (21%). Subjective feeling of cannabis dependence was endorsed by 18 subjects (6.9%). Cannabis use in the first 5minutes after awakening was found in five subjects (1.9%) and 23 (8.9%) had a CUDIT score≥8 points. Cannabis smokers had more often addictive and psychiatric associated medical conditions.General practitioners could ask about cannabis use and self-rated cannabis use disorder because it is frequent and patients with cannabis use disorder deserve specific care.

International audience; BACKGROUND: This study aims at testing for paths from childhood abuse to clinical indicators of complexity in bipolar disorder (BD), through dimensions of affective dysregulation, impulsivity and hostility. METHOD: 485 euthymic patients with BD from the FACE-BD cohort were included from 2009 to 2014. We collect clinical indicators of complexity/severity: age and polarity at onset, suicide attempt, rapid cycling and substance misuse. Patients completed questionnaires to assess childhood emotional, sexual and physical abuses, affective lability, affect intensity, impulsivity, motor and attitudinal hostility.RESULTS: The path-analysis demonstrated significant associations between emotional abuse and all the affective/impulsive dimensions (p < 0.001). Sexual abuse was moderately associated with emotion-related dimensions but not with impulsivity nor motor hostility. In turn, affect intensity and attitudinal hostility were associated with high risk for lifetime presence of suicide attempts (p < 0.001), whereas impulsivity was associated with a higher risk of lifetime presence of substance misuse (p < 0.001). No major additional paths were identified when including Emotional and Physical Neglect in the model.CONCLUSIONS: This study provides refinement of the links between early adversity, dimensions of psychopathology and the complexity/severity of BD. Mainly, dimensions of affective dysregulation, impulsivity/hostility partially mediate the links between childhood emotional to suicide attempts and substance misuse in BD.

Resume L’existence de difficultes cognitives durant les phases d’etat des troubles bipolaires (episodes maniaques depressifs, maniaques, hypomaniaques et mixte) est demontree depuis longtemps et a fait l’objet de nombreuses etudes. L’existence de deficits cognitifs durant les periodes intercritiques ont fait l’objet de moins d’etudes, lesquelles ont longtemps produit des resultats difficiles a interpreter du fait de la faible taille des echantillons et de la non prise en compte de facteurs de confusion influencant les performances cognitives (symptomes residuels, comorbidites, âge…). Plus recemment, des etudes ont permis de documenter tres clairement l’existence de deficits de memoire (en particulier verbale), d’attention et des fonctions executives durant les periodes intercritiques des patients bipolaires. En outre, plusieurs etudes prospectives et meta-analyses indiquent que ces deficits sont associes au fonctionnement des patients et ce de meme apres prise en compte des symptomes residuels thymiques. Le developpement de modules specifiques de prise en charge faisant appel aux techniques de remediation cognitive constitue donc un enjeu majeur. Ces deficits pourraient etre des marqueurs de vulnerabilite a la pathologie bipolaire, mais pourraient egalement constituer des « cicatrices » cognitives des episodes thymiques majeurs.

En France, il est rapporte une tentative de suicide toutes les 40 secondes et un deces par suicide toutes les 40 minutes. Premiere cause de mortalite entre 15 et 45 ans, les conduites suicidaires sont identifiees comme une priorite de sante publique depuis les annees 1990. Les maladies mentales (dont la depression, la schizophrenie et les addictions) ainsi que les antecedents personnels et familiaux de conduites suicidaires representent des facteurs de risque majeurs. Le depistage et la prise en charge des sujets en crise suicidaire et/ou suicidants participent a la prevention des recidives. Les recommandations de bonnes pratiques font de l’hopital, et en particulier des services d’urgences, un lieu incontournable ou une prise en charge pluridisciplinaire est possible. De cela decoule la necessite d’organiser une filiere de soins depuis l’accueil jusqu’a l’orientation, en passant par une triple evaluation somatique, psychologique et sociale. La mise en place d’un projet de soins hospitaliers et/ou d’un suivi ambulatoire intensif doit etre ajustee a chaque situation. La formation des generalistes au depistage et a la prise en charge des personnes suicidaires et/ou souffrant de depression est essentielle. Il en est de meme des equipes travaillant aux urgences ou dans les services de crises avec dans certains lieux, des specialisations dans l’accueil des adolescents suicidants ou des personnes âgees. Les urgences sont aussi, dans un grand nombre de cas, le premier contact avec la psychiatrie. La qualite de l’accueil, des premiers soins, des liens avec les differents intervenants hospitaliers et avec les structures d’aval conditionnent l’adhesion de la personne a la prise en charge ulterieure, garantissent la continuite des soins et contribuent a prevenir les recidives.

Suicidal behaviors are common in the general population and are so a major public health problem. In order to improve suicide prevention and to reduce the mortality by suicide, it appears essential to better identify suicide risk factors. Seasonality, circadian rhythms and sleep abnormalities have been already associated with numerous psychiatric disorders. This review aimed to characterize the associations between seasonality, circadian rhythms, sleep and suicidal behaviors including suicide attempts and completed suicides.We conducted a literature search between 1973 and 2015 in PubMed databases using the following terms: ("suicide" OR "suicidality" OR "suicide attempts" OR "suicidal behavior") AND ("circadian rhythms" OR "seasons" OR "sleep").Many studies confirm a specific seasonality for suicide with a higher peak of suicides in spring for both sex and a lower peak in autumn especially for women. This distribution seems to correlate with depressive symptoms (especially for the autumn peak), gender and different types of suicide. Regarding gender and type of suicide differences, males more commonly commit violent suicide with a higher rate of suicides in spring. Suicide behaviors appear to be influenced by climatic and biological factors like sunshine, daylight cycles, temperature, air pollutants, viruses, parasites and aeroallergens. Circadian variations exist in suicide rates depending on age with a morning peak for elder and an evening peak for youth. In addition, completed suicide peak in early morning whereas suicide attempts peak rather in later afternoon. Several biomarkers dysregulation like melatonin, serotonin and cortisol may be implicated in suicide circadian variations. Furthermore, specific sleep disorders like insomnia, nightmares and sleep deprivation are common risk factors of suicide and possibly independently of the presence of depressive symptoms. Finally, the efficacy of chronotherapeutics (such as luminotherapy, dark therapy, sleep deprivation and melatonin drugs) has been suggested in the reduction of suicidal behaviors.The suicide seasonality is very well documented showing a main peak in spring and another one in autumn. A suicide circadian distribution also exists depending of the suicidal behavior intensity and of the age. Numerous sleep disorders are also suicide risk factors and can be treated with chronotherapeutics. A better identification of seasonality, circadian rhythms and sleep abnormalities in suicidal behaviors could allow a better prevention in suicidal attempts and a reduction in death by suicide.

L’etude de l’evolution et du pronostic du trouble bipolaire s’appuie sur une importante litterature faite d’etudes a court et long terme. Ces etudes ont permis d’objectiver la frequence des symptomes residuels invalidants, la difficulte a obtenir des remissions prolongees chez de nombreux patients, l’existence de troubles cognitifs d’aggravation progressives et la tres grande frequence de pathologies psychiatriques et somatiques comorbides, qui font du trouble bipolaire une maladie chronique handicapante. Ces etudes ont egalement permis de montrer la tres grande heterogeneite du trouble bipolaire du point de vue de l’evolution et du pronostic. La connaissance des profils evolutifs du trouble bipolaire apparait donc un enjeu majeur pour la prise en charge des patients au long cours et pour le developpement de recherches qui permettront de valider des strategies de prevention des differents facteurs qui grevent le pronostic de ces patients.

International audience; Background: The aim of our study was to investigate, in bipolar patients, the association between tobacco status (use and dependence) and history of suicide attempt, and to assess the possible role of inflammation as a missing link in the association between smoking status and history of suicide attempt. Methods: A total of 453 adult bipolar outpatients recruited in the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were divided into two subgroups: 274 patients without past history of suicide attempt (non-SA), and 179 patients with a past history of suicide attempt (SA). Tobacco use and dependence, psychiatric and somatic comorbidities, history of childhood abuse, family history of suicide were assessed. Fasting blood tests yielded samples collected for the measurement of high sensitivity (hs-)CRP. Results: The risk of suicide attempt increased with smoking dependence. Notably, bipolar patients with a history of suicide attempt were three times more likely to have severe tobacco dependence, independently of confounding factors. However, we failed to find arguments promoting the hypothesis of inflammatory markers (through hs-CRP measure) in the link between tobacco dependence and suicidal behavior. Conclusions: We found a significant association between severe tobacco dependence and history of suicide attempt, but not with level of CRP, independently of confusing factors. Longitudinal studies taken into account all these potential confusing factors are needed to confirm our results.

Bipolar disorder is a complex disease which requires multiple healthcare resources and complex medical care programs including pharmacological and non pharmacological treatment. If mood stabilizers remain the corner stone for bipolar disorder treatment, the development of atypical antipsychotics and their use as mood stabilizers has significantly modified therapeutic care. At the present time, psychiatrists have a large variety of psychotropic drugs for bipolar disorder: mood stabilizers, atypical antipsychotics, antidepressants, anxiolytics… However, despite the publication of guidelines on pharmacological treatment, with a high degree of consensus, everyday clinical practices remain heterogeneous. Moreover, there are few longitudinal studies to describe therapeutic management of bipolar disorder, whatever the phase of the disease is. Indeed, most of the studies are carried out on a specific phase of the disease or treatment. And there is no study comparing French and European practices.In this paper, we aim to present the comparison of the management of pharmacological treatments of bipolar disorder between France and Europe, using the data of the observational Wide AmbispectiVE study of the clinical management and burden of bipolar disorder (WAVE-bd study).The WAVE-bd study is a multinational, multicentre and non-interventional cohort study of patients diagnosed with BD type I or type II, according to DSM IV-TR criteria, in any phase of the disorder, who have experienced at least one mood event during the 12 months before enrolment. In total, 2507 patients have been included across 8 countries of Europe (480 in France). Data collection was retrospective (from 3 to 12 months), but also prospective (from 9 to 15 months) for a total study length of 12 to 27 months. Main outcome measures were the healthcare resource use and pharmacological treatments.Our results show differences in the therapeutic management of bipolar disorder between France and other European countries. Regarding healthcare resource use, our results show that French patients consult more frequently a psychiatrist or a psychologist and less frequently a general practitioner or the emergency ward in comparison with patients from other European countries. In the whole European population, including France, atypical antipsychotics are widely used. Only 25% of the patients receive lithium and more than 50% of the patients receive antidepressants, while their use in bipolar disorder remains controversial. Most of the patients receive polymedication. Considering all phases of the disease pooled, less lithium and less atypical antipsychotics are prescribed to French patients, whereas they receive more antidepressants and more benzodiazepines than patients from other European countries. On the over hand, prescription of anticonvulsants and electroconvulsive therapy are equal. Moreover, data analyses by polarity of the episodes globally confirm these trends. There are a few exceptions: mixed states, in which lithium is twice more prescribed in France in comparison to other countries; depressive states, in which antidepressants are even more prescribed in other countries than in France; and less prescription of anticonvulsants in manic, mixed and euthymic phases in France.The WAVE-bd study is the first observational study conducted on a large sample of bipolar I and II patients that compares therapeutic management between France and other European countries. The differences observed in therapeutic care across the different phases of the disease show that treatments differ depending on the countries studied, but also according to the preventive or curative phases, polarity of the bipolar disorder, comorbidities, impact of guidelines, and care organization. Although French patients have been treated by less lithium and less atypical antipsychotics than other European patients, they receive more antidepressants and more benzodiazepines. Finally, patients generally receive polymedication and the diversity in prescriptions shows how bipolar disorder is a complex disorder.

Studies have shown that patients with borderline personality disorder are often misdiagnosed to have bipolar disorder and conversely. Indeed, a number of characteristics common to both disorders could explain this problem: emotional instability as well as impulsivity represent confounding factors and contribute to the risk of misdiagnosis. However, it appears that these characteristics manifest themselves in different ways according to the pathology. The aim of the study is to show differences between affective lability, emotional intensity and impulsivity dimensions. The clinical aim is to refine bipolar disorder and borderline personality disorder diagnosis, to improve psychological care for these patients in the long-term.We compared the emotional and impulsive dimensions in two groups of patients: a group of 21 patients with bipolar disorder and a group of 19 patients with borderline personality disorder. Tools: ALS, a self-report questionnaire to evaluate affective lability, AIM, a self-report questionnaire to see affective intensity, and UPPS, a self-report questionnaire to measure impulsivity according to several dimensions.The results indicate that borderline patients scored significantly higher than bipolar patients at the ALS and AIM scales. Regarding the UPPS, borderline patients scored significantly higher than bipolar patients for the dimensions "lack of premeditation" and "lack of perseverance"; however, bipolar patients had significantly higher scores than borderline patients for the dimension "negative emergency".This study shows that bipolar disorder and borderline personality can be differentiated thanks to emotional dimensions as well as different dimensions of impulsivity: borderline patients appear to have an affective lability and intensity more important than bipolar patients; it also appears that impulsivity manifests itself differently according to the disorder.

ResumenObjetivo:Como algunos perfiles de temperamento pueden ser marcadores de rasgos de vul-nerabilidad genética, tratamos de comparar la búsqueda de sensaciones en pacientes bipolares eutímicos y en controles.Métodos:Se incluyó en este estudio a 194 pacientes que cumplían los criterios diagnóstics del DSM-IV para trastornos bipolares (TB), 81% de los cuales presentaban TB de tipo I, y a 95 controles. La eutimia se evaluó utilizando tanto la MADRS como la escala de manía de Bech. Se evaluó a los sujetos utilizando la forma abreviada francesa de la Escala de Búsqueda de Sensaciones de Zuckerman (SSS), que proporciona una puntuación total (PT) y cuatro subpuntuaciones: Búsqueda de emociones y aventuras (BEA), Búsqueda de experiencias (BE), Desinhibición (Des) y Susceptibilidad al aburrimiento (SA).Resuhados:La puntuación total de la SSS difirió significativamente entre los hom-bres (17,2 ± 0,5) y las mujeres (15,3 ± 0,6) (P = 0,02), y todas las subpuntuaciones correlaciona’ron nega-tivamente con la edad. En el ajuste para el sexo y la edad, encontramos que los pacientes bipolares te-nían una puntuación de Des elevada (P = 0,003). Sin embargo, si el mismo análisis se realizaba con los antecedentes vitales de abuso o dependencia de alcohol como covariable, esta diferencia no se encontra-ba (P = 0,436). La SSS demostró un alto grado de fiabilidad test-retest (ICC = 0,91).Conclusión:Estos resultados indican que la búsqueda de sensaciones evaluada con la SSS no es una característica del temperamento asociada con los trastornos bipolares, pero está relacionada en cambio con una tendencia hacia el abuso de alcohol.

ResumenLa elevada comorbilidad entre el trastorno bipolar y la dependencia de alcohol puede tener explicaciones diferentes, una de las cuales es la existencia de factores genéticos comunes para los dos trastornos. Es posible que estén implicados varios genes candidatos, pero los que actúan en la vía dopa-minérgica pueden estarlo más específicamente. Así, hemos examinado el papel del gen que codifica el receptor D2 de dopamina (alelo Al Taql) en la vulnerabilidad potencialmente compartida a la dependencia de alcohol y el trastorno bipolar. Se seleccionó a 122 pacientes franceses (durante dos genera-ciones al menos) sobre la base de los ficheros hospitalarios u ambulatorios y se los entrevistó con la DIGS. Las frecuencias del alelo Al se compararon entre cuatro grupos, a saber: pacientes bipolares con dependencia de alcohol comórbida (n = 21), pacientes bipolares sin morbilidad de alcohol (n = 31), pacientes con dependencia de alcohol sin trastorno del estado de ánimo (n = 35) y controles no afecta-dos (n = 35). El equilibrio de Hardy-Weinberg para los genotipos Al Taql del DRD2 se respetó para la muestra como un todo, y para cada submuestra. Observamos que el 42,9% de los sujetos de control tie-nen un alelo Al al menos, una frecuencia que no difiere significativamente de la observada en la muestra afectada como un todo (39,1%), ni de la frecuencia de los pacientes con dependencia de alcohol (37,1%), los pacientes con trastorno bipolar (48,4%) o los pacientes con dependencia de alcohol y trastorno bipolar (28,6%). El análisis de regresión basado en las tres variables (trastorno bipolar, dependencia de alcohol e interacción entre estos dos trastornos) no explica la presencia del alelo Al del gen del DRD2. Así, no encontramos datos para un papel significativo del alelo Al del gen del receptor D2 de dopamina en la asociación específica entre el trastorno bipolar y la dependencia de alcohol en nues-tra muestra.

Health care seeking for a problematic use of cannabis is in progress in France.The aim is to assess the addictive and psychiatric comorbidity in cannabis users seen in the specific setting at the Lariboisière hospital.Two hundred and seven cannabis users were included from January 2004 to December 2009. Twelve-month and lifetime diagnosis of abuse and dependence (cannabis, alcohol, cocaine/crack) (DSM-IV), current and lifetime mood disorders, anxiety disorders, eating disorders and psychotic disorders were assessed (Mini-International Neuropsychiatric Interview). Logistic regression analyses identified adjusted odds ratios associated with the gender and the health care seeking (P=0.01).One hundred and forty-seven men (71%) and 60 women (29%), 29.3±8.6 years (15.2-51.6 years). Most of the outpatients ask for health care themselves (59.7%), whereas 19.4% are asked to seek health care by relatives (19.4%) or because of an academic, health or justice injunction (20.4%). In total, 49.3% of the outpatients are single, 35.7% are cohabitating, 9.3% are married and 6.3% are separated/divorced. About 20.4% of the outpatients are students, 35.7% have a professional activity, 19% are jobless, 2.4% are impaired, 0.5% are retired, at home and 12.1% do not have an official income. Twelve-month and lifetime prevalence of abuse/dependence are: cannabis (10.1/82.1% and 8.7/88.4%), alcohol (9.7/8.7% and 19.3/18.8%), cocaine/crack (2.4/3.4% and 4.8/11.6%). The mean duration of cannabis dependence for the current dependent users is 8.4±5.8 years. The mean number of "joints" during the last 6 months is 6±4.3, the mean amount of cannabis per week is 12.5±11.3g. About 51.3% of the dependent users report externalized and/or internalized disorders at school during childhood and adolescence. In total, 19.4% of the dependent users have a suicide attempt history and 18.9% have a psychiatric hospitalisation history, more frequently women (P0.01 and P=0.02). About 73.8% have a psychologist or psychiatrist care history. In total, 38.1% of users have at least one current mood disorder, females more frequently than males (P0.001). Current and lifetime prevalence of mood disorders are: major depressive disorder (MDD) (29.1% and 57.1%); current dysthymia (20.3%); hypomania (1.9 and 6.7%); mania (2.9 and 12.8%). Females have more frequently than males current and lifetime MDD (P0.001). About 53.2% of users have at least one current anxiety disorder, females more frequently than males (P0.001). Current and lifetime prevalence of anxiety disorders are: panic disorder (10 and 16.4%); agoraphobia (13.9 and 17.4%); social phobia (26.9 and 32.8%); obsessive-compulsive disorder (9.5 and 12.9%); post-traumatic stress disorder (PTSD) (6.5 and 16.4%); current generalized anxiety disorder (26.8%). Females have more frequently current and lifetime: agoraphobia (P=0.01 and P0.001); PTSD (P0.001); current social phobia (P=0.049). Current and lifetime eating disorders prevalence are: anorexia (0 and 1.5%); bulimia (4 and 8%); females more frequently have bulimia (P=0.02 and P0.001). In total, 4.8% have a psychotic disorder. Adjusted odds ratios of associated variables to gender (women/men) are lifetime MDD OR=4.71 [2.1-10.61] (P0.001) and later age of onset of cannabis abuse OR=1.1 [1.04-1.17] (P=0.002). Adjusted odds ratios associated with personal health care seeking compared to a non personal motivated health care seeking are the numbers of criteria of 12-month cannabis dependence OR=1.26 [1.06-1.51] (P=0.009) and age OR=1.07 [1.03-1.12] (P=0.002).Our survey confirms the high mood and anxiety disorders comorbidity in cannabis dependent users seen in a specific setting and underlines the need to evaluate those disorders.

International audience; 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.

Introduction La toxicite chronique du lithium comporte une baisse du DFG, un syndrome polyuro-polydipsique (SPP), et/ou une hypercalcemie a PTH inadaptee. Nous avons etudie ces troubles dans une cohorte de patients d’un centre expert des troubles bipolaires. Patients et methodes Chez 78 patients (51 ± 15 ans, 37 % d’hommes) sous lithium depuis 3 mois a 45 ans, nous avons mesure le DFG (clairance du CrEDTA), l’osmolarite urinaire maximale apres 12 h de restriction hydrique puis injection de ddAVP (OsmUMax), la calcemie ionisee (Ca) et la PTH avant et apres charge calcique IV. Les patients ont ete repartis selon la duree de traitement : G1 ( n = 16), G2 (1–5 ans ; n = 20), G3 (5–15 ans ; n = 20), G4 (> 15 ans ; n = 22). Resultats Le DFG est de 95, 79, 72 et 53 mL/min/1,73 m 2 pour G1, G2, G3, et G4 ( p 2 . En regression multiple, le DFG est correle, de facon independante, a la duree de traitement (–0,98 mL/min/1,73 m 2 /an, p 2 /an, p 3L/j) est present chez 26 % des patients (31, 20, 15 et 36 % de G1 a G4, p = ns). Chez ces patients (vs ceux sans SPP), l’OsmUmax (mOsmol/Kg) est de 776 (vs 738), 616 (vs 717), 519 (vs 627) et 296 (vs 530), la charge osmolaire (CO, en mOsmol/j) de 999 (vs 560), 803 (vs 580), 726 (vs 610), 699 (vs 663), de G1 a G4 ( p p p p Discussion La baisse du DFG attribuable au lithium, independamment de l’âge, est d’environ 1 mL/min/1,73 m 2 /an. Le SPP est d’apparition precoce, lie surtout a la CO au stade precoce et au diabete insipide nephrogenique au stade tardif. La frequence et l’intensite de l’hypercalcemie augmentent avec la duree d’exposition, alors que la freination provoquee de la PTH diminue, suggerant une autonomisation de l’anomalie de la relation Ca/PTH. Conclusion Dans notre cohorte, le SPP et l’hypercalcemie apparaissent precocement apres initiation du lithium, meme si leur severite s’accentue avec le temps. La baisse du DFG est progressive, et fortement correlee a la duree d’exposition au lithium.

An accurate treatment of first episodes in schizophrenia and bipolar disorders has a significant impact on compliance and prognosis. However, existing therapeutic guidelines may be poorly respected and may concern only typical clinical situations. Medical attitudes in clinical practice have been collected and structured on the basis of small interactive meetings (Focus Group [FG]), and a synthesis of practical attitudes has been compared with updated guidelines. The FG method applied to treatment initiation in schizophrenia and bipolar disorder is seen as complementary to evidence-based guidelines. It reveals that, in a reflexive manner, clinical attitudes are often more diverse and frequently consider first treatments after global evaluation, taking more into account external factors such as clinicians' experience, patient's history and willingness, clinical setting, and environment. A symptomatic approach is sometimes preferred, and a better alliance is always considered as a main objective. The FG method could be a supplementary support to continuous medical education.

The existence of cognitive deficits during the acute phases of bipolar disorder (manic, depressive, hypomanic or mixed episodes) has long been demonstrated and by numerous studies. The existence of cognitive deficits during euthymic periods has been much less studied. In addition, these studies are hampered by several methodological difficulties (small sample sizes, confounding factors influencing cognitive performance such as residual symptoms, comorbidities, age.. not considered). More recently, several studies have clearly documented the existence of memory deficits (especially, verbal), attention and executive function during euthymic periods in bipolar patients. In addition, several prospective studies and meta-analyses suggest that these deficits independent predictors of the functional. Thus the development of specific cognitive remediation programs is a major stake. These deficits may be markers of vulnerability to bipolar disorder, but may also reflect the cognitive « toxicity » of major mood episodes.

In recent decades our knowledge of the molecular mechanisms of biological clocks has grown expontentially. This has helped to guide the choice of genes studied to explain inter-individual variations seen in circadian rhythms. In recent years analysis of circadian rhythms has advanced considerably into the study of pathological circadian rhythms in human beings. These findings, combined with those obtained from studying mice whose circadian genes have been rendered incapable, have revealed the role of genetic factors in circadian rhythms. This literature review presents an overview of these findings. Beyond our understanding of the functioning of these biological clocks, this knowledge will be extremely useful to analyse genetic factors involved in morbid conditions involving circadian rhythm abnormalities.

Il existe une variabilité inter-individuelle importante dans la réponse aux traitements antidépresseurs (AD), associée à des taux de non-répondeurs qui restent préoccupant (environ 40 %) et à une difficulté à prédire précisément quel patient va répondre à quel traitement. Le développement de biomarqueurs prédictifs de la réponse aux AD constitue donc un enjeu majeur pour l’amélioration de la prise en charge des patients. Ce symposium propose un état des lieux et des illustrations du développement d’une médecine personnalisée dans le domaine des troubles de l’humeur. Le professeur P. Courtet présentera une synthèse des données cliniques et épidémiologiques qui justifient le développement d’une médecine personnalisée dans les troubles de l’humeur et présentera des illustrations. Un premier exemple concerne les idées et conduites suicidaires qui sont fortement associées à la dépression. L’aggravation des idées suicidaires au cours d’une cure d’antidépresseur est un phénomène qui reste mal connu, bien que largement amplifié par les récentes mises en garde et controverses. Si au niveau populationnel, l’utilisation des antidépresseurs est bénéfique pour la prévention du suicide, certains sujets peuvent présenter un risque suicidaire en début de traitement. Il s’agit d’œuvrer pour mieux les identifier et les prendre en charge. Sur une cohorte de 3800 patients déprimés traités par antidépresseur, Nicolas Ramoz présentera les résultats de l’étude des gènes associés, d’une part, à la réponse thérapeutique et d’autre part, à l’apparition ou l’aggravation des idées suicidaires au cours de ce traitement. Enfin, nous disposons maintenant de techniques permettant d’analyser la signature moléculaire dans le sang circulant de patient de différents phénotypes. C’est cette technique qu’a appliqué le Dr Raoul Belzeaux pour rechercher les biomarqueurs associés au phénomène de réponse thérapeutique et d’aggravation des idées suicidaire au cours d’une cure d’antidépresseur.

To evaluate psychological status in consecutive survivors of ICU who needed mechanical ventilation (MV).Prospective study.Twenty-four bed intensive care unit.Fifty-four mechanically ventilated patients were considered for the study; 43 patients were included, but 11 refused or were unable to fill in the form.A 32-question form was filled out by the patients 48-96 hours after weaning from mechanical ventilation.The mean characteristics of the patients were: age 51.6 years, simplified acute physiologic score (SAPS) 14, organ system failure (OSF) 1.57, OMEGA score 277, length of stay 29 days, length of mechanical ventilation 14 days. Thirty-three required sedation, 30 analgesia, 20 paralysis. The results were as follows: Pain: 13 suffered intolerable pain with a mean intensity of pain during care of 3.5/10. Comfort: 25 felt an inability to communicate, 18 were bothered by noise and 15 by light, while nine feared to be abandoned by staff. Sleep disorders: 28 remember dreaming with a personal judgement about these dreams (0 = pleasant, 10 = nightmare) of 7.6/10; 17 noticed increasing sleep disorders during their stay. Anxiety: 22 felt diffuse anxiety disorder and 16 described intense fear of dying at least once. Mood: 38 felt physical depression and 18 intellectual depression. Delirium or confusion: 33 had delirium or a confused state at the time of weaning and nine suffered hallucinations. Nine correctly appreciated their length of stay and 18 knew the date when they were interviewed.These results showed that psychological status is poor in ventilated ICU patients, which should be considered in their care.

CONFUSIONAL STATE IN ICU PATIENTS AFTER. WEANING FROM MECHANICAL VENTILATION AND SEDATION. F Pochard, JJ Lanore, M Belghith, JP Mira, B Renaud, F Bellivier, I Hamy, JF Vax; laire, F Brunet, JF Dhainaut. Confusional state (CS) is known to be frequent in ICU pts. It can result in a poorer prognosis at time of weaning from mechanical ventilation (MV). The aim of this study was to prospectively assess the incidence of CS in pts requiring MV and sedation during more than 24 hours, at time of weaning. Thirty-three survivor pts, Age 48.3, SAPS 15.4, OSF 1.7, OMEGA score 34a, were consecutively included. Reason for admission to ICU was acute lung injury (20), cardiac failure (5), septic shock (3), other (5). Length of MV was 17 days. Pharmacological agents used were flunitrazepam for narcose (33 pts, 35 mg/d, 11 d) and phenoperidine for analgesia (30 pts, 39 mg/d, 12 d). Neither pt had psychosis previous history, nor neurological disease. Fourteen pts suffered CS, defined as the onset of at least 2 of the following signs: disorientation, anxiety, auditory or visual hallucinations, agitation, clouding of consciousness, incoherence, perceptive disturbances, sleep disorders, after weaning from MV. No CS appeared in the 10 pts who had sedation during less than 5 days; in the other23 pts, incidence of CS was 64 % (p < .001). No metabolic etiology was found. The incidence of CS is high in ICU patients when weaning from MV and sedation; this incidence increases with the duration of MV. It should be treated with neuroleptics drugs. Further studies should be performed, in order to consider prevention of CS.

L ’analyse de la composante genetique de traits complexes comme le diabete, certains cancers, les maladies coronariennes ou les demences de type Alzheimer a considerablement beneficie des progres conjoints de la biologie moleculaire et de l’epidemiologie genetique. Les premiers ont conduit a la caracterisation d’un tres grand nombre de marqueurs balisant l’ensemble du genome, les seconds ont permis le developpement de nouvelles methodes d’analyse adaptees a l’etude des maladies complexes. L’enthousiasme ainsi engendre a rapidement atteint la psychiatrie biologique, legitimement renforcee par la publication des 1979 des premiers resultats positifs d’etudes de liaison [1] : on pouvait enfin esperer comprendre l’agregation familiale et progresser dans l’analyse etiopathogenique des maladies psychiatriques telles que la psychose maniaco-depressive (PMD) et la schizophrenie. Mais le bilan, a la fin des annees 1990, est marque par une certaine confusion autant pour les troubles de l’humeur que pour la schizophrenie. En effet, depuis 1987, 14 localisations chromosomiques ont ete suggerees pour d’eventuels genes de susceptibilite a la PMD et au moins 8 pour la schizophrenie (Tableaux I et II), mais aucun de ces resultats n’a ete replique de maniere convaincante [2]. Cette situation a engendre une reflexion sur le choix des methodes de genetique epidemiologique adaptees a l’analyse des traits complexes [3, 4] et, plus recemment, sur l’approche phenotypique en psychiatrie. En effet, le formidable essor de la biologie moleculaire et de la genetique epidemiologique contraste avec le peu d’attention portee aux approches cliniques en psychiatrie. Il s’agit pourtant d’un point important qui pourrait rendre compte de cette situation confuse. Peu d’etudes ont, en effet, cherche a apprecier la « validite » genetique de la nosographie psychiatrique telle qu’elle est evaluee par les criteres diagnostiques des differentes classifications internationales (DSM, ICD, RDC). Dans cet article, nous montrons comment les incertitudes qui entourent la definition clinique des maladies peuvent contribuer a l’echec relatif des etudes de genetique en psychiatrie. Nous decrirons successivement les differents niveaux d’incertitude associes a la definition actuelle des maladies psychiatriques et nous presenterons deux strategies alternatives qui pourraient permettre l’identification d’entites cliniques plus appropriees a l’analyse de la composante genetique.

International audience; Bipolar disorders are severe and complex psychiatric disorders and lithium remains one of the most effective drugs for relapse prevention. Despite its effectiveness, prescription of lithium therapy can be complicated because of its narrow therapeutic range. Furthermore, adherence to treatment is generally low. One means of improving adherence would be to make the patient an actor of his/her treatment. The possibility to control the lithium level with a device that can be used at home would favor this involvement. Although the main part of the work to produce a device is research and development, regulatory analysis, including usability, should not be neglected. Indeed, some design choices should be made taking into account usability constraints. This ensure the fabrication of a device which will be safe, effective and well accepted by the intended users. In this conference, we present actions taken in this direction during the R-Link project.