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Objectives Bipolar Disorder (BD) is frequently comorbid with other psychiatric disorders. However, few studies systematically examine which disorders are more likely to occur pre- or post-BD onset. We examine the prevalence and Age At Onset (AAO) of psychiatric conditions in adults with BD. Methods A structured clinical interview was used to assess lifetime history and AAO of alcohol and cannabis misuse, suicide attempts, anxiety and eating disorders in a French sample of euthymic patients with BD (n = 739). Regression analyses were used to test for statistically significant associations between rates and AAO of comorbidities in BD groups stratified by sex or subtype. Results Prevalence of alcohol and cannabis misuse was associated with male sex and BD-I subtype; whilst most anxiety and eating disorders were associated with female sex. The AAO of most comorbid conditions preceded that of BD, except for panic disorder, agoraphobia and alcohol misuse. Few variations were observed in AAO of comorbidities according to groups. Limitations All assessments were retrospective, so estimates of prevalence rates and especially exact AAO of some comorbidities are at risk of recall bias. Conclusions Sex and BD subtype are associated with different rates of comorbid disorders. However, there were minimal between group differences in median AAO of comorbidities. By describing the chronological sequence of comorbidities in BD we were able to demonstrate that a minority of comorbidities typically occurred post-onset of BD. This is noteworthy as these disorders might be amenable to interventions aimed at early secondary prevention.

Purpose Brain positron emission tomography using 18F-fluorodeoxyglucose (18FDG-PET) provides a metabolic assessment of brain function that is useful for differential diagnosis among several neurodegenerative diseases manifested by cognitive impairment (CI) [1] , [2] , [3] . The purpose of the study is to describe the pattern of 18FDG-PET abnormalities in patients with CI related to alcohol use disorder. Methods Patients admitted to the addiction medicine department of a university hospital in Paris between January 2017 and October 2018 with a confirmed diagnosis of alcohol-related cognitive impairment (ARCI) or Wernicke encephalopathy (WE) were included. Brain 18FDG-PET uptake was measured after at least one month of monitored abstinence from alcohol. Standardized uptake values (SUV) were obtained for 13 regions of interest (ROI) and normalized to the pons. Individual patients’ ROI Z-scores were calculated from healthy sex- and age-matched controls provided by Cortex ID software. A principal component analysis (PCA) on the subjects’ ROIs SUV ratios was conducted. Results Twenty-five patients were included in the analysis (20 males and 5 females; mean age 57.6 years [45 – 76 years old]). The group consisted of 19 ARCI and 6 WE cases. The mean hypometabolism was most severe in the prefrontal medial cortex (PFM) (−2.80 [± 1.30]), the prefrontal lateral cortex (−2.20 [± 1.35]), and the anterior cingulate cortex (ACC) (−2.24 [± 1.19]). Hypometabolism (Z-score Table 1 ). Other regions were also affected (with 5.32/13 hypometabolic ROIs on average [SD = 4.16, range 0 – 13]). The Z-scores in the 13 ROIs did not differ significantly between the ARCI and WE patients (P ≥ 0.05). The PCA identified two principal components. The first principal component explains 59.49% of the variance and it is formed by the clustering of six specific ROIs: sensorimotor cortex, parietal superior cortex, parietal inferior cortex, precuneus, occipital lateral cortex and primary visual cortex. The second explains 14.52% of the variance and it is formed by three ROIs: the PFM, ACC and temporal mesial cortex. Conclusions Predominant prefrontal and cingulate cortex hypometabolism was the most frequent brain 18FDG-PET pattern in our sample of patients with ARCI and WE. We believe that brain 18FDG-PET could be a potential imaging biomarker of ARCI, and predictive values for both differential diagnosis and prognosis should be prospectively tested.

Objective To examine which combination of objectively measured actigraphy parameters best characterizes the sleep-wake cycle of euthymic individuals with bipolar disorder (BD) compared with healthy controls (HC). Methods Sixty-one BD cases and 61 matched HC undertook 21 consecutive days of actigraphy. Groups were compared using discriminant function analyses (DFA) that explored dimensions derived from mean values of sleep parameters (Model 1); variability of sleep parameters (2); daytime activity (3); and combined sleep and activity parameters (4). Exploratory within-group analyses examined characteristics associated with misclassification. Results After controlling for depressive symptoms, the combined model (4) correctly classified 75% cases, while the sleep models (1 and 2) correctly classified 87% controls. The area under the curve favored the combined model (0.86). Age was significantly associated with misclassification among HC, while a diagnosis of BD-II was associated with an increased risk of misclassifications of cases. Conclusion Including sleep variability and activity parameters alongside measures of sleep quantity improves the characterization of cases of euthymic BD and helps distinguish them from HC. If replicated, the findings indicate that traditional approaches to actigraphy (examining mean values for the standard set of sleep parameters) may represent a suboptimal approach to understanding sleep-wake cycles in BD.

Summary Intranasal naloxone aims at preventing opioid overdose related deaths in active drug users. In France, it has been available since July 2016 through a temporary approval which requires a hospital-based pharmacy and a nominative registration of each patient. We present the characteristics of the first patients who could receive this prescription in our hospital-based addiction center and how they used naloxone during follow-up. Results favor a larger dispensing of naloxone. Patients’ as well as peers’ and families’ education is needed.

International audience; 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.

International audience; Bipolar disorder (BD) is a chronic and burdensome psychiatric disease, characterized by variations in mood and energy. The literature has consistently demonstrated an association between BD and childhood maltreatment (CM), and genetic variants of circadian genes have been associated with an increased vulnerability to develop BD. In this context, environmental factors such as CM may also contribute to the susceptibility to BD through alterations in the functioning of the biological clock linked to modifications of expression of circadian genes. In this study, we explored the associations between childhood maltreatment, sleep quality, and the level of expression of a comprehensive set of circadian genes in lymphoblastoid cell lines from patients with BD. The sample consisted of 52 Caucasian euthymic patients with a diagnosis of BD type 1 or type 2. The exposure to CM was assessed with the Childhood Trauma Questionnaire (CTQ), and the sleep quality was assessed using the Pittsburgh Sleep Quality Index. We measured the expression of 18 circadian genes using quantitative RT-PCR: ARNTL2, BHLHE40, BHLHE41, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, DBP, GSK3B, NPAS2, NR1D1, PER1, PER2, PER3, PPARGC1A, RORA, and RORB. Gene expression networks were analyzed with the disjoint graphs method. Compared to the other investigated transcripts, PPARGC1A was the only one whose expression level was differentially affected in patients who have experienced CM and, more specifically, physical abuse. We observed no significant effects of the other CTQ subscores (emotional and sexual abuses, physical and emotional neglects), nor of the sleep quality on the network of circadian genes expression. Although requiring replication in larger cohorts, the result obtained here is consistent with the hypothesis of an influence of CM exposure on circadian systems and highlights the importance of PPARGC1A in these processes.

Aims Establishing the minimum clinically important difference (MCID) in functioning and cognition is essential to the interpretation of the research and clinical work conducted in bipolar disorders (BD). The present study aimed to estimate the MCID for the Functioning Assessment Short Test (FAST) and a battery of neuropsychological tests in BD. Methods Anchor-based and distributive methods were used to estimate the MCID for the FAST and cognition using data from a large, multicentre, observational cohort of individuals with BD. The FAST and cognition were linked with the Clinical Global Impressions Scale-Severity (CGI-S) and Global Assessment of Functioning (GAF) using an equipercentile method. The magnitude of the standard error measurement (s.e.m.) provided another estimate of the MCID. Results In total, 570 participants were followed for 2 years. Cross-sectional CGI-S and GAF scores were linked to a threshold ⩽7 on the FAST for functional remission. The MCID for the FAST equalled 8- or 9-points change from baseline using the CGI-S and GAF. One s.e.m. on the FAST corresponded to 7.6-points change from baseline. Cognitive variables insufficiently correlated with anchor variables (all ρ s.e.m. for cognitive variables corresponded to a range of 0.45 to 0.93-s.d. change from baseline. Conclusions These findings support the value of the estimated MCID for the FAST and cognition and may be a useful tool to evaluate cognitive and functional remediation effects and improve patient functional outcomes in BD. The CGI-S and GAF were inappropriate anchors for cognition. Further studies may use performance-based measures of functioning instead.

International audience; Background: Valproate is associated with teratogenic and neurodevelopmental effects. Several agencies have restricted the conditions of its prescription in bipolar disorders (BD). We aimed to assess the evolution of valproate prescription and the clinical profile of BD women of childbearing age receiving valproate. Methods: Based on a large national cohort, we included all BD women 16–50 years old. Sociodemographic, clinical and pharmacological data were recorded. Logistic regression analyses were used to describe variables associated with valproate prescription. Results: Of the 1018 included women 16–50 years old, 26.9% were treated with valproate with a mean daily dosage of 968 mg. The prevalence of BD women using valproate was 32.6% before May 2015 and 17.3% after May 2015 (p

International audience; Background Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. Method The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. Results The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. Conclusion These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

Objective:To examine any association of birth decade, sex and exposure to alcohol and/or substance use disorders (ASUD) with age at onset (AAO) of bipolar I disorder (BD-I).Methods:Using data from a representative clinical sample of 3896 BD-I cases recruited from 14 European countries, we examined AAO distributions in individuals born in consecutive birth decades. Cumulative probabilities with Mantel-Cox log-rank tests, pairwise comparisons and Odds Ratios (OR) with 95% confidence intervals (95% CI) were employed to analyze AAO according to birth decade, sex, and presence or absence of an ASUD.Results:In the total sample, median AAO of BD-I decreased from about 41 years for those born in the 1930s to about 26 years for those born in the 1960s. In a sub-sample of 1247 individuals (selected to minimize confounding), AAO significantly decreased for males and females born in each consecutive decade between 1930 and 50 (OR: 0.65; 95% CI: 0.51, 0.81), and for cases with an ASUD as compared to without (OR: 0.77, 95% CI: 0.69, 0.87). The best fitting regression model identified an independent effect for each birth decade and an interaction between ASUD status and sex, with a consistently earlier AAO in males with an ASUD (OR: 0.79: 95% CI: 0.70, 0.91).Conclusions:In BD-I cases diagnosed according to internationally recognized criteria and recruited to pan-European clinical observational studies, the AAO distributions are compatible with a birth cohort effect. A potentially modifiable risk factor, namely ASUD status, was associated with the observed reduction in AAO, especially in males.

Resume Les patients atteints du trouble de la personnalite borderline sont souvent diagnostiques a tort comme ayant un trouble bipolaire et inversement. En effet, un certain nombre de caracteristiques communes aux deux troubles pourraient expliquer ce probleme : l’instabilite affective ainsi que l’impulsivite representent des facteurs de confusion et contribuent au risque de mauvais diagnostic. Cependant, ces caracteristiques se manifestent de manieres differentes selon la pathologie. Les dimensions emotionnelles et impulsives de 40 patients (21 patients presentant un trouble bipolaire et 19 patients presentant un trouble de la personnalite borderline) ont ete comparees a l’aide des echelles ALS, AIM et UPPS. Les patients borderline obtiennent des scores significativement plus eleves que les patients bipolaires aux echelles ALS et AIM. En ce qui concerne l’UPPS, les patients borderline presentent des scores significativement plus eleves que les patients bipolaires aux dimensions « manque de premeditation » et « manque de perseverance » ; en revanche, les patients bipolaires ont obtenu des scores significativement plus eleves que les patients borderline a la dimension « urgence negative ». Cette etude montre que l’on peut differencier le trouble bipolaire du trouble de la personnalite borderline grâce aux dimensions affectives ainsi qu’aux differentes dimensions de l’impulsivite.

BACKGROUND: The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) and its components in a cohort of French patients with treatment-resistant depression (TRD) and to determine correlations with sociodemographic, clinical, and treatment-related factors. METHODS: From 2012 to 2018, 205 patients who met DSM-IV criteria for major depressive episode with moderate-to-severe symptoms (Montgomery-Asberg Depression Rating Scale score ≥ 20), and at least Stage II resistance according to Thase and Rush criteria were enrolled in the FondaMental Advanced Centers of Expertise in Resistant Depression (FACE-DR) cohort. Data on sociodemographic and clinical characteristics, lifestyle information, and treatment and comorbidities were collected, and a blood sample was drawn. MetS was defined according to the criteria of the International Diabetes Federation. RESULTS: Overall, 38% of individuals with TRD met criteria for MetS. The frequency of MetS was significantly higher in men than in women only for patients aged 40 years or older (46.3% vs 35.2%, P = .0427). Moreover, whereas the management for diabetes was good, less than one-third of the patients with high blood pressure or dyslipidemia were treated for these conditions. Multivariate analysis showed that individuals with abnormal plasma c-reactive protein levels had a 3-fold increased risk (95% CI, 1.5-5.2) of having MetS, independent of other potential confounders. CONCLUSION: The prevalence of MetS is higher in patients with TRD than in those with other psychiatric disorders and characterized by a considerable undertreatment of some components of MetS in this population. Diagnosis and treatment of the components of MetS should be systematically performed to prevent the occurrence of cardiovascular diseases in patients with TRD. These findings highlight the need for integrated care, with more interaction and coordination between psychiatrists and primary care providers.

Background Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. Method Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians’ opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. Results The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. Conclusion The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations. Electronic supplementary material The online version of this article (10.1186/s12888-019-2237-x) contains supplementary material, which is available to authorized users.

Rationnel La cocaine est la deuxieme drogue illicite la plus utilisee en France et en Europe, mais il n’existe pas de traitement de substitution, et la majorite des patients rechutent apres un sevrage. Il n’existe pas de marqueurs predictifs de la reussite du sevrage qui puissent etre mesures a l’entree. Parmi les facteurs cognitifs qui influencent la rechute dans les addictions, on compte notamment le biais attentionnel vers la substance, c’est-a-dire la tendance a faire plus attention aux stimuli lies a la substance [1] , [2] . On compte egalement la flexibilite cognitive, c’est-a-dire la capacite a changer de comportement pour s’adapter aux changements de l’environnement [3] . Objectif Nous avons voulu tester la valeur predictive de deux mesures cognitives, le biais attentionnel vers la cocaine et la flexibilite cognitive, dans le maintien d’abstinence de cocaine apres sevrage. Methodes Sujets des patients (n = 52) hospitalises pour un sevrage de cocaine a l’hopital Fernand-Widal (Paris) ont participe a cette etude. Design de l’etude Dans les 48 heures suivant l’entree en hospitalisation, nous avons mesure le biais attentionnel par une tâche de Stroop adaptee a la cocaine, et la flexibilite cognitive par une tâche de renversement d’apprentissage. Les patients ont ensuite ete suivis de facon prospective dans les 3 mois suivant la sortie. Analyse statistique Pour le Stroop, exprime comme un ralentissement du temps de reponse des patients lors de l’exposition a des indices rappelant la cocaine, l’association avec la duree d’abstinence sera testee par une correlation de Spearman. Pour le renversement d’apprentissage, exprime par une probabilite de changement immediat de strategie apres un feedback negatif, l’association avec la duree d’abstinence sera testee par une correlation de Spearman. Resultats attendus Sur les 52 sujets evalues a l’entree en sevrage, 38 ont ete suivi prospectivement jusqu’au bout des trois mois, et le temps moyen d’abstinence apres la sortie etait de 28 ± 32 jours. Les resultats des tâches cognitives seront discutes en fonction de la litterature.

Introduction En population generale, les facteurs genetiques associes au THADA de l’enfant sont de mieux en mieux decrits par des etudes genes candidats, des etudes portant sur des zones d’interet du genome ainsi que des etudes d’association pan genomiques (GWAS). Vingt et un genes d’interet ont ete retrouves parmi les publications les plus recentes sur le sujet. Dans la population de patients presentant un trouble de l’usage de substances (TUS), 20 % presentent un diagnostic de THADA de l’adulte et 10 % des adultes presentant une addiction a la cocaine ont des criteres cliniques stricts de THADA. Notre hypothese est que le trouble d’usage de substance et le THADA partagent des facteurs de risques genetiques communs. Aucune etude n’a encore ete publiee sur des facteurs de risque genetiques dans ces populations. Objectif Explorer les facteurs de risque genetique de syndrome de THADA dans une population de sujets poly-toxicomanes. Materiel et methode Sujets : 333 sujets poly-toxicomanes en soins. Mesure : histoire des consommations de substances, echelle WURS 25-items et echelle ASRS 6-items. Genotypage sur puce Illumina* PsychArray 1.1. Statistiques : association genes candidats : 911 snp retenus, regression lineaire pour le score total a la WURS et regression logistique pour le score superieur ou non au seuil clinique publie pour l’ASRS avec un p significatif choisi a 10−5. Association pan genomique : 251 531 snps retenus avec regression lineaire pour le score total a la WURS et un p significatif choisi a 10−8. Resultats Dans l’analyse gene candidat, le variant rs3784956 situe sur le gene CDH13 codant pour une cadherine est significativement associe au score total a la WURS (p = 5,07 × 10−5). La proteine codee par ce gene joue un role dans la croissance axonale lors des processus de differenciation neurale. Dans l’analyse d’association pan genomique, nous ne retrouvons pas de variants genetiques passant le seuil de significativite de 10−8. Conclusion Ce phenotype specifique de syndrome de TAHDA chez les patients poly-toxicomanes est soumis a une variabilite genetique. Parmi les genes associes dans la litterature au TDAHA de l’enfance le CDH13 semble particulierement interessant. Nous repliquons 1 des associations genetiques de la litterature.

Intranasal naloxone aims at preventing opioid overdose related deaths in active drug users. In France, it has been available since July 2016 through a temporary approval which requires a hospital-based pharmacy and a nominative registration of each patient. We present the characteristics of the first patients who could receive this prescription in our hospital-based addiction center and how they used naloxone during follow-up. Results favor a larger dispensing of naloxone. Patients' as well as peers' and families' education is needed.

Resume Les conduites suicidaires sont frequentes en population generale et sont un probleme majeur de sante publique. Dans l’objectif d’une meilleure prevention des conduites suicidaires et d’une reduction globale de la mortalite par suicide, il apparait crucial d’identifier les facteurs de risque de la vulnerabilite suicidaire. Cette revue a pour but de faire le point sur l’influence de la saisonnalite, des rythmes circadiens, et du sommeil sur les conduites suicidaires. Les donnees demontrent l’existence de variations saisonnieres des taux de suicides et des moyens utilises avec un pic principal de suicides au printemps et un second pic en automne qui semble correler avec les symptomes depressifs. Cette saisonnalite du suicide subit l’influence de facteurs climatiques et biologiques dont des anomalies de secretion de la melatonine, du cortisol et de la serotonine. Une distribution journaliere des tentatives de suicides et des suicides aboutis laissent suggerer l’implication de certains genes et biomarqueurs circadiens dans la vulnerabilite suicidaire. Par ailleurs, il existe des troubles du sommeil specifiques aux comportements suicidaires, parfois isoles de toute symptomatologie depressive, ainsi qu’une efficacite dans la suicidalite de certaines therapies centrees sur le sommeil et les rythmes circadiens. Ainsi, une meilleure identification de la saisonnalite, des rythmes circadiens et du sommeil dans les conduites suicidaires pourrait permettre une meilleure prevention du passage a l’acte suicidaire.

Major depression represents among the most frequent psychiatric disorders in the general population with an estimated lifetime prevalence of 16-17%. It is characterized by high levels of comorbidities with other psychiatric conditions or somatic diseases as well as a recurrent or chronic course in 50 to 80% of the cases leading to negative repercussions on the daily functioning, with an impaired quality of life, and to severe direct/indirect costs. Large cohort studies have supported that failure of a first-line antidepressant treatment is observed in more than 60% of patients. In this case, several treatment strategies have been proposed by classical evidence-based guidelines from internationally recognized scientific societies, referring primarily on: I) the switch to another antidepressant of the same or different class; II) the combination with another antidepressant of complementary pharmacological profile; III) the addition of a wide range of pharmacological agents intending to potentiate the therapeutic effects of the ongoing antidepressant medication; IV) the association with appropriate psychological therapies; and, V) the use of non-invasive brain stimulation techniques. However, although based on the most recently available data and rigorous methodology, standard guidelines have the significant disadvantage of not covering a large variety of clinical conditions, while currently observed in everyday clinical practice. From these considerations, formalized recommendations by a large panel of French experts in the management of depressed patients have been developed under the shared sponsorship of the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) and the Fondation FondaMental. These French recommendations are presented in this special issue in order to provide relevant information about the treatment choices to make, depending particularly on the clinical response to previous treatment lines or the complexity of clinical situations (clinical features, specific populations, psychiatric comorbidities, etc.). Thus, the present approach will be especially helpful for the clinicians enabling to substantially facilitate and guide their clinical decision when confronted to difficult-to-treat forms of major depression in the daily clinical practice. This will be expected to significantly improve the poor prognosis of the treatment-resistant depression thereby lowering the clinical, functional and costly impact owing directly to the disease.

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10−7) and PKP4 (P=8.67 × 10−7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10−3]), SCZ (rg=0.34 [P=4.37 × 10−5]) and MDD (rg=0.57 [P=1.04 × 10−3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.

OBJECTIVE: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder.METHOD: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density.RESULTS: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001).CONCLUSION: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.

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.

Resume Le trouble bipolaire (TB) est un trouble severe de l’humeur (2 % de la population generale, sixieme cause de handicap, 50 % des cas avant 21 ans) caracterise par un taux eleve de recurrences (70 a 80 % de rechutes en moyenne a deux ans et malgre le traitement). Le lithium est le traitement de reference pour la prevention de ces rechutes. L’evaluation de cette efficacite prophylactique (espacement et diminution de l’intensite des rechutes) necessite plusieurs annees de traitement continu (au minimum deux ans). Quarante pour cent des patients traites par lithium n’ont pas un cours evolutif ameliore de la maladie, ce qui pourrait etre lie a des connaissances insuffisantes concernant la forme retard (Li LP) essentiellement utilisee : (i) aucune etude pharmacocinetique (PK) de l’adulte, du lithium plasmatique n’est disponible pour le Li LP dont la fourchette therapeutique (mesuree a 12 heures) est fondee sur des correspondances approximatives avec les lithiemies cibles du lithium a liberation immediate (taux residuel), (ii) aucune etude pharmacodynamique (PD) contributive (efficacite prophylactique) n’a permis de valider la fourchette therapeutique utilisee en pratique courante. Les mecanismes de transport du Li au travers de la barriere hemato-encephalique (BHE) sont le siege de regulations qui sont mal connues mais il existe des arguments qui suggerent fortement une plasticite de cette derniere sous l’influence du Li. Dans cet article, nous passons en revue les developpements necessaires de la recherche qui permettront de mieux comprendre les mecanismes qui sous-tendent cette variabilite de la reponse au lithium.

Auditory verbal hallucinations are a cardinal symptom of schizophrenia. Bleuler and Kraepelin distinguished 2 main classes of hallucinations: hallucinations heard outside the head (outer space, or external, hallucinations) and hallucinations heard inside the head (inner space, or internal, hallucinations). This distinction has been confirmed by recent phenomenological studies that identified 3 independent dimensions in auditory hallucinations: language complexity, self-other misattribution, and spatial location. Brain imaging studies in schizophrenia patients with auditory hallucinations have already investigated language complexity and self-other misattribution, but the neural substrate of hallucination spatial location remains unknown. Magnetic resonance images of 45 right-handed patients with schizophrenia and persistent auditory hallucinations and 20 healthy right-handed subjects were acquired. Two homogeneous subgroups of patients were defined based on the hallucination spatial location: patients with only outer space hallucinations (N = 12) and patients with only inner space hallucinations (N = 15). Between-group differences were then assessed using 2 complementary brain morphometry approaches: voxel-based morphometry and sulcus-based morphometry. Convergent anatomical differences were detected between the patient subgroups in the right temporoparietal junction (rTPJ). In comparison to healthy subjects, opposite deviations in white matter volumes and sulcus displacements were found in patients with inner space hallucination and patients with outer space hallucination. The current results indicate that spatial location of auditory hallucinations is associated with the rTPJ anatomy, a key region of the “where” auditory pathway. The detected tilt in the sulcal junction suggests deviations during early brain maturation, when the superior temporal sulcus and its anterior terminal branch appear and merge.

International audience; Genetic factors, specially those related to serotoninergic activities, and childhood maltreatment have both been implicated in suicidal behaviour (SB). However, little attention has been paid to the possible interaction between genes and childhood maltreatment in the comprehension of SB. Brain-derived neurotrophic factor (BDNF) plays an important role in the growth of serotoninergic neurons during childhood and therefore is a good candidate for studies on SB. Moreover, decreased levels of BDNF have been found in the prefrontal cortex of suicide victims. In our study we wanted to see if Val66Met (a BDNF functional single-nucleotide polymorphism) could moderate the effect of childhood maltreatment on the onset, number and violence of SB in a sample of 813 Caucasian suicide attempters. Childhood maltreatment was evaluated using the Childhood Trauma Questionnaire. We used a regression framework to test the interaction between Val66Met and childhood maltreatment. Childhood sexual abuse was associated with violent suicide attempts (SA) in adulthood only among Val/Val individuals and not among Val/Met or Met/Met individuals (P = 0.05). The severity of childhood maltreatment was significantly associated with a higher number of SA and with a younger age at onset of suicide attempt. This result suggests that Val66Met modulates the effect of childhood sexual abuse on the violence of SB. It is proposed that childhood sexual abuse elicits brain structural modifications through BDNF dysfunction and enhances the risk of violent SB in adulthood.

ResumenObjetivo.El deterioro de la capacidad de toma de decisiones es un rasgo importante de los trastornos psiquiátricos. En una población numerosa con diversas enfermedades psiquiátricas exploramos la relación entre el deterioro de los procesos de toma de decisiones y las variables clínicas.Métodos.Usamos la Tarea de Apuestas de lowa (lowa Gambling Task) para medir la capacidad de toma de decisiones en 317 pacientes. Los diagnósticos psiquiátricos se hicieron siguiendo los criterios del DSM-IV. Se usaron autocuestionarios para evaluar varios rasgos de la personalidad. Se identificaron los últimos intentos suicidas y los más graves.Resultados.(1) Después de controlar la edad y la ingesta de medicación, un intento de suicidio anterior (CP = 2 [1,1-3,8]) y los trastornos bipolares normotímicos (CP = 3,4 [1,1-10,5]) se asociaron significativamente y por separado con el deterioro de los procesos de toma de decisiones. (2) La capacidad de toma de decisiones se correlacionó significativamente con la labilidad afectiva. (3) No se encontró ninguna asociación entre las capacidades para la toma de decisiones y las características suicidas.Discusión.Una falta de poder estadístico puede haber enmascarado las asociaciones con el trastorno obsesivo compulsivo y la anorexia nerviosa. No controlamos otras funciones cognitivas excepto la atención.Conclusión.Este estudio confirma la asociación independiente entre el deterioro de la capacidad de toma de decisiones y la vulnerabilidad a la conducta suicida, pero no con el abuso de sustancias. Los trastornos bipolares normotímicos, pero no los trastornos unipolares también se asociaron con el rendimiento bajo. A nivel dimensional, la impulsividad y las capacidades para la toma de decisiones pueden ser procesos distintos. La capacidad de regulación afectiva parece ejercer una influencia importante sobre el rendimiento en la toma de decisiones y, en consecuencia, es un objetivo terapéutico importante.

The left superior temporal cortex, which supports linguistic functions, has consistently been reported to activate during auditory-verbal hallucinations in schizophrenia patients. It has been suggested that auditory hallucinations and the processing of normal external speech compete for common neurophysiological resources. We tested the hypothesis of a negative relationship between the clinical severity of hallucinations and local brain activity in posterior linguistic regions while patients were listening to external speech. Fifteen right-handed patients with schizophrenia and daily auditory hallucinations for at least 3 months were studied with event-related fMRI while listening to sentences in French or to silence. Severity of hallucinations, assessed using the auditory hallucination subscales of the Psychotic Symptom Rating Scales (PSYRATS) and of the Scale for the Assessment of Positive Symptoms (SAPS-AH), negatively correlated with activation in the left temporal superior region in the French minus silence condition. This finding supports the hypothesis that auditory hallucinations compete with normal external speech for processing sites within the temporal cortex in schizophrenia.

ContexteDans une cohorte de patients traités par méthadone, nous avons retrouvé 35 % de tentatives de suicide (TS) sur la vie, 53 % un trouble anxieux et 61 % un trouble de l’humeur. Presque tous étaient fumeurs quotidiens de tabac, les trois quart avaient soit une dépendance au cannabis, à l’alcool ou à la cocaïne associée sur la vie. Dans ce contexte, l’identification de facteurs de variabilité interindividuelle de sévérité et de comorbidité pourrait prédire le risque d’évolution péjorative chez les sujets jeunes ou moins comorbides. Outre les traumas dans l’enfance [1], les styles parentaux [2] semblent avoir un rôle important dans ces trajectoires, tout comme un âge de début (ADD) plus précoce des consommations de substances [3].Objectif/méthodesNous avons ainsi recherché chez 85 patients stabilisés sous méthadone des associations entre les scores à la Measure of Parental Style (MOPS) [4] (séparés pour chaque parent) et l’ADD de tabac, alcool, cannabis, sédatifs et cocaïne ainsi que la présence de comorbidités addictives. Les caractéristiques sociodémographiques, les conduites suicidaires et les comorbidités addictives et psychiatriques (DSM IV) étaient évaluées par entretien semi-structuré.RésultatsNous avons retrouvé des associations significatives (p < 0,00625) après corrections de Bonferroni pour huit tests effectués) entre indifférence paternelle et ADD inférieur du tabac, et entre abus maternel et ADD inférieur des sédatifs, mais pas entre MOPS et présence d’un TA comorbide. Après ajustement sur âge, sexe, dépression majeure et troubles anxieux en régression linéaire, l’abus maternel restait prédictif d’un ADD plus précoce des sédatifs (bêta = –0,24, p = 0,039), tout comme la dépression (bêta = –0,24, p = 0,045).DiscussionMalgré des limites dues à notre évaluation rétrospective et à la faible taille de l’échantillon, ces résultats soulignent l’importance de l’environnement précoce dans la variabilité des trajectoires addictives. Cela suggère l’intérêt d’une prévention primaire chez des patients jeunes présentant ces dysfonctionnements parentaux.

Suicide is one of the ten most common causes of death in Western countries. It involves genetic vulnerability factors and is often associated with major depression. A Japanese team reported an association between the insertion allele of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with completed suicide. The ACE I/D polymorphism was investigated in two independent case-control studies, one involving 64 suicide completers and 90 controls who all underwent forensic investigations, the second one consisting of 588 suicide attempters and 639 controls. In the two population samples studied a statistically significant risk of suicidal behavior was observed for subjects bearing the DD genotype. These results suggest a possible role of the renin-angiotensin system in suicidal behavior.

Objectives: In an attempt to reduce the phenotypical heterogeneity in an ongoing genetic study of suicidal behavior, we investigated the impact of comorbid anxiety disorders on suicidal behavior in bipolar disorder (BD) patients. Methods: Anxiety disorders were compared in 406 BD I and BD II patients with or without lifetime history of suicide attempt. Results: Among anxiety disorders, only social phobia (SP) was significantly associated with history of suicide attempt in BD [p

La littérature suggère qu’une enfance instable engendrerait une résilience plus faible, et qu’une résilience faible serait prédictrice d’un plus haut risque de dépendance et de complications psychiatriques [1,2]. Dans ce contexte, notre objectif a été d’étudier l’ensemble de ces facteurs en une même étude afin d’affiner les trajectoires des patients consommateurs de cocaïne. Nous avons réalisé une étude préliminaire sur 200 patients régulièrement suivis dans 6 centres de soin parisiens. Nous avons évalué la résilience à l’aide de la CD-RISC [3] qui est un auto-questionnaire en 25 questions évaluant 5 dimensions et donnant lieu à un score total. De plus, nous avons procédé à des hétéro-évaluations concernant les variables psychiatriques et les antécédents familiaux (évalués rétrospectivement) et mesuré les dépendances aux différentes substances à l’aide des critères du DSM-IV. Les facteurs de vulnérabilité nous montrent que l’abus (ou dépendance) d’alcool du père, ainsi que le nombre de ruptures parentales sont associés à une plus faible résilience. L’étude des variables psychiatriques révèle qu’une faible résilience serait associée à un plus haut risque de commettre au moins une tentative de suicide dans sa vie, à un plus haut risque d’hospitalisation en service de psychiatrie et de diagnostic de schizophrénie. S’agissant des comorbidités addictives, une faible résilience est prédictrice d’un plus haut risque de dépendance aux opiacés, ainsi qu’aux benzodiazépines, et d’injection de cocaïne. Enfin, les facteurs du CD RISC sont associés à plus de sevrages hospitaliers. En reprenant la théorie de Didier, les adolescents s’intègrerait dans un groupe de pairs dépendants pour palier à une cellule familiale insecure [2]. Une faible résilience de ces patients pourrait conduire à plus de dépendance aux produits anesthésiants comme stratégie de coping. Pour aller plus loin, il pourrait être pertinent d’étudier conjointement résilience, traumatismes et style parentaux.

Background Childhood trauma (CT) is known to impact brain structure and function and is a major risk factor for most of the psychiatric conditions. However, there are few multimodal studies allowing an integrated perspective. Our goal was thus to study the effects of CT on the limbic network using multimodal MRI. Methods We obtained multimodal MRI (T1, diffusion weighted, and resting state fMRI) data from 55 healthy subjects. We performed correlational analyses between Childhood Trauma Questionnaire (CTQ) subscores and anatomo-functional measurements of the limbic network (hippocampal and amygdala volumes, functional connectivity between hippocampus or amygdala with ventromedial prefrontal cortex and fractional anisotropy (FA) in the Uncinate Fasciculus (UF). Results Significant associations of CTQ subscores were found with changes in limbic anatomy, functional and structural connectivity. We observed a positive correlation between CTQ subscores and left amygdala volumes, negative correlations with right amygdala and hippocampus (bilateral) volumes as well negative correlations with left prefrontal-amygdala functional connectivity and with FA in right UF fibers. Conclusions The present study provides new evidences that childhood adversity may be associated with structure and connectivity of the limbic system. Future longitudinal studies may be valuable to further understand the timing effects of CT on the limbic structures and also to obtain a more precise insight about the relation among CT, limbic alterations and the etiology of psychiatric disorders.

Large population based studies demonstrate a link between childhood trauma (CT) and increased prevalence of a wide range of psychiatric disorders, including mood disorders and psychosis. The identification of CT as an environmental risk factor for bipolar disorders (BD) and schizophrenia is of crucial importance to move to GxE interaction studies. In this presentation, we will mainly use the example of bipolar disorders (BD) and draw some parallels with psychosis. First we have demonstrated that CT were associated to BD using case-control studies (with a dose-effect of emotional abuse), as this has been previously demonstrated in psychosis by meta-analytic approaches. We also have shown that CT (mainly emotional and sexual abuses) influenced the clinical expression and course of BD, with associations between CT, earlier age at onset, rapid cycling and suicidal behavior. Some of these associations were also observed in schizophrenia and thus appeared as relatively non-specific. Moreover some cumulative effects of CT and cannabis misuse on the age at onset of BD or on the transition to psychosis have been suggested. Using psychopathological dimensions as outputs, we have been able to demonstrate that CT influence affective regulation and impulsivity-related dimensions, that could mediate the links between CT and clinical categorical outputs. Disentangling these pathways from CT, through dimensions, to clinical expression could shed some light on the clinical and dimensional aspects to could be incorporated in future GenexCT interaction studies. As an example, we will present preliminary data on the interaction between CT and serotonin transporter gene variants but also dysimmunity-related genes variants on the age at onset in BD.

Abnormal dopaminergic function in the prefrontal cortex (PFC) may be a key factor in the etiopathogeny of schizophrenia and bipolar disorder. Both schizophrenic and bipolar subjects have executive functions (EF) deficits, thought to reflect abnormal PFC function. The main inactivation pathways for dopamine in the PFC are enzymatic cleavage by the Carboxy-O-Methyl-Transferase (COMT) and reuptake by the nor-epinephrine transporter (NET). Our aim in this study was to replicate previous studies that investigated influence of the COMT genotype on EF in schizophrenic subjects, their relatives and controls and extend their scope by including bipolar patients, and their relatives and by exploring NET gene polymorphisms influence on executive performances. We investigated one functional polymorphism of the COMT gene and two polymorphisms of the NET gene. EF were assessed by means of the Trail Making Test (TMT) and the Wisconsin Card Sorting Test (WCST). We assessed the effect of each of the three genotypes on EF for the whole sample (N = 318) and separately in schizophrenic (N = 66), bipolar (N = 94) and healthy subjects (i.e., relatives and controls N = 158). Separate analyses were performed because of the presence, in patients samples, of potentially confounding factors, especially medication. Genotype had no significant effect on the cognitive measures in any of the analyses (for the two EF measures, the three polymorphisms, and the four groups). In our sample we found no evidence in favor of a major effect of COMT or NET polymorphisms on the two tests of EF. © 2006 Wiley-Liss, Inc.

International audience; Synaptogenesis, the formation of functional synapses, is a crucial step for the development of the central nervous system. Among the genes involved in this process are cell adhesion molecules, such as protocadherins and neuroligins, which are essential factors for the identification of the appropriate partner cell and the formation of synapses. In this work, we studied the expression and the genetic variability of two closely related members of the protocadherin family PCDH11X/Y, located on the X and the Y chromosome, respectively. PCDH11Y is one of the rare genes specific to the hominoid lineage, being absent in other primates. Expression analysis indicated that transcripts of the PCDH11X/Y genes are mainly detected in the cortex of the human brain. Mutation screening of 30 individuals with autism identified two PCDH11Y polymorphic amino acid changes, F885V and K980N. These variations are in complete association, appeared during human evolution approximately 40,000 years ago and represent informative polymorphisms to study Y chromosome variability in populations. We studied the frequency of these variants in males with autism spectrum disorders (n = 110), attention deficit hyperactivity disorder (ADHD; n = 61), bipolar disorder (n = 61), obsessive-compulsive disorder (n = 51), or schizophrenia (n = 61) and observed no significant differences when compared to ethnically-matched control populations. These findings do not support the role of PCDH11Y, or more generally of a frequent specific Y chromosome, in the susceptibility to these neuropsychiatric disorders.

Gratacos et al. [2001: Cell 106:367-379] described an interstitial duplication dup(15)q24q26 (DUP25) in patients with anxiety disorders; this duplication was found in approximately 90% of patients and in 7% of controls. In order to determine if DUP25 is present in additional individuals susceptible to panic attacks, we tested 44 patients with anxiety disorders, using probes 251c23 and 216c14 mapping in the 15q24 and 15q26 region. We have not detected any DUP25. Our results suggest that DUP25 is not common in people with anxiety disorders in the population tested here.

Introduction Immune dysfunction is thought to play a critical role in the pathophysiology of bipolar disorder (BD). Better insight into the genetic control of innate immune responses is of importance due to possible interactions with environmental risk factors such as infectious agents, particularly early in life. Objectives Given the importance of Toll-like receptors (TLRs) in innate immunity, we analysed the association of selected genetic variants of TLR-2 and TLR-4, both major sensors of pathogenic infectious and non-infectious structures, with BD. Aims Explore possible implications of the innate arm of the immune response in BD. Methods Genomic DNAs from 572 BD patients and 202 controls were analyzed for the distribution of polymorphisms on the TLR-2 and TLR-4 loci using TaqMan ® . Associations were examined using Chi-square test. Results We found that TLR-4 rs 1927914 AA and rs 11536891 TT genotypes were more frequent in BD patients than in controls (corrected p; pc = .02 and .02 respectively) particularly in early-onset BD (EOBD) patients ( pc = .004 and .006) born during the summer season ( pc = 02 and .002 respectively). We also found that TLR-2 rs 3804099 TT and rs 4696480 TT genotypes were significantly more prevalent in EOBD group as compared to the late-onset BD (LOBD) subset, the latter only after excluding patients with positive family history of psychiatric disorders ( pc =0.024 and 0.002 respectively). Conclusions We report an association between BD and TLR-2 and TLR-4 genetic variants suggesting an important role for pathogens in disease development.

Introduction Cocaine users often experience transient psychotic symptoms following cocaine use (Smith et al. 2009). The severity of such psychotic symptoms is influenced by cocaine dose (Vorspan et al. 2011). Several authors observed a higher prevalence of childhood trauma in cocaine addicts than control subjects (Enoch et al. 2010). Objective Describe cocaine induced psychosis and evaluate if it is associated with childhood trauma. Aim Define the population of cocaine users who experiment cocaine induced psychotic symptoms. Method We did a transversal retrospective study. 100 outpatient cocaine users were evaluated with Scale for the Assessment of Positive Symptoms of Crack Induced Psychosis (SAPS-CIP) and Childhood Trauma Questionnaire (CTQ). Informations were obtained about lifetime cocaine use (age of onset, DSM IV dependence criteria, route of administration, daily dose, days of use per month). Results We did not observe any link between SAPS-CIP and CTQ or CTQ and cocaine consumption. About cocaine consumption, more often patients took cocaine during the worst period, higher is the SAPS-CIP score. If patients are (or were) dependent to cocaine, they have higher scores on SAPS-CIP. Moreover, if patients took cocaine intravenously, they have higher scores on SAPS-CIP than if they took it by snorting, or smoking. Conclusion In the conditions of our study, childhood trauma isn’t a mediator for cocaine induced psychosis. About psychotic symptoms, they seem to be more severe among daily cocaine dependents who take it intravenously.

Introduction Circadian rhythm pathways are highlighted in a number of etiological models of bipolar disorder (BD). More than 25% of bipolar patients may present seasonal pattern (SP). However, there is very limited scientific data on the prevalence of SP, its clinical manifestations and any gender influence. Methods Caucasian individuals who met DSM-IV criteria for BD I or II were recruited from three university-affiliated psychiatric departments in France (Paris, Bordeaux, Nancy). SP was defined according to DSM-IV criteria. Clinical and socio- demographic variables were obtained from structured interviews with the patients and their relatives. Results Four hundred and fifty-two bipolar patients (n=452) in euthymic state were included in the study, 102 of them (23%) were considered as having SP according to DSM-IV criteria. Multivariate analysis showed a significant association of BD patients with SP for bipolar II subtype (OR=1.99, p=0.013), rapid cycling (OR=2.04, p=0.02), eating disorder (OR=2.93, p=0.003) and the total number of depressive episodes (OR=1.12, p=0.002). 71% 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=0.02) and total number of depressive episodes (OR=1.21, p=0.002) in males but with rapid cycling (OR=3.02, p=0.003) and eating disorders (OR=2.60, p=0.02) in females. Conclusions The high prevalence of SP in BD, its associated clinical characteristics and the observed differences between genders, suggest that SP represents a potentially important specifier of BD.

Introduction Antidepressants may induce manic or hypomanic episodes. The identification of predictors of antidepressant- induced mania (AIM) is essential to improve the management of bipolar disorder (BD). However, the rare studies on AIM are generally characterized by small sample sizes, varying definitions of AIM and heterogeneous groups of patients, thus leading to conflicting results. Objectives To compare a population of AIM(+) to AIM(-) patients in order to identify specific clinical factors associated with AIM. Methods All 252 participants met the DSM-IV criteria for BD. Only patients who reported AIM in the 90 days after the beginning of an antidepressant (with or without a mood stabilizer) were diagnosed as AIM (+) and those without any lifetime history of AIM despite lifetime antidepressant prescription were considered AIM (-). Sociodemographic and clinical factors were collected using the DIGS, ALS, AIS BIS and WURS. Results AIM(+) (N=74) and AIM(-) (N=178) patients did not differ significantly in terms of age, gender distribution, bipolar disorder duration and age of onset, ALS, BIS and WURS score. However, the rates of rapid cyclers, lifetime history of suicidal acts, alcohol use disorder and AIS score were significantly higher in the AIM(+)group. The type of polarity of onset was significantly different in both groups. Conclusions A history of rapid cycling, of suicidal acts and of alcohol use disorder could be considered as risk factors of AIM in BD. Patients with these factors could therefore be identified as a vulnerable subgroup prone to manic switch with antidepressant.

Introduction Lithium remains the gold standard of prophylactic treatment in bipolar disorder. However 10–40% of patients are not responder to lithium and there is still no operational predictive markers of lithium response. Moreover, previous studies relate some conflicting results due to the absence of an unanimous definition and evaluation of prophylactic lithium response. Our objective was to identify clinical factors associated with prophylactic lithium response assessed by Alda questionnaire that includes 6 categories of prophylactic response from no response for at least two years of treatment to no relapse for three years. Aims To study characteristics associated with lithium response. Methods All 516 participants met the DSM-IV criteria for bipolar disorder. They all received at least once in their life lithium (for at least two years) and all completed the Alda questionnaire. They were compared on several sociodemographic and clinical factors which were collected using the DIGS. Psychological dimensions were assessed with the ALS and AIS (for affective lability and instability), the BIS (for impulsivity) and the WURS (for ADHD screening) and history of childhood trauma. Results Among the 516 subjects, 132 (25,6%) were lithium responders with no relapse during at least two years of treatment; 106 (20,5%) were poor lithium responders. These groups were compared for clinical, dimensional and childhood trauma characteristics, using both univariate and multivariate analyses. Conclusions Characteristics associated with lithium response may help to define personalized strategies.

Introduction Bipolar disorder (BIPD) is a chronic and disabling illness with frequent comorbid addictive disorders (ADD). Little is known about the prevalence and correlates of cannabis use disorders (CUD) in that population. Objectives We sought to characterize clinical, sociodemographic, childhood trauma and psychological correlates associated with CUD in bipolar patients. Aims Our main hypothesis was that BIPD + CUD patients would be more impulsive and affectively unstable than those without. Methods Patients enrolled in a French national network underwent a thorough assessment including lifetime diagnoses using the SCID-IV questionnaire and measures of current symptomatology (Altman and MADRS), impulsivity (BIS-10), emotional instability (AIM and ALS), hostility (BDHI) and history of childhood trauma (CTQ). Univariate and multivariate analyses were used to identify specific associations between several correlates and CUD status. Results Among the 718 patients included, 414 (57.7%) were women, with a mean age of 43 years, and 546 (76.4%) were diagnosed with type I bipolar disorder and 190 (26.9%) had at least one lifetime substance use disorder. CUD were associated with lifetime history of suicidal behavior, psychotic symptoms during an affective episode, rapid cycling and CTQ sub-scores, clinical and psychological dimensions. Parts of these associations remained after controlling for comorbid alcohol use disorders. Conclusions These results suggest a high prevalence of CUD in BIPD, which was associated with a higher severity and worse outcomes of illness. Although the retrospective nature of this study prevents causal interpretations, our results suggest that at-risk traits among CUD+BIPD patients may induce these clinical features.

Introduction Residual symptoms (RS) are common in bipolar disorder. There is no clear consensus on how RS are defined, and individual clinicians may have their own perceptions of this clinical problem. Objective The aim of this study is to define RS and to describe their management using a qualitative analysis. Methods A qualitative study was conducted. Data were collected from five focus groups including 41 psychiatrists all over France. An interview guide was used, including questions about definition of RS, their assessment and influence on the management of bipolar patients. Content analysis was used to identify themes emerging from the focus groups. Results There was no consensus among participants regarding an explicit definition of RS. The definition appears to be multifactorial, interactive and scalable. It is based both on the psychiatrist's therapeutic objectives and patient's complaints. Eight major RS was identified: suicidal risk, emotional dysregulation, compliance, cognitive impairment, sleep disorder, functional disability, complaints from the patients and the development of comorbidities. Content analysis underlines the fact that: standardized tools are not used in clinical practice; RS are a constant preoccupation; they justify optimisation of medication and adjustment of visit frequency. Conclusions Qualitative study is helpful to define and describe RS. Identifying RS is an important way of achieving implementation strategies and improve management of bipolar patients.