Decreased telomere length in a subgroup of young individuals with bipolar disorders: replication in the FACE-BD cohort and association with the shelterin component POT1.

Bipolar disorder (BD) has been associated with premature cellular aging with shortened telomere length (TL) as compared to the general population. We recently identified a subgroup of young individuals with prematurely shortened TL. The aims of the present study were to replicate this observation in a larger sample and analyze the expression levels of genes associated with age or TL in a subsample of these individuals. TL was measured on peripheral blood DNA using quantitative polymerase chain reaction in a sample of 542 individuals with BD and clustering analyses were performed. Gene expression level of 29 genes, associated with aging or with telomere maintenance, was analyzed in RNA samples from a subsample of 129 individuals. Clustering analyses identified a group of young individuals (mean age 29.64 years), with shorter TL. None of the tested clinical variables were significantly associated with this subgroup. Gene expression level analyses showed significant downregulation of MYC, POT1, and CD27 in the prematurely aged young individuals compared to the young individuals with longer TL. After adjustment only POT1 remained significantly differentially expressed between the two groups of young individuals. This study confirms the existence of a subgroup of young individuals with BD with shortened TL. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening.

Vaginal misoprostol versus vaginal dinoprostone for cervical ripening and induction of labour: An individual participant data meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour (IOL) is common practice and different methods carry different effectiveness and safety profiles. OBJECTIVES: To compare the effectiveness, and maternal and perinatal safety outcomes of IOL with vaginal misoprostol versus vaginal dinoprostone using individual participant data from randomised clinical trials. SEARCH STRATEGY: The following databases were searched from inception to March 2023: CINAHL Plus, ClinicalTrials.gov, Cochrane Pregnancy and Childbirth Group Trial Register, Ovid Embase, Ovid Emcare, Ovid MEDLINE, Scopus and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: Randomised controlled trials (RCTs), with viable singleton gestation, no language restrictions, and all published and unpublished data. DATA COLLECTION AND ANALYSIS: An individual participant data meta-analysis was carried out. MAIN RESULTS: Ten of 52 eligible trials provided individual participant data, of which two were excluded after checking data integrity. The remaining eight trials compared low-dose vaginal misoprostol versus dinoprostone, including 4180 women undergoing IOL, which represents 32.8% of all participants in the published RCTs. Of these, 2077 were assigned to low-dose vaginal misoprostol and 2103 were assigned to vaginal dinoprostone. Compared with vaginal dinoprostone, low-dose vaginal misoprostol had a comparable rate of vaginal birth. Composite adverse perinatal outcomes did not differ between the groups. Compared with vaginal dinoprostone, composite adverse maternal outcomes were significantly lower with low-dose vaginal misoprostol (aOR 0.80, 95% CI 0.65-0.98, P = 0.03, I2 = 0%). CONCLUSIONS: Low-dose vaginal misoprostol and vaginal dinoprostone for IOL are comparable in terms of effectiveness and perinatal safety. However, low-dose vaginal misoprostol is likely to lead to a lower rate of composite adverse maternal outcomes than vaginal dinoprostone.

Subjects suffering from bipolar disorder taking lithium are less likely to report physical pain: a FACE-BD study.

BACKGROUND: Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as a mood stabilizer, has shown promising effects on pain. METHODS: This naturalistic study included 760 subjects with BD ( FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood-stabilizing blood concentration of lithium. RESULTS: Subjects with lithium intake were less likely to report pain (odds ratio [OR] = 0.59, 95% confidence interval [CI], 0.35-0.95; p = 0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was ≥0.5 mmol/l (OR = 0.45, 95% CI, 0.24-0.79; p = 0.008). CONCLUSIONS: This is the first naturalistic study to show lithium's promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations.

Telephone Assessment of Suicidal Risk at Prehospital Emergency Medical Services: A Direct Comparison with Face-to-Face Evaluation at Psychiatric Emergency Service.

OBJECTIVE: Assessment of suicidal risk is one of the most challenging tasks faced by health professionals, notably in emergency care. We compared telephone suicide risk assessment at prehospital Emergency Medical Services Dispatch Center (EMS-DC), with subsequent face-to-face evaluation at Psychiatric Emergency Service (PES), using French national Risk-Urgency-Danger standards (RUD). METHOD: Data were collected for all suicidal adult patients (N = 80) who were addressed by EMS-DC to PES between December 2018 and August 2019 and benefited from RUD assessment at both services. Suicidal risk was given a score of 1, 2, 3 or 4, in order of severity. RESULTS: Mean of the differences between the RUD score at EMS-DC and PES was -0.825 (SD = 1.19), and was found to be significant (p < 0.01). The average time between RUD assessments was 420 min (SD = 448) and was negatively correlated with the difference in the RUD score (r = -0.295, p = 0.008). Associated suicide attempt increased the odds of a decrease in the RUD score (OR = 2.989; 95% CI = 1.141-8.069; p < 0.05). CONCLUSIONS: Telephone evaluation of suicidal risk using RUD at EMS-DC yielded moderately higher scores than those obtained by a subsequent face-to face evaluation at PES, with this difference partially explained by the time between assessments, and by clinical and contextual factors.

Confidence in visual detection, familiarity and recollection judgments is preserved in schizophrenia spectrum disorder.

An effective way to quantify metacognitive performance is to ask participants to estimate their confidence in the accuracy of their response during a cognitive task. A recent meta-analysis1 raised the issue that most assessments of metacognitive performance in schizophrenia spectrum disorders may be confounded with cognitive deficits, which are known to be present in this population. Therefore, it remains unclear whether the reported metacognitive deficits are metacognitive in nature or rather inherited from cognitive deficits. Arbitrating between these two possibilities requires equating task performance between experimental groups. Here, we aimed to characterize metacognitive performance among individuals with schizophrenia across three tasks (visual detection, familiarity, recollection) using a within-subject design while controlling experimentally for intra-individual task performance and statistically for between-subject task performance. In line with our hypotheses, we found no metacognitive deficit for visual detection and familiarity judgments. While we expected metacognition for recollection to be specifically impaired among individuals with schizophrenia, we found evidence in favor of an absence of a deficit in that domain also. We found no specific metacognitive deficit in schizophrenia spectrum disorder in the visual or memory domain. The clinical relevance of our findings is discussed in light of a hierarchical framework of metacognition.

The purpose of early maladaptive schemas (EMS) in the relationship dysfunction among people with bipolar disorder in the euthymic phase.

OBJECTIVES: Although free from characterized manic and depressive episodes, the euthymic period in bipolar disorder (BD) remains characterized by a whole host of difficulties, particularly relational. These difficulties are factors of vulnerabilities and relapses. People's perception of their own relationships has an impact on their symptomatology, their responses to treatment and on relapse rates. Young's early maladaptive schemas (EMS) approach proves to be relevant for understanding the construction of these perceptions and working on them. Nevertheless, to this date, few studies have investigated which EMS are related to relationship dysfunction in this particular population. Determining the link between EMS and relationship difficulties would be relevant to understand psychosocial impairment of people with BD in euthymic states. The present study aims to investigate the associations between the different domains of EMS and relationship dysfunction among patients with bipolar disorder in the euthymic phase. METHODS: Data are extracted from the FACE-BD cohort, within the BD Expert Center in Versailles. Inclusion criteria were to be aged between 18 and 65 and to be an outpatient with a diagnosis of bipolar disorder (DSM-IV-TR). Patients had to be euthymic at the time of inclusion, according to DSM-IV-TR criteria with a cut-off score of 14 on the Montgomery-Asberg Depression Rating Scale and the Young Mania Rating Scale. Non-inclusion criteria were meeting at the time of the study the criteria for characteristic depressive episode, hypomania or mania according to the DSM-IV-TR. Sociodemographic data, clinical features associated with relationship dysfunction were assessed. EMS and EMS domains were assessed with the YSQ-R short form (Young Schema Questionnaire 3 Short Form) and current relationship dysfunction were assessed with the FAST (Functioning assessment short test subscale). Successive simple linear regression analyses were performed to investigate the association between the severity scores of each EMS and the intensity of relationship dysfunction. Furthermore, successive simple linear regression analyses investigated the association between EMS domain scores and intensity of relationship dysfunction. Multiple linear regression analyses were performed to test the association between EMS scores, then EMS domains, and the intensity of relationship dysfunction after adjusting for age as well as the intensity of residual depressive and manic symptoms. RESULTS: Relationship dysfunction is partly associated with EMS activation in particular in the separation and rejection domain (P<0.0001), the other-directedness domain (P=0.031) and the over-vigilance and inhibition domain (P=0.005). Having residual depressive symptoms is also among the factors contributing to the relationship dysfunctions of people with bipolar disorder in the euthymic phase. DISCUSSION: This is the first study demonstrating that the activation of several domains of EMS is a risk factor of relationships difficulties for people in euthymic phase of bipolar disorder. It is necessary to identify which EMS are specifically activated and their domains of belonging in order to prevent and reduce them. EMS are a lever for functional remission. It is therefore relevant to refer people reporting relationship problems to schema therapy consistent with a personalized care. Finally, future studies should focus on the mechanisms underlying the complex relationship between EMS domains and relationship dysfunction in people with bipolar disorder in the euthymic phase. It may also be relevant for future research to control for different types of relationship dysfunction. EMS may be differentially associated with several types of interpersonal problems. The relations between different adaptation styles and EMS should be further investigated to offer more personalized care, with the aim to improve functional remission.

Crossed clinical features between eating disorders and types of bipolar disorder: Results from the FondaMental Advanced Centers of Expertise - Bipolar Disorder cohort.

BACKGROUND: Eating disorders (EDs) are liable to alter the disease course of bipolar disorder (BD). We explored the crossed clinical features between EDs and BD, particularly as a function of BD type (BD1 vs. BD2). METHODS: 2929 outpatients attending FondaMental Advanced Centers of Expertise were assessed for BD and lifetime EDs with a semi-structured interview, and their sociodemographic, dimensional and clinical data were collected according to a standardized procedure. For each ED type, bivariate analyses were used to investigate associations between these variables and the type of BD type followed by multinomial regressions with the variables associated with EDs and BDs after Bonferroni correction. RESULTS: Comorbid EDs were diagnosed in 478 (16.4 %) cases, and were more prevalent in patients with BD2 than in those with BD1 (20.6 % vs. 12.4 %, p < 0.001). Regression models showed no difference according to the subtype of bipolar disorder on the characteristics of patients with anorexia nervosa (AN), bulimia nervosa (BN) or binge eating disorder (BED). After multiple adjustments, the factors differentiating BD patients with versus without ED were primarily age, gender, body mass index, more affective lability and comorbidity with anxiety disorders. BD patients with BED also scored higher regarding childhood trauma. BD patients with AN also showed higher risk of past suicide attempts than those with BED. CONCLUSIONS: In a large sample of patients with BD, we found a high prevalence of lifetime EDs, especially for the BD2 type. EDs were associated with several severity indicators, but not with BD type-specific characteristics. This should prompt clinicians to carefully screen patients with BD for EDs, regardless of BD and ED types.

Childhood maltreatment contributes to the medical morbidity of individuals with bipolar disorders.

BACKGROUND: Individuals with bipolar disorders (BD) are at risk of premature death, mainly due to medical comorbidities. Childhood maltreatment might contribute to this medical morbidity, which remains underexplored in the literature. METHODS: We assessed 2891 outpatients with BD (according to DSM-IV criteria). Childhood maltreatment was assessed using the Childhood Trauma Questionnaire. Lifetime diagnoses for medical disorders were retrospectively assessed using a systematic interview and checked against medical notes. Medical morbidity was defined by the sum of medical disorders. We investigated associations between childhood maltreatment (neglect and abuse) and medical morbidity while adjusting for potential confounders. RESULTS: One quarter of individuals had no medical comorbidities, while almost half of them had at least two. Multivariable regression showed that childhood maltreatment (mainly abuse, but also sexual abuse) was associated with a higher medical morbidity. Medical morbidity was also associated with sex, age, body mass index, sleep disturbances, lifetime anxiety disorders and lifetime density of mood episodes. Childhood maltreatment was associated with an increased prevalence of four (i.e. migraine/headache, drug eruption, duodenal ulcer, and thyroid diseases) of the fifteen most frequent medical disorders, however with no difference in terms of age at onset. CONCLUSIONS: This large cross-sectional study confirmed a high medical morbidity in BD and its association with childhood maltreatment. The assessment of childhood maltreatment in individuals with BD should be systematically included in routine care and the potential impact on physical health of psycho-social interventions targeting childhood maltreatment and its consequences should be evaluated.

Physical and mental health status of former smokers and non-smokers patients with bipolar disorder.

OBJECTIVES: Up to 70% individuals with bipolar disorder (BD) are lifetime tobacco smokers, a major modifiable risk factor for morbidity. However, quitting smoking is rarely proposed to individuals with BD, mainly because of fear of unfavorable metabolic or psychiatric changes. Evaluating the physical and mental impact of tobacco cessation is primordial. The aim of this study was to characterize the psychiatric and nonpsychiatric correlates of tobacco smoking status (never- vs. current vs. former smokers) in individuals with BD. METHODS: 3860 individuals with ascertained BD recruited in the network of Fondamental expert centers for BD between 2009 and 2020 were categorized into current, former, and never tobacco smokers. We compared the sociodemographic and clinical characteristics assessed by standard instruments (e.g., BD type, current symptoms load, and non-psychiatric morbidity-including anthropometric and biological data) of the three groups using multinomial regression logistic models. Corrections for multiple testing were applied. RESULTS: Current smokers had higher depression, anxiety, and impulsivity levels than former and never-smokers, and also higher risk of comorbid substance use disorders with a gradient from never to former to current smokers-suggesting shared liability. Current smokers were at higher risk to have a metabolic syndrome than never-smokers, although this was only evidenced in cases, who were not using antipsychotics. CONCLUSIONS: Tobacco smoking was associated with high morbidity level. Strikingly, as in the general population, quitting smoking seemed associated with their return to the never-smokers' levels. Our findings strongly highlight the need to spread strategies to treat tobacco addiction in the BD population.

Definition of early age at onset in bipolar disorder according to distinctive neurodevelopmental pathways: insights from the FACE-BD study.

BACKGROUND: Converging evidence suggests that a subgroup of bipolar disorder (BD) with an early age at onset (AAO) may develop from aberrant neurodevelopment. However, the definition of early AAO remains unprecise. We thus tested which age cut-off for early AAO best corresponds to distinguishable neurodevelopmental pathways. METHODS: We analyzed data from the FondaMental Advanced Center of Expertise-Bipolar Disorder cohort, a naturalistic sample of 4421 patients. First, a supervised learning framework was applied in binary classification experiments using neurodevelopmental history to predict early AAO, defined either with Gaussian mixture models (GMM) clustering or with each of the different cut-offs in the range 14 to 25 years. Second, an unsupervised learning approach was used to find clusters based on neurodevelopmental factors and to examine the overlap between such data-driven groups and definitions of early AAO used for supervised learning. RESULTS: A young cut-off, i.e. 14 up to 16 years, induced higher separability [mean nested cross-validation test AUROC = 0.7327 (± 0.0169) for ⩽16 years]. Predictive performance deteriorated increasing the cut-off or setting early AAO with GMM. Similarly, defining early AAO below 17 years was associated with a higher degree of overlap with data-driven clusters (Normalized Mutual Information = 0.41 for ⩽17 years) relatively to other definitions. CONCLUSIONS: Early AAO best captures distinctive neurodevelopmental patterns when defined as ⩽17 years. GMM-based definition of early AAO falls short of mapping to highly distinguishable neurodevelopmental pathways. These results should be used to improve patients' stratification in future studies of BD pathophysiology and biomarkers.

Preserved electrophysiological markers of confidence in schizophrenia spectrum disorder.

A large number of behavioral studies suggest that confidence judgments are impaired in schizophrenia, motivating the search for neural correlates of an underlying metacognitive impairment. Electrophysiological studies suggest that a specific evoked response potential reflecting performance monitoring, namely the error-related negativity (ERN), is blunted in schizophrenia compared to healthy controls. However, attention has recently been drawn to a potential confound in the study of metacognition, namely that lower task-performance in schizophrenia compared to healthy controls involves a decreased index of metacognitive performance (where metacognitive performance is construed as the ability to calibrate one's confidence relative to response correctness), independently of metacognitive abilities among patients. Here, we assessed how this confound might also apply to ERN-blunting in schizophrenia. We used an adaptive staircase procedure to titrate task-performance on a motion discrimination task in which participants (N = 14 patients and 19 controls) had to report their confidence after each trial while we recorded high density EEG. Interestingly, not only metaperceptual abilities were preserved among patients at the behavioral level, but contrary to our hypothesis, we also found no electrophysiological evidence for altered EEG markers of performance monitoring. These results bring additional evidence suggesting an unaltered ability to monitor perceptual performance on a trial by trial basis in schizophrenia.

Relationships between neuropsychological performance, insight, medication adherence, and social metacognition in schizophrenia.

BACKGROUND: Social metacognition is still poorly understood in schizophrenia, particularly its neuropsychological basis and its impact on insight and medication adherence. We therefore quantified social metacognition as the agreement between objective and subjective mentalization and assessed its correlates in a sample of individuals with schizophrenia spectrum disorders. METHODS: Participants consisted of 143 patients with schizophrenia or schizoaffective disorders who underwent a metacognitive version of a mentalization task, an extensive neuropsychological battery, and a clinical evaluation to assess their insight into illness and medication adherence. We studied potential interactions between confidence judgments and several neuropsychological and clinical variables on mentalization accuracy with mixed-effects multiple logistic regressions. RESULTS: Confidence judgments were closely associated with mentalization accuracy, indicative of good social metacognition in this task. Working memory, visual memory, and reasoning and problem-solving were the three neuropsychological dimensions positively associated with metacognition. By contrast, the two measures of medication adherence were associated with poorer metacognition, whereas no association was found between metacognition and clinical insight. The multiple regression model showed a significant positive impact of better working memory, older age at onset, longer duration of hospitalization, and worse medication adherence on social metacognition. CONCLUSIONS: We discuss possible mechanisms underlying the apparent association between social metacognition and working memory. Adherence should be monitored when remediating social metacognition, and psychoeducation should be given to patients with a high level of awareness of their capacity to mentalize.

Clinical characteristics associated with discrepancies between self- and clinician-rated suicidal ideation in patients with bipolar disorder (FACE-BD cohort).

Suicidal ideation (SI) is a major suicide risk factor; therefore, it is crucial to identify individuals with SI. Discrepancies between the clinicians and patients' estimation of SI may lead to under-evaluating the suicide risk. Yet, studies on discrepancies between self- and clinician-rated SI are lacking, although identifying the patients' sociodemographic and clinical characteristics associated with such discrepancies might help to reduce the under-evaluation risk. Therefore, the aim of this study was to identify features associated with SI rating discrepancies in patients with bipolar disorder (BD) because of the high prevalence of suicide in this population. Among the patients recruited by the French network of FondaMental expert centers for BD, patients with SI (i.e. ≥2 for item 12 of the Quick Inventory of Depressive Symptomatology-Self Report and/or ≥3 for item 10 of the clinician-rated Montgomery and Åsberg Depression Rating Scale) were selected and divided in concordant (i.e. SI in both self- and clinician-rated questionnaires; n = 130; 25.6%), and discordant (i.e. SI in only one questionnaire; n = 377; 74.4%). Depression severity was the feature most associated with SI evaluation discrepancy, especially in patients with SI identified only with the self-rated questionnaire. Clinician may under-evaluate SI presence in patients with low depression level.

Associations of white blood cell and platelet counts with specific depressive symptom dimensions in patients with bipolar disorder: Analysis of data from the FACE-BD cohort.

Evidences suggest that inflammation is increased in a subgroup of patients with depression. Moreover, increased peripheral inflammatory markers (cells and proteins) are associated with some, but not all depressive symptoms. On the other hand, similar studies on bipolar disorders mainly focused on blood cytokines. Here, we analysed data from a large (N = 3440), well-characterized cohort of individuals with bipolar disorder using Kendall partial rank correlation, multivariate linear regression, and network analyses to determine whether peripheral blood cell counts are associated with depression severity, its symptoms, and dimensions. Based on the self-reported 16-Item Quick Inventory of Depressive Symptomatology questionnaire scores, we preselected symptom dimensions based on literature and data-driven principal component analysis. We found that the counts of all blood cell types were only marginally associated with depression severity. Conversely, white blood cell count was significantly associated with the sickness dimension and its four components (anhedonia, slowing down, fatigue, and appetite loss). Platelet count was associated with the insomnia/restlessness dimension and its components (initial, middle, late insomnia and restlessness). Principal component analyses corroborated these results. Platelet count was also associated with suicidal ideation. In analyses stratified by sex, the white blood cell count-sickness dimension association remained significant only in men, and the platelet count-insomnia/restlessness dimension association only in women. Without implying causation, these results suggest that peripheral blood cell counts might be associated with different depressive symptoms in individuals with bipolar disorder, and that white blood cells might be implicated in sickness symptoms and platelets in insomnia/agitation and suicidal ideation.

Factors associated with lamotrigine concentration/dose ratio in individuals with bipolar disorders.

Monitoring of lamotrigine levels is recommended in epilepsy. However, in bipolar disorders (BD), no study has described the therapeutic range in daily practice and factors being associated to it. We used retrospective data of individuals with BD, treated with lamotrigine, and included in the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort. We extracted clinical and biological data and explored associations between these variables and lamotrigine concentration/dose (C/D) ratio. The database included 675 individuals who received lamotrigine at inclusion, whose main characteristics were female sex (68.3%) and BD type 2 (52.1%). Data about lamotrigine C/D ratio were available for 205 individuals. Lamotrigine C/D ratio was significantly associated with: Body Mass Index (BMI) (r=-0.159), estimated GFR (glomerular filtration rate) (r=-0.228), total bilirubin (r = 0.241) and at a trend level, antidepressant co-prescription (U = 3169). The model obtained was: lamotrigine C/D ratio = 1.736 - 0.013*BMI + 0.095*total bilirubin (UI/L) - 0.007*eGFR (ml/min) + 0.210*AST/ALT - 0.004*GGT (UI/L) + 0.014*age (year) + 0.303*currently smoking (yes or no) - 0.588*antidepressant co-prescription (yes or no) - 0.357*gender (F = 1.899, p = 0.057, adjusted R2 = 0.11) Information about plasma lamotrigine C/D ratio were available for only 205 out of the 675 individuals in the database and has been obtained from different laboratories. The representativeness of the included sample may be questionable. This is the first study providing information on a large sample of individuals with BD regarding factors associated with lamotrigine C/D ratio. This study allows to propose a model of lamotrigine C/D ratio that would deserve further replication.

Self-Reported Pain and Emotional Reactivity in Bipolar Disorder: A Prospective FACE-BD Study.

In patients with bipolar disorder (BD), pain prevalence is close to 30%. It is important to determine whether pain influences BD course and to identify factors associated with pain in BD in order to guide BD management. This naturalistic, prospective study used data on 880 patients with BD from the French FACE-BD cohort who were divided into two groups according to the presence or absence of pain. Multivariate models were used to test whether pain was associated with affective states and personality traits while controlling for confounders. Then, multivariate models were used to test whether pain at baseline predicted global life functioning and depressive symptomatology at one year. At baseline, 22% of patients self-reported pain. The pain was associated with depressive symptomatology, levels of emotional reactivity in a quadratic relationship, and a composite variable of personality traits (affective lability, affective intensity, hostility/anger, and impulsivity). At one year, the pain was predictive of depression and lower global life functioning. Pain worsens mental health and well-being in patients with BD. The role of emotions, depression, and personality traits in pain has to be elucidated to better understand the high prevalence of pain in BD and to promote specific therapeutic strategies for patients experiencing pain.

Violent suicide attempt history in elderly patients with bipolar disorder: The role of sex, abdominal obesity, and verbal memory: Results from the FACE-BD cohort (FondaMental Advanced center of Expertise for Bipolar Disorders).

BACKGROUND: Bipolar disorder (BD) is a chronic, lifelong condition, associated with increased risk of obesity, cognitive impairment, and suicidal behaviors. Abdominal obesity and a higher risk of violent suicide attempt (SA) seem to be shared correlates with older age, BD, and male sex until middle age when menopause-related female body changes occur. This study aimed at assessing the role of abdominal obesity and cognition in the violent SA burden of individuals with BD. METHODS: From the well-defined nationwide cohort FACE-BD (FondaMental Advanced center of Expertise for Bipolar Disorders), we extracted data on 619 euthymic BD patients that were 50 years or older at inclusion. Cross-sectional clinical, cognitive, and metabolic assessments were performed. SA history was based on self-report. RESULTS: Violent SA, in contrast to non-violent and no SA, was associated with higher waist circumference, abdominal obesity and poorer California Verbal Learning Test short-delay free recall (CVLT-SDFR) (ANOVA, p < .001, p = .014, and p = .006). Waist circumference and abdominal obesity were associated with violent SA history independently of sex, BD type and anxiety disorder (Exp(B) 1.02, CI 1.00-1.05, p = .018; Exp(B) 2.16, CI 1.00-4.64, p = .009, accordingly). In an exploratory model, waist circumference and CVLT-SDFR performance mediated the association between male sex and violent SA. LIMITATIONS: Cross-sectional design and retrospective reporting. CONCLUSIONS: Violent SA history was associated with abdominal obesity and poorer verbal memory in older age BD patients. These factors were interlinked and might mediate the association between male sex and violent SA.

Relationship between neurocognition and theory of mind as a function of symptomatic profile in schizophrenia: results from the national FACE-SZ cohort.

INTRODUCTION: Deficits in theory of mind (ToM) can vary depending on the predominant schizophrenia symptoms, and though most neurocognitive functions are involved in ToM, all may not be associated with the same symptoms. With consideration to the relationships between symptoms, neurocognition and ToM, the aim of the present study is to identify the neurocognitive functions influencing ToM capacities according to symptomatic profile. METHODS: The study is based on a sample of 124 adults with schizophrenia from a French national cohort. Patients were divided into two groups according to their scores on the five Wallwork factors of the Positive and Negative Syndrome Scale using hierarchical clustering before carrying out multivariable analyses. RESULTS: The "disorganised group" (n = 89) showed high scores on the disorganised factor, and had a ToM associated with reasoning, visual recognition and speed of processing. The "positive group" (n = 35) showed high scores on the positive and depressive factors, and had a ToM associated with working memory. CONCLUSIONS: These results suggest that neurocognitive predictors of ToM in schizophrenia are different according to the predominant clinical dimension, thus refining our knowledge of the relationship between symptoms, neurocognition and ToM, and acknowledging their status as important predictors of patients' functional status.

The puzzle of quality of life in schizophrenia: putting the pieces together with the FACE-SZ cohort.

BACKGROUND: The determinants of quality of life (QoL) in schizophrenia are largely debated, mainly due to methodological discrepancies and divergence about the concepts concerned. As most studies have investigated bi- or tri-variate models, a multivariate model accounting for simultaneous potential mediations is necessary to have a comprehensive view of the determinants of QOL. We sought to estimate the associations between cognitive reserve, cognition, functioning, insight, depression, schizophrenic symptoms, and QoL in schizophrenia and their potential mediation relationships. METHODS: We used structural equation modeling with mediation analyses to test a model based on existing literature in a sample of 776 patients with schizophrenia from the FondaMental Foundation FACE-SZ cohort. RESULTS: Our model showed a good fit to the data. We found better functioning to be positively associated with a better QoL, whereas better cognition, better insight, higher levels of depression, and schizophrenic symptoms were associated with a lower QoL in our sample. Cognitive reserve is not directly linked to QoL, but indirectly in a negative manner via cognition. We confirm the negative relationship between cognition and subjective QoL which was previously evidenced by other studies; moreover, this relationship seems to be robust as it survived in our multivariate model. It was not explained by insight as some suggested, thus the mechanism at stake remains to be explained. CONCLUSION: The pathways to subjective QoL in schizophrenia are complex and the determinants largely influence each other. Longitudinal studies are warranted to confirm these cross-sectional findings.

Handedness in bipolar disorders is associated with specific neurodevelopmental features: results of the BD-FACE cohort.

OBJECTIVES: High rates of non-right-handedness (NRH) and mixed-handedness exist in neurodevelopmental disorders. Dysfunctional neurodevelopmental pathways may be implicated in the underlying pathophysiology of bipolar disorders (BD), at least in some subgroups. Yet little is known about correlates of NRH and mixed-handedness in BD. The objectives of this national study are to determine (i) the prevalence of NRH and mixed-handedness in a well-stabilized sample of BD individuals; (ii) if NRH/mixed-handedness in BD is associated with a different clinical, biological and neurocognitive profile. METHODS: We included 2174 stabilized individuals. Participants were tested with a comprehensive battery of neuropsychological tests. Handedness was assessed using a single oral question. Learning and/or language disorders and obstetrical complications were recorded using childhood records. Common environmental, clinical and biological parameters were assessed. RESULTS: The prevalence of NRH and mixed-handedness were, respectively, 11.6 and 2.4%. Learning/language disorders were found in 9.7% out of the total sample and were associated with atypical handedness (only dyslexia for mixed-handedness (p < 0.01), and dyslexia and dysphasia for NRH (p = 0.01 and p = 0.04, respectively). In multivariate analyses, NRH was associated with a younger age of BD onset (aOR 0.98 (95% CI 0.96-0.99) and lifetime substance use disorder (aOR 1.40 (95% CI 1.03-1.82) but not with any of the cognitive subtasks. Mixed-handedness was associated in univariate analyses with lifetime substance use disorder, lifetime cannabis use disorder (all p < 0.01) and less mood stabilizer prescription (p = 0.028). No association was found between NRH or mixed-handedness and the following parameters: trauma history, obstetrical complications, prior psychotic symptoms, bipolar subtype, attention deficit/hyperactivity disorder, peripheral inflammation or body mass index. CONCLUSIONS: Handedness may be associated with specific features in BD, possibly reflecting a specific subgroup with a neurodevelopmental load.