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.

Association of clinical characteristics, depression remission and suicide risk with discrepancies between self- and clinician-rated suicidal ideation: Two large naturalistic cohorts of outpatients with depression.

Clinician- and self-rating of suicidal ideation (SI) are often discrepant. The aim of this study was to determine: 1) Association between discrepant self- and clinician-rated SI with clinical characteristics, depression remission and SA (SA) risk; 2) which SI assessment (self or clinician) predicted depression remission and risk of SA. LUEUR and GENESE are two large, prospective, naturalistic cohorts of French adult outpatients with unipolar depression treated and followed for 6 weeks. SI presence was assessed and defined with a score to the suicidal item of the Montgomery-Åsberg Depression Rating Scale ≥3. Discordant SI was defined as SI detection by only one of the two evaluators (patient or clinician). In both cohorts, 49.3 % (GENESE) and 34 % (LUEUR) patients had discordant SI. Clinical characteristics were more severe, and risk of SA was higher in patients with current SI (concordant and discordant) than in patients without SI and in the concordant than in the discordant group. Prediction of the risk of SA and of depression non-remission was comparable by the two ratings. Patients with SI (concordant and discordant) have more severe clinical characteristics and patients with concordant SI are the most at risk of SA during the follow-up. It is crucial to assess SI and to improve how it is evaluated.

Esketamine-induced post-traumatic stress disorder flashbacks during treatment-resistant depression indication: is it just a side effect?

Background: Posttraumatic stress disorder (PTSD) is a severe and frequent affection that is highly comorbid to major depressive disorder. Comorbid PTSD and depression are usually treatment-resistant, with a high risk of functional impairment and suicide. Esketamine nasal spray is a recent validated treatment for treatment-resistant depression (TRD), but its efficacy on comorbid TRD-PTSD remains insufficiently documented. In particular, flashbacks can occur during esketamine administration and their influence on clinical outcomes is unknown. Objectives: Our main objective was to describe esketamine-induced traumatic flashbacks and their impact on clinical trajectories within a sample of patients with comorbid TRD-PTSD. Methods: We retrospectively collected clinical data of patients receiving esketamine nasal spray for TRD with comorbid PTSD who experienced at least one flashback of their trauma during esketamine sessions across 11 psychiatric departments. Results: Between February 2020 and March 2023, 22 adult patients with TRD met inclusion criteria. In sixteen patients (72.7%) flashbacks disappeared as the sessions progressed. In six patients (27.3%), esketamine treatment was stopped because of persistent flashbacks. When esketamine was continued, clinical response was observed both for depression and PTSD (depression response rate: 45.5% and remission rate: 22.7%; PTSD response rate: 45.5% and remission: 18.2%). Limitations: The retrospective design of the study and the absence of a comparator group are the main limitations of our study. Conclusions: Our results suggest that the occurrence of esketamine-induced traumatic flashbacks does not hinder clinical response. On the contrary, when managed appropriately and combined with targeted psychotherapy, it could even contribute to positive outcomes.

Efficacy of 12-step mutual-help groups other than Alcoholics Anonymous: a systematic review and meta-analysis.

This paper offers a systematic review of quantitative and qualitative studies on the main twelve-step mutual-help (TSMH) groups (excluding Alcoholics Anonymous) and four meta-analyses exploring the correlation between (i) duration or involvement in TSMH groups and; (ii) severity of symptoms or quality of life. Systematic review was conducted following PRISMA guidelines. Searches of databases (MEDLINE, PsychInfo), a register (ClinicalTrials) and citations were conducted, from inception through November 01 2022. Fifty five articles were included (24 quantitative, 27 qualitative, 4 mixed-methods), corresponding to 47 distinctive studies. 68% of these studies were conducted in North America, 17% in Middle East, 11% in the European Union and 4% in Australia. The most studied TSMH group were Gamblers Anonymous (28% of the 47 studies), Narcotics Anonymous (26%), Double Trouble in Recovery (15%), Overeaters Anonymous (19%) and TSMH groups for compulsive sexual behaviors (11%). The four meta-analyses pooled data from 9 studies. Pooled mean age ranged from 36.5 to 40.5. 80-81% of participants were male. TSMH attendance and involvement were negatively correlated with severity of symptoms (high and medium levels of evidence) and positively correlated with quality of life (low levels of evidence). Twenty-one qualitative papers reported factors influencing recovery: Social (n = 15), emotional (n = 9), spiritual (n = 8), self-identification or psychological (n = 6) factors. Review provides characteristics of TSMH groups others than Alcoholics Anonymous, with implications for both research and healthcare practice. The perspective to implement TSMH groups targeting ontological addiction, at the root of all addiction, is discussed.Protocol registration: Prospero registration number: CRD42022342605.

Pain tolerance and threshold in suicide attempters: A systematic review and meta-analysis.

It has been hypothesized that individuals less sensitive to pain could be at higher risk of suicide. However, data on pain sensitivity in suicide attempters (SA) obtained using experimental procedures are heterogeneous. The aim of this systematic review and meta-analysis was to investigate and compare pain tolerance and threshold in SA (patients with lifetime history of suicide attempt), non-attempters (psychiatric controls, PC), and healthy controls (HC). A random effects meta-analysis was used to estimate the standardized mean differences using data from 16 studies that compared physical pain tolerance and threshold in SA and PC or HC. Pain tolerance and threshold were not significantly different in SA and PC. However, pain tolerance, but not threshold, was higher in SA than HC. Our findings do not support the hypothesis of an altered pain perception related as a trait for suicidal vulnerability, but rather suggest altered pain perception related to psychiatric vulnerability.

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.

Assessment and management of individuals consulting for a suicidal crisis: A European Delphi method-based consensus guidelines.

INTRODUCTION: Managing patient with suicidal thoughts and behaviours presents significant challenges due to the scarcity of robust evidence and clear guidance. This study sought to develop a comprehensive set of practical guidelines for the assessment and management of suicidal crises. MATERIALS AND METHODS: Utilizing the Delphi methodology, 80 suicide clinician and research experts agreed on a series of recommendations. The process involved two iterative rounds of surveys to assess agreement with drafted recommendations, inviting panellists to comment and vote, culminating in 43 consensus recommendations approved with at least 67% agreement. These consensus recommendations fall into three main categories: clinical assessment, immediate care, and long-term approaches. RESULTS: The panel formulated 43 recommendations spanning suicidal crisis recognition to continuous long-term care. These guidelines underscore systematic proactive suicide risk screening, in-depth medical and toxicological assessment, and suicide risk appraisal considering personal, clinical factors and collateral information from family. The immediate care directives emphasize a secure environment, continuous risk surveillance, collaborative decision-making, including potential hospitalization, sensible pharmacological management, safety planning, and lethal means restriction counselling. Every discharge should be accompanied by prompt follow-up care incorporating proactive case management and multi-modal approach involving crisis lines, brief contact, and psychotherapeutic and pharmacological interventions. CONCLUSIONS: This study generated comprehensive guidelines addressing care for individuals in suicidal crises, covering pre- to post-discharge care. These practical recommendations can guide clinicians in managing patients with suicidal thoughts and behaviours, improve patient safety, and ultimately contribute to the prevention of future suicidal crises.

[How can ketamine be used to manage suicidal risk?] / Comment la kétamine peut-elle aider à mieux prendre en charge le risque suicidaire ?

In France, suicidal behaviors remain a major public health issue. Depressed patients with suicidal ideation have more severe depressive symptoms, a more unfavorable disease course, and a greater number of suicide attempts than patients without suicidal ideation. Unfortunately, conventional antidepressants tend to be less effective in patients with suicidal tendencies than in those without. Nevertheless, promising advancements have emerged with the use of ketamine, which has shown significant and rapid efficacy in reducing the intensity of suicidal ideation in depressed patients within the first 72 h after its administration. Several mechanisms are potentially involved: (1) reduction of anhedonia. It has been demonstrated that ketamine reduces both anhedonia and suicidal ideation. In depressed patients, the reduction of anhedonia observed 2 h after ketamine administration is associated with metabolic changes in the anterior cingulate cortex involved in suicidal ideation; (2) activation of neuroplasticity cascades. The reduction in suicidal ideation within 24 h following ketamine administration is correlated with changes in plasma BDNF levels and is modulated by the Val66Met functional polymorphism of the BDNF gene. Moreover, preclinical and clinical studies have shown that ketamine induces functional and connectivity changes in the prefrontal and anterior cingulate regions, which are strongly implicated in suicidal behaviors; (3) reduction of inflammation. It is now widely accepted that suicidal behaviors are associated with low-grade inflammation, and with elevated quinolinic acid and reduced kynurenic acid levels. Interestingly, predictors of a reduction in suicidal ideation after ketamine infusion include initial severity of suicidal thoughts and depression, as well as baseline blood levels of kynurenic acid; (4) involvement of the opioidergic system. Post-mortem studies have indicated alterations in the opioidergic system related to suicidal behaviors. A recent study suggested that the antisuicidal effect of ketamine may depend on this system because naltrexone, an antagonist of mu opioid receptors, abolished the typical antidepressant effect and reduction in suicidal ideation observed following ketamine administration. In conclusion, ketamine exhibits promising potential in mitigating suicidal ideation - its effects are specific, rapid, albeit temporary. The suggested mechanisms driving its efficacy are multifaceted. Nevertheless, it is yet to be determined whether ketamine administration can effectively prevent suicidal behaviors.

Title: Comment la kétamine peut-elle aider à mieux prendre en charge le risque suicidaire ? Abstract: Les patients souffrant de dépression suicidaire répondent moins bien aux traitements antidépresseurs conventionnels que ceux qui n'ont pas d'idées suicidaires. Une avancée prometteuse dans ce domaine est l'utilisation de la kétamine, qui a montré une efficacité significative et rapide dans la réduction de l'intensité des idées suicidaires chez les patients déprimés. Des études ont montré qu'une seule perfusion intraveineuse de kétamine à faible dose pouva3it réduire de manière significative et durable les idées de suicide. De plus, la kétamine semble également réduire l'anhédonie, un symptôme associé aux idées suicidaires. Les mécanismes d'action de la kétamine sont multiples. Elle stimule la neuroplasticité via l'activation de la voie du BDNF (facteur neurotrophique du cerveau) et réduit l'inflammation. De plus, la kétamine semble agir sur le système opioïdergique, qui est impliqué dans les conduites suicidaires. En conclusion, la kétamine présente un intérêt dans la réduction des idées suicidaires chez les patients déprimés. Cependant, il est nécessaire de déterminer si son administration permet de prévenir les actes suicidaires. De plus amples recherches sont nécessaires pour mieux comprendre les mécanismes d'action de la kétamine et développer des stratégies thérapeutiques ciblées pour prévenir les conduites suicidaires.

The capacity to consent to treatment is altered in suicidal patients.

BACKGROUND: Many patients with depression refuse treatment. Moreover, suicide attempters often display low perceived need of treatment and impaired decision-making. These observations raise questions about the capacity to treatment consent in depressed suicide attempters (SA). METHODS: In patients with current depressive episode (N = 33 SAs and N = 27 non-SAs), consent capacity was evaluated with the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), insight with the Beck Cognitive Insight Scale, and depression severity with the Beck Depression Inventory (BDI). RESULTS: The median BDI score in the whole sample (N = 60) was 21 [10;36], and was higher in SAs than non-SAs (27 [11;36] vs. 15 [10:33], p < 0.001). Consent capacity was impaired in 30% (appreciation), 53% (reasoning) and 60% (understanding) of all patients. MacCAT-T sub-scores were lower in SAs than non-SAs (understanding: 4.4 [2.35;5.8] vs. 5.3 [3.13;6]); appreciation: 3 [1;4] vs. 4 [2;4]); reasoning (4 [1;7] vs. 7 [3;8]), and ability to express a choice: 1 [0;2] vs. 2 [0;2]; all p < 0.001). In multivariate analyses, suicide attempt history and depression severity (but not insight) were negatively associated with MacCAT-T sub-scores. CONCLUSION: More research is needed on the capacity to consent to treatment of patients with depression, particularly suicidal individuals, to make informed choices about their treatment. Trial registration The Montpellier University Hospital Institutional Review Board approved the study (No. 202100714).

Mediation effect of anxious attachment on relationship between childhood trauma and suicidal ideation sensitive to psychological pain levels.

BACKGROUND: Childhood trauma (CT), depression, and psychological pain are known predictors of suicidal ideation. Recent literature additionally highlights the importance of the attachment system. METHODS: We aimed to predict suicidal ideation through CT, attachment, and psychological and social pain by using mediation models aiming to predict suicidal ideation through CT (predictor) and attachment (mediator). In the same models, we introduced psychological or social pain as a moderator of the relationship between attachment, CT, and suicidal ideation. We included 161 depressed patients and assessed depression, attachment, CT, suicidal ideation, psychological pain, and social pain. RESULTS: We found (1) a complete mediating effect of anxious attachment (a2b2 = 0.0035, CI95% = [0.0010; 0.0069]) on the relationship between CT on suicidal ideation, and (2) a significant complete conditional mediating effect of anxious attachment and psychological pain (index of moderated mediation VAS: 0.0014; CI95% = [0.0002; 0.0032]) but not social pain on the relationship between CT and suicidal ideation. Both models were controlled for history of suicidal attempt, depression severity, and sex. CONCLUSIONS: Our results suggest a developmental profile of suicidal ideation in mood disorder that is characterized by the presence of CT and insecure attachment, especially anxious attachment, that is sensitive to experiences of psychological pain. Nevertheless, we cannot conclude that avoidantly attached individuals do not present the same mechanism, as they may not disclose those ideas.

Associations of potential plasma biomarkers with suicide attempt history, current suicidal ideation and subsequent suicidal events in patients with depression: A discovery study.

A growing body of evidences suggests that suicidal ideation (SI) and suicidal behaviors have biological bases. However, no biological marker is currently available to evaluate the suicide risk in individuals with SI or suicide attempt (SA). Moreover, the current risk assessment techniques poorly predict future suicidal events. The aim of this study was to examine the association of 39 new and already described peripheral cells and proteins (implicated in the immune system, oxidative stress and plasticity) with lifetime SA, past month SA, current SI, and future suicidal events (visit to the Emergency Department for SI or SA) in 266 treatment-seeking individuals with mood disorders. Equal parts of patients with and without past history of SA were recruited. All individuals at inclusion gave blood, were evaluated for SA recency, current SI, and were followed for two years afterwards. The 39 peripheral blood cellular and protein markers were entered separately for each outcome in Elastic Net models with 10-fold cross-validation, followed by single-analyte covariate-adjusted regression analyses for pre-selected analytes. Past month SA was associated with increased plasma levels of thrombospondin-2 and C-reactive protein, whereas current SI was associated with lower plasma serotonin levels. These associations were robust to adjustments for key covariates and corrections for multiple testing. The Cox proportional hazards regression showed that higher levels of thrombospondin-1 and of platelet-derived growth factor-AB predicted a future suicidal event. These two associations remained after adjustment for sex, age, and SA history, and outperformed the predictive value of past SA. Thrombospondins and platelet-derived growth factors have never been investigated in the context of suicide. Altogether, our results highlight the involvement in the suicidal process of platelet biological response and plasticity modifiers and also of inflammatory factors. They also suggest that SI and SA may have different biological correlates and that biomarkers associated with past SA or current SI do not automatically also predict future events.

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.

Factors associated with transitioning from suicidal ideation to suicide attempt in the short-term: Two large cohorts of depressed outpatients.

BACKGROUND: This study explores factors associated with transitioning from recent suicidal ideation (SI) to suicide attempt (SA) in depressed outpatients. METHODS: This is a case-control study nested in two cohorts (LUEUR and GENESE) of depressed adult outpatients recruited in France and followed up for six weeks. SI, depression, anxiety, insomnia, impulsivity, and hopelessness were assessed with validated scales. Differences between patients with SI who attempted suicide during follow up and those who did not were explored using logistic regressions. RESULTS: There was a slight majority of females in both cohorts. Mean age was 47.2 years in LUEUR and 49.4 years in GENESE. Of the 3785 participants in the LUEUR cohort, 72 (2.1 %) attempted suicide within the 6-week period vs. 19 of the 2698 participants (0.7 %) in the GENESE cohort. In LUEUR, factors associated with SA within the 6-week period were lifetime history of SA (OR = 5.35, 95 % CI = 3.30-8.66), high SI at baseline (OR = 3.87, 95 % CI = 2.4-6.24), associated treatments (OR = 3.28, 95 % CI = 2.00-5.38), and less improvement over follow-up in the following symptoms: SI (OR = 3.64, 95 % CI = 1.89-7.02), depression (OR = 3.66, 95 % CI = 1.76-7.62), and anxiety (OR = 3.26, 95 % CI = 1.46-7.27). In GENESE, associated factors were lifetime history of SAs (OR = 9.93, 95 % CI = 3.83-25.80), and less improvement in SI (OR = 9.20, 95 % CI = 3.61-23.44). LIMITATIONS: Heterogeneity of cohorts prevented from performing a pooled analysis with a greater sample size. CONCLUSIONS: In depressed outpatients, lack of improvement was strongly associated with a short-term SA, particularly in patients with a history of previous SAs. Fast acting treatment on SI and depression may help prevent SAs.

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.

Sensitivity to ostracism is blunted in suicide attempters only when they report suicidal ideation.

BACKGROUND: Modified pain perception is at the core of many theories on suicide; however, studies on the relationship between pain perception and suicidal behavior (attempt) have produced contradictory results. In this experimental study, we investigated whether physical pain and social pain are concomitantly influenced by suicidal ideation (SI) and past suicidal behavior. METHODS: 155 inpatients with depression (90 with and 65 without past history of suicide attempt) were included. They underwent thermal stimulation of the skin to assess physical pain tolerance and played the Cyberball game to assess their sensitivity to ostracism (social pain). Participants self-assessed current SI through the specific item in the Beck Depression Inventory. RESULTS: Pain tolerance was not associated with history of suicide attempt, current SI, and their interaction. Social pain was associated with the interaction between history of suicide attempt and current SI. Social pain was decreased in suicide attempters, compared with non-attempters, only when they reported current SI. LIMITATIONS: Cyberball game may not be representative of everyday stress and ecological social context. CONCLUSIONS: Unlike what suggested by many theories, pain tolerance does not seem to be necessary to attempt suicide. Suicide attempters with current SI displayed blunted sensitivity to ostracism and could be less willing to restore social affiliation compared with non-attempters.

Depression and approach-avoidance decisions to emotional displays: The role of anhedonia.

Depression is linked to dysfunctional appetitive and aversive motivational systems and effort-based decision-making, yet whether such deficits extend to social decisions remains unclear. Participants (23 non-depressed, 48 depressed - 24 with a past history of suicide attempt) completed a social decision-making task consisting in freely choosing whether to approach or avoid individuals displaying happy or angry expressions. Occasionally, participants had to make a further effort (change button press) to obtain the desired outcome. All participants preferentially avoided anger on their first choice. Yet, depressed patients less often chose to approach happy individuals, as a function of anhedonia severity. Depressed patients were also less inclined than controls to change their response when the anticipated outcome of their first choice was undesirable (approach angry and avoid happy). Again, such effect correlated with anhedonia severity. Our results support that both altered valuation and willingness to exert effort impact approach-avoidance decisions in social contexts in depression. On this basis, we propose a new integrating framework for reconciling different hypotheses on the effect of depression and anhedonia on motivational responses to emotional stimuli.

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.

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.