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Background: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. Neurodevelopmental factors were suggested to contribute to the etiology of BD, yet a specific neurodevelopmental phenotype of the disorder remains unidentified. Our objective was to define and characterize a neurodevelopmental phenotype (NDP) in BD and validate its associations with clinical outcomes, polygenic risk scores (PGS), and treatment responses., Method: We analyzed the FACE-BD cohort of 4,468 BD patients, a validation cohort of 101 BD patients, and two independent replication datasets of 274 and 89 BD patients. Using factor analyses, we identified a set of criteria for defining NDP. We next developed a scoring system for NDP-load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and sex with bootstrap replications., Results: Our study established a NDP in BD consisting of nine clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention deficit hyperactivity disorder (ADHD), early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, specific learning disorders. Patients with higher NDP-load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between the NDP-load and PGS for ADHD suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and ADHD., Conclusions: The proposed NDP constitutes a promising clinical tool for patient stratification in BD., (Copyright © 2024. Published by Elsevier Inc.)

Glucagon-like peptide-1 (GLP-1) agonists have been successfully used in clinical practice for the treatment of diabetes and obesity, offering significant clinical benefits. However, concerns regarding their potential link to psychiatric side effects, like suicidal thoughts and behaviours (STB) have emerged. This narrative review investigates the complex interplay between GLP-1 agonists and STB, focusing on the biological stress induced by rapid weight loss, psychological and social consequences, similar mechanism with addiction, and the evaluative lens of the Bradford Hill criteria on causality. While GLP-1 agonists can contribute to substantial health improvements, they also introduce biological and psychological stressors. Disruptions in homeostasis from quick weight reduction can elevate cortisol and norepinephrine levels, heightening the risk for, or exacerbation of STB. Psychological factors, including unfulfilled expectations and identity changes after significant weight loss, compound these risks. Utilizing the Bradford Hill criteria reveals insufficient evidence for a direct causal link between GLP-1 agonists and STB. Yet, the indirect effects related to the metabolic and psychological disturbances associated with rapid weight loss call for a cautious approach. Used carefully in targeted populations GLP-1 agonists may even emerge as protective agents against STB. Therefore, it is crucial to monitor patients during the treatment and screen for preexisting mental health conditions. If detected, appropriate clinical management should be applied. Future studies should aim at optimizing dosing schedules to mitigate the adverse effects of rapid weight loss and further investigate GLP-1 agonists in possible STB prevention., Competing Interests: Declaration of competing Interest None of the authors have any conflicts of interest regarding the content of this work. R.S. and B.N. has nothing to declare. S.G. served as CME speaker for Novo-Nordisk. E.O. received honoraria from Janssen Cilag and Lundbeck. P.C. has been a consultant to or has received honoraria from Janssen Cilag, Novartis and Ethypharm Digital Therapy. A.L. declared honoraria for educational events from Janssen Cilag., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Identifying circulating biomarkers associated with prospective suicidal ideation (SI) and depression could help better understand the dynamics of these phenomena and identify people in need of intense care. In this study, we investigated the associations between baseline peripheral biomarkers implicated in neuroplasticity, vascular homeostasis and inflammation, and prospective SI and depression severity during 6 months of follow-up in patients with mood disorders., Methods: 149 patients underwent a psychiatric evaluation and gave blood to measure 32 plasma soluble proteins. At follow-up, SI incidence over six months was measured with the Columbia Suicide Severity Rating Scale, and depressive symptoms were assessed with the Inventory for Depressive Symptomatology. Ninety-six patients provided repeated blood samples. Statistical analyses included Spearman partial correlation and Elastic Net regression, followed by the covariate-adjusted regression models., Results: 51.4 % (N = 71) of patients reported SI during follow-up. After adjustment for covariates, higher baseline levels of interferon-γ were associated with SI occurrence during follow-up. Higher baseline interferon-γ and lower orexin-A were associated with increased depression severity, and atypical and anxious, but not melancholic, symptoms. There was also a tendency for associations of elevated baseline levels of interferon-γ, interleukin-1β, and lower plasma serotonin levels with SI at the six-month follow-up time point. Meanwhile, reduction in transforming growth factor- β1 (TGF-β1) plasma concentration correlated with atypical symptoms reduction., Conclusion: We identified interferon-γ and orexin-A as potential predictive biomarkers of SI and depression, whereas TGF-β1 was identified as a possible target of atypical symptoms., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Over 700,000 people die by suicide annually. Collecting longitudinal fine-grained data about at-risk individuals, as they occur in the real world, can enhance our understanding of the temporal dynamics of suicide risk, leading to better identification of those in need of immediate intervention. Self-assessment questionnaires were collected over time from 89 at-risk individuals using the EMMA smartphone application. An artificial intelligence (AI) model was trained to assess current level of suicidal ideation (SI), an early indicator of the suicide risk, and to predict its progression in the following days. A key challenge was the unevenly spaced and incomplete nature of the time series data. To address this, the AI was built on a missing value imputation algorithm. The AI successfully distinguished high SI levels from low SI levels both on the current day (AUC = 0.804, F1 = 0.625, MCC = 0.459) and three days in advance (AUC = 0.769, F1 = 0.576, MCC = 0.386). Besides past SI levels, the most significant questions were related to psychological pain, well-being, agitation, emotional tension, and protective factors such as contacts with relatives and leisure activities. This represents a promising step towards early AI-based suicide risk prediction using a smartphone application., (© 2024. The Author(s).)

Background: Obsessive-compulsive disorder (OCD) and eating disorders (ED) share common features, including the presence of obsessions and compulsions, and they often co-occur. Additionally, there is a significant comorbidity between ED and childhood traumatic experiences (CTE), as well as between CTE and OCD. Various biological and environmental factors have been proposed to explain the connection between ED, OCD, and CTE. This study explores the link between CTE and the comorbidity of ED and OCD, with the hypothesis that specific types of CTE may increase the risk of developing OCD in individuals with ED., Methods: Participants (N = 562) were enrolled at an eating disorder unit in Montpellier, France, between March 2013 and January 2020. The Childhood Trauma Questionnaire (CTQ), Eating Disorder Examination Questionnaire (EDE-Q), and Mini International Neuropsychiatric Interview (MINI) were used to evaluate childhood maltreatment, assess clinical characteristics associated with ED, and categorize participants into two groups: patients with and without OCD., Results: Bivariate analysis revealed that patients with comorbid ED and OCD had higher EDE-Q scores (p < 0.001), more anxiety disorders (p < 0.001), depressive disorders (p = 0.02), post-traumatic stress disorder (PTSD) (p < 0.001), and a higher incidence of sexual abuse (p < 0.001) and physical neglect (p = 0.04) compared to those without OCD. Multivariate analysis showed that the association between CTE and OCD was influenced by the presence of an anxiety disorder (p = 0.01) and a higher EDE-Q total score (p = 0.03), with a significant association with a history of sexual abuse (p = 0.04)., Conclusions: This demonstrates that CTE increases the risk of comorbid OCD in ED patients, correlating with more clinically severe ED and a higher likelihood of anxiety disorders., (© 2024. The Author(s).)

The object of this study is test whether mitochondrial blood-based biomarkers are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. In a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder (FACE-BD) was conducted, including 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 237 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Multivariable regression analyses show significant lactate association with triglycerides, fasting glucose and systolic and diastolic blood pressure. Significantly higher levels of lactate were associated with presence of metabolic syndrome after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. This thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, while showing the mitochondrial metabolites can further stratify metabolic profiles in patients with BD. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities., Competing Interests: Declaration of competing interest Kassandra A. Zachos: none Jaehyoung Choi: none Ophelia Godin: none Timofei Chernega: none Haejin Angela Kwak: none Jae H. Jung: none Bruno Aouizerate: none Valérie Aubin: none Frank Bellivier: none Raoul Belzeaux R: none Philippe Courtet: none Caroline Dubertret: none Bruno Etain: none Emmanuel Haffen: none Antoine Lefrere A: none Pierre-Michel Llorca: none Emilie Olié: none Mircea Polosan: none Ludovic Samalin: none Raymund Schwan: none Paul Roux: none Caroline Barau: none Jean Romain Richard: none Ryad Tamouza: none Ana C. Andreazza: none Marion Leboyer: none, (Copyright © 2024. Published by Elsevier B.V.)

Suicidal behavior and Non-Suicidal Self-Injuries (NSSIs) are a major health problem in the adolescent population. New technologies can contribute to the development of innovative interventions in suicide prevention. Here, we present the SmartCrisis-Teen study protocol. The study consists of a randomized clinical trial which aims to evaluate the effectiveness of a digital safety plan to prevent suicidal behavior and NSSIs in adolescents. This is a multicentric study which will be conducted among the adolescent population, both in clinical and student settings, with a target sample of 1080 participants. The intervention group will receive an Ecological Momentary Intervention (EMI) consisting of a digital safety plan on their mobile phone. All participants will receive their Treatment As Usual (TAU). Participants will be followed for six months, with weekly and monthly telephone visits and face-to-face visits at three and six months. Participants will be assessed using traditional questionnaires as well as Ecological Momentary Assessment (EMA) and Implicit Association Tests (IATs). With this intervention, we expect a reduction in NSSIs through the acquisition of coping strategies and a decrease in suicidal behavior over the course of follow-up. This study provides a novel, scalable digital intervention for preventing suicidal behavior and NSSIs in adolescents, which could contribute to improving adolescent mental health outcomes globally.

Objective: The Psychological-Physical-Pain Visual Analogue Scale (PPP-VAS) was thought to probably help in identifying patients at risk of suicide. However, no data on its validity to measure psychological pain was available. Our main aim was to investigate the convergent validity of the PPP-VAS using two well-validated scales of psychological pain, the Orbach and Mikulincer Mental Pain scale (OMMP) and the Holden et al. Psychache Scale., Methods: This multicentre study recruited a total of 1618 adult psychiatric inpatients and outpatients in Italy. Psychological pain was evaluated using the OMMP, Holden et al., and PPP-VAS scales. Psychiatric status, suicidal status, physical pain, depression, and hopelessness were also assessed., Results: A structural equation model (SEM) using the items of psychological pain from the PPP-VAS showed that items loaded significantly on the psychological pain factor and showed good fit. Similarly, a second SEM model using the three scales of psychological pain showed acceptable fit and converged into a psychological pain construct. Correlations between the PPP-VAS and depression, hopelessness, and physical pain showed moderate correlations (r = 0.43 to r = 0.67). Finally, psychological pain evaluated with the PPP-VAS was significantly related with recent suicidal ideation in all patients (OR [95 % CI] = 1.07 [1.05, 1.09]) and recent suicide attempts in moderately to severely depressed patients, OR [95 % CI] = 1.01 [1.02, 1.03]., Conclusion: The PPP-VAS showed good psychometric properties in evaluating psychological pain. The characteristics of the PPP-VAS makes this scale a great option for its use in clinical practice to detect patients at risk of suicide., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Nutrition is largely affected in bipolar disorder (BD), however, there is a lack of understanding on the relationship between dietary categories, BD, and the prevalence of metabolic syndrome. The objective of this study is to examine dietary trends in BD and it is hypothesized that diets with increased consumption of seafood and high-fiber carbohydrates will be correlated to improved patient outcomes, and a lower frequency of metabolic syndrome., Methods: This retrospective cohort study includes two French cohorts. The primary cohort, FACE-BD, includes 268 stable BD patients. The second cohort, I-GIVE, includes healthy controls, both stable and acute BD and schizophrenia patients. Four dietary categories were assessed: meat, seafood, low-fiber and high-fiber carbohydrates. Dietary data from two food frequency questionnaires were normalized using min-max scaling and assessed using various statistical analyses., Results: In our primary cohort, the increased high-fiber carbohydrate consumption was correlated to lower prevalence of metabolic syndrome and improved mood. Low-fiber carbohydrate consumption is associated with higher BMI, while higher seafood consumption was correlated to improved mood and delayed age of onset. Results were not replicated in our secondary cohort., Limitations: Our populations were small and two different dietary questionnaires were used; thus, results were used to examine similarities in trends., Conclusions: Overall, various dietary trends were associated with metabolic syndrome, BMI, lactate, mood and age of onset. Improving our understanding of nutrition in BD can provide mechanistic insight, clinically relevant nutritional guidelines for precision medicine and ultimately improve the quality of lives for those with BD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Individuals with bipolar disorders (BD) have an estimated loss of life expectancy around 10-15 years. Several laboratory-measured biomarkers of accelerated aging exist (e.g., telomere length), however with a questionable transferability to bedside. There is a need for easily and inexpensively measurable markers of aging, usable in routine practice, such as BioAge., Methods: We calculated BioAge that estimates biological age based on routine blood tests and a physical exam, in a sample of 2220 outpatients with BD. We investigated associations between BioAge Acceleration (BioAgeAccel), which is an indicator of accelerated aging, and sociodemographic variables, clinical variables, and current psychotropic medication use., Results: Mean chronological age was 40.2 (±12.9). Mean BioAge was 39.1 (±12.4). Mean BioAgeAccel was 0.08 (±1.8). A minority of individuals (15%) had a BioAgeAccel above 2 years. Multivariable analyses suggested strong associations between a higher BioAgeAccel and younger age, male sex, overweight and sleep disturbances. Regarding current psychotropic medication use, discrepancies between univariate and multivariate analyses were observed., Conclusions: A minority of individuals with BD had an accelerated aging as measured by BioAge. We identified associations with potentially modifiable factors, such as higher body mass index and sleep disturbances, that are however nonspecific to BD. These results require replications in independent samples of individuals with BD, and comparisons with a control group matched for age and gender. Longitudinal studies are also required to test whether any change in metabolic health, or sleep might decrease BioAgeAccel., (© 2024 The Author(s). Bipolar Disorders published by John Wiley & Sons Ltd.)

Objectives: Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines., Methods: In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests., Results: We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT., Conclusion: Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long., (© 2024. The Author(s).)

Purpose of Review: In this narrative review we wanted to describe the relationship of autonomic nervous system activity with social environment and suicidal spectrum behaviors., Recent Findings: Patients with suicidal ideation/suicide attempt have higher sympathetic nervous system (SNS) and lower parasympathetic nervous system (PNS) activity in resting conditions and during acute stress tasks compared with patients without suicidal ideation/suicide attempt. Death by suicide and violent suicide attempt also are related to SNS hyperactivation. Similarly, a SNS/PNS imbalance has been observed in people with childhood trauma, stressful life events or feelings of loneliness and isolation. Social support seems to increase PNS control and resilience. Due to the importance of the social context and stressful life events in suicidal behavior, SNS/PNS imbalance could act as a mediator in this relationship and be a source of relevant biomarkers. Childhood trauma and stressful life events may impair the autonomic nervous system response in suicidal patients. Loneliness, isolation and social support may act as moderators in acute stress situations., (© 2024. The Author(s).)

Background: Major depressive disorder is one of the leading causes of disability worldwide. Although most international guidelines recommend psychological and psychosocial interventions as first-line treatment for mild to moderate depression, access remains limited in France due to the limited availability of trained clinicians, high costs for patients in the context of nonreimbursement, and the fear of stigmatization. Therefore, online blended psychological treatment such as Deprexis could improve access to care for people with depression. It has several advantages, such as easy accessibility and scalability, and it is supported by evidence., Objective: This study aims to evaluate the real-life acceptability of Deprexis for people with depression in France outside of a reimbursement pathway., Methods: Deprexis Acceptability Study Measure in Real Life (DARE) was designed as a multicenter cross-sectional study in which Deprexis was offered to any patient meeting the inclusion criteria during the fixed inclusion period (June 2022-March 2023). Inclusion criteria were (1) depression, (2) age between 18 and 65 years, (3) sufficient French language skills, and (4) access to the internet with a device to connect to the Deprexis platform. Exclusion criteria were previous or current diagnoses of bipolar disorder, psychotic symptoms, and suicidal thoughts during the current episode. The primary objective was to measure the prospective acceptability of Deprexis, a new digital therapy. Secondary objectives were to examine differences in acceptability according to patient and clinician characteristics and to identify reasons for refusal. All investigators received video-based training on Deprexis before enrollment to ensure that they all had the same level of information and understanding of the program., Results: A total of 245 patients were eligible (n=159, 64.9% were women and n=138, 56.3% were single). The mean age was 40.7 (SD 14.1) years. A total of 78% (n=191) of the patients had moderate to severe depression (according to the Patient Health Questionnaire-9 [PHQ-9]). More than half of the population had another psychiatric comorbidity (excluding bipolar disorder, psychotic disorders, and suicidal ideation). A total of 33.9% (n=83) of patients accepted the idea of using Deprexis; the main reason for refusal was financial at 83.3% (n=135). Multivariate logistic regression identified factors that might favor the acceptability of Deprexis. Among these, being a couple, being treated with an antidepressant, or having a low severity level favored the acceptance of Deprexis., Conclusions: DARE is the first French study aiming at evaluating the prospective acceptability of digital therapy in the treatment of depression. The main reason for the refusal of Deprexis was financial. DARE will allow better identification of factors influencing acceptability in a natural setting. This study highlights the importance of investigating factors that may be associated with the acceptability of digital interventions, such as marital status, medication use, and severity of depression., (©Odile Amiot, Anne Sauvaget, Isabelle Alamome, Samuel Bulteau, Thomas Charpeaud, Anne-Hélène Clair, Philippe Courtet, Dominique Drapier, Emmanuel Haffen, Eric Fakra, Christian Gaudeau-Bosma, Adeline Gaillard, Stéphane Mouchabac, Fanny Pineau, Véronique Narboni, Anne Duburcq, Laurent Lecardeur. Originally published in JMIR Formative Research (https://formative.jmir.org), 20.05.2024.)

Objectives: We describe an artwork observation training program proposed to the first-year psychiatry residents in the school of medicine of Montpellier-Nîmes (Université de Montpellier). This course aimed at improving the ability to observe, tolerate ambiguity in healthcare, work as a team, communicate, and develop empathy. We also evaluated the impact of this program on the enhancement of emotional and communication skills in a pilot study., Materials and Methods: The artwork observation program based on Visual Thinking Strategies consisted of three sessions of ninety minutes involving two groups of eight medical students. First-year volunteer psychiatry residents were recruited. Before the sessions participants completed the Groningen Reflection ability Scale to evaluate reflection skills. Then, all the participants examined paintings and drawings of the Atger collection, were encouraged to observe carefully, and to engage in active group discussion by means of a structured questioning. Following the session, participants responded to a short survey to assess potential improvement of socio-emotional and communication skills., Results: Fifteen psychiatry residents participated in the pilot study, eight were males. The median age was twenty-five years. The artwork observation program was well accepted by the participants. All the respondents reported improvement of emotional and communication skills, except regarding three empathy items, including the ability to feel the suffering of others which was increased only for 62% of respondents., Discussion: Our program relying on Visual Thinking Strategies may improve the ability to observe carefully, to perceive the mental states of others, and to tolerate uncertainty. Training of such skills may encourage the adoption of self-reflective attitudes., Conclusions: Such an artistic innovative program should be extended to undergraduate students in medical curriculum., (Copyright © 2024 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

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., Competing Interests: Declaration of competing interest None of the authors declare conflict of interests related to this manuscript., (Copyright © 2024. Published by Elsevier B.V.)

Decision-making styles are a habit-based propensity that drive behavior and affect daily life. Rational and intuitive decision-making styles have been associated with good mental health. However, the underlying mechanisms are not clear. In the last decade, high basal levels of heart rate variability (HRV) have been proposed as an index of health and emotional control, and this could be one of the variables involved in the effects of decision making on health. Therefore, the aim of this study is to analyze the capability of decision-making styles to predict resting HRV. A cross-sectional study was conducted in a sample of 199 (119 women) young university students, and a resting ECG was recorded to extract frequency domain HRV variables. Subsequently, participants completed sociodemographic data and the General Decision-Making Style questionnaire (GDMS). Results showed that the intuitive style predicted high-frequency HRV, while the avoidant style predicted less low-frequency HRV. This study presents new data on the relationship between decision-making style and HRV, suggesting that the intuitive style has a cardioprotective effect, while the avoidant style is related to lower HRV, which has been associated with health vulnerability. In conclusion, this study contributes to the understanding of HRV and its potential as a biomarker for cognitive styles that may improve health.

Objectives: Weight suppression (WS) defines the difference between the highest weight in adulthood and the current weight. WS at lowest weight is the difference between the highest and the lowest ever weight. Weight rebound is the difference between the past lowest weight and current weight. The distinction in the capacities of WS, weight rebound, and WS at the lowest weight remains unclear regarding their efficacy in forecasting clinical endpoints. This study assessed the relationship between WS, WS at lowest weight and/or weight rebound and eating disorder (ED) clinical severity., Methods: In this retrospective cohort study, adult participants were selected at the Outpatient Unit for multidisciplinary assessment of ED, Montpellier, France, between February 2012 and October 2014 and May 2017 and January 2020. ED clinical severity was evaluated using the Eating Disorder Examination Questionnaire (EDE-Q)., Results: The sample included 303 patients: 204 with anorexia nervosa (AN) and 99 with bulimia nervosa (BN). The EDE-Q total score was positively correlated with WS at lowest weight in patients with AN (Spearman's rho = 0.181, p = 0.015) and with BN (Spearman's rho = 0.377; p < 0.001). It was also positively correlated with weight rebound (Spearman's rho = 0.319; p = 0.003) in patients with BN. In the multivariate analysis, EDE-Q total score was associated with WS at lowest weight only in patients with BN (β = 0.265; p = 0.03)., Conclusion: WS at lowest weight seems to be a good measure of ED clinical severity. More research is needed for better understanding WS at lowest weight in assessment and treatment of patients with ED., Competing Interests: Declaration of competing interest No conflict of interest for all authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Understanding the factors that lead to relapse is a major challenge for the clinical support of smoking cessation. Neurocognitive abilities such as attention, executive functioning and working memory, are possible predictors of relapse and can be easily assessed in everyday clinical practice. In this prospective longitudinal study, we investigated the relationship between pre-smoking cessation neurocognitive performance and relapse at six months in a sample of patients being treated for their tobacco dependence., Methods: 130 tobacco consumers were included in the study. They completed a comprehensive neuropsychological and clinical assessment before smoking cessation. The targeted abilities were intelligence, inhibition, shifting, working memory updating, verbal fluency and decision-making., Results: The rate of tobacco relapse at 6 months was 58%. Logistic regressions were used to assess which variables best explained relapse. None of the neuropsychological tests was a significant predictor of relapse at either 1, 3 or 6 months, either alone, or controlling for other covariates acting as significant predictors of relapse., Conclusions: Common neuropsychological tests, even those specifically targeting executive functioning such as inhibition, are not useful predictors of the success of a smoking cessation program in a clinical setting. Other variables, such as motivation to quit smoking or the presence of comorbid depression or anxiety disorders, appear to be more useful predictors of relapse., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: With 11,558 deaths and 200,000 suicide attempts in 2019, France is among the European countries most affected. The aim of this study was to determine the costs and burden of suicides and suicide attempts in France (population 67 million)., Methods: We estimated direct costs, comprising healthcare, as well as post-mortem costs including autopsy, body removal, funeral expenses, police intervention and support groups; indirect costs comprised lost productivity, daily allowances; the burden of disease calculations used a monetary value for death and disability based on incidence data. Data was obtained from the national statistics, health and social care database, registries, global burden of disease, supplemented by expert opinion. We combined top down and bottom up approaches., Results: The total costs and burden of suicides and suicide attempts was estimated at €18.5 billion and €5.4 billion, respectively. Direct costs were €566 million and €75 million; indirect costs were €3.8 billion and €3.5 billion; monetary value for death and disability was €14.6 billion and €1.3. The monetary value for death and disability represented 79.1% and 24.8% of total costs for suicide and suicide attempt respectively. Some costs were based upon expert opinion, caregivers' burden was not counted and pre COVID data only is reported., Conclusions: In France, the total cost and burden of suicides and suicide attempts was several billion €, suggesting major potential savings from public health interventions., (© 2024. The Author(s).)

Background: Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians' treatment choices for post-traumatic stress disorder (PTSD)., Methods: The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) ( n = 279), Southern Europe (SE) ( n = 92), Northern Europe (NE) ( n = 92), and Western Europe (WE) ( N = 148)., Results: About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct "profiles" of clinicians. In Class 1 ( N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 ( N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 ( N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 ( N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines., Conclusions: Clinicians' decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

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., (© 2024. The Author(s).)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: Suicide is a major health issue. Its prevalence is particularly high in subjects presenting major depression disorder (MDD), making this a key suicide-related risk factor. Suicide attempts in severe forms of MDD were assumed to be linked to impulsivity and loss of control. Nevertheless, we failed to find data specifically investigating the link between impulsivity and suicide risk in treatment-resistant depression (TRD). This study seeks to review this relationship., Method: Patients were recruited for a prospective cohort. Suicide risk and impulsivity were assessed using the International Neuropsychiatric Interview and Barratt Impulsiveness Scale, Version 10, respectively, while the severity of depressive symptoms was assessed using the Montgomery-Asberg Depression Rating Scale, anxiety with the State-Trait Anxiety Inventory and childhood maltreatment using the Childhood Trauma Questionnaire., Results: 220 TRD patients were enrolled in the study. The impulsivity score was correlated with self-esteem, marital status, professional status and anxiety. There was no direct link to suicide risk. However, impulsivity was associated with self-esteem (coefficient: -0.24; p value 0.043) and depressive symptom severity (coefficient: 0.; p value 0.045). The suicide risk was significantly correlated with depressive symptom severity (coefficient = 0.38, p < 0.001) and self-esteem (coefficient = -0.34, p = 0.01). Considering these correlations, we postulated that the effect of impulsivity on suicide risk could be mediated by self-esteem in terms of depressive symptom severity and we finally found a relevant mediation model within impulsivity having an indirect effect on suicide risk by impacting self-esteem and depressive symptoms with anxiety also playing a significant role as a covariable., Conclusion: We found that impulsivity could play an indirect role with the involvement of self-esteem and depressive symptoms and the contributing role of anxiety., Competing Interests: Declaration of competing interest AY received speaker's honoraria from AstraZeneca, Janssen, Lundbeck, Otsuka and Servier, and carried out clinical studies in relation to the development of Janssen and Lundbeck medicines unrelated to this work. J-BG received a speaker's honorarium from Servier. P-ML received grants, honoraria and consulting fees from Allergan, Gedeon Richter, Janssen- Cilag, Lundbeck, Otsuka, Recordati, Sanofi-Aventis and Teva. RRi received a speaker's honorarium from Janssen Cilag. FS received honoraria from Otsuka. EH acted in an advisory capacity, carried out clinical studies in relation to the development of a medicine, received funding for research and studies along with travel allowances, gave presentations at meetings and received remuneration for input from the following pharmaceutical companies: AstraZeneca, BMS, Cellgene, Euthérapie-Servier, Janssen, Elli Lilly, Lundbeck, LivaNova, Otsuka, Pfizer and Sanofi. WE-H received speaker's honoraria from Chugai, Eisai, Lundbeck, Janssen-Cilag, Otsuka and UCB unrelated to this work. BA received speaker's honoraria and/or a travel allowance from Lundbeck, Sanofi, Janssen-Cilag and Eli Lilly. He has also served on the advisory board of Janssen-Cilag. BE received honoraria for consulting activities for Sanofi. The remaining authors have no commercial or financial relationships to declare that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Here we present the findings of the pilot phase of the SmartCrisis 2.0 Randomized Clinical Trial. This pilot study aimed to explore the feasibility and acceptability of a safety plan contained in a smartphone app. Our sample consisted patients with a history of recent suicidal behaviour who installed a smartphone-based safety plan. To explore the satisfaction with of the safety plan, two patient satisfaction surveys were conducted: one qualitative and one quantitative. To explore the objective use of the safety plan, we gained access to texts contained in the safety plans completed by the patients. Participation rate was 77%, while 48.9% patients completed both satisfaction surveys at the end of the pilot phase. N = 105 successfully installed the safety plan. In a scale from 1 to 10, users rated the usefulness of the security plan at 7.4, the usability at 8.9, the degree to which they would recommend it to others at 8.6 and the overall satisfaction with the project including evaluations at 9.6. The most widely completed tab was warning signs. Feeling sad or lonely was the warning sign most commonly reported by patients. The second most completed tab was internal coping strategies. Walking or practicing any other exercise was the strategy most commonly resorted to. Our smartphone-based safety plan appears to be a feasible intervention. Data obtained from this pilot study showed high participation rates and high acceptability by patients. This, together with the general satisfaction with the project, supports its implementation in the clinical practice., Competing Interests: Declaration of competing interest EBG has been a consultant to or has received honoraria or grants from Janssen Cilag, Lundbeck, Otsuka, Pziffer, Servier and Sanoffi. EBG and AAR designed the MEmind application. The other authors confirm they have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests related to this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (Copyright © 2023 Sociedad Española de Psiquiatría y Salud Mental (SEPSM). Published by Elsevier España S.L.U. All rights reserved.)

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.

Since the middle of the 20th century, synthetic sex hormones (estrogens and progestins) have been administered to millions of pregnant or not women worldwide, mainly to avoid miscarriage or for comfort, although their mode of action and their effects on the mother and fetus were ignored. Despite the alerts and the description of somatic and psychiatric disorders in children exposed in utero , synthetic estrogens were prohibited for pregnant women only in the 1970s and 1980s, but some progestins are still authorized. In this review, we summarize the psychiatric disorders described in children exposed in utero to such hormones, focusing particularly on schizophrenia, bipolar disorders, severe depression, eating disorders, suicide and suicide attempts. Moreover, only in 2017 the mechanism of action of these xenohormones has started to be deciphered. Some studies showed that in the fetus exposed in utero , they alter the DNA methylation profile (mainly hypermethylation), and consequently the expression of genes implicated in neurodevelopment and in regulating the sexual organ morphogenesis and also of the promoter of estrogen receptors, located in the amygdala. These deleterious effects may be transmitted also to the next generations, thus affecting the children directly exposed and also the following generations., Competing Interests: M-OS-G is a researcher, president (unpaid) of the HHORAGES-France Association and a mother concerned with DES and other synthetic hormones. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Soyer-Gobillard, Gaspari, Paris, Courtet and Sultan.)

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.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Depressive disorders represent the largest proportion of mental illnesses, and by 2030, they are expected to be the first cause of disability-adjusted life years [1]. The COVID-19 pandemic exacerbated prevalence and burden of depression and increased the occurrence of depressive symptoms in general population [2]. The urgency of implementing mental health services to address new barriers to care persuaded clinicians to use telemedicine to follow patients and stay in touch with them, and to explore digital therapeutics (DTx) as potential tools for clinical intervention [2]. The combination of antidepressants and psychotherapy is widely recommended for depression by international guidelines [3] but is less frequently applied in real-world practice. Commonly used treatments are pharmacological, but while being effective, some aspects such as adherence to the drug regimen, residual symptoms, resistance, lack of information, and stigma may hinder successful treatment. In case of less severe depression, standalone psychological therapies should be the first-line treatment option [3], but access to trained psychotherapists remains inequitable. DTx are evidence-based therapies driven by software programs to treat or complement treatment of a specific disease. DTx are classified as Medical Devices, and given their therapeutic purpose, they need to be validated through randomized controlled clinical trials, as for drug-based therapies. In the last 10 years, studies of digital interventions have proliferated; these studies demonstrate that digital interventions increase remission rates and lower the severity of depressive symptoms compared with waitlist, treatment as usual, and attention control conditions [4]. Despite the efficacy demonstrated in clinical trials, many of these tools never reach real-life patients; thus, it might be necessary to implement DTx in the public health system to expand access to valid treatment options. In this framework, DTx represent a good opportunity to help people with depression receive optimal psychotherapeutic care [5].

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 (a 2 b 2 = 0.0035, CI 95% = [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; CI 95% = [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.

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., Competing Interests: Declaration of competing interest The authors declare no conflict of interests related to this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Bipolar disorder (BD) is a chronic and severe psychiatric disorder associated with significant medical morbidity and reduced life expectancy. In this study, we assessed accelerated epigenetic aging in individuals with BD using various DNA methylation (DNAm)-based markers. For this purpose, we used five epigenetic clocks (Horvath, Hannum, EN, PhenoAge, and GrimAge) and a DNAm-based telomere length clock (DNAmTL). DNAm profiles were obtained using Infinium MethylationEPIC Arrays from whole-blood samples of 184 individuals with BD. We also estimated blood cell counts based on DNAm levels for adjustment. Significant correlations between chronological age and each epigenetic age estimated using the six different clocks were observed. Following adjustment for blood cell counts, we found that the six epigenetic AgeAccels (age accelerations) were significantly associated with the body mass index. GrimAge AgeAccel was significantly associated with male sex, smoking status and childhood maltreatment. DNAmTL AgeAccel was significantly associated with smoking status. Overall, this study showed that distinct epigenetic clocks are sensitive to different aspects of aging process in BD. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings of potential determinants of an accelerated epigenetic aging in BD., Competing Interests: Declaration of Competing Interest None to be declared in links with this study., (Copyright © 2023. Published by Elsevier B.V.)

Background: Suicide is a major global public health issue that is becoming increasingly common despite preventive efforts. Though current methods for predicting suicide risk are not sufficiently accurate, technological advances provide invaluable tools with which we may evolve toward a personalized, predictive approach., Objective: We aim to predict the short-term (1-week) risk of suicide by identifying changes in behavioral patterns characterized through real-time smartphone monitoring in a cohort of patients with suicidal ideation., Methods: We recruited 225 patients between February 2018 and March 2020 with a history of suicidal thoughts and behavior as part of the multicenter SmartCrisis study. Throughout 6 months of follow-up, we collected information on the risk of suicide or mental health crises. All participants underwent voluntary passive monitoring using data generated by their own smartphones, including distance walked and steps taken, time spent at home, and app usage. The algorithm constructs daily activity profiles for each patient according to these data and detects changes in the distribution of these profiles over time. Such changes are considered critical periods, and their relationship with suicide-risk events was tested., Results: During follow-up, 18 (8%) participants attempted suicide, and 14 (6.2%) presented to the emergency department for psychiatric care. The behavioral changes identified by the algorithm predicted suicide risk in a time frame of 1 week with an area under the curve of 0.78, indicating good accuracy., Conclusions: We describe an innovative method to identify mental health crises based on passively collected information from patients' smartphones. This technology could be applied to homogeneous groups of patients to identify different types of crises., (©Maria Luisa Barrigon, Lorena Romero-Medrano, Pablo Moreno-Muñoz, Alejandro Porras-Segovia, Jorge Lopez-Castroman, Philippe Courtet, Antonio Artés-Rodríguez, Enrique Baca-Garcia. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 01.09.2023.)

Background: Benzodiazepine long-term use (BLTU) is a public health challenge. We lack data on the consequences of LBTU on the trajectory of treatment-resistant depression (TRD)., Objective: To determine the prevalence of BLTU in a nationwide non-selected population of patients with TRD, to determine the rate of patients succeeding at withdrawing benzodiazepines at one year and to determine if persistent BLTU is associated with poorer mental health outcomes., Method: The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at one year. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at one year., Results: At baseline, 45.2% of the patients were classified in the BLTU group. In multivariate analysis, compared to patients without BLTU, patients with BLTU were more frequently classified in the "low physical activity" group (adjusted odds ratio (aOR) = 1.885, p = 0.036), and had higher primary healthcare consumption (B = 0.158, p = 0.031) independently of age, sex and antipsychotic consumption. We found no significant difference for personality traits, suicidal ideation, impulsivity, childhood trauma exposure, earlier age at first major depressive episode, anxiety and sleep disorders (all p > 0.05). Despite recommendations for withdrawal, <5% of BLTU patients withdraw benzodiazepines during the one-year follow-up. Persistent BLTU at one-year was associated with higher depression severity (B = 0.189, p = 0.029), higher clinical global severity (B = 0.210, p = 0.016), higher state-anxiety (B = 0.266, p = 0.003), impaired sleep quality (B = 0.249, p = 0.008), increased peripheral inflammation (B = 0.241, p = 0.027), lower functioning level (B = -0.240, p = 0.006), decreased processing speed (B = -0.195, p = 0.020) and verbal episodic memory (B = -0.178, p = 0.048), higher absenteeism and productivity loss (B = 0.595, p = 0.016) and lower subjective global health status (B = -0.198, p = 0.028)., Conclusion: Benzodiazepines are over-prescribed in TRD (in almost a half of the patients). Despite recommendations for withdrawal and psychiatric follow-up, <5% of patients successfully stopped taking benzodiazepines at one-year. Maintaining BLTU may contribute to the worsening of clinical and cognitive symptoms and of daily functioning in TRD patients. Progressive and planed withdrawal of benzodiazepines seems therefore strongly recommended in TRD patients with BLTU. Pharmacological and non-pharmacological alternatives should be promoted when possible., Competing Interests: Declaration of Competing Interest the authors report no conflicts of interest with the present article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Suicide is one of the most largely preventable causes of death worldwide. The aim of the STRONG study is to assess the effectiveness of a specific intervention (an extended Safety Planning Intervention) called iFightDepression-SURVIVE (iFD-S) in suicidal attempters by changes in psychosocial functioning. As secondary outcomes, quality of life, cognitive performance, clinical state and neuroimaging correlates will be considered., Objective: To describe the rationale and design of the STRONG study, an extension of the SURVIVE study, a national multicenter cohort about on prevention in suicidal attempters., Methods: The STRONG study is a two-year clinical trial. A total sample of 60 patients will be randomly allocated to two arms: a group will receive a iFD-S and treatment as usual (TAU) (n=30 treatment group), while another group will exclusively receive TAU (n=30 control group). There will be three study points: baseline; 3-month; and 6-month follow-up assessments, all of which will include rater-blinded evaluation of psychosocial functioning, quality of life, clinical state, cognitive performance and neuroimaging acquisition., Results: It is expected to obtain data on the efficacy of iFD-S in patients who have committed a suicide attempt., Conclusion: Results will provide insight into the effectiveness of IFD-S in suicidal attempters with respect to improvements in psychosocial functioning, quality of life, cognition, and neuroimaging correlates., Clinical Trials Id: NCT05655390., (Copyright © 2023 The Authors. Published by Elsevier España S.L.U. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests with regard to the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

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 R 2  = 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., Competing Interests: Declaration of Competing Interest Ludovic Samalin has received CME-related honoraria and served as consultant for Janssen- Cilag, Lundbeck, Otsuka, Sanofi-Aventis with no financial or other relationship relevant to the subject of this article. Bruno Etain has served as consultant for Sanofi-Aventis with no financial or other relationship relevant to the subject of this article. Raoul Belzeaux received CME- related honoraria and served as consultant for Janssen-Cilag, Lundbeck, Sanofi-Aventis with no financial or other relationship relevant to the subject of this article. The other authors declared no conflict of interest in relation to this article., (Copyright © 2023 Elsevier B.V. and ECNP. All rights reserved.)

Previous studies set out profound cognitive impairments in subjects with treatment-resistant depression (TRD). However, little is known about the course of such alterations depending on levels of improvement in those patients followed longitudinally. The main objective of this study was to describe the course of cognitive impairments in responder versus non-responder TRD patients at one-year follow-up. The second aim was to evaluate the predictive aspect of cognitive impairments to treatment resistance in patients suffering from TRD. We included 131 patients from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centers. They undertook comprehensive sociodemographic, clinical, global functioning, and neuropsychological testing (TMT, Baddeley task, verbal fluencies, WAIS-4 subtests, D2 and RLRI-16) at baseline (V0) and one-year follow-up (V1). Most patients ( n = 83; 63.36%) did not respond (47 women, 49.47 ± 12.64 years old), while one-third of patients responded ( n = 48, 30 women, 54.06 ± 12.03 years old). We compared the cognitive performances of participants to average theoretical performances in the general population. In addition, we compared the cognitive performances of patients between V1 and V0 and responder versus non-responder patients at V1. We observed cognitive impairments during the episode and after a therapeutic response. Overall, each of them tended to show an increase in their cognitive scores. Improvement was more prominent in responders at V1 compared to their non-responder counterparts. They experienced a more marked improvement in code, digit span, arithmetic, similarities, and D2 tasks. Patients suffering from TRD have significant cognitive impairments that persist but alleviate after therapeutic response. Cognitive remediation should be proposed after therapeutic response to improve efficiency and increase the daily functioning.

The high mortality rate in nursing homes during the COVID-19 pandemic may be linked to psychological disorders in staff. Hence, we assessed the prevalence and associated factors of probable post-traumatic stress disorder (PTSD), anxiety, depression, and burnout of nursing home staff during the COVID-19 pandemic in a cross-sectional study including 66 randomly selected nursing homes in southern France. 537 of the contacted 3 821 nursing home workers (14.0%) responded between April and October 2021. We collected information on center organization, severity of COVID-19 exposure, and socio-demographic information in an online survey. The prevalence of probable PTSD (PCL-5), anxiety and depressive disorders (Hospital Anxiety Depression Scale) and the sub-scores of burnout syndrome (Maslach Burnout Inventory Human Services Survey for Medical Personnel) were assessed. Probable PTSD was reported in 115/537 responders (21.4% (95% CI [18.0%-24.9%])). After adjustment, low-level exposure to COVID-19 in nursing home residents (AOR, 0.5; 95% CI [0.3-0.9]), fear of managing COVID-19 residents (AOR, 3.5; 95% CI [1.9-6.4]), conflicts with residents (AOR, 2.3; 95% CI, [1.2-4.4]), conflicts with colleagues (AOR, 3.6; 95% CI [1.7-8.6]), cancellation of leave (AOR, 4.8; 95% CI [2.0-11.7]) and temporary worker employment (AOR, 3.4; 95% CI [1.7-6.9]) were associated with higher prevalence of probable PTSD. The prevalence of probable anxiety and depression were 28.8% (95% CI [24.9%-32.7%]) and 10.4% (95% CI [7.8%-13.1%]), respectively. Psychological disorders were observed in nearly one third of nursing home workers during the COVID-19 pandemic. Hence, continuous surveys and preventive measures are needed in this particularly at-risk population., (© 2023. The Author(s).)

Background: Patients suffering from treatment-resistant depression (TRD) are at risk of suicide. Sleep and circadian rhythm alterations are widely recognized as core symptoms of major depressive disorder and are associated with suicidal ideation. Thus, sleep and circadian rhythm alterations may be targeted to prevent suicide., Methods: Patients were recruited from a prospective cohort of the French network of TRD expert centers. Mood, sleep and circadian rhythms were assessed at baseline; suicidal risk was assessed both at baseline and during a one-year follow-up with standardized subjective questionnaires., Results: Excessive daytime sleepiness (adjusted odds ratio aOR = 1.7(1-3.3), p = 0.04) and daytime dysfunction (aOR = 1.81(1.16-2.81), p = 0.0085) increased the risk of suicidal thoughts over the one-year follow-up period in patients with TRD after adjustment on age, gender, depression, trauma, anxiety, impulsivity, current daily tobacco smoking and body mass index. Hypnotics intake is associated with a reduced risk of suicidal ideation at one-year follow-up after the same adjustments (OR = 0.73(0.56-0.95), p = 0.019). Other associations between sleep quality or circadian rhythms and suicidal ideations at either baseline or one year did not remain significant in multivariate analyses after the same adjustments., Limitations: Sleep assessments were based on self-reported questionnaires rather than objective measures., Conclusions: Daytime sleepiness and dysfunction are predictors of suicidal ideations, whereas hypnotics intake is associated with a reduced risk of suicidal ideations. Diurnal symptoms of sleep disturbances are therefore red flags to target for preventing suicide in depressed patients, and hypnotics seem efficient in preventing suicide for patients with TRD., (Copyright © 2023. Published by Elsevier B.V.)

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., Competing Interests: Declaration of competing interest Authors for this manuscript have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)