Does depression with current suicidal ideation lead to treatment-resistant depression? Two large naturalistic cohorts of outpatients with depression and current suicidal ideation.

As treatment-resistant depression (TRD) is linked to suicidal behaviors and suicidal risk is a predictor of TRD, depression with current suicidal ideation (SI) may lead to TRD. Early identification of TRD risk factors in patients with depression and current SI is crucial. The aims of our study were: i) to identify risk factors for depression non-remission and TRD in patients with depression and current SI; ii) to assess if SI at baseline mediated the relationship between depression severity at baseline and depression remission at week 6. We analyzed data from two large, prospective, naturalistic French cohorts of adult outpatients with depression (DSM-IV criteria) followed for 6 weeks after starting or changing antidepressants (LUEUR and GENESE). Sociodemographic and clinical characteristics, along with early symptom improvement, were compared between patients with and without current SI using logistic regression models (univariate and multivariate). Patients with antidepressant change or initiation were analyzed separately. Those without depression remission at week 6 after an antidepressant change were considered TRD cases. In patients with antidepressant change, the major predictor of non-remission was poorer early improvement (at week 2) of anxiety. For patients with treatment initiation, SI at baseline mediated the relation between depression severity at baseline and depression remission. Depression severity at baseline alone did not explain depression remission. Clinicians should systematically target with specific pharmacological and non-pharmacological treatments anxiety and SI and assess their changes in the short term to increase the chance of depression remission in depressed patients with current SI.

Refining criteria for a neurodevelopmental sub-phenotype of bipolar disorders: a FondaMental Advanced Centers of Expertise for Bipolar Disorders study.

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.

Time perception and suicidal ideation during COVID-19 pandemic: A longitudinal study.

BACKGROUND: There are several reports of disruptions in time perception during lockdown periods throughout the COVID-19 pandemic. Our aim was to study the role of subjective flow of time (SFT) in the triggering of suicidal ideation in patients with a history of suicide attempt (SA), as compared with affective controls without such history (AC). METHODS: This study involved 296 psychiatric patients that were assessed five times between 2020 and 2021. We analyzed the SFT using a mixed logistic model and characterized SFT during significant periods of governmental restrictions. Multivariate logistic regressions were used to identify independent SFT characteristics. We evaluated the association between SFT and suicidal ideation, considering interactions with depression, insomnia, loneliness, and social support. RESULTS: The findings revealed a significant alteration in SFT, closely linked to the implementation and easing of governmental restrictions. During the initial lockdown, SA exhibited lower SFT levels compared to AC. Furthermore, the relationship between SFT and suicidal ideation was influenced by depression. In the interim period between lockdowns, SFT's impact on suicidal ideation was mediated by insomnia. DISCUSSION: Disturbances in SFT could be related to adaptability to lockdown conditions or may be a coping mechanism with depression, insomnia, suicidal ideation and overall psychological distress. Understanding the interplay of SFT with these factors provides crucial insights into the complex psychological mechanisms involved.

Diet quality and associations with lactate and metabolic syndrome in bipolar disorder.

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.

Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder.

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.

Baseline circulating biomarkers, their changes, and subsequent suicidal ideation and depression severity at 6 months: A prospective analysis in patients with mood disorders.

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-1ß, and lower plasma serotonin levels with SI at the six-month follow-up time point. Meanwhile, reduction in transforming growth factor- ß1 (TGF-ß1) 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-ß1 was identified as a possible target of atypical symptoms.

GLP-1 agonists and risk of suicidal thoughts and behaviours: Confound by indication once again? A narrative review.

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.

Does BioAge identify accelerated aging in individuals with bipolar disorder? An exploratory study in the FACE-BD cohort.

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.

Learning to observe art to better understand the patients: A pilot study.

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.

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.

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.

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).

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.