From Social Stress and Isolation to Autonomic Nervous System Dysregulation in Suicidal Behavior.

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.

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.

Are visual analogue scales valid instruments to measure psychological pain in psychiatric patients?

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.

Do Decision-Making Styles Predict Vagal Control? The Role of Resting Heart Rate Variability.

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.

Prospective Acceptability of Digital Therapy for Major Depressive Disorder in France: Multicentric Real-Life Study.

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.

Clinician treatment choices for post-traumatic stress disorder: ambassadors survey of psychiatrists in 39 European countries.

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.

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.

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.

The cost of illness and burden of suicide and suicide attempts in France.

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.

Weight suppression at lowest weight as an indicator of eating disorder clinical severity: A retrospective cohort study.

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 (ß = 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.

Smartphone-based safety plan for suicidal crisis: The SmartCrisis 2.0 pilot study.

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.

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.

Indirect effect of impulsivity on suicide risk through self-esteem and depressive symptoms in a population with treatment-resistant depression: A FACE-DR study.

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.

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.

Neuropsychological assessment fails to predict relapse among cigarette smokers: A prospective study of neurocognitive abilities.

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.

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.

Effects of prenatal exposure to synthetic sex hormones on neurodevelopment: a biological mechanism.

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.