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Benedicte Nobile,1,2 Emilie Olie,1– 3 Nicolas Ramoz,4 Jonathan Dubois,1,2 Sebastien Guillaume,1– 3 Philip Gorwood,4 Philippe Courtet1– 3 1Department of Emergency Psychiatry and Acute Care, CHU Montpellier, Montpellier, France; 2IGF, University of Montpellier, CNRS, INSERM, Montpellier, France; 3FondaMental Foundation, Créteil, France; 4Inserm UMRS1266, Institute of Psychiatry and Neuroscience of Paris, Paris, FranceCorrespondence: Benedicte Nobile Email benedicte.nobile@gmail.comBackground: Growing evidences suggest that depression with suicidal ideation (SI) could be a specific phenotype with its own characteristics. Moreover, opioid system deregulation might be implicated in suicidal behaviour (SB). The aim of this study was to determine whether the A118G polymorphism (rs1799971) in ORPM1 (the gene encoding opioid receptor mu 1) is associated with suicidal depression (ie, moderate to severe depression with SI) in a large cohort of outpatients with depression.Methods: GENESE is a large, prospective, naturalistic cohort of French adult outpatients with depression (DSM-IV criteria), treated and followed for 6 weeks. Depression severity was assessed with the Hospital Anxiety and Depression Scale (HADS), and SI with the suicidal item of the Montgomery–Åsberg Depression Rating Scale (MADRS-SI). From this cohort, patients with moderate or severe depression (HADS-D subscale score > 11) were selected and classified as without SI (MADRS-SI < 2), or with SI (MADRS-SI ≥ 2).Results: The AA/AG genotypes of the A118G polymorphism were significantly associated with suicidal depression in the non-adjusted (OR = 2.32, 95% CI = [1.28; 4.18]; p-value = 0.005) and in the adjusted models (OR = 2.54, 95% CI = [1.35; 4.78]; p-value = 0.004).Conclusion: Outpatients with depression harbouring the A allele are at higher risk of SI (and possibly SB) than those carrying the G allele. More studies are needed to better understand the link between this polymorphism and SB.Keywords: suicide, suicidal ideation, opioid system, A118G, OPRM1

International audience; Current methodologies employed in collecting data for suicide research present several limitations. In this article, we describe a novel method and tool to prospectively study suicidal behavior and its related risk and protective factors in different countries. This tool is a web-based database, which will initially be developed and piloted by suicide research groups from Austria, Brazil, Chile, France, Italy, Mexico, Spain, Sweden, and the US. The database will develop and integrate research tools key to collaboration, permit exploration of ethical considerations, and provide a universal interface in English, Spanish, French, Portuguese, Italian, and German that will make it possible to incorporate new groups from different countries to the network. The common database resulting of this cross-national effort will allow researchers to share and compare data across countries in a large sample of patients. Using anonymous electronic records of patients, we will: 1) determine the impact of risk and protective factors (viz. aggression and religious affiliation) in different socio-cultural environments; 2) develop a clinical model of suicidal behavior that integrates the multiple dimensions implicated; 3) try differentiating the effects of biological, environmental, and cultural factors on suicidal behavior, and 4) offer the global psychiatric research community a tool that will standardize assessment across nations, allowing for better generalization.

Acyl coenzyme A binding protein (ACBP), also known as diazepam binding inhibitor (DBI) is a multifunctional protein with an intracellular action (as ACBP), as well as with an extracellular role (as DBI). The plasma levels of soluble ACBP/DBI are elevated in human obesity and reduced in anorexia nervosa. Accumulating evidence indicates that genetic or antibody-mediated neutralization of ACBP/DBI has anorexigenic effects, thus inhibiting food intake and inducing lipo-catabolic reactions in mice. A number of anorexiants have been withdrawn from clinical development because of their side effects including an increase in depression and suicide. For this reason, we investigated the psychiatric impact of ACBP/DBI in mouse models and patient cohorts. Intravenously (i.v.) injected ACBP/DBI protein conserved its orexigenic function when the protein was mutated to abolish acyl coenzyme A binding, but lost its appetite-stimulatory effect in mice bearing a mutation in the γ2 subunit of the γ-aminobutyric acid (GABA) A receptor (GABAAR). ACBP/DBI neutralization by intraperitoneal (i.p.) injection of a specific mAb blunted excessive food intake in starved and leptin-deficient mice, but not in ghrelin-treated animals. Neither i.v. nor i.p. injected anti-ACBP/DBI antibody affected the behavior of mice in the dark–light box and open-field test. In contrast, ACBP/DBI increased immobility in the forced swim test, while anti-ACBP/DBI antibody counteracted this sign of depression. In patients diagnosed with therapy-resistant bipolar disorder or schizophrenia, ACBP/DBI similarly correlated with body mass index (BMI), not with the psychiatric diagnosis. Patients with high levels of ACBP/DBI were at risk of dyslipidemia and this effect was independent from BMI, as indicated by multivariate analysis. In summary, it appears that ACBP/DBI neutralization has no negative impact on mood and that human depression is not associated with alterations in ACBP/DBI concentrations.

International audience; Background: Suicidal behavior is a major public health concern worldwide, and the interest in the development of novel and more efficient treatment strategies and therapies to reduce suicidal risk is increasing. Some recent studies have summarized the results of randomized clinical trials (RCTs) assessing the efficacy of psychotherapeutic tools designed to treat patients at suicidal risk. However, observational studies, which reflect real-world effectiveness and may use original approaches, have not been reviewed. Method: The aim of this study is to systematically review the available scientific evidence issued from observational studies on the clinical effectiveness of psychotherapeutic tools designed to treat patients at suicide risk. We have thus performed a systematic search of PubMed and Web of Science databases. Results: Out of 1578 papers, 40 original observational studies fulfilled our selection criteria. The most used psychotherapeutic treatments were dialectical behavioral therapy (DBT, 27.5%) and cognitive behavioral therapy (CBT, 15.0%) in patients with a diagnosis of borderline personality disorder (32.5%) and depression (15.0%). Despite the between-study heterogeneity, interventions lead to a reduction in suicidal outcomes, i.e., suicidal ideation (55.0%) and suicide attempts (37.5%). The content and reporting quality varied considerably between the studies. Conclusion: DBT and CBT are the most widely used psychotherapeutic interventions and show promising results in existing observational studies. Some of the included studies provide innovative approaches. Group therapies and internet-based therapies, which are cost-effective methods, are promising treatments and would need further study.

Background Social isolation is one of the main risk factors associated with suicidal outcomes. The aim of this narrative review was to provide an overview on the link between social isolation and suicidal thoughts and behaviors. Methods We used the PubMed database to identify relevant articles published until April 13, 2018. We focused on: (a) systematic reviews, meta-analyses, and narrative reviews; (b) original observational studies with large samples (N ≥ 500); and (c) qualitative studies. We included all relevant suicidal outcomes: suicidal ideation (SI), suicidal planning, non-suicidal self-injury, deliberate self-harm, suicide attempt (SA), and suicide. Results The main social constructs associated with suicidal outcomes were marital status (being single, separated, divorced, or widowed) and living alone, social isolation, loneliness, alienation, and belongingness. We included 40 original observational studies, the majority of them performed on adolescents and/or young adults (k = 23, 57.5%). Both the objective condition (e.g., living alone) and the subjective feeling of being alone (i.e., loneliness) were strongly associated with suicidal outcomes, in particular with SA and SI. However, loneliness, which was investigated in most studies (k = 24, 60%), had a major impact on both SI and SA. These associations were transculturally consistent. Limitations Confounding factors can limit the weight of the results obtained in observational studies. Conclusions Data from the observational studies suggest that both objective social isolation and the subjective feeling of loneliness should be incorporated in the risk assessment of suicide. Interventional studies targeting social isolation for suicide prevention are needed.

International audience; PURPOSE OF REVIEW: The definition of psychological pain is complex. It is a lasting unpleasant and unsustainable feeling characterized by a perception of inability or deficiency of the self, as well as frustrated psychological needs and social disconnection. The aim of our review was to summarize the most recent and updated findings supporting the role of psychological pain in the pathophysiology of depression and suicidal behavior. We also explored the relationship between psychological and physical pain in depression and suicide. RECENT FINDINGS: Psychological pain is a prominent dimension of depressive disorder and has been associated with higher risk of suicidal ideation and suicidal behavior. Sensitivity to psychological and physical pain is increased in depression. Conversely, higher tolerance to physical pain is associated with suicidal behavior. A better understanding of the pathophysiology of pain processing in depression and suicide offers new therapeutic options for the treatment of depression through the use of analgesic drugs.

Objective: Perform a meta-analysis to quantify the association between psychological pain and current or lifetime history of suicidal ideation or suicide attempt. Data Sources: Search MEDLINE, Web of Science, and PsycINFO from 1965 to 2015 for (psychache OR mental pain OR psychological pain) AND (suicid*). Study Selection: Observational case-control studies addressing the difference in psychological pain between individuals with and without current or lifetime history of suicidal ideation or suicide attempt. Data Extraction: Data were independently extracted into a standard electronic form. All authors were contacted for unpublished data related to current or lifetime history of suicide ideation or attempt. Data Synthesis: Twenty studies were included. Comparisons concerned 760 subjects with versus 8,803 subjects without lifetime history of suicide attempt; 344 subjects with versus 357 patients without current suicide attempt; 262 patients with versus 64 patients without lifetime history of suicidal ideation; and 551 subjects with versus 7,383 subjects without current suicidal ideation. The intensity of psychological pain was higher (1) in both subjects with lifetime history of suicide attempts and subjects with current suicide attempts versus without (effect sizes= 0.72, P< 10(-2) and 0.66, P< 10(-2), respectively) and (2) in both subjects with lifetime history of suicide ideation and subjects with current suicidal ideation versus without (effect sizes= 1.49, P = .01 and 1.15, P< 10(-2), respectively). Association between psychological pain and suicidality remained significant even when depression levels were not different between subjects. Conclusions: Higher psychological pain levels are associated with suicidal ideation and acts. Considering psychological pain to be at the core of suicidality is important for daily clinical practice and for the promotion of innovative therapeutic strategies for suicide prevention

Background: The management of suicidal crisis remains a major issue for clinicians, driving the development of new strategies to improve suicide prevention. Methods: We conducted a randomized controlled trial comparing a 7-week acceptance and commitment therapy (ACT) versus relaxation group, as adjunct to treatment as usual for adult outpatients suffering from a current suicidal behavior disorder. The primary outcome was the rate of change in the Columbia Suicide Severity Rating Scale suicidal ideation subscore (adding severity and intensity subscores). Secondary outcomes were the rates of change for depressive symptomatology, psychological pain, anxiety, hopelessness, anger, quality of life, and therapeutic processes. Assessments were performed in the 2 weeks preceding the beginning of the treatment (pretreatment assessment), and within 1 week (posttherapy assessment) and 3 months (follow-up assessment) after therapy completion. Results: Forty adults were included and randomized. The rate of change in ACT for suicidal ideation at the posttherapy assessment was higher than in the relaxation group (beta [SE] = -1.88 [0.34] vs. -0.79 [0.37], respectively; p = 0.03). ACT effectiveness remained stable at the 3-month follow-up. We found a similar pattern of change for depressive symptomatology and anxiety, psychological pain, hopelessness, anger, and quality of life. Therapeutic processes improved more in the ACT group than in the relaxation group. Treatment adherence was high in the ACT group, all participants reported satisfaction with the program. Conclusions: Through its effectiveness in reducing suicidal ideation and improving the clinical dimensions associated with suicidal risk in patients suffering from a suicidal behavior disorder, ACT could be developed as an adjunctive strategy in programs for suicide prevention. (C) 2018 S. Karger AG, Basel Background: The management of suicidal crisis remains a major issue for clinicians, driving the development of new strategies to improve suicide prevention. Methods: We conducted a randomized controlled trial comparing a 7-week acceptance and commitment therapy (ACT) versus relaxation group, as adjunct to treatment as usual for adult outpatients suffering from a current suicidal behavior disorder. The primary outcome was the rate of change in the Columbia Suicide Severity Rating Scale suicidal ideation subscore (adding severity and intensity subscores). Secondary outcomes were the rates of change for depressive symptomatology, psychological pain, anxiety, hopelessness, anger, quality of life, and therapeutic processes. Assessments were performed in the 2 weeks preceding the beginning of the treatment (pretreatment assessment), and within 1 week (posttherapy assessment) and 3 months (follow-up assessment) after therapy completion. Results: Forty adults were included and randomized. The rate of change in ACT for suicidal ideation at the posttherapy assessment was higher than in the relaxation group (β [SE] = -1.88 [0.34] vs. -0.79 [0.37], respectively; p = 0.03). ACT effectiveness remained stable at the 3-month follow-up. We found a similar pattern of change for depressive symptomatology and anxiety, psychological pain, hopelessness, anger, and quality of life. Therapeutic processes improved more in the ACT group than in the relaxation group. Treatment adherence was high in the ACT group, all participants reported satisfaction with the program. Conclusions: Through its effectiveness in reducing suicidal ideation and improving the clinical dimensions associated with suicidal risk in patients suffering from a suicidal behavior disorder, ACT could be developed as an adjunctive strategy in programs for suicide prevention.

Suicidal behavior in older adults (65 years old and over) is a major public health issue in many countries. Suicide rates increase during the life course and are as high as 48.7/100,000 among older white men in the USA. Specific health conditions and stress factors increase the complexity of the explanatory model for suicide in older adults. A PubMed literature search was performed to identify most recent and representative studies on suicide risk factors in older adults. The aim of our narrative review was to provide a critical evaluation of recent findings concerning specific risk factors for suicidal thoughts and behaviors among older people: psychiatric and neurocognitive disorders, social exclusion, bereavement, cognitive impairment, decision making and cognitive inhibition, physical illnesses, and physical and psychological pain. We also aimed to approach the problem of euthanasia or physician-assisted suicide in older adults. Our main findings emphasize the need to integrate specific stress factors, such as feelings of social disconnectedness, neurocognitive impairment or decision making, as well as chronic physical illnesses and disability in suicide models and in suicide prevention programs in older adults. Furthermore, the chronic care model should be adapted for the treatment of older people with long-term conditions in order to improve the treatment of depressive disorders and the prevention of suicidal thoughts and acts. Suicidal behavior in older adults (65 years old and over) is a major public health issue in many countries. Suicide rates increase during the life course and are as high as 48.7/100,000 among older white men in the USA. Specific health conditions and stress factors increase the complexity of the explanatory model for suicide in older adults. A PubMed literature search was performed to identify most recent and representative studies on suicide risk factors in older adults. The aim of our narrative review was to provide a critical evaluation of recent findings concerning specific risk factors for suicidal thoughts and behaviors among older people: psychiatric and neurocognitive disorders, social exclusion, bereavement, cognitive impairment, decision making and cognitive inhibition, physical illnesses, and physical and psychological pain. We also aimed to approach the problem of euthanasia or physician-assisted suicide in older adults. Our main findings emphasize the need to integrate specific stress factors, such as feelings of social disconnectedness, neurocognitive impairment or decision making, as well as chronic physical illnesses and disability in suicide models and in suicide prevention programs in older adults. Furthermore, the chronic care model should be adapted for the treatment of older people with long-term conditions in order to improve the treatment of depressive disorders and the prevention of suicidal thoughts and acts.

International audience; No abstract

ContexteLes conduites suicidaires (CS) constituent un problème de santé publique majeur à travers le monde. Elles présentent une vulnérabilité propre, et sont maintenant considérées comme une entité diagnostique indépendante dans le DSM5. La thérapie d’acceptation et d’engagement (ACT) est une thérapie intégrative ayant démontré son utilité dans une grande variété de troubles psychiatriques, à travers une diminution de l’évitement expérientiel et une amélioration de la flexibilité psychologique (socles communs à l’ensemble des troubles psychiatriques) .InnovationNous avons conduit une étude pilote suggérant la faisabilité de la thérapie ACT, sous forme de groupes, chez les patients suicidants (CHRU de Montpellier, Pr Courtet) . À travers la présentation des processus thérapeutiques utilisés dans la thérapie ACT, nous aborderons les hypothèses d’action de la thérapie ACT dans les conduites suicidaires. Puis nous présenterons l’étude IMPACT, en cours de réalisation dans le service urgences et post-urgences psychiatriques (CHRU de Montpellier, Pr Courtet). Il s’agit de la première étude contrôlée randomisée recherchant des biomarqueurs neuroanatomiques et fonctionnels de réponse à la thérapie ACT chez des patients ayant un trouble des conduites suicidaires. Nous aborderons enfin, de façon pratique, comment présenter la thérapie ACT à un patient, à travers une matrice . Il s’agit d’une analyse fonctionnelle permettant de faire percevoir au patient le fonctionnement actuel dans lequel il se sent enlisé, de mettre en lumière ce qui est important dans sa vie, et donc d’avoir un outil motivationnel simple et efficace pour l’accompagner vers le changement.PerspectivesLa thérapie ACT semble être une thérapie prometteuse dans la prise en charge des conduites suicidaires. L’étude IMPACT servira à accroître les connaissances sur les conduites suicidaires par l’identification de biomarqueurs de réponse thérapeutique et la mise en évidence des régions cérébrales associées aux processus thérapeutiques.