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      Association Between the A118G Polymorphism of the OPRM1 Gene and Suicidal Depression in a Large Cohort of Outpatients with Depression

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          Abstract

          Background

          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.

          Most cited references50

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          Risk factors for suicidal thoughts and behaviors: A meta-analysis of 50 years of research.

          Suicidal thoughts and behaviors (STBs) are major public health problems that have not declined appreciably in several decades. One of the first steps to improving the prevention and treatment of STBs is to establish risk factors (i.e., longitudinal predictors). To provide a summary of current knowledge about risk factors, we conducted a meta-analysis of studies that have attempted to longitudinally predict a specific STB-related outcome. This included 365 studies (3,428 total risk factor effect sizes) from the past 50 years. The present random-effects meta-analysis produced several unexpected findings: across odds ratio, hazard ratio, and diagnostic accuracy analyses, prediction was only slightly better than chance for all outcomes; no broad category or subcategory accurately predicted far above chance levels; predictive ability has not improved across 50 years of research; studies rarely examined the combined effect of multiple risk factors; risk factors have been homogenous over time, with 5 broad categories accounting for nearly 80% of all risk factor tests; and the average study was nearly 10 years long, but longer studies did not produce better prediction. The homogeneity of existing research means that the present meta-analysis could only speak to STB risk factor associations within very narrow methodological limits-limits that have not allowed for tests that approximate most STB theories. The present meta-analysis accordingly highlights several fundamental changes needed in future studies. In particular, these findings suggest the need for a shift in focus from risk factors to machine learning-based risk algorithms. (PsycINFO Database Record
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            Cross-national prevalence and risk factors for suicidal ideation, plans and attempts.

            Suicide is a leading cause of death worldwide; however, the prevalence and risk factors for the immediate precursors to suicide - suicidal ideation, plans and attempts - are not wellknown, especially in low- and middle-income countries. To report on the prevalence and risk factors for suicidal behaviours across 17 countries. A total of 84 850 adults were interviewed regarding suicidal behaviours and socio-demographic and psychiatric risk factors. The cross-national lifetime prevalence of suicidal ideation, plans, and attempts is 9.2% (s.e.=0.1), 3.1% (s.e.=0.1), and 2.7% (s.e.=0.1). Across all countries, 60% of transitions from ideation to plan and attempt occur within the first year after ideation onset. Consistent cross-national risk factors included being female, younger, less educated, unmarried and having a mental disorder. Interestingly, the strongest diagnostic risk factors were mood disorders in high-income countries but impulse control disorders in low- and middle-income countries. There is cross-national variability in the prevalence of suicidal behaviours, but strong consistency in the characteristics and risk factors for these behaviours. These findings have significant implications for the prediction and prevention of suicidal behaviours.
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              Prevalence, correlates, and treatment of lifetime suicidal behavior among adolescents: results from the National Comorbidity Survey Replication Adolescent Supplement.

              Although suicide is the third leading cause of death among US adolescents, little is known about the prevalence, correlates, or treatment of its immediate precursors, adolescent suicidal behaviors (ie, suicide ideation, plans, and attempts). To estimate the lifetime prevalence of suicidal behaviors among US adolescents and the associations of retrospectively reported, temporally primary DSM-IV disorders with the subsequent onset of suicidal behaviors. Dual-frame national sample of adolescents from the National Comorbidity Survey Replication Adolescent Supplement. Face-to-face household interviews with adolescents and questionnaires for parents. A total of 6483 adolescents 13 to 18 years of age and their parents. Lifetime suicide ideation, plans, and attempts. The estimated lifetime prevalences of suicide ideation, plans, and attempts among the respondents are 12.1%, 4.0%, and 4.1%, respectively. The vast majority of adolescents with these behaviors meet lifetime criteria for at least one DSM-IV mental disorder assessed in the survey. Most temporally primary (based on retrospective age-of-onset reports) fear/anger, distress, disruptive behavior, and substance disorders significantly predict elevated odds of subsequent suicidal behaviors in bivariate models. The most consistently significant associations of these disorders are with suicide ideation, although a number of disorders are also predictors of plans and both planned and unplanned attempts among ideators. Most suicidal adolescents (>80%) receive some form of mental health treatment. In most cases (>55%), treatment starts prior to onset of suicidal behaviors but fails to prevent these behaviors from occurring. Suicidal behaviors are common among US adolescents, with rates that approach those of adults. The vast majority of youth with suicidal behaviors have preexisting mental disorders. The disorders most powerfully predicting ideation, though, are different from those most powerfully predicting conditional transitions from ideation to plans and attempts. These differences suggest that distinct prediction and prevention strategies are needed for ideation, plans among ideators, planned attempts, and unplanned attempts.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                ndt
                Neuropsychiatric Disease and Treatment
                Dove
                1176-6328
                1178-2021
                14 October 2021
                2021
                : 17
                : 3109-3118
                Affiliations
                [1 ]Department of Emergency Psychiatry and Acute Care, CHU Montpellier , Montpellier, France
                [2 ]IGF, University of Montpellier, CNRS, INSERM , Montpellier, France
                [3 ]FondaMental Foundation , Créteil, France
                [4 ]Inserm UMRS1266, Institute of Psychiatry and Neuroscience of Paris , Paris, France
                Author notes
                Correspondence: Benedicte Nobile Email benedicte.nobile@gmail.com
                Author information
                http://orcid.org/0000-0002-2570-6996
                http://orcid.org/0000-0002-8070-9938
                Article
                324868
                10.2147/NDT.S324868
                8525413
                55f9c02d-fddf-412d-ae47-120647eee15e
                © 2021 Nobile et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 18 June 2021
                : 19 August 2021
                Page count
                Figures: 0, Tables: 11, References: 50, Pages: 10
                Categories
                Original Research

                Neurology
                suicide,suicidal ideation,opioid system,a118g,oprm1
                Neurology
                suicide, suicidal ideation, opioid system, a118g, oprm1

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