Predictors of serious suicidal behavior in late-life depression.
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ABSTRACT:
SUBMITTER: Szanto K
PROVIDER: S-EPMC7655527 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Suicidal behavior is associated with impaired decision making in contexts of uncertainty. Existing studies, however, do not definitively address whether suidice attempers have 1) impairment in learning from experience or 2) impairment in choice based on comparison of estimated option values. Our reinforcement learning model-based behavioral study tested these hypotheses directly in middle-aged and older suicide attempters representative of those who die by suicide. METHODS:Two samples (sample 1, n = 135; sample 2, n = 125) of suicide attempters with depression (nattempters = 54 and 39, respectively), suicide ideators, nonsuicidal patients with depression, and healthy control participants completed a probabilistic three-choice decision-making task. A second experiment in sample 2 experimentally dissociated long-term learned value from reward magnitude. Analyses combined computational reinforcement learning and mixed-effects models of decision times and choices. RESULTS:With regard to learning, suicide attempters (vs. all comparison groups) were less sensitive to one-back reinforcement, as indicated by a reduced effect on both choices and decision times. Learning deficits scaled with attempt lethality and were partially explained by poor cognitive control. With regard to value-based choice, suicide attempters (vs. all comparison groups) displayed abnormally long decision times when choosing between similarly valued options and were less able to distinguish between the best and second-best options. Group differences in value-based choice were robust to controlling for cognitive performance, comorbidities, impulsivity, psychotropic exposure, and possible brain damage from attempts. CONCLUSIONS:Serious suicidal behavior is associated with impaired reward learning, likely undermining the search for alternative solutions. Attempted suicide is associated with impaired value comparison during the choice process, potentially interfering with the consideration of deterrents and alternatives in a crisis.
| S-EPMC6380943 | biostudies-literature
Project description:This study aimed to identify subgroups of depressed older adults with distinct trajectories of suicidal ideation during brief psychotherapy and to detect modifiable predictors of membership to the trajectories of suicidal ideation. Latent growth mixed models were used to identify trajectories of the presence of suicidal ideation in participants to a randomized controlled trial comparing Problem Solving Therapy with "Engage" therapy in older adults with major depression over 9 weeks. Predictors of membership to trajectories of suicidal ideation were identified by the convergence of four machine learning models, i.e., least absolute shrinkage and selection operator logistic regression, random forest, gradient boosting machine, and classification tree. The course of suicidal ideation was best captured by two trajectories, a favorable and an unfavorable trajectory comprising 173 and 76 participants respectively. Members of the favorable trajectory had no suicidal ideation by week 8. In contrast, members of the unfavorable trajectory had a 60% probability of suicidal ideation by treatment end. Convergent findings of the four machine learning models identified hopelessness, neuroticism, and low general self-efficacy as the strongest predictors of membership to the unfavorable trajectory of suicidal ideation during psychotherapy. Assessment of suicide risk should include hopelessness, neuroticism, and general self-efficacy as they are predictors of an unfavorable course of suicidal ideation in depressed older adults receiving psychotherapy. Psychotherapeutic interventions exist for hopelessness, emotional reactivity related to neuroticism, and low self-efficacy, and if used during therapy, may improve the course of suicidal ideation.
| S-EPMC8523563 | biostudies-literature
Project description:OBJECTIVE:Clinical heterogeneity is a key challenge to understanding suicidal risk, as different pathways to suicidal behavior are likely to exist. We aimed to identify such pathways by uncovering latent classes of late-life depression cases and relating them to prior and future suicidal behavior. METHODS:Data were collected from June 2010 to September 2015. In this longitudinal study we examined distinct associations of clinical and cognitive/decision-making factors with suicidal behavior in 194 older (50+ years) nondemented, depressed patients; 57 nonpsychiatric healthy controls provided benchmark data. The DSM-IV was used to establish diagnostic criteria. We identified multivariate patterns of risk factors, defining clusters based on personality traits, perceived social support, cognitive performance, and decision-making in an analysis blinded to participants' history of suicidal behavior. We validated these clusters using past and prospective suicidal ideation and behavior. RESULTS:Of 5 clusters identified, 3 were associated with high risk for suicidal behavior: (1) cognitive deficits, dysfunctional personality, low social support, high willingness to delay future rewards, and overrepresentation of high-lethality attempters; (2) high-personality pathology (ie, low self-esteem), minimal or no cognitive deficits, and overrepresentation of low-lethality attempters and ideators; (3) cognitive deficits, inability to delay future rewards, and similar distribution of high- and low-lethality attempters. There were significant between-cluster differences in number (P < .001) and lethality (P = .002) of past suicide attempts and in the likelihood of future suicide attempts (P = .010, 30 attempts by 22 patients, 2 fatal) and emergency psychiatric hospitalizations to prevent suicide (P = .005, 31 participants). CONCLUSIONS:Three pathways to suicidal behavior in older patients were found, marked by (1) very high levels of cognitive and dispositional risk factors suggesting a dementia prodrome, (2) dysfunctional personality traits, and (3) impulsive decision-making and cognitive deficits.
| S-EPMC5932247 | biostudies-literature
Project description:BackgroundLate-life depression (LLD) is associated with a fragile antidepressant response and high recurrence risk. This study examined what measures predict recurrence in remitted LLD.MethodsIndividuals of age 60 years or older with a Diagnostic and Statistical Manual - IV (DSM-IV) diagnosis of major depressive disorder were enrolled in the neurocognitive outcomes of depression in the elderly study. Participants received manualized antidepressant treatment and were followed longitudinally for an average of 5 years. Study analyses included participants who remitted. Measures included demographic and clinical measures, medical comorbidity, disability, life stress, social support, and neuropsychological testing. A subset underwent structural magnetic resonance imaging (MRI).ResultsOf 241 remitted elders, approximately over 4 years, 137 (56.8%) experienced recurrence and 104 (43.2%) maintained remission. In the final model, greater recurrence risk was associated with female sex (hazard ratio [HR] = 1.536; confidence interval [CI] = 1.027-2.297), younger age of onset (HR = 0.990; CI = 0.981-0.999), higher perceived stress (HR = 1.121; CI = 1.022-1.229), disability (HR = 1.060; CI = 1.005-1.119), and less support with activities (HR = 0.885; CI = 0.812-0.963). Recurrence risk was also associated with higher Montgomery-Asberg Depression Rating Scale (MADRS) scores prior to censoring (HR = 1.081; CI = 1.033-1.131) and baseline symptoms of suicidal thoughts by MADRS (HR = 1.175; CI = 1.002-1.377) and sadness by Center for Epidemiologic Studies-Depression (HR = 1.302; CI, 1.080-1.569). Sex, age of onset, and suicidal thoughts were no longer associated with recurrence in a model incorporating report of multiple prior episodes (HR = 2.107; CI = 1.252-3.548). Neither neuropsychological test performance nor MRI measures of aging pathology were associated with recurrence.ConclusionsOver half of the depressed elders who remitted experienced recurrence, mostly within 2 years. Multiple clinical and environmental measures predict recurrence risk. Work is needed to develop instruments that stratify risk.
| S-EPMC6035781 | biostudies-literature
Project description:BackgroundTwo treatments for smoking cessation--varenicline and bupropion--carry Boxed Warnings from the U.S. Food and Drug Administration (FDA) about suicidal/self-injurious behavior and depression. However, some epidemiological studies report an increased risk in smoking or smoking cessation independent of treatment, and differences between drugs are unknown.MethodologyFrom the FDA's Adverse Event Reporting System (AERS) database from 1998 through September 2010 we selected domestic, serious case reports for varenicline (n = 9,575), bupropion for smoking cessation (n = 1,751), and nicotine replacement products (n = 1,917). A composite endpoint of suicidal/self-injurious behavior or depression was defined as a case with one or more Preferred Terms in Standardized MedDRA Query (SMQ) for those adverse effects. The main outcome measure was the ratio of reported suicide/self-injury or depression cases for each drug compared to all other serious events for that drug.ResultsOverall we identified 3,249 reported cases of suicidal/self-injurious behavior or depression, 2,925 (90%) for varenicline, 229 (7%) for bupropion, and 95 (3%) for nicotine replacement. Compared to nicotine replacement, the disproportionality results (OR (95% CI)) were varenicline 8.4 (6.8-10.4), and bupropion 2.9 (2.3-3.7). The disproportionality persisted after excluding reports indicating concomitant therapy with any of 58 drugs with suicidal behavior warnings or precautions in the prescribing information. An additional antibiotic comparison group showed that adverse event reports of suicidal/self-injurious behavior or depression were otherwise rare in a healthy population receiving short-term drug treatment.ConclusionsVarenicline shows a substantial, statistically significant increased risk of reported depression and suicidal/self-injurious behavior. Bupropion for smoking cessation had smaller increased risks. The findings for varenicline, combined with other problems with its safety profile, render it unsuitable for first-line use in smoking cessation.
| S-EPMC3206890 | biostudies-literature
Project description:Objective: In young and middle-aged adults, suicidal ideation is an important predictor of prospective suicide attempts, but its predictive power in late life remains unclear. In this study, we used Latent Profile Analysis (LPA) in a cohort of depressed older adults to identify distinct ideation profiles and their clinical correlates and test their association with risk of suicidal behavior longitudinally.Methods: A total of 337 depressed older adults (aged 50-93 years) were assessed for suicidal ideation and behavior for up to 14 years (median = 3 years), at least once per year (study period: 2002-2020). LPA was used, which derived 4 profiles of ideation scores based on subject-level aggregates. Groups were compared using analysis of variance (ANOVA) and χ2 tests at baseline and competing risk survival analysis during follow-up.Results: Ideation showed significant decline over time, on average (P < .001). LPA identified 4 suicidal ideation profiles. Risk of suicide attempt/death was higher for chronic severe ideators (age-adjusted hazard ratio [HR] = 5.75; 95% CI, 2.25-14.7; P < .001) and highly variable ideators (HR = 3.21; 95% CI, 1.03-10.1; P = .045) compared to fast-remitting ideators, despite comparable current ideation severity at baseline. Fast-remitting ideators had higher risk than low/non-ideators with no attempts or suicides (P < .001). Chronic severe ideators displayed the most severe dysfunction across personality, social characteristics, and impulsivity measures, whereas highly variable and fast-remitting ideators displayed specific deficits.Conclusions: Assessing suicidal ideation over months/years has clinical relevance, as it enabled the identification of distinct ideation patterns associated with substantive differences in clinical presentation and risk of future suicidal behavior despite similar ideation levels at baseline.
| S-EPMC10026371 | biostudies-literature
Project description:Late-life depression (LLD), compared to depression at a young age, is more likely to have poor prognosis and high risk of progression to dementia. A recent systemic review and meta-analysis of the present antidepressants for LLD showed that the treatment response rate was 48% and the remission rate was only 33.7%, thus implying the need to improve the treatment with other approaches in the future. Recently, agents modulating the glutamatergic system have been tested for mental disorders such as schizophrenia, dementia, and depressive disorder. Ketamine, a noncompetitive NMDA receptor (NMDAR) antagonist, requires more evidence from randomized clinical trials (RCTs) to prove its efficacy and safety in treating LLD. The metabotropic receptors (mGluRs) of the glutamatergic system are family G-protein-coupled receptors, and inhibition of the Group II mGluRs subtypes (mGlu2 and mGlu3) was found to be as effective as ketamine in exerting rapid antidepressant activity in some animal studies. Inflammation has been thought to contribute to depression for a long time. The cytokine levels not only increase with age but also decrease serotonin. Regarding LLD, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) released in vivo are likely to contribute to the reduced serotonin level. Brain-derived neurotrophic factor (BDNF), a growth factor and a modulator in the tropomyosin receptor kinase (Trk) family of tyrosine kinase receptors, probably declines quantitatively with age. Recent studies suggest that BDNF/TrkB decrement may contribute to learning deficits and memory impairment. In the process of aging, physiological changes in combination with geriatric diseases such as vascular diseases result in poorer prognosis of LLD in comparison with that of young-age depression. Treatments with present antidepressants have been generally unsatisfactory. Novel treatments such as anti-inflammatory agents or NMDAR agonists/antagonists require more studies in LLD. Last but not least, LLD and dementia, which share common pathways and interrelate reciprocally, are a great concern. If it is possible to enhance the treatment of LDD, dementia can be prevented or delated.
| S-EPMC8303929 | biostudies-literature
Project description:Depression is a debilitating mental disorder that frequently occurs in older adults, especially in those with vascular diseases. Nutritional factors have the potential to decrease the occurrence of late-life depression but have not been adequately studied. Low folate levels, disturbed omega-3 fatty acid metabolism and obesity have been associated with depression, and may be causal factors. Longitudinal studies are urgently needed in order to examine the potential of dietary factors to prevent late-life depression.
| S-EPMC2841351 | biostudies-other
Project description:Individuals with psychiatric disorders are vulnerable to adverse mental health outcomes following physical illness. This longitudinal cohort study defined risk profiles for readmission for suicidal behavior and self-harm after general hospitalization of adults with serious mental illness. Structured electronic health record data were analyzed from 15,644 general non-psychiatric index hospitalizations of individuals with depression, bipolar, and psychotic disorders admitted to an urban health system in the southwestern United States between 2006 and 2017. Using data from one-year prior to and including index hospitalization, supervised machine learning was implemented to predict risk of readmission for suicide attempt and self-harm in the following year. The Classification and Regression Tree algorithm produced a classification prediction with an area under the receiver operating curve (AUC) of 0.86 (95% confidence interval (CI) 0.74-0.97). Incidence of suicide-related behavior was highest after general non-psychiatric hospitalizations of individuals with prior suicide attempt or self-harm (18%; 69 cases/389 hospitalizations) and lowest after hospitalizations associated with very high medical morbidity burden (0 cases/3090 hospitalizations). Predictor combinations, rather than single risk factors, explained the majority of risk, including concomitant alcohol use disorder with moderate medical morbidity, and age ≤55-years-old with low medical morbidity. Findings suggest that applying an efficient and highly interpretable machine learning algorithm to electronic health record data may inform general hospital clinical decision support, resource allocation, and preventative interventions for medically ill adults with serious mental illness.
| S-EPMC8009812 | biostudies-literature
Project description:Suicide is the most severe consequence of depression which has become a leading cause of disability and a global disease burden. Recent evidence indicates a central role of small molecules in the pathogenesis of depression and associated suicidal behaviors. However, there lacks a systemic exploration of small molecules in the development of depression-associated suicide, and it remains unclear how they affect an individual's behavior. In order to compare the metabonomic profiles between drug-naïve patients with depression-associated suicidal behaviors and healthy individuals, we conducted a systemic database search for studies of metabolic characteristics in depression-associated suicidal behavior. Manual data curation and statistical analysis and integration were performed in Excel. We further performed an enrichment analysis of signaling pathway prediction using the Reactome Pathway Analysis tool. We have identified 17 metabolites that expressed differently between drug-naïve patients with depression-associated suicidal behaviors and healthy controls. We have integrated these metabolites into biological signaling pathways and provided a visualized signaling network in depressed suicidal patients. We have revealed that "transport of small molecules", "disease", "metabolism" and "metabolism of proteins" were the most relevant signaling sections, among which "transport of inorganic cations/anions and amino acids/oligopeptides", "SLC-mediated transmembrane transport", and "metabolism of amino acids and derivatives" should be further studied to elucidate their potential pathogenic mechanism in the development of depression and associated suicidal behavior. In conclusion, our findings of these 17 metabolites and associated signaling pathways could provide an insight into the molecular pathogenesis of depression-associated suicidal behavior and potential targets for new drug inventions.
| S-EPMC7177018 | biostudies-literature