Dataset Information

Pathways to Late-Life Suicidal Behavior: Cluster Analysis and Predictive Validation of Suicidal Behavior in a Sample of Older Adults With Major Depression.

ABSTRACT: 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.

SUBMITTER: Szanto K

PROVIDER: S-EPMC5932247 | biostudies-literature | 2018 Mar/Apr

REPOSITORIES: biostudies-literature

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Pathways to Late-Life Suicidal Behavior: Cluster Analysis and Predictive Validation of Suicidal Behavior in a Sample of Older Adults With Major Depression.

Szanto Katalin K Galfalvy Hanga H Vanyukov Polina M PM Keilp John G JG Dombrovski Alexandre Y AY

The Journal of clinical psychiatry 20180301 2

<h4>Objective</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 29489076

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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.

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.

Project description:Late-life depression is associated with significant cognitive impairment. Meta-analyses showed that depression is associated with an increased risk for Alzheimer's disease (AD) and it might be an etiological factor for AD. Since late-life depression is often connected with cognitive impairment and dementia is usually associated with depressive symptoms, a simple diagnostic approach to distinguish between the disorders is challenging. Several overlapping pathophysiological substrates might explain the comorbidity of both syndromes. Firstly, a stress syndrome, i.e., elevated cortisol levels, has been observed in up to 70% of depressed patients and also in AD pathology. Stress conditions can cause hippocampal neuronal damage as well as cognitive impairment. Secondly, the development of a depression and dementia after the onset of vascular diseases, the profile of cerebrovascular risk factors in both disorders and the impairments depending on the location of cerebrovascular lesions, speak in favor of a vascular hypothesis as a common factor for both disorders. Thirdly, neuroinflammatory processes play a key role in the etiology of depression as well as in dementia. Increased activation of microglia, changes in Transforming-Growth-Factor beta1 (TGF-beta1) signaling, production of pro-inflammatory cytokines as well as reduction of anti-inflammatory molecules are examples of common pathways impaired in dementia and depression. Fourthly, the neurotrophin BDNF is highly expressed in the central nervous system, especially in the hippocampus, where it plays a key role in the proliferation, differentiation and the maintenance of neuronal integrity throughout lifespan. It has been associated not only with antidepressant properties but also a reduction of cognitive impairment and therefore could be involved also in AD. Another etiologic factor is amyloid accumulation, as plasma amyloid beta-42 independently predicts both late-onset depression and AD. Higher plasma amyloid beta-42 predicts the development of late onset depression and conversion to possible AD. However, clinical trials with antibodies against beta amyloid recently failed, i.e., Solanezumab, Aducanumab, and Crenezumab. An overproduction of amyloid-beta might simply reflect a form of synaptic plasticity to compensate for neuronal dysfunction in different kind of neurological and psychiatric diseases of multiple etiologies. The tau hypothesis, sex/gender specific differences, epigenetics and the gut microbiota-brain axis imply other potential common pathways connecting late-life depression and dementia. In conclusion, different potential pathophysiological links between dementia and depression highlight several specific synergistic and multifaceted treatment possibilities, depending on the individual risk profile of the patient.

Dataset Information

Pathways to Late-Life Suicidal Behavior: Cluster Analysis and Predictive Validation of Suicidal Behavior in a Sample of Older Adults With Major Depression.

Publications

Pathways to Late-Life Suicidal Behavior: Cluster Analysis and Predictive Validation of Suicidal Behavior in a Sample of Older Adults With Major Depression.

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