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Future suicide attempt and responses to serotonergic challenge.

ABSTRACT: Blunted neurohormonal responses to serotonergic agents are found in major depression and suicidal behavior, but there have been no prospective studies of their relationship to later suicide attempt. In this study, healthy volunteers and depressed subjects were administered a fenfluramine (FEN) and placebo challenge test at baseline and then followed for 2 years. Seven subjects made suicide attempts within the follow-up period. Healthy volunteers, depressed non-attempters, depressed past suicide attempters, and depressed future attempters were compared on plasma prolactin and cortisol responses, as well as on mood (Profile of Mood States; POMS) and behavioral measures that were assessed at baseline and at the end of each challenge testing day. Both past and future attempters had lower total prolactin output (area under the curve) in response to FEN relative to non-patients. Future attempters had lower cortisol response relative to all other groups. All subject groups reported a decrease in POMS Fatigue subscale score and increase in finger tapping rate after receiving FEN. Depressed subjects reported a significant decline in POMS Total, Depression, and Tension/Anxiety scores, but future attempters' did not, showing a slight mean increase. Lower cortisol response correlated with greater suicidal ideation 3 months and 1 year post-study. Logistic regression revealed that blunting of cortisol response and worsening of mood after FEN, and younger age could be used to predict later suicide attempt in the majority of cases (4/7). Results suggest that blunted cortisol and unfavorable acute mood response to serotonergic challenge, in the context of the general activating effects of these drugs, may be a risk factor for later suicide attempt.

SUBMITTER: Keilp JG

PROVIDER: S-EPMC3055397 | biostudies-other | 2010 Apr

REPOSITORIES: biostudies-other

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Project description:Suicide accounts for nearly 800,000 deaths per year worldwide with rates of both deaths and attempts rising. Family studies have estimated substantial heritability of suicidal behavior; however, collecting the sample sizes necessary for successful genetic studies has remained a challenge. We utilized two different approaches in independent datasets to characterize the contribution of common genetic variation to suicide attempt. The first is a patient reported suicide attempt phenotype asked as part of an online mental health survey taken by a subset of participants (n = 157,366) in the UK Biobank. After quality control, we leveraged a genotyped set of unrelated, white British ancestry participants including 2433 cases and 334,766 controls that included those that did not participate in the survey or were not explicitly asked about attempting suicide. The second leveraged electronic health record (EHR) data from the Vanderbilt University Medical Center (VUMC, 2.8 million patients, 3250 cases) and machine learning to derive probabilities of attempting suicide in 24,546 genotyped patients. We identified significant and comparable heritability estimates of suicide attempt from both the patient reported phenotype in the UK Biobank (h2SNP = 0.035, p = 7.12 × 10-4) and the clinically predicted phenotype from VUMC (h2SNP = 0.046, p = 1.51 × 10-2). A significant genetic overlap was demonstrated between the two measures of suicide attempt in these independent samples through polygenic risk score analysis (t = 4.02, p = 5.75 × 10-5) and genetic correlation (rg = 1.073, SE = 0.36, p = 0.003). Finally, we show significant but incomplete genetic correlation of suicide attempt with insomnia (rg = 0.34-0.81) as well as several psychiatric disorders (rg = 0.26-0.79). This work demonstrates the contribution of common genetic variation to suicide attempt. It points to a genetic underpinning to clinically predicted risk of attempting suicide that is similar to the genetic profile from a patient reported outcome. Lastly, it presents an approach for using EHR data and clinical prediction to generate quantitative measures from binary phenotypes that can improve power for genetic studies.

Project description:BackgroundSuicidal thoughts and non-suicidal self-harm are common in adolescents and are strongly associated with suicide attempts. We aimed to identify predictors of future suicide attempts in these high-risk groups.MethodsParticipants were from the Avon Longitudinal Study of Parents and Children, a population-based birth cohort study in the UK. The sample included 456 adolescents who reported suicidal thoughts and 569 who reported non-suicidal self-harm at 16 years of age. Logistic regression analyses were used to explore associations between a wide range of prospectively recorded risk factors and future suicide attempts, assessed at the age of 21 years.Findings38 (12%) of 310 participants with suicidal thoughts and 46 (12%) of 380 participants who had engaged in non-suicidal self-harm reported having attempted suicide for the first time by the follow-up at 21 years of age. Among participants with suicidal thoughts, the strongest predictors of transition to attempts were non-suicidal self-harm (odds ratio [OR] 2·78, 95% CI 1·35-5·74; p=0·0059), cannabis use (2·61, 1·11-6·14; p=0·029), other illicit drug use (2·47, 1·02-5·96; p=0·045), exposure to self-harm (family 2·03, 0·93-4·44, p=0·076; friend 1·85, 0·93-3·69, p=0·081), and higher levels of the personality type intellect/openness (1·62, 1·06-2·46; p=0·025). Among participants with non-suicidal self-harm at baseline, the strongest predictors were cannabis use (OR 2·14, 95% CI 1·04-4·41; p=0·038), other illicit drug use (2·17, 1·10-4·27; p=0·025), sleep problems (waking in the night 1·91, 0·95-3·84, p=0·069; insufficient sleep 1·97, 1·02-3·81, p=0·043), and lower levels of the personality type extraversion (0·71, 0·49-1·03; p=0·068).InterpretationMost adolescents who think about suicide or engage in non-suicidal self-harm will not make an attempt on their life. Many commonly cited risk factors were not associated with transition to suicide attempt among these high-risk groups. Our findings suggest that asking about substance use, non-suicidal self-harm, sleep, personality traits, and exposure to self-harm could inform risk assessments, and might help clinicians to identify which adolescents are at greatest risk of attempting suicide in the future.FundingAmerican Foundation for Suicide Prevention, National Institute for Health Research Biomedical Research Centre at the University Hospitals Bristol National Health Service Foundation Trust, and the University of Bristol.

Project description:ImportanceMental health of soldiers is adversely affected by the death and injury of other unit members, but whether risk of suicide attempt is influenced by previous suicide attempts in a soldier's unit is unknown.ObjectiveTo examine whether a soldier's risk of suicide attempt is influenced by previous suicide attempts in that soldier's unit.Design, setting, and participantsUsing administrative data from the Army Study to Assess Risk and Resilience in Servicemembers (STARRS), this study identified person-month records for all active-duty, regular US Army, enlisted soldiers who attempted suicide from January 1, 2004, through December 31, 2009 (n = 9650), and an equal-probability sample of control person-months (n = 153 528). Data analysis was performed from August 8, 2016, to April 10, 2017.Main outcomes and measuresLogistic regression analyses examined the number of past-year suicide attempts in a soldier's unit as a predictor of subsequent suicide attempt, controlling for sociodemographic features, service-related characteristics, prior mental health diagnosis, and other unit variables, including suicide-, combat-, and unintentional injury-related unit deaths. The study also examined whether the influence of previous unit suicide attempts varied by military occupational specialty (MOS) and unit size.ResultsOf the final analytic sample of 9512 enlisted soldiers who attempted suicide and 151 526 control person-months, most were male (86.4%), 29 years or younger (68.4%), younger than 21 years when entering the army (62.2%), white (59.8%), high school educated (76.6%), and currently married (54.8%). In adjusted models, soldiers were more likely to attempt suicide if 1 or more suicide attempts occurred in their unit during the past year (odds ratios [ORs], 1.4-2.3; P < .001), with odds increasing as the number of unit attempts increased. The odds of suicide attempt among soldiers in a unit with 5 or more past-year attempts was more than twice that of soldiers in a unit with no previous attempts (OR, 2.3; 95% CI, 2.1-2.6). The association of previous unit suicide attempts with subsequent risk was significant whether soldiers had a combat arms MOS or other MOS (ORs, 1.4-2.3; P < .001) and regardless of unit size, with the highest risk among those in smaller units (1-40 soldiers) (ORs, 2.1-5.9; P < .001). The population-attributable risk proportion for 1 or more unit suicide attempts in the past year indicated that, if this risk could be reduced to no unit attempts, 18.2% of attempts would not occur.Conclusions and relevanceRisk of suicide attempt among soldiers increased as the number of past-year suicide attempts within their unit increased for combat arms and other MOSs and for units of any size but particularly for smaller units. Units with a history of suicide attempts may be important targets for preventive interventions.

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Future suicide attempt and responses to serotonergic challenge.

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