Diminished responses to bodily threat and blunted interoception in suicide attempters.
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ABSTRACT:
SUBMITTER: DeVille DC
PROVIDER: S-EPMC7138608 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
Diminished responses to bodily threat and blunted interoception in suicide attempters.
DeVille Danielle C DC Kuplicki Rayus R Stewart Jennifer L JL Paulus Martin P MP Khalsa Sahib S SS
eLife 20200407
Psychological theories of suicide suggest that certain traits may reduce aversion to physical threat and increase the probability of transitioning from suicidal ideation to action. Here, we investigated whether blunted sensitivity to bodily signals is associated with suicidal action by comparing individuals with a history of attempted suicide to a matched psychiatric reference sample without suicide attempts. We examined interoceptive processing across a panel of tasks: breath-hold challenge, co ...[more]
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Project description:BackgroundHypothalamic-Pituitary-Adrenal (HPA) axis dysregulation is associated with increased risk for suicidal behavior. However, it is not clear whether such dysregulation exists prior to or is a consequence of attempt. Studies also show an activation of inflammatory responses in suicidal behavior but often combine attempters with those with ideation.MethodsThe sample consisted of psychiatric inpatients, aged 15-30 years, admitted for suicide attempt (SA, n=38), inpatients admitted for suicidal ideation with no prior history of attempts (SI, n=40), and healthy controls (n=37). We compared SA, SI, and controls on hair cortisol concentrations (HCC), which provides retrospective levels of cortisol and thus prior to the attempt in SA. We also compared them on the expression of genes in the HPA axis and inflammatory pathways previously implicated in suicidal behavior (GR or NR3C1, SKA2, FKBP5, IL-1β, TNF-α); plasma C-Reactive Protein (CRP); and cellular measures of glucocorticoid receptor (GR) sensitivity and stimulated production of IL-6.ResultsWe found lower HCC [β=-0.55, 95% CI (-0.96, -0.13), p=0.01, ES=-0.54] in first-time SA compared to SI and controls. In addition, SA showed lower GR or NR3C1 (α isoform) mRNA [β=-5.11, 95% CI (-10.9, 0.73), p=0.09, ES=-0.46], higher CRP [β=0.94, 95% CI (-0.004, 1.9), p=0.05, ES=0.60], and higher TNF-α mRNA [β=26.4, 95% CI (7.7, 45.2), p=0.006, ES=0.73].ConclusionsThis is the first study to differentiate youth who attempt suicide from those with suicidal ideation on HCC and to show that low HCC precedes suicide attempt. Suicide attempters also showed a distinct biological profile on several markers in both the HPA axis and inflammatory pathways. Future longitudinal studies are needed to examine the ability of these biomarkers to predict suicidal behavior.
| S-EPMC5336407 | biostudies-literature
Project description:Studies looking at the relationship of the hypothalamic-pituitary-adrenal (HPA) axis to suicidal behavior and its risk factors, such as depression, childhood abuse, and impulsive aggression, report inconsistent results. These studies also do not always differentiate between subjects who go on to attempt suicide, suicidal subjects who never attempted suicide, and non-suicidal subjects with psychiatric disorders. In this study, we examined cortisol responses to an experimental stressor, the Trier Social Stress Test (TSST), in 208 offspring of parents with mood disorder. Offspring suicide attempters showed lower total cortisol output (β=-0.47, 95% CI (-0.83, -0.11), p=0.01) compared with offspring with suicide-related behavior (SRB) but never attempted, non-suicidal offspring, and a healthy control group. The result remained significant even after controlling for sex, age, race, ethnicity, site, socio-economic status, and hour of the day when the TSST was conducted. Suicide attempters also showed lower baseline cortisol before the TSST (β=-0.45, 95% CI (-0.74, -0.17), p=0.002). However, there were no significant differences between the groups on cortisol reactivity to stress (β=4.5, 95% CI (-12.9, 22), p=0.61). Although subjects with suicide attempt and SRB have similar clinical and psychosocial characteristics, this is the first study to differentiate them biologically on HPA axis indices. Blunted HPA axis activity may increase risk for suicide attempt among individuals with psychopathology by reducing their ability to respond adaptively to ongoing stressors. These results may help better identify subjects at high risk for suicidal behavior for targeted prevention and intervention efforts.
| S-EPMC4832012 | biostudies-literature
Project description:BACKGROUND:Few studies have examined white matter abnormalities in suicide attempters using diffusion tensor imaging (DTI). This study sought to identify white matter regions altered in individuals with a prior suicide attempt. METHODS:DTI scans were acquired in 13 suicide attempters with major depressive disorder (MDD), 39 non-attempters with MDD, and 46 healthy participants (HP). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were determined in the brain using two methods: region of interest (ROI) and tract-based spatial statistics (TBSS). ROIs were limited a priori to white matter adjacent to the caudal anterior cingulate cortex, rostral anterior cingulate cortex, dorsomedial prefrontal cortex, and medial orbitofrontal cortex. RESULTS:Using the ROI approach, suicide attempters had lower FA than MDD non-attempters and HP in the dorsomedial prefrontal cortex. Uncorrected TBSS results confirmed a significant cluster within the right dorsomedial prefrontal cortex indicating lower FA in suicide attempters compared to non-attempters. There were no differences in ADC when comparing suicide attempters, non-attempters and HP groups using ROI or TBSS methods. CONCLUSIONS:Low FA in the dorsomedial prefrontal cortex was associated with a suicide attempt history. Converging findings from other imaging modalities support this finding, making this region of potential interest in determining the diathesis for suicidal behavior.
| S-EPMC4060601 | biostudies-literature
Project description:Suicide rates are high in old age, and the contribution of cognitive risk factors remains poorly understood. Suicide may be viewed as an outcome of an altered decision process. The authors hypothesized that impairment in reward/punishment-based learning, a component of affective decision making, is associated with attempted suicide in late-life depression. They expected that suicide attempters would discount past reward/punishment history, focusing excessively on the most recent rewards and punishments. The authors further hypothesized that this impairment could be dissociated from executive abilities, such as forward planning.The authors assessed reward/punishment-based learning using the probabilistic reversal learning task in 65 individuals age 60 and older: suicide attempters, suicide ideators, nonsuicidal depressed elderly, and nondepressed comparison subjects. The authors used a reinforcement learning computational model to decompose reward/punishment processing over time. The Stockings of Cambridge test served as a control measure of executive function.Suicide attempters but not suicide ideators showed impaired probabilistic reversal learning compared to both nonsuicidal depressed elderly and nondepressed comparison subjects, after controlling for effects of education, global cognitive function, and substance use. Model-based analyses revealed that suicide attempters discounted previous history to a higher degree relative to comparison subjects, basing their choice largely on reward/punishment received on the last trial. Groups did not differ in their performance on the Stockings of Cambridge test.Older suicide attempters display impaired reward/punishment-based learning. The authors propose a hypothesis that older suicide attempters make overly present-focused decisions, ignoring past experiences. Modification of this "myopia for the past" may have therapeutic potential.
| S-EPMC3020386 | biostudies-literature
Project description:Suicide is a global cause of death, a chronic disability, and a significant public health problem. Recent works emphasize the importance of differentiating people with suicide ideation (SI) and people with suicidal attempts (SA), so we conducted a clinical cross-sectional study to better characterize the features most associated with SA. We enrolled 88 adolescents (77 females) from 12 to 18 years of age (M = 15.21, SD = 1.63) admitted to Northern Italian Child Neurology and Psychiatry Service who presented SI and/or SA. We conducted an assessment using the Columbia-Suicide Severity Rating Scale, and divided participants into two groups: adolescents with SA, and adolescents with thoughts about killing themselves which may include a plan but no suicidal attempts (SI). We found that the SA group showed greater severity of SI [t (86) = -3.485, p < 0.001], higher levels of subjective depression [t (70) = -2.65, p = 0.01)], and a higher prevalence of personality disorders [ χ(3)2 = 8.775, p = 0.032] than the SI group. Both groups presented a prevalence of internalizing problems compared to the externalizing ones in the Youth Self-Report (YSR). Higher scores on YSR internalizing problems correlate positively with the "Repulsion by Life" subscale of the Multi-Attitude Suicide Tendency (MAST) Scale in both SA and SI groups (p = 0.41 and p = 0.67, respectively), while low levels of the MAST "Attraction to Life" subscale appear more often in the SA one (p = -0.71). In conclusion, results showed that some features (e.g., prevalence of personality disorders, SI intensity, and subjective depression) might help clinicians distinguish between patients with SI and those with SA and support the importance of carefully pursuing this distinction in research.
| S-EPMC9589341 | biostudies-literature
Project description:ObjectivesThe primary aim of the present study was to investigate the putative excess mortality by suicide in suicide attempters. As a secondary aim, we investigate excess mortality in specific, clinically relevant subgroups: individuals with repeated suicide attempts (RA); individuals who used violent method at the attempt (VA); and those who scored high on the Suicide Intent Scale (HS) at the time of the baseline attempt. Finally, we investigate excess mortality in men and women separately and within 5 years and over 5 years after hospital admission for attempted suicide.DesignProspective register-based follow-up for 21-32 years. Standardised mortality ratio (SMR) was calculated for suicide using national census data. Clinically relevant subgroups were investigated separately.SettingMedical emergency inpatient unit in the south of Sweden.Participants1039 individuals who were psychiatrically assessed at admission to medical inpatient care for attempted suicide between 1987 and 1998.Outcome measureSuicide.ResultsThe overall SMR for suicide was 23.50 (95% CI 18.68 to 29.56); significantly higher (p<0.001) among women (30.49 (95% CI 22.27 to 41.72)) than men (18.61 (95% CI 13.30 to 26.05)). Mortality was highest within the first 5 years after the index suicide attempt (48.79 (95% CI 35.64 to 66.77)) compared with those who died after 5 years (p<0.001) (14.74 (10.53 to 20.63)). The highest independent SMR was found for VA (70.22 (95% CI 38.89 to 126.80)). In a regression model including RA, VA and HS all contributed significantly to excess suicide mortality.ConclusionsAn elevated risk of premature death by suicide was found in suicide attempters compared with the general population. Assessment of previous suicide attempts is important, even though the attempt/s may have occurred decades ago. When assessing suicide risk, clinicians should consider repeated attempts and whether the attempts involved high suicidal intent and violent method. Healthcare interventions may benefit from targeting identified subgroups of attempters.
| S-EPMC9150171 | biostudies-literature
Project description:BACKGROUND: Suicidal and violent behaviours are interlinked and share common biological underpinnings. In the present study we analysed the association between violent behaviour as a child, childhood trauma, adult psychiatric illness, and substance abuse in relation to interpersonal violence as an adult in suicide attempters with mood disorders. METHODS: A total of 161 suicide attempters were diagnosed with Structured Clinical Interviews and assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to violence and expressed violent behaviour in childhood (between 6-14 years of age) and during adult life (15 years or older). Ninety five healthy volunteers were used as a comparison group. A logistic regression analysis was conducted with the two KIVS subscales, expressed violent behaviour as a child and exposure to violence in childhood together with substance abuse, personality disorder diagnoses and age as possible predictors of adult interpersonal violence in suicide attempters. RESULTS: Violent behaviour as a child, age and substance abuse were significant predictors of adult interpersonal violence. ROC analysis for the prediction model for adult violence with the KIVS subscale expressed violence as a child gave an AUC of 0.79. Using two predictors: violent behaviour as a child and substance abuse diagnosis gave an AUC of 0.84. The optimal cut-off for the KIVS subscale expressed violence as a child was higher for male suicide attempters. CONCLUSIONS: Violent behaviour in childhood and substance abuse are important risk factors for adult interpersonal violent behaviour in suicide attempters.
| S-EPMC4227101 | biostudies-literature
Project description:BackgroundSuicide and cardiovascular disease rank among the leading causes of disability and premature mortality worldwide. Young adult suicide attempters are at increased risk of mortality from cardiovascular disease even compared to those with major depressive disorder suggesting an increased burden of cardiovascular risk factors. We compared the cardiovascular risk burden between youth attempters and other high-risk individuals.MethodsParticipants were from the Collaborative Psychiatric Epidemiology Surveys (CPES), a U.S. population-based study, aged 18-30 years [suicide attempt (SA): n = 303; suicidal ideation (SI): n = 451; controls: n = 3671]; and psychiatric inpatients admitted for a SA (n = 38) or SI (n = 40) and healthy controls (n = 37) aged 15-30 years. We computed a cardiovascular risk score and high- and low-risk latent classes based on risk factors of high blood pressure, obesity, and smoking.ResultsSuicide attempters showed an increased cardiovascular risk score (CPES: B = 0.43, 95% confidence interval (CI) 0.31-0.54, p < 0.001; inpatient sample: B = 1.61, 95% CI 0.53-2.68, p = 0.004) compared to controls. They were also more likely to be classified in the high cardiovascular risk group (CPES: odds ratio (OR) 3.36, 95% CI 1.67-6.78, p = 0.001; inpatient sample: OR 9.89, 95% CI 1.38-85.39, p = 0.03) compared to those with SI (CPES: OR 1.15, 95% CI 0.55-2.39, p = 0.71; inpatient sample: OR 1.91, 95% CI 0.25-15.00, p = 0.53).ConclusionsYouth attempters show an increased burden for cardiovascular risk compared to other high-risk individuals in inpatient and population-based samples. Clinicians should pay particular attention to cardiovascular risk factors among suicide attempters in order to reduce their risk for cardiovascular events.
| S-EPMC8053730 | biostudies-literature
Project description:ObjectivesWhile suicidal behavior often manifests in adolescence and early adulthood, some people first attempt suicide in late life, often with remarkable lethal intent and determination. Given these individuals' more adaptive functioning earlier in life, they may possess traits that hinder adjustment to aging, such as high conscientiousness, rather than impulsive-aggressive traits associated with suicidal behavior in younger adults.MethodsA cross-sectional case-control study was conducted in older adults aged ≥50 (mean: 65), divided into early- and late-onset attempters (age at first attempt ≤ or >50, mean: 31 vs 61), suicide ideators as well as non-suicidal depressed and healthy controls. Personality was assessed in terms of the five-factor model (FFM, n = 200) and five DSM personality disorders analyzed on the trait level as continuous scores (PDs, n = 160). Given our starting hypothesis about late-onset attempters, the FFM dimension conscientiousness was further tested on the subcomponent level.ResultsAll clinical groups displayed more maladaptive profiles than healthy subjects. Compared to depressed controls, higher neuroticism, and borderline traits characterized both suicide ideators and early-onset attempters, while only early-onset attempters further displayed lower extraversion and higher antisocial traits. Late-onset attempters were similar to depressed controls on most measures, but scored higher than them on orderliness, a conscientiousness subcomponent.ConclusionsWhile neuroticism, introversion, and cluster B traits are prominent in early-onset suicidal behavior, late-onset cases generally lack these features. In contrast, higher levels of orderliness in late-onset suicidal behavior are compatible with the age-selective maladjustment hypothesis. Key points Personality of elderly attempters differed between those with early- and late-onset first attempts. Early-onset attempters possessed personality traits generally found in younger suicidal populations (high neuroticism, low extraversion, antisocial, and borderline PD traits), supporting that constitutional suicide risk factors persist into late life in some individuals. Late-onset suicide attempters had higher levels of orderliness than non-suicidal depressed participants, suggesting that this generally adaptive trait may facilitate suicidal behavior in a subset of depressed elderly.
| S-EPMC7291767 | biostudies-literature
Project description:FKBP5 is a critical component of the Hypothalamic-Pituitary-Adrenal (HPA) axis, a system which regulates our response to stress. It forms part of a complex of chaperones, which inhibits binding of cortisol and glucocorticoid receptor translocation to the nucleus. Variations in both the HPA axis and FKBP5 have been associated with suicidal behavior. We developed a systematic, targeted sequencing approach to investigate coding and regulatory regions in or near FKBP5 in 476 bipolar disorder suicide attempters and 473 bipolar disorder non-attempters. Following stringent quality control checks, we performed single-variant, gene-level and haplotype tests on the resulting 481 variants. Secondary analyses investigated whether sex-specific variations in FKBP5 increased the risk of attempted suicide. One variant, rs141713011, showed an excess of minor alleles in suicide attempters that was statistically significant following correction for multiple testing (Odds Ratio = 6.65, P-value = 7.5 x 10-4, Permuted P-value = 0.038). However, this result could not be replicated in an independent cohort (Odds Ratio = 0.90, P-value = 0.78). Three female-specific and four male-specific variants of nominal significance were also identified (P-value < 0.05). The gene-level and haplotype association tests did not produce any significant results. This comprehensive study of common and rare variants in FKBP5 focused on both regulatory and coding regions in relation to attempted suicide. One rare variant remained significant following correction for multiple testing but could not be replicated. Further investigation is required in larger sample sets to fully elucidate the association of this variant with suicidal behavior.
| S-EPMC5193409 | biostudies-literature