Impulsivity as a Risk Factor for Suicide in Bipolar Disorder.
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ABSTRACT:
SUBMITTER: Zakowicz P
PROVIDER: S-EPMC8342888 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Impulsive risk taking contributes to deleterious outcomes among clinical populations. Indeed, pathological impulsivity and risk taking are common in patients with serious mental illness, and have severe clinical repercussions including novelty seeking, response disinhibition, aggression, and substance abuse. Thus, the current study seeks to examine self-reported impulsivity (Barratt Impulsivity Scale) and performance-based behavioral risk taking (Balloon Analogue Risk Task) in bipolar disorder and schizophrenia. Participants included 68 individuals with bipolar disorder, 38 with schizophrenia, and 36 healthy controls. Self-reported impulsivity was elevated in the bipolar group compared with schizophrenia patients and healthy controls, who did not differ from each other. On the risk-taking task, schizophrenia patients were significantly more risk averse than the bipolar patients and controls. Aside from the diagnostic group differences, there was a significant effect of antipsychotic (AP) medication within the bipolar group: bipolar patients taking AP medications were more risk averse than those not taking AP medications. This difference in risk taking because of AP medications was not explained by history of psychosis. Similarly, the differences in risk taking between schizophrenia and bipolar disorder were not fully explained by AP effects. Implications for clinical practice and future research are discussed.
| S-EPMC3870783 | biostudies-literature
Project description:Suicide and bipolar disorder (BD) are challenging, complex, and intertwined areas of study in contemporary psychiatry. Indeed, BD is associated with the highest lifetime risk for suicide attempt and completion of all the psychiatric conditions. Given that several clinical risk factors for both suicide and BD have been well noted in the literature, exploring the neurobiological aspects of suicide in BD may provide insights into both preventive measures and future novel treatments. This review synthesizes findings regarding the neurobiological aspects of suicide and, when applicable, their link to BD. Neurochemical findings, genes/epigenetics, and potential molecular targets for current or future treatments are discussed. The role of endophenotypes and related proximal and distal risk factors underlying suicidal behavior are also explored. Lastly, we discuss the manner in which preclinical work on aggression and impulsivity may provide additional insights for the future development of novel treatments.
| S-EPMC3840723 | biostudies-literature
Project description:To compare risks for suicidality and criminality in a national cohort of people diagnosed with bipolar disorder, and to assess how risk factor profiles differ between these outcomes.We conducted 2 case-cohort studies using interlinked Swedish national registers. Primarily, using International Classification of Diseases (ICD) coding, we identified 15,337 people diagnosed with bipolar disorder, 1973-2009, matched by age and gender to 20 individuals per case sampled randomly from the general population. We estimated risks of suicide and hospital-presenting attempted suicide, and violent and nonviolent criminal offending. We separately assessed these risks among 14,677 unaffected siblings matched to a second general population sample.22.2% of bipolar disorder cohort members engaged in suicidal or criminal acts after diagnosis. They were at greatly elevated risk for completed suicide (risk ratio = 18.8; 95% CI, 16.0-22.2), attempted suicide (risk ratio = 14.3; 95% CI, 13.5-15.2), violent crime (risk ratio = 5.0; 95% CI, 4.6-5.4), and nonviolent crime (risk ratio = 2.9; 95% CI, 2.8-3.1) compared with the general population. Elevations in risk were far less marked among the unaffected siblings than in the bipolar disorder cohort. Three factors independently predicted raised risk of all 4 adverse outcomes: if the first 2 patient episodes for bipolar disorder required admission, a history of attempted suicide, and a history of diagnosed alcohol/drug disorder. Criminal offending before bipolar diagnosis was an especially strong independent predictor of criminality after diagnosis.The combined risk of suicidality or criminality is substantially elevated in both relative and absolute terms. Clinical prediction rules focusing on multiple vulnerabilities following onset of bipolar disorder, especially when there is history of attempted suicide, substance misuse disorders, or criminal offending, may improve risk management.
| S-EPMC4226039 | biostudies-literature
Project description:The addition of a methyl group to, typically, a cytosine-guanine dinucleotide (CpG) creates distinct DNA methylation patterns across the genome that can regulate gene expression. Aberrant DNA methylation of CpG sites has been associated with many psychiatric disorders including bipolar disorder (BD) and suicide. Using the SureSelectXT system, Methyl-Seq, we investigated the DNA methylation status of CpG sites throughout the genome in 50 BD individuals (23 subjects who died by suicide and 27 subjects who died from other causes) and 31 nonpsychiatric controls. We identified differentially methylated regions (DMRs) from three analyses: (a) BD subjects compared to nonpsychiatric controls (BD-NC), (b) BD subjects who died by suicide compared to nonpsychiatric controls (BDS-NC), and (c) BDS subjects compared to BD subjects who died from other causes (BDS-BDNS). One DMR from the BDS-NC analysis, located in ARHGEF38, was significantly hypomethylated (23.4%) in BDS subjects. This finding remained significant after multiple testing (PBootstrapped = 9.0 × 10-3 ), was validated using pyrosequencing, and was more significant in males. A secondary analysis utilized Ingenuity Pathway Analysis to identify enrichment in nominally significant DMRs. This identified an association with several pathways including axonal guidance signaling, calcium signaling, β-adrenergic signaling, and opioid signaling. Our comprehensive study provides further support that DNA methylation alterations influence the risk for BD and suicide. However, further investigation is required to confirm these associations and identify their functional consequences.
| S-EPMC8375453 | biostudies-literature
Project description:ObjectiveBipolar disorder carries a high risk of suicide. Identification of risk factors is important. The aim of this study was to study risk factors for suicide in a large cohort of men and women with bipolar disorder.MethodA prospective cohort study using clinical data from the Swedish National Quality Register for Bipolar Affective Disorder (BipoläR). The outcome variable was suicide captured in the Cause of Death Register between 2004 and 2014. Hazard ratios (HR) were calculated using Cox proportional hazards models.ResultsOf 12 850 persons (4844 men and 8006 women) with bipolar disorder, 90 (55 men and 35 women) died by suicide during the follow-up period (between 1 and 10 years). Male sex (HR 2.56), living alone (HR 2.45), previous suicide attempts (HR 4.10), comorbid psychiatric disorder (HR 2.64), recent affective episodes (HR 2.39), criminal conviction (HR 4.43), psychiatric inpatient care (HR 2.79), and involuntary commitment (HR 3.50) were significant risk factors for suicide. Several of the statistically significant risk factors for suicide in bipolar disorder differed between men and women.ConclusionsRisk factors for suicide in bipolar disorder include factors associated with suicide in general, but also diagnosis-specific factors.
| S-EPMC6220973 | biostudies-literature
Project description:We conducted a retrospective investigation of potential clinical, demographic, and neuropsychological risk factors for suicide attempts in patients diagnosed with bipolar disorder.Participants included 67 adult inpatients and outpatients aged 18-60 years meeting DSM-IV criteria for bipolar disorder (bipolar I and II disorders, bipolar disorder not otherwise specified). We assessed demographic factors, mood symptoms, psychosis, trauma history, trait impulsivity, trait aggression, and reasons for living. The primary outcome measures were the Barratt Impulsiveness Scale-version II, Aggression Questionnaire, and 10 cognitive outcome variables. The cognitive outcome variables assessed cognitive performance across several domains, including processing speed, attention, verbal learning, and executive function. Another aspect of cognitive function, decision making, was assessed using the Iowa Gambling Task. The study was conducted from July 2007-July 2009.We found that nonattempters reported significantly higher trait impulsivity scores on the Barratt Impulsiveness Scale compared to attempters (t(57) = 2.2, P = .03) and that, among attempters, lower trait impulsivity score was associated with higher scores of lethality of prior attempts (r(25) = -0.53, P = .01). Analyses revealed no other group differences on demographic, clinical, or neurocognitive variables when comparing attempters versus nonattempters. Regression models failed to identify any significant predictors of past suicide attempt.The largely negative results of our study are particularly important in highlighting the clinical dilemma faced by many clinicians when trying to predict which patients will make serious suicide attempts and which patients are at a lower risk for acting on suicidal thoughts. A limitation of our work is that we examined stable trait measures of impulsivity among a euthymic sample rather than mood state or the impact of mood state on traits. Overall, we conclude that suicidal behavior is extremely difficult to predict, even when comprehensive clinical and neurocognitive information is available.
| S-EPMC4035109 | biostudies-literature
Project description:Bipolar II disorder (BD-II) major depression episode is highly associated with suicidality, and objective neural biomarkers could be key elements to assist in early prevention and intervention. This study aimed to integrate altered brain functionality in the frontolimbic system and machine learning techniques to classify suicidal BD-II patients and predict suicidality risk at the individual level. A cohort of 169 participants were enrolled, including 43 BD-II depression patients with at least one suicide attempt during a current depressive episode (SA), 62 BD-II depression patients without a history of attempted suicide (NSA), and 64 demographically matched healthy controls (HCs). We compared resting-state functional connectivity (rsFC) in the frontolimbic system among the three groups and explored the correlation between abnormal rsFCs and the level of suicide risk (assessed using the Nurses' Global Assessment of Suicide Risk, NGASR) in SA patients. Then, we applied support vector machines (SVMs) to classify SA vs. NSA in BD-II patients and predicted the risk of suicidality. SA patients showed significantly decreased frontolimbic rsFCs compared to NSA patients. The left amygdala-right middle frontal gyrus (orbital part) rsFC was negatively correlated with NGASR in the SA group, but not the severity of depressive or anxiety symptoms. Using frontolimbic rsFCs as features, the SVMs obtained an overall 84% classification accuracy in distinguishing SA and NSA. A significant correlation was observed between the SVMs-predicted NGASR and clinical assessed NGASR (r = 0.51, p = 0.001). Our results demonstrated that decreased rsFCs in the frontolimbic system might be critical objective features of suicidality in BD-II patients, and could be useful for objective prediction of suicidality risk in individuals.
| S-EPMC7725800 | biostudies-literature
Project description:OBJECTIVES:To differentiate the relation between the structure and timing of rest-activity patterns and symptoms of impulsivity and mood instability in bipolar disorder (BD), borderline personality disorder (BPD) and healthy controls (HC). METHODS:Eighty-seven participants (31 BD, 21 BPD and 35 HC) underwent actigraph monitoring for 28 days as part of the Automated Monitoring of Symptom Severity (AMoSS) study. Impulsivity was assessed at study entry using the BIS-11. Mood instability was subsequently longitudinally monitored using the digital Mood Zoom questionnaire. RESULTS:BPD participants show several robust and significant correlations between non-parametric circadian rest-activity variables and worsened symptoms. Impulsivity was associated with low interdaily stability (r = -0.663) and weak amplitude (r = -0.616). Mood instability was associated with low interdaily stability (r = -0.773), greater rhythm fragmentation (r = 0.662), weak amplitude (r = -0.694) and later onset of daily activity (r = 0.553). These associations were not present for BD or HCs. Classification analysis using actigraphic measures determined that later L5 onset reliably distinguished BPD from BD and HC but did not sufficiently discriminate between BD and HC. CONCLUSIONS:Rest-activity pattern disturbance indicative of perturbed sleep and circadian function is an important predictor of symptom severity in BPD. This appears to validate the greater subjective complaints of BPD individuals that are sometimes regarded as exaggerated by clinicians. We suggest that treatment strategies directed towards improving sleep and circadian entrainment may in the future be investigated in BPD.
| S-EPMC7216871 | 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
Project description:OBJECTIVES:Bipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder. METHODS:Within the framework of the International Society for Bipolar Disorders Task Force on Suicide, a systematic review of articles published since 1980, characterized by the key terms bipolar disorder and 'suicide attempts' or 'suicide', was conducted, and data extracted for analysis from all eligible articles. Demographic and clinical variables for which ? 3 studies with usable data were available were meta-analyzed using fixed or random-effects models for association with suicide attempts and suicide deaths. There was considerable heterogeneity in the methods employed by the included studies. RESULTS:Variables significantly associated with suicide attempts were: female gender, younger age at illness onset, depressive polarity of first illness episode, depressive polarity of current or most recent episode, comorbid anxiety disorder, any comorbid substance use disorder, alcohol use disorder, any illicit substance use, comorbid cluster B/borderline personality disorder, and first-degree family history of suicide. Suicide deaths were significantly associated with male gender and first-degree family history of suicide. CONCLUSIONS:This paper reports on the presence and magnitude of the correlates of suicide attempts and suicide deaths in bipolar disorder. These findings do not address causation, and the heterogeneity of data sources should limit the direct clinical ranking of correlates. Our results nonetheless support the notion of incorporating diagnosis-specific data in the development of models of understanding suicide in bipolar disorder.
| S-EPMC6296224 | biostudies-literature