Dataset Information

The association of attempted suicide with genetic variants in the SLC6A4 and TPH genes depends on the definition of suicidal behavior: a systematic review and meta-analysis.

ABSTRACT: The global prevalence of suicide has increased substantially over the last four decades. Suicidal behavior manifests owing to a combination of biological, behavioral and social factors; however, the etiology of suicidality remains elusive. Even though twin studies have reported a significant heritability of 30-50%, meta-analyses have not highlighted a common genetic variant associated with the spectrum of suicidal behavior. Here, we performed a systematic review of the literature (n = 112) to assess the association between serotonergic and non-serotonergic genetic polymorphisms and suicidal behavior. Using an inverse variance random-effects model, we developed pooled odds ratios for the 10 most commonly studied genetic variants related to suicidal behavior, each with at least five independent studies that met our stringent inclusion criteria. Our pooled results indicate no significant correlation between genetic polymorphisms and overall suicidal behavior. However, subgroups of suicide attempts demonstrated actual significance with the serotonin transporter (SLC6A4) 5HTTLPR (OR = 1.13 (95% confidence interval = 1.05-1.21), P = 0.001) and reached nominal significance with the tryptophan hydroxylase rs1800532 (1.22 (1.05-1.41), P = 0.007) variant. Subgroups of suicidal behavior (completions and attempts) displayed reduced heterogeneity compared with the overall suicidal behavior spectrum. Our findings suggest that the 5HTTLPR and rs1800532 polymorphisms are significantly associated with suicide attempts, but not associated with completed suicides. The high degree of heterogeneity in past studies may be attributed to the lack of a phenotypic distinction between suicidal attempts and completions. Consequently, we have identified an important source of phenotypic heterogeneity that provides a rationale for the current lack of a common genetic variant associated with suicidal behavior.

SUBMITTER: Clayden RC

PROVIDER: S-EPMC3565826 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The association of attempted suicide with genetic variants in the SLC6A4 and TPH genes depends on the definition of suicidal behavior: a systematic review and meta-analysis.

Clayden R C RC Zaruk A A Meyre D D Thabane L L Samaan Z Z

Translational psychiatry 20121002

The global prevalence of suicide has increased substantially over the last four decades. Suicidal behavior manifests owing to a combination of biological, behavioral and social factors; however, the etiology of suicidality remains elusive. Even though twin studies have reported a significant heritability of 30-50%, meta-analyses have not highlighted a common genetic variant associated with the spectrum of suicidal behavior. Here, we performed a systematic review of the literature (n = 112) to as ...[more]

PMID: 23032942

Similar Datasets

Project description:BackgroundExposure to suicidal behavior may be associated with increased risk of suicide, suicide attempt, and suicidal ideation and is a significant public health problem. However, evidence to date has not reliably distinguished between exposure to suicide versus suicide attempt, nor whether the risk differs across suicide-related outcomes, which have markedly different public health implications. Our aim therefore was to quantitatively assess the independent risk associated with exposure to suicide and suicide attempt on suicide, suicide attempt, and suicidal ideation outcomes and to identify moderators of this risk using multilevel meta-analysis.Methods and findingsWe systematically searched MEDLINE, Embase, PsycINFO, CINAHL, ASSIA, Sociological Abstracts, IBSS, and Social Services Abstracts from inception to 19 November 2019. Eligible studies included comparative data on prior exposure to suicide, suicide attempt, or suicidal behavior (composite measure-suicide or suicide attempt) and the outcomes of suicide, suicide attempt, and suicidal ideation in relatives, friends, and acquaintances. Dichotomous events or odds ratios (ORs) of suicide, suicide attempt, and suicidal ideation were analyzed using multilevel meta-analyses to accommodate the non-independence of effect sizes. We assessed study quality using the National Heart, Lung, and Blood Institute quality assessment tool for observational studies. Thirty-four independent studies that presented 71 effect sizes (exposure to suicide: k = 42, from 22 independent studies; exposure to suicide attempt: k = 19, from 13 independent studies; exposure to suicidal behavior (composite): k = 10, from 5 independent studies) encompassing 13,923,029 individuals were eligible. Exposure to suicide was associated with increased odds of suicide (11 studies, N = 13,464,582; OR = 3.23, 95% CI = 2.32 to 4.51, P < 0.001) and suicide attempt (10 studies, N = 121,836; OR = 2.91, 95% CI = 2.01 to 4.23, P < 0.001). However, no evidence of an association was observed for suicidal ideation outcomes (2 studies, N = 43,354; OR = 1.85, 95% CI = 0.97 to 3.51, P = 0.06). Exposure to suicide attempt was associated with increased odds of suicide attempt (10 studies, N = 341,793; OR = 3.53, 95% CI = 2.63 to 4.73, P < 0.001), but not suicide death (3 studies, N = 723; OR = 1.64, 95% CI = 0.90 to 2.98, P = 0.11). By contrast, exposure to suicidal behavior (composite) was associated with increased odds of suicide (4 studies, N = 1,479; OR = 3.83, 95% CI = 2.38 to 6.17, P < 0.001) but not suicide attempt (1 study, N = 666; OR = 1.10, 95% CI = 0.69 to 1.76, P = 0.90), a finding that was inconsistent with the separate analyses of exposure to suicide and suicide attempt. Key limitations of this study include fair study quality and the possibility of unmeasured confounders influencing the findings. The review has been prospectively registered with PROSPERO (CRD42018104629).ConclusionsThe findings of this systematic review and meta-analysis indicate that prior exposure to suicide and prior exposure to suicide attempt in the general population are associated with increased odds of subsequent suicidal behavior, but these exposures do not incur uniform risk across the full range of suicide-related outcomes. Therefore, future studies should refrain from combining these exposures into single composite measures of exposure to suicidal behavior. Finally, future studies should consider designing interventions that target suicide-related outcomes in those exposed to suicide and that include efforts to mitigate the adverse effects of exposure to suicide attempt on subsequent suicide attempt outcomes.

Project description:BackgroundOnly one-third of young people who experience suicidal ideation attempt suicide. It is important to identify factors which differentiate those who attempt suicide from those who experience suicidal ideation but do not act on these thoughts.MethodsParticipants were 4,772 members of the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK population-based birth cohort. Suicide ideation and attempts were assessed at age 16 years via self-report questionnaire. Multinomial regression was used to examine associations between factors that differentiated adolescents in three groups: no suicidal ideation or attempts, suicidal ideation only and suicide attempts. Analyses were conducted on an imputed data set based on those with complete outcome data (suicidal thoughts and attempts) at age 16 years (N = 4,772).ResultsThe lifetime prevalence of suicidal ideation and attempts in the sample was 9.6% and 6.8% respectively. Compared to adolescents who had experienced suicidal ideation, those who attempted suicide were more likely to report exposure to self-harm in others (adjusted OR for family member self-harm: 1.95, for friend self-harm: 2.61 and for both family and friend self-harm: 5.26). They were also more likely to have a psychiatric disorder (adjusted OR for depression: 3.63; adjusted OR for anxiety disorder: 2.20; adjusted OR for behavioural disorder: 2.90). Other risk factors included female gender, lower IQ, higher impulsivity, higher intensity seeking, lower conscientiousness, a greater number of life events, body dissatisfaction, hopelessness, smoking and illicit drug use (excluding cannabis).ConclusionsThe extent of exposure to self-harm in others and the presence of psychiatric disorder most clearly differentiate adolescents who attempt suicide from those who only experience suicidal ideation. Further longitudinal research is needed to explore whether these risk factors predict progression from suicidal ideation to attempts over time.

Project description:BackgroundRates of suicide and poor mental health are high in environments (neighbourhoods and institutions) where individuals have only weak social ties, feel socially disconnected and experience anomie - a mismatch between individual and community norms and values. Young people spend much of their time within the school environment, but the influence of school context (school connectedness, ethos and contextual factors such as school size or denomination) on suicide-risk is understudied. Our aim is to explore if school context is associated with rates of attempted suicide and suicide-risk at age 15 and self-harm at age 19, adjusting for confounders.MethodsA longitudinal school-based survey of 1698 young people surveyed when aged 11, (primary school), 15 (secondary school) and in early adulthood (age 19). Participants provided data about attempted suicide and suicide-risk at age 15 and deliberate self-harm at 19. In addition, data were collected about mental health at age 11, social background (gender, religion, etc.), and at age 15, perception of local area (e.g. neighbourhood cohesion, safety/civility and facilities), school connectedness (school engagement, involvement, etc.) and school context (size, denomination, etc.). A dummy variable was created indicating a religious 'mismatch', where pupils held a different faith from their school denomination. Data were analysed using multilevel logistic regression.ResultsAfter adjustment for confounders, pupils attempted suicide, suicide-risk and self-harm were all more likely among pupils with low school engagement (15-18% increase in odds for each SD change in engagement). While holding Catholic religious beliefs was protective, attending a Catholic school was a risk factor for suicidal behaviours. This pattern was explained by religious 'mismatch': pupils of a different religion from their school were approximately 2-4 times more likely to attempt suicide, be a suicide-risk or self-harm.ConclusionsWith several caveats, we found support for the importance of school context for suicidality and self-harm. School policies promoting school connectedness are uncontroversial. Devising a policy to reduce risks to pupils holding a different faith from that of their school may be more problematic.

Project description:Background: Suicide is a leading cause of death worldwide, affecting ~800,000 people every year. Fibromyalgia is an extremely prevalent rheumatic disease with a predisposition for comorbid anxiety and depression, which are known risk factors for suicidal behavior. Suicidality and relevant risk factors for suicidal behavior have not been thoroughly studied in patients with fibromyalgia. Objectives: To investigate the risk of suicidal ideation and attempts in patients with fibromyalgia. Methods: A systematic review and meta-analysis was conducted and reported according to the "Preferred Reporting Items for Systematic reviews and Meta-analyses" (PRISMA) standards. Also, the gray literature was extensively searched. Results: Thirteen studies were included in the present systematic review and meta-analysis, including 394,087 fibromyalgia patients. Sample size ranged from 44 to 199,739 subjects, mean age ranged from 45.8 to 54.5 years while the female percentage with fibromyalgia ranged from 17.1 to 100.0%. The overall suicide ideation prevalence was 29.57% (95%CI 1.84-72.07), with an OR 9.12 of (95%CI 1.42-58.77), ranging from 2.34 (95%CI 1.49-3.66) to 26.89 (95%CI 5.72-126.42). Pooled suicide attempt prevalence was 5.69% [95%CI 1.26-31.34], with an OR of 3.12 [95%CI 1.37-7.12]. Suicide risk was higher with respect to the general population with an OR of 36.77 (95%CI 15.55-96.94), as well as suicide events with an HR of 1.38 (95%CI 1.17-1.71). Determinants of suicidality were found to be: employment status, disease severity, obesity and drug dependence, chronic pain and co-morbidities, in particular depression, anxiety, poor sleep, and global mental health. However, in some cases, after adjusting for psychiatric conditions, the threshold of statistical significance was not achieved. Conclusion: Fibromyalgia patients are particularly prone to suicide, in terms of ideation, attempt, risk and events, warranting a pre-emptive screening of their mental health status. Given the few studies available, the high amount of heterogeneity, the evidence of publications bias and the lack of statistical significance when adjusting for underlying psychiatric co-morbidities, further high-quality studies should be conducted. Clinical Trial Registration: ClinicalTrial.gov, identifier 10.17605/OSF.IO/Y4BUE.

Project description:ObjectiveThe propensity of people vulnerable to suicide to make poor life decisions is increasingly well documented. Do they display an extreme degree of decision biases? The present study used a behavioral-decision approach to examine the susceptibility of low-lethality and high-lethality suicide attempters to common decision biases that may ultimately obscure alternative solutions and deterrents to suicide in a crisis.MethodWe assessed older and middle-aged (42-97 years) individuals who made high-lethality (medically serious) (n = 31) and low-lethality suicide attempts (n = 29). Comparison groups included suicide ideators (n = 30), nonsuicidal depressed participants (n = 53), and psychiatrically healthy participants (n = 28). Attempters, ideators, and nonsuicidal depressed participants had nonpsychotic major depression (DSM-IV criteria). Decision biases included sunk cost (inability to abort an action for which costs are irrecoverable), framing (responding to superficial features of how a problem is presented), underconfidence/overconfidence (appropriateness of confidence in knowledge), and inconsistent risk perception. Data were collected between June 2010 and February 2014.ResultsBoth high- and low-lethality attempters were more susceptible to framing effects as compared to the other groups included in this study (P ≤ .05, ηp2 = 0.06). In contrast, low-lethality attempters were more susceptible to sunk costs than both the comparison groups and high-lethality attempters (P ≤ .01, ηp2 = 0.09). These group differences remained after accounting for age, global cognitive performance, and impulsive traits. Premorbid IQ partially explained group differences in framing effects.ConclusionsSuicide attempters' failure to resist framing may reflect their inability to consider a decision from an objective standpoint in a crisis. Failure of low-lethality attempters to resist sunk cost may reflect their tendency to confuse past and future costs of their behavior, lowering their threshold for acting on suicidal thoughts.

Project description:BackgroundThere is a lack of consensus about the effect of the COVID-19 pandemic on the mental health of children and adolescents. We aimed to compare rates of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation during the pandemic with those before the pandemic.MethodsFor this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies published between Jan 1, 2020, and Dec 19, 2022. Studies published in English with data on paediatric (ie, those aged <19 years) emergency department visits before and during the COVID-19 pandemic were included. Case studies and qualitative analyses were excluded. Changes in attempted suicide, self-harm, suicidal ideation, and other mental-illness indicators (eg, anxiety, depression, and psychosis) were expressed as ratios of the rates of emergency department visits during the pandemic compared with those before the pandemic, and we analysed these with a random-effects meta-analysis. This study was registered with PROSPERO, CRD42022341897.Findings10 360 non-duplicate records were retrieved, which yielded 42 relevant studies (with 130 sample-estimates) representing 11·1 million emergency department visits for all indications of children and adolescents across 18 countries. The mean age of the samples of children and adolescents across studies was 11·7 years (SD 3·1, range 5·5-16·3), and there were on average 57·6% girls and 43·4% boys as a proportion of emergency department visits for any health reasons (ie, physical and mental). Only one study had data related to race or ethnicity. There was good evidence of an increase in emergency department visits for attempted suicide during the pandemic (rate ratio 1·22, 90% CI 1·08-1·37), modest evidence of an increase in emergency department visits for suicidal ideation (1·08, 0·93-1·25), and good evidence for only a slight change in self-harm (0·96, 0·89-1·04). Rates of emergency department visits for other mental-illness indications showed very good evidence of a decline (0·81, 0·74-0·89), and paediatric visits for all health indications showed strong evidence of a reduction (0·68, 0·62-0·75). When rates for attempted suicide and suicidal ideation were combined as a single measure, there was good evidence of an increase in emergency department visits among girls (1·39, 1·04-1·88) and only modest evidence of an increase among boys (1·06, 0·92-1·24). Self-harm among older children (mean age 16·3 years, range 13·0-16·3) showed good evidence of an increase (1·18, 1·00-1·39), but among younger children (mean age 9·0 years, range 5·5-12·0) there was modest evidence of a decrease (0·85, 0·70-1·05).InterpretationThe integration of mental health support within community health and the education system-including promotion, prevention, early intervention, and treatment-is urgently needed to increase the reach of mental health support that can mitigate child and adolescent mental distress. In future pandemics, increased resourcing in some emergency department settings would help to address their expected increase in visits for acute mental distress among children and adolescents.FundingNone.

Dataset Information

The association of attempted suicide with genetic variants in the SLC6A4 and TPH genes depends on the definition of suicidal behavior: a systematic review and meta-analysis.

Publications

The association of attempted suicide with genetic variants in the SLC6A4 and TPH genes depends on the definition of suicidal behavior: a systematic review and meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets