Genome-wide association study identifies four pan-ancestry loci for suicidal ideation in the Million Veteran Program.

Suicidal ideation (SI) often precedes and predicts suicide attempt and death, is the most common suicidal phenotype and is over-represented in veterans. The genetic architecture of SI in the absence of suicide attempt (SA) is unknown, yet believed to have distinct and overlapping risk with other suicidal behaviors. We performed the first GWAS of SI without SA in the Million Veteran Program (MVP), identifying 99,814 SI cases from electronic health records without a history of SA or suicide death (SD) and 512,567 controls without SI, SA or SD. GWAS was performed separately in the four largest ancestry groups, controlling for sex, age and genetic substructure. Ancestry-specific results were combined via meta-analysis to identify pan-ancestry loci. Four genome-wide significant (GWS) loci were identified in the pan-ancestry meta-analysis with loci on chromosomes 6 and 9 associated with suicide attempt in an independent sample. Pan-ancestry gene-based analysis identified GWS associations with DRD2, DCC, FBXL19, BCL7C, CTF1, ANNK1, and EXD3. Gene-set analysis implicated synaptic and startle response pathways (q's<0.05). European ancestry (EA) analysis identified GWS loci on chromosomes 6 and 9, as well as GWS gene associations in EXD3, DRD2, and DCC. No other ancestry-specific GWS results were identified, underscoring the need to increase representation of diverse individuals. The genetic correlation of SI and SA within MVP was high (rG = 0.87; p = 1.09e-50), as well as with post-traumatic stress disorder (PTSD; rG = 0.78; p = 1.98e-95) and major depressive disorder (MDD; rG = 0.78; p = 8.33e-83). Conditional analysis on PTSD and MDD attenuated most pan-ancestry and EA GWS signals for SI without SA to nominal significance, with the exception of EXD3 which remained GWS. Our novel findings support a polygenic and complex architecture for SI without SA which is largely shared with SA and overlaps with psychiatric conditions frequently comorbid with suicidal behaviors.

Brain structural and functional signatures of multi-generational family history of suicidal behaviors in preadolescent children.

Parent-child transmission of suicidal behaviors has been extensively studied, but the investigation of a three-generation family suicide risk paradigm remains limited. In this study, we aimed to explore the behavioral and brain signatures of multi-generational family history of suicidal behaviors (FHoS) in preadolescents, utilizing a longitudinal design and the dataset from Adolescent Brain and Cognitive DevelopmentSM Study (ABCD Study®), which comprised 4 years of data and includes a total of 9,653 preadolescents. Our findings revealed that multi-generational FHoS was significantly associated with an increased risk of problematic behaviors and suicidal behaviors (suicide ideation and suicide attempt) in offspring. Interestingly, the problematic behaviors were further identified as a mediator in the multi-generational transmission of suicidal behaviors. Additionally, we observed alterations in brain structure within superior temporal gyrus (STG), precentral/postcentral cortex, posterior parietal cortex (PPC), cingulate cortex (CC), and planum temporale (PT), as well as disrupted functional connectivity of default mode network (DMN), ventral attention network (VAN), dorsal attention network (DAN), fronto-parietal network (FPN), and cingulo-opercular network (CON) among preadolescents with FHoS. These results provide compelling longitudinal evidence at the population level, highlighting the associations between multi-generational FHoS and maladaptive behavioral and neurodevelopmental outcomes in offspring. These findings underscore the need for early preventive measures aimed at mitigating the familial transmission of suicide risk and reducing the global burden of deaths among children and adolescents.

Association of chronic pain with suicide attempt and death by suicide: a two-sample Mendelian randomization.

Prior studies have suggested an association between chronic pain and suicidal behavior. However, evidence supporting the causal nature of this association, and the role played by depression, remain difficult to establish due to confounding. We investigated associations of chronic pain with suicide attempt and death by suicide as well as the mediating role of depression in this association using a genetically informed method strengthening causal inference. We conducted a two-sample Mendelian randomization. Independent SNPs (N = 97) from the multisite chronic pain GWAS (NGWAS = 387,649) were used as instrumental variables to test associations of chronic pain with suicide attempt (measured from hospital records; NGWAS = 50,264) and death by suicide (measured from official death causes; NGWAS = 18,085). Indirect associations of chronic pain with suicide attempt and death by suicide via major depressive disorder (NGWAS = 173,005) were estimated. Primary analyses were supported by a range of sensitivity and outlier analyses. We found evidence supporting the contribution of chronic pain to increasing the risk of suicide attempt (OR = 1.67, CI = 1.21-2.35) and death by suicide (OR = 2.00, CI = 1.10-3.62). Associations were consistent across sensitivity analysis methods, and no evidence for outliers driving these associations was found. Through mediation analyses, we found that major depressive disorder explained a substantial proportion of the association between chronic pain and suicide attempt (proportion mediated = 39%; ORindirect association = 1.32, CI = 1.09-1.61) and death by suicide (proportion mediated = 34%; ORindirect association = 1.40, CI = 1.13-1.73). Our findings suggest that both pain management interventions and prevention of depression are likely to be effective strategies to reduce suicide risk in individuals with chronic pain.

Divergent suicidal symptomatic activations converge on somato-cognitive action network in depression.

Individuals with depression have the highest lifetime prevalence of suicide attempts (SA) among mental illnesses. Numerous neuroimaging studies have developed biomarkers from task-related neural activation in depressive patients with SA, but the findings are inconsistent. Empowered by the contemporary interconnected view of depression as a neural system disorder, we sought to identify a specific brain circuit utilizing published heterogeneous neural activations. We systematically reviewed all published cognitive and emotional task-related functional MRI studies that investigated differences in the location of neural activations between depressive patients with and without SA. We subsequently mapped an underlying brain circuit functionally connecting to each experimental activation using a large normative connectome database (n = 1000). The identified SA-related functional network was compared to the network derived from the disease control group. Finally, we decoded this convergent functional connectivity network using microscale transcriptomic and chemo-architectures, and macroscale psychological processes. We enrolled 11 experimental tasks from eight studies, including depressive patients with SA (n = 147) and without SA (n = 196). The heterogeneous SA-related neural activations localized to the somato-cognitive action network (SCAN), exhibiting robustness to little perturbations and specificity for depression. Furthermore, the SA-related functional network was colocalized with brain-wide gene expression involved in inflammatory and immunity-related biological processes and aligned with the distribution of the GABA and noradrenaline neurotransmitter systems. The findings demonstrate that the SA-related functional network of depression is predominantly located at the SCAN, which is an essential implication for understanding depressive patients with SA.

Perception of social inclusion/exclusion and response inhibition in adolescents with past suicide attempt: a multidomain task-based fMRI study.

The occurrence of suicidal behaviors increases during adolescence. Hypersensitivity to negative social signals and deficits in cognitive control are putative mechanisms of suicidal behaviors, which necessitate confirmation in youths. Multidomain functional neuroimaging could enhance the identification of patients at suicidal risk beyond standard clinical measures. Three groups of adolescents (N = 96; 78% females, age = 11.6-18.1) were included: patients with depressive disorders and previous suicide attempts (SA, n = 29); patient controls with depressive disorders but without any suicide attempt history (PC, n = 35); and healthy controls (HC, n = 32). We scanned participants with 3T-MRI during social inclusion/exclusion (Cyberball Game) and response inhibition (Go-NoGo) tasks. Neural activation was indexed by the blood-oxygenation-level dependent (BOLD) of the hemodynamic response during three conditions in the Cyberball Game ("Control condition", "Social Inclusion", and "Social Exclusion"), and two conditions in Go-NoGo task ("Go" and "NoGo" blocks). ANCOVA-style analysis identified group effects across three whole-brain contrasts: 1) NoGo vs. Go, 2) Social inclusion vs. control condition, 3) Social exclusion vs. control condition. We found that SA had lower activation in the left insula during social inclusion vs. control condition compared to PC and HC. Moreover, SA compared to PC had higher activity in the right middle prefrontal gyrus during social exclusion vs. control condition, and in bilateral precentral gyri during NoGo vs. Go conditions. Task-related behavioral and self-report measures (Self-reported emotional reactivity in the Cyberball Game, response times and number of errors in the Go-NoGo Task) did not discriminate groups. In conclusion, adolescent suicidal behaviors are likely associated with neural alterations related to the processing of social perception and response inhibition. Further research, involving prospective designs and diverse cohorts of patients, is necessary to explore the potential of neuroimaging as a tool in understanding the emergence and progression of suicidal behaviors.

Alcohol use and suicide-related outcomes in people with a diagnosis of schizophrenia: a comprehensive systematic review and meta-analysis.

Suicide is the leading cause of unnatural death among people with a diagnosis of schizophrenia. Alcohol use is a prevalent comorbid feature of schizophrenia and a modifiable risk factor for suicide. We conducted a prospectively registered (PROSPERO, CRD42022358214) systematic review and meta-analysis to quantify the relationship between alcohol use and suicide-related outcomes in schizophrenia.We searched Medline, Embase, and PsycINFO for cross-sectional, case-control and longitudinal studies using exhaustive terms from database inception to December 2022 inclusive. Computation of odds ratios (ORs) and hazard ratios (HRs) were performed using a random-effects model with DerSimonian-Laird estimation. We also evaluated publication bias, study quality, and performed subgroup analysis and meta-regression. Fifty studies, comprising 65 samples, met eligibility criteria. Overall, alcohol use was associated with suicide (OR 1.38, 95% CI 1.21-1.58; HR = 1.32, 95% CI 1.00-1.74), attempted suicide (OR 1.69, 95% CI 1.45-1.98), and suicidal ideation (OR 1.69, 95% CI 1.22-2.34). While there was no evidence of publication bias, between-sample heterogeneity was moderate in analyses of attempted suicide (I2 = 39.6%, p = 0.01) and suicidal ideation (I2 = 56.0%, p = 0.01). Summary effects were significant in all subgroups except for longitudinal studies of attempted suicide (OR 1.60, 95% CI 0.86-3.00) and studies of suicidal ideation using gender combined samples (OR 1.63, 95% CI 0.99-2.67). Alcohol use is significantly associated with suicide-related outcomes in schizophrenia. Clinicians should routinely inquire about alcohol use in mental health services to focus preventative treatment efforts.

Prospective association of attachment style with suicide attempts among US Army soldiers.

BACKGROUND: Insecure attachment styles are associated with retrospectively reported suicide attempts (SAs). It is not known if attachment styles are prospectively associated with medically documented SAs. METHODS: A representative sample of US Army soldiers entering service (n = 21 772) was surveyed and followed via administrative records for their first 48 months of service. Attachment style (secure, preoccupied, fearful, dismissing) was assessed at baseline. Administrative medical records identified SAs. Discrete-time survival analysis examined associations of attachment style with future SA during service, adjusting for time in service, socio-demographics, service-related variables, and mental health diagnosis (MH-Dx). We examined whether associations of attachment style with SA differed based on sex and MH-Dx. RESULTS: In total, 253 respondents attempted suicide. Endorsed attachment styles included secure (46.8%), preoccupied (9.1%), fearful (15.7%), and dismissing (19.2%). Examined separately, insecure attachment styles were associated with increased odds of SA: preoccupied [OR 2.5 (95% CI 1.7-3.4)], fearful [OR 1.6 (95% CI 1.1-2.3)], dismissing [OR 1.8 (95% CI 1.3-2.6)]. Examining attachment styles simultaneously along with other covariates, preoccupied [OR 1.9 (95% CI 1.4-2.7)] and dismissing [OR 1.7 (95% CI 1.2-2.4)] remained significant. The dismissing attachment and MH-Dx interaction was significant. In stratified analyses, dismissing attachment was associated with SA only among soldiers without MH-Dx. Other interactions were non-significant. Soldiers endorsing any insecure attachment style had elevated SA risk across the first 48 months in service, particularly during the first 12 months. CONCLUSIONS: Insecure attachment styles, particularly preoccupied and dismissing, are associated with increased future SA risk among soldiers. Elevated risk is most substantial during first year of service but persists through the first 48 months. Dismissing attachment may indicate risk specifically among soldiers not identified by the mental healthcare system.

Risk factors for suicide reattempt: a systematic review and meta-analysis.

BACKGROUND: Suicide is one of the main external causes of death worldwide. People who have already attempted suicide are at high risk of new suicidal behavior. However, there is a lack of information on the risk factors that facilitate the appearance of reattempts. The aim of this study was to calculate the risk of suicide reattempt in the presence of suicidal history and psychosocial risk factors and to estimate the effect of each individual risk factor. METHODS: This systematic review and meta-analysis were conducted following the PRISMA-2020 guidelines. Studies on suicide reattempt that measured risk factors were searched from inception to 2022. The risk factors studied were those directly related to suicide history: history of suicide prior to the index attempt, and those that mediate the transition from suicidal ideation to attempt (alcohol or drug misuse, impulsivity, trauma, and non-suicidal self-injury). RESULTS: The initial search resulted in 11 905 articles. Of these, 34 articles were selected for this meta-analysis, jointly presenting 52 different effect sizes. The pooled effect size across the risk factors was significant (OR 2.16). Reattempt risk may be increased in presence of any of the following risk factors: previous history, active suicidal ideation, trauma, alcohol misuse, and drug misuse. However, impulsivity, and non-suicidal self-injury did not show a significant effect on reattempt. CONCLUSION: Most of the risk factors traditionally associated with suicide are also relevant when talking about suicide reattempts. Knowing the traits that define reattempters can help develop better preventive and intervention plans.

A longitudinal network analysis of suicide risk factors among service members and veterans sampled for suicidal ideation or attempt.

BACKGROUND: Suicidal thoughts and behaviors are elevated among active-duty service members (ADSM) and veterans compared to the general population. Hence, it is a priority to examine maintenance factors underlying suicidal ideation among ADSM and veterans to develop effective, targeted interventions. In particular, interpersonal risk factors, hopelessness, and overarousal have been robustly connected to suicidal ideation and intent. METHODS: To identify the suicidal ideation risk factors that are most relevant, we employed network analysis to examine between-subjects (cross-sectional), contemporaneous (within seconds), and temporal (across four hours) group-level networks of suicidal ideation and related risk factors in a sample of ADSM and veterans (participant n = 92, observations n = 10 650). Participants completed ecological momentary assessment (EMA) surveys four times a day for 30 days, where they answered questions related to suicidal ideation, interpersonal risk factors, hopelessness, and overarousal. RESULTS: The between-subjects and contemporaneous networks identified agitation, not feeling close to others, and ineffectiveness as the most central symptoms. The temporal network revealed that feeling ineffective was most likely to influence other symptoms in the network over time. CONCLUSION: Our findings suggest that ineffectiveness, low belongingness, and agitation are important drivers of moment-to-moment and longitudinal relations between risk factors for suicidal ideation in ADSM and veterans. Targeting these symptoms may disrupt suicidal ideation.

Genome-wide association study meta-analysis of suicide death and suicidal behavior.

Suicide is a worldwide health crisis. We aimed to identify genetic risk variants associated with suicide death and suicidal behavior. Meta-analysis for suicide death was performed using 3765 cases from Utah and matching 6572 controls of European ancestry. Meta-analysis for suicidal behavior using data across five cohorts (n = 8315 cases and 256,478 psychiatric or populational controls of European ancestry) was also performed. One locus in neuroligin 1 (NLGN1) passing the genome-wide significance threshold for suicide death was identified (top SNP rs73182688, with p = 5.48 × 10-8 before and p = 4.55 × 10-8 after mtCOJO analysis conditioning on MDD to remove genetic effects on suicide mediated by MDD). Conditioning on suicidal attempts did not significantly change the association strength (p = 6.02 × 10-8), suggesting suicide death specificity. NLGN1 encodes a member of a family of neuronal cell surface proteins. Members of this family act as splice site-specific ligands for beta-neurexins and may be involved in synaptogenesis. The NRXN-NLGN pathway was previously implicated in suicide, autism, and schizophrenia. We additionally identified ROBO2 and ZNF28 associations with suicidal behavior in the meta-analysis across five cohorts in gene-based association analysis using MAGMA. Lastly, we replicated two loci including variants near SOX5 and LOC101928519 associated with suicidal attempts identified in the ISGC and MVP meta-analysis using the independent FinnGen samples. Suicide death and suicidal behavior showed positive genetic correlations with depression, schizophrenia, pain, and suicidal attempt, and negative genetic correlation with educational attainment. These correlations remained significant after conditioning on depression, suggesting pleiotropic effects among these traits. Bidirectional generalized summary-data-based Mendelian randomization analysis suggests that genetic risk for the suicidal attempt and suicide death are both bi-directionally causal for MDD.

Functional and molecular characterization of suicidality factors using phenotypic and genome-wide data.

Genome-wide association studies (GWAS) of suicidal thoughts and behaviors support the existence of genetic contributions. Continuous measures of psychiatric disorder symptom severity can sometimes model polygenic risk better than binarized definitions. We compared two severity measures of suicidal thoughts and behaviors at the molecular and functional levels using genome-wide data. We used summary association data from GWAS of four traits analyzed in 122,935 individuals of European ancestry: thought life was not worth living (TLNWL), thoughts of self-harm, actual self-harm, and attempted suicide. A new trait for suicidal thoughts and behaviors was constructed first, phenotypically, by aggregating the previous four traits (termed "suicidality") and second, genetically, by using genomic structural equation modeling (gSEM; termed S-factor). Suicidality and S-factor were compared using SNP-heritability (h2) estimates, genetic correlation (rg), partitioned h2, effect size distribution, transcriptomic correlations (ρGE) in the brain, and cross-population polygenic scoring (PGS). The S-factor had good model fit (χ2 = 0.21, AIC = 16.21, CFI = 1.00, SRMR = 0.024). Suicidality (h2 = 7.6%) had higher h2 than the S-factor (h2 = 2.54, Pdiff = 4.78 × 10-13). Although the S-factor had a larger number of non-null susceptibility loci (πc = 0.010), these loci had small effect sizes compared to those influencing suicidality (πc = 0.005, Pdiff = 0.045). The h2 of both traits was enriched for conserved biological pathways. The rg and ρGE support highly overlapping genetic and transcriptomic features between suicidality and the S-factor. PGS using European-ancestry SNP effect sizes strongly associated with TLNWL in Admixed Americans: Nagelkerke's R2 = 8.56%, P = 0.009 (PGSsuicidality) and Nagelkerke's R2 = 7.48%, P = 0.045 (PGSS-factor). An aggregate suicidality phenotype was statistically more heritable than the S-factor across all analyses and may be more informative for future genetic study designs interested in common genetic factors among different suicide related phenotypes.

Suicidal behavior across a broad range of psychiatric disorders.

Suicide is a leading cause of death worldwide. In 2020, some 12.2 million Americans seriously contemplated suicide, 3.2 million planned suicide attempts, and 1.2 million attempted suicide. Traditionally, the approach to treating suicidal behavior (SB) has been to treat the "underlying" psychiatric disorder. However, the number of diagnoses associated with SB is considerable. We could find no studies describing the range of disorders reported to be comorbid with SB. This narrative review summarizes literature documenting the occurrence of SB across the lifespan and the full range of psychiatric diagnoses, not only BPD and those that comprise MDE, It also describes the relevance of these observations to clinical practice, research, and nosology. The literature searches contained the terms "suicid*" and each individual psychiatric diagnosis and identified 587 studies. We did not include case reports, case series, studies only addressing suicidal ideation or non-suicidal self-injury (NSSI), studies on self-harm, not distinguishing between SB and NSSI and studies that did not include any individuals that met criteria for a specific DSM-5 diagnosis (n = 366). We found that SB (suicide and/or suicide attempt) was reported to be associated with 72 out of 145 diagnoses, although data quality varied. Thus, SB is not exclusively germane to Major Depressive Episode (MDE) and Borderline Personality Disorder (BPD), the only conditions for which it is a diagnostic criterion. That SB co-occurs with so many diagnoses reinforces the need to assess current and past SB regardless of diagnosis, and supports the addition of charting codes to the DSM-5 to indicate current or past SB. It also comports with new data that specific genes are associated with SB independent of psychiatric diagnoses, and suggests that SB should be managed with specific suicide prevention interventions in addition to treatments indicated for co-occurring diagnoses. SB diagnostic codes would help researchers and clinicians document and measure SB's trajectory and response to treatment over time, and, ultimately, help develop secondary and tertiary prevention strategies. As a separate diagnosis, SB would preclude situations in which a potentially life-threatening behavior is not accounted for by a diagnosis, a problem that is particularly salient when no mental disorder is present, as is sometimes the case.

The impact of body mass index on the clinical features of bipolar disorder: A STEP-BD study.

INTRODUCTION: The effects of body mass index (BMI) on the core symptoms of bipolar disorder (BD) and its implications for disease trajectory are largely unexplored. OBJECTIVE: To examine whether BMI impacted hospitalization rate, medical and psychiatric comorbidities, and core symptom domains such as depression and suicidality in BD. METHODS: Participants (15 years and older) were 2790 BD outpatients enrolled in the longitudinal STEP-BD study; all met DSM-IV criteria for BD-I, BD-II, cyclothymia, BD NOS, or schizoaffective disorder, bipolar subtype. BMI, demographic information, psychiatric and medical comorbidities, and other clinical variables such as bipolarity index, history of electroconvulsive therapy (ECT), and history of suicide attempts were collected at baseline. Longitudinal changes in Montgomery-Åsberg Depression Rating Scale (MADRS) score, Young Mania Rating Scale (YMRS) score, and hospitalizations during the study were also assessed. Depending on the variable of interest, odds-ratios, regression analyses, factor analyses, and graph analyses were applied. RESULTS: A robust increase in psychiatric and medical comorbidities was observed, particularly for baseline BMIs >35. A significant relationship was noted between higher BMI and history of suicide attempts, and individuals with BMIs >40 had the highest prevalence of suicide attempts. Obese and overweight individuals had a higher bipolarity index (a questionnaire measuring disease severity) and were more likely to have received ECT. Higher BMIs correlated with worsening trajectory of core depression symptoms and with worsening lassitude and inability to feel. CONCLUSIONS: In BD participants, elevated BMI was associated with worsening clinical features, including higher rates of suicidality, comorbidities, and core depression symptoms.

Testing the interpersonal theory of suicide in adolescents: A multi-wave longitudinal study.

BACKGROUND: Suicide is a major public health crisis among youth. Several prominent theories, including the Interpersonal Theory of Suicide (IPTS), aim to characterize the factors leading from suicide ideation to action. These theories are largely based on findings in adults and require testing and elaboration in adolescents. METHODS: Data were examined from high-risk 13-18-year-old adolescents (N = 167) participating in a multi-wave, longitudinal study; 63% of the sample exhibited current suicidal thoughts or recent behaviors (n = 105). The study included a 6-month follow-up period with clinical interviews and self-report measures at each of the four assessments as well as weekly smartphone-based assessments of suicidal thoughts and behaviors. Regression and structural equation models were used to probe hypotheses related to the core tenets of the IPTS. RESULTS: Feelings of perceived burdensomeness were associated with more severe self-reported suicidal ideation (b = 0.58, t(158) = 7.64, p < .001). Similarly, burdensomeness was associated with more frequent ideation based on weekly smartphone ratings (b = 0.11, t(1460) = 3.41, p < .001). Contrary to IPTS hypotheses, neither feelings of thwarted belongingness, nor interactions between burdensomeness and thwarted belongingness were significantly associated with ideation (ps > .05). Only elevated depression severity was associated with greater odds of suicide events (i.e., suicide attempts, psychiatric hospitalizations, and/or emergency department visits for suicide concerns) during the follow-up period (OR = 1.83, t(158) = 2.44, p = .01). No effect of acquired capability was found. CONCLUSIONS: Perceptions of burdensomeness to others reflect a critical risk factor for suicidal ideation among high-risk adolescents. Null findings with other IPTS constructs may suggest a need to adopt more developmentally sensitive models or measures of interpersonal and acquired capability risk factors for youth. Refining methods and theoretical models of suicide risk may help improve the identification of high-risk cases and inform clinical intervention.

Is Late-Onset Suicidal Behavior a Distinct Subtype?

This clinical viewpoint article aims to draw attention to a yet unexplored factor influencing suicidal behavior: age of onset of suicidal behavior. To tackle the substantial heterogeneity among depressed older attempters, we suggest consideration of at least two distinct pathways to suicidal behavior in late life based on when the first suicidal crisis occurred. Specifically, we discuss the current state of research and the rationale behind the suggested early-late-onset categorization of late-life suicidal behavior. We summarize available evidence so far on early-onset and late-onset attempters, and the potential heterogeneity in the interplay of risk/precipitating factors. Certain risk factors for suicide, such as impulsivity and borderline traits, decrease with age, while memory and broader cognitive impairments increase with age. Research indicates that familial/social exposure to suicidal behavior, childhood trauma, impulsivity, maladaptive personality traits, longstanding interpersonal difficulties, and legal problems are found predominantly in attempters experiencing their first suicidal crisis between youth and early midlife. In contrast, dementia prodrome is one of the most promising but understudied candidates for late-onset suicide risk, especially in the context of other risk factors. Moreover, personality traits conferring increased vulnerability to late-onset suicidal behavior (such as high conscientiousness) are not the same as ones classically identified in younger attempters and in older suicide attempters who have early-onset suicidal behavior (such as neuroticism and Cluster B traits). We discuss methodological points about studying age of onset of suicidal behavior, outline clinical implications, share ideas for future directions, and call for research on this understudied topic.

Association of 7-Day Follow-Up With 6-Month Suicide Mortality Following Hospitalization for Suicidal Thoughts or Behaviors Among Older Adults.

OBJECTIVE: To evaluate whether timely follow-up outpatient mental health care is associated with reduced short-term suicide risk following hospitalization for suicidal thoughts or behaviors. METHODS: Retrospective cohort analysis using 2015 Medicare data for adults aged ≥ 65 years who were hospitalized for suicidal ideation or behaviors (n = 36,557) linked with the National Death Index. Adjusted risk ratios (ARR) estimated the association between 7-day follow-up and suicide risk at 30-, 90-, and 180-days, adjusted for confounding by indication using inverse probability of treatment weights of observable covariates. RESULTS: Overall, 39.3% of patients received 7-day follow-up, which was associated with 41% higher risk of suicide within 180 days. Follow-up care was associated with higher suicide risk for Medicare Advantage enrollees, patients with no recent prior mental health care, and those admitted for suicidal behaviors. CONCLUSION: Results suggest 7-day follow-up care was not associated with lower post-discharge suicide risk. For this high-risk group, suicide-specific interventions may be needed during the critical postdischarge period.

Clarifying the relationship between physical injuries and risk for suicide attempt in a Swedish national sample.

INTRODUCTION: The Interpersonal-Psychological Theory of Suicide proposes that capability for suicide is acquired through exposure to painful and provocative events (PPEs). Although there is robust evidence for a positive association between aggregate measures of PPEs and risk for suicidal behavior, little is known about the contributions of physical injuries. The present study investigated the relationship between injuries and risk of subsequent suicide attempt (SA). METHODS: Data were from Swedish population-based registers. All individuals born in Sweden between 1970 and 1990 were included (N = 1,011,725 females and 1,067,709 males). We used Cox regression models to test associations between 10 types of injuries (eye injury; fracture; dislocation/sprain/strain; injury to nerves and spinal cord; injury to blood vessels; intracranial injury; crushing injury; internal injury; traumatic amputation; and other or unspecified injuries) and risk for later SA. Analyses were stratified by sex and adjusted for year of birth and parental education. Additional models tested for differences in the pattern of associations based on age group and genetic liability for SA. In co-relative models, we tested the association between each injury type and risk for SA in relative pairs of varying genetic relatedness to control for unmeasured familial confounders. RESULTS: All 10 injury types were associated with elevated risk for SA (hazard ratios [HRs] = 1.2-7.0). Associations were stronger in the first year following an injury (HRs = 1.8-7.0), but HRs remained above 1 more than 1 year after injury exposure (HRs = 1.2-2.6). The strength of associations varied across injury type, sex, age, and genetic liability for SA. For example, the magnitude of the association between crushing injury and risk for SA was larger in females than males, whereas other injuries showed a similar pattern of associations across sex. Moreover, there was evidence to support positive additive interaction effects between several injury types and aggregate genetic liability for SA (relative excess risk due to interaction [RERI] = 0.1-0.3), but the majority of these interactions became non-significant or changed direction after accounting for comorbid psychiatric and substance use disorders. In co-relative models, the pattern of associations differed by injury type, such that there was evidence to support a potential causal effect of eye injury, fracture, dislocation/sprain/strain, intracranial injury, and other and unspecified injuries on risk for SA. For the remaining injury types, HRs were not significantly different from 1 in monozygotic twins, which is consistent with confounding by familial factors. CONCLUSIONS: Injuries are associated with increased risk for subsequent SA, particularly in the first year following an injury. While genetic and familial environmental factors may partly explain these associations, there is also evidence to support a potential causal effect of several injury types on future risk for SA.

Impulsivity and Psychiatric Diagnoses as Mediators of Suicidal Ideation and Suicide Attempts Among Veterans With Traumatic Brain Injury.

OBJECTIVE: Traumatic brain injury (TBI) is a risk factor for suicide, but questions related to mechanisms remain unanswered. Impulsivity is a risk factor for suicide and is a common sequela of TBI. The authors explored the relationships between TBI and both suicidal ideation and suicide attempts and explored whether impulsivity and comorbid psychiatric diagnoses mediate these relationships. METHODS: This cross-sectional retrospective chart review study included 164 veterans enrolled in a previous study. Sixty-nine veterans had no TBI history, and 95 had a TBI history (mild, N=44; moderate, N=13; severe, N=12; and unclear severity, N=26). To examine the associations between TBI and suicidal ideation or suicide attempts, as well as potential mediators of these relationships, chi-square tests, t tests, and logistic regression models were used. RESULTS: Unadjusted analyses indicated that veterans with TBI were more likely to report suicidal ideation; however, in analyses controlling for mediators, this relationship was no longer significant. Among veterans with TBI, suicidal ideation was related most strongly to high impulsivity (odds ratio=15.35, 95% CI=2.43-96.79), followed by depression (odds ratio=5.73, 95% CI=2.53-12.99) and posttraumatic stress disorder (odds ratio=2.57, 95% CI=1.03-6.42). TBI was not related to suicide attempts, yet suicide attempts were related to high impulsivity (odds ratio=6.95, 95% CI=1.24-38.75) and depression (odds ratio=3.89, 95% CI=1.56-9.40). CONCLUSIONS: These findings suggest that impulsivity, followed by psychiatric diagnoses, most strongly mediate the relationships between TBI and both suicidal ideation and suicide attempts. Impulsivity may be mechanistically related to, and serve as a future treatment target for, suicidality among veterans with TBI.

From Social Stress and Isolation to Autonomic Nervous System Dysregulation in Suicidal Behavior.

PURPOSE OF REVIEW: In this narrative review we wanted to describe the relationship of autonomic nervous system activity with social environment and suicidal spectrum behaviors. RECENT FINDINGS: Patients with suicidal ideation/suicide attempt have higher sympathetic nervous system (SNS) and lower parasympathetic nervous system (PNS) activity in resting conditions and during acute stress tasks compared with patients without suicidal ideation/suicide attempt. Death by suicide and violent suicide attempt also are related to SNS hyperactivation. Similarly, a SNS/PNS imbalance has been observed in people with childhood trauma, stressful life events or feelings of loneliness and isolation. Social support seems to increase PNS control and resilience. Due to the importance of the social context and stressful life events in suicidal behavior, SNS/PNS imbalance could act as a mediator in this relationship and be a source of relevant biomarkers. Childhood trauma and stressful life events may impair the autonomic nervous system response in suicidal patients. Loneliness, isolation and social support may act as moderators in acute stress situations.

Cross-sectional study about suicide ideation and attempts among Brazilian pre-adolescents.

BACKGROUND: Suicide is a global public health problem. In childhood, the risk factors are less clear, highlighting family and individual factors. This study aims to investigate the prevalence and sociodemographic, social, family, and individual factors associated with suicide ideation and attempts in pre-adolescents in a Brazilian city. METHODS: The sample comes from a cohort of 500 schoolchildren of a city in Rio de Janeiro/Brazil. The data are analyzed cross-sectionally. The research incorporated data from the years 2005, 2006, and 2008 to evaluate suicide ideation and attempts in childhood, as reported by parents/caregivers, teachers and children. A hierarchical logistic model evaluated the association between the explanatory variables related to sociodemographic, social, family, and individual factors and the outcome. RESULTS: 22.2% of the children (95% CI 18.0%-27.0%) had suicide ideation/attempts, reported either by their mothers, teachers, or the child at some point in a cohort. The following variables were associated with suicidal ideation/attempts in the final adjusted model: regular or poor quality of relationship with friends (OR = 1.84; 95% CI 1.31-2.58), having a family member incarcerated (OR = 1.44; 95% CI 1.07-1.92) and having worse performance in portuguese or mathematics than other students (OR = 2.05; 95% CI 1.29-3.26). CONCLUSION: Suicidal behavior in childhood is severe and affects everyone around the case, demanding to promote friendships, helping with school activities, and providing greater support and attention to children at risk. Bad relationships with friends and incarcerated family members are particularly key risk factors for suicide ideation and attempts. It is essential to improve prevention policies and to disseminate protective behaviors. There is a critical need to augment community mental health resources, mainly in less developed countries and regions that lack these services.