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Background: Impaired emotion regulation (ER) contributes to major depression and suicidal ideation and behavior. ER is typically studied by explicitly directing participants to regulate, but this may not capture spontaneous tendencies of individuals with depression to engage ER in daily life., Methods: In 82 participants with major depressive disorder, we examined the relationship of spontaneous engagement of ER to real-world responses to stress. We used a machine learning-derived neural signature reflecting neural systems that underlie cognitive reappraisal (an ER strategy) to identify reappraisal-related activity while participants recalled negative autobiographical memories under the following conditions: 1) unstructured recall; 2) distanced recall, a form of reappraisal; and 3) immersed recall (comparison condition). Participants also completed a week of ecological momentary assessment measuring daily stressors, suicidal ideation, and negative affect., Results: Higher reappraisal signature output for the unstructured period, a proxy for the spontaneous tendency to engage ER, was associated with greater increases in suicidal ideation following stressors (b = 0.083, p = .041). Higher signature output for distanced recall, a proxy for the capacity to engage ER when directed, was associated with lower negative affect following stressors (b = -0.085, p = .029). Output for the immerse period was not associated with ecological momentary assessment outcomes., Conclusions: Findings suggest that in major depressive disorder, the spontaneous tendency to react to negative memories with attempts to reappraise may indicate greater reactivity to negative cues, while intact capacity to use reappraisal when directed may be associated with more adaptive responses to stress. These data have implications for understanding stress-related increases in suicide risk in depression., (Copyright © 2024. Published by Elsevier Inc.)

Decedents with no known mental disorder comprise 5-40% of suicides, suggesting that suicide ideation (SI) and behavior may occur in the psychiatrically healthy with important implications for suicide risk screening. Healthy Volunteers (HV) and patients with Major Depressive Disorder (MDD) provided 7 days of Ecological Momentary Assessment (EMA) data about SI and stressors. Longitudinal mixed effects logistic regression models compared HV and patient SI and stressors. Mixed effects linear regression models compared HVs' and patients' SI score change from the previous epoch's SI score when each stressor occurred. HVs (n = 42) reported less frequent (p < 0.001) and less intense SI (p < 0.003) than patients (n = 80), yet did endorse SI and/or SI-related items in 44% of EMA epochs, endorsing SI items in 25% of epochs with non-zero SI scores. For 7 of 8 stressors, patients reported stressors more often than HVs (all p < 0.001) responding to them with increased SI (0.0001 < p < 0.0472). HVs were relatively resilient to stressors, reporting SI increases only in response to neglect (p < 0.0147). Although SI and SAs are documented among psychiatrically healthy individuals, scientific attention to these observations has been scant. Real-time SI measurement showed that HVs' SI was less pronounced than MDD patients', but was endorsed, nonetheless. Patients were more likely to report stressors than HVs, perhaps due to greater sensitivity to the environment, and reported SI in response to stressors, which was less common in HVs. Both MDD patients and HVs most often manifested passive SI (viz, "decreased wish to live"). However, passive SI (viz, "desire for death"), may predict suicide, even absent SI per se (thinking about killing yourself). This study validates the utility of real-time SI assessment, showing that HVs endorse SI items in 11% of epochs, which implies that suicide risk screening focused on those with mental disorders may be too narrow an approach., (© 2024. The Author(s).)

Introduction: Understanding the specific strategies individuals use to cope with their suicidal thoughts may have implications for suicide prevention. This study developed a classification system of coping strategies and applied this system to individual coping behaviors documented in a safety planning intervention smartphone application called Beyond Now., Method: 725 Beyond Now safety planning app users, aged 16 to over 55 years, entered coping strategies that were used to develop a classification system through content analysis. Entries were either user generated or selected from a list of suggested coping strategies, and 2960 entries were classified using the system., Results: Our classification system featured 11 distinct descriptive categories, with media consumption being the most popular coping strategy among Beyond Now users, followed by relaxation and self-care activities, exercise and creative activities. More than half (57%) of the entries were suggested coping strategies with the remainder being user-generated entries (43%)., Conclusion: A wide range of coping strategies were entered into safety plans, with activities that aim to either distract or provide reductions in emotional arousal common. Future research is needed to evaluate the efficacy of the coping strategies listed in safety plans., (© 2024 The Authors. Suicide and Life‐Threatening Behavior published by Wiley Periodicals LLC on behalf of American Association of Suicidology.)

Higher intent suicide attempts carry elevated risk of future suicidal behavior. Abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis is both linked to nonfatal suicidal behavior and suicide deaths in major depressive disorder. Few studies, however, have identified biological markers of a high-intent suicidal subgroup. We examined HPA axis output and reactivity to the Trier Social Stress Test (TSST) via salivary cortisol in depressed individuals (N=68) with a suicide attempt (SA) history. A median split of higher and lower suicidal intent scores was used to define groups. Individuals with high intent SA had attenuated total cortisol output (AUC g ), F(1,60)=10.04, SE=5.095, p=.003, and lower HPA-axis stress responsivity to the TSST (AUC i ), F(1,60)=4.50, SE=4.604, p=.039, compared with the low intent SA group. The high intent group also reported more pronounced negative affect than the low intent group (F[1,61]=6.413, SE=10.55, p=.014) both at baseline (mean diff =22.32, p=.038) and in response to the stressor task (mean diff =37.62, p=.003). Vulnerability to suicidal behavior in high-intent individuals may be related to the combined profile of impaired physiological responses to stress and greater negative affectivity. This clinical and biologic subgroup may benefit from targeted suicide prevention interventions., Competing Interests: Declaration of Competing Interest Drs. Mann, Oquendo and Stanley receive royalties for commercial use of the Columbia Suicide Severity Rating Scale from the Research Foundation for Mental Hygiene. Dr. Oquendo serves as an advisor to Alkermes, Mind Medicine, Sage Therapeutics, St. George's University and Fundacion Jimenez Diaz. Her family owns stock in Bristol Myers Squibb., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Neurocognitive testing may advance the goal of predicting near-term suicide risk. The current study examined whether performance on a Go/No-go (GNG) task, and computational modeling to extract latent cognitive variables, could enhance prediction of suicide attempts within next 90 days, among individuals at high-risk for suicide., Method: 136 Veterans at high-risk for suicide previously completed a computer-based GNG task requiring rapid responding (Go) to target stimuli, while withholding responses (No-go) to infrequent foil stimuli; behavioral variables included false alarms to foils (failure to inhibit) and missed responses to targets. We conducted a secondary analysis of these data, with outcomes defined as actual suicide attempt (ASA), other suicide-related event (OtherSE) such as interrupted/aborted attempt or preparatory behavior, or neither (noSE), within 90-days after GNG testing, to examine whether GNG variables could improve ASA prediction over standard clinical variables. A computational model (linear ballistic accumulator, LBA) was also applied, to elucidate cognitive mechanisms underlying group differences., Results: On GNG, increased miss rate selectively predicted ASA, while increased false alarm rate predicted OtherSE (without ASA) within the 90-day follow-up window. In LBA modeling, ASA (but not OtherSE) was associated with decreases in decisional efficiency to targets, suggesting differences in the evidence accumulation process were specifically associated with upcoming ASA., Conclusions: These findings suggest that GNG may improve prediction of near-term suicide risk, with distinct behavioral patterns in those who will attempt suicide within the next 90 days. Computational modeling suggests qualitative differences in cognition in individuals at near-term risk of suicide attempt.

Suicidal behavior is associated with deficits in cognitive control; however, suicidal ideation (SI), a key precursor to suicidal behavior, has been less consistently linked to neuropsychological functioning. Additionally, no study to date has examined attentional control capacities in relation to variability in suicidal ideation, defined as fluctuation in SI intensity and duration across short periods of time. Prior research suggests that suicidal individuals with highly variable SI experience greater stress-responsive increases in SI and cortisol, potentially raising risk for suicidal behavior. Here, we examined attentional control capacities associated with SI variability and severity in ninety-five subjects with major depressive disorder. Variability and severity of SI and depressive affect were quantified using Ecological Momentary Assessment (EMA) over a 7-day period. Participants completed the Continuous Performance Task (CPT) and a computerized Stroop task for assessment of attentional control. EMA SI variability was associated with greater attentional interference on the Stroop task, and this was not accounted for by severity of SI, concurrently assessed depressive affect, or baseline depression. CPT performance was not related to SI variability or intensity. Findings highlight the utility of EMA methods in characterizing patterned experiences of SI and suggest that attentional control deficits may contribute to these characteristic patterns., Competing Interests: Conflict of interest Drs. Stanley and Mann receive royalties from the Research Foundation for Mental Hygiene for the commercial use of the CSSRS. All other authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Clinical and empirical reports suggest that individuals use non-suicidal self-injury (NSSI) not only to ameliorate dysphoria, but to curb suicidal ideation or avoid suicidal behaviour. To date, however, no study has quantitatively assessed whether NSSI leads to short-term reductions in suicidal ideation. Using real-time monitoring over 7 days in a sample with borderline personality disorder, we found evidence that NSSI is followed by reductions in suicidal ideation in the subsequent hours. This suggests that NSSI may serve as an effective, albeit maladaptive, coping strategy for suicidal states. These findings have important implications for the management of suicide risk and self-harm.

Background: During adolescence, suicide risk increases; effective treatments are needed to reduce risk., Methods: Databases were searched (1995-2020) for randomized controlled trials (RCTs) concerning psychosocial treatments for suicide prevention in adolescents (10-18 yrs). Data were extracted from the timepoint closest to 6 months. Cohen's ds were estimated for reducing suicidal ideation (SI), self-harming behaviors (SHB) excluding strictly non-suicidal self-injury, and suicide attempts (SA) and analyzed using generalized least square regression. Meta-analytic innovations included within-person correlations to reflect trait suicidality; annualization to control for exposure; estimated lifetime risk based on ages; and modeling inclusion/exclusion criteria. Alternate approaches included relative risk and comparison of intervention and control treatments to baseline., Results: Of 30 RCTs, 6 assessing SHB (4 measuring SA), and 7 assessing SI demonstrated treatment effectiveness. Overall, interventions decreased SI (n = 25) with low effect size (d = 0.08, p = 0.01), non-significant after controlling for publication bias (d = 0.05, p = 0.1); interventions were non-significant for SHB (n = 25, d = 0.001, p = 0.97) or SA (n = 18, d = 0.03, p = 0.52). To prevent one SHB, the number needed to treat (NNT) was 45[26,156]; for SA, NNT=42[24,149]. Non-superiority may relate to effectiveness of control treatments. Thus, experimental and control treatments also were compared to baseline: both reduced SI (p < 0.0001), and effectiveness improved for SHB (NNT=12) and SA (NNT=11)., Limitations: Study heterogeneity and inconsistent statistical reporting limited meta-analysis., Conclusions: Psychosocial interventions for suicide risk in adolescents showed little effectiveness compared with control treatments; suicide outcomes improved in both groups compared to baseline. Different approaches may be needed, including precision medicine methodologies and standardized statistical reporting criteria., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Suicidal behavior (SB) can be impulsive or methodical; violent or not; follow a stressor or no obvious precipitant. This study tested whether childhood trauma, affective lability, and aggressive and impulsive traits predicted greater SI variability. We also assessed whether affective lability, aggressive or impulsive traits explain childhood trauma's effects on SI variability and whether those with highly variable SI respond to stressful events with increases in SI. Finally, we assessed variable SI's trajectory over 2 years. Depressed participants (n = 51) had ecological momentary assessments (EMA) over 7 days at baseline, 3, 6, 12, 18, and 24 months. SI variability was assessed using the square Root of the Mean Square of Successive Deviations. Mixed Effects Models were fit as appropriate. Childhood trauma was associated with subsequent aggression. Physical abuse predicted both aggression and affective lability as well as SI variability, but not impulsivity. In two-predictor models, physical abuse's effect on SI variability was no longer significant, when controlling for the effect of higher aggression and impulsivity. Those with high SI variability exhibited greater increases in SI after stressors compared with those with less variability. We did not find that SI variability changed over time, suggesting it might be trait-like, at least over 2 years. Variable SI predisposes to marked SI increases after stressful events and may be a trait increasing risk for impulsive SB, at least over 2 years., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective : Suicidal individuals are a heterogeneous population and may differ in systematic ways in their responsiveness to stress. The primary aim of the present study was to identify whether a different pattern of physiological stress response exists among adult suicide attempters with a history of behavioral problems during childhood and adolescence, which earlier studies have related to both decreased activity of the HPA axis and to suicidal behaviors. Method : Seventy-eight participants with Borderline Personality Disorder were assessed using the SCID-II, and completed self-report measures assessing their history of suicide attempts, history of aggressive behaviors, depressive symptoms, history of lifetime abuse and demographics. Participants' cortisol reactivity was assessed using the Trier Social Stress Test . Results : Analyses indicated that suicide attempters with a history of behavioral problems in youth (n = 30) had a significantly lower response to stress than both suicide attempters without such a history (n = 26) and non-attempters (n = 22), when controlling for lifetime history of abuse. The groups did not differ in basal cortisol. Conclusions : These findings suggest a unique subtype of suicide attempter among those with Borderline Personality Disorder, characterized by a blunted physiological stress response.

Objective: To examine factors differentiating individuals whose first suicide attempt was during childhood (ages 5-12 yrs) from those who first attempted suicide during adolescence (13-19 yrs) and during adulthood (≥20 yrs)., Method: A sample of 418 participants (ages 18-64 yrs) with a mood disorder and ≥1 lifetime suicide attempt was divided into three groups according to age of first suicide attempt (childhood: N = 43, adolescent: N = 149, adulthood: N = 226) and compared on demographics, childhood adversity, parental psychopathology, comorbid lifetime axis I diagnoses, self-harm and characteristics of first attempt., Results: Participants in the Childhood Attempt group were more likely to report childhood adversity, parental alcohol use disorder and subsequent suicide attempts than the two other groups. They were also more likely to have a depressed mother, non-suicidal self-injury (NSSI) during childhood and adolescence, lifetime PTSD and aggressive behavior than the Adulthood Attempt group. The Adolescent Attempt group had more childhood adversity, parental suicidal behavior, lifetime PTSD and NSSI during adolescence than the Adulthood Attempt group. The groups differed on methods of first attempt, and its lethality was related to age of attempt., Conclusions: Early adversity and parental psychopathology are particularly prominent in those who make childhood suicide attempts, suggesting that this group may represent a suicidal behavior subtype., Competing Interests: Declaration of competing interest This work was supported by the NIMH#P50 MH090964 (PI: Mann) and NIMH#R01 MH109326 (PIs: Stanley and Oquendo) and NIMH#R01 MH062665 (PI: Stanley). Disclosure: Drs Burke, Mann, Oquendo, and Stanley receive royalties for commercial use of the C-SSRS from the Research Foundation for Mental Hygiene. Dr. Oquendo's family owns stock in Bristol Myers Squibb. No other author conflicts to disclose., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Neurocognitive detection of suicidal states has the potential to significantly advance objective risk assessment. This goal requires establishing that neurocognitive deficits fluctuate around the time of a suicide attempt. The current study therefore evaluated whether neurocognitive performance is temporally related to suicide attempt, in a sample at highrisk for suicide (n = 141). Evaluations consisted of a clinician-administered interview, self-report questionnaires, and neurocognitive tasks assessing response inhibition, attentional control, and memory recognition. Analyses examined whether neurocognitive scores significantly differed according to the following temporal suicide attempt categories: (a) past-week attempt; (b) past-year attempt (not in past week); and (c) no past-year attempt. Univariate results showed that response inhibition and memory recognition were significantly related to suicide attempt recency. Post-hoc pairwise tests showed that participants with a past-week suicide attempt showed greater impairments than those without a past-year attempt. Multivariate tests showed the same pattern of results, adjusting for age, suicide attempts prior to past year, mood disturbance, and suicidal ideation. These results show that neurocognitive assessment of response inhibition and memory recognition shows sensitivity to the recency of a suicide attempt. While future prospective studies are needed, results suggest that phasic neurocognitive deficits may serve as objective markers of short-term suicide risk., (Published by Elsevier B.V.)

Although recent years have seen large decreases in the overall global rate of suicide fatalities, this trend is not reflected everywhere. Suicide and suicidal behaviour continue to present key challenges for public policy and health services, with increasing suicide deaths in some countries such as the USA. The development of suicide risk is complex, involving contributions from biological (including genetics), psychological (such as certain personality traits), clinical (such as comorbid psychiatric illness), social and environmental factors. The involvement of multiple risk factors in conveying risk of suicide means that determining an individual's risk of suicide is challenging. Improving risk assessment, for example, by using computer testing and genetic screening, is an area of ongoing research. Prevention is key to reduce the number of suicide deaths and prevention efforts include universal, selective and indicated interventions, although these interventions are often delivered in combination. These interventions, combined with psychological (such as cognitive behavioural therapy, caring contacts and safety planning) and pharmacological treatments (for example, clozapine and ketamine) along with coordinated social and public health initiatives, should continue to improve the management of individuals who are suicidal and decrease suicide-associated morbidity.

Background: Knowledge is lacking on the long-term outcomes of treatment for adolescents with repetitive suicidal and self-harming behavior. Furthermore, the pathways through which treatment effects may operate are poorly understood. Our aims were to investigate enduring treatment effects of dialectical behavior therapy adapted for adolescents (DBT-A) compared to enhanced usual care (EUC) through a prospective 3-year follow-up and to analyze possible mediators of treatment effects., Methods: Interview and self-report data covering the follow-up interval were collected from 92% of the adolescents who participated in the original randomized trial., Trial Registration Number: NCT01593202 (www.ClinicalTrials.gov)., Results: At the 3-year follow-up DBT-A remained superior to EUC in reducing the frequency of self-harm, whereas for suicidal ideation, hopelessness and depressive and borderline symptoms and global level of functioning there were no inter-group differences, with no sign of symptom relapse in either of the participant groups. A substantial proportion (70.8%) of the effect of DBT-A on self-harm frequency over the long-term was mediated through a reduction in participants' experience of hopelessness during the trial treatment phase. Receiving more than 3 months follow-up treatment after completion of the trial treatment was associated with further enhanced outcomes in patients who had received DBT-A., Conclusions: There were on average no between-group differences at the 3-year follow-up in clinical outcomes such as suicidal ideation, hopelessness, depressive and borderline symptoms. The significantly and consistently larger long-term reduction in self-harm behavior for adolescents having received DBT-A compared with enhanced usual care, however, suggests that DBT-A may be a favorable treatment alternative for adolescents with repetitive self-harming behavior., (© 2019 Association for Child and Adolescent Mental Health.)

Background: Abnormalities in the hypothalamic-pituitary-adrenal axis, serotonergic system, and stress response have been linked to the pathogenesis of major depressive disorder. State-dependent hyper-reactivity of the hypothalamic-pituitary-adrenal axis is seen in major depressive disorder, and higher binding to the serotonin 1A receptor is observed as a trait in both currently depressed and remitted untreated major depressive disorder. Here, we sought to examine whether a relationship exists between cortisol secretion in response to a stressor and serotonin 1A receptor binding throughout the brain, both in healthy controls and participants with major depressive disorder., Methods: Research participants included 42 medication-free, depressed subjects and 31 healthy volunteers. Participants were exposed to either an acute, physical stressor (radial artery catheter insertion) or a psychological stressor (Trier Social Stress Test). Levels of serotonin 1A receptor binding on positron emission tomography with [11C]WAY-100635 were also obtained from all participants. The relationship between [11C]WAY-100635 binding and cortisol was examined using mixed linear effects models with group (major depressive disorder vs control), cortisol, brain region, and their interactions as fixed effects and subject as a random effect., Results: We found a positive correlation between post-stress cortisol measures and serotonin 1A receptor ligand binding levels across multiple cortical and subcortical regions, independent of diagnosis and with both types of stress. The relationship between [11C]WAY-100635 binding and cortisol was homogenous across all a priori brain regions. In contrast, resting cortisol levels were negatively correlated with serotonin 1A receptor ligand binding levels independently of diagnosis, except in the RN. There was no significant difference in cortisol between major depressive disorder participants and healthy volunteers with either stressor. Similarly, there was no correlation between cortisol and depression severity in either stressor group., Conclusions: This study suggests that there may be a common underlying mechanism that links abnormalities in the serotonin system and hypothalamic-pituitary-adrenal axis hyper-reactivity to stress. Future studies need to determine how hypothalamic-pituitary-adrenal axis dysfunction affects mood to increase the risk of suicide in major depression., (© The Author(s) 2019. Published by Oxford University Press on behalf of CINP.)

Suicide is the second leading cause of death among undergraduate students, with an annual rate of 7.5 per 100,000. Suicidal behavior (SB) is complex and heterogeneous, which might be explained by there being multiple etiologies of SB. Data-driven identification of distinct at-risk subgroups among undergraduates would bolster this argument. We conducted a latent class analysis (LCA) on survey data from a large convenience sample of undergraduates to identify subgroups, and validated the resulting latent class model on a sample of graduate students. Data were collected through the Interactive Screening Program deployed by the American Foundation for Suicide Prevention. LCA identified 6 subgroups from the undergraduate sample (N = 5654). In the group with the most students reporting current suicidal thoughts (N = 623, 66% suicidal), 22.5% reported a prior suicide attempt, and 97.6% endorsed moderately severe or worse depressive symptoms. Notably, LCA identified a second at-risk group (N = 662, 27% suicidal), in which only 1.5% of respondents noted moderately severe or worse depressive symptoms. When graduate students (N = 1138) were classified using the model, a similar frequency distribution of groups was found. Finding multiple replicable groups at-risk for suicidal behavior, each with a distinct prevalence of risk factors, including a group of students who would not be classified as high risk with depression-based screening, is consistent with previous studies that identified multiple potential etiologies of SB., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: We conducted a 1-year prospective follow-up study of posttreatment clinical outcomes in adolescents with recent and repetitive self-harm who had been randomly allocated to receive 19 weeks of either dialectical behavior therapy adapted for adolescents (DBT-A) or enhanced usual care (EUC) at community child and adolescent psychiatric outpatient clinics., Method: Assessments of self-harm, suicidal ideation, depression, hopelessness, borderline symptoms, and global level of functioning were made at the end of the 19-week treatment period and at follow-up 1 year later. Altogether 75 of the 77 (97%) adolescents participated at both time points. Frequencies of hospitalizations, emergency department visits and other use of mental health care during the 1-year follow-up period were recorded. Change analyses were performed using mixed effects linear spline regression and mixed effect Poisson regression with robust variance., Results: Over the 52-week follow-up period, DBT-A remained superior to EUC in reducing the frequency of self-harm. For other outcomes such as suicidal ideation, hopelessness, and depressive or borderline symptoms and for the global level of functioning, inter-group differences apparent at the 19-week assessment were no longer observed, mainly due to participants in the EUC group having significantly improved on these dimensions over the follow-up year, whereas DBT-A participants remained unchanged., Conclusion: A stronger long-term reduction in self-harm and a more rapid recovery in suicidal ideation, depression, and borderline symptoms suggest that DBT-A may be a favorable treatment alternative for adolescents with repetitive self-harming behavior., Clinical Trial Registration Information: Treatment for Adolescents With Deliberate Self Harm; http://clinicaltrials.gov/; NCT00675129., (Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Many, but not all studies of suicide attempters' cortisol response to stress-either social stress or pharmacological challenge-report an exaggerated response. Recent studies of resting baseline cortisol in past suicide attempters, however, have found lower baseline levels., Methods: In this study, baseline salivary cortisols were obtained prior to a stress procedure from adults with lifetime diagnoses of a mood disorder (N=69), 31.9% of whom had made a prior suicide attempt. Data were collected during the piloting of this stress procedure, at various times of day and with/without an additional confederate in the room., Results: Adjusting for procedural, demographic and clinical variables that affect salivary cortisol levels-including time of day of sampling, order of procedure with respect to other assessments, past alcohol abuse, current medication use, and bipolar diagnosis-past suicide attempters had lower baseline cortisol levels compared to non-attempters., Limitations: This is a pilot study with modest sample sizes using statistical, rather than experimental control of numerous variables affecting salivary cortisol levels., Conclusions: Results confirm previous studies. Low baseline cortisol levels have been associated with childhood adversity and externalizing disorders, suggesting a potential role in reducing inhibitions for risky and dangerous behaviors. Further research is needed to more fully characterize these associations and their role in suicidal behavior risk., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Suicide, a major cause of death worldwide, has distinct biological underpinnings. The authors review and synthesize the research literature on biomarkers of suicide, with the aim of using the findings of these studies to develop a coherent model for the biological diathesis for suicide., Method: The authors examined studies covering a large range of neurobiological systems implicated in suicide. They provide succinct descriptions of each system to provide a context for interpreting the meaning of findings in suicide., Results: Several lines of evidence implicate dysregulation in stress response systems, especially the hypothalamic-pituitary-adrenal axis, as a diathesis for suicide. Additional findings related to neuroinflammatory indices, glutamatergic function, and neuronal plasticity at the cellular and circuitry level may reflect downstream effects of such dysregulation. Whether serotonergic abnormalities observed in individuals who have died by suicide are independent of stress response abnormalities is an unresolved question., Conclusions: The most compelling biomarkers for suicide are linked to altered stress responses and their downstream effects, and to abnormalities in the serotonergic system. Studying these systems in parallel and in the same populations may elucidate the role of each and their interplay, possibly leading to identification of new treatment targets and biological predictors.

Objective: We examined whether a shortened form of dialectical behavior therapy, dialectical behavior therapy for adolescents (DBT-A) is more effective than enhanced usual care (EUC) to reduce self-harm in adolescents., Method: This was a randomized study of 77 adolescents with recent and repetitive self-harm treated at community child and adolescent psychiatric outpatient clinics who were randomly allocated to either DBT-A or EUC. Assessments of self-harm, suicidal ideation, depression, hopelessness, and symptoms of borderline personality disorder were made at baseline and after 9, 15, and 19 weeks (end of trial period), and frequency of hospitalizations and emergency department visits over the trial period were recorded., Results: Treatment retention was generally good in both treatment conditions, and the use of emergency services was low. DBT-A was superior to EUC in reducing self-harm, suicidal ideation, and depressive symptoms. Effect sizes were large for treatment outcomes in patients who received DBT-A, whereas effect sizes were small for outcomes in patients receiving EUC. Total number of treatment contacts was found to be a partial mediator of the association between treatment and changes in the severity of suicidal ideation, whereas no mediation effects were found on the other outcomes or for total treatment time., Conclusion: DBT-A may be an effective intervention to reduce self-harm, suicidal ideation, and depression in adolescents with repetitive self-harming behavior. Clinical trial registration information-Treatment for Adolescents With Deliberate Self Harm; http://ClinicalTrials.gov/; NCT00675129., (Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the demographic and clinical correlates of nonsuicidal self-injury., Method: This is a cross-sectional analysis of a longitudinal cohort study of the familial transmission of suicidal behavior, conducted at referral centers in Pittsburgh, Pennsylvania, and New York, New York. Participants included 291 probands with DSM-IV mood disorder, one-half of whom had attempted suicide, and 507 of their offspring. The primary outcome assessed was nonsuicidal self-injury in offspring. Psychosocial correlates of nonsuicidal self-injury were determined by comparing personal, parental, and familial characteristics of offspring with and without nonsuicidal self-injury, assessed using a variety of interview and self-report measures at study entry. Data were collected between August 1998 and August 2007., Results: Of 507 offspring, 7.7% (n=39) had engaged in nonsuicidal self-injury. The most salient correlates of nonsuicidal self-injury on multivariate logistic regression were diagnosis of depression (OR=3.78, P<.001) and greater aggression (OR=1.07, P=.01), depressive symptoms (OR=1.59, P=.009), and suicidal ideation (OR=1.24, P=.004). Parental history of abuse, as well as family histories of suicide attempt and nonsuicidal self-injury, was noncontributory., Conclusions: Nonsuicidal self-injury is associated with the presence and severity of depression, suicidal ideation, and behavioral dysregulation. On multivariate analysis, only individual predictors remained significant; this result is distinct from that for correlates of suicide attempt reported in this sample, for which familial variables played a significant role., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Objective: To determine the demographic and clinical predictors of nonsuicidal self-injury and to examine the longitudinal relationship between nonsuicidal self-injury and suicide attempt., Method: This was a longitudinal cohort study of the familial transmission of suicidal behavior. The sample consisted of probands with DSM-IV mood disorder (n = 212), 54.2% of whom were suicide attempters, and their offspring aged at least 10 years (n = 352), followed for a mean of 3.8 years. Personal, parental, and familial characteristics were assessed annually to identify the most parsimonious subset of these variables associated with nonsuicidal self-injury, the primary outcome. Data were collected between August 1998 and August 2007., Results: Of 352 offspring, 7.4% (n = 26) engaged in nonsuicidal self-injury during follow-up. In the final model examining predictors at baseline, the most severe time point, and the time point prior to nonsuicidal self-injury, only predictors from the most proximal time point were significant, namely younger age (odds ratio [OR] = 0.75, P = .002), diagnosis of current major depression (OR = 5.09, P < .001), and suicidal ideation (OR = 1.46, P = .02). In 2 of the 3 single time point models, baseline nonsuicidal self-injury was the most significant predictor of nonsuicidal self-injury during follow-up. Suicide attempt was predicted by both baseline nonsuicidal self-injury and suicide attempt, but when both were included in the model, nonsuicidal self-injury was a significant predictor (OR = 7.50, P = .009), but suicide attempter was not (OR = 3.78, P = .08); offspring aggression (OR = 1.11, P = .01) predicted suicide attempt but not nonsuicidal self-injury. Parental histories of nonsuicidal self-injury, suicide attempt, and abuse were not predictive of nonsuicidal self-injury., Conclusions: Nonsuicidal self-injury may be an earlier manifestation of a shared diathesis with suicide attempt, consisting of depression and suicidal ideation, and that diathesis may lead to suicidal behavior in the face of greater offspring aggression and family pathology. The apparent bidirectional temporal relationship between nonsuicidal self-injury and suicide attempt may be explained by this shared diathesis., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Comorbidity of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) is associated with higher morbidity including suicidal ideation and behavior. Selective serotonin reuptake inhibitors (SSRIs) are a known treatment for PTSD, MDD and comorbid PTSD and MDD. Since the patients with comorbid MDD and PTSD (PTSD-MDD) are sicker, we hypothesize a poorer response to treatment compared to patients with MDD only. Ninety-six MDD patients were included in the study: 76 with MDD only and 20 with PTSD-MDD. Demographic and clinical parameters at baseline were assessed. We examined clinical parameters before and after 3 months of open SSRI treatment in subjects with PTSD-MDD and compared this group to individuals with MDD only. At baseline, PTSD-MDD patients had higher Hamilton Depression Rating Scale and Buss-Durkee Hostility Scale scores compared with MDD only subjects. There was a significant decrease in scores on the Hamilton Depression Rating Scale, Beck Depression Inventory, Beck Hopelessness Scale, and Beck Scale for Suicidal Ideation after 3 months of treatment with SSRIs in both groups. The magnitude of improvement in Beck Scale for Suicidal Ideation scores was greater in the PTSD-MDD group compared to the MDD only subjects. Symptoms of depression including suicidal ideation improved in MDD patients with or without comorbid PTSD after 3 months of treatment with SSRIs but improvement in suicidal ideation was greater in the PTSD-MDD group. Our finding has not supported the hypothesis that a response to treatment is poorer in the PTSD-MDD group which may indicate that sicker patients benefit more from the treatment., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A simulation model of the temporal and spatial dynamics and population genetics of western corn rootworm, Diabrotica virgifera virgifera LeConte, was created to evaluate the use of block refuges and seed blends in the management of resistance to transgenic insecticidal corn (Zea mays L.). This Bt corn expresses one transgenic corn event, DAS-59122-7, that produces a binary insecticidal protein toxin (Cry34Ab1/Cry35Ab1) and provides host-plant resistance. The model incorporates the latest information about larval and adult behavior. Results of this modeling effort indicate that the seed-blend scenarios in many cases produced equal or greater durability than block refuges that were relocated each year. Resistance evolved in the most likely scenarios in 10-16 yr. Our standard analysis presumed complete adoption of 59122 corn by all farmers in our hypothetical region, no crop rotation, and 100% compliance with Insect Resistant Management (IRM) regulations. As compliance levels declined, resistance evolved faster when block refuges were deployed. Seed treatments that killed the pest when applied to all seeds in a seed blend or just to seeds in Bt corn blocks delayed evolution of resistance. Greater control of the pest population by the seed treatment facilitated longer durability of the transgenic trait. Therefore, data support the concept that pyramiding a transgenic insecticidal trait with a highly efficacious insecticidal seed treatment can delay evolution of resistance.

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

Acute alcohol use is an important risk factor for attempted and completed suicide. We evaluated the effect of acute alcohol intake on the lethality of suicide attempts to test the hypothesis that acute alcohol intoxication is associated with more lethal suicide attempts. This retrospective study included 317 suicide attempters enrolled in mood disorders protocols. Demographic and clinical parameters were assessed. The use of alcohol at the time of the most lethal suicide attempt was determined. On the basis of their responses participants were classified into three groups: participants who reported "Enough alcohol intake to impair judgment, reality testing and diminish responsibility" or "Intentional intake of alcohol in order to facilitate implementation of attempt" were included in the group "Alcohol" (A); participants who reported "Some alcohol intake prior to but not related to attempt, reportedly not enough to impair judgment, reality testing" were included in the group "Some Alcohol" (SA); and participants who reported "No alcohol intake immediately prior to attempt" were included in the group "No Alcohol" (NA). Lethality of the most lethal suicide attempts was higher in the A group compared to the SA and NA groups. Prevalence of patients with alcohol use disorders was higher in the A group compared to the SA and NA groups. SA participants reported more reasons for living and lower suicide intent scores at the time of their most lethal suicide attempt compared to the A and NA groups. Acute alcohol use increases the lethality of suicide attempts in individuals with mood disorders.

Background: We aimed to examine the adequacy of antidepressant treatment and compliance with treatment in bipolar patients with and without alcohol use disorders (AUD). We hypothesize that the adequacy of antidepressant treatment and the compliance with treatment for those with AUD are lower than for those without AUD., Methods: Subjects were 97 patients with current bipolar major depressive episode, 39 (40.2%) with lifetime history of AUD and 58 (59.8%) without AUD. Adequacy of antidepressant medication treatment in the 3 previous months was assessed using the Antidepressant Treatment History Form. Compliance rates were estimated., Results: Rates of inadequate treatment were high in all patients. Bipolar patients with AUD (74.3%) showed higher rates of inadequate antidepressant treatment than those without AUD (67.3%). The proportion of intensive treatment was higher in bipolars without AUD (15.5%) than in those with AUD (2.6%). Median compliance was similar in bipolars with and without AUD., Limitations: We lack serum medication levels to assess the compliance. We do not have data to address the possibility that the presence of AUD adversely affected prescribing practices., Conclusions: Bipolars with AUD had lower rates of adequate treatment than those without AUD, but the two groups were not different in terms of self-reported treatment adherence. The finding that bipolar patients with or without comorbid AUD did not receive adequate treatment is of considerable clinical relevance. It raises the question as to whether inadequate treatment of depression contributes to the high rates of morbidity, and attempted and completed suicides in bipolar patient populations.

A number of studies have compared clinical diagnostic and suicide assessments to standardized schedules to determine the level of agreement. At best there is only moderate diagnostic agreement, but most often it is fair. There are only a few reports comparing clinical assessments for suicidal behavior with standardized schedules. We present the data from 201 inpatient admissions for major depression that had both clinical diagnostic and suicide evaluations by PGYII resident physicians under supervision from an attending psychiatrist and research evaluations using standardized schedules for diagnosis and suicide by at least masters' level clinicians. There was moderate agreement for diagnosis and suicide attempt history but only fair agreement for the presence of suicidal ideation using Cohen's kappa statistic. In regards to suicide attempt history a cross-tabulation demonstrated that 18.7% of those patients identified by a research schedule as having a past suicide attempt were not identified as such by the clinicians. A cross-tabulation demonstrated that 29.7% of those patients identified by structured interview as having suicidal ideation were not identified as such by the clinician. There was a statistically significant difference in the level of agreement for suicide attempt history between clinical and research assessments for attempts within a year of admission and those beyond a year. These findings suggest the importance of adding a structured diagnostic and suicide assessment to routine clinical care to improve the reliability and validity of clinical evaluations and to inform treatment planning to benefit our patients.

Dysfunction of serotonergic neurotransmission has been implicated in the etiopathogenesis of major depression (MDD) and alcohol use disorders (AUD). To compare serotonin function in MDD with co-occurring AUD (MDD/AUD), MDD without co-occurring AUD (MDD only) and healthy controls (HC) we sought to study differences in prolactin responses to fenfluramine administration in patients with MDD/AUD, patients with MDD only and HC. In all, 169 subjects (62 MDD/AUD, 75 MDD only, and 32 HC) were entered into the study. Controlling for gender, prolactin responses were lower in the MDD/AUD group compared to the MDD only or the HC group. Controlling for gender and aggression, prolactin responses in the MDD/AUD group remained significantly lower compared to the HC group but the difference between the MDD/AUD and the MDD only groups disappeared. The difference in prolactin responses between MDD/AUD and MDD only could be attributed to higher aggression scores in the MDD/AUD group compared to the MDD group.

Objective: Alcohol use and depressive disorders are frequently comorbid. Few studies have assessed the impact of comorbid alcohol use disorders (AUDs) on clinical aspects of major depression. We compared depressed subjects with and without co-occurring AUDs with respect to demographic and clinical parameters., Method: 505 individuals participated. 318 subjects had DSM-IV major depressive disorder (MDD) without a history of any alcohol or substance abuse/dependence (MDD only), and 187 individuals had MDD and a history of alcohol abuse/dependence (MDD/AUD). Demographic, clinical, and psychiatric history measures of patients in the 2 groups were examined and compared. The study was conducted from January 1990 to June 2005., Results: MDD/AUD patients were younger at their first psychiatric hospitalization (p = .014), their first major depressive episode (p = .041), and their first suicide attempt (p = .001). They reported more previous major depressive episodes (p = .001), suicide attempts (p = .001), and recent life events (p = .001); and had higher lifetime aggression (p < .001), impulsivity (p < .001), and hostility (p < .001) scores. MDD/AUD patients were also more likely to report tobacco smoking (p < .001), a lifetime history of abuse (p = .004), and a history of AUD among first-degree relatives (p < .001) compared to MDD only patients. MDD/AUD individuals also had higher childhood (p < .001), adolescent (p < .001), and adult (p < .001) aggression scores and reported more behavioral problems during their childhood compared to their counterparts. Logistic regression analysis demonstrates that the number of previous depressive episodes, lifetime aggression, and smoking drive the difference between the groups., Conclusions: Our findings suggest that comorbid MDD/AUD may result from worse antecedents and lead to early onset, more comorbidity, and a more severe course of illness.

Multiple lines of evidence suggest that endogenous opioids are involved in the pathogenesis of non-suicidal self-injury (NSSI). Evidence for such a role is based on the partial success of opioid antagonist treatment to ameliorate NSSI, reports of altered pain sensitivity during episodes of NSSI, and findings of altered endogenous opioid levels in individuals with NSSI. While suicidal behavior (SB) and NSSI are distinct behaviors, NSSI is a significant risk factor for suicide attempts and suicide. The high co-occurrence of SB and NSSI suggests that they may share a common biology. Available data indicate that endogenous opioids may be involved in the pathophysiology of SB. Future studies of the role of opioids in the biological mechanisms of NSSI and SB are merited and may lead to the development of new treatment modalities.

Unlabelled: Adolescent suicide is a major social and medical problem. Alcohol use disorders with comorbid major depression represent an especially high-risk profile for suicidal behavior, repeated suicidal behavior and completed suicide. We compared demographic and clinical characteristics, prevalence of interpersonal triggers and the number of triggers for suicidal behavior in depressed late adolescents and young adults with or without comorbid alcohol use disorders., Methods: 18-26-year-old subjects were recruited through advertising and referrals and participated in mood disorders research in a university hospital. Thirty-eight depressed suicide attempters without a history of any alcohol or substance abuse/dependence and 29 depressed suicide attempters with comorbid alcohol abuse or dependence participated in the study. Demographic and clinical parameters including parameters related to suicidal behavior were examined and recorded., Results: There was no difference with regard to demographic parameters between the two groups. Depressed suicide attempters with comorbid alcohol use disorders had higher aggression and impulsivity scale scores and were more likely to be tobacco smokers compared to their counterparts without alcohol use disorders. Additionally, there was a trend towards higher lethality of suicide attempts in subjects with alcohol use disorders compared to the other group. We found no difference in the prevalence of interpersonal triggers or in the number of triggers for suicidal behavior between the two groups., Conclusion: It appears that among 18-26-year-old depressed suicide attempters, individuals with comorbid alcohol use disorders are more impaired with regard to aggressiveness and impulsivity compared to persons without comorbid alcohol abuse/dependence.

Adolescent suicide is the 3rd leading cause of death in the United States and alcohol consumption is estimated to cause adolescent males to be up to 17 times more likely to attempt suicide, and females three times more likely to attempt suicide. Suicide and suicide attempt rates vary across different ethnicities. Also, associated psychopathology, stressors and substance use differ across ethnic groups in adolescents. In an exhaustive review of the literature, we found that depressed Asian-American youth were four times more likely to display suicidal behavior when compared to other Asian youths with other diagnoses; and depressed African-American females were more likely to report suicidal ideation than male adolescents. We also found that Asian-Americans who experience high parental conflict are 30 times more likely to engage in suicidal behavior when compared to Asian-American youths with low parental conflict. African-American adolescents are 6.4 times more likely to attempt suicide as a result of parental conflict. With respect to alcohol use and dependence, Caucasian adolescents were twice as likely as the African American victims to have used alcohol before committing suicide. Alcohol use among adolescents was associated with increased suicidal behavior. Cultural differences in alcohol consumption may account for disparities, however future research is needed to further examine cultural trends in suicidal behavior and alcoholism.

Background: Studies suggest that the dopaminergic system is involved in the pathogenesis of major depression, Axis II disorders, and suicidal behavior. Depressed suicide attempters constitute a heterogenous group and important differences may exist between depressed suicide attempters with or without Axis II disorders. Therefore, we compared demographic and clinical parameters, and cerebrospinal fluid (CSF) homovanillic acid (HVA) levels in depressed suicide attempters without comorbid Axis II disorders, depressed non-attempters without comorbid Axis II disorders, and normal controls., Methods: Thirty-one depressed subjects with a history of a suicide attempt, 27 depressed subjects without a history of a suicide attempt, and 50 healthy controls were included in the study. Subjects with comorbid Axis II disorders were excluded. Demographic and clinical parameters, and CSF HVA levels were examined., Results: The two depressed groups did not differ with regard to depression, aggression, hopelessness, and total hostility scale scores. Depressed suicide attempters had higher current suicidal ideation scores compared to depressed non-attempters. Depressed suicide attempters had lower CSF HVA levels compared to depressed non-attempters (t = 4.4, df = 56, p < 0.0001) and to controls (t = -4.09, df = 79, p < 0.0001). There was no difference in CSF HVA levels between depressed non-attempters and controls (t < 1, df = 75, NS)., Conclusions: Dopaminergic abnormalities are associated with suicidality but not with depression. The variability in the rates of comorbid Axis II disorders and in the prevalence of suicide attempters in different patient populations may affect both clinical and biological results of studies of mood disorders.

An empirical screening level approach was developed to assess the probability of toxicity to benthic organisms associated with contaminated sediment exposure. The study was based on simple logistic regression models (LRMs) of matching sediment chemistry and toxicity data retrieved from a large database of field-collected sediment samples contaminated with multiple chemicals. Three decisions were made to simplify the application of LRMs to sediment samples contaminated with multiple chemicals. First, percent mortality information associated with each sediment sample was condensed into a dichotomous response (i.e., toxic or nontoxic). Second, each LRM assumed that toxicity was attributable to a single contaminant. Third, individual contaminants present at low concentrations were excluded from toxic sediment samples. Based on an analysis of the National Sediment Inventory database, the LRM approach classified 55% of nontoxic sediments as toxic (i.e., false-positives). Because this approach has been used to assess the probability of benthic toxicity as reported by the U.S. Environmental Protection Agency (U.S. EPA), the resultant estimates of potential toxicity convey a misleading impression of the increased hazard that sediments pose to the health of aquatic organisms at many sites in the United States. This could result in important resources needlessly being diverted from truly contaminated sites to evaluate and possibly remediate sediments at uncontaminated sites.

Graphs and simple Gaussian plume equations are presented for estimating the maximum horizontal area within a pheromone plume. In its simplest form the area,A R , for a given scaling factor,R = Q/(Ku), isA R = AI R (β), whereQ is the release rate,K is a specified concentration threshold,u is the wind velocity, and β is an atmospheric stability index. Estimates ofA I and β are given for several atmospheric stability typing schemes applicable to field and forest habitats.