Potential association between suicide risk, aggression, impulsivity, and the somatosensory system.

Aggression and impulsivity are linked to suicidal behaviors, but their relationship to the suicidal crisis remains unclear. This magnetoencephalography (MEG) study investigated the link between aggression, impulsivity, and resting-state MEG power and connectivity. Four risk groups were enrolled: high-risk (HR; n = 14), who had a recent suicidal crisis; lower-risk (LR; n = 41), who had a history of suicide attempts but no suicide attempt or ideation in the past year; clinical control (CC; n = 38), who had anxiety/mood disorders but no suicidal history; and minimal risk (MR; n = 28), who had no psychiatric/suicidal history. No difference in resting-state MEG power was observed between the groups. Individuals in the HR group with high self-reported aggression and impulsivity scores had reduced MEG power in regions responsible for sensory/emotion regulation vs. those in the HR group with low scores. The HR group also showed downregulated bidirectional glutamatergic feedback between the precuneus (PRE) and insula (INS) compared to the LR, CC, and MR groups. High self-reported impulsivity was linked to reduced PRE to INS feedback, whereas high risk-taking impulsivity was linked to upregulated INS to postcentral gyrus (PCG) and PCG to INS feedback. These preliminary findings suggest that glutamatergic-mediated sensory and emotion-regulation processes may function as potential suicide risk markers.

Active suicidal ideation associated with dysfunction in default mode network using resting-state EEG and functional MRI - Findings from the T-RAD Study.

Suicide in youth and young adults is a serious public health problem. However, the biological mechanisms of suicidal ideation (SI) remain poorly understood. The primary goal of these analyses was to identify the connectome profile of suicidal ideation using resting state electroencephalography (EEG). We evaluated the neurocircuitry of SI in a sample of youths and young adults (aged 10-26 years, n = 111) with current or past diagnoses of either a depressive disorder or bipolar disorder who were enrolled in the Texas Resilience Against Depression Study (T-RAD). Neurocircuitry was analyzed using orthogonalized power envelope connectivity computed from resting state EEG. Suicidal ideation was assessed with the 3-item Suicidal Thoughts factor of the Concise Health Risk Tracking self-report scale. The statistical pipeline involved dimension reduction using principal component analysis, and the association of neuroimaging data with SI using regularized canonical correlation analysis. From the original 111 participants and the correlation matrix of 4950 EEG connectivity pairs in each band (alpha, beta, theta), dimension reduction generated 1305 EEG connectivity pairs in the theta band, 2337 EEG pairs in the alpha band, and 914 EEG connectivity pairs in the beta band. Overall, SI was consistently involved with dysfunction of the default mode network (DMN). This report provides preliminary evidence of DMN dysfunction associated with active suicidal ideation in adolescents. Using EEG using power envelopes to compute connectivity moves us closer to using neurocircuit dysfunction in the clinical setting to identify suicidal ideation.

Functional changes in sleep-related arousal after ketamine administration in individuals with treatment-resistant depression.

The glutamatergic modulator ketamine is associated with changes in sleep, depression, and suicidal ideation (SI). This study sought to evaluate differences in arousal-related sleep metrics between 36 individuals with treatment-resistant major depression (TRD) and 25 healthy volunteers (HVs). It also sought to determine whether ketamine normalizes arousal in individuals with TRD and whether ketamine's effects on arousal mediate its antidepressant and anti-SI effects. This was a secondary analysis of a biomarker-focused, randomized, double-blind, crossover trial of ketamine (0.5 mg/kg) compared to saline placebo. Polysomnography (PSG) studies were conducted one day before and one day after ketamine/placebo infusions. Sleep arousal was measured using spectral power functions over time including alpha (quiet wakefulness), beta (alert wakefulness), and delta (deep sleep) power, as well as macroarchitecture variables, including wakefulness after sleep onset (WASO), total sleep time (TST), rapid eye movement (REM) latency, and Post-Sleep Onset Sleep Efficiency (PSOSE). At baseline, diagnostic differences in sleep macroarchitecture included lower TST (p = 0.006) and shorter REM latency (p = 0.04) in the TRD versus HV group. Ketamine's temporal dynamic effects (relative to placebo) in TRD included increased delta power earlier in the night and increased alpha and delta power later in the night. However, there were no significant diagnostic differences in temporal patterns of alpha, beta, or delta power, no ketamine effects on sleep macroarchitecture arousal metrics, and no mediation effects of sleep variables on ketamine's antidepressant or anti-SI effects. These results highlight the role of sleep-related variables as part of the systemic neurobiological changes initiated after ketamine administration. Clinical Trials Identifier: NCT00088699.

Long-term follow-up of participants in ketamine clinical trials for mood disorders.

BACKGROUND: Participants who received ketamine at the NIMH were among the first to receive ketamine for depression in controlled clinical trials, providing a unique opportunity to assess long-term outcomes. This analysis evaluated the relationship between participating in a ketamine clinical trial and subsequent ketamine/esketamine use after leaving the research setting. METHODS: Participants seen within the NIMH Experimental Therapeutics and Pathophysiology Branch from 2002 to 2022 (n = 1000) were contacted for follow-up assessment. Participants reported whether they had used ketamine/esketamine, sought non-prescribed ketamine, attempted suicide, or been psychiatrically hospitalized since discharge. Information regarding their recent depressive symptoms, dissociative symptoms, and hallucinations was also collected. RESULTS: Of the 203 participants in follow-up assessments (55 % female, average time since leaving NIMH = 9.04 years), 52 (25.6 %) had originally received ketamine at the NIMH, and the rest had participated in non-ketamine studies. Individuals who had received ketamine at the NIMH were more likely to have received ketamine/esketamine post-discharge than those who did not receive ketamine at the NIMH (OR = 0.25, p < .001). Participants who reported using ketamine/esketamine post-discharge reported more depressive symptoms than those who had not (p < .001). Receiving ketamine at the NIMH was not associated with differences in suicide attempts, psychiatric hospitalizations, dissociation, hallucinations, or attempt to obtain non-prescribed ketamine. LIMITATIONS: Low follow-up study participation rate; varying time since discharge. CONCLUSIONS: Participants who received ketamine in an NIMH clinical trial were more likely to receive ketamine/esketamine post-discharge, but none reported symptoms indicating abuse. Results underscore the critical need for long-term follow-up of individuals receiving these and other rapid-acting antidepressants. CLINICAL TRIALS IDENTIFIER: NCT04877977.

Clinical and electrophysiological correlates of hopelessness in the context of suicide risk✰.

Hopelessness is a key risk factor for suicide. This analysis explored whether hopelessness indicates a recent suicide crisis state and is linked with magnetoencephalography (MEG) oscillatory power and effective connectivity differences. Change in hopelessness ratings and effective connectivity post-ketamine were also evaluated in a subsample of high-risk individuals to evaluate correlates of dynamic changes over time. Participants (66F;44 M;1 transgender) included individuals with suicide crisis in the last two weeks (High Risk (HR), n = 14), those with past suicide attempt but no recent suicide ideation (SI) (Low Risk (LR), n = 37), clinical controls (CC, n = 33), and healthy volunteers at minimal risk (MinR, n = 27). MEG oscillatory power and clinical hopelessness ratings (via the Beck Hopelessness Scale (BHS)) were evaluated across groups. Dynamic casual modeling (DCM) evaluated connectivity within and between the anterior insula (AI) and anterior cingulate cortex (ACC). A subsample of HR individuals who received ketamine (n = 10) were evaluated at Day 1 post-infusion. The HR group reported the highest levels of hopelessness, even when adjusting for SI. MEG results linked hopelessness with reduced activity across frequency bands in salience network regions, with no group or group-by-interaction effects. Using DCM, the HR group had reduced intrinsic drive from granular Layer IV stellate cells to superficial pyramidal cells in the ACC and AI. In the pilot HR study, reduced hopelessness was linked with increased drive for this same connection post-ketamine. Hopelessness is a possible proxy for suicide risk. Electrophysiological targets for hopelessness include widespread reductions in salience network activity, particularly in the ACC and AI.

Pandemic-Related Post-traumatic Stress Symptomatology in COVID-19 Patients with and without Post-COVID Conditions.

Trauma and stressor-related symptoms have been frequently reported during the COVID-19 pandemic. Few studies compare post-traumatic stress symptoms (PTSS) between patients and non-infected controls. Using data from an ongoing natural history study of COVID-19, this study compared PTSS between patients infected with SARS-CoV-2 during the first year of the pandemic and controls. Within the COVID-19 patient cohort, we also compared PTSS between patients with and without post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study also examined the association of PTSS with trait resilience and prior trauma exposure. PTSS were assessed using the Impact of Event Scaled-Revised (IES-R), which has a validated probable PTSD cutoff (score ≥33). The results showed that patients (n=131) reported significantly higher IES-R scores than controls (n=82) and had significantly higher odds of having scores indicative of PTSD [AOR: 4.17 p: 0.029]. IES-R scores among PASC patients (n=68) were significantly elevated compared to patients without PASC (n=63) and PASC patients did not have higher odds for probable PTSD [AOR: 2.60; p: 0.14]. Trait resilience was associated with lower PTSS. These findings help characterize the mental health impact of the COVID-19 illness experience and highlight elevated PTSS in patients with persistent post-COVID conditions.

Clinical, behavioral, and electrophysiological profiles along a continuum of suicide risk: evidence from an implicit association task.

BACKGROUND: An urgent need exists to identify neural correlates associated with differing levels of suicide risk and develop novel, rapid-acting therapeutics to modulate activity within these neural networks. METHODS: Electrophysiological correlates of suicide were evaluated using magnetoencephalography (MEG) in 75 adults with differing levels of suicide risk. During MEG scanning, participants completed a modified Life-Death Implicit Association Task. MEG data were source-localized in the gamma (30-58 Hz) frequency, a proxy measure of excitation-inhibition balance. Dynamic causal modeling was used to evaluate differences in connectivity estimates between risk groups. A proof-of-concept, open-label, pilot study of five high risk participants examined changes in gamma power after administration of ketamine (0.5 mg/kg), an NMDAR antagonist with rapid anti-suicide ideation effects. RESULTS: Implicit self-associations with death were stronger in the highest suicide risk group relative to all other groups, which did not differ from each other. Higher gamma power for self-death compared to self-life associations was found in the orbitofrontal cortex for the highest risk group and the insula and posterior cingulate cortex for the lowest risk group. Connectivity estimates between these regions differentiated the highest risk group from the full sample. Implicit associations with death were not affected by ketamine, but enhanced gamma power was found for self-death associations in the left insula post-ketamine compared to baseline. CONCLUSIONS: Differential implicit cognitive processing of life and death appears to be linked to suicide risk, highlighting the need for objective measures of suicidal states. Pharmacotherapies that modulate gamma activity, particularly in the insula, may help mitigate risk.Clinicaltrials.gov identifier: NCT02543983, NCT00397111.

Toward objective characterizations of suicide risk: A narrative review of laboratory-based cognitive and behavioral tasks.

Although suicide is a leading cause of preventable death worldwide, current prevention efforts have failed to substantively mitigate suicide risk. Suicide research has traditionally relied on subjective reports that may not accurately differentiate those at high versus minimal risk. This narrative review supports the inclusion of objective task-based measures in suicide research to complement existing subjective batteries. The article: 1) outlines risk factors proposed by contemporary theories of suicide and highlights recent empirical findings supporting these theories; 2) discusses ongoing challenges associated with current risk assessment tools and their ability to accurately evaluate risk factors; and 3) analyzes objective laboratory measures that can be implemented alongside traditional measures to enhance the precision of risk assessment. To illustrate the potential of these methods to improve our understanding of suicide risk, the article reviews how acute stress responses in a laboratory setting can be modeled, given that stress is a major precipitant for suicidal behavior. More precise risk assessment strategies can emerge if objective measures are implemented in conjunction with traditional subjective measures.

Safety plan use in the daily lives of adolescents after psychiatric hospitalization.

INTRODUCTION: Safety planning type interventions (SPTI's) are brief suicide-specific interventions. Little is known about safety plan use during high-risk periods, and whether safety plan use is influenced by baseline characteristics. This study examined how adolescents recently hospitalized for suicide risk use their safety plans post-discharge, tested moderators of safety plan utilization, and explored the relationship between changes in utilization and changes in suicidal ideation (SI) over time. METHODS: Seventy-eight adolescents hospitalized for suicide risk who participated in a pilot trial of safety planning responded to one survey/day for 4 weeks post-discharge and completed a 1-month assessment. RESULTS: Over 90% of adolescents reported having access to their safety plan during the month post-discharge. Safety plan use and SI declined over time. No baseline characteristics predicted safety plan use in the 4 weeks after discharge, or changes in safety plan use over time. However, the relationship between changes in safety plan use and changes in SI was moderated. For girls, SI and safety plan use rose and fell together; for boys, safety plan use declined regardless of changes in SI. CONCLUSIONS: High-risk adolescents retain and use their safety plans. Results underscore the importance of looking at sex effects on SPTI utilization.

Immune-related biomarkers and suicidal behaviors: A meta-analysis.

Biomarkers that can differentiate between psychiatric disorders with and without suicidal behavior history from each other and from healthy volunteers may explain part of the pathogenesis of suicidal behavior. We conducted the hitherto largest meta-analysis comparing immune biomarkers between subjects with and without suicide attempt history or death by suicide. The study protocol was registered with PROSPERO, CRD42020212841. Standardized mean differences (SMD) were pooled with random-effects models. Heterogeneity between studies was assessed with the I2-statistic and publication bias was evaluated by the Egger test and funnel plots. Data were based on 36 studies including 2679 persons with suicidal behaviors and 6839 comparison subjects, and four immune-related biomarkers (CRP, IL-6, TNF-α and IL-1ß). Suicidal behavior was associated with higher CRP blood levels compared with: healthy controls (SMD [95%CI] = 1.42[0.85-1.98]); patients with depression alone (SMD [95%CI] = 1.23[0.20-2.26]); and patients with any psychiatric disorders (SMD [95%CI] = 0.39[0.22-0.55]). IL-6 blood level was higher in patients with suicidal behaviors compared with healthy controls (SMD [95%CI] = 1.13[0.45-1.82]) and when compared with psychiatric patients without suicidal behaviors (SMD [95%CI] = 0.22 [0.11-0.33]). Meta-regression and subgroup analyses revealed that increased CRP in suicidal behavior is primarily driven by recent suicidal behavior. These results implicate the immune system and inflammatory response in suicidal behavior independent of a relationship to major psychiatric disorders, and that these biological measures are predominantly state-dependent markers. Future studies are needed to determine the cause-and-effect relationship of these immune system biomarkers with suicidal behavior, and their potential predictive properties.

Concurrent validity and reliability of suicide risk assessment instruments: A meta-analysis of 20 instruments across 27 international cohorts.

OBJECTIVE: A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behavior. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. METHOD: Here, we examine this issue through two approaches: (a) an extensive literature search on the reliability and concurrent validity of the most commonly used instruments and (b) by pooling data (N ∼ 6,000 participants) from cohorts from the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Major Depressive Disorder and ENIGMA-Suicidal Thoughts and Behaviour working groups, to assess the concurrent validity of instruments currently used for assessing suicidal thoughts or behavior. RESULTS: We observed moderate-to-high correlations between measures, consistent with the wide range (κ range: 0.15-0.97; r range: 0.21-0.94) reported in the literature. Two common multi-item instruments, the Columbia Suicide Severity Rating Scale and the Beck Scale for Suicidal Ideation were highly correlated with each other (r = 0.83). Sensitivity analyses identified sources of heterogeneity such as the time frame of the instrument and whether it relies on self-report or a clinical interview. Finally, construct-specific analyses suggest that suicide ideation items from common psychiatric questionnaires are most concordant with the suicide ideation construct of multi-item instruments. CONCLUSIONS: Our findings suggest that multi-item instruments provide valuable information on different aspects of suicidal thoughts or behavior but share a modest core factor with single suicidal ideation items. Retrospective, multisite collaborations including distinct instruments should be feasible provided they harmonize across instruments or focus on specific constructs of suicidality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Social Anxiety and Suicidality in Youth: A Systematic Review and Meta-analysis.

Suicide is a leading cause of death among young people every year. Identifying risk factors provides opportunities to intervene, and social anxiety may represent one such factor. This systematic review and meta-analysis aimed to review the evidence of associations between social anxiety and suicidality in youth (10-25 years). Embase, PsycInfo, and Medline were searched to identify relevant articles. Meta-analysis was conducted to examine the mean effect sizes of concurrent and prospective associations between social anxiety and three indices of suicidality in adolescents aged 10-25 years. Meta-analyses of 16 studies showed that social anxiety was associated cross-sectionally with suicide attempt (r = 0.10, 95% CI: 0.04, 0.15), suicidal ideation (r = 0.22, 95% CI: 0.02, 0.41), and suicide risk (r = 0.24, 95% CI: 0.05, 0.41), and prospectively at trend level with suicidal ideation (r = 0.62, 95% CI: -0.03, 0.90). An examination of the prospective associations with suicide attempt and risk was not possible due to a lack of studies. Several studies suggested that results could not be solely attributed to depressive symptoms. A high level of heterogeneity was observed in each meta-analysis. Moderation analysis was possible for gender and publication year only; neither was significant. Findings provide further evidence of a link between social anxiety and suicidal thoughts and behaviors in youth but are limited by the small number of studies of mixed quality. This review supports future research into social anxiety symptoms as potential risk factors and treatment targets for suicidal youth.

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators.

Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials [pooled n = 809]. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median = 55.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute [~24-hours; ß*(95% CI) = 0.58 (0.44, 0.72); p < 0.0001] and post-acute [~7 days; ß*(95% CI) = 0.38 (0.23, 0.54); p < 0.0001] depression severity were observed. Two study-level moderators emerged as significant: ketamine effects (relative to placebo) were larger in studies that required a higher degree of previous treatment resistance to federal regulatory agency-approved antidepressant medications (≥2 failed trials) for study entry; and in studies that used a crossover design. A comprehensive data-driven search for combined moderators identified statistically significant, but modest and clinically uninformative, effects (effect size r ≤ 0.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions.Review Registration: PROSPERO Identifier: CRD42021235630.

A Participant-Level Integrative Data Analysis of Differential Placebo Response for Suicidal Ideation and Nonsuicidal Depressive Symptoms in Clinical Trials of Intravenous Racemic Ketamine.

BACKGROUND: Clinical trials of intravenous (IV) racemic (R,S)-ketamine (hereafter referred to as IV ketamine) have consistently reported rapid and substantial reductions in overall depressive symptoms compared with saline (inactive placebo) or midazolam (active placebo). The evidence for IV ketamine's specific effects on suicidal ideation is less clear, however. This study sought to examine whether differential placebo (saline or midazolam) response to overall depressive symptoms vs suicidal ideation may help explain these divergent findings. METHODS: Data for this participant-level integrative data analysis were drawn from 151 participants across 10 studies, and linear regression was used to examine the relationship between placebo response for suicidal ideation vs other depressive symptoms indexed from standard rating scales-specifically, depressed mood, anhedonia, anxiety, and guilt-over time. RESULTS: For participants receiving saline placebo (n = 46), greater placebo response was observed for suicidal ideation compared with other symptoms indexed from standard depression rating scales, except for anxiety. For those receiving midazolam placebo (n = 105), greater placebo response was observed for suicidal ideation compared with depressed mood or anhedonia, and no significant differences were observed when comparing suicidal ideation with anxiety or guilt. CONCLUSIONS: Taken together, the results provide preliminary evidence of a differential placebo response for suicidal ideation vs other depressive symptoms, while anxiety and suicidal ideation appear to produce similar placebo response profiles. These findings may help explain the more modest findings in clinical IV ketamine trials for suicidal ideation than overall depression.

Effects of stress on endophenotypes of suicide across species: A role for ketamine in risk mitigation.

Suicide is a leading cause of death and morbidity worldwide, yet few interventions are available to mitigate its risk. Barriers to effective treatments involve a limited understanding of factors that predict the onset of suicidal thoughts and behaviors. In the context of suicide risk, stress is a precipitating factor that is largely overlooked in the literature. Indeed, the pathophysiology of stress and suicide are heavily interconnected, underscoring the need to target the stress system in suicide prevention. In this review, we integrate findings from the preclinical and clinical literature that links stress and suicide. We focus specifically on the effects of stress on underlying biological functions and processes associated with suicide, allowing for the review of research using animal models. Owing to the rapid anti-suicidal effects of (R,S)-ketamine, we discuss its ability to modulate various stress-related endophenotypes of suicide, as well as its potential role in preventing suicide in those with a history of chronic life stress (e.g., early life adversity). We highlight future research directions that could advance our understanding of stress-related effects on suicide risk, advocating a dimensional, endophenotype approach to suicide research.

The association between variability, intensity, and persistence of suicidal ideation and prospective suicidal behavior in the systematic treatment enhancement program for bipolar disorder (STEP-BD) study.

BACKGROUND: This study sought to examine the association between prospective suicidal behavior and variability, intensity, and persistence of suicidal ideation (SI) in bipolar disorder (BD). METHODS: Data were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a naturalistic study of 4360 outpatients 15 years or older with BD. In separate models, logistic regressions with suicidal behavior (first attempt or death by suicide) as the outcome variable and SI variability (fluctuating levels of SI over time, measured as ordinal dispersion of SI score), intensity (median SI score over time in study), or persistence (number of visits with reported SI) as the explanatory variables were used to examine the relationship between SI characteristics and odds of future suicidal behavior events. RESULTS: After adjusting for possible confounders, the odds of prospective suicidal behavior were 1.2 times greater per 10% increase in SI variability. SI persistence was not associated with suicidal behavior. For SI intensity, a median SI score of 'rare/fleeting' or 'several days' of SI was not associated with suicidal behavior, but the odds of prospective suicidal behavior were nearly five times greater for participants with the highest observed median SI intensity score of 'nearly every day'. CONCLUSIONS: The findings suggest that, in BD participants, monitoring SI variability may be clinically useful for assessing suicide risk.

Magnetoencephalography biomarkers of suicide attempt history and antidepressant response to ketamine in treatment-resistant major depression.

BACKGROUND: This study examined magnetoencephalographic (MEG) correlates of suicidal ideation (SI) and suicide attempt history in patients with treatment-resistant major depression (TRD) at baseline and following subanesthetic-dose ketamine infusion. METHODS: Twenty-nine drug-free TRD patients (12 suicide attempters/17 non-attempters) participated in a crossover randomized trial of ketamine. MEG data were collected during an attentional dot probe task with emotional face stimuli at baseline and several hours post-ketamine infusion. Synthetic aperture magnetometry was used to project source power in the theta, alpha, beta, and gamma frequencies for angry-neutral, happy-neutral, and neutral-neutral face pairings during a one-second peristimulus period. Mixed models were used to test for clinical, behavioral, and electrophysiological effects of group, emotion, session, and SI score. RESULTS: Ketamine significantly reduced SI and depression across the sample. Post-ketamine, attempters had improved accuracy and non-attempters had reduced accuracy on the task. SI was positively associated with gamma power in regions of the frontal and parietal cortices across groups. In an extended amygdala-hippocampal region, attempters differed significantly in their emotional reactivity to angry versus happy faces as indexed by theta power differences, irrespective of drug. Ketamine significantly reduced the association between alpha power and SI for angry compared with happy faces in a fronto-insular/anterior cingulate region important for regulating sensory attentiveness. LIMITATIONS: Limitations include a small sample size of attempters. CONCLUSIONS: The findings highlight key differences in band-limited power between attempters and non-attempters and reinforce previous findings that ketamine has distinct response properties in patients with a suicide history.

Suicide attempt endophenotypes: Latent profiles of child and adolescent aggression and impulsivity differentially predict suicide attempt in females.

Suicide is a leading cause of death in young adulthood. Identifying early prevention targets to reduce later suicide is a public health priority. Impulsivity and aggression in early childhood may represent actionable early prevention candidate endophenotypes for later suicidal behavior. Our objective is to to understand the association of aggression and impulsivity trajectories with mental health outcomes to inform future prevention efforts. Participants were part of a longitudinal cohort of a preventative intervention trial (n = 597) and predominantly Black. They were assessed for aggressive and impulsive behaviors yearly in 1st-3rd and 6th-12th grades, and provided mental health data via self-report beginning in 6th grade. Longitudinal latent profiles of aggressive and impulsive behaviors were derived for males and females and used to determine whether profiles was associated with lifetime suicide attempt and meeting diagnostic criteria for major depressive disorder. Two impulsivity and aggression classes were found for males, characterized by low behaviors or moderate to high behaviors across development. Three classes were found for females, one of which was characterized by an undulating pattern of behaviors. For females, the class of severe behaviors was associated with significant risk of suicide attempt (Wald = 6.01, p = 0.05). No relationship was found for males or for MDD diagnosis. An endophenotype model of impulsivity and aggression in predicting later suicide attempt was supported in females, but not males. Results underscore the importance of evaluating sex differences in suicide research and the potential identification of females at risk for later suicidal behavior in school settings.

The Dynamic Relationship Between Alpha and Beta Power and Next-Day Suicidal Ideation in Individuals With Treatment-Resistant Depression.

BACKGROUND: Nocturnal wakefulness has emerged as a potential predictor of short-term suicide risk. This analysis used dynamic temporal patterns in alpha and beta power and global sleep metrics to explore the possible link between next-day suicidal ideation (NDSI) and wakefulness measures in unmedicated participants with treatment-resistant depression. METHODS: Thirty-three medication-free participants with treatment-resistant depression completed overnight polysomnography. Alpha and beta spectral power as functions over time were used to represent arousal-related components of the dynamic sleep process. A functional data analytic approach (multilevel functional principal component analysis [MFPCA]) was used to preserve the oscillatory nature of the data; MFPCA PC scores were then associated with NDSI. Associations between NDSI and polysomnography-defined wakefulness after sleep onset, sleep efficiency, and total sleep time were also evaluated. RESULTS: NDSI had the strongest relationship with the second beta PC score (slope = 0.09 [90% credible interval, 0.03 to 0.14]), which represented an oscillating pattern that reflected disturbed sleep. The first PCs from both alpha and beta MFPCAs represented the overall magnitude of power and were most closely associated with traditional polysomnography metrics but were not related to NDSI. Results were equivocal for wakefulness after sleep onset with NDSI and did not support a relationship between NDSI and either sleep efficiency or total sleep time, highlighting the value of information contained in oscillating electroencephalogram patterns for identifying physiological links between nocturnal wakefulness and NDSI. CONCLUSIONS: This study leveraged the dynamic nature of wakefulness-related electroencephalogram frequencies and provides a potential electrophysiological link between suicidal ideation and wakefulness during sleep in individuals with treatment-resistant depression.