Temporal Interactions between Neural Proxies forMemory Recall, Negative Affect, and EmotionRegulation in Major Depression.

Dysfunction in emotion regulation (ER) and autobiographical memory are components of major depressive disorder (MDD). However, little is known about how they mechanistically interact with mood disturbances in real time. Using machine learning-based neural signatures, we can quantify negative affect (NA), ER, and memory continuously to evaluate how these processes dynamically interact in MDD. Unmedicated individuals with MDD (N=45) and healthy volunteers (HV; N=38) completed a negative autobiographical memory functional magnetic resonance imaging task wherein they recalled, distanced from (an ER strategy), and immersed into memories. We used a negative affect signature (PINES) and an emotion regulation signature (ERS) to quantify moment-to-moment NA and ER. We then examined whether memory engagement, indexed by hippocampal activity, predicted subsequent change in PINES and ERS over time. During memory recall and immersion, greater hippocampal activity predicted increased PINES across groups. During distancing, greater hippocampal activity in HVs predicted increased ERS but not PINES. In MDD, greater hippocampal activity predicted increased PINES but not ERS. Findings suggest abnormalities in the real-time relationship between memory, NA, and ER in MDD. During distancing, as predicted, HVs showed an attenuation of the linkage between memory engagement and NA, and they had subsequent increases in ER following memory reactivation. In contrast, MDD was characterized by continued linkage between memory engagement and NA, without subsequent increases in ER. Deficits in engagement of ER and ineffective modulation of NA following negative memory recall may contribute to the mood disturbances in MDD and are potential targets for clinical intervention.

Temporal prediction of suicidal ideation in an ecological momentary assessment study with recurrent neural networks.

INTRODUCTION: Ecological Momentary Assessment (EMA) holds promise for providing insights into daily life experiences when studying mental health phenomena. However, commonly used mixed-effects linear statistical models do not fully utilize the richness of the ultidimensional time-varying data that EMA yields. Recurrent Neural Networks (RNNs) provide an alternative data analytic method to leverage more information and potentially improve prediction, particularly for non-normally distributed outcomes. METHODS: As part of a broader research study of suicidal thoughts and behavior in people with borderline personality disorder (BPD), eighty-four participants engaged in EMA data collection over one week, answering questions multiple times each day about suicidal ideation (SI), stressful events, coping strategy use, and affect. RNNs and mixed-effects linear regression models (MEMs) were trained and used to predict SI. Root mean squared error (RMSE), mean absolute percent error (MAPE), and a pseudo-R2 accuracy metric were used to compare SI prediction accuracy between the two modeling methods. RESULTS: RNNs had superior accuracy metrics (full model: RMSE = 3.41, MAPE = 42 %, pseudo-R2 = 26 %) compared with MEMs (full model: RMSE = 3.84, MAPE = 56 %, pseudo-R2 = 16 %). Importantly, RNNs showed significantly more accurate prediction at higher values of SI. Additionally, RNNs predicted, with significantly higher accuracy, the SI scores of participants with depression diagnoses and of participants with higher depression scores at baseline. CONCLUSION: In this EMA study with a moderately sized sample, RNNs were better able to learn and predict daily SI compared with mixed-effects models. RNNs should be considered as an option for EMA analysis.

Occurrence and characteristics of suicidal ideation in psychiatrically healthy individuals based on ecological momentary assessment.

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.

Relationship of stress-reactive cortisol to suicidal intent of prior attempts in major depression.

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 (AUCg), F(1,60)=10.04, SE=5.095, p=.003, and lower HPA-axis stress responsivity to the TSST (AUCi), 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 (meandiff=22.32, p=.038) and in response to the stressor task (meandiff=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.

The Temporal Dynamics of Emotion Regulation in Subjects With Major Depression and Healthy Control Subjects.

BACKGROUND: Emotion regulation (ER) processes help support well-being, but ineffective ER is implicated in several psychiatric disorders. Engaging ER flexibly by going online and offline as needs and capacities shift may be more effective than engaging ER rigidly across time. Here, we sought to observe the neural temporal dynamics of an ER process, reappraisal, during regulation of responses to negative memories in healthy control subjects (n = 33) and subjects with major depressive disorder (n = 36). METHODS: To track the temporal dynamics of reappraisal neural systems, we used a functional magnetic resonance imaging neural decoding approach. In task 1, subjects explicitly engaged reappraisal on instruction in response to aversive images, and we used this task to develop the decoder for detecting reappraisal. In task 2, subjects experienced negative autobiographical memories from a distant (third person, ER condition) or immersed (first person, control condition) perspective. RESULTS: The neural decoder, trained to detect reappraisal in task 1, predicted greater reappraisal occurring during the task 2 distance versus immerse trials and was engaged more intensely during memories that were rated as being more negative. Across time, decoder output manifested a temporal dynamic of early engagement followed by disengagement. These results were replicated in an independent subject dataset (n = 59). Relative to healthy control subjects, subjects with major depressive disorder had a comparable initial increase in decoder engagement at the beginning of the trial but an attenuated decrease at the end. CONCLUSIONS: Subjects with major depressive disorder evidenced a more rigid neural dynamic of reappraisal compared with healthy control subjects. Rigid ER may indicate diminished ability to flexibly and effectively regulate emotion.

Attentional control deficits and suicidal ideation variability: An ecological momentary assessment study in major depression.

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.

Community-level phylogenetic diversity does not differ between rare and common lineages across tallgrass prairies in the northern Great Plains.

Niche differentiation has served as one explanation for species coexistence, and phylogenetic relatedness provides a means to approximate how ecologically similar species are to each other. To explore the contribution of rare species to community phylogenetic diversity, we sampled 21 plant communities across the Prairie Coteau ecoregion, an area of high conservation concern. We used breakpoint analysis through the iterative addition of less abundant species to the phylogenetic tree for each community to assess the contribution of rare species to community phylogenetic diversity. We also quantify the phylogenetic signal of abundance using Blomberg's K statistic and calculated the phylogenetic similarity between rare and common species using a phylogenetic beta-diversity metric (D nn). To estimate the phylogenetic structuring of these prairie communities, we calculated two common metrics that capture evolutionary relatedness at different scales (MPD and MNTD). Additionally, we examine the correlation between Faith's PD, MPD, and MNTD and species richness. We found rare species do not generally contribute higher levels of phylogenetic diversity than common species. Eight communities had significant breakpoints, with only four communities having an increasing trend for the rarest species. The phylogenetic signal for abundance was low but significant in only four communities, and communities had lower phylogenetic diversity than expected from the regional species pool. Finally, the strength of the correlation between species richness and phylogenetic diversity was mixed. Our results indicate niche differentiation does not explain the persistence of rare species in tallgrass prairies, as they were more closely related than expected from random, suggesting high functional redundancy between rare and common species. This is promising for the long-term resilience of this ecosystem, but only insofar as enough species remain in the system. With ongoing biodiversity loss, it is essential that we understand the role rare species play in their communities.

Identifying factors associated with elevated suicidal intent among U.S. military veterans.

OBJECTIVE: Suicidal intent is a risk factor for engagement in suicidal behavior, use of violent means, and suicide mortality. Yet, scarce research has examined factors associated with suicidal intent among U.S. military veterans, a population at high risk for suicide. This study examined vulnerability factors associated with suicidal intent in a population-based sample of U.S. veterans. METHODS: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a representative sample of 4069 U.S. veterans. Analyses estimated the prevalence of current suicidal intent (i.e., veterans' report that they would likely attempt suicide in the future) and examined factors most strongly associated with suicidal intent. RESULTS: Forty-nine veterans (1.4%; 95% confidence interval = 1.0-1.8%) reported suicidal intent. Recurrent past-year suicidal ideation (≥2 times), low dispositional gratitude, current depression, current insomnia, childhood sexual abuse, and a prior suicide attempt were most strongly associated with suicidal intent (7.1-50.1% of the total explained variance). Veterans with several of these co-occurring factors were at highest risk for suicidal intent; of veterans with 0, ≥1, ≥2, ≥3, and ≥4 of these factors, 0.1%, 4.4%, 10.8%, 19.5%, and 28.1% reported suicidal intent, respectively. DISCUSSION: Specific vulnerability factors, particularly when co-occurring, may increase veterans' intention of attempting suicide. Findings underscore the importance for clinicians to continuously assess suicidal intent when working with this population, particularly as veterans' reports of suicidal thinking increases.

Factors associated with remission of suicidal thoughts and behaviors in U.S. military veterans with a history of suicide attempt.

Suicide is a major public health problem in U.S. military veterans, but little is known about factors associated with remission from suicide attempts in this population. We aimed to identify risk and protective correlates of remission from suicidal thoughts and behavior (STB) in U.S. veterans with a prior suicide attempt. Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study survey. A broad range of sociodemographic, military, physical and mental health, and psychosocial variable were assessed. Purpose in life, dispositional gratitude, and conscientiousness emerged as independent correlates of STB remission (24.3%-40.3% of explained variance), even after accounting for other relevant risk and protective factors. While the cross-sectional nature of the study precludes the ability to determine whether the identified protective factors are causally related to STB remission, results suggest three potentially modifiable targets for suicide prevention efforts in veterans. Longitudinal studies are needed to better understand the role of purpose in life, dispositional gratitude, and conscientiousness in promoting remission from STBs in veterans and other populations at risk for suicide.

Cannabis use among U.S. military veterans with subthreshold or threshold posttraumatic stress disorder: Psychiatric comorbidities, functioning, and strategies for coping with posttraumatic stress symptoms.

Cannabis use is common among individuals with posttraumatic stress disorder (PTSD) symptoms, but its impact on psychiatric symptoms and functioning in this population is unclear. To clarify the clinical and functional correlates of cannabis use in individuals with PTSD symptoms, we analyzed data from the 2019-2020 National Health and Resilience in Veterans Study, a nationally representative survey of U.S. military veterans. Participants with current subthreshold or full PTSD (N = 608) reported on their past-6-month cannabis use and current psychiatric symptoms, functioning, treatment utilization, and PTSD symptom management strategies. Veterans with subthreshold/full PTSD who used cannabis more than weekly were more likely to screen positive for co-occurring depression, anxiety, and suicidal ideation than those who did not use cannabis, ORs = 3.4-3.8, or used cannabis less than weekly, ORs = 2.7-3.7. Veterans who used cannabis more than weekly also scored lower in cognitive functioning than veterans with no use, d = 0.25, or infrequent use, d = 0.71, and were substantially more likely to endorse avoidance coping strategies, ORs = 8.2-12.2, including substance use, OR = 4.4, and behavioral disengagement, ORs = 2.7-9.1, to manage PTSD symptoms. Despite more psychiatric and functional problems, veterans with frequent cannabis use were not more likely to engage in mental health treatment, ORs = 0.87-0.99. The results suggest enhanced cannabis use screening, interventions targeting risky use, and strategies promoting treatment engagement may help ameliorate more severe clinical presentations associated with frequent cannabis use among veterans with subthreshold/full PTSD.

Effect of non-suicidal self-injury on suicidal ideation: real-time monitoring study.

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.

Risk factors for suicide attempts among U.S. military veterans: A 7-year population-based, longitudinal cohort study.

BACKGROUND: Population-based data on risk factors for suicide attempts among veterans remains limited. METHODS: A national probability sample of 2307 veterans was followed over the course of four timepoints spanning seven years to examine how a range of baseline risk factors predict incident suicide attempt. Suicide attempt data were aggregated into a single follow-up timepoint. RESULTS: Sixty-two veterans (3.1%) reported attempting suicide during the 7-year period. The strongest risk factors for suicide attempts were higher baseline levels of loneliness, lower baseline levels of adaptive psychosocial traits (e.g., dispositional gratitude), baseline thoughts of self-harm, and greater post-baseline trauma exposures (12.3%-41.3% of explained variance). Veterans with multiple co-occurring risk factors were at greatest risk for attempts; of veterans with 0, 1, 2, 3, and all 4 of these factors, the predicted probability of suicide attempt was 2.0%, 5.3%, 13.5%, 30.4%, and 55.0%, respectively. CONCLUSIONS: Baseline loneliness, dispositional gratitude, thoughts of self-harm, and new-onset traumas emerged as the strongest risk factors for suicide attempts among veterans, underscoring the potential importance of targeting these factors in prevention efforts. Veterans with multiple co-occurring risk factors have substantially greater risk for suicide attempts, suggesting that examination of multiple coinciding vulnerability factors may help improve suicide risk prediction models.

ESR1 mutations and therapeutic resistance in metastatic breast cancer: progress and remaining challenges.

Breast cancer accounts for 25% of the cancers in women worldwide. The most common subtype of breast cancer diagnosed is hormone receptor positive, which expresses the oestrogen receptor (ER). Targeting of the ER with endocrine therapy (ET) is the current standard of care for ER-positive (ER+) breast cancer, reducing the mortality by up to 40%. Resistance to ET, however, remains a major issue for ER + breast cancer, leading to recurrence and metastasis. One major driver of ET resistance is mutations in the ER gene (ESR1) leading to constitutive transcriptional activity and reduced ET sensitivity. These mutations are particularly detrimental in metastatic breast cancer (MBC) as they are present in as high as 36% of the patients. This review summarises the pre-clinical characterisation of ESR1 mutations and their association with clinical outcomes in MBC and primary disease. The clinically approved and investigational therapeutic options for ESR1 mutant breast cancer and the current clinical trials evaluating ESR1 mutations and ET resistance are also discussed. Finally, this review addresses pre-clinical models and multi-'omics' approaches for developing the next generation of therapeutics for ESR1 mutant and ET-resistant breast cancer.

Non-suicidal self-injury in US military veterans: Results from the National Health and Resilience in Veterans Study.

BACKGROUND: To evaluate the prevalence of lifetime non-suicidal self-injury (NSSI) among US military veterans and identify sociodemographic, military, psychiatric and clinical correlates associated with NSSI. METHODS: Data were analysed from the 2019-2020 National Health and Resilience in Veterans Study, a contemporary, nationally representative survey of 4069 US veterans. Outcomes measured included lifetime history of NSSI, trauma history, lifetime and current DSM-V mental disorders and lifetime and recent suicidal behaviours. RESULTS: The overall prevalence of lifetime NSSI was 4.2% (95% confidence interval [3.6%, 4.9%]). Multivariable analyses revealed that veterans who endorsed lifetime NSSI were more likely to be younger, female, non-Caucasian, unmarried or unpartnered, and to have a lower annual household income. Veterans who endorsed lifetime NSSI reported more adverse childhood experiences and lifetime traumas and were more likely to have experienced military sexual trauma. They also were more likely to screen positive for lifetime posttraumatic stress disorder, major depressive disorder (MDD) and substance use disorders and to have attempted suicide. Finally, lifetime NSSI was associated with current MDD, generalized anxiety disorder, and substance use disorders, as well as past-year suicidal ideation. CONCLUSION: Results of this study provide the first-known data on the epidemiology of NSSI in US military veterans. They suggest that certain correlates can help identify veterans who may be at greater risk for engaging in NSSI, as well as the potential prognostic utility of lifetime NSSI in predicting current psychiatric problems and suicide risk in this population.

Differentiating U.S. military veterans who think about suicide from those who attempt suicide: A population-based study.

OBJECTIVE: Several vulnerability factors for suicidal behavior in U.S. veterans have been identified. However, little is known about factors that differentiate veterans who contemplate suicide from those who attempt suicide. This study examined sociodemographic and clinical characteristics that distinguish veterans who think about suicide from those who attempt suicide. METHOD: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a population-based sample of 4069 veterans. Analyses estimated the lifetime prevalence of suicide ideation (SI) and suicide attempts (SA); and examined differences between veterans with a history of attempt(s), and SI without a history of attempt(s). RESULTS: A total 25.9% of U.S. veterans reported lifetime SI and 3.9% reported a SA. Several factors distinguished veterans with a history of SA from those with SI only: the strongest were younger age (odds ratio [OR] = 0.97, 95% CI = 0.95-0.98), nonsuicidal self-injury (OR = 1.81, 95% CI = 1.11-3.03), adverse childhood experiences (OR = 1.14; 95% CI = 1.06-1.23), alcohol use disorder (OR = 1.99; 95% CI = 1.28-3.12), lower household income (OR = 0.62; 95% CI = 0.40-0.95), and physical disability (OR = 1.69; 95% CI = 1.07-2.70). CONCLUSIONS: Although a quarter of U.S. veterans contemplate suicide in their lifetimes, the majority do not attempt suicide. Specific sociodemographic and clinical features may differentiate veterans who contemplate versus attempt suicide.

Factors associated with multiple suicide attempts in a nationally representative study of U.S. military veterans.

OBJECTIVE: Veterans with a history of multiple suicide attempts are at increased risk for suicide mortality relative to those with a single attempt. However, little is known about factors that differentiate veterans who attempt suicide once compared to more than once. This study examined factors that distinguish single suicide attempters (SSA) from multiple suicide attempters (MSA) in a nationally representative sample of U.S. military veterans. METHODS: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a representative sample of 4069 U.S. veterans. ANALYSES: (a) estimated the lifetime prevalence of SSA and MSA; and (b) examined factors that differentiated veterans with a SSA from MSA. RESULTS: The lifetime prevalences of SSA and MSA were 1.9% and 2.0%. The strongest correlates of MSA were history of lifetime depression (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.43-8.35), non-suicidal self-injury (OR, 3.28; 95% CI, 1.27-8.45), drug use disorder (OR, 4.0; 95% CI, 1.67-9.54), and marital status (OR, 0.40, 95% CI, 0.18-0.87), which accounted for 15.5%-41.4% of the total explained variance in MSA. DISCUSSION: Half of military veterans who have attempted suicide in the United States report more than one attempt, suggesting that suicide attempts are not a one-time occurrence for a substantial proportion of veterans. Veterans who attempt suicide more than once show more deliberate self-harm behavior and have greater psychiatric comorbidities relative to single attempters. Implications for future research examining risk factors for suicide attempts among veterans are discussed.

Suicide Risk and Addiction: The Impact of Alcohol and Opioid Use Disorders.

Purpose of Review: Suicide is a major public health concern and a leading cause of death in the US. Alcohol and opioid use disorders (AUD/OUD) significantly increase risk for suicidal ideation, attempts, and death, and are the two most frequently implicated substances in suicide risk. We provide a brief overview of shared risk factors and pathways in the pathogenesis of AUD/OUD and suicidal thoughts and behaviors. We also review clinical recommendations on inpatient care, pharmacotherapy, and psychotherapeutic interventions for people with AUD/OUD and co-occurring suicidal ideation and behavior. Recent Findings: Among people with an underlying vulnerability to risk-taking and impulsive behaviors, chronic alcohol intoxication can increase maladaptive coping behaviors and hinder self-regulation, thereby increasing the risk of suicide. Additionally, chronic opioid use can result in neurobiological changes that lead to increases in negative affective states, jointly contributing to suicide risk and continued opioid use. Despite significantly elevated suicide risk in individuals with AUD/OUD, there is a dearth of research on pharmacological and psychosocial interventions for co-occurring AUD/OUD and suicidal ideation and behavior. Summary: Further research is needed to understand the effects of alcohol and opioid use on suicide risk, as well as address notable gaps in the literature on psychosocial and pharmacological interventions to lower risk for suicide among individuals with AUD/OUD.

Longitudinal courses of suicidal ideation in U.S. military veterans: a 7-year population-based, prospective cohort study.

BACKGROUND: Varied longitudinal courses of suicidal ideation (SI) may be linked to unique sets of risk and protective factors. METHOD: A national probability sample of 2291 U.S. veterans was followed over four assessments spanning 7 years to examine how a broad range of baseline risk and protective factors predict varying courses of SI. RESULTS: Most veterans (82.6%) denied SI at baseline and all follow-ups, while 8.7% had new onset SI, 5.4% chronic SI, and 3.3% remitted SI. Compared to the no-SI group, chronic SI was associated with childhood trauma, baseline major depressive and/or posttraumatic stress disorder (MDD/PTSD), physical health difficulties, and recent traumatic stressors. Remitted veterans had the highest risk of a prior suicide attempt (SA) compared to no-SI [relative risk ratio (RRR) = 3.31] and chronic SI groups (RRR = 4.65); and high rates of MDD/PTSD (RRR = 7.62). New onset SI was associated with recent stressors and physical health difficulties. All symptomatic SI groups reported decrements in protective factors, specifically, social connectedness, trait curiosity/exploration, and purpose in life. CONCLUSION: Nearly one-in-five veterans reported SI over a 7-year period, most of whom evidenced new onset or remitted SI courses. Chronic and remitted SI may represent particularly high-risk SI courses; the former was associated with higher rates of prospective SA, and psychiatric and physical distress, and the latter with increased likelihood of prior SA, and isolation from social and mental health supports. Physical disability, MDD/PTSD, and recent stressors may be important precipitating or maintaining factors of SI, while social connectedness may be a key target for suicide prevention efforts.