Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer.

BACKGROUND: Endocrine therapy remains the mainstay of treatment for estrogen receptor-positive (ER+) breast cancer. Constitutively active mutations in the ligand binding domain of ERα render tumors resistant to endocrine agents. Breast cancers with the two most common ERα mutations, Y537S and D538G, have low sensitivity to fulvestrant inhibition, a typical second-line endocrine therapy. Lasofoxifene is a selective estrogen receptor modulator with benefits on bone health and breast cancer prevention potential. This study investigated the anti-tumor activity of lasofoxifene in breast cancer xenografts expressing Y537S and D538G ERα mutants. The combination of lasofoxifene with palbociclib, a CDK4/6 inhibitor, was also evaluated. METHODS: Luciferase-GFP tagged MCF7 cells bearing wild-type, Y537S, or D538G ERα were injected into the mammary ducts of NSG mice (MIND model), which were subsequently treated with lasofoxifene or fulvestrant as single agents or in combination with palbociclib. Tumor growth and metastasis were monitored with in vivo and ex vivo luminescence imaging, terminal tumor weight measurements, and histological analysis. RESULTS: As a monotherapy, lasofoxifene was more effective than fulvestrant at inhibiting primary tumor growth and reducing metastases. Adding palbociclib improved the effectiveness of both lasofoxifene and fulvestrant for tumor suppression and metastasis prevention at four distal sites (lung, liver, bone, and brain), with the combination of lasofoxifene/palbociclib being generally more potent than that of fulvestrant/palbociclib. X-ray crystallography of the ERα ligand binding domain (LBD) shows that lasofoxifene stabilizes an antagonist conformation of both wild-type and Y537S LBD. The ability of lasofoxifene to promote an antagonist conformation of Y537S, combined with its long half-life and bioavailability, likely contributes to the observed potent inhibition of primary tumor growth and metastasis of MCF7 Y537S cells. CONCLUSIONS: We report for the first time the anti-tumor activity of lasofoxifene in mouse models of endocrine therapy-resistant breast cancer. The results demonstrate the potential of using lasofoxifene as an effective therapy for women with advanced or metastatic ER+ breast cancers expressing the most common constitutively active ERα mutations.

Glucocorticoid receptor modulation decreases ER-positive breast cancer cell proliferation and suppresses wild-type and mutant ER chromatin association.

BACKGROUND: Non-ER nuclear receptor activity can alter estrogen receptor (ER) chromatin association and resultant ER-mediated transcription. Consistent with GR modulation of ER activity, high tumor glucocorticoid receptor (GR) expression correlates with improved relapse-free survival in ER+ breast cancer (BC) patients. METHODS: In vitro cell proliferation assays were used to assess ER-mediated BC cell proliferation following GR modulation. ER chromatin association following ER/GR co-liganding was measured using global ChIP sequencing and directed ChIP analysis of proliferative gene enhancers. RESULTS: We found that GR liganding with either a pure agonist or a selective GR modulator (SGRM) slowed estradiol (E2)-mediated proliferation in ER+ BC models. SGRMs that antagonized transcription of GR-unique genes both promoted GR chromatin association and inhibited ER chromatin localization at common DNA enhancer sites. Gene expression analysis revealed that ER and GR co-activation decreased proliferative gene activation (compared to ER activation alone), specifically reducing CCND1, CDK2, and CDK6 gene expression. We also found that ligand-dependent GR occupancy of common ER-bound enhancer regions suppressed both wild-type and mutant ER chromatin association and decreased corresponding gene expression. In vivo, treatment with structurally diverse SGRMs also reduced MCF-7 Y537S ER-expressing BC xenograft growth. CONCLUSION: These studies demonstrate that liganded GR can suppress ER chromatin occupancy at shared ER-regulated enhancers, including CCND1 (Cyclin D1), regardless of whether the ligand is a classic GR agonist or antagonist. Resulting GR-mediated suppression of ER+ BC proliferative gene expression and cell division suggests that SGRMs could decrease ER-driven gene expression.

Military personnel compared to multiple suicide attempters: Interpersonal theory of suicide constructs.

The current study aimed to address the discrepancy between suicide rates in the military and general population by comparing facets of the interpersonal theory of suicide between civilians with multiple suicide attempts and U.S. military personnel. Military personnel exhibited higher levels of capability for suicide but lower levels of perceived burdensomeness and thwarted belongingness than civilian multiple attempters. When comparing only personnel endorsing ideation and civilian multiple attempters, the significant difference for capability remained, but the differences for perceived burdensomeness and thwarted belongingness became nonsignificant. Results suggest the emergence of ideation places personnel at a greater risk for suicide than many civilian multiple attempters.

The association between specific combat experiences and aspects of the Interpersonal Theory of Suicide.

BACKGROUND: Studies examining the relationship between combat exposure and suicide risk typically focus on combat exposure overall, combining numerous different combat experiences. Our study expands upon prior research by examining the association between specific combat experiences and components of both suicidal desire and the capability for suicide. METHOD: We hypothesized that most combat experiences would be associated with capability for suicide. Furthermore, we hypothesized that experiences that involved direct exposure to death and injury (e.g. personally witnessing the death or injury of other soldiers) would be associated with higher levels of thwarted belongingness, perceived burdensomeness, and suicidal ideation. Participants were 400 service members drawn largely from the Army National Guard who had been deployed at least once and endorsed having experienced combat. RESULTS: Consistent with hypotheses, combat experiences involving direct exposure to injury or death exhibited a more pronounced pattern of associations with suicide risk factors than did other experiences. However, only a minority of combat experiences were associated with the capability for suicide. DISCUSSION: These results, while preliminary, indicate that different combat experiences are associated with different outcomes and that, in this sense, not all combat experiences are created equal with respect to suicide risk.

The Associations Between Army National Guard Versus Active Duty Soldier Status and Perceived Burdensomeness, Thwarted Belongingness, and Acquired Capability.

OBJECTIVE: This study aimed to examine if levels of thwarted belongingness, perceived burdensomeness, and acquired capability significantly differed between guardsmen and active duty soldiers. METHOD: Multivariate analysis of covariance was used to test for differences between active duty Army (n = 1,393) and Army National Guard (n = 623) groups, before and after controlling for the effects of age, gender, race, marital status, level of education, and deployment history. RESULTS: Guardsmen reported significantly higher mean levels of thwarted belongingness and perceived burdensomeness than did active duty soldiers, even after adjusting for demographic differences. Guardsmen also reported slightly lower levels of acquired capability, though this effect was accounted for by demographic differences. CONCLUSION: These findings support the notion that National Guard and active duty soldiers differ on perceived burdensomeness and thwarted belongingness. Additional research investigating sources of perceived burdensomeness and thwarted belongingness among guardsmen is needed.

Homosexuality as a Discrete Class.

Previous research on the latent structure of sexual orientation has returned conflicting results, with some studies finding a dimensional structure (i.e., ranging quantitatively along a spectrum) and others a taxonic structure (i.e., categories of individuals with distinct orientations). The current study used a sample (N = 33,525) from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). A series of taxometric analyses were conducted using three indicators of sexual orientation: identity, behavior, and attraction. These analyses, performed separately for women and men, revealed low-base-rate same-sex-oriented taxa for men (base rate = 3.0%) and women (base rate = 2.7%). Generally, taxon membership conferred an increased risk for psychiatric and substance-use disorders. Although taxa were present for men and women, women demonstrated greater sexual fluidity, such that any level of same-sex sexuality conferred taxon membership for men but not for women.

Testing the main hypotheses of the interpersonal-psychological theory of suicidal behavior in a large diverse sample of United States military personnel.

BACKGROUND: Preliminary data indicate the suicide rate in the United States military decreased in 2013, but the National Guard saw a continued increase. METHOD: We examined the utility of the interpersonal-psychological theory of suicidal behavior (IPTS) in a sample of US military personnel drawn largely from the National Guard (n=934; 77.7% male; 59.5% white). RESULTS: Results indicated the interaction of thwarted belongingness and perceived burdensomeness predicted suicidal ideation and resolved plans and preparations for suicide. In each case, risk was greatest at higher levels of both predictors. Furthermore, results indicated the interaction of thwarted belongingness, perceived burdensomeness, and acquired capability for suicide predicted prior suicide attempts. In this interaction term, the relationship between suicidal desire (thwarted belongingness and perceived burdensomeness) and suicide attempts was significant and positive only at high levels of acquired capability. All analyses were cross-sectional. CONCLUSIONS: Results indicate the IPTS may be useful for conceptualizing suicide risk in the National Guard.

Examining the relationship between coping strategies and suicidal desire in a sample of United States military personnel.

Suicidal desire in the military has been previously examined through the lens of the Interpersonal-Psychological Theory of Suicide (IPTS). However, no research has examined the impact of specific coping strategies on perceived burdensomeness, thwarted belongingness, and suicidal ideation in a large population of individuals serving in the US military. Furthermore, the factor structure of previously utilized coping clusters did not apply to our sample of military personnel. Therefore, we found a three-factor solution to be tested in this sample. We hypothesized that specific types of coping behavior clusters (Adaptive and Maladaptive) would predict both IPTS constructs and suicidal ideation. Results indicated that Adaptive and Maladaptive coping clusters predicted the IPTS constructs in the hypothesized directions. However, only the Maladaptive cluster predicted suicidal ideation. These findings implicate the need for further research and suicide prevention efforts focusing on coping strategies, specifically those that are maladaptive in nature, in relation to suicidal ideation in military members.

The Impact of Varying Levels of Confidentiality on Disclosure of Suicidal Thoughts in a Sample of United States National Guard Personnel.

OBJECTIVES: Increasing rates of suicide in the military indicate current assessment approaches are not yielding accurate determinations of risk. Concern that endorsement of suicidal ideation may result in obstacles to career advancement may be resulting in nondisclosure. METHOD: To test this, we recruited a sample of US National Guard personnel (n = 789; 81.7% male; 63.2% white) and administered two measures of current thoughts of suicide. One measure was integrated into our risk assessment protocol and soldiers were thus aware that answers could result in referral to on site military mental health professionals. The other measure was not integrated into the risk assessment protocol and soldiers were thus aware that results would not be reported to on site military mental health professionals. RESULTS: As hypothesized, a higher proportion of individuals reported current thoughts of suicide on the measure not integrated into the risk protocol (9.4%) than on the measure that was (6.0%). Also as hypothesized, a higher proportion of those willing to endorse current thoughts of suicide on the measure not integrated into the risk protocol denied current thoughts of suicide on the one that was (61.5%) than vice versa (39.0%). Limitations include cross-sectional self-report data and a lack of counter-balancing of measures. CONCLUSIONS: The results indicate that increasing the confidentiality of risk assessments within the National Guard increases the likelihood of reporting of current thoughts of suicide.

Logistic Regression With Machine Learning Sheds Light on the Problematic Sexual Behavior Phenotype.

OBJECTIVES: There has been a longstanding debate about whether the mechanisms involved in problematic sexual behavior (PSB) are similar to those observed in addictive disorders, or related to impulse control or to compulsivity. The aim of this report was to contribute to this debate by investigating the association between PSB, addictive disorders (internet addiction, compulsive buying), measures associated with the construct known as reward deficiency (RDS), and obsessive-compulsive disorder (OCD). METHODS: A Canadian university Office of the Registrar invited 68,846 eligible students and postdoctoral fellows. Of 4710 expressing interest in participating, 3359 completed online questionnaires, and 1801 completed the Mini-International Neuropsychiatric Interview. PSB was measured by combining those screening positive (score at least 6) on the Sexual Addiction Screening Test-Revised Core with those self-reporting PSB. Current mental health condition(s) and childhood trauma were measured by self-report. OCD was assessed by a combination of self-report and Mini-International Neuropsychiatric Interview data. RESULTS: Of 3341 participants, 407 (12.18%) screened positive on the Sexual Addiction Screening Test-Revised Core. On logistic regression, OCD, attention deficit, internet addiction, a family history of PSB, childhood trauma, compulsive buying, and male gender were associated with PSB. On multiple correspondence analysis, OCD appeared to cluster separately from the other measures, and the pattern of data differed by gender. CONCLUSIONS: In our sample, factors that have previously been associated with RDS and OCD are both associated with increased odds of PSB. The factors associated with RDS appear to contribute to a separate data cluster from OCD and to lie closer to PSB.

Taxometric analyses of paranoid and schizoid personality disorders.

There remains debate about whether personality disorders (PDs) are better conceptualized as categorical, reflecting discontinuity from normal personality; or dimensional, existing on a continuum of severity with normal personality traits. Evidence suggests that most PDs are dimensional but there is a lack of consensus about the structure of Cluster A disorders. Taxometric methods are adaptable to investigating the taxonic status of psychiatric disorders. The current study investigated the latent structure of paranoid and schizoid PDs in an epidemiological sample (N=43,093) drawn from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) using taxometric analyses. The current study used taxometric methods to analyze three indicators of paranoid PD - mistrust, resentment, and functional disturbance - and three indicators of schizoid PD - emotional detachment, social withdrawal, and functional disturbance - derived factor analytically. Overall, taxometrics supported a dimensional rather than taxonic structure for paranoid and schizoid PDs through examination of taxometric graphs and comparative curve fit indices. Dimensional models of paranoid and schizoid PDs better predicted social functioning, role-emotional, and mental health scales in the survey than categorical models. Evidence from the current study supports recent efforts to represent paranoid and schizoid PDs as well as other PDs along broad personality dimensions.

Locus of control as a contributing factor in the relation between self-perception and adolescent aggression.

Researchers continue to debate the role of self-esteem in aggression, but research has shown a consistent association between narcissism and aggression in adults and adolescents [e.g., Barry et al., 2007; Bushman and Baumeister, 1998; Stucke, 2007]. The primary aim of the current study was to examine whether locus of control (LOC) moderated the relation between self-perception variables (i.e., self-esteem and narcissism) and aggression in adolescents. Participants were 174 youth (145 males, 26 females) between the ages of 16 and 19 who were enrolled in a voluntary residential program for youth who have dropped out of school. The results showed that LOC moderated the association between self-esteem and aggression such that low self-esteem was associated with higher levels of aggression for individuals with an external LOC. Contrary to expectations, LOC failed to moderate the narcissism-aggression relation. The implications of this study for understanding how self-perception is related to adolescent aggression are discussed.

The feasibility and acceptability of mobile application-based assessment of suicidality using self-report components of a novel tool, the Suicide Ideation and Behavior Assessment Tool (SIBAT).

The aim of this study was to assess the validity of a mobile application-based self-report questionnaire in the assessment of suicidality. We developed a program for the administration of self-report components of the Suicide Ideation and Behavior Assessment Tool (SIBAT). We invited university students and trainees enrolled in a study of addictions to complete this component of the SIBAT using the program on their mobile devices or personal computer. 196 participants completed all required modules of the SIBAT, with 97 using their mobile device and 99 using their personal computer. Rates of completed questionnaires between the two groups were compared, as were the responses to the items and the total scores. There was a significant difference between proportions of scale completion in both groups, with a greater number of participants who used a personal computer to complete the scale not responding to all questions compared to participants who used a mobile device to complete the scale. Data collected via mobile device showed good concurrent validity with data collected via personal computer. A trend toward greater disclosure of suicidality was observed in the mobile device group however, replication of these findings using larger sample sizes is needed.

Latent structure of unipolar and bipolar mood symptoms.

OBJECTIVES: The taxonic versus dimensional status of mood symptoms has been the subject of debate among mental health professionals. Conventional diagnostic models suggest that mood disorders are categorical; however, the inability of categorical models to adequately account for subthreshold unipolar and bipolar presentations and the heterotypic continuity of symptoms in unipolar and bipolar cases has resulted in growing support for dimensional views. The current study sought to evaluate the relative viabilities of categorical and dimensional models of mood symptoms within a taxometric framework. METHODS: We examined the latent structure of mood symptoms in an epidemiological sample drawn from the Collaborative Psychiatric Epidemiological Surveys. Using three taxometric procedures (MAMBAC, MAXEIG, and L-Mode), we analyzed indicators of mania and depression created from the mood symptoms section of the survey. RESULTS: The taxometric analyses supported a taxonic rather than dimensional structure for mania and depression. Membership in the mania and depressive taxa was associated with meeting criteria for DSM-IV lifetime manic episode and major depressive disorder, respectively. We identified a subset of 700 individuals falling into both taxa; membership in this subset was associated with lifetime bipolar disorder status. Group membership predicted designated external variables including help-seeking, family history, and duration of impairment. Within taxon and/or complement groups, severity scores still appeared to predict external variables. CONCLUSION: Our findings suggest that although taxonic, mood disorders possess meaningful dimensional variation.

Masculinity's association with the interpersonal theory of suicide among military personnel.

OBJECTIVE: Given that the majority of those who die by suicide are male, masculine traits have been examined as a potential link to the development of capability for suicide. However, research has not examined if such traits influence suicidal desire (i.e., thwarted belongingness, perceived burdensomeness). This study examined the influence of stereotypically masculine traits of stoicism, sensation seeking, physical aggression, verbal aggression, and self-reliance on all three components of the Interpersonal Theory of Suicide within a sample of male and female service members. METHODS: A total of 953 service members were recruited as part of a larger study. RESULTS: Sensation seeking and stoicism were positively associated with capability for suicide. With regard to suicidal desire, self-reliance and verbal aggression were positively associated with both perceived burdensomeness and thwarted belongingness. Stoicism was positively associated with thwarted belongingness. CONCLUSIONS: Findings suggest that different masculine traits are associated with the three components of the Interpersonal Theory of Suicide in various ways. Stoicism may be an especially important masculine trait that influences a component of suicidal desire and capability for suicide.

Quantifying groundwater flow variability in a poorly cemented fractured sandstone aquifer to inform in situ remediation.

This study applies innovative methods to characterize and quantify the magnitude of groundwater flow in a fractured and variably cemented sandstone aquifer to inform an in-situ remediation strategy for trichloroethene (TCE) contamination. A modified active-distributed temperature sensing (A-DTS) approach in which fiber optic cables were permanently grouted in the borehole was used to quantify groundwater flow rates. Two additional tracer tests were conducted: 1) fluorescein tracer injection followed by rock coring and sampling for visual mapping and porewater analysis, and 2) deployment of passive flux meters in conventional monitoring wells to evaluate groundwater velocity and mass flux distributions. Forced gradient injection of fluorescein tracer suggests a dual porosity flow system wherein higher rates of groundwater flow occur within discrete features including highly permeable bedding planes and fractures, with slower flow occurring within the rock matrix. Tracer was observed and detected in the unfractured matrix porewater >1.5 m away from the injection well. Beyond this distance, >6 m radially away from the injection hole, tracer was primarily detected within and adjacent to high transmissivity fractures serving as preferential flow paths. The Darcy flux calculated using active distributed temperature sensing (A-DTS) shows depth-discrete values ranging from 7 to 60 cm/day, with average and median values of 23 and 17 cm/day, respectively. Passive Flux Meters (PFMs) deployed in three conventional monitoring wells with slotted screens and sand filter packs showed groundwater flux values ranging from 2 to 11 cm/day, with an overall average of 4 cm/day and are likely biased low due to spreading in the sand pack. The study results were used to inform an in-situ remediation system design including the proposed injection well spacing and the amendment delivery approach. In addition, the results were used to build confidence in the viability of delivering an oxidant to the rock matrix via advective processes. This is important because 1) the matrix is where the majority of the TCE mass occurs, and 2) it provides insights on processes that directly affect remedial performance expectations given advective delivery to preferential pathways and the matrix overcomes diffusion only conditions.

Internal consistency and concurrent validity of self-report components of a new instrument for the assessment of suicidality, the Suicide Ideation and Behavior Assessment Tool (SIBAT).

This study aimed to assess the internal consistency of self-report components of the Suicide Ideation and Behavior Assessment Tool (SIBAT) and validate it with relevant elements of the Mini International Neuropsychiatric Interview (MINI). The SIBAT is a newly developed instrument for the evaluation of suicidality. In this study, we invited university students and trainees participating in a study of addictions to complete the self-report component of the SIBAT as an add-on study. We evaluated the internal consistency of the self-report component of the SIBAT and validated it against the suicidality component of the MINI. Data were analysed using both complete case analysis and multiple imputation. SIBAT data were collected for 394 participants, 314 of whom had also completed the MINI. The internal consistency of modules 2, 3, and 5 of the SIBAT was high. Each item from module 5 had a statistically significant association with the corresponding item from the MINI. The sum of scores from modules 2 and 3 had a moderate correlation with the assessment of suicide risk determined by the MINI, and a strong correlation with the total score of SIBAT module 5. The completion median time of modules 2, 3 and 5 was 14.3 min.

Internal Battles: Examining How Anger/Hostility Moderate the Association Between Negative Urgency and Suicidal Desire Variables in Military and Civilian Samples.

OBJECTIVE: Suicide is consistently within the top ten leading causes of death in the United States. The suicide rate of National Guard personnel is elevated relative to the general population; however, research suggests that many of the suicide risk factors for military personnel are similar to the suicide risk factors for civilians. We examined whether negative urgency moderated the relationships between anger/hostility and perceived burdensomeness/thwarted belongingness in both a military and civilian samples. METHOD: There were two samples in the current study: (1) military personnel (majority national guard) and (2) community members oversampled for suicide attempt history. RESULTS: Our hypotheses were partially supported with the interaction of hostility and negative urgency predicting perceived burdensomeness in the military sample. Within civilians, anger interacted with negative urgency to predict perceived burdensomeness. There were nonsignificant findings for analyses predicting thwarted belongingness. Exploratory analyses indicated that in both samples, anger and hostility interacted with negative urgency to predict suicidal ideation. CONCLUSIONS: Results suggest that aggressive attributes may contribute to individuals feeling as though they are a burden on others when moderate to high levels of negative urgency are present. Additionally, this study provides foundational support for the differences between suicidal desire and ideation.

A Smartphone App to Manage Cirrhotic Ascites Among Outpatients: Feasibility Study.

BACKGROUND: Ascites is a common, painful, and serious complication of cirrhosis. Body weight is a reliable proxy for ascites volume; therefore, daily weight monitoring is recommended to optimize ascites management. OBJECTIVE: This study aims to evaluate the feasibility of a smartphone app in facilitating outpatient ascites management. METHODS: In this feasibility study, patients with cirrhotic ascites requiring active management were identified in both inpatient and outpatient settings. Patients were provided with a Bluetooth-connected scale, which transmitted weight data to a smartphone app and then via the internet to an electronic medical record (EMR). Weights were monitored every weekday. In the event of a weight change of ≥5 lbs in 1 week, patients were called and administered a short symptom questionnaire, and providers received an email alert. The primary outcomes of this study were the percentage of enrolled days during which weight data were successfully transmitted to an EMR and the percentage of weight alerts that prompted responses by the provider. RESULTS: In this study, 25 patients were enrolled: 12 (48%) were male, and the mean age was 58 (SD 13; range 35-81) years. A total of 18 (72%) inpatients were enrolled. Weight data were successfully transmitted to an EMR during 71.2% (697/979) of the study enrollment days, with technology issues reported on 16.5% (162/979) of the days. Of a total of 79 weight change alerts fired, 41 (52%) were triggered by weight loss and 38 (48%) were by weight gain. Providers responded in some fashion to 66 (84%) of the weight alerts and intervened in response to 45 (57%) of the alerts, for example, by contacting the patient, scheduling clinic or paracentesis appointments, modifying the diuretic dose, or requesting a laboratory workup. Providers responded equally to weight increase and decrease alerts (P=.87). The staff called patients a mean of 3.7 (SD 3.5) times per patient, and the number of phone calls correlated with technology issues (r=0.60; P=.002). A total of 60% (15/25) of the patients chose to extend their participation beyond 30 days. A total of 17 patient readmissions occurred during the study period, with only 4 (24%) related to ascites. CONCLUSIONS: We demonstrated the feasibility of a smartphone app to facilitate the management of ascites and reported excellent rates of patient and provider engagement. This innovation could enable early therapeutic intervention, thereby decreasing the burden of morbidity and mortality among patients with cirrhosis.

The Relationship between Post-Battle Experiences and Thwarted Belongingness and Perceived Burdensomeness in Three United States Military Samples.

Suicide rates within the military are elevated relative to the general population; however, research suggests that many of the suicide risk factors for military personnel are similar to the suicide risk factors for civilians. Given that many military specific experiences (e.g., number of deployments) are not considered robust predictors of either suicidal ideation or behavior, it has been posited that deployment specific experiences (e.g., post-battle experiences) may be better able to explain the increased rates of suicide among military personnel. Therefore, the current study aimed to examine the relationship between post-battle experiences and perceived burdensomeness (PB), thwarted belongingness (TB), and suicidal ideation within 3 different military samples: a non-clinical sample of Army National Guard personnel, a non-clinical sample of active duty U.S. Air Force Security Forces personnel, and a clinical sample of U.S. Army personnel receiving outpatient treatment. Post-battle experiences were found to be significantly associated with TB in both non-clinical samples; however, the association between post-battle experiences and TB was non-significant within the clinical sample. Furthermore, results indicated that post-battle experiences were not significantly associated with either PB or suicidal ideation in any of the samples. These findings suggest that in non-clinical samples, post-battle experiences impact a soldier's ability to feel connected to others. Within clinical samples, results indicate that post-battle experiences may not be a direct contributor to either PB or TB. These results indicate a need for universal intervention promoting interpersonal support of military personnel and their families prior to development of further need for psychological interventions. This upstream approach may decrease further development of TB and potentially prevent suicidal desire.