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Adolescents' suicidal behavior frequently is preceded by interpersonal stress, but not all who experience distress attempt to end their lives. Recent theories have posited individual differences in stress-related inflammatory reactivity may be associated with psychopathology risk; this study examined inflammatory reactivity as a moderator of the prospective association between interpersonal stress and adolescents' suicidal behavior. Participants included 157 at-risk adolescent females (ages 12 to 16 years) and assessed individual differences in proinflammatory cytokine responses to a brief laboratory-based social stressor, both interpersonal and non-interpersonal life events, and suicidal behavior over an 18-month follow-up period. Measuring levels of the key proinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) before and after an experimentally-induced social stressor, results revealed that blunted cytokine reactivity heightened the effect of high interpersonal stress exposure on risk for suicidal behaviors over the subsequent 9 months. Significant effects were not revealed for non-interpersonally themed stress. Finding highlight the urgent need for more research examining inflammation reactivity among adolescents.

The motivation to socially connect with peers increases during adolescence in parallel with changes in neurodevelopment. These changes in social motivation create opportunities for experiences that can impact risk for psychopathology, but the specific motivational presentations that confer greater psychopathology risk are not fully understood. To address this issue, we used a latent profile analysis to identify the multidimensional presentations of self-reported social goals in a sample of 220 girls (9-15 years old, M = 11.81, SD = 1.81) that was enriched for internalizing symptoms, and tested the association between social goal profiles and psychopathology. Associations between social goals and brain network connectivity were also examined in a subsample of 138 youth. Preregistered analyses revealed four unique profiles of social goal presentations in these girls. Greater psychopathology was associated with heightened social goals such that higher clinical symptoms were related to a greater desire to attain social competence, avoid negative feedback and gain positive feedback from peers. The profiles endorsing these excessive social goals were characterized by denser connections among social-affective and cognitive control brain regions. These findings thus provide preliminary support for adolescent-onset changes in motivating factors supporting social engagement that may contribute to risk for psychopathology in vulnerable girls.

Adolescent risk for self-injurious thoughts and behaviors (STBs) involves disturbance across multiple systems (e.g., affective valence, arousal regulatory, cognitive and social processes). However, research integrating information across these systems is lacking. Utilizing a multiple-levels-of-analysis approach, this person-centered study identified psychobiological stress response profiles and linked them to cognitive processes, interpersonal behaviors, and STBs. At baseline, adolescent girls (N = 241, Mage = 14.68 years, Range = 12-17) at risk for STBs completed the Trier Social Stress Test (TSST), questionnaires, and STB interviews. Positive affect (PA), negative affect (NA), and salivary cortisol (SC) were assessed before and after the TSST. STBs were assessed again during 3, 6, and 9 month follow-up interviews. Multitrajectory modeling of girls' PA, NA, and SC revealed four profiles, which were compared on cognitive and behavioral correlates as well as STB outcomes. Relative to normative, girls in the affective distress, hyperresponsive, and hyporesponsive subgroups were more likely to report negative cognitive style (all three groups) and excessive reassurance seeking (hyporesponsive only) at baseline, as well as nonsuicidal self-injury (all three groups) and suicidal ideation and attempt (hyporesponsive only) at follow-up. Girls' close friendship characteristics moderated several profile-STB links. A synthesis of the findings is presented alongside implications for person-centered tailoring of intervention efforts.

Prior research has struggled to differentiate cortisol stress response patterns reflective of well-regulated versus dysregulated hypothalamic-pituitary-adrenal (HPA) axis function among adolescents. Here, we show how exploring profiles of joint HPA-inflammatory stress responsivity, and linking those profiles to pubertal development and peer stress exposure may aid such distinction. Adolescent girls (N = 157, Mage  = 14.72 years, SD = 1.38) at risk for psychopathology completed assessments of salivary cortisol and pro-inflammatory cytokines (i.e., tumor necrosis factor-α, interleukin-1β, and interleukin-6) prior to and following the Trier Social Stress Test. Adolescents, a close friend, and a caregiver completed questionnaire measures of peer stress and pubertal status. Multitrajectory modeling of adolescents' cortisol and cytokine levels revealed three profiles: low cortisol response-stably low cytokine (n = 75), high cortisol response-stably moderate cytokine (n = 47), and low cortisol response-stably high cytokine (n = 35). Relative to low cortisol response-stably low cytokine, adolescents exhibiting the high cortisol response-stably moderate cytokine profile were more advanced in their pubertal development, but presented with similarly low levels of peer stress exposure. Despite showing cortisol responses that were indistinguishable from low cortisol response-stably low cytokine, adolescents exhibiting the low cortisol response-stably high cytokine profile were more pubertally advanced, but also more likely to have experienced chronic peer strain (self-report) and relational peer victimization (close friend-report). These findings thus illustrate the potential value of taking a multisystem approach to studying adolescent stress responsivity and underscore the importance of considering developmental and social factors when interpreting cortisol stress response patterns. Ultimately, such work may help inform developmental models of neuroendocrine dysregulation and related risk for psychopathology.

BackgroundDepression rates increase markedly for girls across the adolescent transition, but the social-environmental and biological processes underlying this phenomenon remain unclear. To address this issue, we tested a key hypothesis from Social Signal Transduction Theory of Depression, which posits that individuals who mount stronger inflammatory responses to social stress should exhibit greater increases in depressive symptoms following interpersonal life stress exposure than those who mount weaker inflammatory responses to such stress.MethodParticipants were 116 adolescent girls (Mage  = 14.71) at risk for psychopathology, defined as having a history of mental health concerns (e.g., psychiatric treatment, significant symptoms) over the past 2 years. At baseline, we characterized their inflammatory reactivity to social stress by quantifying their salivary proinflammatory cytokine responses to a laboratory-based social stressor. Then, 9 months later, we assessed the interpersonal and noninterpersonal stressful life events that they experienced over the prior 9 months using an interview-based measure of life stress.ResultsAs hypothesized, greater interpersonal life stress exposure was associated with significant increases in depression over time, but only for girls exhibiting stronger salivary tumor necrosis factor-α and interleukin-1β reactivity to social stress. In contrast, noninterpersonal stress exposure was unrelated to changes in depression longitudinally, both alone and when combined with youths' cytokine reactivity scores.DiscussionThese results are consistent with Social Signal Transduction Theory of Depression and suggest that heightened inflammatory reactivity to social stress may increase adolescents' risk for depression. Consequently, it may be possible to reduce depression risk by modifying inflammatory responses to social stress.

In recent decades, stress response models of adolescent depression have gained attention, but it remains unclear why only certain adolescents are vulnerable to the depressogenic effects of stress while others are not. Building on evidence that affective and physiological responses to stress moderate the impact of stress exposure on depression, the current study examined whether the interaction between severity of interpersonal stress, subjective affective reactivity, and hypothalamic-pituitary-adrenal (HPA) axis reactivity to an acute, in-vivo psychosocial stressor prospectively predicted depressive symptoms nine months later. Hypotheses were examined with a clinically-oversampled group of 182 adolescent girls (aged 12-16) to ensure an examination of the widest possible range of risk. Self-report measures of affect and salivary cortisol samples were collected before and after an in-vivo stress task to assess affective reactivity and HPA axis reactivity, respectively. Severity of interpersonal stress between baseline and nine months was assessed using a semi-structured interview and was objectively coded for severity and content theme (i.e., interpersonal vs. non-interpersonal). Results indicate that experiences of severe interpersonally-themed stress predict elevated levels of depressive symptoms longitudinally only for adolescent girls with elevated affective reactivity to stress, and suggest that these deleterious effects of stress are most exacerbated for girls with elevated physiological responses to stress. Findings suggest that it may be critical to examine both affective and physiological stress responses when assessing risk for depression in adolescents.

This study examined associations between multiple types of interpersonal and noninterpersonal stressors and the subsequent occurrence of suicide ideation and attempts among female adolescents. Adolescents ages 12 to 18 years old (n = 160) at elevated risk for suicidal thoughts and behaviors were followed for 18 months, divided into two 9-month epochs for data analysis (Periods 1 and 2). Exposure to acute relational victimization, targeted rejection, nonspecified interpersonal, and noninterpersonal life stressors over the first 9-month epoch (Period 1) was assessed using semistructured interviews and an independent life stress rating team. Participants also completed phone-based semistructured interviews of suicidal thoughts and behaviors. Preliminary analyses showed significant prospective associations between acute targeted rejection and nonspecified interpersonal stress during Period 1 and suicide ideation during Period 2, as well as relational victimization and noninterpersonal stress during Period 1 and suicide attempts during Period 2. However, in logistic regression analyses that adjusted for prior suicidality and depressive symptoms, relational victimization during Period 1 (but not targeted rejection, nonspecified interpersonal or noninterpersonal events) was associated with increased odds of suicide attempt during Period 2. Therefore, acute relational victimization exposure is associated with heightened risk for suicidal behaviors in female adolescents. Future studies should examine potential mediators and moderators of this association, and these stressors should be considered for inclusion in clinical screening tools.

Most studies aimed at understanding suicidal behavior have focused on quantifying the associations between putative risk factors and suicidal behavior in comparative studies of cases and controls. The current study, in comparison, exclusively focused on cases—89 Army soldiers presenting for hospital care following a suicide attempt—and attempted to reveal the antecedents of, reasons for, and consequences of suicide attempts. This mixed-methods study using qualitative interviews and self-report surveys/interviews revealed that in most cases, the most recent onset of suicidal thoughts began shortly before the suicide attempt and were not disclosed to others, limiting opportunities for intervention via traditional approaches. The primary reason given for attempting suicide was to escape from psychologically aversive conditions after concluding that no other effective strategies or options were available. Participants reported both negative (e.g., self-view, guilt) and positive (e.g., learning new skills, receiving support) consequences of their suicide attempt—and described things they believe would have prevented them from making the attempt. These findings provide new insights into the motivational and contextual factors for suicidal behavior and highlight several novel directions for prevention and intervention efforts. General Scientific Summary: In this study, researchers conducted in-depth interviews with 89 Army soldiers who had just tried to kill themselves. The aim was to increase understanding of why people engage in such behavior. Results revealed that the primary motivation for suicide was to escape from seemingly intolerable psychological states. Most people attempting suicide did not tell someone else about their plans ahead of time. Respondents described things that would have made them change their minds about making a suicide attempt. The results of this study provide valuable information about why people try to kill themselves and how we might better prevent them from doing so. [ABSTRACT FROM AUTHOR]

This paper discusses the scientific rationale and methodological considerations for incorporating the menstrual cycle as a time-varying intra-individual factor in personalized medicine models, such as Just-In-Time Adaptive Interventions (JITAIs). Among patients, accumulating evidence suggests that the normal hormone fluctuations of the menstrual cycle represent a time-varying factor that can trigger or exacerbate psychiatric symptoms, including but not limited to affective dysregulation, suicidality, and irritability. While only a minority of the general female population experiences significant cyclical changes, this hormone-sensitive response appears to be greater among patients with psychiatric disorders, with studies demonstrating that a majority of patients recruited for past-month suicidal ideation demonstrate worsening of their suicidality around menses. However, no interventions target suicidality during this monthly period of elevated risk despite evidence of a clear recurring biological trigger. This unique and recurrent "biotype" of suicidality is well-suited for JITAIs. In addition to providing a rationale for the inclusion of the cycle in JITAI, we provide illustrative options and examples regarding the measurement and implementation of cycle variables in JITAIs. We discuss how JITAIs might be leveraged to use menstrual cycle data to identify states of vulnerability within people and strategically select and deploy interventions based upon their receptivity at various phases in the cycle. Furthermore, we discuss how to integrate passive measures for tracking the menstrual cycle. Although much research is needed before implementation, we maintain that the menstrual cycle represents a critically understudied time-varying feature that may markedly improve the accuracy of JITAI models for predicting suicidality. [ABSTRACT FROM AUTHOR]

Objectives: To develop a composite score for differential resilience to effects of combat‐related stressors (CRS) on persistent DSM‐IV post‐traumatic stress disorder (PTSD) among US Army combat arms soldiers using survey data collected before deployment. Methods: A sample of n = 2542 US Army combat arms soldiers completed a survey shortly before deployment to Afghanistan and then again two to three and 8–9 months after redeployment. Retrospective self‐reports were obtained about CRS. Precision treatment methods were used to determine whether differential resilience to persistent PTSD in the follow‐up surveys could be developed from pre‐deployment survey data in a 60% training sample and validated in a 40% test sample. Results: 40.8% of respondents experienced high CRS and 5.4% developed persistent PTSD. Significant test sample heterogeneity was found in resilience (t = 2.1, p = 0.032), with average treatment effect (ATE) of high CRS in the 20% least resilient soldiers of 17.1% (SE = 5.5%) compared to ATE = 3.8% (SE = 1.2%) in the remaining 80%. The most important predictors involved recent and lifetime pre‐deployment distress disorders. Conclusions: A reliable pre‐deployment resilience score can be constructed to predict variation in the effects of high CRS on persistent PTSD among combat arms soldiers. Such a score could be used to target preventive interventions to reduce PTSD or other resilience‐related outcomes. [ABSTRACT FROM AUTHOR]

Background: The period after psychiatric hospital discharge is one of elevated risk for suicide‐related behaviors (SRBs). Post‐discharge clinical outreach, although potentially effective in preventing SRBs, would be more cost‐effective if targeted at high‐risk patients. To this end, a machine learning model was developed to predict post‐discharge suicides among Veterans Health Administration (VHA) psychiatric inpatients and target a high‐risk preventive intervention. Methods: The Veterans Coordinated Community Care (3C) Study is a multicenter randomized controlled trial using this model to identify high‐risk VHA psychiatric inpatients (n = 850) randomized with equal allocation to either the Coping Long Term with Active Suicide Program (CLASP) post‐discharge clinical outreach intervention or treatment‐as‐usual (TAU). The primary outcome is SRBs over a 6‐month follow‐up. We will estimate average treatment effects adjusted for loss to follow‐up and investigate the possibility of heterogeneity of treatment effects. Results: Recruitment is underway and will end September 2024. Six‐month follow‐up will end and analysis will begin in Summer 2025. Conclusion: Results will provide information about the effectiveness of CLASP versus TAU in reducing post‐discharge SRBs and provide guidance to VHA clinicians and policymakers about the implications of targeted use of CLASP among high‐risk psychiatric inpatients in the months after hospital discharge. Clinical trials registration: ClinicalTrials.Gov identifier: NCT05272176 (https://www.clinicaltrials.gov/ct2/show/NCT05272176). [ABSTRACT FROM AUTHOR]

Prior studies suggest that hypothalamic-pituitary-adrenal (HPA) axis stress response is a relatively stable risk factor for suicidal behavior in adults, and also that fluctuations in developmentally salient social stress (i.e., peer stress) predict acute suicidal ideation and behavior in adolescent females. Here, we test the hypothesis that periods of high peer stress are prospectively associated with concurrent episodes of suicidal ideation and behavior, but that abnormal cortisol responses to stress at baseline act as a diathesis that strengthens this stressor-suicidality link, using a longitudinal, multi-wave study design. We measured cortisol responses to an adolescent modification of the Trier Social Stress Test in 220 adolescent females recruited for mental health concerns, and measured stress (peer, academic, and mother-child) and suicidal ideation and behaviors repeatedly across 18 months. Logistic multilevel models revealed the predicted interaction between altered cortisol response and elevated periods of peer stress in predicting suicidal behavior, but not ideation. Higher-than-usual peer stress predicted suicidal ideation regardless of HPA function, but predicted suicide attempt only among those with blunted cortisol responses. Results suggest that peer stress serves to trigger suicidal ideation among female youth, but only triggers suicidal behavior among those with blunted cortisol reactivity.

PurposeNonsuicidal self-injury (NSSI) is associated with increased risk of suicide attempts. Theories of NSSI assert interpersonal stress as a common risk factor for, and perhaps consequence of, NSSI. Prior research has not examined reciprocal associations between chronic interpersonal stress and NSSI. This study used a multiwave, prospective design to address this gap in a sample of adolescent girls, a group with elevated risk for both chronic interpersonal stress and NSSI. Pubertal development was examined as a moderator of the reciprocal associations.MethodsAdolescent girls (N = 220; ages 12-16, M age = 14.69 years) at heightened risk for NSSI completed a baseline assessment and follow-up assessments over 18 months, divided into two 9-month epochs (Time 1 and 2). Pubertal development was assessed via self- and parent-report. Chronic interpersonal stress was assessed using a semistructured interview at the end of each time period. NSSI was measured using a semistructured clinical interview every 3 months within both time periods to enhance accurate reporting.ResultsPath models revealed that chronic romantic stress during Time 1, but not peer or parent-child stress, predicted NSSI during Time 2 among girls with more advanced pubertal development. Moreover, NSSI during Time 1 predicted higher levels of chronic romantic and parent-child stress during Time 2.ConclusionsResults revealed a reciprocal relationship between chronic romantic stress and engagement in NSSI. Further, this association may be best understood in the context of pubertal development.

Insomnia is a worldwide problem with substantial deleterious health effects. Twin studies have shown a heritable basis for various sleep-related traits, including insomnia, but robust genetic risk variants have just recently begun to be identified. We conducted genome-wide association studies (GWAS) of soldiers in the Army Study To Assess Risk and Resilience in Servicemembers (STARRS). GWAS were carried out separately for each ancestral group (EUR, AFR, LAT) using logistic regression for each of the STARRS component studies (including 3,237 cases and 14,414 controls), and then meta-analysis was conducted across studies and ancestral groups. Heritability (SNP-based) for lifetime insomnia disorder was significant (h2g = 0.115, p = 1.78 × 10-4 in EUR). A meta-analysis including three ancestral groups and three study cohorts revealed a genome-wide significant locus on Chr 7 (q11.22) (top SNP rs186736700, OR = 0.607, p = 4.88 × 10-9) and a genome-wide significant gene-based association (p = 7.61 × 10-7) in EUR for RFX3 on Chr 9. Polygenic risk for sleeplessness/insomnia severity in UK Biobank was significantly positively associated with likelihood of insomnia disorder in STARRS. Genetic contributions to insomnia disorder in STARRS were significantly positively correlated with major depressive disorder (rg = 0.44, se = 0.22, p = 0.047) and type 2 diabetes (rg = 0.43, se = 0.20, p = 0.037), and negatively with morningness chronotype (rg = -0.34, se = 0.17, p = 0.039) and subjective well being (rg = -0.59, se = 0.23, p = 0.009) in external datasets. Insomnia associated loci may contribute to the genetic risk underlying a range of health conditions including psychiatric disorders and metabolic disease.

ObjectiveUnderstanding suicide risk is a priority for the US military. We aimed to estimate associations of childhood maltreatment with pre-enlistment suicidal behaviors in new Army soldiers.MethodsCross-sectional survey data from 38,237 soldiers reporting for basic training from April 2011 through November 2012 were analyzed. Scales assessing retrospectively reported childhood abuse and neglect were derived and subjected to latent class analysis, which yielded 5 profiles: No Maltreatment, Episodic Emotional Maltreatment, Frequent Emotional/Physical Maltreatment, Episodic Emotional/Sexual Abuse, and Frequent Emotional/Physical/Sexual Maltreatment. Discrete-time survival analysis was used to estimate associations of maltreatment profiles with suicidal behaviors (assessed with a modified Columbia-Suicide Severity Rating Scale), adjusting for sociodemographics and mental disorders.ResultsNearly 1 in 5 new soldiers was classified as experiencing childhood maltreatment. Relative to No Maltreatment, all multivariate maltreatment profiles were associated (P values < .001) with elevated odds of lifetime suicidal ideation (adjusted odds ratios [AORs] = 3.10-4.93), plan (AORs = 3.75-10.77), attempt (AORs = 3.60-15.95), and onset of plan among those with ideation (AORs = 1.40-3.10). Several profiles also predicted attempts among those with plans (AORs = 2.01-2.47), and Frequent Emotional/Physical/Sexual Maltreatment predicted unplanned attempts among ideators (AOR = 5.32). Adjustment for mental disorders attenuated but did not eliminate these associations.ConclusionsChildhood maltreatment is strongly associated with suicidal behavior among new soldiers, even after adjusting for intervening mental disorders. Among soldiers with lifetime ideation, certain maltreatment profiles are associated with elevated odds of subsequently planning and/or attempting suicide. Focus on childhood maltreatment might reveal avenues for risk reduction among new soldiers.