BackgroundPersistent symptoms of autonomic dysregulation are common after COVID-19 infection and may result from alterations in central and/or peripheral autonomic regulatory processes. Traumatic stress can cause persistent alterations in autonomic function, potentially changing the response to future traumatic or physiologic stressors. However, the relationship between prior history of traumatic stress and autonomic symptom burden after COVID-19 infection has not been explored.ObjectivesExamine the potential for additive and/or interactive effects of traumatic stress and COVID-19 infection on autonomic symptom burden, and compare this with other common post-acute sequelae of COVID-19 (PASC) symptom domains.DesignObservational, self-report, single time-point online assessment.Participants404 United States adults with (N = 289) and without (N = 112) a self-reported history of COVID-19 infection.Main Outcomes and MeasuresAutonomic symptom burden (Composite Autonomic Symptom Score [COMPASS 31]), lifetime traumatic stressors (Life Events Checklist), posttraumatic stress disorder (PTSD Checklist-5), self-reported neurocognitive functioning (Neuro-QoL), insomnia (Insomnia Severity Index), and fatigue and pain (PROMIS Fatigue and Pain Interference measures).ResultsAutonomic symptom burden was significantly and positively related to both history of COVID-19 infection and number of probable lifetime traumatic stressors, with probable lifetime traumatic stressors functioning as a positive moderator of the relationship between history of COVID-19 infection and autonomic symptom burden (Cohen's partial f2 = .11, .07 and .02 for COVID history, trauma history and interaction term respectively, all p < .05, in a model also including age and gender). The moderation effect remained significant when adjusting for both current PTSD symptoms and pre-existing multi-system PASC-like symptoms prior to COVID-19. History of traumatic stress and of COVID-19 infection each had significant and positive associations with other PASC symptom domains, but with domain-specific patterns.Conclusions and RelevancePrior history of traumatic stress has a positive and interactive effect on symptoms of autonomic dysregulation following COVID-19 infection, independent of PTSD symptoms. This suggests that exposure to traumatic stress may affect the response to future stressors, including physiologic stressors such as COVID-19 infection, through persistent changes in stress-threat response systems. This relationship may provide a physiologic explanation for prior observations that baseline anxiety prior to COVID-19 infection is associated with increased likelihood of PASC.

This study explored the mediating role of self-efficacy in the relationship between shyness and help-seeking behavior among Filipino college students. With mental health concerns rising in the Philippines, help-seeking behaviors are crucial in addressing issues like emotional distress, and suicidal ideation. A sample of 440 college students aged 18–30 from Metro Manila were surveyed to determine whether self-efficacy affects the likelihood of seeking help for personal/emotional problems and suicidal ideation. Three validated instruments– the McCroskey Shyness Scale, the General Help-Seeking Questionnaire, and the General Self-Efficacy Scale– were used through an online survey. The results indicated that self-efficacy was found to be an indirect pathway linking shyness and help-seeking behavior for suicidal ideation but did not have the same effect for personal/emotional problems. Also, shyness alone did not significantly predict help-seeking behavior for either problem. Furthermore, moderated mediation analyses showed that these pathways did not significantly differ by sex, although conditional effects suggested that mediating role of self-efficacy may be more pronounced among females. Our findings suggest that enhancing college students’ self-efficacy may improve help-seeking behaviors, particularly in serious mental health situations like suicidal ideation, and highlight the need for interventions addressing cultural and psychological barriers to help-seeking. Given the cross-sectional design of this study, the observed associations should not be interpreted as causal relationships.

Background Suicidal thoughts and behaviors are an acute public health issue, particularly among US Veterans. The interpersonal-psychological theory of suicide posits that unmet interpersonal needs, specifically thwarted belongingness (TB) and perceived burdensomeness (PB) contribute to desire for death by suicide and increased suicidal ideation (SI). However, little is known about the neurochemical correlates of TB and PB. Prior research using proton magnetic resonance spectroscopy (1H-MRS) has implicated glutamate (Glu) and glutamine (Gln), as well as gamma-aminobutyric acid (GABA), in SI and related psychiatric disorders. The current study sought to examine the relationship between thwarted belongingness and perceived burdensomeness and concentrations of Gln, Glu, and GABA in US Veterans with and without a history of SI. Methods In this preliminary exploratory study, 25 US Veterans underwent a two-dimensional J-resolved 1H-MRS exam to measure in vivo concentrations of Gln, Glu, and GABA in the anterior cingulate cortex. Veterans also completed the Columbia Suicide Severity Rating Scale to characterize lifetime history of suicidal thoughts and behaviors and the Interpersonal Needs Questionnaire to measure TB and PB. Results Reduced Gln/water was associated with increased TB and PB scores. Reduced Gln/Glu was associated with increased TB scores. Veterans with a lifetime history of SI also exhibited reduced Gln/water and Gln/Glu. Follow-up regression models showed that neither TB, PB, nor SI history were uniquely associated with Gln, but TB was uniquely associated with Gln/Glu. Conclusion Results provide preliminary evidence that TB and PB may be linked to abnormalities in Gln. This work further integrates biological and psychosocial perspectives on SI.

Chronic stress and traumatic events affect the psychological and physiological state of a person. Post-traumatic stress disorder (PTSD) is a type of psychological stress that occurs in critical situations that pose a direct threat to the life of the person and/or his or her loved ones. The prevalence of PTSD is increasing every year due to growing exposure to traumatic factors such as wars, natural disasters, and other crises. These events lead to severe psychological consequences, affecting a rising number of people worldwide. Currently, PTSD can be challenging to treat due to the complex nature of the disorder, variability in individual responses to treatment, and limitations in available therapeutic options. Considering the emergency need for effective PTSD treatment, a drug repurposing strategy presents a promising avenue to accelerate the availability of therapies. Here, we summarized and described drugs that were repurposed for alleviating PTSD symptoms. Moreover, we discussed the potential of some drugs, including alpha-adrenergic modulators, cannabinoids, glutamatergic modulators, and antipsychotics, for being repurposed for PTSD treatment. Drug repurposing implies the rapid identification of compounds with an established safety profile and known therapeutic effects that may be effective in PTSD. Repurposing existing drugs with already established pharmacokinetics and pharmacodynamics may shorten development timelines, facilitate a direct transition to the second phase of clinical trials, and lower costs. However, potential drawbacks and negative aspects should be discussed comprehensively.

Objectives Current patient-facing health information may unintentionally reinforce unhelpful and less adaptive mindsets regarding musculoskeletal symptoms. This prospective randomized trial evaluated the impact of psychologically-informed educational material, explicitly designed to promote healthier interpretations of bodily sensations according to cognitive science principles, on patient experience when compared to standard professional society materials. Methods In this trial, 133 adults presenting to an upper extremity specialist with one of eight common non-traumatic musculoskeletal conditions were randomly assigned to review health information produced by either: 1) a professional musculoskeletal society or 2) revised material created by the authors and psychologist collaborators. Participants completed surveys containing validated measures assessing personal health agency (PAM-13), perceived clinician empathy (JSPPPE) and emotional response to the material. Results There were no significant differences based on the type of material reviewed. However, on multivariable analysis, participants diagnosed with rotator cuff tendinopathy, ganglion cyst, or carpal and cubital tunnel syndrome reported more negative emotional responses compared to those with lateral epicondylitis, regardless of the type of written material reviewed. Conclusions Cognitively-informed musculoskeletal health information was acceptable to patients but did not yield measurable improvements in emotional response, agency, or perceived empathy when compared to standard material. During the visit, diagnosis-specific factors may influence patient reactions more than information framing. Practice Implications Patients find clear, accessible material designed to cultivate the healthiest possible interpretation of bodily sensations acceptable and non-distressing. Future interventions should explore diagnosis-specific tailoring of information or repeated exposure to impact outcomes. Level of Evidence II.

Chronic stress disrupts the integrity of the gut environment, including leaking of the intestinal epithelium. Reelin, an extracellular matrix protein, is released from cells of the lamina propria and promotes epithelial cell proliferation and migration up the crypt-villus axis to facilitate renewal of the gut lining. In the present study, we evaluated Reelin expression and apoptosis in the small intestine of Long Evan's rats treated with recombinant Reelin (3 µg) or vehicle following 3 weeks of daily corticosterone (40 mg/kg/day) or vehicle injections. We show that Reelin- and cleaved caspase-3- immunoreactive cells are diminished in the lamina propria or epithelial cells of the gut lining following chronic stress (∼ 50% and 55%, respectively), and that a single injection of 3 µg of Reelin delivered intravenously can reverse these parameters. We also found Reelin cell counts in the small intestine did not correlate to counts in the hippocampus regardless of exposure to chronic stress or Reelin treatment. Our results suggest that Reelin may serve a protective function over gut barrier integrity through the restoration of epithelial cell turnover, and that Reelin may have a role in reversing chronic stress-induced changes to the gut environment.

Background Exposure to traumatic events is an inherent aspect of first responder work, placing individuals at heightened risk for post-traumatic stress disorder (PTSD) and burnout. This study examined the relationship between PTSD symptoms and two key dimensions of burnout—emotional exhaustion and depersonalization—among South African first responders, with a particular focus on the mediating role of psychological hardiness. Methods A total of 429 participants (police officers and paramedics) completed the PTSD Checklist for DSM-5 (PCL-5), the Short Hardiness Scale, and the Emotional Exhaustion and Depersonalization subscales of the Maslach Burnout Inventory. Results Path analysis revealed that the control and challenge dimensions of hardiness partially mediated the relationship between PTSD and burnout. While higher control was associated with lower burnout, higher challenge was unexpectedly associated with greater burnout. This suggests that different hardiness dimensions play distinct roles in the PTSD–burnout relationship. In contrast, the commitment dimension did not mediate this relationship. Conclusion These findings highlight the nuanced and multidimensional role of hardiness in trauma-exposed populations and underscore the importance of resilience-focused interventions that enhance perceived control and constructive engagement with challenge to mitigate burnout in high-risk occupational groups.

Background Up to 25% of stroke survivors develop post-traumatic stress disorder (PTSD) symptoms, yet the predisposing factors remain largely unknown. The C-C-Chemokine receptor-5 gene (CCR5) loss-of-function mutation (LOFM, CCR5-Δ32) has been identified as a protective factor against post-stroke depression. This study investigates whether CCR5-Δ32 also confers protection against post-stroke PTSD, in conjunction with two additional polymorphisms: the 5-HTTLPR in the serotonin transporter gene and the BDNF Val66Met variant. Methods We conducted a prospective analysis of 432 survivors of first-ever mild-to-moderate ischemic stroke, assessing PTSD symptomatology at 6, 12, and 24 months post-stroke. Genetic screening for CCR5-Δ32 status and PTSD symptom data were available for these participants. Results PTSD was diagnosed in 48 participants (11%) within the first year post-stroke. CCR5-Δ32 carriers exhibited significantly fewer PTSD symptoms at 6, 12, and 24 months compared to non-carriers (P < .001, P < .001, P = .02, respectively), with sustained improvement over time. Multivariate analysis confirmed that CCR5-Δ32 status was independently associated with lower PTSD risk after adjusting for relevant confounders. Furthermore, individuals with a maladaptive coping style who were non-carriers of CCR5-Δ32 exhibited a higher risk of PTSD development (HR = 4.03; 95% CI, 1.95-6.32, P < .001). Carriers of both 5-HTTLPR-L and CCR5-Δ32 had significantly lower PTSD symptoms at 6 and 12 months post-stroke (P = .026, P = .05), as did carriers of both the BDNF Val allele and CCR5-Δ32 at 6 months (P = .022). Conclusions Our findings suggest that CCR5-Δ32 carriers are less likely to develop PTSD symptoms following stroke, including individuals with pre-existing maladaptive coping styles. These results highlight a potential genetic target for future intervention strategies, with CCR5 blockade emerging as a promising therapeutic avenue for post-stroke PTSD prevention.

Background Trauma exposure, posttraumatic stress disorder (PTSD), and substance use commonly co-occur among youth. Identifying specific subgroups of youth based on unique constellations across these domains may provide a novel way to identify and target youth at prospective risk for specific types of negative clinical outcomes. Methods Trauma exposed youth completed structured clinical assessments as part of a longitudinal study (N = 1826; ages 13-21). Latent class analyses identified distinct subgroups of youth based on lifetime trauma histories and current PTSD symptom and substance use inventories collected at the baseline study visit. Logistic regression analyses determined if the latent classes were associated with elevated risk for PTSD or substance use disorder (SUD) diagnoses as the 12-month follow-up study visit (n = 1029). Logistic regression models controlled for baseline clinical characteristics and demographic factors in a stepwise fashion to elucidate if latent classes carried conferred risk beyond established risk factors. Sensitivity analyses included latent profile analyses and predictive modeling with an alternative number of latent classes. Results Four latent classes were identified which differentiated participants based on the type of trauma exposure, the number of PTSD symptoms endorsed, and the propensity to be engaged in polysubstance use. Latent classes which were characterized by exposure to interpersonal violence at the baseline study visit had an elevated risk of PTSD 12 months later, relative to the latent class which was principally exposed to incidental trauma (odds ratios ranged from 4.11-5.88). Likewise, a distinct latent class which was characterized by poly-substance use at the baseline study visit had an elevated risk of SUD diagnoses at the 12-month follow-up (odds ratio = 2.48). The findings were robust to sensitivity analyses. Conclusion These results highlight nuanced patterns of co-occurrences between trauma exposure, PTSD symptomatology, and substance use that differentiate unique sub-groups of youth at varying degrees of risk for negative clinical outcomes one year later. Evaluating the co-expression of trauma and psychopathology inventories, as opposed to only assessing the summative epidemiological indices of these constructs, may help identify adolescents who are most at risk for sustaining deleterious health outcomes.