Remote Short Sessions of Heart Rate Variability Biofeedback Monitored With Wearable Technology: Open-Label Prospective Feasibility Study.

BACKGROUND: Heart rate variability (HRV) biofeedback is often performed with structured education, laboratory-based assessments, and practice sessions. It has been shown to improve psychological and physiological function across populations. However, a means to remotely use and monitor this approach would allow for wider use of this technique. Advancements in wearable and digital technology present an opportunity for the widespread application of this approach. OBJECTIVE: The primary aim of the study was to determine the feasibility of fully remote, self-administered short sessions of HRV-directed biofeedback in a diverse population of health care workers (HCWs). The secondary aim was to determine whether a fully remote, HRV-directed biofeedback intervention significantly alters longitudinal HRV over the intervention period, as monitored by wearable devices. The tertiary aim was to estimate the impact of this intervention on metrics of psychological well-being. METHODS: To determine whether remotely implemented short sessions of HRV biofeedback can improve autonomic metrics and psychological well-being, we enrolled HCWs across 7 hospitals in New York City in the United States. They downloaded our study app, watched brief educational videos about HRV biofeedback, and used a well-studied HRV biofeedback program remotely through their smartphone. HRV biofeedback sessions were used for 5 minutes per day for 5 weeks. HCWs were then followed for 12 weeks after the intervention period. Psychological measures were obtained over the study period, and they wore an Apple Watch for at least 7 weeks to monitor the circadian features of HRV. RESULTS: In total, 127 HCWs were enrolled in the study. Overall, only 21 (16.5%) were at least 50% compliant with the HRV biofeedback intervention, representing a small portion of the total sample. This demonstrates that this study design does not feasibly result in adequate rates of compliance with the intervention. Numerical improvement in psychological metrics was observed over the 17-week study period, although it did not reach statistical significance (all P>.05). Using a mixed effect cosinor model, the mean midline-estimating statistic of rhythm (MESOR) of the circadian pattern of the SD of the interbeat interval of normal sinus beats (SDNN), an HRV metric, was observed to increase over the first 4 weeks of the biofeedback intervention in HCWs who were at least 50% compliant. CONCLUSIONS: In conclusion, we found that using brief remote HRV biofeedback sessions and monitoring its physiological effect using wearable devices, in the manner that the study was conducted, was not feasible. This is considering the low compliance rates with the study intervention. We found that remote short sessions of HRV biofeedback demonstrate potential promise in improving autonomic nervous function and warrant further study. Wearable devices can monitor the physiological effects of psychological interventions.

Development and initial validation of the Mount Sinai Resilience Scale.

OBJECTIVE: The construct of psychological resilience has received increasing attention in the mental health field. This article describes the development and initial validation of a novel self-report resilience scale, which addresses gaps in the resilience measurement literature by assessing thoughts and behaviors that help promote resilience rather than traits, and simultaneously evaluating multiple factors previously associated with resilience. METHOD: Following consensus meetings focused on scale development, we conducted an online study (n = 1,864) of U.S. adults to develop and validate an initial version of the Mount Sinai Resilience Scale (MSRS). RESULTS: An exploratory factor analysis in a random 50% of the sample suggested a seven-factor solution; this solution was then generally supported by a follow-up confirmatory factor analysis in the remaining 50% of the sample. After removing poor-fitting items, a revised 24-item scale correlated in the expected directions with established measures of perceived resilience and resilience-related constructs (e.g., social support and optimism). CONCLUSIONS: Collectively, the results of this study provide initial support for the convergent and discriminant validity of the MSRS and describe its factor structure. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder.

Objective: Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors' previous proof-of-concept randomized controlled trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first randomized controlled trial to test the efficacy and safety of repeated intravenous ketamine infusions for the treatment of chronic PTSD. Methods: Individuals with chronic PTSD (N=30) were randomly assigned (1:1) to receive six infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) (psychoactive placebo control) over 2 consecutive weeks. Clinician-rated and self-report assessments were administered 24 hours after the first infusion and at weekly visits. The primary outcome measure was change in PTSD symptom severity, as assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), from baseline to 2 weeks (after completion of all infusions). Secondary outcome measures included the Impact of Event Scale-Revised, the Montgomery-Åsberg Depression Rating Scale (MADRS), and side effect measures. Results: The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2. At week 2, the mean CAPS-5 total score was 11.88 points (SE=3.96) lower in the ketamine group than in the midazolam group (d=1.13, 95% CI=0.36, 1.91). Sixty-seven percent of participants in the ketamine group were treatment responders, compared with 20% in the midazolam group. Among ketamine responders, the median time to loss of response was 27.5 days following the 2-week course of infusions. Ketamine infusions were well tolerated overall, without serious adverse events. Conclusions: This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD. Further studies are warranted to understand ketamine's full potential as a treatment for chronic PTSD.Reprinted from Am J Psychiatry 2021; 178:193-202, with permission from American Psychiatric Association Publishing. Copyright © 2021.

Association of Depression and Cardiovascular Disease.

BACKGROUND: Cardiovascular disease remains the leading worldwide cause of mortality. There has been increased awareness of the impact of psychological health on cardiovascular disease. In particular, major depression has been linked to increased all-cause mortality, development of cardiovascular disease, and worse outcomes in those with existing cardiovascular disease. METHODS: We conducted a meta-analysis assessing the incidence of cardiovascular disease and cardiovascular disease outcomes among those with major depressive disorder. RESULTS: Among 26 studies of 1,957,621 individuals, depression was associated with increased risk of incident stroke (hazard ratio [HR] 1.13; 95% confidence interval [CI], 1.00-1.28), myocardial infarction (HR 1.28; 95% CI, 1.14-1.45), congestive heart failure (HR 1.04; 95% CI, 1.00-1.09), or any cardiovascular disease (HR 1.16; 95% CI, 1.04-1.30). Depression was associated with increased risk of all-cause mortality (HR 1.43; 95% CI, 1.27-1.60), cardiovascular disease mortality (HR 1.44; 95% CI, 1.27-1.63), and congestive heart failure mortality (HR 3.20; 95% CI, 1.29-7.94). CONCLUSION: Depression has a significant negative impact on development of cardiovascular disease and on cardiovascular disease outcomes. Further efforts to understand and mitigate these impacts are prudent.

A machine learning approach to determine resilience utilizing wearable device data: analysis of an observational cohort.

Objective: To assess whether an individual's degree of psychological resilience can be determined from physiological metrics passively collected from a wearable device. Materials and Methods: Data were analyzed in this secondary analysis of the Warrior Watch Study dataset, a prospective cohort of healthcare workers enrolled across 7 hospitals in New York City. Subjects wore an Apple Watch for the duration of their participation. Surveys were collected measuring resilience, optimism, and emotional support at baseline. Results: We evaluated data from 329 subjects (mean age 37.4 years, 37.1% male). Across all testing sets, gradient-boosting machines (GBM) and extreme gradient-boosting models performed best for high- versus low-resilience prediction, stratified on a median Connor-Davidson Resilience Scale-2 score of 6 (interquartile range = 5-7), with an AUC of 0.60. When predicting resilience as a continuous variable, multivariate linear models had a correlation of 0.24 (P = .029) and RMSE of 1.37 in the testing data. A positive psychological construct, comprised of resilience, optimism, and emotional support was also evaluated. The oblique random forest method performed best in estimating high- versus low-composite scores stratified on a median of 32.5, with an AUC of 0.65, a sensitivity of 0.60, and a specificity of 0.70. Discussion: In a post hoc analysis, machine learning models applied to physiological metrics collected from wearable devices had some predictive ability in identifying resilience states and a positive psychological construct. Conclusions: These findings support the further assessment of psychological characteristics from passively collected wearable data in dedicated studies.

Symptom characteristics of health care workers seeking outpatient psychiatric care during the COVID-19 pandemic.

BACKGROUND: Though there is a growing body of research establishing a broad negative psychological impact of COVID-19 among healthcare workers (HCWs), there are comparably fewer studies evaluating symptom presentation and clinical diagnoses among treatment-seeking HCWs. The present report seeks to fill this gap in the literature by establishing the prevalence of anxiety, depression, post-traumatic stress, alcohol misuse, and well-being among treatment-seeking HCWs. METHOD: Data were collected from 421 treatment-seeking HCWs in an outpatient hospital-based mental health setting. Both self-report measures and semi-structured interviews were utilized to assess symptom severity and render psychiatric diagnosis at intake. RESULTS: Adjustment disorders were the most prevalent diagnosis at 44.2%. Of the 347 who completed self-report measures, over 47% endorsed moderate-to-severe depressive symptoms, with 13% endorsing suicidal ideation (SI). Fifty-eight percent scored in the moderate-to-severe range for anxiety, and 19% screened positive for COVID-related post-traumatic stress disorder. Further analyses revealed that those in medical support roles endorsed significantly greater depression symptoms relative to other groups and also reported SI at greater frequency. Medical trainees also endorsed SI at higher frequencies. CONCLUSIONS: These findings are consistent with previous research on the adverse impact of COVID-19 stressors on HCWs' mental health. We further identified vulnerable groups that are underrepresented in the literature. These findings highlight the need for targeted outreach and intervention among overlooked HCWs populations.

A Longitudinal Cohort Study of Factors Impacting Healthcare Worker Burnout in New York City During the COVID-19 Pandemic.

OBJECTIVE: This study aimed to longitudinally examine the prevalence and correlates of burnout in frontline healthcare workers (FHCWs) during COVID-19 in New York City. METHODS: A prospective cohort study of 786 FHCWs at Mount Sinai Hospital was conducted during the initial COVID surge in April to May 2020 (T1) and November 2020 to January 2021 (T2) to assess factors impacting burnout. RESULTS: Burnout increased from 38.9% to 44.8% ( P = 0.002); 222 FHCWs (28.3%) had persistent burnout, 82 (10.5%) had early burnout, and 129 (16.5%) had delayed burnout. Relative to FHCWs with no burnout ( n = 350; 44.7%), those with persistent burnout reported more prepandemic burnout (relative risk [RR], 6.67), less value by supervisors (RR, 1.79), and lower optimism (RR, 0.82), whereas FHCWs with delayed burnout reported more prepandemic burnout (RR, 1.75) and caring for patients who died (RR, 3.12). CONCLUSION: FHCW burnout may be mitigated through increasing their sense of value, support, and optimism; treating mental health symptoms; and counseling regarding workplace distress.

A randomized pilot study of the prophylactic effect of ketamine on laboratory-induced stress in healthy adults.

Background: Stress exposure is a key risk factor for the development of major depressive disorder and posttraumatic stress disorder. Enhancing stress resilience in at-risk populations could potentially protect against stress-induced disorders. The administration of ketamine one week prior to an acute stressor prevents the development of stress-induced depressive-like behavior in rodents. This study aimed to test if the prophylactic effect of ketamine against stress also applies to humans. Methods: We conducted a double-blind, placebo-controlled study wherein 24 healthy subjects (n = 11 males) were randomized to receive either ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) intravenously one week prior to an acute stress [Trier Social Stress Test (TSST)]. The primary endpoint was the anxious-composed subscale of the Profile of Mood States Bipolar Scale (POMS-Bi) administered immediately after the TSST. Salivary and plasma cortisol and salivary alpha amylase were also measured at 15-min intervals for 60 min following the stressor, as proxies of hypothalamic pituitary adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axis activity, respectively. Results: Compared to the midazolam group (n = 12), the ketamine group (n = 12) showed a moderate to large (Cohen's d = 0.7) reduction in levels of anxiety immediately following stress, although this was not significant (p = 0.06). There was no effect of group on change in salivary cortisol or salivary alpha amylase following stress. We conducted a secondary analysis excluding one participant who did not show an expected correlation between plasma and salivary cortisol (n = 23, ketamine n = 11). In this subgroup, we observed a significant reduction in the level of salivary alpha amylase in the ketamine group compared to midazolam (Cohen's d = 0.7, p = 0.03). No formal adjustment for multiple testing was made as this is a pilot study and all secondary analyses are considered hypothesis-generating. Conclusions: Ketamine was associated with a numeric reduction in TSST-induced anxiety, equivalent to a medium-to-large effect size. However, this did not reach statistical significance . In a subset of subjects, ketamine appeared to blunt SAM reactivity following an acute stressor. Future studies with larger sample size are required to further investigate the pro-resilient effect of ketamine.

Longitudinal Mental Health Outcomes of Third-year Medical Students Rotating Through the Wards During COVID-19.

This study investigated third year medical students' psychological well-being during clinical rotations at Mount Sinai hospitals in New York City during the COVID-19 pandemic. All students (n = 147) starting rotations (psychiatry, surgery, obstetrics-gynecology, neurology, pediatrics, and medicine) could participate in quarterly, online, anonymous surveys comprised of validated screeners for: psychological symptoms, risk, coping, and protective factors, demographics, COVID-19 worries, and stressful clerkship-related events. Associations between variables were examined with Chi-squared, Fisher's exact, t-, Wilcoxon Rank Sum, one-way ANOVA, and McNemar tests. Significant univariate predictors of psychological distress were included in stepwise multivariable linear regression models. The baseline survey was completed by 110 (74.8%) students; ninety-two (62.6%) completed at least one other survey. During the year, 68 (73.9%) students screened positive for depression, anxiety, or PTSD. The prevalence of psychiatric symptoms peaked in June 2020 without significant changes in average scores over time. COVID-19 worries decreased over time but did not influence psychological symptoms at year-end. Eighty-three students (90.2%) experienced stressful clerkship-related events, which were traumatic and/or COVID-19-related for 26 (28.3%) and 22 students (24.0%), respectively. Baseline psychological distress, childhood emotional abuse, and resilience predicted depression, anxiety, and/or PTSD by year-end. This study highlights the importance of recognizing psychological distress and implementing interventions to support students' well-being.

Association of pessimism with cardiovascular events and all-cause mortality.

Poor psychological health is associated with Takotsubo cardiomyopathy, cardiac syndrome X, coronary microcirculatory dysfunction, peripheral artery disease, or spontaneous coronary artery dissection. Data regarding pessimism, cardiovascular disease (CVD) events and mortality and all-cause mortality remained inconclusive. This systematic review and meta-analysis aim to provide an overview of the association between pessimism, CVD outcomes and mortality. A systematic search of electronic databases was conducted from inception through July 2022 for studies evaluating pessimism and adverse outcomes. A total of 17 studies published between 1966 and July 2022 met our inclusion criteria, for a total of 232,533 individuals. Pooled hazard ratios were calculated in random-effects meta-analyses. Based on pooled analysis of adjusted HRs, pessimism was associated with adjusted HR of 1.13 (95% CI 1.07-1.19) for all-cause mortality with minimal heterogeneity (I2 = 28.5%). Based on pooled analysis of adjusted HRs, pessimism was associated with adjusted HR of 1.30 (95% CI 0.43-3.95) for CHD mortality, adjusted HR of 1.41 (95% CI 1.05-1.91) for CVD mortality, and adjusted HR of 1.43 (95% CI 0.64-3.16) for stroke. In conclusion, pessimism seems to be significantly associated with a higher risk for and poorer outcomes from CVD events than optimistic styles. There are genetic and other bases for these life approaches, but behavioral, cognitive and meditative interventions can modify patients' level of pessimism, hopefully leading to better medical outcomes. Testing this theory would yield highly useful and practical data for clinical care.

Neuropsychiatric Consequences of COVID-19 Pandemic: A Synthetic Review from a Global Perspective.

Some research suggests that distress, secondary to isolation and fear following COVID-19 infection, can negatively affect the long-term more than the COVID-19 infection itself. This narrative review aims to provide a global view on the neuropsychiatric consequences of COVID-19 that can be ascribed to several factors, ranging from the direct effect of infection, to the body's responses against the infection, or to the psychological sequelae of social isolation, unemployment, and fear for one's health and livelihood. Current findings show that the more severe the respiratory infection, the more likely are central nervous system (CNS) complications regarding the infection itself. The immune reactions to the infection may result in symptoms similar to chronic fatigue as well as neurocognitive deficits, which last long after the infection is gone. An increase in symptoms of depression, anxiety, and trauma-related stress may also follow upon economic fears and isolation from friends and family. The consequences of the pandemic are not limited to adults; children learning remotely and away from classmates and routine activities may develop adjustment disorders, acute stress disorder, and a variety of manifestations of grief. A summary of case reports suggests that COVID-19-related stress, economic recession, and political unrest increase the risk of suicidal behaviors and acts of violence. However, it is unknown whether manifestations of mental disorders result from social causes or whether CNS complications may be responsible.

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

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

Ketamine as a prophylactic resilience-enhancing agent.

Stress exposure is one of the greatest risk factors for psychiatric illnesses, including major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Enhancing stress resilience could potentially protect against the development of stress-induced psychiatric disorders, yet no resilience-enhancing pharmaceuticals have been developed to date. This review serves to consider the existing evidence for a potential pro-resilience effect of ketamine in rodents as well as the preliminary evidence of ketamine as a prophylactic treatment for postpartum depression (PPD) in humans. Several animal studies have demonstrated that ketamine administered 1 week prior to a stressor (e.g., chronic social defeat and learned helplessness) may protect against depressive-like behavior. A similar protective effect has been demonstrated against PTSD-like behavior following Contextual Fear Conditioning (CFC). Recent work has sought to explore if the administration of ketamine prevented the development of postpartum depression (PPD) in humans. Researchers administered ketamine immediately following caesarian-section and found a significantly reduced prevalence of PPD in the ketamine-treated groups compared to the control groups. Utilizing ketamine as a resilience-enhancing treatment may have unique applications, including leading to a deeper understanding of the neurobiological mechanism underlying resilience. Future trials aiming to translate and replicate these findings with humans are warranted.

Evaluation of a machine learning approach utilizing wearable data for prediction of SARS-CoV-2 infection in healthcare workers.

Objective: To determine whether a machine learning model can detect SARS-CoV-2 infection from physiological metrics collected from wearable devices. Materials and Methods: Health care workers from 7 hospitals were enrolled and prospectively followed in a multicenter observational study. Subjects downloaded a custom smart phone app and wore Apple Watches for the duration of the study period. Daily surveys related to symptoms and the diagnosis of Coronavirus Disease 2019 were answered in the app. Results: We enrolled 407 participants with 49 (12%) having a positive nasal SARS-CoV-2 polymerase chain reaction test during follow-up. We examined 5 machine-learning approaches and found that gradient-boosting machines (GBM) had the most favorable validation performance. Across all testing sets, our GBM model predicted SARS-CoV-2 infection with an average area under the receiver operating characteristic (auROC) = 86.4% (confidence interval [CI] 84-89%). The model was calibrated to value sensitivity over specificity, achieving an average sensitivity of 82% (CI ±âˆ¼4%) and specificity of 77% (CI ±âˆ¼1%). The most important predictors included parameters describing the circadian heart rate variability mean (MESOR) and peak-timing (acrophase), and age. Discussion: We show that a tree-based ML algorithm applied to physiological metrics passively collected from a wearable device can identify and predict SARS-CoV-2 infection. Conclusion: Applying machine learning models to the passively collected physiological metrics from wearable devices may improve SARS-CoV-2 screening methods and infection tracking.

A prospective study of transdiagnostic psychiatric symptoms associated with burnout and functional difficulties in COVID-19 frontline healthcare workers.

OBJECTIVE: Frontline healthcare workers (FHCWs) responding to the COVID-19 pandemic develop posttraumatic stress disorder (PTSD), major depressive disorder (MDD) and generalized anxiety disorder (GAD) symptoms. Such symptoms are associated with burnout, occupational and relational difficulties. In the current study, we examined the prospective association between acute transdiagnostic COVID-19-related PTSD, MDD, and GAD symptoms at pandemic outset, and burnout and functional difficulties several months later in FHCWs in New York City. METHODS: Wave 1 symptoms of COVID-19-related PTSD, MDD, and GAD, were assessed in 787 FHCWs from April 14 to May 11th, 2020. Burnout and occupational difficulties were assessed at wave 1 and wave 2, approximately 7 months later. RESULTS: After adjusting for wave 1 burnout, wave 1 MDD symptoms, particularly sleep difficulties, loss of interest, and feeling tired/having little energy, collectively explained 42% incremental variance in this outcome. After adjusting for wave 1 work difficulties, MDD and PTSD symptoms, particularly feeling tired/having little energy, loss of interest, and negative expectations of self/world, collectively explained 42% incremental variance in this outcome. After adjusting for wave 1 relationship difficulties, MDD, GAD, and PTSD symptoms, particularly depressed mood, irritability, and appetite disturbance, explained 26% incremental variance in this outcome. CONCLUSIONS: Results highlight psychiatric symptoms assessed during the acute phase of the COVID-19 pandemic that may help predict burnout and work and relationship difficulties in FHCWs. Early interventions aimed at ameliorating transdiagnostic symptoms of MDD, PTSD, and GAD may help mitigate risk for burnout and functional difficulties in this population.

Altered gene expression and PTSD symptom dimensions in World Trade Center responders.

Despite experiencing a significant trauma, only a subset of World Trade Center (WTC) rescue and recovery workers developed posttraumatic stress disorder (PTSD). Identification of biomarkers is critical to the development of targeted interventions for treating disaster responders and potentially preventing the development of PTSD in this population. Analysis of gene expression from these individuals can help in identifying biomarkers of PTSD. We established a well-phenotyped sample of 371 WTC responders, recruited from a longitudinal WTC responder cohort using stratified random sampling, by obtaining blood, self-reported and clinical interview data. Using bulk RNA-sequencing from whole blood, we examined the association between gene expression and WTC-related PTSD symptom severity on (i) highest lifetime Clinician-Administered PTSD Scale (CAPS) score, (ii) past-month CAPS score, and (iii) PTSD symptom dimensions using a 5-factor model of re-experiencing, avoidance, emotional numbing, dysphoric arousal and anxious arousal symptoms. We corrected for sex, age, genotype-derived principal components and surrogate variables. Finally, we performed a meta-analysis with existing PTSD studies (total N = 1016), using case/control status as the predictor and correcting for these variables. We identified 66 genes significantly associated with total highest lifetime CAPS score (FDR-corrected p < 0.05), and 31 genes associated with total past-month CAPS score. Our more granular analyses of PTSD symptom dimensions identified additional genes that did not reach statistical significance in our analyses with total CAPS scores. In particular, we identified 82 genes significantly associated with lifetime anxious arousal symptoms. Several genes significantly associated with multiple PTSD symptom dimensions and total lifetime CAPS score (SERPINA1, RPS6KA1, and STAT3) have been previously associated with PTSD. Geneset enrichment of these findings has identified pathways significant in metabolism, immune signaling, other psychiatric disorders, neurological signaling, and cellular structure. Our meta-analysis revealed 10 genes that reached genome-wide significance, all of which were downregulated in cases compared to controls (CIRBP, TMSB10, FCGRT, CLIC1, RPS6KB2, HNRNPUL1, ALDOA, NACA, ZNF429 and COPE). Additionally, cellular deconvolution highlighted an enrichment in CD4 T cells and eosinophils in responders with PTSD compared to controls. The distinction in significant genes between total lifetime CAPS score and the anxious arousal symptom dimension of PTSD highlights a potential biological difference in the mechanism underlying the heterogeneity of the PTSD phenotype. Future studies should be clear about methods used to analyze PTSD status, as phenotypes based on PTSD symptom dimensions may yield different gene sets than combined CAPS score analysis. Potential biomarkers implicated from our meta-analysis may help improve therapeutic target development for PTSD.

Association of Optimism with Cardiovascular Events and All-Cause Mortality: Systematic Review and Meta-Analysis.

BACKGROUND: The effect of psychological health on cardiovascular disease is an underappreciated yet important area of study. Understanding the relationship between these two entities may allow for more comprehensive care of those with cardiovascular disease. The primary objective of this meta-analysis is to evaluate the relationship between optimism and risk of developing adverse events such as all-cause mortality or fatal and non-fatal cardiovascular disease in community-based populations. METHOD: A systematic search of electronic databases was conducted from inception through November 2021 for prospective studies evaluating optimism and adverse outcomes. Two reviewers independently selected prospective cohort studies that evaluated optimism and either all-cause mortality or cardiovascular disease and reported hazard ratios of these outcomes between optimistic and non-optimistic groups. Studies that reported odds ratio or other risk assessments were excluded. Pooled hazard ratios were calculated in random-effects meta-analyses. RESULTS: Pooled analysis of six studies (n = 181,709) showed a pooled hazard ratio of 0.87 (95% confidence interval [CI], 0.82-0.92) for all-cause mortality among those with more optimistic mindset. Analysis of seven studies (n = 201,210) showed a pooled hazard ratio of 0.59 (95% CI, 0.37-0.93) for cardiovascular disease and pooled hazard ratio of 0.57 (95% CI, 0.07-4.56) for stroke. CONCLUSIONS: In this pooled meta-analysis, optimism was associated with a reduced risk of all-cause mortality and of cardiovascular disease. These results suggest an important relationship between psychological health and cardiovascular disease that may serve as an area for intervention by clinicians.