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This study aimed to identify factors associated with burnout in nurses and nurses' opinions regarding interventions to promote well-being during crisis conditions such as those experienced during the COVID-19 pandemic.Burnout among nurses is prevalent under usual conditions and may increase during crises such as COVID-19.Researchers conducted a survey of 1103 frontline nurses in a single New York City hospital during the first (spring 2020) and second (fall 2020/winter 2021) local waves of COVID-19.Burnout prevalence increased from 45% to 52% between the first and second wave. Younger age, female gender, posttraumatic stress, anxiety or depressive symptoms, history of burnout, feeling less valued by hospital leadership, less informed of responsibilities, less certain about duration of enhanced workload, and prepared by prepandemic experience were predictive of burnout in multivariable analyses.Although some identified risk factors for burnout were nonmodifiable, others may be modifiable by hospital leadership.

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; β*(95% CI) = 0.58 (0.44, 0.72); p β*(95% CI) = 0.38 (0.23, 0.54); p 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

Suicidal ideation (SI) is an early risk factor for suicide among disaster responders. To date, however, no known study has examined the prevalence, and pre-, peri-, and post-disaster risk correlates of SI in World Trade Center (WTC) responders, one of the largest disaster response populations in U.S.The prevalence, and pre-, peri- and post-event correlates of SI were assessed in a population-based health monitoring cohort of 14,314 police responders and 16,389 non-traditional responders (e.g., construction workers) who engaged in response, recovery, and clean-up efforts following the 9/11/2001 terrorist attacks on the WTC. Multivariable analyses were conducted to identify correlates and individual psychiatric symptoms associated with SI in each group.A total 12.5% of non-traditional and 2.2% of police WTC responders reported SI. Depression, functional impairment, alcohol use problems, and lower family support while working at the WTC site were associated with SI in both groups of responders. Symptom-level analyses revealed that three symptoms accounted for approximately half of the variance in SI for both groups-feeling bad about oneself, or that one has let down oneself or family; feeling down, depressed, or hopeless; and sense of foreshortened future (44.7% in non-traditional and 71% in police).Use of self-report measures and potentially limited generalizability.SI is prevalent in WTC disaster responders, particularly non-traditional responders. Post-9/11 psychiatric symptoms reflecting guilt, shame, hopelessness, and associated functional impairment are most strongly linked to SI, suggesting that interventions targeting these factors may help mitigate suicide risk in this population.

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.

Objectives We sought to describe the course and correlates of psychological distress in frontline healthcare workers (FHCWs) during the COVID-19 pandemic in New York City (NYC). Methods A prospective cohort study of FHCWs at the Mount Sinai Hospital was conducted during the initial 2020 surge (T1) and 7 months later (T2). Psychological distress [i.e., positive screen for pandemic-related post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and/or generalized anxiety disorder (GAD)], occupational and personal exposures to COVID-19, coping strategies, and psychosocial characteristics were assessed. Four courses of psychological distress response were identified: no/minimal, remitted, persistent, and new-onset. Multinomial logistic regression and relative importance analyses were conducted to identify factors associated with courses of distress. Results Of 786 FHCWs, 126 (16.0%) FHCWs had persistent distress; 150 (19.1%) remitted distress; 35 (4.5%) new-onset distress; and 475 (60.4%) no/minimal distress. Relative to FHCWs with no/minimal distress, those with persistent distress reported greater relationship worries [19.8% relative variance explained (RVE)], pre-pandemic burnout (18.7% RVE), lower dispositional optimism (9.8% RVE), less emotional support (8.6% RVE), and feeling less valued by hospital leadership (8.4% RVE). Relative to FHCWs with remitted symptoms, those with persistent distress reported less emotional support (29.7% RVE), fewer years in practice (28.3% RVE), and psychiatric history (23.6% RVE). Conclusions One-fifth of FHCWs in our study experienced psychological distress 7 months following the COVID-19 surge in NYC. Pandemic-related worries, pre-pandemic burnout, emotional support, and feeling valued by leaders were linked to persistent distress. Implications for prevention, treatment, and organizational efforts to mitigate distress in FHCWs are discussed. Supplementary Information The online version contains supplementary material available at 10.1007/s00420-022-01832-0.

Supplemental Digital Content is available in the text., Purpose To examine the psychological impact of the COVID-19 pandemic on medical trainees (residents and fellows) working at Mount Sinai Hospital (MSH) in New York City (NYC), the initial epicenter of the United States pandemic. Method The authors administered a survey to 991 trainees in frontline specialties working at MSH in NYC between April and May 2020. The instrument assessed symptoms of major depressive disorder, generalized anxiety disorder, COVID-19-related posttraumatic stress disorder, and burnout. Psychiatric screens were aggregated into 1 composite measure, and meeting criteria on any of the 3 scales was considered a positive screen for psychiatric symptoms. The survey also assessed COVID-19-related exposures, worries, coping strategies, and desired interventions. Multivariable logistic regressions were conducted to identify factors associated with psychiatric symptoms and burnout. Results Of the 560 respondents (56.6% response rate), 29.7% screened positive for psychiatric symptoms and 35.8% screened positive for burnout. History of a mental illness, COVID-19-related duties and personal/career worries, and coping by substance use were associated with increased likelihood of screening positive for psychiatric symptoms. Positive emotion-focused coping and feeling valued by supervisors were associated with decreased likelihood. Internal medicine and surgical specialties, a history of mental illness, increased duty hours, duty-related worries, personal/career worries, coping via self-blame and venting, and coping via substance use were associated with higher odds of burnout. Feeling valued by supervisors was associated with decreased burnout odds. The most common crisis-related needs included access to personal protective equipment, food provisions, and financial support. Conclusions Psychological distress and burnout affected approximately one-third of trainees sampled during the height of the pandemic in NYC. As the pandemic surged beyond NYC, these findings suggest that interventions should include addressing basic needs, promoting leadership affirmation, moderating duty hours, supporting trainees financially, and enhancing mental health support.

Background The COVID-19 pandemic has led to significant mental health consequences for frontline health care workers (FHCWs). However, no known study has examined the prevalence, determinants, or correlates of posttraumatic growth (PTG) in this population. Methods Data were analyzed from a prospective cohort of FHCWs at an urban tertiary care hospital in New York City (NYC). Assessments were conducted during the spring 2020 pandemic peak (Wave 1) and seven months later (Wave 2). Multivariable logistic regression analyses were conducted to identify Wave 1 sociodemographic, occupational, and psychosocial factors associated with PTG at Wave 2, and the association between aspects of PTG with burnout and pandemic-related PTSD symptoms at Wave 2. Results A total 76.8% of FHCWs endorsed moderate or greater PTG; the most prevalent domains were increased appreciation of life (67.0%), improved relationships (48.7%), and greater personal strength (44.1%). Non-White race/ethnicity, greater levels of positive emotions, pandemic-related PTSD symptoms, dispositional gratitude, and feelings of inspiration were independently associated with PTG. At Wave 2, endorsement of spiritual growth during the pandemic was associated with 52% and 44% lower odds of screening positive for pandemic-related PTSD symptoms and burnout, respectively; greater improvement in relationships was associated with 36% lower odds of screening positive for burnout. Limitations Single institution study and use of self-report instruments. Conclusions Nearly 4-of-5 FHCWs report pandemic-related PTG, driven largely by salutogenic factors assessed during the pandemic surge. Interventions to bolster these factors may help promote PTG and mitigate risk for burnout and pandemic-related PTSD symptoms in this population.

Promising initial data indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine may be beneficial in post-traumatic stress disorder (PTSD). Here, we explore the neural correlates of ketamine-related changes in PTSD symptoms, using a rich battery of functional imaging data (two emotion-processing tasks and one task-free scan), collected from a subset of participants of a randomized clinical trial of repeated-dose intravenous ketamine vs midazolam (total N=21). In a pre-registered analysis, we tested whether changes in an a priori set of imaging measures from a target neural circuit were predictive of improvement in PTSD symptoms, using leave-one-out cross-validated elastic-net regression models (regions of interest in the target circuit consisted of the dorsal and rostral anterior cingulate cortex, ventromedial prefrontal cortex, anterior hippocampus, anterior insula, and amygdala). Improvements in PTSD severity were associated with increased functional connectivity between the ventromedial prefrontal cortex (vmPFC) and amygdala during emotional face-viewing (change score retained in model with minimum predictive error in left-out subjects, standardized regression coefficient [β]=2.90). This effect was stronger in participants who received ketamine compared to midazolam (interaction β=0.86), and persisted following inclusion of concomitant change in depressive symptoms in the analysis model (β=0.69). Improvement following ketamine was also predicted by decreased dorsal anterior cingulate activity during emotional conflict regulation, and increased task-free connectivity between the vmPFC and anterior insula (βs=-2.82, 0.60). Exploratory follow-up analysis via dynamic causal modelling revealed that whilst improvement in PTSD symptoms following either drug was associated with decreased excitatory modulation of amygdala→vmPFC connectivity during emotional face-viewing, increased top-down inhibition of the amygdala by the vmPFC was only observed in participants who improved under ketamine. Individuals with low prefrontal inhibition of amygdala responses to faces at baseline also showed greater improvements following ketamine treatment. These preliminary findings suggest that, specifically under ketamine, improvements in PTSD symptoms are accompanied by normalization of hypofrontal control over amygdala responses to social signals of threat.

SUMMARYResilience is broadly defined as the ability to bounce back from adversity or trauma. Recent advances in resilience research have shifted away from merely describing individual characteristics towards focusing on the complex interactions between individuals and their dynamic personal, community and cultural contexts. It is clear that resilience involves both neurobiological and cultural processes. Neurobiological contributions include genes, epigenetics, stress-response systems, the immune system and neural circuitry. Culture helps to elucidate collective systems of belief and accepted positive adaptations. Importantly, resilience can also be affected by evidence-based interventions and deliberate practice on the part of the individual. This review seeks to understand resilience as a complex and active process that is shaped by neurobiological profiles, developmental experiences, cultural and temporal contexts, and practical training. It uses the COVID-19 pandemic as a case example to better understand individual and group responses to tragedy. We suggest practical recommendations to help populations around the world cope and recover from the global threat of COVID-19.

Background Nearly 20 years after the terrorist attacks of September 11, 2001, multiple studies have documented the adverse mental consequences among World Trade Center (WTC) rescue, recovery, and clean-up workers. However, scarce research has examined mental health stigma and barriers to care in WTC-exposed individuals, and no known study has examined whether rates of endorsement may differ between police and "nontraditional" responders, the latter comprising a heterogeneous group of workers and volunteers. Objective To identify the prevalence and correlates of mental health stigma and barriers to care in WTC responders. Methods Mental health stigma and barriers to care and their correlates were examined in 6,777 police and 6,272 nontraditional WTC responders. Results Nontraditional responders endorsed more stigma or barriers to care concerns than police responders. Within a subsample who screened positive for a psychiatric disorder, police were more likely than nontraditional responders to endorse "concerns that negative job consequences might result" (17.9% vs. 9.1%), while nontraditional responders were more likely to endorse "I don't know where to go to find counseling services" (18.4% vs.6.6%). Within this subsample, mental health service need and more severe WTC-related posttraumatic stress disorder symptoms were associated with increased likelihood of endorsing stigma or barriers; pre-9/11 psychiatric history and non-Hispanic Black race/ethnicity were associated with lower likelihood of endorsing stigma or barriers. Conclusions Results of this study underscore the burden of mental health stigma and barriers to care in WTC responders, and highlight the need for targeted interventions to address these concerns and promote mental healthcare utilization in this population.

Posttraumatic stress disorder (PTSD) is a highly prevalent, chronic, and disabling condition for which currently available pharmacotherapies are insufficiently effective. Ketamine, which is a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a promising and rapid-acting novel treatment intervention for this disorder. Findings from a proof-of-concept, randomized, controlled crossover study of single-dose intravenous ketamine administration (compared to single-dose midazolam) in patients with chronic PTSD suggest that ketamine is associated with rapid improvement in core PTSD symptoms and comorbid depressive symptoms, and is generally well tolerated. Additional research is needed to confirm its efficacy and safety for patients with PTSD. Results from ongoing trials of repeated intravenous administration for PTSD are expected to yield more definitive evidence. Potential mechanisms of action as well as future research directions are discussed. [ Psychiatr Ann . 2020;50(2):68–76.]

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.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.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.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.

(1) Background: This study examined the prevalence and correlates of factors associated with self-reported mental health service use in a longitudinal cohort of frontline health care workers (FHCWs) providing care to patients with COVID-19 throughout 2020. (2) Methods: The study comprised a two-wave survey (n = 780) administered in April–May 2020 (T1) and November 2020–January 2021 (T2) to faculty, staff, and trainees in a large urban medical center. Factors associated with initiation, cessation, or continuation of mental health care over time were examined. (3) Results: A total of 19.1% of FHCWs endorsed currently utilizing mental health services, with 11.4% continuing, 4.2% initiating, and 3.5% ceasing services between T1 and T2. Predisposing and need-related factors, most notably a history of a mental health diagnosis and distress related to systemic racism, predicted service initiation and continuation. Among FHCWs with a prior mental health history, those with greater perceived resilience were less likely to initiate treatment at T2. Descriptive data highlighted the importance of services around basic and safety needs (e.g., reliable access to personal protective equipment) relative to mental health support in the acute phase of the pandemic. (4) Conclusions: Results may be helpful in identifying FHCWs who may benefit from mental health services.

To evaluate the direct and interacting effects of personal and systemic factors that contribute to psychological distress among frontline healthcare workers (FHCWs) during the COVID-19 pandemic.Data were collected using a hospital-wide, cross-sectional survey. A multivariable binary logistic regression and relative importance analysis was conducted to identify factors associated with screening positive for C19-distress.A total of 1005 (39.0%, 95%CI - 37.1-40.9%) out of 2579 FHCWs met the prespecified cutoff values for significant symptoms of C19-distress. Fewer sleep hours and lower perceptions of leadership support explained the majority of variance (19.4% relative variance explained [RVE]) in C19-distress, followed by team camaraderie (6.4% RVE), physical exercise (4.9% RVE), and engagement in hobbies (3.2% RVE).These results underscore the importance of restorative behaviors as potential targets to help decrease distress and promote resilience in FHCWs.

Many biological systems are altered in association with posttraumatic stress disorder (PTSD) and resilience. However, there are only few approved pharmacological treatments for PTSD, and no approved medications to enhance resilience. This article provides a critical review of select neurobiological findings in PTSD and resilience, and also of pharmacologic approaches that have emerged from this work. The medications summarized involve engagement with targets in the adrenergic, hypothalamic-pituitary-adrenal axis, and neuropeptide Y systems. Other highlighted approaches involve the use of ketamine and 3,4-methylenedioxymethamphetamine-assisted psychotherapy, which recently surfaced as promising strategies for PTSD, though the neurobiological mechanisms underlying their actions, including for promoting resilience, are not yet fully understood. The former approaches fall within the broad concept of "rational pharmacotherapy," in that they attempt to directly target dysregulated systems known to be associated with posttraumatic symptoms. To the extent that use of ketamine and 3,4-methylenedioxymethamphetamine promotes symptom improvement and resilience in PTSD, this provides an opportunity for reverse translation and identification of relevant targets and mechanisms of action through careful study of biological changes resulting from these interventions. Promoting resilience in trauma-exposed individuals may involve more than pharmacologically manipulating dysregulated molecules and pathways associated with developing and sustaining PTSD symptom severity, but also producing a substantial change in mental state that increases the ability to engage with traumatic material in psychotherapy. Neurobiological examination in the context of treatment studies may yield novel targets and promote a greater understanding of mechanisms of recovery from trauma.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has led to an increased risk of psychiatric symptoms among frontline health care workers (FHCWs). In the current study, a novel "symptomics" approach was employed to examine the association between acute transdiagnostic symptoms of posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD) and burnout and work and relationship difficulties in FHCWs at an urban tertiary care hospital in New York City. METHODS: Symptoms of COVID-19-related PTSD (4-item PTSD Checklist-5), MDD (Patient Health Questionnaire-8), GAD (Generalized Anxiety Disorder-7), burnout (Single-Item Mini-Z Burnout Assessment), and functional difficulties (Brief Inventory of Psychosocial Functioning) were assessed. Relative importance analyses were conducted to identify PTSD, MDD, and GAD symptoms associated with burnout and functional difficulties. RESULTS: The total number of eligible participants included 6,026 presumed FHCWs, of which 3,360 (55.8%) completed the survey and 2,579 (76.8%) of whom endorsed directly treating patients with COVID-19 and provided sufficient responses to our outcome variables for analysis. Feeling tired/having little energy, being easily annoyed or irritable, and feeling nervous, anxious, or on edge were most strongly associated with burnout; feeling tired/having little energy accounted for the greatest amount of explained variance (> 15%). Negative expectations of oneself or the world, trouble concentrating, and feeling easily annoyed or irritable were most strongly associated with work difficulties; negative expectations of oneself or the world accounted for the greatest amount of explained variance (> 9%). Feeling easily annoyed or irritable, negative expectations about oneself or the world, and feeling bad about oneself were most strongly associated with relationship difficulties; feeling easily annoyed or irritable accounted for the greatest amount of explained variance (> 10%). CONCLUSIONS: Results of this study underscore the importance of a transdiagnostic, symptom-based approach when examining associations between acute psychopathology and burnout and functional difficulties in FHCWs. Further work is needed to determine if early interventions aimed at ameliorating specific psychiatric symptoms may help mitigate risk for peri- and posttraumatic burnout and functional difficulties in this population.

Introduction Little is known about the relationship between moral distress and mental health problems. We examined moral distress in 2579 frontline healthcare workers (FHCWs) caring for coronavirus disease 2019 (COVID‐19) patients during the height of the spring 2020 pandemic surge in New York City. The goals of the study were to identify common dimensions of COVID‐19 moral distress; and to examine the relationship between moral distress, and positive screen for COVID‐19‐related posttraumatic stress disorder (PTSD) symptoms, burnout, and work and interpersonal functional difficulties. Method Data were collected in spring 2020, through an anonymous survey delivered to a purposively‐selected sample of 6026 FHCWs at Mount Sinai Hospital; 2579 endorsed treating COVID‐19 patients and provided complete survey responses. Physicians, house staff, nurses, physician assistants, social workers, chaplains, and clinical dietitians comprised the sample. Results The majority of the sample (52.7%–87.8%) endorsed moral distress. Factor analyses revealed three dimensions of COVID‐19 moral distress: negative impact on family, fear of infecting others, and work‐related concerns. All three factors were significantly associated with severity and positive screen for COVID‐19‐related PTSD symptoms, burnout, and work and interpersonal difficulties. Relative importance analyses revealed that concerns about work competencies and personal relationships were most strongly related to all outcomes. Conclusion Moral distress is prevalent in FHCWs and includes family‐, infection‐, and work‐related concerns. Prevention and treatment efforts to address moral distress during the acute phase of potentially morally injurious events may help mitigate risk for PTSD, burnout, and functional difficulties.

BackgroundProblems in learning that sights, sounds, or situations that were once associated with danger have become safe (extinction learning) may explain why some individuals suffer prolonged psychological distress following traumatic experiences. Although simple learning models have been unable to provide a convincing account of why this learning fails, it has recently been proposed that this may be explained by individual differences in beliefs about the causal structure of the environment.MethodsHere, we tested two competing hypotheses as to how differences in causal inference might be related to trauma-related psychopathology, using extinction learning data collected from clinically well-characterised individuals with varying degrees of post-traumatic stress (N = 56). Model parameters describing individual differences in causal inference were related to multiple post-traumatic stress disorder (PTSD) and depression symptom dimensions via network analysis.ResultsIndividuals with more severe PTSD were more likely to assign observations from conditioning and extinction stages to a single underlying cause. Specifically, greater re-experiencing symptom severity was associated with a lower likelihood of inferring that multiple causes were active in the environment.ConclusionsWe interpret these results as providing evidence of a primary deficit in discriminative learning in participants with more severe PTSD. Specifically, a tendency to attribute a greater diversity of stimulus configurations to the same underlying cause resulted in greater uncertainty about stimulus-outcome associations, impeding learning both that certain stimuli were safe, and that certain stimuli were no longer dangerous. In the future, better understanding of the role of causal inference in trauma-related psychopathology may help refine cognitive therapies for these disorders.

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, 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=1,016), using case/control status as the predictor and correcting for these variables.We identified 66 genes significantly associated with highest lifetime CAPS score (FDR-corrected pSERPINA1, RPS6KA1,andSTAT3) 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 down-regulated 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 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.

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.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.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.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.

Objective: Research examining the responders of the World Trade Center terrorist attacks of 9/11 has found that Hispanic responders are at greater risk for posttraumatic stress disorder (PTSD) than non-Hispanic White responders. However, no studies have examined how acculturation may influence the relationship between coping and PTSD in Hispanic 9/11 responders. This novel study is the first to examine differences in coping and PTSD among Hispanic responders by level of acculturation. Methods: The sample is composed of 845 Hispanic 9/11 responders who were seen at the World Trade Center Health Program and participated in a web-based survey. Using logistic and multiple linear regression, we examined how acculturation is related to their coping strategies and risk for PTSD. We also tested for interaction to examine whether level of acculturation moderated the relationship between coping and PTSD symptom severity. Results: Key findings revealed that higher acculturation is associated with the use of substances, venting, and humor to cope, while lower acculturation is associated with the use of active coping and self-distraction in this sample. We also found that less acculturated responders were more likely to experience more severe PTSD. Lastly, our findings revealed that Hispanics who are more acculturated and used substances to cope had more severe PTSD than less acculturated responders. Conclusion: These findings highlight the need to consider the role of acculturation in Hispanic responders' coping and PTSD. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Data were collected between April 14 and May 11, 2020, during the peak and initial decline of the acute patient surge. An anonymous, incentivized ($25 gift card) survey was emailed to a purposively selected sample of 6,026 FHCWs at Mount Sinai Hospital, an urban tertiary care hospital in NYC. Importance analyses revealed that positive emotions (interested [relative variance explained [RVE] = 14.7%], enthusiastic [RVE = 11.2%]), self-efficacy (RVE = 13.8%), nonengagement in substance use coping (RVE = 9.9%), higher purpose in life (RVE = 7.8%), and emotional support (RVE = 6.9%) and leadership support (RVE = 6.8%) were most strongly associated with psychological resilience, collectively explaining > 70% of the variance in these scores. To our knowledge, this is the first study to examine factors associated with psychological resilience in FHCWs during the acute phase of the COVID-19 pandemic.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition triggered by exposure to trauma. The study of PTSD is complicated by highly heterogeneous presentations and experiences of trauma between individuals. Capitalizing on the existence of the World Trade Center General Responder Cohort (WTC-GRC) of rescue, recovery and clean-up workers who responded during and in the aftermath of the World Trade Center (WTC) 9/11/2001 attacks, we studied genetic correlates of PTSD in a sample of 371 WTC responders, selected from the WTC-GRC utilizing stratified random sampling. This deeply phenotyped sample of WTC responders – ranging from no/low PTSD symptom levels to severe PTSD– provide a unique opportunity to study genetic risk factors for PTSD severity and chronicity following a single, shared, well-documented trauma, also incorporating measures of childhood and other lifetime traumas.We examined associations of polygenic risk scores (PRS) –derived from a range of genome-wide association studies (GWAS) of behavioral traits, psychiatric disorders, and brain volumetric phenotypes– with PTSD severity and chronicity among these 371 individuals. Our results demonstrate significant genetic regulation of lifetime PTSD severity, assessed with the lifetime version Clinician-Administered PTSD Scale (CAPS), and chronicity, assessed with the past-month CAPS. PRS derived from GWAS of attention deficit-hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and brain imaging phenotypes (amygdala and putamen volumes) were associated with several PTSD symptom dimensions. Interestingly, we found greater genetic contribution to PTSD among cases compared to our full sample. In addition, we tested for associations between exposures to traumatic stressors, including WTC-related exposures, childhood trauma, and other lifetime traumatic life events in our full sample. Together, polygenic risk and exposures to traumatic stress explained ~45% of variance in lifetime CAPS (R2=0.454), and ~48% of variance in past-month CAPS (R2=0.480) in the full sample.These participants represent a highly vulnerable population, with exposures to severe trauma during 9/11 and the following days and months. These novel identified associations between PTSD and PRS of behavioral traits and brain volume phenotypes, as well as replicated associations with PRS of other psychiatric disorders, may contribute to understanding the biological factors associated with risk for and chronicity of PTSD. In particular, the identification of neuroimaging phenotypes indicates that coupling of neuroimaging with genetic risk score calculations may predict PTSD outcomes.

The COVID-19 pandemic is anticipated to have a prolonged adverse mental health impact on health care workers (HCWs). The supportive services implemented by the Mount Sinai Hospital System in New York for its workers culminated in the founding of the Mount Sinai Center for Stress, Resilience, and Personal Growth (CSRPG). CSRPG is an innovative mental health and resilience-building service that includes strong community engagement, self- and clinician-administered screening, peer co-led resilience training workshops, and care matching. The long-term sustainability of similar programs across the United States will require federal funding.

A serious lack of effective pharmacotherapeutic interventions for posttraumatic stress disorder (PTSD) raises the urgent need for the development of novel treatments. Ketamine-a noncompetitive glutamate N-methyl-d-aspartate (NMDA) receptor antagonist in use for decades as an anesthetic and analgesic agent-has more recently been demonstrated to have rapid-onset antidepressant effects in patients with treatment-resistant depression (TRD). In the present review of ketamine as an emerging novel pharmacotherapeutic intervention for chronic PTSD, we discuss findings from the first proof-of-concept, randomized clinical trial (RCT) of single-dose intravenous ketamine in patients with chronic PTSD, as well as open-label studies and current practice. We introduce ongoing RCTs investigating the efficacy of repeated ketamine infusions in rapidly reducing symptoms and maintaining improvement in samples of individuals with PTSD stemming from civilian and military traumas. Additionally, we discuss mixed findings from published reports on ketamine administration in the acute aftermath of trauma. Studies in animal models of chronic stress have investigated molecular mechanisms underlying ketamine's effects, generating a shift in the conceptualization of PTSD as a disorder of impaired neural connectivity. We review animal studies examining the potential of ketamine to modify the expression of fear by altering memory reconsolidation or enhancing fear extinction, as well as others investigating ketamine administration prophylactically prior to stress exposure. We introduce the need for additional study in humans to evaluate whether ketamine might enhance the efficacy of psychotherapeutic interventions in individuals with chronic PTSD, harnessing a window of ketamine-induced neuroplasticity. While research on ketamine for PTSD is still in its early stages, it brings about the promise of novel and more effective treatments for this disabling condition.

PURPOSE. Nearly two decades after the 9/11 attacks on the World Trade Center (WTC), the prevalence of mental disorders remains elevated among traditional (e.g., police) and non-traditional (e.g., construction workers) responders who were involved in the WTC rescue, recovery, and clean-up efforts. To date, however, scarce research has examined factors associated with perceived need for mental health care, which is critical to promoting engagement in mental health treatment in this population. METHODS. Data were analyzed from 16,170 WTC responders, including 8,881 police responders and 7,289 non-traditional responders, who completed their first annual health monitoring visit with the WTC Health Program an average of 6.5 years after 9/11/2001. Predisposing, enabling, and need-based factors associated with perceived need for mental health care were examined using multivariable logistic regression analyses. RESULTS. Nearly half (48.7%) of non-traditional responders and a fifth (20.6%) of police responders reported a need for mental health care. The most common perceived needs were for psychotropic medication, individual psychotherapy, and stress management counseling. Predisposing (e.g., female gender) and need-based factors (e.g., WTC-related posttraumatic stress disorder) predicted perceived need for mental health care in both groups. Among non-traditional responders, Hispanic ethnicity and current suicidal ideation were additionally associated with this outcome. CONCLUSIONS. Non-traditional WTC responders are substantially more likely than police WTC responders to perceive a need for mental health treatment. Characterization of factors associated with perceived need for treatment can help inform population-based outreach and monitoring efforts designed to promote engagement in mental health treatment in WTC responders.

A serious lack of effective pharmacotherapeutic interventions for posttraumatic stress disorder (PTSD) raises the urgent need for the development of novel treatments. Ketamine-a noncompetitive glutamate N-methyl-d-aspartate (NMDA) receptor antagonist in use for decades as an anesthetic and analgesic agent-has more recently been demonstrated to have rapid-onset antidepressant effects in patients with treatment-resistant depression (TRD). In the present review of ketamine as an emerging novel pharmacotherapeutic intervention for chronic PTSD, we discuss findings from the first proof-of-concept, randomized clinical trial (RCT) of single-dose intravenous ketamine in patients with chronic PTSD, as well as open-label studies and current practice. We introduce ongoing RCTs investigating the efficacy of repeated ketamine infusions in rapidly reducing symptoms and maintaining improvement in samples of individuals with PTSD stemming from civilian and military traumas. Additionally, we discuss mixed findings from published reports on ketamine administration in the acute aftermath of trauma. Studies in animal models of chronic stress have investigated molecular mechanisms underlying ketamine's effects, generating a shift in the conceptualization of PTSD as a disorder of impaired neural connectivity. We review animal studies examining the potential of ketamine to modify the expression of fear by altering memory reconsolidation or enhancing fear extinction, as well as others investigating ketamine administration prophylactically prior to stress exposure. We introduce the need for additional study in humans to evaluate whether ketamine might enhance the efficacy of psychotherapeutic interventions in individuals with chronic PTSD, harnessing a window of ketamine-induced neuroplasticity. While research on ketamine for PTSD is still in its early stages, it brings about the promise of novel and more effective treatments for this disabling condition.

Background We investigated trans-generational associations between Post Traumatic Stress Disorder (PTSD) symptoms in World Trade Center (WTC) responders and behavioral problems in their children. Methods Participants were WTC responders-8034 police and 8352 non-traditional (eg, construction workers)-with one or more children at the time of their first visit to the World Trade Center Health Program (WTC-HP). Self-report questionnaires were administered approximately 4 years after the 9/11 WTC attack. Results A total of 31.4% of non-traditional and 20.0% of police responders reported behavioral problems in their children. Non-traditional responder status, female sex, Hispanic ethnicity, more life stressors, more WTC-related PTSD symptoms, and dysphoric arousal symptoms were significant correlates of behavioral problems in responders' children. Conclusions Specific parental sociodemographic, psychosocial and clinical characteristics, as well as PTSD symptom severity, were significant correlates of child behavior problems. Findings encourage monitoring and early intervention for children of disaster responders, particularly those at highest risk.

Background: Nearly two decades following the 9/11/2001 world trade center (WTC) attacks, a substantial proportion of WTC rescue and recovery workers (“responders”) and WTC survivors continue to experience WTC-related posttraumatic stress disorder (PTSD) symptoms. Internet-based cognitive behavioral therapies (I-CBT) are short-term, evidence-based, scalable treatments with the potential to reach large numbers of symptomatic WTC workers and survivors. However, no I-CBT studies have been conducted in the WTC cohort.Methods: This report describes the rationale and design of an ongoing randomized controlled trial comparing integrative testimonial therapy (ITT), an I-CBT, to an active comparison treatment, internet-based modified present-centered therapy. The primary aim is to evaluate the efficacy of ITT in mitigating WTC-related PTSD symptoms in WTC responders and survivors with full or subthreshold WTC-related PTSD. The efficacy of ITT in reducing comorbid depressive and anxiety symptoms, and improving functioning, quality of life, and post-traumatic growth will additionally be evaluated. Saliva samples are also collected to explore genetic and epigenetic biomarkers of treatment response.Conclusions: This is the first I-CBT trial to compare ITT to a credible and active treatment, controlling for critical third-variable explanations of superiority (e.g., non-specific therapy effects). This RCT bridges an important research gap in the rising field of I-CBT interventions and adds to the literature on the design of trials investigating evidence-based treatments for PTSD in WTC- and other trauma-affected populations. Trial registration: This trial was registered on clinicalTrials.gov on May 16, 2017 (NCT03154151).

Background Anxiety and trauma-related disorders are among the most prevalent and disabling medical conditions in the United States, and posttraumatic stress disorder in particular exacts a tremendous public health toll. We examined the tolerability and anxiolytic efficacy of neuropeptide Y administered via an intranasal route in patients with posttraumatic stress disorder. Methods Twenty-six individuals were randomized in a cross-over, single ascending dose study into 1 of 5 cohorts: 1.4 mg (n=3), 2.8 mg (n=6), 4.6 mg (n=5), 6.8 mg (n=6), and 9.6 mg (n=6). Each individual was dosed with neuropeptide Y or placebo on separate treatment days 1 week apart in random order under double-blind conditions. Assessments were conducted at baseline and following a trauma script symptom provocation procedure subsequent to dosing. Occurrence of adverse events represented the primary tolerability outcome. The difference between treatment conditions on anxiety as measured by the Beck Anxiety Inventory and the State-Trait Anxiety Inventory immediately following the trauma script represented efficacy outcomes. Results Twenty-four individuals completed both treatment days. Neuropeptide Y was well tolerated up to and including the highest dose. There was a significant interaction between treatment and dose; higher doses of neuropeptide Y were associated with a greater treatment effect, favoring neuropeptide Y over placebo on Beck Anxiety Inventory score (F1,20=4.95, P=.038). There was no significant interaction for State-Trait Anxiety Inventory score. Conclusions Our study suggests that a single dose of neuropeptide Y is well tolerated up to 9.6 mg and may be associated with anxiolytic effects. Future studies exploring the safety and efficacy of neuropeptide Y in stress-related disorders are warranted. The reported study is registered at: http://clinicaltrials.gov (ID: NCT01533519)., Significance StatementAnxiety and trauma-related disorders are among the most prevalent medical conditions in the United States. Posttraumatic stress disorder (PTSD) in particular is a debilitating disorder that develops in a subset of individuals exposed to extreme stress. Drug discovery for PTSD and anxiety disorders has been largely stagnant, contributing to a substantial disease burden and continued patient suffering. A large body of evidence implicates neuropeptide Y (NPY) in the regulation of stress-related behaviors, and preclinical data suggest that enhancing NPY signaling may reduce anxiety and symptoms of PTSD. Herein, we conducted phase Ib double-blind, randomized, placebo-controlled, dose-ranging study of intranasal administration of NPY in subjects with PTSD. We found that NPY was well tolerated at all tested doses and that high, but not low, doses of NPY were associated with reduced anxiety on some measures. The NPY system may represent a promising target for treatment development for anxiety and trauma-related disorders.

Resilience, or the phenomenon of successful adaptation following significant trauma exposure, is a complex, multidimensional, and dynamic process. To date, research on neural mechanisms involved in human resilience has comprised of two major research streams – involving individuals with childhood and adulthood trauma exposure, respectively. Although there are systematic differences in how both trauma and resilience have been defined across these two bodies of research, some striking regions of convergence emerge when considering the literature as a whole. Here, we review functional imaging studies from across these two research streams, alongside discussion of some of the methodological difficulties involved in quantifying both trauma and resilience in human participants. Due to the broad scope of this literature, we restrict the scope of our narrative to several key domains where studies from across these two bodies of work implicate common neural circuitry. These areas of convergence include brain networks implicated in emotion regulation, responses to rewards, and cognitive control. Further, we briefly review functional imaging evidence related to proposed mechanisms underlying resilient outcomes: namely active coping, cognitive reappraisal and successful fear extinction. Finally, we also touch upon several ongoing issues in neuroimaging study design and analysis that will need to be addressed in order to enable us to harness insight from such studies to improve treatments for – or, ideally, guard against the development of – debilitating post-traumatic stress syndromes.

Objective To characterize the prevalence, risk and protective correlates, and clinical characteristics associated with probable subthreshold posttraumatic stress disorder (PTSD) in police and nontraditional (eg, construction workers) World Trade Center (WTC) responders a median of 12.2 years after September 11, 2001. Methods A total of 4,196 WTC responders, monitored via the WTC Health Program, completed a web-based survey between 2012 and 2014 assessing a range of variables, including demographics, WTC exposures, medical and psychiatric comorbidities, and mental health services use. The sample included 2,029 police responders and 2,167 nontraditional responders. Current (past-month) probable WTC-related PTSD level (none, subthreshold, or full PTSD) was assessed based on DSM-IV criteria using the PTSD Checklist-Specific Stressor version (PCL-S). Results The prevalence of current probable full and subthreshold WTC-related PTSD in police responders was 9.3% and 17.5%, respectively, and in nontraditional responders was 21.9% and 24.1%, respectively. Risk and protective correlates for subthreshold PTSD included post-9/11 medical comorbidities and traumatic events (odds ratios [ORs] = 1.1-1.2). Clinical characteristics included elevated rates of comorbid depression (OR = 3.2 and 3.9 for subthreshold PTSD and 17.2 and 30.3 for full PTSD for nontraditional and police responders, respectively). Among responders with subthreshold PTSD, police were more likely to have accessed mental health services and utilized a greater variety of treatments than nontraditional responders. Conclusions Overall, 26.8% of police and 46.0% of nontraditional responders met criteria for probable WTC-related full or subthreshold PTSD an average of 12 years after 9/11. Probable subthreshold PTSD, which is not typically assessed in clinical settings, was more prevalent than probable full PTSD and was associated with significantly elevated rates of psychiatric comorbidities, functional impairment, and reduced quality of life. These findings underscore the importance of assessing, monitoring, and possibly treating subthreshold PTSD in WTC and other disaster responders.

Recent scientific and technological advances have brought us closer to being able to apply a true biopsychosocial approach to the study of resilience in humans. Decades of research have identified a range of psychosocial protective factors in the face of stress and trauma. Progress in resilience research is now advancing our understanding of the biology underlying these protective factors at multiple phenotypic levels, including stress response systems, neural circuitry function, and immune responses, in interaction with genetic factors. It is becoming clear that resilience involves active and unique biological processes that buffer the organism against the impact of stress, not simply involve a reversal of pathological mechanisms. Here, we provide an overview of recent progress in the field, highlighting key psychosocial milestones and accompanying biological changes during development, and into adulthood and old age. Continued advances in our understanding of psychological, social, and biological determinants of resilience will contribute to the development of novel interventions and help optimize the type and timing of intervention for those most at risk, resulting in a possible new framework for enhancing resilience across the life span.

The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine is associated with rapid but transient antidepressant effects in patients with treatment resistant unipolar depression (TRD). Based on work suggesting that ketamine and lithium may share overlapping mechanisms of action, we tested lithium compared to placebo as a continuation strategy following ketamine in subjects with TRD. Participants who met all eligibility criteria and showed at least an initial partial response to a single intravenous infusion of ketamine 0.5 mg/kg were randomized under double-blind conditions to lithium or matching placebo before receiving an additional three infusions of ketamine. Subsequent to the ketamine treatments, participants remained on lithium or placebo during a double-blind continuation phase. The primary study outcome was depression severity as measured by the Montgomery–Åsberg Depression Rating Scale compared between the two groups at Study Day 28, which occurred ~2 weeks following the final ketamine of four infusions. Forty-seven participants with TRD were enrolled in the study and underwent an initial ketamine infusion, of whom 34 participants were deemed to have at least a partial antidepressant response and were eligible for randomization. Comparison between treatment with daily oral lithium (n = 18) or matching placebo (n = 16) at the primary outcome showed no difference in depression severity between groups (t(32) = 0.11, p = 0.91, 95% CI [−7.87, 8.76]). There was no difference between lithium and placebo in continuing the acute antidepressant response to ketamine. The identification of a safe and effective strategy for preventing depression relapse following an acute course of ketamine treatment remains an important goal for future studies.

Background This study sought to assess the magnitude of and factors associated with mental health outcomes among frontline health care workers (FHCWs) providing care during the Spring 2020 COVID-19 pandemic surge in New York City. Methods A cross-sectional, survey-based study over 4 weeks during the Spring 2020 pandemic surge was used to assess symptoms of COVID-19-related posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD) in 2,579 FHCWs at the Mount Sinai Hospital. Participants were additionally asked about their occupational and personal exposures to COVID-19. Multivariable logistic regression and relative importance analyses were conducted to identify factors associated with these outcomes. Results A total of 3,360 of 6,026 individuals completed the survey (55.8% participation), with 2,579 (76.8%) analyzed based on endorsing frontline responsibilities and providing information related to the three outcomes. 1,005 (39.0%) met criteria for symptoms of COVID-19-related PTSD, MDD, or GAD. 599 (23.3%) screened positively for PTSD symptoms, 683 (26.6%) for MDD symptoms, and 642 (25.0%) for GAD symptoms. Multivariable analyses revealed that past-year burnout was associated with the highest risk of developing symptoms for COVID-19-related PTSD (odds ratio [OR] = 2.10), MDD (OR = 2.83), and GAD (OR = 2.68). Higher perceived support from hospital leadership was associated with a lowest risk of all outcomes [PTSD (OR = 0.75), MDD (OR = 0.72), and GAD (OR = 0.76). Conclusion In this large sample of FHCWs providing care during the 2020 NYC pandemic surge, 39% experienced symptoms of COVID-19-related PTSD, MDD, and/or GAD and pre-pandemic burnout as well as leadership support were identified as the most highly associated factors. These findings suggest that interventions aimed at reducing burnout and augmenting support from hospital leadership may be appropriate targets to mitigate the risk for developing further psychopathology in this population and others working in the midst of crisis.