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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.

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.

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.

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.

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.

Importance Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition. Objective To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associated depressive symptoms in patients with chronic PTSD. Design, Setting, and Participants Proof-of-concept, randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, conducted at a single site (Icahn School of Medicine at Mount Sinai, New York, New York). Forty-one patients with chronic PTSD related to a range of trauma exposures were recruited via advertisements. Interventions Intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and midazolam (0.045 mg/kg). Main Outcomes and Measures The primary outcome measure was change in PTSD symptom severity, measured using the Impact of Event Scale–Revised. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression–Severity and –Improvement scales, and adverse effect measures, including the Clinician-Administered Dissociative States Scale, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale. Results Ketamine infusion was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale–Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms. Conclusions and Relevance This study provides the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with this disabling condition. Trial Registration clinicaltrials.gov Identifier:NCT00749203

The N-methyl-D-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression. The current study was designed to test the safety, tolerability, and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial.In a randomized, double-blind, crossover study, 20 patients with major depression were randomly assigned, and 18 completed 2 treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution. The primary efficacy outcome measure was change in depression severity 24 hours after ketamine or placebo, measured using the Montgomery-Åsberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured.Patients showed significant improvement in depressive symptoms at 24 hours after ketamine compared to placebo (t = 4.39, p.001; estimated mean Montgomery-Åsberg Depression Rating Scale score difference of 7.6 ± 3.7; 95% confidence interval, 3.9-11.3). Response criteria were met by 8 of 18 patients (44%) 24 hours after ketamine administration compared with 1 of 18 (6%) after placebo (p = .033). Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters.This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression.

Every individual experiences stressful life events. In some cases acute or chronic stress leads to depression and other psychiatric disorders, but most people are resilient to such effects. Recent research has begun to identify the environmental, genetic, epigenetic and neural mechanisms that underlie resilience, and has shown that resilience is mediated by adaptive changes in several neural circuits involving numerous neurotransmitter and molecular pathways. These changes shape the functioning of the neural circuits that regulate reward, fear, emotion reactivity and social behaviour, which together are thought to mediate successful coping with stress.

Background—Although several studies have documented a higher prevalence of psychiatric disorders in children of depressed than nondepressed parents, previous research was conducted in predominantly White, middle, or upper-middle class populations. Only limited information is available on psychiatric disorders and psychosocial functioning in children of low-income depressed mothers. Methods—We report the findings in children of mothers with and without a lifetime history of major depressive disorder, who were recruited from a large urban primary-care practice. Bilingual clinical interviewers assessed 58 children with structured diagnostic interviews administered to most children (90%) and to their mothers as informants. Diagnostic assessments and best estimate diagnoses of the children were blind to the mothers’ diagnostic status. Results—The families were poor and predominantly Hispanic, more than half of them headed by single mothers. After adjusting for child age and gender, and for any possible sibling correlation, children of depressed mothers had significantly higher rates of lifetime depressive, separation anxiety, oppositional defiant, and any psychiatric disorders than children of control mothers, with a lifetime prevalence of any psychiatric disorder of 84.6 versus 50.0%, respectively. Children of depressed mothers also reported significantly lower psychosocial functioning and had higher rates of psychiatric treatment. Conclusions—We conclude that the risk for psychiatric disorders may be particularly high in children of low-income depressed mothers. The primary-care setting offers a unique opportunity for early intervention with this underserved group.

The purpose of this study was to ascertain whether panic disorder (PD) and suicidal ideation are associated in an inner-city primary care clinic and whether this association remains significant after controlling for commonly co-occurring psychiatric disorders. We surveyed 2,043 patients attending a primary care clinic using the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire, a screening instrument that yields provisional diagnoses of selected psychiatric disorders. We estimated the prevalence of current suicidal ideation and of common psychiatric disorders including panic disorder and major depression. A provisional diagnosis of current PD was received by 127 patients (6.2%). After adjusting for potential confounders (age, gender, major depressive disorder [MDD], generalized anxiety disorder, and substance use disorders), patients with PD were about twice as likely to present with current suicidal ideation, as compared to those without PD (adjusted odds ratio [AOR] = 1.84; 95% confidence interval [CI]: 1.06-3.18; P = .03). After adjusting for PD and the above-mentioned potential confounders, patients with MDD had a sevenfold increase in the odds of suicidal ideation, as compared to those without MDD (AOR = 7.00; 95% CI: 4.42-11.08; P < .0001). Primary care patients with PD are at high risk for suicidal ideation, and patients with PD and co-occurring MDD are at especially high risk. PD patients in primary care thus should be assessed routinely for suicidal ideation and depression.

Objective To screen for posttraumatic stress disorder (PTSD) in primary care patients 7–16 months after 9/11 attacks and to examine its comorbidity, clinical presentation and relationships with mental health treatment and service utilization. Method A systematic sample (n=930) of adult primary care patients who were seeking primary care at an urban general medicine clinic were interviewed using the PTSD Checklist: the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire and the Medical Outcome Study 12-Item Short Form Health Survey (SF-12). Health care utilization data were obtained by a cross linkage to the administrative computerized database. Results Prevalence estimates of current 9/11-related probable PTSD ranged from 4.7% (based on a cutoff PCL-C score of 50 and over) to 10.2% (based on the DSM-IV criteria). A comorbid mental disorder was more common among patients with PTSD than patients without PTSD (80% vs. 30%). Patients with PTSD were more functionally impaired and reported increased use of mental health medication as compared to patients without PTSD (70% vs. 18%). Among patients with PTSD there was no increase in hospital and emergency room (ER) admissions or outpatient care during the first year after the attacks. Conclusions In an urban general medicine setting, 1 year after 9/11, the frequency of probable PTSD appears to be common and clinically significant. These results suggest an unmet need for mental health care in this clinical population and are especially important in view of available treatments for PTSD.

Childhood trauma (CT) is associated with mood and anxiety disorders in adulthood, especially with posttraumatic stress disorder (PTSD). These disorders frequently co-occur, yet few PTSD comorbidity studies have focused on samples with a range of CT severity and none have included participants with adulthood-only trauma in the same study. We investigated SCID diagnoses of comorbid mood and anxiety disorders among 69 adult PTSD patients (M age = 37.94, SD=11.13; 53.6% female), with CT exposures (CTQ scores) ranging from absent to extreme. The CAPS and QIDS-SR measured PTSD and depression severity, respectively. Total CT exposure correlated with having at least one comorbid anxiety disorder diagnosis (r pb=.42, p