Chronic Stress最新文献

Posttraumatic stress disorder is common among military Veterans. While effective treatments exist, many Veterans either do not engage in treatment or fail to achieve full remission. Thus, there is a need to develop adjunctive complementary interventions to enhance treatment engagement and/or response. Equine-assisted activities and therapies (EAAT) are one category of animal assisted interventions that might serve this function. The aim of this article is to review the current state and challenges regarding the use of EAAT for Veterans with PTSD and provide a roadmap to move the field forward. EAAT hold promise as adjunctive complementary interventions for symptom reduction among Veterans with PTSD. Additionally, there is evidence that these approaches may enhance wellbeing in this population. At this time, many gaps in the literature exist and rigorous randomized controlled trials are needed before definitive conclusions can be drawn. The authors of this work provide recommendations as a roadmap to move the field forward. These include standardizing the EAAT nomenclature, focusing mechanism of action studies on the human-horse bond using biological metrics and using a standardized intervention model across studies.

Background: The α₁-adrenoreceptor antagonist prazosin has in many but not all studies been found to be effective for PTSD associated nightmares, hyperarousal symptoms, and total symptom severity. The particular efficacy of prazosin for nightmares and hyperarousal symptoms suggests there may be a subset of PTSD symptoms that are more tightly associated with an α₁-adrenoreceptor mediated noradrenergic mechanism, but cross traditional diagnostic symptom clusters. However, the efficacy of prazosin for individual symptoms other than nightmares and sleep disruption has not previously been examined.

Methods: In a post hoc reanalysis of a previously published, randomized controlled trial of twice daily prazosin for PTSD, we examined the relative effect of prazosin on individual items of the CAPS for DSM-IV, and tested whether prazosin responsiveness predicted the partial correlation of the changes in symptom intensity at the level of individual subjects. Results were not adjusted for multiple comparisons.

Results: Prazosin showed the largest effect for distressing dreams, anhedonia, difficulty falling or staying asleep, difficulty concentrating, and hypervigilance. These items were also (a) of higher baseline severity in the underlying population, and (b) more related in how they fluctuated at the level of individual subjects. Covariance analysis did not support a clear cutoff between highly prazosin responsive items and those showing a smaller, not statistically significant response.

Conclusions: In this data set, twice daily prazosin substantially reduced not only nightmares and sleep disruption, but the majority of hyperarousal symptoms, with some evidence of efficacy for avoidance symptoms. The relationship of baseline symptom distribution to which symptoms showed significant response to prazosin reinforces the possibility that differences in a clinical trial's participant populations may significantly influence trial outcome. The pattern of symptom endorsement at the level of individual subjects was consistent with prazosin-responsive items sharing a common pathophysiologic mechanism.

Rodent models are an invaluable tool for studying the pathophysiological mechanisms underlying stress and depressive disorders. However, the widely used behavioral assays to measure depressive-like states in rodents have serious limitations. In this commentary, we suggest that learning tasks, particularly those that can be analyzed with the framework of reinforcement learning, are ideal for assaying reward processing deficits relevant to depression. The key advantages of these tasks are their repeatable, quantifiable nature and the link to clinical studies. By optimizing the behavioral readout of stress-induced phenotypes in rodents, a reinforcement learning-based approach may help bridge the translational gap and advance antidepressant discovery.

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.

Background: Major depressive disorder (MDD) treatment is characterized by low remission rate and often involves weeks to months of treatment. Identification of pretreatment biomarkers of response may play a critical role in novel drug development, in enhanced prognostic predictions, and perhaps in providing more personalized medicine. Using a network restricted strength predictive modeling (NRS-PM) approach, the goal of the current study was to identify pretreatment functional connectome fingerprints (CFPs) that (1) predict symptom improvement regardless of treatment modality and (2) predict treatment specific improvement.

Methods: Functional magnetic resonance imaging and behavioral data from unmedicated patients with MDD (n = 200) were investigated. Participants were randomized to daily treatment of sertraline or placebo for 8 weeks. NRS-PM with 1000 iterations of 10 cross-validation were implemented to identify brain connectivity signatures that predict percent improvement in depression severity at week-8.

Results: The study identified a pretreatment CFP that significantly predicts symptom improvement independent of treatment modality but failed to identify a treatment specific CFP. Regardless of treatment modality, improved antidepressant response was predicted by high pretreatment connectivity between modules in the default mode network and the rest of the brain, but low external connectivity in the executive network. Moreover, high pretreatment internal nodal connectivity in the bilateral caudate predicted better response.

Conclusions: The identified CFP may contribute to drug development and ultimately to enhanced prognostic predictions. However, the results do not assist with providing personalized medicine, as pretreatment functional connectivity failed to predict treatment specific response.

Background: Ketamine is a novel fast-acting antidepressant. Acute ketamine treatment can reverse microstructure deficits and normalize functional alterations in the brain, but little is known about the impacts of ketamine on brain volumes in individuals with depression.

Methods: We used 3 T magnetic resonance imaging (MRI) and tensorbased morphological methods to investigate the regional volume differences for 29 healthy control (HC) subjects and 21 subjects with major depressive disorder (MDD), including 10 subjects with comorbid post-traumatic stress disorder (PTSD). All the subjects participated in MRI scanning before and 24 h post intravenous ketamine infusion. The effects of acute ketamine administration on HC, MDD, and MDD/PTSD groups were examined separately by whole-brain voxel-wise t-tests.

Results: Our data showed smaller volume of inferior frontal gyrus (IFG, opercular part) in MDD and MDD/PTSD subjects compared to HC, and a significant correlation between opercular IFG volume and depressive severity in MDD subjects only. Ketamine administration normalized the structural alterations of opercular IFG in both MDD and MDD/PTSD groups, and significantly improved depressive and PTSD symptoms. Twenty-four hours after a single ketamine infusion, there were two clusters of voxels with volume changes in MDD subjects, including significantly increased volumes of opercular IFG. No significant structural alterations were found in the MDD/PTSD or HC groups.

Conclusion: These findings provide direct evidence that acute ketamine administration can normalize structural alterations associated with depression and highlight the importance of IFG in the guidance of future therapeutic targets.

Objective: To date, treatment options (i.e. psychotherapy, antidepressant medications) for patients with posttraumatic stress disorder (PTSD), are relatively few, and considering their limited efficacy, novel therapies have gained interest among researchers and treatment providers alike. Among patients with chronic pain (CP) about one third experience comorbid PTSD, which further complicates their already challenging pharmacological regimens. Low dose ketamine infusion has shown promise in PTSD, and in treatment of CP, however they have not been studied in comorbid population and under rigorous control conditions.

Methods: We compared the effects of a single dose of either ketamine (0.5 mg/kg) or ketorolac (15 mg) over a 40-minute of IV infusion in CP patients with and without PTSD, in double blind, randomized study. Measures were collected before, during, one day and seven days after the infusion. A planned sample size of 40 patients randomly assigned to treatment order was estimated to provide 80% power to detect a hypothesized treatment difference after the infusion.Main Outcome and Measures: The primary outcome measures were change in PTSD symptom severity assessed with the Impact of Event Scale-Revised (IES-R) and Visual Analogue Scale (VAS) for pain administered by a study clinician 24 hours post infusion. Secondary outcome measures included Impact of Event Scale-Revised (IES-R), VAS and Brief Pain Inventory (Short Form) for pain 1 week after the infusion.

Results: Both treatments offered comparable improvement of PTSD and CP symptoms that persisted for 7 days after the infusion. Patients with comorbid PTSD and CP experienced less dissociative side effects compared to the CP group. Surprisingly, ketorolac infusion resulted in dissociative symptoms in CP patients only.

Conclusions: This first prospective study comparing effects of subanesthetic ketamine versus ketorolac infusions for comorbid PTSD and CP, suggests that both ketamine and ketorolac might offer meaningful and durable response for both PTSD and CP symptoms.

Objective: The relationship between psychosocial stress and chronic pain is bidirectional. An improved understanding regarding the relationships among chronic pain, life stress, and ethnicity/race will inform identification of factors contributing to health disparities in chronic pain and improve health outcomes. This study aims to assess relationships between measures of clinical pain, life stress, sociodemographics, and salivary cortisol levels.

Methods: A cross-sectional analysis involving data from 105 non-Hispanic White (NHW) and non-Hispanic Black (NHB) participants aged 45-85 years old with or at risk for knee osteoarthritis. Data included sociodemographics, clinical pain, psychosocial stress, and salivary cortisol across five time points over an approximate 12-hour period. Non-parametric correlation analysis, sociodemographic group comparisons, and regression analyses were performed.

Results: Clinical pain and psychosocial stress were associated with salivary cortisol levels, particularly morning waking and the evening to morning awakening slope. With the inclusion of recognized explanatory variables, the Graded Chronic Pain Scale characteristic pain intensity and financial satisfaction were identified as the primary pain and psychosocial measures associated with cortisol levels. Sociodemographic group differences were indicated such that NHB participants reported higher pain-related disability, higher levels of discrimination, lower financial and material satisfaction, and showed higher evening salivary cortisol levels compared to NHW participants. In combined pain and psychosocial stress analyses, greater financial satisfaction, lower pain intensity, and lower depression were associated with higher morning waking saliva cortisol levels while greater financial satisfaction was the only variable associated with greater evening to morning awakening slope.

Conclusion: Our findings show relationships among clinical pain, psychosocial stress, sociodemographic factors, and salivary cortisol levels. Importantly, with inclusion of recognized explanatory variables, financial satisfaction remained the primary factor accounting for differences in morning waking cortisol and evening to morning awakening cortisol slope in an ethnic/racially diverse group of middle aged and older adults with or at risk for knee osteoarthritis.