Translational approaches to the neurobiological study of conditional discrimination and inhibition: Implications for psychiatric disease.

There is a growing number of studies investigating discriminatory fear conditioning and conditioned inhibition of fear to assess safety learning, in addition to extinction of cued fear. Despite all of these paradigms resulting in a reduction in fear expression, there are nuanced differences among them, which could be mediated through distinct behavioral and neural mechanisms. These differences could impact how we approach potential treatment options in clinical disorders with dysregulated fear responses. The objective of this review is to give an overview of the conditional discrimination and inhibition findings reported in both animal models and human neuropsychiatric disorders. Both behavioral and neural findings are reviewed among human and rodent studies that include conditional fear discrimination via conditional stimuli with and without reinforcement (CS+ vs. CS-, respectively) and/or conditional inhibition of fear through assessment of the fear response to a compound CS-/CS+ cue versus CS+. There are several parallels across species in behavioral fear expression as well as neural circuits promoting fear reduction in response to a CS- and/or CS-/CS+ compound cue. Continued and increased efforts to compare similar behavioral fear inhibition paradigms across species are needed to make breakthrough advances in our understanding and treatment approaches to individuals with fear disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Childhood Maltreatment and Amygdala-Mediated Anxiety and Posttraumatic Stress Following Adult Trauma.

Background: Childhood abuse (physical, emotional, and sexual) is associated with aberrant connectivity of the amygdala, a key threat-processing region. Heightened amygdala activity also predicts adult anxiety and posttraumatic stress disorder (PTSD) symptoms, as do experiences of childhood abuse. The current study explored whether amygdala resting-state functional connectivity may explain the relationship between childhood abuse and anxiety and PTSD symptoms following trauma exposure in adults. Methods: Two weeks posttrauma, adult trauma survivors (n = 152, mean age [SD] = 32.61 [10.35] years; women = 57.2%) completed the Childhood Trauma Questionnaire and underwent resting-state functional magnetic resonance imaging. PTSD and anxiety symptoms were assessed 6 months posttrauma. Seed-to-voxel analyses evaluated the association between childhood abuse and amygdala resting-state functional connectivity. A mediation model evaluated the potential mediating role of amygdala connectivity in the relationship between childhood abuse and posttrauma anxiety and PTSD. Results: Childhood abuse was associated with increased amygdala connectivity with the precuneus while covarying for age, gender, childhood neglect, and baseline PTSD symptoms. Amygdala-precuneus resting-state functional connectivity was a significant mediator of the effect of childhood abuse on anxiety symptoms 6 months posttrauma (B = 0.065; 95% CI, 0.013-0.130; SE = 0.030), but not PTSD. A secondary mediation analysis investigating depression as an outcome was not significant. Conclusions: Amygdala-precuneus connectivity may be an underlying neural mechanism by which childhood abuse increases risk for anxiety following adult trauma. Specifically, this heightened connectivity may reflect attentional vigilance for threat or a tendency toward negative self-referential thoughts. Findings suggest that childhood abuse may contribute to longstanding upregulation of attentional vigilance circuits, which makes one vulnerable to anxiety-related symptoms in adulthood.

Experiences of childhood abuse are related to long-term mental health outcomes, but the mechanisms of this relationship have been unclear. In this study of adult trauma survivors, Harb et al. found that experiences of childhood abuse are related to abnormal connectivity patterns of the amygdala, a key region for fear and threat processing, and precuneus. These connectivity patterns were identified as a mechanism through which experiences of child abuse are related to adult anxiety symptoms posttrauma. These findings advance our understanding of the specific downstream impacts of experiencing childhood abuse and can inform targeted assessment and intervention methods, especially in an adult trauma sample.

Intrusive Traumatic Re-Experiencing Domain: Functional Connectivity Feature Classification by the ENIGMA PTSD Consortium.

Background: Intrusive traumatic re-experiencing domain (ITRED) was recently introduced as a novel perspective on posttraumatic psychopathology, proposing to focus research of posttraumatic stress disorder (PTSD) on the unique symptoms of intrusive and involuntary re-experiencing of the trauma, namely, intrusive memories, nightmares, and flashbacks. The aim of the present study was to explore ITRED from a neural network connectivity perspective. Methods: Data were collected from 9 sites taking part in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) PTSD Consortium (n= 584) and included itemized PTSD symptom scores and resting-state functional connectivity (rsFC) data. We assessed the utility of rsFC in classifying PTSD, ITRED-only (no PTSD diagnosis), and trauma-exposed (TE)-only (no PTSD or ITRED) groups using a machine learning approach, examining well-known networks implicated in PTSD. A random forest classification model was built on a training set using cross-validation, and the averaged cross-validation model performance for classification was evaluated using the area under the curve. The model was tested using a fully independent portion of the data (test dataset), and the test area under the curve was evaluated. Results: rsFC signatures differentiated TE-only participants from PTSD and ITRED-only participants at about 60% accuracy. Conversely, rsFC signatures did not differentiate PTSD from ITRED-only individuals (45% accuracy). Common features differentiating TE-only participants from PTSD and ITRED-only participants mainly involved default mode network-related pathways. Some unique features, such as connectivity within the frontoparietal network, differentiated TE-only participants from one group (PTSD or ITRED-only) but to a lesser extent from the other group. Conclusions: Neural network connectivity supports ITRED as a novel neurobiologically based approach to classifying posttrauma psychopathology.

The Dichotomy of Threat and Deprivation as Subtypes of Childhood Maltreatment: Differential Functional Connectivity Patterns of Threat and Reward Circuits in an Adult Trauma Sample.

BACKGROUND: Childhood maltreatment is associated with reduced activation of the nucleus accumbens, a central region in the reward network, and overactivity in the amygdala, a key region in threat processing. However, the long-lasting impact of these associations in the context of later-life stress is not well understood. The current study explored the association between childhood threat and deprivation and functional connectivity of threat and reward regions in an adult trauma sample. METHODS: Trauma survivors (N = 169; mean age [SD] = 32.2 [10.3] years; female = 55.6%) were recruited from a level I trauma center. Two weeks after injury, participants completed the Childhood Trauma Questionnaire (measuring experiences of threat and deprivation) and underwent resting-state functional magnetic resonance imaging. Seed-to-voxel analyses evaluated the effect of childhood threat and deprivation on amygdala and nucleus accumbens resting-state connectivity. RESULTS: Higher levels of threat were associated with increased connectivity between the right nucleus accumbens with temporal fusiform gyrus/parahippocampal gyrus and the left amygdala and the precuneus (false discovery rate-corrected p < .05). After controlling for posttraumatic symptoms 2 weeks posttrauma and lifetime trauma exposure, only the nucleus accumbens findings survived. There were no significant relationships between experiences of childhood deprivation and amygdala or nucleus accumbens connectivity. CONCLUSIONS: Experiences of threat are associated with increased nucleus accumbens and amygdala connectivity, which may reflect a preparedness to detect salient and visual stimuli. This may also reflect a propensity toward dysregulated reward processing. Overall, these results suggest that childhood threat may be contributing to aberrant neural baseline reward and threat sensitivity later in life in an adult trauma sample.

Endocannabinoids, cortisol, and development of post-traumatic psychopathological trajectories.

OBJECTIVE: Our prior published work using the 2-factor model of PTSD identified four subgroups of trauma survivors on average 6 months following trauma: Resilient, Dysphoria, High Comorbid, and Severe Comorbid. Some findings indicate that low and high cortisol responses may increase risk for the development of PTSD and depression respectively, yet ways in which cortisol interacts with other physiological systems to enhance risk is unclear. This study examined the role of circulating eCBs in the development of previously identified psychopathological trajectories that is differentiated by cortisol in traumatically injured adults (N = 169). METHODS: Circulating concentrations of eCBs, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA) were measured during post-injury hospitalization and on average 6 months following trauma. Differences in 2-AG and AEA among the subgroups were tested using multivariate ANCOVA. RESULTS: Dysphoria (with highest cortisol levels) and High Comorbid subgroups exhibited higher post-injury AEA compared to the Resilient group. Dysphoria subgroup showed a significant decline in AEA by 6 months compared to Resilient and High Comorbid subgroups. CONCLUSION: Change in AEA over time in individuals with high post-injury cortisol may serve as a buffer against risk for severe psychopathology. Assessing AEA and cortisol levels concurrently across time may serve as indicators of risk.

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium.

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Relationship between heart rate variability and differential patterns of cortisol response to acute stressors in mid-life adults: A data-driven investigation.

Cortisol and heart rate variability (HRV) are well-established biomarkers of the human stress response system. While a relationship between cortisol and HRV is assumed, few studies have found evidence of their correlation within single study designs. One complication for isolating such a relationship may lie in individual variability in the cortisol response to stress such that atypical cortisol responding (i.e., elevated or blunted) occurs. To-date, studies on the cortisol response have employed traditional mean-difference-based approaches to examine average magnitude change in cortisol over time. Alternatively, data-driven trajectory modelling, such as latent growth mixture modelling, may be advantageous for quantifying cortisol based on patterns of response over time. Latent growth mixture modelling was used in N = 386 adults to identify subgroups based on trajectories of cortisol responses to stress. The relationship between cortisol and HRV was tested within subgroups. Results revealed a 'prototypical' subgroup characterised by expected rise and fall in cortisol response to stress (n = 309), a 'decline' subgroup (n = 28) that declined in cortisol after stress, and a 'rise' subgroup (n = 49) that increased in cortisol after stress. Within the 'prototypical' subgroup, greater HRV during stress was associated with decline in cortisol after stress from its maximum (r (306) = 0.19, p < 0.001). This relationship failed to emerge in the 'decline' and 'rise' subgroups (p > 0.271). Results document different patterns of cortisol response to stress; among those who exhibit a 'prototypical' response, changes in HRV during stress are related to changes in cortisol after stress.

Neural processes of emotional conflict detection and prediction of posttraumatic stress disorder symptom clusters in traumatic injury survivors.

OBJECTIVE: Given the prevalence and significant burden of posttraumatic stress disorder (PTSD), identifying early predictors of symptom development following trauma is critical. PTSD is a heterogeneous disorder comprised of distinct symptom clusters-reexperiencing, avoidance, negative mood, and hyperarousal-that contribute to the broad range of possible symptom profiles. Affective and attentional regulation processes, such as emotional conflict detection, are impaired in individuals with PTSD; however, the neural mechanisms underlying these alterations and their predictive utility for the development of PTSD symptoms remain unclear. METHOD: Traumatic injury survivors (N = 49) without traumatic brain injury were recruited from the emergency department of an urban, Level-1 trauma center. Within 1 month of trauma exposure, participants completed a well-characterized emotional conflict task during a functional magnetic resonance imaging scan. Participants returned 6-month later for a clinical assessment of PTSD symptoms. Using a region-of-interest mask derived from whole-brain voxelwise analyses during emotional conflict detection (vs. no emotional conflict detection) we examined whether differential neural activity predicted 6-month PTSD symptom cluster severity. RESULTS: Greater activation of the right middle frontal gyrus during emotional conflict detection prospectively predicted lower PTSD avoidance symptom severity 6 months later (above and beyond the effects of self-reported baseline PTSD and depressive symptoms, previous traumatic life events, racial discrimination, age, sex, and injury severity). CONCLUSIONS: Neural processes of emotion conflict detection measured in the early aftermath of a potentially traumatic event are useful as predictors for the development of PTSD symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neural Correlates of Reward Processing in the Onset, Maintenance, and Treatment of Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a prevalent, debilitating, and heterogeneous psychiatric condition marked by both exaggerated threat responding and diminished positive affect. While symptom profiles of PTSD differ across individuals, symptoms also vary within individuals over the course of illness. Functional magnetic resonance imaging studies have provided crucial insights into the neurobiology of heightened threat responsivity in PTSD, which has aided in identifying neurobiological risk factors and treatment targets for this disorder. Despite this demonstrated utility, the application of functional magnetic resonance imaging to understanding deficits in reward responsivity in PTSD remains underexplored. Significantly, over 60% of individuals with PTSD experience anhedonia, or an inability to feel pleasure, which may reflect reward processing deficits. To better understand the neural underpinnings of reward deficits and their relevance to the onset, maintenance, and treatment of PTSD, we reviewed the functional magnetic resonance imaging literature through the framework of disease prognosis. Here, we provide insights on whether reward deficits are central to PTSD or are better explained by comorbid major depressive disorder, and we clarify how reward-related deficiencies in PTSD fit into the context of more intensely studied threat-related deficits.

Psychological and physiological correlates of stimulus discrimination in adults.

The discrimination of cues in the environment that signal danger ("fear cue") is important for survival but depends critically on the discernment of such cues from ones that pose no threat ("safety cues"). In rodents, we previously demonstrated the underlying neurobiological mechanisms that support fear versus safety discrimination and documented that these mechanisms extend to the discrimination of reward as well. While learning about reward is equally important for survival, it remains an under-studied area of research, particularly in human studies of conditional discrimination. In the present study, we translated our rodent task of fear reward and neutral discrimination (fear, reward, and neutral discrimination [FRND]) for use in humans. Undergraduate students (N = 53) completed the FRND while electrodermal activity was recorded. Skin conductance response (SCR) amplitude, a marker of arousal response, was derived for fear, reward, and neutral cues that signaled no outcome; critical trials assessed conditional discrimination using combined fear + neutral and reward + neutral cues. Participants provided likeability ratings for each cue type. Results demonstrated that participants rated reward cues the best, fear cues the worst, and neutral cues in between, while SCR amplitude was largest for fear and reward cues and lowest for neutral cues. SCR amplitudes were reduced for fear + neutral (compared to fear) and reward + neutral cues (compared to reward). Results demonstrate that the FRND is a useful paradigm for the assessment of psychological and physiological discrimination of fear and reward. Implications and directions for future work are discussed.

The early impact of COVID-19 on intensive care nurses' personal and professional well-being: A qualitative study.

OBJECTIVE: To describe the impact of the COVID-19 pandemic on intensive care nurses personal and professional well-being. RESEARCH METHODOLOGY/DESIGN: A descriptive, qualitative design was used. Two nurse researchers conducted one-on-one interviews via Zoom or TEAMS using a semi-structured interview guide. SETTING: Thirteen nurses who were working in an intensive care unit in the United States participated in the study. A convenience sample of nurses who completed a survey in the larger parent study provided an email and were contacted by the research team to participate in interviews to discuss their experiences. MAIN OUTCOME MEASURES: An inductive approach to content analysis was used to develop categories. FINDINGS: Five major categories emerged from the interviews: (1) We are not heroes, (2) inadequate support, (3) helplessness, (4) exhaustion, and (5) Nurses the second victim. CONCLUSION: The COVID-19 pandemic has taken a physical and mental health toll on intensive care nurses. The impact of the pandemic on personal and professional well-being has serious implications for retaining and expanding the nursing workforce. IMPLICATIONS FOR CLINICAL PRACTICE: This work highlights the importance for bedside nurses to advocate for systemic change to improve the work environment. It is imperative for nurses to have effective training including evidence-based practice and clinical skills. There needs to be systems in place to monitor and support nurses' mental health and encourage bedside nurses to use self-care methods and practices to prevent anxiety, depression, post-traumatic stress disorder and burnout.

Machine learning prediction of posttraumatic stress disorder trajectories following traumatic injury: Identification and validation in two independent samples.

Due to its heterogeneity, the prediction of posttraumatic stress disorder (PTSD) development after traumtic injury is difficult. Recent machine learning approaches have yielded insight into predicting PTSD symptom trajectories. Using data collected within 1 month of traumatic injury, we applied eXtreme Gradient Boosting (XGB) to classify admitted and discharged patients (hospitalized, n = 192; nonhospitalized, n = 214), recruited from a Level 1 trauma center, according to PTSD symptom trajectories. Trajectories were identified using latent class mixed models on PCL-5 scores collected at baseline, 1-3 months posttrauma, and 6 months posttrauma. In both samples, nonremitting, remitting, and resilient PTSD symptom trajectories were identified. In the admitted patient sample, a unique delayed trajectory emerged. Machine learning classifiers (i.e., XGB) were developed and tested on the admitted patient sample and externally validated on the discharged sample with biological and clinical self-report baseline variables as predictors. For external validation sets, prediction was fair for nonremitting versus other trajectories, areas under the curve (AUC = .70); good for nonremitting versus resilient trajectories, AUCs = .73-.76; and prediction failed for nonremitting versus remitting trajectories, AUCs = .46-.48. However, poor precision (< .57) across all models suggests limited generalizability of nonremitting symptom trajectory prediction from admitted to discharged patient samples. Consistency in symptom trajectory identification across samples supports prior studies on the stability of PTSD symptom trajectories following trauma exposure; however, continued work and replication with larger samples are warranted to understand overlapping and unique predictive features of PTSD in different traumatic injury populations.

Neighborhood Socioeconomic Disadvantage and the Neurobiology of Uncertainty in Traumatically Injured Adults.

BACKGROUND: Individuals residing in more socioeconomically disadvantaged neighborhoods experience greater uncertainty through insecurity of basic needs such as food, employment, and housing, compared with more advantaged neighborhoods. Although the neurobiology of uncertainty has been less frequently examined in relation to neighborhood disadvantage, there is evidence that neighborhood disadvantage is associated with widespread neural alterations. METHODS: Recently traumatically injured participants (n = 90) completed a picture anticipation task in the magnetic resonance imaging scanner, in which they viewed images presented in a temporally predictable or unpredictable manner. We investigated how neighborhood disadvantage (via area deprivation index [ADI]) was related to neural activation during anticipation and presentation of negative and neutral images after accounting for individual factors (i.e., age, gender, income, acute posttraumatic stress symptoms). RESULTS: There was a significant interaction during the anticipation period such that higher ADI rankings were related to greater activation of the right anterior cingulate cortex to predictable versus unpredictable neutral stimuli. Although no other robust interactions emerged related to ADI, we note several novel simple effects of ADI during anticipation and presentation periods in the hippocampus and prefrontal, cingulate, and occipital cortices. CONCLUSIONS: Together, these results may represent an adaptive response to predictable and/or negative stimuli, stemming from chronic exposure to socioeconomic-based uncertainties. Although effects were modest, future work should continue to examine pretrauma context on posttrauma outcomes. To better understand trauma outcomes, it is imperative that researchers consider the broader context in which trauma survivors reside.

Critical Care Nurse Burnout, Moral Distress, and Mental Health During the COVID-19 Pandemic: A United States Survey.

BACKGROUND: The COVID-19 pandemic has and will continue to have a tremendous influence on intensive care unit (ICU) nurses' mental health. OBJECTIVES: The purpose of this study was to describe the impact of COVID-19 on nurse moral distress, burnout, and mental health. METHODS: Between October 2020 and January 2021 this descriptive study recruited a national sample of nurses who worked in the ICU during the COVID-19 pandemic through American Association of Critical Care Nurses newsletters and social media. RESULTS: A total of 488 survey responses were received from critical care nurses working in the U.S. during the COVID pandemic. Over two thirds of respondents experienced a shortage of personal protective equipment (PPE). Nurse respondents reported moderate/high levels of moral distress and burnout. Symptoms of moderate to severe depression and anxiety were reported by 44.6% and 31.1% of respondents, respectively. Forty-seven percent of respondents were at risk for having posttraumatic stress disorder (PTSD). Lack of perceived support from administration and shortage of PPE were associated with higher levels of burnout, moral distress, and PTSD symptoms. CONCLUSIONS: Respondents had higher anxiety and depression than the general population and higher risk for having PTSD than recent veterans or patients after traumatic injury. High levels of reported burnout and moral distress increase the risk of nurses leaving ICU practice or the profession. This study offers important insights about the mental health of nurses during a global pandemic that can guide the development of customized interventions for ICU nurses related to this health care crisis.

Psychophysiological predictors of change in emotion dysregulation 6 months after traumatic injury.

Emotion dysregulation that occurs after trauma conveys risk for multiple disorders, including posttraumatic stress disorder, depression, and anxiety. Psychophysiological data (e.g., skin conductance level [SCL]) may be a useful biomarker for quantifying emotion dysregulation given that autonomic nervous system (ANS)-mediated arousal may underlie this feature. In this longitudinal study, we tested whether SCL collected following a single-incident traumatic injury could predict changes in emotion dysregulation over 6 months. Sixty-six adults were recruited from the emergency department; SCL was quantified during an active trauma narrative, in which participants re-told their traumatic event to a research staff member, as well as a neutral narrative for a control condition. Change in SCL (ΔSCL) was calculated using a maximum activation - minimum activation difference score. Multilevel linear modeling was used to test ΔSCL as a predictor of emotion dysregulation using the Emotion Dysregulation Scale (EDS) over time (3 timepoints over 6 months). Results showed that greater ΔSCL - indicative of increasing arousal- during both the trauma (p = 0.037) and neutral (p = 0.013) narratives was a significant predictor of greater emotion dysregulation at each subsequent timepoint. Further, we found a ΔSCL by time interaction, such that less ΔSCL during the neutral narrative predicted decreased emotion dysregulation over time (b = -1.26, SE = 0.43, t = -2.91, p = 0.004). Results validate the use of lab-based assessments of arousal to study emotion dysregulation in trauma survivors. That recovery from emotion dysregulation was predicted by less arousal during a neutral event underscores the importance of clinically targeting response to safety in trauma survivors.

Racial Discrimination and Resting-State Functional Connectivity of Salience Network Nodes in Trauma-Exposed Black Adults in the United States.

Importance: For Black US residents, experiences of racial discrimination are still pervasive and frequent. Recent empirical work has amplified the lived experiences and narratives of Black people and further documented the detrimental effects of racial discrimination on both mental and physical health; however, there is still a need for further research to uncover the mechanisms connecting experiences of racial discrimination with adverse health outcomes. Objective: To examine neurobiological mechanisms that may offer novel insight into the association of racial discrimination with adverse health outcomes. Design, Setting, and Participants: This cross-sectional study included 102 Black adults who had recently experienced a traumatic injury. In the acute aftermath of the trauma, participants underwent a resting-state functional magnetic resonance imaging scan. Individuals were recruited from the emergency department at a Midwestern level 1 trauma center in the United States between March 2016 and July 2020. Data were analyzed from February to May 2021. Exposures: Self-reported lifetime exposure to racial discrimination, lifetime trauma exposure, annual household income, and current posttraumatic stress disorder (PTSD) symptoms were evaluated. Main Outcomes and Measures: Seed-to-voxel analyses were conducted to examine the association of racial discrimination with connectivity of salience network nodes (ie, amygdala and anterior insula). Results: A total of 102 individuals were included, with a mean (SD) age of 33 (10) years and 58 (57%) women. After adjusting for acute PTSD symptoms, annual household income, and lifetime trauma exposure, greater connectivity between the amygdala and thalamus was associated with greater exposure to discrimination (t(97) = 6.05; false discovery rate (FDR)-corrected P = .03). Similarly, racial discrimination was associated with greater connectivity between the insula and precuneus (t(97) = 4.32; FDR-corrected P = .02). Conclusions and Relevance: These results add to the mounting literature that racial discrimination is associated with neural correlates of vigilance and hyperarousal. The study findings extend this theory by showing that this association is apparent even when accounting for socioeconomic position, lifetime trauma, and symptoms of psychological distress related to an acute trauma.

A cluster analytic approach to examining the role of cortisol in the development of post-traumatic stress and dysphoria in adult traumatic injury survivors.

Identification of specific risk factors for posttraumatic stress disorder (PTSD) versus depression after trauma has been challenging, in part due to the high comorbidity of these disorders. As exposure to trauma triggers activation of the hypothalamic-pituitary-adrenal (HPA)-axis, examining atypical stress responses via HPA-axis hormones, namely cortisol, may help in the delineation of these disorders. Indeed, extant research demonstrates that, following stress, individuals with chronic PTSD exhibit hypocortisolism (e.g., lower cortisol response than controls), while those with chronic depression exhibit hypercortisolism (e.g., higher response than controls). Less is known about the role of cortisol and these seemingly disparate profiles immediately following traumatic injury as well as whether cortisol can be used as a predictor of future development of PTSD versus depression symptoms. In this study cortisol was measured blood from 172 traumatic injury survivors during hospitalization (on average 2.5 days post-injury). PTSD and depression severity were assessed from Clinician Assessed PTSD Scale (CAPS-5) six-eight months later using a two-factor dimensional approach that measures trauma-specific symptoms of PTSD versus dysphoria (akin to depression). Cluster analysis was used to group individuals based on post-injury cortisol, PTSD, and dysphoria. Results demonstrated that trauma survivors who only developed symptoms of dysphoria at six months (with minimal symptoms of PTSD) were differentiated by high post-injury cortisol compared to other groups. By contrast, individuals who developed symptoms of both PTSD and dysphoria were differentiated by low post-injury cortisol and most severe symptoms of PTSD. Findings provide support for the presence of subgroups of trauma survivors defined, in part, by post-trauma cortisol.

Critical Care Nurses' Experiences During the COVID-19 Pandemic: A US National Survey.

BACKGROUND: Given critical care nurses' high prepandemic levels of moral distress and burnout, the COVID-19 pandemic will most likely have a tremendous influence on intensive care unit (ICU) nurses' mental health and continuation in the ICU workforce. OBJECTIVE: To describe the experiences of ICU nurses during the COVID-19 pandemic in the United States. METHODS: Nurses who worked in ICUs in the United States during the COVID-19 pandemic were recruited to complete a survey from October 2020 through early January 2021 through social media and the American Association of Critical-Care Nurses. Three open-ended questions focused on the experiences of ICU nurses during the pandemic. RESULTS: Of 498 nurses who completed the survey, 285 answered the open-ended questions. Nurses reported stress related to a lack of evidence-based treatment, poor patient prognosis, and lack of family presence in the ICU. Nurses perceived inadequate leadership support and inequity within the health care team. Lack of consistent community support to slow the spread of COVID-19 or recognition that COVID-19 was real increased nurses' feelings of isolation. Nurses reported physical and emotional symptoms including exhaustion, anxiety, sleeplessness, and moral distress. Fear of contracting COVID-19 or of infecting family and friends was also prevalent. CONCLUSIONS: Intensive care unit nurses in the United States experienced unprecedented and immense burden during the COVID-19 pandemic. Understanding these experiences provides insights into areas that must be addressed to build and sustain an ICU nurse workforce. Studies are needed to further describe nurses' experiences during the COVID-19 pandemic and identify effective resources that support ICU nurse well-being.

Hippocampal Resting-State Functional Connectivity Forecasts Individual Posttraumatic Stress Disorder Symptoms: A Data-Driven Approach.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a debilitating disorder, and there is no current accurate prediction of who develops it after trauma. Neurobiologically, individuals with chronic PTSD exhibit aberrant resting-state functional connectivity (rsFC) between the hippocampus and other brain regions (e.g., amygdala, prefrontal cortex, posterior cingulate), and these aberrations correlate with severity of illness. Previous small-scale research (n < 25) has also shown that hippocampal rsFC measured acutely after trauma is predictive of future severity using a region-of-interest-based approach. While this is a promising biomarker, to date, no study has used a data-driven approach to test whole-brain hippocampal FC patterns in forecasting the development of PTSD symptoms. METHODS: A total of 98 adults at risk of PTSD were recruited from the emergency department after traumatic injury and completed resting-state functional magnetic resonance imaging (8 min) within 1 month; 6 months later, they completed the Clinician-Administered PTSD Scale for DSM-5 for assessment of PTSD symptom severity. Whole-brain rsFC values with bilateral hippocampi were extracted (using CONN) and used in a machine learning kernel ridge regression analysis (PRoNTo); a k-folds (k = 10) and 70/30 testing versus training split approach were used for cross-validation (1000 iterations to bootstrap confidence intervals for significance values). RESULTS: Acute hippocampal rsFC significantly predicted Clinician-Administered PTSD Scale for DSM-5 scores at 6 months (r = 0.30, p = .006; mean squared error = 120.58, p = .006; R2 = 0.09, p = .025). In post hoc analyses, hippocampal rsFC remained significant after controlling for demographics, PTSD symptoms at baseline, and depression, anxiety, and stress severity at 6 months (B = 0.59, SE = 0.20, p = .003). CONCLUSIONS: Findings suggest that functional connectivity of the hippocampus across the brain acutely after traumatic injury is associated with prospective PTSD symptom severity.