Neural effects of controllability as a key dimension of stress exposure.

Cross-species evidence suggests that the ability to exert control over a stressor is a key dimension of stress exposure that may sensitize frontostriatal-amygdala circuitry to promote more adaptive responses to subsequent stressors. The present study examined neural correlates of stressor controllability in young adults. Participants (N = 56; Mage = 23.74, range = 18-30 years) completed either the controllable or uncontrollable stress condition of the first of two novel stressor controllability tasks during functional magnetic resonance imaging (fMRI) acquisition. Participants in the uncontrollable stress condition were yoked to age- and sex-matched participants in the controllable stress condition. All participants were subsequently exposed to uncontrollable stress in the second task, which is the focus of fMRI analyses reported here. A whole-brain searchlight classification analysis revealed that patterns of activity in the right dorsal anterior insula (dAI) during subsequent exposure to uncontrollable stress could be used to classify participants' initial exposure to either controllable or uncontrollable stress with a peak of 73% accuracy. Previous experience of exerting control over a stressor may change the computations performed within the right dAI during subsequent stress exposure, shedding further light on the neural underpinnings of stressor controllability.

Development and validation of the Dimensional Inventory of Stress and Trauma Across the Lifespan (DISTAL): A novel assessment tool to facilitate the dimensional study of psychobiological sequelae of exposure to adversity.

Decades of research underscore the profound impact of adversity on brain and behavioral development. Recent theoretical models have highlighted the importance of considering specific features of adversity that may have dissociable effects at distinct developmental timepoints. However, existing measures do not query these dimensions in sufficient detail to support the proliferation of this approach. The Dimensional Inventory of Stress and Trauma Across the Lifespan (DISTAL) was developed with the aim to thoroughly and retrospectively assess the timing, severity (of exposure and reaction), type, persons involved, controllability, predictability, threat, deprivation, proximity, betrayal, and discrimination inherent in an individual's exposure to adversity. Here, we introduce this instrument, present descriptive statistics drawn from a sample of N = 187 adults who completed the DISTAL, and provide initial information about its psychometric properties. This novel measure facilitates the expansion of research focused on assessing the relative impact of exposure to key dimensions of adversity on the brain and behavior across development.

Parental Assistance with Emotion Regulation Moderates Link Between COVID-19 Stress and Child Mental Health.

OBJECTIVE: The COVID-19 pandemic has severely impacted children's mental health. All children have not been affected equally, however, and whether parental emotion socialization might buffer or exacerbate the impact of COVID-19 on children's mental health remains an important question. METHOD: During the first peak of the COVID-19 pandemic in the U.S. N = 200 parents of children ages 0-17 (52.5% female) completed questionnaires related to parental assistance with children's emotion regulation, symptomatology, and exposure to COVID-19-related stress. Parents were 74% Non-Hispanic/Latino/a White, 13% Asian, 4.5% Hispanic/Latino/a, 4% Black/African American, 2.5% Native American, and 1.5% bi/multiracial; 0.5% of participants preferred not to state their race/ethnicity. In a series of linear regression analyses, we examined whether parental assistance with children's execution of emotion regulation strategies - across a variety of prototypically-adaptive and -maladaptive strategies - moderates the association between children's exposure to COVID-19-related stress and symptomatology. RESULTS: Results suggest that parental assistance with the execution of prototypically-adaptive strategies (i.e., acceptance, problem solving, behavioral disengagement) and prototypically-maladaptive strategies (i.e., suppression, rumination) may buffer or exacerbate, respectively, the impact of COVID-19-related stress on youth mental health. CONCLUSIONS: Though interpretation of findings is constrained by limitations inherent in collecting data during a pandemic, results highlight the importance of supporting parents - who play a critical role of supporting children - during public health emergencies that affect family life. Interventions designed to improve child wellbeing during the ongoing pandemic may benefit from training parents to assist their children with specific emotion regulation strategies.

Migration-related trauma and mental health among migrant children emigrating from Mexico and Central America to the United States: Effects on developmental neurobiology and implications for policy.

Children make up over half of the world's migrants and refugees and face a multitude of traumatic experiences prior to, during, and following migration. Here, we focus on migrant children emigrating from Mexico and Central America to the United States and review trauma related to migration, as well as its implications for the mental health of migrant and refugee children. We then draw upon the early adversity literature to highlight potential behavioral and neurobiological sequalae of migration-related trauma exposure, focusing on attachment, emotion regulation, and fear learning and extinction as transdiagnostic mechanisms underlying the development of internalizing and externalizing symptomatology following early-life adversity. This review underscores the need for interdisciplinary efforts to both mitigate the effects of trauma faced by migrant and refugee youth emigrating from Mexico and Central America and, of primary importance, to prevent child exposure to trauma in the context of migration. Thus, we conclude by outlining policy recommendations aimed at improving the mental health of migrant and refugee youth.

Pharmacotherapeutics of capecitabine and trastuzumab in the treatment of metastatic breast cancer.

Metastatic HER2-positive breast cancer is an incurable disease with a poor prognosis. This article presents a critical appraisal of two treatments commonly used in the treatment of metastatic HER2-positive breast cancer: the oral chemotherapy drug, capecitabine, and the monoclonal antibody, trastuzumab. What follows is a critical discussion of the pharmacotherapeutics of capecitabine and trastuzumab, which considers their use both as single agents and as a combination regimen in the treatment of metastatic breast cancer. The implications of side effects of these drugs are discussed, both individually and in combination, as are the challenges these bring to the prescriber. The article evaluates the use of these agents and concludes that the combination of capecitabine and trastuzumab is an attractive treatment option for patients and for the prescriber.

Evaluation of patient satisfaction of receiving Systemic Anti-Cancer Therapy prescribed by nurse Non-Medical Prescribers.

PURPOSE: To evaluate patient satisfaction of patients receiving Systemic Anti-Cancer Treatment prescribed by nurse Non-Medical Prescribers as a new model of care at a Cancer Unit in Northern Ireland, United Kingdom. METHODS: A cross-sectional survey design, with a convenience sample of patients from five tumour groups who received Systemic Anti-Cancer Therapy by nurse Non-Medical Prescribers, across a 3-month period in 2022 was employed. Anonymised data were collected via postal survey, which incorporated a minimally modified version of the 45-item Leeds Satisfaction Questionnaire (LSQ). RESULTS: One-hundred and sixteen surveys were returned, yielding a 36% response rate. Overall patients' satisfaction levels with nurse non-medical prescribing of systemic anti-cancer therapy were high across all six subscales of the modified LSQ corroborated by qualitative free-text comments. Eighty-five percent of participants indicated they were happy to continue being prescribed systemic anti-cancer therapy by the nurse non-medical prescribers. CONCLUSION: Overall patient satisfaction of Systemic Anti-Cancer Treatment prescribed by nurse Non-Medical Prescribers was positively rated; with high standards of compassionate, person-centred care reported, demonstrating an acceptable transformation in care delivery from a consultant-led model. Nonetheless, there was scope for improved health literacy to enhance patients' understanding and compliance with treatment.

Hippocampal Involvement in Safety Signal Learning Varies With Anxiety Among Healthy Adults.

Background: Safety signal learning (SSL), based on conditioned inhibition of fear in the presence of learned safety, can effectively attenuate threat responses in animal models and humans. Difficulty regulating threat responses is a core feature of anxiety disorders, suggesting that SSL may provide a novel mechanism for fear reduction. Cross-species evidence suggests that SSL involves functional connectivity between the anterior hippocampus and the dorsal anterior cingulate cortex. However, the neural mechanisms supporting SSL have not been examined in relation to trait anxiety or while controlling for the effect of novelty. Methods: Here, we investigated the neural mechanisms involved in SSL and associations with trait anxiety in a sample of 64 healthy (non-clinically anxious) adults (ages 18-30 years; 43 female, 21 male) using physiological, behavioral, and neuroimaging (functional magnetic resonance imaging) data collected during an SSL task. Results: During SSL, compared with individuals with lower trait anxiety, individuals with higher trait anxiety showed less fear reduction as well as altered hippocampal activation and hippocampal-dorsal anterior cingulate cortex functional connectivity, and lower inferior frontal gyrus and ventrolateral prefrontal cortex activation. Importantly, the findings show that SSL reduces threat responding, across learning and over and above the effect of novelty, and involves hippocampal activation. Conclusions: These findings provide new insights into the nature of SSL and suggest that there may be meaningful variation in SSL and related neural correlates as a function of trait anxiety, with implications for better understanding fear reduction and optimizing interventions for individuals with anxiety disorders.

Parents' emotion suppression exacerbates the effect of COVID-19 stress on youth internalizing symptomatology.

The COVID-19 pandemic has resulted in heightened stress for families in the United States, and exposure to pandemic-related stress has been found to confer risk for mental health problems among both children and parents. To isolate risk and protective factors for children living through the ongoing pandemic, several studies have begun to examine family-level factors that may exacerbate or buffer the impact of exposure to COVID-19-related stress on children's symptomatology. Building upon the extant literature documenting associations between parents' emotion regulation and children's mental health, especially during times of stress, the present study aimed to examine parents' regulation of their own emotions as a potential moderator of the association between children's exposure to family-level COVID-19-related stress and internalizing and externalizing problems. Results suggest that parents' regulation of their own emotions using expressive suppression, specifically, may exacerbate the effect of exposure to pandemic-related stress on children's internalizing problems, but not externalizing problems. Results highlight the importance of prioritizing parents' mental health and self-regulation in prevention and intervention efforts aimed at improving family-wide mental health outcomes during public health crises that place family systems under significant stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Validation of an electronic self-administered version of the Dimensional Inventory of Stress and Trauma Across the Lifespan in a large sample of young adults.

Recent advances in the dimensional assessment of traumatic stress have initiated research examining correlates of exposure to specific features of stress. However, existing tools require intensive, in-person, clinician administration to generate the rich phenotypic data required for such analyses. These approaches are time consuming, costly, and substantially restrict the degree to which assessment tools can be disseminated in large-scale studies, constraining the refinement of existing dimensional models of early adversity. Here, we present an electronic adaptation of the Dimensional Inventory of Stress and Trauma Across the Lifespan (DISTAL), called the DISTAL-Electronic (DISTAL-E), present descriptive statistics drawn from a large sample of N = 500 young adult participants who completed the novel measure, and provide information about its psychometric properties. Results suggest that the DISTAL-E adequately assesses the following dimensional indices of traumatic stress exposure: type, chronicity, age of onset, severity, proximity, caregiver involvement, controllability, predictability, betrayal, threat, and deprivation and that it has excellent content and convergent validity and good test-retest reliability over a 7-11 day period. Although the development of the DISTAL-E facilitates the broad assessment of dimensions of stress exposure in large-scale datasets and has the potential to increase access to stress-related research to a wider group of participants who may not be able to access clinical research in traditional, in-person, clinic-based settings, the generalizability of results of the present study may be constrained by the fact that study participants were primarily White, educated, and with middle-to-high income. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Multivariate links between the developmental timing of adversity exposure and white matter tract integrity in adulthood.

Early-life adversity is pervasive worldwide and represents a potent risk factor for increased mental health burden across the lifespan. However, there is substantial individual heterogeneity in associations between adversity exposure, neurobiological changes, and mental health problems. Accounting for key features of adversity such as the developmental timing of exposure may clarify associations between adversity, neurodevelopment, and mental health. The present study leverages sparse canonical correlation analysis to characterize modes of covariation between age of adversity exposure and the integrity of white matter tracts throughout the brain in a sample of 107 adults. We find that adversity exposure during middle childhood (ages 5-6 and 8-9 in particular) is consistently linked with alterations in white matter tract integrity, such that tracts supporting sensorimotor functions display higher integrity in relation to adversity exposure while tracts supporting cortico-cortical communication display lower integrity. Further, latent patterns of tract integrity linked with adversity experienced across preschool age and middle childhood (ages 4-9) were associated with trauma-related symptoms in adulthood. Our findings underscore that adversity exposure may differentially affect white matter in a function- and developmental-timing specific manner and suggest that adversity experienced between ages 4-9 may shape the development of global white matter tracts in ways that are relevant for adult mental health.

Development and Validation of the Parental Assistance with Child Emotion Regulation (PACER) Questionnaire.

Caregivers play a central role in promoting emotion regulation throughout infancy, childhood, and adolescence. However, there are no existing psychometric measures to assess how parents assist children in employing emotion regulation strategies for negative emotions. We therefore developed the Parental Assistance with Child Emotion Regulation (PACER) Questionnaire to assess the degree to which parents assist their children in their use of ten different regulation strategies. In this paper, we describe the development of the PACER and examine its psychometric properties (N = 407 parents of children ages birth to 17 years). In so doing, we also use the PACER to comprehensively explore the links between parent-assisted emotion regulation and indices of parent and child stress, symptomatology, and attachment. Confirmatory factor analyses of the PACER items supported its intended ten-factor structure (corresponding to ten specific regulation strategies), which was invariant across different child age and sex categories. PACER scale scores had excellent internal consistency and generally acceptable test-retest reliability over a one-week period. Convergent validity was established via correlations between PACER scales and indices of parental emotion sensitivity, expressivity, and regulation, as well as parents' perception of the efficacy of their assistance with children's execution of emotion regulatory strategies. Lower parental facilitation of stereotypically adaptive emotion regulatory strategies was associated with higher child internalizing and externalizing problems and with poorer parent-child relationship quality. Overall, these findings suggest that the PACER may be a useful tool for the assessment of parental assistance with child emotion regulation across development.

Neural circuitry involved in conditioned inhibition via safety signal learning is sensitive to trauma exposure.

Exposure to trauma throughout the lifespan is prevalent and increases the likelihood for the development of mental health conditions such as anxiety and post-traumatic stress disorder (PTSD). Safety signal learning (SSL)--a form of conditioned inhibition that involves reducing fear via conditioned safety--has been shown to effectively attenuate fear responses among individuals with trauma exposure, but the association between trauma exposure and the neural mechanisms of SSL remains unknown. Adults with varied prior exposure to trauma completed a conditioned inhibition task during functional MRI scanning and collection of skin conductance response (SCR). Conditioned safety signals reduced psychophysiological reactivity (i.e., SCR) in the overall sample. Although exposure to a higher number of traumatic events was associated with elevated SCR across all task conditions, SCR did not differ between threat in the presence of conditioned safety (i.e., SSL) relative to threat alone in a trauma-related manner. At the neural level, however, higher levels of trauma exposure were associated with lower hippocampal, amygdala, and dorsolateral prefrontal cortical activation during SSL. These findings suggest that while conditioned safety signals can reduce fear in the presence of threat even among individuals exposed to higher degrees of trauma, the neural circuitry involved in SSL is in fact sensitive to trauma exposure. Future research investigating neural processes during SSL among individuals with PTSD or anxiety can further elucidate the ways in which SSL and its neural correlates may reduce fear and link trauma exposure with later mental health conditions.

Lack of robust associations between prepandemic coping strategies and frontolimbic circuitry with depression and anxiety symptoms during the COVID-19 pandemic: A preregistered longitudinal study.

The COVID-19 pandemic is an ongoing stressor that has resulted in the exacerbation of mental health problems worldwide. However, longitudinal studies that identify preexisting behavioral and neurobiological factors associated with mental health outcomes during the pandemic are lacking. Here, we examined associations between prepandemic coping strategy engagement and frontolimbic circuitry with internalizing symptoms during the pandemic. In 85 adults (71.8% female; age 18-30 years), we assessed prototypically adaptive coping strategies (Connor-Davidson Resilience Scale), resting-state functional magnetic resonance imaging functional connectivity (FC) of frontolimbic circuitry, and depression and anxiety symptoms (Beck Depression Inventory, Screen for Child Anxiety-Related Emotional Disorders-Adult, respectively). We conducted general linear models to test preregistered hypotheses that (1) lower coping engagement prepandemic and (2) weaker frontolimbic FC prepandemic would predict elevated symptoms during the pandemic; and (3) coping would interact with FC to predict symptoms during the pandemic. Depression and anxiety symptoms worsened during the pandemic (ps < .001). Prepandemic adaptive coping engagement and frontolimbic FC were not associated with depression or anxiety symptoms during the pandemic (uncorrected ps > .05). Coping interacted with insula-rostral anterior cingulate cortex (ACC) FC (p = .003, pFDR = .014) and with insula-ventral ACC FC (p < .001, pFDR < .001) to predict depression symptoms, but these findings did not survive FDR correction after removal of outliers. Findings from our preregistered study suggest that specific prepandemic factors, particularly adaptive coping and frontolimbic circuitry, are not robustly associated with emotional responses to the pandemic. Additional studies that identify preexisting neurobehavioral factors implicated in mental health outcomes during global health crises are needed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Associations between early-life stress exposure and internalizing symptomatology during the COVID-19 pandemic: Assessing the role of neurobehavioral mediators.

Background: The ongoing COVID-19 pandemic is a major stressor that has been associated with increased risk for psychiatric illness in the general population. Recent work has highlighted that experiences of early-life stress (ELS) may impact individuals' psychological functioning and vulnerability for developing internalizing psychopathology in response to pandemic-related stress. However, little is known about the neurobehavioral factors that may mediate the association between ELS exposure and COVID-related internalizing symptomatology. The current study sought to examine the mediating roles of pre-pandemic resting-state frontoamygdala connectivity and concurrent emotion regulation (ER) in the association between ELS and pandemic-related internalizing symptomatology. Methods: Retrospective life-stress histories, concurrent self-reported ER strategies (i.e., reappraisal and suppression), concurrent self-reported internalizing symptomatology (i.e., depression- and anxiety-related symptomatology), and resting-state functional connectivity data from a sample of adults (N = 64, M age = 22.12, female = 68.75%) were utilized. Results: There were no significant direct associations between ELS and COVID-related internalizing symptomatology. Neither frontoamygdala functional connectivity nor ER strategy use mediated an association between ELS and COVID-related internalizing symptomatology (ps > 0.05). Exploratory analyses identified a significant moderating effect of reappraisal use on the association between ELS and internalizing symptomatology (ß = -0.818, p = 0.047), such that increased reappraisal use buffered the impact of ELS on psychopathology. Conclusions: While frontoamygdala connectivity and ER do not appear to mediate the association between ELS and COVID-related internalizing symptomatology, our findings suggest that the use of reappraisal may buffer against the effect of ELS on mental health during the pandemic.

Parental Buffering of Stress in the Time of COVID-19: Family-Level Factors May Moderate the Association Between Pandemic-Related Stress and Youth Symptomatology.

Nearly all families in the United States were exposed to varying degrees of stress related to the COVID-19 pandemic during the spring of 2020. Building on previous research documenting the pernicious effects of stress on youth mental health, we aimed to test the effects of exposure to COVID-19-related stress on youth symptomatology. Further, in light of evidence suggesting that parents play an important role in buffering children from environmental stress, we assessed how specific parental behaviors (i.e., parental emotion socialization, maintenance of home routines, and availability to discuss the pandemic with child) contributed to effective parental buffering of the impact of pandemic-related stress on children's symptomatology. Conversely, we tested whether parental anxiety-related symptomatology and parenting stress exacerbated the effect of children's exposure to pandemic-related stress on children's symptomatology. Results suggest that parents who engaged in relatively higher levels of emotion coaching of children's negative emotions and who maintained more stable home routines during the pandemic were more effectively able to buffer the effects of pandemic-related stress on children's symptomatology. Parents who reported higher levels of parenting stress and anxiety-related symptomatology were less likely to effectively buffer stress. Though interpretation of the findings is limited due to sole reliance on parental report and the cross-sectional study design due to the constraints of collecting data during a global pandemic, findings underscore the importance of assessing family-level factors when considering the impact of stressors on children's symptomatology and highlight the need to support parents during global events that place families under significant stress.