Genetic control of the dynamic transcriptional response to immune stimuli and glucocorticoids at single-cell resolution.

Synthetic glucocorticoids, such as dexamethasone, have been used as a treatment for many immune conditions, such as asthma and, more recently, severe COVID-19. Single-cell data can capture more fine-grained details on transcriptional variability and dynamics to gain a better understanding of the molecular underpinnings of inter-individual variation in drug response. Here, we used single-cell RNA-seq to study the dynamics of the transcriptional response to glucocorticoids in activated peripheral blood mononuclear cells from 96 African American children. We used novel statistical approaches to calculate a mean-independent measure of gene expression variability and a measure of transcriptional response pseudotime. Using these approaches, we showed that glucocorticoids reverse the effects of immune stimulation on both gene expression mean and variability. Our novel measure of gene expression response dynamics, based on the diagonal linear discriminant analysis, separated individual cells by response status on the basis of their transcriptional profiles and allowed us to identify different dynamic patterns of gene expression along the response pseudotime. We identified genetic variants regulating gene expression mean and variability, including treatment-specific effects, and showed widespread genetic regulation of the transcriptional dynamics of the gene expression response.

A descriptive literature review of early research on COVID-19 and close relationships.

This in-depth critical review investigates the impact of COVID-19 on personal relationships from the start of the pandemic in early 2020 to September 2021. Research examining six themes are identified and described in detail: the impact of COVID-19 on (1) family and intimate relationships; (2) LGBTQ+ relationships; (3) how COVID-19 is linked to technologically mediated communication and personal relationships; (4) potential shifts in sexual behaviors and desire; (5) potential shifts in relational conflict and intimate partner violence; and (6) constructive aspects of personal relationships, which is a broad theme that includes outcomes such as resilience, relational quality, coping, and social support. Findings for overarching patterns are offered to highlight implications for current research and identify future directions to consider when continuing to study personal relationships during the COVID-19 pandemic and similar future crises.

Diversity, equity, and inclusivity in observational ambulatory assessment: Recommendations from two decades of Electronically Activated Recorder (EAR) research.

Ambient audio sampling methods such as the Electronically Activated Recorder (EAR) have become increasingly prominent in clinical and social sciences research. These methods record snippets of naturalistically assessed audio from participants' daily lives, enabling novel observational research about the daily social interactions, identities, environments, behaviors, and speech of populations of interest. In practice, these scientific opportunities are equaled by methodological challenges: researchers' own cultural backgrounds and identities can easily and unknowingly permeate the collection, coding, analysis, and interpretation of social data from daily life. Ambient audio sampling poses unique and significant challenges to cultural humility, diversity, equity, and inclusivity (DEI) in scientific research that require systematized attention. Motivated by this observation, an international consortium of 21 researchers who have used ambient audio sampling methodologies created a workgroup with the aim of improving upon existing published guidelines. We pooled formally and informally documented challenges pertaining to DEI in ambient audio sampling from our collective experience on 40+ studies (most of which used the EAR app) in clinical and healthy populations ranging from children to older adults. This article presents our resultant recommendations and argues for the incorporation of community-engaged research methods in observational ambulatory assessment designs looking forward. We provide concrete recommendations across each stage typical of an ambient audio sampling study (recruiting and enrolling participants, developing coding systems, training coders, handling multi-linguistic participants, data analysis and interpretation, and dissemination of results) as well as guiding questions that can be used to adapt these recommendations to project-specific constraints and needs.

Sexual Desire in the Time of COVID-19: How COVID-Related Stressors Are Associated with Sexual Desire in Romantic Relationships.

The COVID-19 pandemic and the resulting social distancing measures have caused widespread social and economic disruptions, resulting in spikes in unemployment and financial instability, along with drastic changes to people's ability to feel socially connected. Many of the changes resulting from the COVID-19 pandemic are risk factors for depressive symptoms, which are associated with lower levels of sexual desire. The current research (N = 4,993) examined whether responses to external stressors brought on by COVID-19 (i.e., financial concern, worry, loneliness, stress) were associated with sexual desire among a multi-national sample of people in relationships (Studies 1-2), and whether this association was, in part, due to reports of depressive symptoms (Study 2). In the period immediately following the onset of the pandemic, more financial concern (Study 1) and worry (Study 2) were associated with higher sexual desire, while other factors, like stress (Studies 1-2), were associated with lower desire. We also followed a subset of participants every two weeks during the initial stages of the pandemic and at times when people reported greater stress, loneliness, financial strain, or worry than their average, they reported greater depressive symptoms, which was, in turn, associated with lower sexual desire. Results suggest that the social isolation and stress resulting from the COVID-19 pandemic have mixed associations with sexual desire at the onset of the pandemic. But over time, when people report heightened COVID-related stressors, they tend to report lower sexual desire for their partner, in part because these stressors are associated with more depressive symptoms.

Relationship difficulties and "technoference" during the COVID-19 pandemic.

The COVID-19 pandemic has touched many aspects of people's lives around the world, including their romantic relationships. While media outlets have reported that the pandemic is difficult for couples, empirical evidence is needed to test these claims and understand why this may be. In two highly powered studies (N = 3271) using repeated measure and longitudinal approaches, we found that people who experienced COVID-19 related challenges (i.e., lockdown, reduced face-to-face interactions, boredom, or worry) also reported greater self and partner phone use (Study 1) and time spent on social media (Study 2), and subsequently experienced more conflict and less satisfaction in their romantic relationship. The findings provide insight into the struggles people faced in their relationships during the pandemic and suggest that the increase in screen time - a rising phenomenon due to the migration of many parts of life online - may be a challenge for couples.

Socioeconomic status, financial stress, and glucocorticoid resistance among youth with asthma: Testing the moderation effects of maternal involvement and warmth.

OBJECTIVES: Children who grow up in more socioeconomically disadvantaged homes experience greater levels of inflammation and worse asthma symptoms than children from more advantaged families. However, recent evidence suggests that certain family-level factors can mitigate health disparities associated with socioeconomic status (SES). In a sample of youth with asthma, we investigated the potential buffering effects of maternal involvement and warmth on SES disparities in asthma-related immune responses, assessed via glucocorticoid resistance (GR) of immune cells. METHODS: One hundred and forty-three youth (10-16 years of age) with asthma completed measures of maternal involvement and warmth, and their primary caregivers reported their levels of education, income, and financial stress. Peripheral blood mononuclear cells from youth's blood were isolated, cultured, and assayed to determine mitogen-stimulated (PMA/INO + Etho) and mitogen/hydrocortisone-stimulated (PMA/INO + Cort) levels of two Th-2 cytokines (i.e., interleukin-5, interleukin-13) and one Th-1 cytokine (i.e., interferon-γ). GR was calculated by subtracting log-transformed cytokine concentration in the PMA/INO + Etho samples from log-transformed cytokine concentration in the PMA/INO + Cort samples. RESULTS: Both maternal involvement and warmth moderated the indirect pathway from family SES to GR of Th-2 cytokines via financial stress. Specifically, we found that low family SES was associated with elevated GR of Th-2 cytokines via increased financial stress among youth reporting low levels of maternal involvement and warmth, but not among those reporting high levels of maternal involvement or warmth. CONCLUSIONS: These results highlight the protective role of maternal involvement and warmth in health-related biological processes modulated by family SES among youth with asthma.

"Beyond the Rink": A Multilevel Analysis of Social Identity Behaviors Captured Using the Electronically Activated Recorder.

This study used ecological sampling methods to examine associations between youth athletes' experiences receiving and engaging in behaviors indicative of in-group ties, cognitive centrality, and in-group affect (i.e., social identity) during a 3-day competitive ice hockey tournament. Forty-five youth (Mage = 12.39 years; SDage = 1.14 years; 94% male) from nine teams wore an electronically activated recorder that captured brief (50-s) audio observations throughout the tournament. Participants also completed daily diary questionnaires for each day of competition. Multilevel structural equation modeling demonstrated that athletes were more likely to engage in behaviors indicative of in-group affect and cognitive centrality on days when they received as higher-than-average frequency of behaviors indicative of cognitive centrality from teammates, coaches, and parents. The findings suggest that when team members interact in ways that demonstrate they are thinking about their team, they influence fellow members to behave in ways that promote a sense of "us."

Perceived Partner Responsiveness, Daily Negative Affect Reactivity, and All-Cause Mortality: A 20-Year Longitudinal Study.

OBJECTIVE: This study tested longitudinal associations between absolute levels of perceived partner responsiveness (PPR; how much people perceive that their romantic partners understand, care for, and appreciate them), daily negative affect reactivity and positive affect reactivity, and all-cause mortality in a sample of 1,208 adults for three waves of data collection spanning 20 years. We also tested whether longitudinal changes in PPR predicted mortality via affect reactivity. METHODS: Data were taken from the National Survey of Midlife Development in the United States. PPR was assessed at waves 1 and 2, affect reactivity to stressors was assessed by daily diary reports at wave 2, and mortality status was obtained at wave 3. RESULTS: Mediation analyses revealed absolute levels of PPR at wave 1 predicted wave 3 mortality via wave 2 affective reactivity in the predicted direction, but this did not remain robust when statistically accounting for covariates (e.g., marital risk, neuroticism), ß = .004, 95% confidence interval = -.03 to .04. However, wave 1-2 PPR change predicted negative affect (but not positive affect) reactivity to daily stressors at wave 2, which then predicted mortality risk a decade later (wave 3); these results held when adjusting for relevant demographic, health, and psychosocial covariates, ß = -.04, 95% confidence interval = -.09 to -.002. CONCLUSIONS: These findings are among the first to provide direct evidence of psychological mechanisms underlying the links between intimate relationships and mortality and have implications for research aiming to develop interventions that increase or maintain responsiveness in relationships over time.

Maternal attachment avoidance is linked to youth diurnal cortisol slopes in children with asthma.

Prior evidence suggests that an individual's attachment orientation is linked to the health and health-related biology of his/her romantic relationship partners. The current study examined whether this effect extends to parent-child relationships. Specifically, we investigated the association between maternal attachment anxiety and avoidance and diurnal cortisol of offspring. In a sample of 138 youth with asthma and their primary caregivers, caregivers reported their attachment orientations, and their children (aged 10-17) supplied four saliva samples per day over four days to assess diurnal cortisol patterns. Growth curve analyses revealed no links to caregiver attachment anxiety, but caregiver attachment avoidance was significantly associated with children's diurnal cortisol slopes, such that greater attachment avoidance predicted flatter diurnal cortisol slopes. Maternal warmth did not mediate this link. These results support the possibility that an individual's adult attachment orientation may "get under the skin" of family members to influence their health-related biology. Future research should seek to determine the causal direction of this association and mechanisms of this effect.

Physician Racial Bias and Word Use during Racially Discordant Medical Interactions.

Physician racial bias can negatively affect Black patients' reactions to racially discordant medical interactions, suggesting that racial bias is manifested in physicians' communication with their Black patients. However, little is known about how physician racial bias actually influences their communication during these interactions. This study investigated how non-Black physicians' racial bias is related to their word use during medical interactions with Black patients. One hundred and seventeen video-recorded racially discordant medical interactions from a larger study were transcribed and analyzed using Linguistic Inquiry and Word Count (LIWC) software. Physicians with higher levels of implicit racial bias used first-person plural pronouns and anxiety-related words more frequently than physicians with lower levels of implicit bias. There was also a trend for physicians with higher levels of explicit racial bias to use first-person singular pronouns more frequently than physicians with lower levels of explicit bias. These findings suggest that non-Black physicians with higher levels of implicit racial bias may tend to use more words that reflect social dominance (i.e., first-person plural pronouns) and anxiety when interacting with Black patients.

Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles Across the Life Span.

Childhood adversity is associated with poor health outcomes in adulthood; the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a crucial biological intermediary of these long-term effects. Here, we tested whether childhood adversity was associated with diurnal cortisol parameters and whether this link was partially explained by self-esteem. In both adults and youths, childhood adversity was associated with lower levels of cortisol at awakening, and this association was partially driven by low self-esteem. Further, we found a significant indirect pathway through which greater adversity during childhood was linked to a flatter cortisol slope via self-esteem. Finally, youths who had a caregiver with high self-esteem experienced a steeper decline in cortisol throughout the day compared with youths whose caregiver reported low self-esteem. We conclude that self-esteem is a plausible psychological mechanism through which childhood adversity may get embedded in the activity of the HPA axis across the life span.

Neighborhood Stress, Depressive Symptoms, and Asthma Morbidity in Youth.

OBJECTIVE: Living in a dangerous and disadvantaged neighborhood is consistently linked with poor health outcomes; however, few studies have investigated psychosocial mechanisms of this relationship. We hypothesized that a specific facet of depression-anhedonia-would partially explain the relationship between stressful neighborhoods and poor health in youth with asthma. METHOD: 156 youths provided reports on their depressive symptoms, daily asthma symptoms, and peak expiratory flow rate (PEFR). Caregivers provided reports on neighborhood characteristics. RESULTS: Youth residing in more at-risk neighborhoods experienced more symptoms of depression, greater asthma symptoms (both during the day and night), and marginally lower PEFR. Indirect effect analyses revealed that the relationship between neighborhood stress and youth asthma symptoms was partially explained by a key symptom of depression, anhedonia. CONCLUSIONS: These findings suggest that the neighborhood-health link is partially explained by symptoms of depression tapping into difficulties experiencing pleasure and motivation.

Asthma-Related Immune Responses in Youth With Asthma: Associations With Maternal Responsiveness and Expressions of Positive and Negative Affect in Daily Life.

OBJECTIVES: Stressful family environments early in life have negative effects on physical health. However, less is known about the health effects of positive aspects of families. We examined the associations between maternal responsiveness and immune markers among youth with asthma and identified youth expressions of positive affect as a potential mechanism of these associations. METHODS: Forty-three youths with asthma (26 boys; aged 10-17 years) wore the Electronically Activated Recorder for 4 days to assess maternal responsiveness and youth expressions of affect from audio-recordings of daily life. Trained coders rated Electronically Activated Recorder sound files for expressions of maternal responsiveness and affect displayed by the youth. Peripheral blood mononuclear cells were isolated, cultured, and assayed to determine stimulated levels of interleukin (IL)-5, IL-13, and interferon-γ. RESULTS: Greater maternal responsiveness was associated with decreased stimulated production of IL-5 (r = -0.38, p = .012) and IL-13 (r = -0.33, p = .031). Greater total positive affect in youth was linked to decreased stimulated production of IL-5 (r = -0.46, p = .002) and IL-13 (r = -0.37, p = .014). Total negative affect among youth was unrelated to immune responses. There was a significant indirect effect of maternal responsiveness via positive affect in youth on lower levels of IL-5 (95% confidence interval = -3.41 to -0.03) and IL-13 (95% confidence interval = -2.34 to -0.01) when adjusting for caregiver-youth conflict and negative affect among youth. CONCLUSIONS: These results indicate the importance of positive family interactions for youth and provide preliminary evidence for a mechanism through which parenting can influence immune responses in youth with asthma.

Perceived Partner Responsiveness Predicts Diurnal Cortisol Profiles 10 Years Later.

Several decades of research have demonstrated that marital relationships have a powerful influence on physical health. However, surprisingly little is known about how marriage affects health--both in terms of psychological processes and biological ones. Over a 10-year period, we investigated the associations between perceived partner responsiveness--the extent to which people feel understood, cared for, and appreciated by their romantic partners--and diurnal cortisol in a large sample of married and cohabitating couples in the United States. Partner responsiveness predicted higher cortisol values at awakening and steeper (i.e., healthier) cortisol slopes at the 10-year follow-up. These associations remained strong after we controlled for demographic factors, depressive symptoms, agreeableness, and other positive and negative relationship factors. Furthermore, declines in negative affect over the 10-year period mediated the prospective association between responsiveness and cortisol slope. These findings suggest that diurnal cortisol may be a key biological pathway through which social relationships affect long-term health.

Perceived Stigmatization, Resilience, and Diurnal Cortisol Rhythm Among Children of Parents Living With HIV.

Stigmatization often puts at risk the health and well-being of children from marginalized groups. One potential protective factor for such children is resilience--one's capability to adapt flexibly, persistently, and resourcefully to stressful situations. In this study, we investigated the associations among stigmatization, resilience, and hypothalamic-pituitary-adrenal (HPA) axis function in a sample of 645 youths affected by parents infected with HIV. Perceived stigmatization was associated with lower cortisol levels at awakening and flatter cortisol slopes, whereas resilience was independently associated with higher levels of salivary cortisol at awakening and steeper cortisol slopes. We found evidence for an indirect effect of resilience on diurnal cortisol through lower perceived stigmatization. These associations remained significant after we controlled for demographic and health factors and stressful life events. Our findings demonstrate that perceived stigmatization and resilience are associated with HPA-axis functioning in childhood. Broadly, the data suggest that resilience-promoting and stigma-reducing efforts should be considered to improve the health of children from disadvantaged groups.

Effects of socioeconomic status on maternal and child positive behaviors in daily life among youth with asthma.

OBJECTIVE: Socioeconomic disadvantage is associated with poorer behavioral and emotional outcomes in children with asthma. This study investigated the associations between maternal income and education and naturalistically observed behaviors and affect during everyday parent-child interactions. METHODS: 53 predominantly low-income youth with asthma, aged 10-17 years, wore a naturalistic event-sampling device, the Electronically Activated Recorder, for 4 days to assess mother and child positive behaviors and affect in daily life. RESULTS: Maternal education, but not income, was positively associated with child positive behaviors, displays of mother and child positive affect, and increased maternal responsiveness. Maternal positive affect and maternal responsiveness mediated the effect of maternal education on child positive affect. CONCLUSIONS: Our findings suggest that maternal education has an important influence on the socioemotional adjustment of youth with asthma and point to the importance of investigating the independent influence of socioeconomic status components on everyday parent-child interactions.

Language Analysis as a Window to Bereaved Parents' Emotions During a Parent-Physician Bereavement Meeting.

Parent-physician bereavement meetings may benefit parents by facilitating sense making, which is associated with healthy adjustment after a traumatic event. Prior research suggests a reciprocal relationship between sense making and positive emotions. We analyzed parents' use of emotion words during bereavement meetings to better understand parents' emotional reactions during the meeting and how their emotional reactions related to their appraisals of the meeting. Parents' use of positive emotion words increased, suggesting the meetings help parents make sense of the death. Parents' use of positive emotion words was negatively related to their own and/or their spouse's appraisals of the meeting, suggesting that parents who have a positive emotional experience during the meeting may also have a short-term negative reaction. Language analysis can be an effective tool to understand individuals' ongoing emotions and meaning making processes during interventions to reduce adverse consequences of a traumatic event, such as a child's death.

The relationship of chronic and momentary work stress to cardiac reactivity in female managers: feasibility of a smart phone-assisted assessment system.

OBJECTIVES: To evaluate a wireless smart phone-assisted (SPA) system that assesses ongoing heart rate (HR) and HR-triggered participant reports of momentary stress when HR is elevated during daily life. This SPA system was used to determine the independent and interactive roles of chronic and momentary work stress on HR reactivity among female managers. METHODS: A sample of 40 female managers reported their chronic work stress and wore the SPA system during a regular workday. They provided multiple reports of their momentary stress, both when triggered by increased HR and at random times. Relationships among chronic stress, momentary stress, and HR were analyzed with hierarchical linear modeling. RESULTS: Both chronic work stress (b = 0.08, standard error [SE] = 0.03, p = .003) and momentary work stress (b = 1.25, SE = 0.62, p = .052) independently predicted greater HR reactivity, adjusting for baseline HR, age, smoking, caffeine, alcohol use, and momentary physical activity levels. More importantly, chronic and momentary stress significantly interacted (b = 1.00, SE = 0.04, p = .036); high momentary stress predicted elevated HR only in the context of high chronic stress. CONCLUSIONS: Female managers who experience chronic work stress displayed elevated cardiac reactivity during momentary stress at work. The joint assessment of chronic stress and momentary stress and their relationship to physiological functioning during work clarifies the potential health risks associated with work stress. Moreover, this wireless SPA system captures the immediate subjective context of individuals when physiological arousal occurs, which may lead to tailored stress management programs in the workplace.

Examining Racial/Ethnic Disparities in Coping and Stress Within an Environmental Riskscape.

Existing research on racial/ethnic differences in stress and coping is limited by small samples, single-item measures, and lack of inclusion of Mexican Americans. We address these gaps by analyzing data from the Texas City Stress and Health Study, a cross-sectional sample of Black (N = 257), White (N = 304), US-born (N = 689), and foreign-born (N = 749) Mexican Americans residing in proximity to a petrochemical complex. We compared active and avoidant coping by race/ethnicity and explored multivariable associations between coping and perceived stress. Black and foreign-born Mexican American respondents had the highest stressor exposure yet displayed different patterns of coping and perceived stress patterns. Active coping may be particularly effective for African Americans but may not offset extreme stress disparities. For Mexican Americans, the lack of association between coping and stress underscores the need for more work focused on the culturally diverse coping experiences.

Naturalistically observed interpersonal problems and diabetes management in older adolescents and young adults with type 1 diabetes.

OBJECTIVE: This study investigated the links between naturalistically observed and self-reported interpersonal problems, diabetes management, and glucose levels in older adolescents and young adults with type 1 diabetes. DESIGN: Sixty-eight older adolescents and young adults (aged 17-20 years) participated in a cross-sectional study that consisted of three home visits and a daily diary segment. MAIN OUTCOME MEASURES: Participants wore the Electronically Activated Recorder (EAR) for four days to capture interpersonal problems and wore a continuous glucose monitor for blood glucose levels. Researchers also collected HbA1c values, conducted an interview to assess diabetes management, and collected participant-reported severity of interpersonal problems. RESULTS: High EAR-observed interpersonal problems were associated with poor diabetes management. Multiple regression analyses revealed that high EAR-observed interpersonal problems continued to explain variance in poor diabetes management after including self-reported interpersonal problems and covariates. CONCLUSION: These findings corroborate literature suggesting that negative interactions are associated with type 1 diabetes management. This study is the first to use the EAR to capture naturalistically observed interactions in this population and identify its utility beyond self-reports. These findings highlight the importance of considering naturalistically observed interactions when developing interventions to promote better diabetes management in older adolescents and young adults.