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.

Age and Sex Differences in the Associations Among Socioeconomic Status, Affective Reactivity to Daily Stressors, and Physical Health in the MIDUS Study.

BACKGROUND: Low socioeconomic status (SES) is robustly associated with increased risks of morbidity and mortality. Affective reactivity to daily stressors has been proposed to be a mediator for this association. However, few longitudinal studies have empirically tested the indirect effect of SES on health through affective reactivity to daily stressors. PURPOSE: This study aimed to test the indirect effect of SES on physical health via affective reactivity to daily stressors over a 10-year period and to explore age and sex differences in such indirect effect. METHODS: Data were drawn from a subsample of 1,522 middle-aged and older adults (34-83 years of age, 57.2% female, 83.5% White) from the Midlife in the United States study. SES (i.e., education, household income, indicators of financial distress) was assessed in 2004-2006. Affective reactivity to daily stressors was computed using data collected during the 8-day daily stress assessment in 2004-2009. Self-reported physical health conditions were assessed in 2004-2006 and 2013-2014. RESULTS: There was a significant indirect effect of lower SES on more physical health conditions via elevated negative affective reactivity to daily stressors among women but not men. The indirect effect of SES on physical health conditions via negative affective reactivity to daily stressors was consistent across the middle and older adulthood. CONCLUSIONS: Our findings suggest that negative affective reactivity to daily stressors might be a key intermediate process contributing to persistent SES disparities in physical health, particularly among women.

Individuals from low socioeconomic backgrounds tend to experience poor physical health, partially because they might be more vulnerable to stress exposure due to limited resources to cope with stress than those from high socioeconomic backgrounds. This study examined the indirect link between socioeconomic status (SES) and physical health through emotional responses following exposure to stress. We also explored whether there were age and sex differences in this indirect link. We analyzed the survey and daily diary data from 1,522 middle-aged and older adults. Individuals reported indicators of SES and a count of medical health conditions. Individuals also reported their experiences of stressors and negative and positive emotions each day over 8 days to capture changes in negative and positive emotions on stressor days versus non-stressor days. We found that among women, but not men, lower SES was related to larger increases in negative emotions on stressor days, which, in turn, was related to more chronic health conditions. Differences in individuals' negative emotions following exposure to daily stressors may be a critical indirect pathway linking SES to physical health.

The heart of Detroit study: a window into urban middle-aged and older African Americans' daily lives to understand psychosocial determinants of cardiovascular disease risk.

BACKGROUND: Cardiovascular disease disproportionately affects African Americans. Psychosocial factors, including the experience of and emotional reactivity to racism and interpersonal stressors, contribute to the etiology and progression of cardiovascular disease through effects on health behaviors, stress-responsive neuroendocrine axes, and immune processes. The full pathway and complexities of these associations remain underexamined in African Americans. The Heart of Detroit Study aims to identify and model the biopsychosocial pathways that influence cardiovascular disease risk in a sample of urban middle-aged and older African American adults. METHODS: The proposed sample will be composed of 500 African American adults between the ages of 55 and 75 from the Detroit urban area. This longitudinal study will consist of two waves of data collection, two years apart. Biomarkers of stress, inflammation, and cardiovascular surrogate endpoints (i.e., heart rate variability and blood pressure) will be collected at each wave. Ecological momentary assessments will characterize momentary and daily experiences of stress, affect, and health behaviors during the first wave. A proposed subsample of 60 individuals will also complete an in-depth qualitative interview to contextualize quantitative results. The central hypothesis of this project is that interpersonal stressors predict poor cardiovascular outcomes, cumulative physiological stress, poor sleep, and inflammation by altering daily affect, daily health behaviors, and daily physiological stress. DISCUSSION: This study will provide insight into the biopsychosocial pathways through which experiences of stress and discrimination increase cardiovascular disease risk over micro and macro time scales among urban African American adults. Its discoveries will guide the design of future contextualized, time-sensitive, and culturally tailored behavioral interventions to reduce racial disparities in cardiovascular disease risk.

Social connectedness in older Urban African-American adults during the COVID-19 pandemic: the roles of education and partnership.

OBJECTIVE: This study examined education, partnership status, and the moderating role of the lockdown period on social connectedness during the COVID-19 pandemic in a sample of urban African-American older adults. METHODS: Five hundred thirty-four African-American adults living in Detroit (91.0% female, Mage = 74.53) reported demographic information pre-pandemic and answered one social connectedness questionnaire between April and December 2020. RESULTS: Participants interviewed after the lockdown (post-June 2020) reported more loneliness than those interviewed during the lockdown (April-June, 2020). Married/partnered participants reported less loneliness and social isolation. Loneliness did not differ between those with high education levels interviewed during the lockdown compared to post-lockdown. However, among individuals with low education levels, those interviewed after the lockdown reported more loneliness than those interviewed during the lockdown period. CONCLUSION: Our findings suggest partnership status is associated with more social connectedness during the pandemic and education accentuates the effects of forced isolation related to loneliness among urban African-American older adults.

Parent-Child Separation and Diurnal Cortisol Rhythms Among Left-Behind Adolescents: The Moderating Role of Sex.

Prior research examining parent-child separation and the hypothalamic-pituitary-adrenal (HPA) axis functioning has primarily focused on separation due to parental divorce or loss or forced migration. Less clear is the impact of parental economic migration on adolescents' HPA axis functioning. The present study fills this gap by examining diurnal cortisol patterns among left-behind adolescents who experienced separation from their migrant parents. Participants were 293 Chinese adolescents (33.4% girls, 66.21% left-behind adolescents; Mage = 10.80 years old, SD = 0.82 years). Two-level multilevel modeling was conducted to examine the associations between parent-child separation experiences and diurnal cortisol patterns. Although no significant differences were found between left-behind adolescents and their non-left-behind peers, results revealed that left-behind adolescents who experienced parent-child separation at earlier ages had more blunted diurnal cortisol slopes (usually signaling poorer mental and physical health), compared to their counterparts who experienced separation at older ages. Left-behind adolescent girls who had more adverse separation experiences exhibited smaller waking cortisol and blunted diurnal slopes; these findings were not observed among left-behind adolescent boys. Observing the association between timing of parent-child separation and adolescents' diurnal cortisol and the moderating effects of child sex, this study contributes uniquely to the developmental science of left-behind adolescents' physiological health.

Psychological and Physical Abuse and Cortisol Response to Stress: The Moderating Role of Psychosocial Resources.

Child abuse is associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis functioning. However, the unique effects of psychological and physical abuse and protective factors against these effects remain largely unknown. To close these gaps, the present study examined the unique effects of psychological and physical abuse on cortisol stress response and explored the moderating role of psychosocial resources in these associations among a sample of Chinese preadolescent children (N = 150; aged 9-13 years; Mage = 10.69 years; 51% boys). The results showed that both psychological and physical abuse were associated with blunted cortisol reactivity slopes. Psychological abuse, but not physical abuse, was associated with lower peak cortisol values and flatter cortisol recovery slopes. Further, psychosocial resources moderated the association between abuse and hyporesponsiveness of the HPA axis. The association between psychological abuse and lower peak cortisol values and the association between physical abuse and steeper cortisol recovery slopes (faster cortisol recovery following the stressor) were observed only among children with low levels of psychosocial resources. These findings indicate the differential effects of psychological and physical abuse on various phases of cortisol stress response, and the protective role of psychosocial resources. This study also has practical implications, given that preadolescence serves as a critical period for maximizing benefit of interventions of adversity.

Links Between Socioeconomic Status, Daily Depressive Affect, Diurnal Cortisol Patterns, and All-Cause Mortality.

OBJECTIVE: Socioeconomic status (SES) remains a robust risk factor for mortality. Various theoretical models postulate that lower SES is associated with higher negative affect, which then initiates a cascade of physiological disturbances that contribute to illness and early mortality. However, few studies have explicitly investigated the interplay between psychological and biological factors in determining SES disparities in mortality. This study examined the role of daily negative affect and cortisol secretion in explaining the SES-mortality link in a large sample of US adults. METHODS: Using data from the Midlife in the United States study (n = 1735, mean [standard deviation] age = 56.40 [12.10] years, 56.4% female), we tested longitudinal associations between SES, daily negative affect, daily cortisol levels, and all-cause mortality 13 years later. Daily negative affect was classified into three clusters reflecting depressive affect, anxiety, and anger. RESULTS: Higher SES was linked to a lower risk of all-cause mortality (hazard ratio = 0.94, 95% confidence interval = 0.90 to 0.97). Furthermore, there was a sequential link between higher SES and lower mortality through lower daily depressive affect and a steeper ("healthier") diurnal cortisol slope (indirect effect = -0.0007, 95% confidence interval = -0.0014 to -0.0002). Daily anxiety and anger were not associated with cortisol levels or mortality (p values > .05). CONCLUSIONS: These findings suggest that daily negative emotional experiences and the hypothalamic-pituitary-adrenal axis functioning may constitute important psychological and physiological pathways underlying the link between SES and all-cause mortality.

Effects of parental care and overprotection on adolescents' diurnal cortisol profiles.

Parental bonding is a strong determinant of children's health. One of the proposed pathways through which parenting impacts children's health is by altering the functioning of stress response systems. The current study aims to investigate the associations between two types of parental bonding (care and overprotection) and functioning of hypothalamic-pituitary-adrenal (HPA) axis (i.e., diurnal cortisol secretion) in a sample of 255 healthy adolescents (46.3% girls; aged 11-14 years). Participants completed the Parental Bonding Instrument and provided eight cortisol samples across two consecutive days to assess patterns of diurnal cortisol secretion. Multilevel modeling and multiple linear regression were utilized to test the main effects and interactive effects of parental care and overprotection on adolescents' wakeup cortisol, cortisol awakening response, cortisol slope, and total cortisol secretion. Results showed that parental care was associated with higher cortisol levels at awakening, while parental overprotection was associated with lower cortisol levels at awakening. Parental overprotection, but not parental care, was associated with flatter cortisol slopes. No interactive effects between parental care and overprotection on cortisol parameters emerged. The current findings add to the existing literature on parenting behavior and HPA functioning by showing that parental care and overprotection differently regulated daily cortisol parameters implicated in health.

Effects of the Great Recession on Educational Disparities in Cardiometabolic Health.

BACKGROUND: Macroeconomic crises can exaggerate existing educational disparities in health. Few studies, however, have examined whether macroeconomic crises get under the skin to affect educational disparities in health-related biological processes. PURPOSE: This study aimed to examine the effect of the economic recession of 2008 (i.e., Great Recession) on educational disparities in cardiometabolic risk and self-reported psychological distress. METHODS: Data were drawn from two subsamples of the Midlife in the United States (MIDUS) study: the second wave of the MIDUS sample (pre-recession cohort, N = 985) and the refresher sample (post-recession cohort, N = 863). Educational attainment was categorized into high school education or less, some college, and bachelor's degree or higher. Outcomes included metabolic syndrome, C-reactive protein, and interleukin-6, as well as self-reported perceived stress, depressive symptoms, and financial distress. RESULTS: Results showed that having a bachelor's degree or higher (compared to having a high school education or less) was more strongly associated with decreased metabolic syndrome symptoms in the post-recession cohort than the pre-recession cohort, above and beyond demographic, health, and behavioral covariates. These findings did not extend to systemic inflammation or psychological distress. CONCLUSIONS: Our findings suggest that chronic macroeconomic stressors may widen the educational gap in physical health, particularly cardiometabolic health, by modifying biological and anthropometric risk factors implicated in metabolic syndrome.

Current and Cumulative Stress Experiences: A Model for Arab American Young Adults.

BACKGROUND: The effect of multiple stressors on immigrant young adults' endocrine functioning and health outcomes has not been comprehensively investigated. AIMS: This study tested a theoretical model of cumulative and current stressor effects on the hypothalamic-pituitary-adrenocortical (HPA) axis functioning and health-related quality of life (HRQL) among Arab American young adults. METHODS: Using a cross-sectional design, we recruited 160 participants, ages 18 to 24 years, from an urban university in the Midwest. Cumulative stress was assessed by self-report measures of childhood adversity, bullying victimization, and perceived ethnic discrimination. Current perceived stress was measured using the Perceived Stress Scale (PSS) while cortisol levels were measured in participants' hair. Structural equation modeling tested the effects of cumulative and current stress on cortisol and HRQL. RESULTS: Cumulative stress was negatively associated with HRQL (standardized path coefficient = -.51, p < .05). Interestingly, however, cumulative stress was inversely associated with hair cortisol level (standardized path coefficient = -.51, p < .05). Current stress was positively associated with cortisol level (standardized path coefficient = .43, p < .05) and negatively associated with the mental HRQL (standardized path coefficient < -.37, p < .05). CONCLUSION: Cumulative stress exhibited a different effect on HPA functioning from current perceived stress. Mental health was significantly impaired by both cumulative and current perceived stress. Implications for mental health nursing practice and research among Arab Americans are discussed.

The School-Ladder Effect: Subjective Socioeconomic Status and Diurnal Cortisol Profile Among Adolescents.

OBJECTIVE: Subjective socioeconomic status (SES) is a well-established psychosocial determinant of adolescents' self-report health. However, whether low subjective SES is associated with stress-related physiological risks (e.g., dysregulations in the hypothalamic-pituitary-adrenal axis activity) remains uncertain. This study examined the impact of subjective SES with different reference groups (i.e., perception of family SES relative to other students in the school versus other people in the city) on adolescents' diurnal cortisol profiles. METHODS: A sample of 255 adolescents (aged 11-14 years; 53.7% boys) completed a battery of psychological scales, including school-referenced subjective SES and city-referenced subjective SES. Diurnal cortisol was assessed by collecting saliva samples four times a day across two consecutive days. Four cortisol parameters (cortisol at awakening, cortisol awakening response [CAR], cortisol slope, and total cortisol secretion [area under the curve with respect to ground {AUCg}]) were derived. RESULTS: Higher levels of school-referenced subjective SES were associated with higher cortisol levels at awakening (ß = 0.0483, standard error [SE] = 0.0219, p = .028), steeper cortisol slopes (ß = -0.0036, SE = 0.0017, p = .034), and higher cortisol AUCg (b = 0.50, SE = 0.24, p = .036), but not with CAR (p = .77), after adjusting for covariates. In contrast, city-referenced subjective SES was not associated with any of the cortisol parameters (cortisol at awakening [p = .90], CAR [p = .74], cortisol slope [p = .84], and cortisol AUCg [p = .68]). CONCLUSIONS: Our findings highlight the importance of the reference group for subjective SES and provide a further understanding of socioeconomic disparities in adolescents' stress physiology.

Perceived Social Support and Children's Physiological Responses to Stress: An Examination of the Stress-Buffering Hypothesis.

OBJECTIVE: The current study aimed to examine the stress-buffering effect of children's perceived social support on their hypothalamic-pituitary-adrenocortical axis and autonomic nervous system reactivity to an acute laboratory stressor. METHODS: A sample of 150 children (aged 9-13 years, mean [standard deviation] age = 10.69 [0.93] years, 74 girls) reported perceived social support, stressful life events, and underwent the Modified Trier Social Stress Test, during which six saliva samples were collected. A two-piece multilevel growth curve model with landmark registration was used to detect trajectory differences in the reactivity and recovery phases of the stress response and account for individual variation in the timing of poststressor peak hormone concentrations. RESULTS: The interaction between stressful life events and perceived social support significantly predicted poststressor peak cortisol levels (ß = 0.0805, SE = 0.0328, p = .015) and cortisol recovery slope (ß = -0.0011, SE = 0.0005, p = .040). Children with more life events and low social support exhibited the lowest poststressor peak cortisol levels and the flattest cortisol recovery slope. In contrast, children high in stressful life events and high in social support displayed cortisol response profiles more similar to those of children with low stressful life events. Conversely, there were no statistically significant two-way interactions of stressful life events and perceived social support on salivary α-amylase parameters (i.e., poststressor peak [p = .38], reactivity slope [p = .81], and recovery slope [p = .32]). CONCLUSIONS: These results provide preliminary evidence for the buffering effect of children's perceived social support on the association between life stress and hypothalamic-pituitary-adrenocortical axis response profiles.

Perceived Social Support and Latent Herpesvirus Reactivation: Testing Main and Stress-Buffering Effects in an Ethnically Diverse Sample of Adults.

OBJECTIVE: Perceived social support is consistently associated with physical health outcomes, and one potential physiological mechanism underlying this association is immune function. In this study, we tested both the main and stress-buffering effects of perceived social support on cellular immunity measured via latent herpesvirus reactivation. METHODS: Data were collected from a community-based sample of 1443 ethnically diverse adults between the ages of 25 and 90 years. Participants self-reported measures of perceived social support, stressful life events, daily hassles, and perceived stress, and provided a blood sample to assess antibody titers to the herpes simplex virus type 1 and Epstein-Barr virus (EBV). RESULTS: In accordance with the main effect hypothesis, results indicated that perceived social support was directly associated with EBV viral capsid antigen antibody titers (ß = -0.06, 95% confidence interval = -0.12 to -0.01, p = .029). Perceived social support, however, did not interact with stressful life events, daily hassles, or perceived stress to influence latent herpesvirus reactivation (p values > .05). Neither race/ethnicity nor age moderated any of the interactions between perceived social support and the stress measures on latent herpesvirus reactivation (p values > .10). CONCLUSIONS: Overall, the current study supports the main effect hypothesis, according to which higher levels of perceived social support were associated with lower levels of herpesvirus antibody titers.

Perceived stress is linked to heightened biomarkers of inflammation via diurnal cortisol in a national sample of adults.

Exposure to and perceptions of stress have been associated with altered systemic inflammation, but the intermediate processes by which stress links to inflammation are not fully understood. Diurnal cortisol slopes were examined as a pathway by which self-reported psychosocial stress is associated with inflammation [i.e., C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, E-Selectin, and Intercellular Adhesion Molecule-1 (ICAM-1)] in a large sample of adults (the Midlife in the US study; N = 914; 55.9% female; aged 34-84 years). Structural equation modeling indicated that perceived psychological stress was associated with flattened diurnal cortisol slopes and flatter diurnal cortisol slopes were, in turn, associated with heightened inflammation in these cross-sectional analyses (index of indirect pathway, ω = 0.003, 95% CI [0.001, 0.004], ωSTD = 0.027; with covariates, ω = 0.001, [0.0002, 0.002], ωSTD = 0.011). A similar indirect effect was evident for self-reported traumatic life events (ω = 0.007, [0.004, 0.012], ωSTD = 0.030); however, inclusion of covariates (i.e., age, gender, race, ethnicity, body mass index, and other factors associated with physical health) accounted for this finding (ω = 0.001, [-0.001, 0.004], ωSTD = 0.005). These results support an allostatic load model of psychosomatic health, in which cortisol (along with other stress-responsive signaling molecules) is a necessary component for understanding links between stress exposure, perceived stress, and immune functioning.

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.

Exogenous testosterone increases the audience effect in healthy males: evidence for the social status hypothesis.

Several studies have implicated testosterone in the modulation of altruistic behaviours instrumental to advancing social status. Independent studies have also shown that people tend to behave more altruistically when being watched (i.e. audience effect). To date, little is known about whether testosterone could modulate the audience effect. In the current study, we tested the effect of testosterone on altruistic behaviour using a donation task, wherein participants were asked to either accept or reject a monetary transfer to a charity organization accompanying a personal cost either in the presence or absence of an observer. We administered testosterone gel or placebo to healthy young men (n = 140) in a double-blind, placebo-controlled, mixed design. Our results showed that participants were more likely to accept the monetary transfer to the charity when being observed compared to when they completed the task alone. More importantly, this audience effect was amplified among people receiving testosterone versus placebo. Our findings suggest that testosterone administration increases the audience effect and further buttress the social status hypothesis, according to which testosterone promotes status-seeking behaviour in a context-dependent manner.

Socioeconomic status and differential psychological and immune responses to a human-caused disaster.

OBJECTIVE: Individuals from different socioeconomic status (SES) backgrounds may respond variably to stressful events, and such differences are likely to contribute to health disparities. The current study leveraged data collected before and after a petrochemical explosion and aimed to investigate how individuals from different SES backgrounds responded to this unexpected stressor in terms of perceived social support, perceived stress, and systemic inflammation. METHODS: Data were drawn from 124 participants (Mage = 55.9 ± 16.1 years, 69.4% female, 29.0% White) living close to a petrochemical complex where the explosion occurred in 2005. SES was assessed at baseline, and perceived stress and inflammatory markers (i.e., C-reactive protein [CRP], interleukin-6 [IL-6]) were assessed at both pre- and post-explosion. Perceived social support was assessed at post-explosion. RESULTS: Lower SES was associated with less perceived social support. Lower SES was also associated with a larger increase in perceived stress and higher levels of IL-6, but not CRP. Perceived social support did not moderate or mediate the effects of SES on changes in perceived stress, IL-6, or CRP. The associations between SES and inflammatory markers were also not explained by changes in perceived stress. CONCLUSION: Findings from this study support the idea that individuals from different SES backgrounds respond differently to stressors at both the psychosocial (perceived social support and perceived stress) and biological (inflammation) levels. Our findings also suggest that these two processes appear to act independently from each other.

Single dose testosterone administration increases impulsivity in the intertemporal choice task among healthy males.

Circulating levels of testosterone have been positively associated with impulsivity. The present study investigates the effect of testosterone administration on impulsivity in an intertemporal choice task, where participants are given a choice between smaller-sooner rewards and larger-later rewards. Healthy young male participants (n = 111) received a single-dose of 150 mg testosterone gel in a double-blind, placebo-controlled, between-subjects design. At 180 min post-administration, participants performed the decision-making task. Both model-free (i.e., higher indifference point) and model-based (i.e., steeper discounting rate) parameters revealed that testosterone administration increased impulsive choice. This finding supports the hypothesis that exogenous testosterone increases impulsivity among healthy young males in a laboratory task.

Human reproductive behavior, life history, and the Challenge Hypothesis: A 30-year review, retrospective and future directions.

The Challenge Hypothesis (Wingfield et al., 1990) originally focused on adult male avian testosterone elevated in response to same-sex competition in reproductive contexts. The purpose of the present paper is to demonstrate how the Challenge Hypothesis has shaped ideas about human life histories. We conduct a citation analysis, drawing upon 400 Google Scholar citations in the human literature to identify patterns in this body of scholarship. We cover key factors, such as context and personality traits, that help explain variable testosterone responses such as winning/losing to adult competitive behavior. Findings from studies on courtship and sexual behavior indicate some variation in testosterone responses depending on factors such as motivation. A large body of research indicates that male testosterone levels are often lower in contexts of long-term committed partnerships and nurturant fathering and aligned with variation in male mating and parenting effort. As the Challenge Hypothesis is extended across the life course, DHEA and androstenedione (rather than testosterone) appear more responsive to juvenile male competitive behavior, and during reproductive senescence, baseline male testosterone levels decrease just as male life history allocations show decreased mating effort. We discuss how research on testosterone administration, particularly in older men, provides causal insight into effects of testosterone in humans, and how this "natural experiment" can be viewed in light of the Challenge Hypothesis. We synthesize central concepts and findings, such as an expanded array of costs of testosterone that inform life history tradeoffs between maintenance and reproductive effort, and we conclude with directions for future research.

Diurnal Cortisol in a Sample of Socioeconomically Disadvantaged Chinese Children: Evidence for the Shift-and-Persist Hypothesis.

OBJECTIVE: Low socioeconomic status (SES) is one of the most well-established social determinants of health. However, little is known about what can protect the health of individuals (especially children) living in low-SES circumstances. This study explored whether the psychological strategy of "shift-and-persist" protects low-SES children from stress-related physiological risks, as measured through blunted (unhealthy) diurnal cortisol profiles. METHODS: A sample of 645 children (aged 8-15 years) from low-SES backgrounds and having at least one HIV-positive parent completed a battery of psychological scales. Diurnal cortisol assessments included collection of saliva samples four times a day for 3 days, from which three cortisol parameters (cortisol at awakening, cortisol awakening response, and cortisol slope) were derived. RESULTS: Higher levels of shift-and-persist, considered as a single variable, were associated with higher cortisol at awakening (B = 0.0119, SE = 0.0034, p < .001) and a steeper cortisol slope (B = -0.0007, SE = 0.0003, p = .023). These associations remained significant after adjusting for covariates and did not vary by age. In supplementary analyses, where shifting and persisting were treated as separate variables, the interaction between these two coping strategies significantly predicted cortisol at awakening (B = 0.0250, SE = 0.0107, p = .020) and the cortisol slope (B = -0.0022, SE = 0.0011, p = .040), suggesting that the combination of shift-and-persist is important for predicting diurnal cortisol profiles. CONCLUSIONS: Our findings demonstrate that shift-and-persist is associated with healthier diurnal cortisol profiles among socioeconomically disadvantaged children and introduce the possibility that this coping strategy is protective against other stressors, such as those uniquely faced by children in our study (i.e., being affected by parental HIV).