Intergenerational transmission of lifetime stressor exposure in adolescent girls at differential maternal risk for depression.

OBJECTIVE: Adolescent girls who grow up with mothers who are depressed are themselves highly vulnerable to developing depression (i.e., "intergenerational transmission of depression"). Stressor exposure is a strong risk factor for depression, and the transmission of depression risk from mothers to daughters is partly due to mothers experiencing more stressors, increasing daughters' stressor burden. However, research in this area has only assessed recent stressors, making the role of cumulative lifetime stressors unclear. METHOD: To address this issue, we recruited 52 dyads of mothers and adolescent daughters, of which 22 daughters were at high maternal risk for depression. Participants completed diagnostic interviews, and daughters additionally self-reported their depressive symptoms. Participants also completed the Stress and Adversity Inventory, a new-generation instrument for assessing cumulative lifetime history of acute and chronic stressors based on the contextual threat approach. We tested moderated mediation models evaluating the conditional indirect effects of mothers' lifetime stressors on high- versus low-risk daughters' depressive symptoms through daughters' lifetime stressors. RESULTS: As hypothesized, mothers of high-risk (but not low-risk) adolescent daughters who reported more lifetime acute stressors had daughters who reported more lifetime acute stressors and current depressive symptoms. Moreover, this finding was driven specifically by mothers' stressors occurring after their daughters' births. There was also tentative evidence that high-risk daughters' lifetime chronic stressors potentiated the impact of daughters' acute stressors on their depressive symptoms. CONCLUSION: These findings provide new insights into how stressful contexts are transmitted intergenerationally.

Recalled Neighborhood Environments, Parental Control, and Cytokine-Mediated Response to Viral Challenge.

OBJECTIVE: Neighborhood risk in childhood is associated with poor health across the life span. However, many people who are reared in risky neighborhoods remain healthy in adulthood. In the context of high-risk neighborhoods, parenting practices that are controlling might promote better physical health outcomes later in life. The current study used a viral challenge paradigm to examine whether parental control throughout childhood moderated the association between recalled neighborhood risk and cytokine-mediated cold susceptibility. METHODS: A sample of 209 healthy adults completed questionnaires to assess recalled neighborhood risk and parental control over the first 15 years of life, were exposed to a common cold virus, and were quarantined for 6 days. Researchers assessed nasal proinflammatory cytokine production and objective markers of illness. Participants were diagnosed with a clinical cold if they met the infection and objective illness criteria. RESULTS: A significant Neighborhood Risk by Parental Control interaction emerged to predict proinflammatory cytokine production. Furthermore, parental control moderated the cytokine-mediated association between neighborhood risk and cold diagnosis (index = -0.073, 95% confidence interval [CI] = -0.170 to -0.016), likelihood of infection (index = -0.071, 95% CI = -0.172 to -0.015), and meeting the objective symptom criteria (index = -0.074, 95% CI = -0.195 to -0.005). Specifically, there was a negative association between neighborhood risk and objective cold diagnosis and infection status at higher levels of parental control, but a nonsignificant association at lower levels of parental control. CONCLUSIONS: Findings suggest that the degree to which recalled neighborhood risk is related to adult health varies as a function of parental control throughout childhood.

Ten Surprising Facts About Stressful Life Events and Disease Risk.

After over 70 years of research on the association between stressful life events and health, it is generally accepted that we have a good understanding of the role of stressors in disease risk. In this review, we highlight that knowledge but also emphasize misunderstandings and weaknesses in this literature with the hope of triggering further theoretical and empirical development. We organize this review in a somewhat provocative manner, with each section focusing on an important issue in the literature where we feel that there has been some misunderstanding of the evidence and its implications. Issues that we address include the definition of a stressful event, characteristics of diseases that are impacted by events, differences in the effects of chronic and acute events, the cumulative effects of events, differences in events across the life course, differences in events for men and women, resilience to events, and methodological challenges in the literature.

Receiving a hug is associated with the attenuation of negative mood that occurs on days with interpersonal conflict.

Interpersonal touch is emerging as an important topic in the study of adult relationships, with recent research showing that such behaviors can promote better relationship functioning and individual well-being. This investigation considers whether being hugged is associated with reduced conflict-related decreases in positive affect and increases in negative affect as well as whether these associations differ between women and men. A sample of 404 adults were interviewed every night for 14 consecutive days about their conflicts, hug receipt, and positive and negative affect. Results indicated that there was an interaction between hug receipt and conflict exposure such that receiving a hug was associated with a smaller conflict-related decrease in positive affect and a smaller conflict-related increase in negative affect when assessed concurrently. Hug receipt was also prospectively associated with a smaller conflict-related increase in next day negative affect but was not associated with next day positive affect. Associations between hug receipt and conflict-related changes in affect did not differ between women and men, between individuals who were married or in a marital-like relationship and those who were not, or as a function of individual differences in baseline perceived social support. While correlational, these results are consistent with the hypothesis that hugs buffer against deleterious changes in affect associated with experiencing interpersonal conflict. Possible mechanisms through which hugs facilitate positive adaptation to conflict are discussed.

Social integration and age-related decline in lung function.

OBJECTIVES: We tested the hypothesis that social integration, measured as number of social roles, is associated with less age-related loss of lung function, an important marker of health and longevity. We also investigated possible psychological factors through which social integration might influence lung health. METHODS: Data were analyzed from the Health and Retirement Study (ages 52-94, n = 4,224). RESULTS AND CONCLUSIONS: Each additional social role reported at baseline was associated with less of a decline in lung function between baseline and the follow-up assessment four years later. The association withstood controls for demographics, weight, and height and was mediated by more positive and less negative affect and lower rates of cigarette smoking and more physical activity. Roles were mostly substitutable, with both high (spouse, parent, friends, relatives) and low (employee, religious service attendee, volunteer, members of other groups) intimacy roles independently contributing to less age-related decline in lung function. (PsycINFO Database Record

Age moderates the association between social integration and diurnal cortisol measures.

Social integration is defined as the degree to which an individual participates in a broad range of social relationships. Although measures of social integration vary across studies, it is often assessed as the number of social roles (e.g., parent, friend, student, volunteer) that an individual reports actively participating in. More socially integrated individuals tend to be healthier than those less socially integrated, but the biological mechanisms through which this occurs remain unclear. One possibility is that social integration might alter the function of the hypothalamic-pituitary-adrenal axis, of which cortisol is a key product, and in turn influence a broad range of health outcomes. This study examined the association between social integration and two indices of cortisol in a community sample of 680 healthy men and women aged 18-55. Because the social roles held by younger individuals may be more numerous yet superficial than those held by older individuals, this study also tested the hypothesis that these associations could be moderated by age such that lower levels of integration would be associated with cortisol dysregulation for older but not younger individuals in our sample. Participants provided salivary cortisol samples during waking hours on three days that were used to calculate diurnal cortisol levels and slopes. Increased social integration was associated with lower cortisol AUC among older (ages 35-55) but not younger (ages 18-34) individuals in our sample. Moreover, while increased social integration was associated with steeper diurnal cortisol slopes regardless of age, this association was strongest among older individuals. Differences in health behaviors, affect, and psychological stress did not mediate these associations. The results of this study support cortisol as a candidate biological mechanism through which increased social integration is associated with better physical health among older individuals.

Psychosocial functioning and the cortisol awakening response: Meta-analysis, P-curve analysis, and evaluation of the evidential value in existing studies.

Cortisol levels rise immediately after awakening and peak approximately 30-45min thereafter. Psychosocial functioning influences this cortisol awakening response (CAR), but there is considerable heterogeneity in the literature. The current study used p-curve and meta-analysis on 709 findings from 212 studies to test the evidential value and estimate effect sizes of four sets of findings: those associating worse psychosocial functioning with higher or lower cortisol increase relative to the waking period (CARi) and to the output of the waking period (AUCw). All four sets of findings demonstrated evidential value. Psychosocial predictors explained 1%-3.6% of variance in CARi and AUCw responses. Based on these effect sizes, cross-sectional studies assessing CAR would need a minimum sample size of 617-783 to detect true effects with 80% power. Depression was linked to higher AUCw and posttraumatic stress to lower AUCw, whereas inconclusive results were obtained for predictor-specific effects on CARi. Suggestions for future CAR research are discussed.

Offspring of parents who were separated and not speaking to one another have reduced resistance to the common cold as adults.

Exposure to parental separation or divorce during childhood has been associated with an increased risk for physical morbidity during adulthood. Here we tested the hypothesis that this association is primarily attributable to separated parents who do not communicate with each other. We also examined whether early exposure to separated parents in conflict is associated with greater viral-induced inflammatory response in adulthood and in turn with increased susceptibility to viral-induced upper respiratory disease. After assessment of their parents' relationship during their childhood, 201 healthy volunteers, age 18-55 y, were quarantined, experimentally exposed to a virus that causes a common cold, and monitored for 5 d for the development of a respiratory illness. Monitoring included daily assessments of viral-specific infection, objective markers of illness, and local production of proinflammatory cytokines. Adults whose parents lived apart and never spoke during their childhood were more than three times as likely to develop a cold when exposed to the upper respiratory virus than adults from intact families. Conversely, individuals whose parents were separated but communicated with each other showed no increase in risk compared with those from intact families. These differences persisted in analyses adjusted for potentially confounding variables (demographics, current socioeconomic status, body mass index, season, baseline immunity to the challenge virus, affectivity, and childhood socioeconomic status). Mediation analyses were consistent with the hypothesis that greater susceptibility to respiratory infectious illness among the offspring of noncommunicating parents was attributable to a greater local proinflammatory response to infection.

Marital status as a predictor of diurnal salivary cortisol levels and slopes in a community sample of healthy adults.

Married people tend to be healthier than both the previously (bereaved, divorced, and separated) and never married, but the mechanisms through which this occurs remain unclear. To this end, research has increasingly focused on how psychological stress experienced by unmarried versus married individuals may differentially impact physiological systems related to health. One key system that is modulated by stress is the hypothalamic-pituitary-adrenal (HPA) axis, of which cortisol is a key hormonal product. Increased cortisol production and disruption of cortisol's daily rhythm have been linked to poorer health outcomes. This study examined the association between current marital status and these two indices of cortisol in a community sample of 572 healthy men and women aged 21-55. It also tested whether marriage buffers against the effect of stress (perceived stress by marital status interaction) on cortisol production. Participants provided salivary cortisol samples during waking hours on three nonconsecutive separate days to calculate diurnal cortisol levels and slopes. Married individuals had lower cortisol levels than either their never married or previously married counterparts. Differences in cortisol levels were due at least in part to currently married individuals having a more rapid decline in cortisol through the afternoon hours compared to individuals who were never married (but not those who were previously married). Furthermore, there was an interaction between perceived stress and marital status in predicting cortisol levels. Specifically, higher stress was associated with higher cortisol levels for previously married individuals but not for the married or never married. The results of this study support cortisol as one candidate mechanism accounting for the association of marital status and health.

Targeted rejection predicts decreased anti-inflammatory gene expression and increased symptom severity in youth with asthma.

Although responses to different stressors are sometimes assumed to be similar, recent research has demonstrated that certain types of stress, such as targeted rejection, are particularly potent. To test such associations in a chronic-disease model, we examined how noninterpersonal, interpersonal, and targeted-rejection major life events predicted changes in gene expression and symptom severity in 121 youths with asthma who were assessed every 6 months for 2 years. Youths who had recently experienced targeted rejection had lower messenger RNA expression for signaling molecules that control airway inflammation and obstruction (specifically, the glucocorticoid receptor and ß2-adrenergic receptor) than youths who had not experienced targeted rejection. These associations were specific to targeted rejection and stronger for youths higher in subjective social status. Higher-status youths exposed to targeted rejection (but not other types of stress) also reported more asthma symptoms. These data demonstrate stressor-specific associations with molecular-signaling pathways and the severity of asthma, and they suggest that threats to the social self may be particularly deleterious.

Greater inflammatory activity and blunted glucocorticoid signaling in monocytes of chronically stressed caregivers.

Chronic stress is associated with morbidity and mortality from numerous conditions, many of whose pathogenesis involves persistent inflammation. Here, we examine how chronic stress influences signaling pathways that regulate inflammation in monocytes. The sample consisted of 33 adults caring for a family member with glioblastoma and 47 controls whose lives were free of major stressors. The subjects were assessed four times over eight months. Relative to controls, caregivers' monocytes showed increased expression of genes bearing response elements for nuclear-factor kappa B, a key pro-inflammatory transcription factor. Simultaneously, caregivers showed reduced expression of genes with response elements for the glucocorticoid receptor, a transcription factor that conveys cortisol's anti-inflammatory signals to monocytes. Transcript origin analyses revealed that CD14+/CD16- cells, a population of immature monocytes, were the predominate source of inflammatory gene expression among caregivers. We considered hormonal, molecular, and functional explanations for caregivers' decreased glucocorticoid-mediated transcription. Across twelve days, the groups displayed similar diurnal cortisol profiles, suggesting that differential adrenocortical activity was not involved. Moreover, the groups' monocytes expressed similar amounts of glucocorticoid receptor protein, suggesting that differential receptor availability was not involved. In ex vivo studies, subjects' monocytes were stimulated with lipopolysaccharide, and caregivers showed greater production of the inflammatory cytokine interleukin-6 relative to controls. However, no group differences in functional glucocorticoid sensitivity were apparent; hydrocortisone was equally effective at inhibiting cytokine production in caregivers and controls. These findings may help shed light on the mechanisms through which caregiving increases vulnerability to inflammation-related diseases.

How stable are diurnal cortisol activity indices in healthy individuals? Evidence from three multi-wave studies.

BACKGROUND: Indices of cortisol activity, including the cortisol awakening response (CAR), diurnal slope, and cortisol output across the day (total daily output), are often studied as mechanistic indicators that could link stress with health. Yet there is a paucity of data speaking to their temporal features, particularly whether they behave in a more state- or trait-like manner across time. METHODS: To address this issue, data from 3 studies were used to assess CAR, diurnal slope and total daily output stability over different age groups and time spans: 130 healthy children and adolescents collected salivary cortisol samples 5 times/day (1, 4, 9 and 11h after wake) over 2 days at 5 visits spaced 6 months apart (Study 1); 147 adolescent girls collected saliva 6 times/day (wake, 1, 4, 9 and 14 h after wake) for 2 days at 3 visits, each a year apart (Study 2); and 47 healthy, primarily middle age adults collected saliva 6 times/day (wake, 1, 4, 9 and 14 h after wake) for 3 days at 4 visits spaced 2-3 months apart (Study 3). Stability was estimated by multilevel model-derived intraclass correlation coefficients (ICCs). RESULTS: Across studies, approximately 50% of the variance in cortisol indices was attributable to day-to-day fluctuations, suggesting state-like properties. Of the indices, total daily output emerged as the most stable over time, followed by diurnal slope and CAR, but stability estimates were generally quite modest regardless of index and sample. Over time spans of >1 year, ICCs were ≤ .13. CONCLUSIONS: Most of the variance in CAR, diurnal slope and total daily output reflects day-to-day fluctuation; there was little evidence for more stable trait-like influences. These findings suggest that future research should focus on short-term fluctuations in stress, cortisol and health, as opposed to lengthy disease processes.

Targeted Rejection Triggers Differential Pro- and Anti-Inflammatory Gene Expression in Adolescents as a Function of Social Status.

Social difficulties during adolescence influence life-span health. To elucidate underlying mechanisms, we examined whether a noxious social event, targeted rejection (TR), influences the signaling pathways that regulate inflammation, which is implicated in a number of health problems. For this study, 147 adolescent women at risk for developing a first episode of major depression were interviewed every 6 months for 2.5 years to assess recent TR exposure, and blood was drawn to quantify leukocyte messenger RNA (mRNA) for nuclear factor-κB (NF-κB) and inhibitor of κB (I-κB) and the inflammatory biomarkers C-reactive protein and interleukin-6. Participants had more NF-κB and I-κB mRNA at visits when TR had occurred. These shifts in inflammatory signaling were most pronounced for adolescents high in perceived social status. These findings demonstrate that social rejection upregulates inflammatory gene expression in youth at risk for depression, particularly for those high in status. If sustained, this heightened inflammatory signaling could have implications for life-span health.

Conscientiousness and stress exposure and reactivity: a prospective study of adolescent females.

Conscientiousness is associated with health, but the mechanisms remain poorly understood. To explore the role that stress might play, this study examined whether conscientiousness was associated with exposure and reactivity to life stress. This study followed 133 adolescent women every 6 months for 2.5 years. Participants completed a baseline measure of conscientiousness, and at each visit underwent a structured interview to catalogue episodic and chronic stress and had blood drawn to assess inflammatory processes. Participants higher in conscientiousness experienced fewer self-dependent episodic stressors and less academic and interpersonal chronic stress throughout the study. However, at times when they experienced higher levels of chronic interpersonal stress, they became more resistant to glucocorticoids. Higher levels of conscientiousness may protect adolescent women from exposure to certain stressors. However, when stress occurs, highly conscientious individuals may become more resistant to glucocorticoids, increasing their risk for processes that influence inflammatory conditions.

Multiwave associations between depressive symptoms and endothelial function in adolescent and young adult females.

OBJECTIVE: Depression has been linked to endothelial dysfunction, and some research suggests that past depressive episodes are associated with a lasting, negative impact on the endothelium. However, investigations in this area have been predominantly cross-sectional, raising questions about the direction of these associations. Using a multiwave design, we sought to extend previous research in this area by examining whether depressive symptoms have a lasting negative influence on endothelial function. METHODS: A total of 135 adolescent and young adult females with no known or suspected major health problems were followed for 2½ years. Endothelial function was assessed at three time points throughout the study. The Beck Depression Inventory was administered, and information about health practices was collected every 6 months. RESULTS: Self-reported depressive symptoms covaried with endothelial functioning on a within-person basis (ß = -0.23, p < .05). As a participant's depression symptoms rose beyond her typical level, her endothelial function declined commensurately. This association persisted after controlling for health practices and adiposity. There was no evidence that depressive symptoms predicted endothelial function at later time points or interacted with time to predict the trajectories of endothelial function over the follow-up period. CONCLUSIONS: Depressive symptoms were concurrently associated with endothelial function in this cohort of healthy adolescent girls and young women. On visits when participants endorsed depressive symptoms that were higher than their mean level of depression, they tended to have worse endothelial function. We did not observe a lasting negative effect of depression on endothelial function.