Daily interpersonal stress, sleep duration, and gene regulation during late adolescence.

BACKGROUND: Psychological stress and poor sleep are associated with a wide range of negative health outcomes, which are thought to be mediated in part by alterations in immune processes. However, the molecular bases of links among stress, sleep, and immune processes are not completely understood, particularly during adolescence when sensitivity to stress and problems with sleep tend to increase. In the current study, we investigated whether various stressors (daily stress, major life events, perceived stress), sleep indices (duration, efficiency), and their interactions (e.g., moderating effects) are associated with expression of genes bearing response elements for transcription factors that regulate inflammatory and anti-viral processes. METHOD: Eighty-seven late adolescents completed daily checklists of their social experiences across a 15-day period and reported on their major life events during the previous year. They also completed actigraphy-based assessments of sleep quality and duration during 8 consecutive nights. An average of 5.5 months later, participants reported on their global perceptions of stress during the previous month and provided blood samples for genome-wide expression profiling of mRNA from peripheral blood mononuclear cells (PBMCs). RESULTS: Higher levels of daily interpersonal stress and shorter sleep duration were associated with upregulation of inflammation-related genes bearing response elements for proinflammatory transcription factor nuclear factor kappa B (NF-κB). Shorter sleep duration was also linked to downregulation of antiviral-related genes bearing response elements for interferon response factors (IRFs). Lastly, there was a significant interaction between daily stress and shorter sleep duration, such that the association between daily stress and inflammation-related gene expression was exacerbated in the context of shorter sleep duration. Results were independent of sex, ethnicity, parent education, body mass index, and smoking and alcohol history. CONCLUSION: Everyday interpersonal stress and shortened sleep can be consequential for upstream NF-κB signaling pathways relevant to inflammatory processes during late adolescence. Notably, the occurrence of both may lead to even greater activation of NF-κB signaling.

Stress, Psychological Resources, and HPA and Inflammatory Reactivity During Late Adolescence.

Psychosocial stress during childhood and adolescence is associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis and with heightened inflammation, both of which are implicated in poor health; however, factors that may protect against these effects relatively early in life are not well understood. Thus, we examined whether psychosocial resources protect against stress-related alterations in the HPA axis and heightened inflammation in a sample of 91 late adolescents. Participants completed measures of various stressors (major life events, daily interpersonal stress, early adversity), and psychosocial resources (mastery, optimism, self-esteem, and positive reappraisal). They also completed the Trier Social Stress Test and provided saliva and blood samples for the assessment of cortisol and interleukin-6 reactivity. Each of the stressors was associated with lower cortisol reactivity. Additionally, associations with major life events and daily stress were moderated by psychological resources, such that more life events and daily stress were associated with decreased HPA reactivity among adolescents with lower levels of psychological resources, but not among those with higher levels of psychological resources. This pattern of findings was observed only for cortisol reactivity and not for interleukin-6 reactivity. Findings suggest that psychological resources may counteract the effects of certain adversity-related decreases in cortisol reactivity.

Adiposity moderates links from early adversity and depressive symptoms to inflammatory reactivity to acute stress during late adolescence.

Both early adversity and depression are associated with heightened inflammation. However, few studies have focused on inflammatory reactivity to psychosocial stress and examined adiposity as a potential moderator. Yet, repeated heightened inflammatory reactivity over time is thought to contribute to low-grade chronic inflammation and adipose tissue is a key source of pro-inflammatory cytokines. The purpose of the present study was to examine whether early adversity and depressive symptoms were related to stress-induced inflammation and whether these associations varied by total body and abdominal adiposity as measured by body mass index (BMI) and waist circumference (WC) in a sample of late adolescents. Participants reported on their early family environment and current depressive symptoms, had their height, weight, and WC assessed for adiposity markers, and provided blood samples for IL-6 assessment before and after a standardized laboratory stress task. No main effect of early adversity on IL-6 reactivity to acute stress was observed. However, significant interactions between early adversity and BMI and WC emerged. Greater exposure to early adversity was associated with greater IL-6 responses only among adolescents with higher BMI or WC. The same pattern of findings was observed for depressive symptoms. Additionally, moderated mediation analyses indicated that among adolescents with greater adiposity, early adversity indirectly influenced IL-6 reactivity via current depressive symptoms. These findings contribute to our understanding of vulnerability factors that may amplify the associations between early adversity and depressive symptoms and inflammation during relatively early stages of life.

Childhood family psychosocial environment and carotid intima media thickness: the CARDIA study.

Little is known about whether the childhood family psychosocial environment (characterized by cold, unaffectionate interactions, conflict, aggression, neglect and/or low nurturance) affects coronary heart disease (CHD) risk. Objectives were to evaluate associations of childhood family psychosocial environment with carotid intima media thickness (IMT), a subclinical measure of atherosclerosis. The study population included 2659 CARDIA study participants, aged 37-52 years. Childhood family psychosocial environment was measured using a risky family questionnaire via self-report. Carotid IMT was calculated using the average of 20 measurements of mean common carotid, bulb and internal carotid IMT, assessed using high-resolution B-mode ultrasound images. Utilizing linear regression analyses adjusted for age, a 1-unit (range 0-21) increase in risky family score was associated with 0.0036 (95% CI: 0.0006,0.0066 mm) and 0.0020 (95% CI: 0.0002,0.0038) mm increase in mean IMT in white males and females, respectively. Formal mediation analyses and covariate adjustments suggested childhood socioeconomic position and smoking may be important mechanisms in white males and females, as well as education and depressive symptomatology in white males. No associations were found in black participants. Formal statistical tests for interaction between risky family score and sex, and between risky family score and race/ethnicity, demonstrated borderline evidence of interactions for both sex (p = 0.12) and race/ethnicity (p = 0.14) with risky family score for associations with mean IMT. In conclusion, childhood family psychosocial environment was positively associated with IMT in white participants, with little evidence of association in black participants. Mechanisms in white participants may include potential negative impacts of socioeconomic constraints on parenting quality, potentially influencing offspring's cardiovascular risk factors (e.g. smoking), socioeconomic position (e.g. education), and/or psychosocial functioning (e.g. depression), which may in turn lead to atherosclerotic processes. Borderline racial/ethnic differences in findings should be replicated, but add to literature exploring race/ethnicity-specific associations of parenting approaches with health outcomes.

Negative and competitive social interactions are related to heightened proinflammatory cytokine activity.

Research has consistently documented that social relationships influence physical health, a link that may implicate systemic inflammation. We examined whether daily social interactions predict levels of proinflammatory cytokines IL-6 and the soluble receptor for tumor necrosis factor-α (sTNFαRII) and their reactivity to a social stressor. One-hundred twenty-two healthy young adults completed daily diaries for 8 d that assessed positive, negative, and competitive social interactions. Participants then engaged in laboratory stress challenges, and IL-6 and sTNFαRII were collected at baseline and at 25- and 80-min poststressor, from oral mucosal transudate. Negative social interactions predicted elevated sTNFαRII at baseline, and IL-6 and sTNFαRII 25-min poststressor, as well as total output of sTNFαRII. Competitive social interactions predicted elevated baseline levels of IL-6 and sTNFαRII and total output of both cytokines. These findings suggest that daily social interactions that are negative and competitive are associated prospectively with heightened proinflammatory cytokine activity.

Childhood family psychosocial environment and coronary heart disease risk.

OBJECTIVE: Little is known about whether the childhood family psychosocial environment affects coronary heart disease (CHD). Study objectives were to evaluate associations of childhood family psychosocial environment (termed "risky families"; characterized by cold, unaffectionate interactions, conflict, aggression, neglect, and/or low nurturance) with calculated risk for CHD. METHODS: Study participants included 3554 participants of the Coronary Artery Risk Development in Young Adults Study, aged 33 to 45 years. Childhood family psychosocial environment was measured using a risky family questionnaire via self-report. Ten-year CHD risk was calculated using the validated Framingham risk algorithm. RESULTS: In a multivariable-adjusted regression analysis adjusted for age, race/ethnicity, and childhood socioeconomic position, a 1-unit (range, 0-21) increase in risky family score was associated with 1.0% (95% confidence interval = 0.4%-1.7%) and 1.0% (95% confidence interval = 0.2%-1.8%) higher CHD risk in women and men, respectively. Multiple mediation analyses suggested significant indirect effects of education, income, depressive symptomatology, and anger-out expression in women and education in men, indicating that these may be mediating mechanisms between childhood psychosocial environment and CHD risk. Of the modifiable Framingham algorithm components, smoking (in women and men) and high-density lipoprotein (in women) were the factors most strongly associated with risky family score. CONCLUSIONS: Childhood family psychosocial environment was positively associated with the calculated 10-year CHD risk. Mechanisms may include the potential negative impact of childhood family psychosocial environment on later-life socioeconomic position (e.g., education in men and women) and/or psychosocial functioning (e.g., depression and anger-out expression in women), which may in turn lead to higher CHD risk, particularly through smoking (in men and women) and low level of high-density lipoprotein cholesterol (in women).

Neural sensitivity to social rejection is associated with inflammatory responses to social stress.

Although stress-induced increases in inflammation have been implicated in several major disorders, including cardiovascular disease and depression, the neurocognitive pathways that underlie inflammatory responses to stress remain largely unknown. To examine these processes, we recruited 124 healthy young adult participants to complete a laboratory-based social stressor while markers of inflammatory activity were obtained from oral fluids. A subset of participants (n = 31) later completed an fMRI session in which their neural responses to social rejection were assessed. As predicted, exposure to the laboratory-based social stressor was associated with significant increases in two markers of inflammatory activity, namely a soluble receptor for tumor necrosis factor-alpha (sTNFalphaRII) and interleukin-6 (IL-6). In the neuroimaging subsample, greater increases in sTNFalphaRII (but not IL-6) were associated with greater activity in the dorsal anterior cingulate cortex and anterior insula, brain regions that have previously been associated with processing rejection-related distress and negative affect. These data thus elucidate a neurocognitive pathway that may be involved in potentiated inflammatory responses to acute social stress. As such, they have implications for understanding how social stressors may promote susceptibility to diseases with an inflammatory component.

Anger and fear responses to stress have different biological profiles.

In contrast to a general model of stress, a functional model suggests that emotions may regulate stress responses in specific adaptive ways. The current study examined whether anger and fear during a challenging stress task (Trier Social Stress Task) were differentially associated with cortisol and proinflammatory cytokine responses to an acute stressor. Baseline anger and fear were related to greater cortisol and proinflammatory cytokines. However, anger reactions to the stressor were associated with greater stress-related increases in cortisol over time but not proinflammatory cytokines. In contrast, fear reactions to the stressor were associated with increases in stress-related proinflammatory cytokines over time and a decrease in cortisol. Results are consistent with the functional perspective that distinct emotional experiences appear to trigger temporally-patterned adaptive biological processes to mobilize energy in response to anger and to promote withdrawal in response to fear. Discussion focuses on the role of the HPA axis to increase available metabolic fuel and proinflammatory cytokines to prompt behavioral withdrawal.

Neurobiological correlates of coping through emotional approach.

This investigation considered possible health-related neurobiological processes associated with "emotional approach coping" (EAC), or intentional efforts to identify, process, and express emotions surrounding stressors. It was hypothesized that higher dispositional use of EAC strategies would be related to neural activity indicative of greater trait approach motivational orientation and to lower proinflammatory cytokine and cortisol responses to stress. To assess these relationships, 46 healthy participants completed a questionnaire assessing the two components of EAC (i.e., emotional processing and emotional expression), and their resting frontal cortical asymmetry was measured using electroencephalography (EEG). A subset (N=22) of these participants' levels of the soluble receptor for tumor necrosis factor-alpha (sTNFalphaRII), interleukin-6 (IL-6), and cortisol (all obtained from oral fluids) were also assessed before and after exposure to an acute laboratory stressor. Consistent with predictions, higher reported levels of emotional expression were significantly associated with greater relative left-sided frontal EEG asymmetry, indicative of greater trait approach motivation. Additionally, people who scored higher on EAC, particularly the emotional processing component, tended to show a less-pronounced TNF-alpha stress response. EAC was unrelated to levels of IL-6 and cortisol. Greater left-sided frontal EEG asymmetry was significantly related to lower baseline levels of IL-6 and to lower stress-related levels of sTNFalphaRII, and was marginally related to lower stress-related levels of IL-6. The findings suggest that the salubrious effects of EAC strategies for managing stress may be linked to an approach-oriented neurocognitive profile and to well-regulated proinflammatory cytokine responses to stress.

Neural pathways link social support to attenuated neuroendocrine stress responses.

It is well established that a lack of social support constitutes a major risk factor for morbidity and mortality, comparable to risk factors such as smoking, obesity, and high blood pressure. Although it has been hypothesized that social support may benefit health by reducing physiological reactivity to stressors, the mechanisms underlying this process remain unclear. Moreover, to date, no studies have investigated the neurocognitive mechanisms that translate experiences of social support into the health outcomes that follow. To investigate these processes, thirty participants completed three tasks in which daily social support, neurocognitive reactivity to a social stressor, and neuroendocrine responses to a social stressor were assessed. Individuals who interacted regularly with supportive individuals across a 10-day period showed diminished cortisol reactivity to a social stressor. Moreover, greater social support and diminished cortisol responses were associated with diminished activity in the dorsal anterior cingulate cortex (dACC) and Brodmann's area (BA) 8, regions previously associated with the distress of social separation. Lastly, individual differences in dACC and BA 8 reactivity mediated the relationship between high daily social support and low cortisol reactivity, such that supported individuals showed reduced neurocognitive reactivity to social stressors, which in turn was associated with reduced neuroendocrine stress responses. This study is the first to investigate the neural underpinnings of the social support-health relationship and provides evidence that social support may ultimately benefit health by diminishing neural and physiological reactivity to social stressors.

Does self-affirmation, cognitive processing, or discovery of meaning explain cancer-related health benefits of expressive writing?

Although expressive writing has positive effects on health, little is known about the underlying psychological mechanisms for these effects. The present study assessed self-affirmation, cognitive processing, and discovery of meaning as potential mediators of the effects of expressive writing on physical health in early-stage breast cancer survivors. A content analysis of the essays showed that self-affirmation writing was associated with fewer physical symptoms at a 3-month follow-up assessment, with self-affirmation writing fully mediating the effects of the emotional expression and benefit-finding writing conditions on reduced physical symptoms. Cognitive processing and discovery of meaning writing were not associated with any physical health outcomes. Consistent with evidence showing that self-affirmation plays an important role in buffering stress, the present study provides the first evidence for self-affirmation as a viable mechanism underlying the health benefits of expressive writing.

Relation of oxytocin to psychological stress responses and hypothalamic-pituitary-adrenocortical axis activity in older women.

OBJECTIVE: Animal research suggests that oxytocin (OT) plays a role in stress responses and that in females, this role is modulated by estrogen. Yet little is known about the relation of OT to human stress responses. This study was conducted to examine the relations between estrogen activity and OT, identify stressors distinctively associated with elevations in OT, and investigate whether OT is related to cardiovascular and hypothalamic-pituitary-adrenocortical (HPA) activity in a laboratory challenge paradigm. METHODS: Seventy-three postmenopausal women who were on hormone therapy (HT) or not completed questionnaires assessing psychological distress and social relationships and then participated in a laboratory stress challenge (Trier Social Stress Task), during which OT, cortisol, and blood pressure were assessed. RESULTS: HT was significantly associated with higher plasma OT. Controlling for HT, elevated plasma OT was significantly associated with gaps in social relationships, with less positive relationships with a primary partner, and with elevated cortisol levels. OT was not associated with stress reactivity or recovery. CONCLUSION: In women, plasma OT signals relationship stress and is associated with elevated cortisol; it does not appear to significantly affect cortisol or blood pressure responses to acute stress.

Finding positive meaning and its association with natural killer cell cytotoxicity among participants in a bereavement-related disclosure intervention.

This study tested the hypothesis that cognitive processing about a past bereavement would produce increases in goals and priorities indicative of finding positive meaning from the loss. It was further hypothesized that increases in meaning-related goals would be associated with changes in immune function, specifically increased natural killer cell cytotoxicity (NKCC). Cognitive processing was manipulated using written emotional disclosure. Forty-three women who had lost a close relative to breast cancer wrote about the death (cognitive processing/disclosure group) or about nonemotional topics weekly for 4 weeks. Contrary to predictions, written disclosure did not induce changes in meaning-related goals or NK cell parameters. However, women in both experimental groups who reported positive changes in meaning-related goals over the study period also showed increases in NKCC. Results suggest that prioritizing goals emphasizing relationships, personal growth, and striving for meaning in life may have positive biological correlates but that solitary written disclosure may not be sufficient to induce changes in these goals in response to a past bereavement.