Kirsten M. Poehlmann

Autonomic, Neuroendocrine, and Immune Responses to Psychological Stress: The Reactivity Hypothesisa

Abstract: We examined the effects of brief psychological stressors on cardiovascular, neuroendocrine, and cellular immune response in 22 older women to investigate the common effects of stress across systems. Results revealed that psychological stressors heightened cardiac sympathetic activation, elevated plasma catecholamine concentrations, and affected the cellular immune response (ps < 0.05). In a replication and extension, 27 women caring for a spouse with a progressive dementia (high chronic stress) and 37 controls category matched for age and family income (low chronic stress) performed the 12‐min laboratory stressor. Measures were taken before (low acute stress) and immediately following (high acute stress) exposure to the laboratory stressors as well as 30 min after termination of the stressor (recovery period). Acute stress again heightened cardiac sympathetic activation, elevated plasma catecholamine concentrations, and affected cellular immune responses (ps < 0.05), whereas chronic stress was associated with higher reports of negative affect, enhanced cardiac sympathetic activation, elevated blood pressure and plasma levels of ACTH, and diminished production of interleukin‐1β (ps < 0.05). Correlational analyses in both studies further suggested that individuals who showed the greatest stress‐related changes in HPA activation also exhibited the greatest diminution in cellular immune response.

Subjective Overachievement: Individual Differences in Self-Doubt and Concern With Performance

We discuss the construct of doubt about ones competence and suggest that doubt can have myriad consequences (e.g., self-handicapping, defensive pessimism). We focus on the effect of self-doubt when it is combined with a concern with performance and assert that this combination leads to the phenomenon of subjective overachievement. In two studies, we present a new 17-item Subjective Overachievement Scale (SOS), which includes two independent subscales measuring individual differences in self-doubt and concern with performance. The first study, consisting of two large samples (Ns = 2,311 and 1,703), provides evidence that the scale has high internal consistency and a clear two-factor structure. Additionally, the subscales have adequate test-retest reliability (Ns = 67 and 115). A second study reveals that the SOS has good convergent and discriminant validity. Both subscales are unrelated to social desirability but exhibit the predicted patterns of associations with other related constructs. The Concern with Performance Subscale is correlated with achievement motivation, whereas the Self-Doubt Subscale is correlated with scales assessing negative affectivity (e.g., self-esteem, social anxiety) and other self-related strategies associated with concerns about ones competence (e.g., self-handicapping, defensive pessimism, impostor phenomenon). The SOS, which combines the two subscales, appears to tap a unique strategy that individuals may use to deal with doubts about their own competence.

POSTMENOPAUSAL HORMONE REPLACEMENT : EFFECTS ON AUTONOMIC, NEUROENDOCRINE,AND IMMUNE REACTIVITY TO BRIEF PSYCHOLOGICAL STRESSORS

Objective Postmenopausal status increases some aspects of womens physiological responses to psychological stress; however, the influences of chronic hormone replacement with estrogen and progestogen on these responses are not known. We investigated possible effects of long-term estrogen replacement therapy (ERT), both with and without progestogen, on physiological reactivity to brief laboratory stressors. Method We studied three groups of postmenopausal women: 16 on estrogen alone, 14 on estrogen and progestogen, and 25 control participants receiving no replacement therapy. Cardiovascular, neuroendocrine, and immune data were collected at baseline and after speech and math tasks. Results In all groups, the stressors reduced vagal cardiac control (indexed by respiratory sinus arrhythmia); increased heart rate and plasma epinephrine, adrenocorticotropic hormone, and cortisol levels; and altered T lymphocyte response (measured by mitogen-induced cell proliferation), natural killer cell lysis, and circulating leukocyte subsets. Women on either type of ERT had higher total cortisol levels (reflecting an estrogen effect on cortisol binding globulin) and greater mitogen-induced blastogenesis across measurement periods than controls. They also showed greater vagal withdrawal and less decline in mitogen-stimulated blastogenesis in response to the stressors. Combined estrogen and progestogen was associated with higher epinephrine and lower circulating total lymphocytes, T cells, and CD4+ T cells across measurement periods, and with intermediate levels of vagal withdrawal in response to the stressors. Conclusions Long-term ERT was associated with enhanced parasympathetic responsiveness to stress, suggesting possible reduced demand for potentially detrimental sympathetic activation; and with higher overall levels and smaller stress-induced reductions of mitogen-stimulated blastogenesis, suggesting up-regulated T cell function.

Autonomic and Glucocorticoid Associations with the Steady-State Expression of Latent Epstein-Barr Virus

Previous studies have demonstrated the impact of psychological stress on the steady-state expression/reactivation of latent Epstein-Barr virus (EBV). Stress-induced decrements in the cellular immune response result in less control over the expression of the latent virus, resulting in increases in antibody to the virus. In Study 1, we investigated whether the steady-state expression of latent EBV in vivo differed between high and low stress reactors, as defined by sympathetic cardiac reactivity. Autonomic activity and antibody titers to Epstein-Barr virus capsid antigen (VCA) were measured in 50 elderly women latently infected with EBV. Results revealed that women who were high stress reactors were characterized by higher antibody titers to the latent virus than low stress reactors. High reactors tended to show larger stress-related increases in cortisol than low reactors, but the differences were not significant. Daily stressors can activate the autonomic nervous system and promote the release of pituitary and adrenal hormones, especially in high reactors. Glucocorticoid hormones have been shown to reactivate EBV in vitro from cells latently infected with the virus. We hypothesized that absolute levels of plasma cortisol may not be the only explanation for stress-induced reactivation of latent EBV and that the diurnal changes in the production of cortisol may be an important factor in these interactions. To examine the feasibility of this hypothesis, an in vitro study was conducted (Study 2) to determine whether changing glucocorticoid concentrations in the medium, in which EBV latently infected cells were cultured, to mimic diurnal changes in plasma cortisol concentrations would enhance the reactivation of the latent virus. Cells latently infected with EBV were exposed to either constant or varying concentrations of the synthetic glucocorticoid hormone dexamethasone (Dex), for 72 h. Results revealed a three- to eightfold enhancement of reactivation of latent EBV in cells pulsed with varying Dex concentrations when compared with cells exposed to a constant and/or a higher mean level of one Dex concentration. Together, these studies raise the possibility that differences in the kinetics of glucocorticoid concentrations may contribute to differences in the reactivation of latent EBV.

Autonomic and neuroendocrine responses to mild psychological stressors: Effects of chronic stress on older women

We investigated autonomic and endocrine responses to acute stressors in 27 women who were or are presently caring for a spouse with a progressive dementia (high chronic stress) and 37 noncaregivers who were category matched for age and family income (low chronic stress). Measures were taken before (low acute stress) and in response to brief laboratory stressors (high acute stress). We replicated prior research showing that caregivers report greater stress, depression, and loneliness than the comparison groups, and acute stressors elevate autonomic and neuroendocrine activity. We also found that caregivers, relative to noncaregivers, exhibited shorter preejection periods and elevated blood pressure and heart rate, but the magnitude of autonomic and neuroendocrine reactivity to the experimental stressors was comparable across these groups. This pattern of autonomic differentiation replicates prior research showing that caregivers are characterized by higher sympathetic activation than noncaregivers and suggests that the effects of chronic stress on physiological reactivity may be a less robust effect in older adults.

Neuroendocrine and cardiovascular reactivity to stress in mid-aged and older women: long-term temporal consistency of individual differences.

We report long-term temporal consistency of stress-related neuroendocrine and cardiovascular variables in mid-aged and older women who performed mental math and speech stress tasks two times approximately 1 year apart. Epinephrine, norepinephrine, ACTH, cortisol, cardiac preejection period (PEP), respiratory sinus arrhythmia, heart rate (HR), blood pressure, and respiration rate were measured at baseline, after or during stressors, and 30 min posttask. Although there were exceptions, year-to-year Spearman coefficients showed mostly moderate to high consistency (rs approximately equal to .5-.8) for baseline, stressor, and posttask values. For reactivity, HR and PEP were most consistent (rs approximately equal to .65); consistency for other variables was moderate to low (rs approximately equal to .1-.4). Means of most variables changed from year to year. Results support the use of baseline, stressor, and posttask values in longitudinal studies.

Cellular immune responses to acute stress in female caregivers of dementia patients and matched controls

This study investigated whether the stress of caregiving alters cellular immune responses to acute psychological stressors. Twenty-seven women caring for a spouse with a progressive dementia (high chronic stress) and 37 controls matched for age and family income performed a 12-min laboratory stressor. Cellular immune function was assessed by both functional and quantitative measures taken before (low acute stress), immediately after (high acute stress), and 30 min after (recovery from stress) exposure to the laboratory stressors. The laboratory challenges were associated with diminished proliferative responses but elevated natural killer (NK) cell cytotoxicity; however, subsequent analyses suggested that this elevated cytotoxicity was largely attributable to an increase in the number of NK cells in peripheral blood. The results suggest that although the stress of caregiving diminishes cellular immune function, caregiving appears to have little effect on cellular immune responses to or recovery from brief psychological challenges.

Differential effects of estrogen and medroxyprogesterone on basal and stress-induced growth hormone release, IGF-1 levels, and cellular immunity in postmenopausal women

We evaluated the influence of continual estrogen replacement therapy (ERT) as presently practiced by postmenopausal women with conjugated estrogens and medroxyprogesterone acetate (MPA) on the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and cellular immunity. Thirty-nine postmenopausal women were evaluated (12 on no replacement, 14 on estrogen only, and 13 on estrogen and MPA). In the women receiving only conjugated estrogens, increased GH levels and decreased IGF-1 levels were found, which replicated previous research and probably reflected estrogen inhibition of hepatic IGF-1 production with a secondary increase in GH release because of reduced feedback inhibition. In women taking both MPA and estrogen, GH was increased and the previously observed estrogen induced decrease in IGF-1 levels was inhibited.In order to determine the influence of ERT on psychosocial stress-induced GH release, math (mental stress) and speech (social stress) challenges were utilized, and they produced significant increases in heart rate in all three groups. The heart rate following stress was significantly enhanced by estrogen replacement. These stressors also led to increased GH secretion in the women taking estrogen and MPA, but not in the other two groups.Gonadal steroids and GH can influence cellular immunity. We observed that ERT in both groups was associated with significantly enhanced lymphocyte responsiveness to the T-cell mitogens phytohemaglutinin (PHA) and Conconavalin A (Con A), and basal GH levels were correlated with the PHA response in the estrogen only group. ERT did not influence natural killer (NK) cell activity. We also found significant differences in the steady-state expression of latent Epstein-Barr virus (EBV) with increased antibody titers in the women in the estrogen only group and lower antibody titers in the MPA plus estrogen group. GH levels were correlated with EBV antibody titers in the estrogen plus MPA group.This study supports the hypothesis that GH and immune modulation can be influenced by ERT in postmenopausal woman. Given the extant literature on the immune-enhancing effects of GH, these data suggest that ERT may slow the declien of GH secretion with aging, an event that has been implicated in immunosenescence.

Chronic stress down-regulates growth hormone gene expression in peripheral blood mononuclear cells of older adults

Abstract“Pituitary” peptides are produced in both endocrine and immune cells. Acute and chronic stress can alter pituitary peptide secretion and might also influence neuroendocrine gene expression in human immune cells. We reasoned that, in Alzheimer caregivers, the chronic stress of caregiving would impact on the sympathetic-adrenal-medullary and hypothalamicpituitary-adrenal axis possibly leading to alterations in GH mRNA in their peripheral blood mononuclear cells (PBMCs). Therefore, we evaluated 10 caregivers and 10 controls subjects using a math and speech stress protocol to determine their neuroendocrine profile and to evaluate any relationship with mononuclear cell GH mRNA levels simultaneously acquired and then evaluated by a quantitative competitive RT-PCR technique. We found a significant (p<.0001) decrease 50% in GH mRNA levels in cells from caregivers. Plasma ACTH and norepinephrine levels were negatively correlated with GH mRNA levels, suggesting their possible role in the down-regulation of mononuclear cell GH gene expression. These observations support the hypothesis that experiences associated with caregiving alter the brains autonomic nervous system and neuroendocrine control of the hypothalamic-pituitary axis. These and perhaps other influences may then produce altered GH gene expression in mononuclear cells of chronically stressed individuals. It is tempting to speculate that the decreased GH mRNA that we found in these chronically stressed caregivers was partially responsible for their poor response to influenza vaccine and their delayed wound healing.

Cardiovascular and endocrine reactivity in older females: Intertask consistency

Age-related structural and functional changes in the cardiovascular, sympathoadrenomedullary (SAM), and hypothalamic-pituitary-adrenocortical (HPA) systems may affect the ability to reliably identify individual differences in response to stress. Heart rate, preejection period, respiratory sinus arrhythmia, respiratory rate, norepinephrine, epinephrine, adrenocorticotropic hormone, and cortisol were assessed in 64 healthy older women (mean = 67 years) in response to a mental arithmetic and public-speaking task. All cardiovascular and endocrine measures changed significantly during the tasks. All measures were consistent across the two tasks (r(s)s = .50 to .97). Moreover, a majority of women in this sample exhibited cross-task consistency in the relative activation of the autonomic, SAM, and HPA systems (i.e., response profiles). Further research is recommended to examine the significance of consistent individual differences in response profile.