Noha H. Farag

Lifetime Adversity Leads to Blunted Stress Axis Reactivity: Studies from the Oklahoma Family Health Patterns Project

BACKGROUND Can stressful events in early life alter the response characteristics of the human stress axis? Individual differences in stress reactivity are considered potentially important in long-term health and disease; however, little is known about the sources of these individual differences. We present evidence that adverse experience in childhood and adolescence can alter core components of the stress axis, including cortisol and heart rate reactivity. METHODS We exposed 354 healthy young adults (196 women) to public speaking and mental arithmetic stressors in the laboratory. Stress responses were indexed by self-report, heart rate, and cortisol levels relative to measures on a nonstress control day. Subjects were grouped into those who had experienced 0, 1, or 2 or more significant adverse life events, including Physical or Sexual Adversity (mugged, threatened with a weapon, experienced a break-in or robbery or raped or sexually assaulted by a relative or nonrelative) or Emotional Adversity (separation from biological mother or father for at least 6 months before age 15). RESULTS Experience of adversity predicted smaller heart rate and cortisol responses to the stressors in a dose-dependent fashion (0 > 1 > 2 or more events) (F values = 5.79 and 8.11, p values < .004) for both men and women. This was not explained by differences in socioeconomic status, the underlying cortisol diurnal cycle, or subjective experience during the stress procedure. CONCLUSIONS The results indicate a long-term impact of stressful life experience on the reactivity of the human stress axis.

Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women

Caffeine elevates cortisol secretion, and caffeine is often consumed in conjunction with exercise or mental stress. The interactions of caffeine and stress on cortisol secretion have not been explored adequately in women. We measured cortisol levels at eight times on days when healthy men and women consumed caffeine (250 mg x 3) and underwent either mental stress or dynamic exercise protocols, followed by a midday meal, in a double blind, placebo-controlled, crossover design. Men and women had similar cortisol levels at the predrug baselines, but they responded differently to mental stress and exercise. The cortisol response to mental stress was smaller in women than in men (p=.003). Caffeine acted in concert with mental stress to further increase cortisol levels (p=.011), the effect was similar in men and women. Exercise alone did not increase cortisol, but caffeine taken before exercise elevated cortisol in both men and women (ps<.05). After a postexercise meal, the women had a larger cortisol response than the men, and this effect was greater after caffeine (p<.01). Cortisol release in response to stress and caffeine therefore appears to be a function of the type of stressor and the sex of the subject. However, repeated caffeine doses increased cortisol levels across the test day without regard to the sex of the subject or type of stressor employed (p<.00001). Caffeine may elevate cortisol by stimulating the central nervous system in men but may interact with peripheral metabolic mechanisms in women.

Immune cell CD62L and CD11a expression in response to a psychological stressor in human hypertension.

This study examined the effects of hypertension and an acute psychological stressor on white blood cells and their expression of CD62L and CD11a. Seventeen mild hypertensive and 23 normotensive volunteers were studied prior to and following a standardized laboratory public speech. In response to the speech, all subjects increased the number of circulating leukocyte populations (ps<.01). Patients with hypertension increased the number of circulating white blood cells more than normotensives (p<.01). Hypertensives also showed a greater increase in the number of circulating CD3(+)CD8(+) T cells (p<.02) in response to the speech. Only hypertensives increased the number of circulating CD8(+)CD62L(high) T cells (p=.001). The density of CD11a on lymphocytes was increased in all subjects following the speech (p<.001). Hypertensives showed a greater mean density of CD11a on lymphocytes (p<.01). Coupled with observations of increased expression of the endothelial CD11a ligand ICAM-1 in hypertension, these findings are consistent with the notion that patients with hypertension exhibit a circulatory environment conducive to increased leukocyte adhesion. Exposure to repeated psychological stressors may further augment this potentially adverse circulatory environment.

Use of a resting control day in measuring the cortisol response to mental stress: Diurnal patterns, time of day, and gender effects

In laboratory studies of individual differences in stress reactivity, cortisol responses are typically measured by comparing a prestress baseline with values obtained at the end of the stressor. In the present study, we measured cortisol in this manner on a stress day, but we also took samples on a second day when the volunteers rested in the lab at the same time of day and for the same duration. We compared stress responses as the difference from pre- to poststress and also poststress vs. rest day control. The latter method allowed a greater appreciation of how stress perturbed the underlying diurnal baseline. Although the effect of stress was statistically significant when measured as the change from pre- to poststress, the magnitude of the effect was 54% larger when measured against the time-of-day control from the rest day. In particular the diurnal control method provided a wider range of stress values that potentially provide a greater range of response values in carrying out analyses of individual differences.

Hypothalamic-Pituitary-Adrenal Axis Function: Relative Contributions of Perceived Stress and Obesity in Women

OBJECTIVE A range of behavioral and psychosocial factors may contribute to a chronically stimulated hypothalamic-pituitary-adrenal (HPA) axis and subsequently altered diurnal patterns. The goal of this cross-sectional study was to examine associations among diurnal cortisol levels, perceived stress, and obesity patterns. METHODS Seventy-eight women (aged 24-72 years) employed in a rural public school system completed the perceived stress scale, collected diurnal saliva samples, and underwent anthropometric assessments. Reduced peak-to-nadir cortisol values across the day were considered a sign of impairment in HPA function. A series of linear regression models determined the best predictors of diurnal cortisol variation. RESULTS There was a marginal linear trend in stress levels across body mass index (BMI) categories, with obese women reporting the highest levels of stress (p = 0.07). Perceived stress was the only significant predictor of the degree of flattening of the diurnal cortisol curve in the sample as a whole (beta = -0.042, R(2) = 0.11, F = 8.6, p = 0.005), indicating reduction in the normal diurnal pattern. Among overweight women (BMI = 25-29.9 kg/m(2)), stress and waist circumference combined predicted 35% of the variability in diurnal cortisol. In contrast, among obese women (BMI > or = 30 kg/m(2)), BMI predicted 31% of the variability in diurnal cortisol (F = 13.8, p = 0.001), but stress was no longer significantly related to diurnal cortisol. CONCLUSIONS Psychological stress predicts a significant portion of HPA axis functioning. In overweight women, perceived stress and waist circumference were of approximately equal importance in predicting adrenal cortisol secretion. However, among obese women, a major portion of the diurnal cortisol variation was predicted by BMI alone, not stress or waist circumference. This may help elucidate the mechanisms linking obesity to increased risk of cardiovascular disease (CVD).

Effects of regular exercise on lymphocyte subsets and CD62L after psychological vs. physical stress

OBJECTIVE To examine the effects of regular physical activity on lymphocyte responses to a speech stressor and an exercise challenge. METHODS We assessed lymphocyte subsets and CD62L expression pre, immediately after and 15 min after a speech task vs. exercise in 24 high vs. 24 low physically active subjects. Catecholamine levels were determined by radioenzymatic assay, and enumeration of cells was assessed by flow cytometry. RESULTS Both tasks induced significant increases in plasma epinephrine (EPI; P<.05) and norepinephrine (NE; P<.001) levels. Similarly, both tasks led to increases in the numbers of lymphocyte subsets (P<.05). Physically active individuals showed attenuated responses to the speech stressor in numbers of CD62L(+), CD45RA(+), CD45RO(+) CD8(+), CD45RO(+) T(H) and CD62L(-) natural killer (NK) cells (Ps<.05). In contrast, physical activity level had no significant effect on lymphocyte subsets or CD62L expression in response to exercise. CONCLUSION The findings suggest that physical fitness affects immune responses to a psychological but not a physical stressor. It is an interesting but open question whether attenuated lymphocyte trafficking responses to stress in regular exercisers might have clinical implications regarding host defense by the immune system.

Autonomic responses to psychological stress: the influence of menopausal status.

Cardiovascular disease is the leading killer of women in developed countries. Menopause, stress, and lack of social support may contribute to the increased risk of heart disease morbidity and mortality in women. This study examined the effects of psychological stress and social support on autonomic nervous system control of the heart in 18 pre- and 34 postmenopausal women. Autonomic activity, as indexed by high-frequency heart rate variability and pre-ejection period, was assessed at rest and during a public speech task. Social support was determined using the Berkman Social Support Inventory. Postmenopausal women had higher heart rate (F = 4.4, p ≤ .04) and less para-sympathetic activity (F = 11.9, p ≤ .001) compared with premenopausal women at rest. In response to stress, sympathetic nervous system activity increased in postmemopausal women (F = 6.1,p≤. 02); however, this effect was no longer significant when age was used as a covariate in the analysis. Social support did not significantly affect measures of autonomic activity in either the pre- or postmenopausal women. Postmenopausal women have greater sympathetic and less parasympa-thetic activity than premenopausal women, which may account for their increased risk of coronary artery disease.

Caffeine and Blood Pressure Response: Sex, Age, and Hormonal Status

PURPOSE The pressor effect of caffeine has been established in young men and premenopausal women. The effect of caffeine on blood pressure (BP) remains unknown in postmenopausal women and in relation to hormone replacement therapy (HRT) use. MATERIALS AND METHODS In a randomized, 2-week cross-over design, we studied 165 healthy men and women in 6 groups: men and premenopausal women (35-49 yrs) vs. men and postmenopausal women (50-64 yrs), with postmenopausal women divided into those taking no hormone replacements (HR), estrogen alone, or estrogen and progesterone. Testing during one week of the study involved 6 days of caffeine maintenance at home (80 mg, 3x/day) followed by testing of responses to a challenge dose of caffeine (250 mg) in the laboratory. The other week involved ingesting placebos on maintenance and lab days. Resting BP responses to caffeine were measured at baseline and at 45 to 60 min following caffeine vs placebo ingestion, using automated monitors. RESULTS Ingestion of caffeine resulted in a significant increase in systolic BP in all 6 groups (4 +/- .6, p < 0.01). Diastolic BP significantly increased in response to caffeine in all (3 +/- .4, p < 0.04) but the group of older men (2 +/- 1.0, p = 0.1). The observed pressor responses to caffeine did not vary by age. CONCLUSIONS Caffeine resulted in an increase in BP in healthy, normotensive, young and older men and women. This finding warrants the consideration of caffeine in the lifestyle interventions recommended for BP control across the age span.

Evaluation of a community-based participatory physical activity promotion project: effect on cardiovascular disease risk profiles of school employees

BackgroundThe efficacy of physical activity in improving cardiovascular disease (CVD) risk profiles has been well established. However, the effectiveness of health promotion programs implemented at the community level remains controversial. This study evaluated a school-based work-site physical activity program.MethodsUsing a community-based participatory research model, a work-site wellness intervention was implemented in a rural public school system in Southwestern Oklahoma. During the 2005-2006 school year, 187 participants (mean age 45 years) completed a pre intervention screening for CVD risk factors followed by a physical activity promotion program. Post intervention screening was conducted after a 6 month period. During both screening sessions, body composition, blood pressure, lipids, glucose and self-reported physical activity levels were assessed. The focus of the intervention was on promoting physical activity. Opportunities for in school physical activity were created by marking hallways, adding a treadmill in each school, and allowing teachers to use planning periods for physical activity.ResultsDuring the post intervention screening, compared to pre intervention levels, participants had lower total, low, and high density lipoprotein-cholesterol (t = 5.9, p < 0.0001, t = 2.6, p = 0.01, and t = 13.2, p < 0.0001 respectively), lower systolic blood pressure (t = 2.9, p = 0.004), and higher self-reported physical activity levels (Sign t = -1.901, p = 0.06).ConclusionsA successful participatory program was associated with improvements in several CVD risk factors among school employees. Limitations of this study such as seasonal variation in the outcome variables and lack of a control group limit our ability to draw solid conclusions about the effectiveness of the intervention.

Effects of estrogen and psychological stress on plasma homocysteine levels

OBJECTIVE To investigate the effects of estrogen (E) and psychological stress on plasma total homocysteine levels in relation to menopausal status. DESIGN Double-blind, randomized, placebo-controlled study. SETTING The General Clinical Research Center of a university hospital. PATIENT(S) Thirty-six postmenopausal women and 26 premenopausal women. Both samples were healthy nonsmokers. INTERVENTION(S) Both premenopausal and postmenopausal women were subjected to a 6-minute psychological stressor. Postmenopausal women were randomized to one of three treatment arms: 2 mg of E2 or 2 mg of E2 + 5 mg of medroxyprogesterone acetate (MPA), or a placebo, all of which were given orally for 3 months. The psychological stressor was readministered after the 3-month regimen. MAIN OUTCOME MEASURE(S) Plasma total homocysteine levels were measured before and after the psychological stressor on one occasion for premenopausal women and before and after hormone replacement or placebo for postmenopausal women. RESULT(S) There were no significant differences in homocysteine levels between premenopausal (7.2 +/- 1.7 micromol/L; mean +/- SD) and postmenopausal women (7.9 +/- 2.06; mean +/- SD). There was no effect of stress or hormone replacement on homocysteine levels. CONCLUSION(S) Psychological stress, menopausal status, and oral hormone replacement therapy (HRT) do not affect plasma total homocysteine levels in women with normal basal homocysteine levels.