Laura Redwine

Responses to Laboratory Psychosocial Stress in Postpartum Women

Objective Lactation has been associated with attenuated hormonal responses to exercise stress in humans. This study was designed to determine the effect of lactation on hypothalamic-pituitary-adrenal axis, autonomic nervous system, and anxiety responses to psychological stress. Method The Trier Social Stress Test was administered to 24 lactating women, 13 postpartum nonlactating women, and 14 healthy control women in the early follicular phase of the menstrual cycle. Lactating women were stressed at least 40 minutes after last feeding their infant. Results ACTH, cortisol, heart rate, diastolic blood pressure, systolic blood pressure, and subjective anxiety ratings were all significantly increased in response to the psychological stress (all p < .0001). There were no differences among the three groups in any of these responses to the stress. However, postpartum nonlactating women did have a persistently higher systolic blood pressure and lower cardiac vagal tone than the lactating women and control subjects. In addition, the typical negative correlation between cardiac vagal tone and heart rate was consistently higher in lactating women than nonlactating postpartum women and controls, which suggests stronger vagal control of heart rate in lactating women. In addition, there was no change in oxytocin or allopregnanolone in response to the stress, and baseline oxytocin and allopregnanolone levels did not differ among the three groups. Conclusions These results indicate that physiological and subjective responses to social stress are not attenuated in lactating women tested at least one hour after feeding their infant. However, enhanced vagal control of cardiac reactivity was observed in lactating women. In addition, postpartum women who did not lactate showed evidence of increased sympathetic and decreased parasympathetic nervous system tone.

A Meta-Analysis of Mental Health Treatments and Cardiac Rehabilitation for Improving Clinical Outcomes and Depression Among Patients With Coronary Heart Disease

Objective To quantify the efficacy of mental health (antidepressants & psychotherapies) and cardiac rehabilitation treatments for improving secondary event risk and depression among patients with coronary heart disease (CHD). Methods Using meta-analytic methods, we evaluated mental health and cardiac rehabilitation therapies for a) reducing secondary events and 2) improving depression severity in patients with CHD. Key word searches of PubMed and Psychlit databases and previous reviews identified relevant trials. Results Eighteen mental health trials evaluated secondary events and 22 trials evaluated depression reduction. Cardiac rehabilitation trials for the same categories numbered 17 and 13, respectively. Mental health treatments did not reduce total mortality (absolute risk reduction [ARR] = −0.001, confidence interval [95% CI] = −0.016 to 0.015; number needed to treat [NNT] = ∞), showed moderate efficacy for reducing CHD events (ARR = 0.029, 95% CI = 0.007 to 0.051; NNT = 34), and a medium effect size for improving depression (Cohen d = 0.297). Cardiac rehabilitation showed similar efficacy for treating depression (d = 0.23) and reducing CHD events (ARR = 0.017, 95% CI = 0.007 to 0.026; NNT = 59) and reduced total mortality (ARR = 0.016, 95% CI = 0.005 to 0.027; NNT = 63). Conclusions Among patients with CHD, mental health treatments and cardiac rehabilitation may each reduce depression and CHD events, whereas cardiac rehabilitation is superior for reducing total mortality risk. The results support a continued role for mental health treatments and a larger role for mental health professionals in cardiac rehabilitation.

Effects of Spiritual Mantram Repetition on HIV Outcomes: A Randomized Controlled Trial

We examined the efficacy of a psycho-spiritual intervention of mantram repetition—a word or phrase with spiritual associations repeated silently throughout the day–on psychological distress (intrusive thoughts, stress, anxiety, anger, depression), quality of life enjoyment and satisfaction, and existential spiritual well-being in HIV-infected adults. Using a 2-group by 4-time repeated measures design, 93 participants were randomly assigned to mantram (n = 46) or attention control group (n = 47). Over time, the mantram group improved significantly more than the control group in reducing trait-anger and increasing spiritual faith and spiritual connectedness. Actual mantram practice measured by wrist counters was inversely associated with non-HIV related intrusive thoughts and positively associated with quality of life, total existential spiritual well-being, meaning/peace, and spiritual faith. Intent-to-treat findings suggest that a mantram group intervention and actual mantram practice each make unique contributions for managing psychological distress and enhancing existential spiritual well-being in adults living with HIV/AIDS.

Reduced Sensitivity to Glucocorticoid Feedback and Reduced Glucocorticoid Receptor mRNA Expression in the Luteal Phase of the Menstrual Cycle

We examined the effects of the menstrual cycle on hypothalamic-pituitary adrenal axis regulation in healthy women with no history of psychiatric illness by measuring plasma cortisol responses to a low-dose (0.25 mg) of dexamethasone (N = 23) and by measuring glucocorticoid receptor (type II) mRNA expression in lymphocytes using Northern blotting (N = 19). Both measures were performed in the early follicular and mid-luteal phases of the menstrual cycle. Dexamethasone suppression of plasma cortisol was greater in the follicular phase of the menstrual cycle compared to the mid-luteal phase (p <. 01). In addition, type II glucocorticoid receptor mRNA expression in lymphocytes was 78% higher in the follicular phase compared to the mid-luteal phase (p <. 02). These results indicate that glucocorticoid feedback regulation of the hypothalamic-pituitary-adrenal axis is reduced in the mid-luteal phase of the menstrual cycle. Reduced feedback regulation of central stress response systems may play a role in generation of common premenstrual symptoms of irritability and dysphoria.

Nocturnal proinflammatory cytokine-associated sleep disturbances in abstinent African American alcoholics

Animal studies reveal that cytokines play a key role in the regulation of sleep. Alcoholic patients show profound alterations of sleep and a defect in the homeostatic recovery of sleep following sleep loss. In this study, we investigated whether nocturnal plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF) were associated with disordered sleep in alcohol dependence by testing the temporal relationships between these inflammatory cytokines and sleep, before and after sleep deprivation. All-night polysomnography and serial blood sampling at 23:00, 03:00, and 06:30 h were conducted across baseline, partial sleep deprivation, and recovery nights in abstinent African American alcoholics (n=16) and matched controls (n=15). Coupled with prolonged sleep latency and increased rapid eye movement sleep, alcoholics showed nocturnal elevations of IL-6 and TNF as compared to controls after adjustment for alcohol consumption and body mass index. Following sleep deprivation, alcoholics showed greater nocturnal levels of IL-6 and greater nocturnal increases of TNF as compared to controls. Pre-sleep IL-6 levels at 23:00 h correlated with prolonged sleep latency after adjustment for potential confounders whereas IL-6 levels at 03:00 h correlated with rapid eye movement sleep in the second half of the night. Taken together, these findings indicate that circulating levels of proinflammatory cytokines may have a negative influence on sleep initiation. These findings have implications for determining why sleep is disordered in alcoholics and may aid in the development of novel treatments to optimize sleep in this population.

Post-traumatic Stress Disorder A Fast Track to Premature Cardiovascular Disease?

An increasing body of evidence reported in the literature indicates a possible role for post-traumatic stress disorder (PTSD) as a cause for cardiovascular disease (CVD). However, mechanistic evidence on the progression of adverse cardiac outcomes in PTSD is lacking. In this review, we examine the potential paths by which CVD could occur in those with PTSD. Dysregulation of the hypothalamic-pituitary-adrenal axis and autonomic nervous dysfunction are commonly observed in PTSD, which in turn leads to a variety of physiological changes potentially damaging to the heart. Increased inflammation, dysfunction of the vascular endothelium, hypercoagulability, and cardiac hyperreactivity all have been noted in patients with PTSD. Altered neurochemistry, most notably increased arginine vasopressin, as well as an increased prevalence of the metabolic syndrome, may also contribute to adverse cardiac outcomes. Although the association between PTSD and physical disease is often complicated by health risk behaviors or comorbid psychiatric conditions, the evidence for a link between PTSD and CVD is substantial. In our examination, we attempt to identify potential cardiac biomarkers that may be useful in detecting increased cardiac risk in patients with PTSD. As research in this area is exceedingly limited, we hope to inspire further research, as there is great potential value in identifying prognostically useful cardiac biomarkers so as to predict and prevent the onset of CVD in patients with PTSD.

Differential Immune Cell Chemotaxis Responses to Acute Psychological Stress in Alzheimer Caregivers Compared to Non-caregiver Controls

Objective: Caregiving for a spouse with Alzheimer’s disease is associated with alterations in various immune cell responses. Chemotaxis of immune cells to chemokines is an important factor involved in lymphocyte migration, which plays an essential role in inflammatory responses to infection and may also be involved in atherogenesis. However, the effects of chronic stress on chemotaxis have not been investigated. The objective of this study was to examine lymphocyte chemotaxis to chemokines, stromal cell-derived factor-1 (SDF-1), N-formyl-methionyl-leucyl-phenylalanine (FMLP), and a beta-adrenergic agonist, isoproteronol (ISO), in response to an acute stressor in Alzheimer’s caregivers. Correlations between immune cell chemotaxis and epinephrine and norepinephrine levels were also examined. Methods: Caregivers (n = 18) and noncaregiver controls (n = 9) completed a public speaking task. Blood was drawn before and immediately after the task for changes in chemotaxis to FMLP, SDF-1, and ISO, and for epinephrine and norepinephrine levels. Results: Caregivers had reduced chemotaxis to FMLP, SDF-1, and ISO in response to the speech task, compared with non-caregivers. Also, the direction of the correlations between chemotaxis to FMLP, SDF-1, and ISO and epinephrine levels differed between groups. Conclusions: These findings suggest that immune cells released into circulation in response to acute stress are altered in caregivers. Group differences in immune responses may be due to sympathetically mediated alterations, which may have implications for caregivers’ ability to successfully mount viable immune responses, as well as, atherogenesis. AD = Alzheimer’s disease; ANOVA = analysis of variance; FMLP = N-formyl-methionyl-leucyl-phenylalanine; ISO = isoproterenol; PBMC = peripheral blood mononuclear cell; SAM = sympathetic-adrenal medullary; SDF-1 = stromal cell-derived factor-1; UCSD = University of California, San Diego.

Cardiac-related hospitalization and/or death associated with immune dysregulation and symptoms of depression in heart failure patients

Objective: Congestive heart failure (CHF) patients with depressive symptoms have a greater risk of morbidity and mortality. Immune activity such as inflammation is increasingly implicated as underlying this relationship. However, it is unknown whether there is a broader spectrum of immune dysregulation beyond inflammatory activity. This study examined in CHF patients the relationship of depressive symptoms with cellular immune activity measured by Th1/Th2 ratios and cardiac rehospitalization and/or death. Method: Eighteen patients with CHF (mean age = 62, NYHA classes II–IV) were enrolled and depressive symptoms were measured with interviewer ratings using the Hamilton Rating Scale-Depression. For the determination of Th1/Th2 ratios, intracellular cytokine expression of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) CD4+ T cells were measured by flow cytometry. Plasma interleukin-6 levels were measured to ascertain circulating inflammatory cytokine activity. Patient records were examined for cardiac related rehospitalization or cardiac related death over a two-year period after baseline depression and immune measures were taken. Results: Higher depression scores were associated with a prospective increase in incidence of cardiac related hospitalizations and/or death (p = .037). Lesser IFN-gamma/IL-10 expressing CD4+ T cell ratios were related to higher depressive symptom scores at baseline (p = .005) and a prospective increased incidence of cardiac related hospitalization or death over a two-year period (p = .05). Conclusions: A shift in the Th1/Th2 ratio may play a role in the association between depressive symptoms and morbidity and mortality in CHF patients, suggesting broader immune dysregulation than previously considered. CHF = congestive heart failure; IFN = interferon; IL = interleukin; NYHA = New York Heart Association; BNP = B-type natriuretic peptide; HAM-D = Hamilton Depression Scale; EF = ejection fraction; BMI = body mass index.

Effects of faith/assurance on cortisol levels are enhanced by a spiritual mantram intervention in adults with HIV : A randomized trial

OBJECTIVES Previous research among HIV-infected individuals suggests that spiritual well-being is inversely related to psychological distress and rates of disease progression. Use of a mantram, a spiritual word or phrase repeated frequently and silently throughout the day, has been associated with decreased psychological distress and increased spiritual well-being. This study compared the effects of 2 interventions-a spiritually-based mantram intervention versus an attention-matched control group-on faith/assurance and average salivary cortisol levels among HIV-infected individuals. METHODS Using a randomized design, HIV-infected adults were assigned to the intervention (n = 36) or control condition (n = 35). Faith scores and saliva (collected at 7 a.m., 11 a.m., 4 p.m., and 9 p.m.) were assessed at preintervention, postintervention, and 5-week follow-up. Path analyses tested competing models that specify both concurrent and sequential relationships between faith and average daily cortisol levels while comparing groups. RESULTS Faith levels increased among mantram participants from pre- to postintervention. Greater faith at preintervention was significantly associated with lower average cortisol at postintervention in the mantram group but not in the controls. The associations between faith at postintervention and cortisol levels at 5-week follow-up were significant among both groups but weaker than the pre- to postintervention association identified in the mantram group. CONCLUSIONS These results suggest the presence of lagged or antecedent consequent relationships between faith and cortisol, which may be enhanced by mantram use. Decreased cortisol could potentially benefit immune functioning among HIV-infected individuals.

Lymphocyte responses to stress in postpartum women: relationship to vagal tone

Although women spend their lives in various phases of the reproductive cycle, including menstrual, pregnancy, postpartum, lactation and menopause, few studies have examined immune responses to stress in women as a function of events associated with reproduction. The objective of this study was to evaluate differential effects of breastfeeding (n = 16), bottlefeeding (n = 10) and non-postpartum (n = 10) status on lymphocyte responses to stressful tasks (public speaking and mental arithmetic). To measure cellular immune responses, lymphocyte proliferation to plant lectins, poke weed mitogen (PWM) and phytohemagglutinin (PHA) were used. The autonomic measures, heart rate, vagal tone, blood pressure and the hormones of the HPA axis, ACTH and cortisol, were measured and their possible roles in mediating lymphocyte proliferation responses were examined. Recently parturient women who were breastfeeding or bottlefeeding had attenuated stress-induced change in lymphocyte responses to PWM compared with non-postpartum women, tested in the follicular phase of their cycle (P < 0.05). Also, lymphocyte responses to PHA were higher in the breastfeeding group compared with non-postpartum controls (P < 0.05). Regression analyses revealed that an index of cardiac vagal tone, but not other autonomic or endocrine measures, was positively predictive of lymphocyte proliferation to PWM. To summarize, these findings suggest that lactation and parturition can influence lymphocyte proliferation and that activity in the vagal system may influence lymphocyte responses to stress.