Gender differences in cardiovascular and hypothalamic-pituitary-adrenal axis responses to psychological stress in healthy older adult men and women

Gender differences in the neuroendocrine and cardiovascular response to psychological stress may contribute to the gender differences in the prevalence of diseases associated with hypothalamic-pituitary-adrenal (HPA) axis reactivity such as cardiovascular disease (CVD), diabetes and hypertension. We measured plasma ACTH, cortisol, heart rate (HR), and blood pressure (BP) responses in 8 men and 8 women (55-75 years) exposed to the Matt Stress Reactivity Protocol (MSRP), a psychological challenge. The MSRP elicited significant increases in HR, systolic-, and diastolic BP, ACTH and cortisol (all p<0.01). Men had significantly greater cortisol and diastolic BP responses compared to women (p<0.05). Additionally, a positive correlation between the ACTH and cortisol responses was only found in the males (r=0.71, p<0.05). There were no group differences in HR, systolic BP, or ACTH responses. We conclude, that among older adults, men respond to psychological stress with greater increases in cortisol, compared to women. This greater activation of the HPA axis could translate into an elevated risk for CVD, diabetes and hypertension and may be related to the higher prevalence of these diseases in males. Gender differences in brain structures and/or cognitive processes may be responsible for these sexually dimorphic stress responses.     

Mental activation of supportive ties, hostility, and cardiovascular reactivity to laboratory stress in young men and women.

In addition to actual social interactions, internal representations of supportive ties could affect mechanisms linking relationships and health. Undergraduates (41 men, 41 women) wrote about supportive ties or casual acquaintances. Supportive ties were rated as warmer and less controlling than acquaintances, and writing about them evoked reductions in negative affect, especially for low-hostile participants. Compared with the acquaintance condition, the supportive tie condition resulted in reduced heart rate and blood pressure response during a subsequent speech stressor. Among women, the supportive tie condition reduced blood pressure response among low- but not among high-hostile participants. Hence, mental activation of supportive ties altered effects of laboratory stress and might be relevant to the effects of social relations on health.     

Psychophysiological reactivity to mental arithmetic stress in black and white normotensive men

Racial differences in physiological responses to a behavioral stressor were examined. Thirty-four Black and 42 White male normotensives 34 to 55 years old (mean age = 43.01 years) performed a mental arithmetic task while blood pressure, heart rate, and skin conductance were recorded. Compared to Whites, Blacks had significantly higher baseline diastolic blood pressure (77.93 mm Hg vs. 73.11 mm Hg) and lower skin conductance levels (11.08 microS vs. 12.25 microS). These effects persisted during performance of the mental arithmetic task. However, when baseline differences were covaried, there were no significant physiological effects associated with the task. Analysis of changes in response levels from baseline revealed a nonsignificant trend for Whites to show greater increases in systolic blood pressure than Blacks. There were no significant race or family history effects. Further, task performance did not influence the outcome. Failure to demonstrate greater cardiovascular reactivity in Blacks and all men with a positive family history of hypertension is discussed with regard to possible "survivor effects" and methodologic limitations.     

Variation in hypothalamic-pituitary-adrenal axis activity among bullied and non-bullied children

We examined the relationship between being bullied during childhood and activity of the hypothalamic-pituitary-adrenal (HPA) axis as assessed through repeated measures of salivary cortisol. A non-clinical sample of 154 (74 boys) predominantly Caucasian middle-class 12-year-olds each provided detailed information about their experiences with bullying and six saliva samples were standardized across time and day. Children with a history of child maltreatment, diagnosed psychiatric illness, foster care placement, medication use (psychotropic and oral contraception) and aggression directed toward peers and/or family members were excluded. Using multilevel regression and applying orthogonal polynomial contrasts to model the observed circadian pattern in the data, we found that occasional and frequent verbal peer victimization was associated with hyposecretion of cortisol when controlling for sex, pubertal status, age, depression and anxiety. This relation, however, was moderated by sex. For boys, occasional exposure was associated with higher cortisol levels, whereas for girls exposure was associated with lower cortisol levels. The present study highlights the need to consider the plight of peer-victimized children seriously, as it is associated with alterations to the HPA axis that affect males and females differently, and likely diminishes a person's ability to cope with stress, possibly placing them at risk for psychopathology and ill health.     

Resilience and vagal tone predict cardiac recovery from acute social stress

Previous studies showed that heart period decreases during and recovers after an acute stress. We investigated if individual predispositions and emotional priming influence heart period recovery after a speech stress task. Psychometric scales and resting cardiac vagal tone were used to measure individual traits. The presentation of a sequence of either pleasant or unpleasant pictures, as emotional primers, preceded the speech stress. Heart period was measured throughout the experiment. Stress induced tachycardia irrespective of emotional priming or traits. In the recovery period, participants with higher resting cardiac vagal tone or presenting higher resilience significantly reduced the heart acceleration. Furthermore, these traits interacted synergistically in the promotion of the recovery of heart period. Pleasant priming also improved recovery for participants with lower negative affect. In conclusion, the stress recovery measured through heart period seemed dependent upon individual predispositions and emotional priming. These findings further strengthen previous observations on the association between greater cardiac vagal tone and the ability to regulate emotion.     

Social isolation-induced changes in the hypothalamic-pituitary-adrenal axis in the rat

Social isolation of rats both reduces the cerebrocortical and plasma concentrations of 3a-hydroxy-5a-pregnan-20-one (3a,5a-TH PROG) and 3a,5a-tetrahydrodeoxycorticosterone and potentiates the positive effects of acute stress and ethanol on the concentrations of these neuroactive steroids. We now show that social isolation decreased the plasma level of adrenocorticotropin (ACTH), moreover, intracerebroventricular administration of corticotropin releasing factor (CRF) induced a marked increase in the plasma corticosterone level in both isolated and group-housed rats, but this effect was significantly greater in the isolated rats (+121%) than in the group-housed rats (+86%). In addition, in isolated rats, a low dose of dexamethasone had no effect on the plasma corticosterone concentration, whereas, a high dose significantly reduced it; both doses of dexamethasone reduced plasma corticosterone in group-housed rats. Furthermore, the corticosterone level after injection of dexamethasone at the high dose was significantly greater in the isolated animals than in the group-housed rats. These results suggest that social isolation increased sensitivity of the pituitary to CRF and impaired negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis.     

Psychosocial stress enhances time-based prospective memory in healthy young men

Forgetting of intentions (such as to take one's medication) is the most frequent everyday memory failure. No study so far has looked into the possible consequences stress might exert on memory for intentions (i.e., prospective memory). Twenty healthy young male adults were exposed to a psychosocial stress test and a non-stress condition. After a delay of 15 min, a time- and an event-based prospective memory task were administered during the peak of cortisol concentrations. Results show that participants performed significantly better in the time-based memory task after stress in comparison to the non-stress condition. In contrast, there was no stress effect on event-based prospective memory. The results demonstrate that prospective memory might be enhanced when participants are exposed to stress prior to the memory task and that this effect is associated to stress-related glucocorticoid effects.     

Circadian activity of the hypothalamic-pituitary-adrenal axis is differentially affected in the rat chronic mild stress model of depression

The altered activity of the hypothalamic-pituitary-adrenal (HPA) axis is often observed in stress-related disorders. According to the literature, about 60% of patients with major depressive disorder elicit high levels of cortisol. It is still unclear why high cortisol levels are not observed in all patients. In this study, we used the chronic mild stress (CMS) rat model of depression, which is based on continuous exposure to unpredictable stressors, to track longitudinal changes in HPA function using fecal corticosterone metabolites (FCM) as a read out. The dexamethasone suppression test was used to assess negative feedback inhibition of the HPA axis. Our results show (1) a disturbance in diurnal corticosterone rhythm measured as fluctuations of the diurnal FCM peak, (2) differences in corticosterone levels between stress-susceptible and stress-resilient animals, (3) recovery of diurnal corticosterone rhythm after 8 weeks of CMS, and (4) alterations in sensitivity to dexamethasone in negative feedback regulation of corticosterone secretion during the time course of CMS. Thus, a disruption of HPA axis circadian rhythmicity coincides with the initial state in the development of depression-like behavior. This chronobiological abnormality, as well as the hypersecretion of corticosterone, is state, rather than trait, dependent.     

Vigilance, active coping, and cardiovascular reactivity during social interaction in young men.

This study of 72 undergraduate men examined the effects of two determinants of cardiovascular response-active coping and vigilance-on blood pressure and heart rate responses to social stressors. Observation of a future debate partner (i.e., vigilance) evoked larger increases in blood pressure than did observation of a less relevant person, apparently through the combination of increases in cardiac output and vascular resistance. Preparation and enactment of efforts to exert social influence (i.e., active coping) evoked heightened blood pressure and heart rate responses through increased cardiac contractility and output. Thus, both vigilance and active coping in social contexts increased cardiovascular reactivity, but apparently through different psychophysiological processes.     

Eugenol as an anti-stress agent: modulation of hypothalamic-pituitary-adrenal axis and brain monoaminergic systems in a rat model of stress

Stress is the leading psychopathological cause for several mental disorders. Physiological and psychological responses to stress are mediated by the hypothalamic?pituitary?adrenal (HPA), sympathoadrenal system (SAS), and brain monoaminergic systems (BMS). Eugenol is reported to substantially modulate brain functions by regulating voltage-gated cation channels and release of neurotransmitters. This study was designed to evaluate the anti-stress effect of eugenol in the 4-h restraint model using rats. Ulcer index was measured as a parameter of the stress response. HPA axis and the SAS were monitored by estimating plasma corticosterone and norepinephrine (NE), respectively. Analysis of NE, serotonin (5-HT), dopamine, and their metabolites in discrete brain regions was performed to understand the role of BMS in the anti-stress effect of eugenol. Stress exposure increased the ulcer index as well as plasma corticosterone and NE levels. Eugenol pretreatment for 7 days decreased the stress-induced increase in ulcer index and plasma corticosterone but not NE levels, indicating a preferential effect on the HPA axis. Furthermore, eugenol showed a ?U?-shaped dose?response curve in decreasing ulcer index and plasma corticosterone levels. Eugenol also reversed the stress-induced changes in 5-HT levels in all brain regions, whereas NE levels were reversed in all brain regions except hippocampus. These results suggest that eugenol possesses significant anti-stress activity in the 4-h restraint model and the effect is due to modulation of HPA and BMS.     

The social dimension of stress reactivity: acute stress increases prosocial behavior in humans

Psychosocial stress precipitates a wide spectrum of diseases with major public-health significance. The fight-or-flight response is generally regarded as the prototypic human stress response, both physiologically and behaviorally. Given that having positive social interactions before being exposed to acute stress plays a preeminent role in helping individuals control their stress response, engaging in prosocial behavior in response to stress (tend-and-befriend) might also be a protective pattern. Little is known, however, about the immediate social responses following stress in humans. Here we show that participants who experienced acute social stress, induced by a standardized laboratory stressor, engaged in substantially more prosocial behavior (trust, trustworthiness, and sharing) compared with participants in a control condition, who did not experience socioevaluative threat. These effects were highly specific: Stress did not affect the readiness to exhibit antisocial behavior or to bear nonsocial risks. These results show that stress triggers social approach behavior, which operates as a potent stress-buffering strategy in humans, thereby providing evidence for the tend-and-befriend hypothesis.     

Multiple social identities and reactivity to daily stress among ethnically diverse young adults

In a sample of 181 young adults from Filipino, European, Latin and Asian American backgrounds, cluster analytic techniques were employed to determine how ethnic, American, family, and religious identity interact to form unique identity configurations. Four clusters emerged: Many Social Identities (MSI), Blended/Low Religious (B/LR), Blended/Low Ethnic and American (B/LEA), and Few Social Identities (FSI). Based on daily diary reports over 14 days, differential reactivity to daily stressors was examined on feelings of anxiety and positive mood. Results suggested that individuals in the MSI, B/LR and B/LEA clusters reported increased anxiety on days when they experienced more stressors. In addition, individuals in the MSI and B/LR clusters reported feeling less positive when they experienced stressors. Multiple identity configurations and their implications for stress reactivity are discussed.     

Hypertension risk and caffeine's effect on cardiovascular activity during mental stress in young men

Examined the cardiovascular effects of caffeine plus behavioral stress in men low versus high in risk of essential hypertension. Caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) or placebo was given on alternate days to 19 low-risk men (negative for parental hypertension and low-normal resting blood pressure, BP) and 20 high-risk men (positive history, high-normal BP). Forty minutes later, each worked for 15 min on a demanding psychomotor task during which BP, cardiac output, and vascular resistance were determined. During rest, caffeine raised vascular resistance in both groups. During the task, it supra-additively increased the systolic BP response by enhancing the rise in cardiac output, producing equivalent BP rises in both groups. Due to the higher resting pressures of the high-risk men, caffeine plus the task resulted in 50% of these having transient BP of 140/90 mg Hg or greater. Caffeine in combination with mental stress may produce undesirable BP in those at risk for hypertension.     

Chronic stress influences cardiovascular and neuroendocrine responses during acute stress and recovery, especially in men.

This study tests the influence of chronic stress on cardiovascular and neuroendocrine responses to and recovery from acute stressors and whether the effects are gender specific. Sixty-two healthy, middle-aged persons (50% women) performed mental-arithmetic and public-speaking tasks and relaxed thereafter for 1 hr while their cardiovascular and neuroendocrine function was measured. Participants with higher levels of chronic stress showed lower systolic blood pressure (SBP) and epinephrine (E; men only) and marginally lower levels of norepinephrine (NE) responses to the tasks and showed lower levels of cortisol and marginally lower NE responses during recovery. Relative to women, men had high diastolic blood pressure (DBP) responses to the tasks and high SBP, DBP, and E responses during recovery. Gender differences in cardiovascular disease in midlife may be due to gender differences in the inability to recover quickly, in addition to enhanced acute-stress response.     

Aging and cardiovascular reactivity to stress: longitudinal evidence for changes in stress reactivity

Although age differences in cardiovascular function are well documented, little research has provided longitudinal evidence for age-related changes in cardiovascular reactivity to stress. In this study, the authors report such data from a follow-up of their prior work (B. N. Uchino, D. Uno, J. Holt-Lunstad, & J. B. Flinders, 1999) with participants between the ages of 30 to 70 (n=108, mean follow-up=10 months, range=7 to 16 months). Results revealed longitudinal evidence for an age-related increase in systolic blood-pressure reactivity and parasympathetic withdrawal to acute stress. The implications of these findings are discussed in light of the increased cardiovascular disease risk with age, as well as the links between aging, emotions, and physiology.     

Associations between stress, trait negative affect, acute immune reactivity, and antibody response to hepatitis B injection in healthy young adults.

Eighty-four healthy graduate participants were administered the standard course of 3 hepatitis B vaccinations. Five months after the first dose (shortly after the second injection), each participant completed psychosocial measures, and a blood sample was drawn for determination of hepatitis B surface antibody titer. After completion of the vaccination series, participants performed an acute stress protocol, consisting of a 30-min adaptation period and a 5-min evaluative speech task. Blood was drawn at the end of the resting and task periods for assessment of cellular immune measures. Lower antibody response, as assessed after the second hepatitis B injection, was predicted independently by (a) high trait negative affect and (b) diminished T-cell proliferation in response to PHA. These data provide evidence that trait negative affect and the magnitude of stress-induced suppression of immune function may have clinical significance.     

Cognitive coping strategies and blood pressure responses to real-life stress in healthy young men.

Coping style is an important feature in the understanding of the relation between real-life stress and associated blood pressure (BP) responses. In this study, 10 high- and 10 low-"self-focused-coping" (SFC) male college students were tested with ambulatory BP monitoring on two typical schooldays, one of which included an examination. It was found that the high-SFC subjects, defined as those who tend to keep to themselves and/or blame themselves in stressful situations, showed higher BP responses than the low-SFC subjects, but only on the exam day. Further, the high-SFC subjects showed higher BP during the exam but also had BP elevations that were sustained during other activities throughout the same day, including evening rest. These results are discussed in terms of the relation between psychological and physiological responding.     

Effects of chronic unemployment and acute psychological stress on sexual arousal in men

Effects on sexual arousal of unemployment and acute stress were studied in men. Ten unemployed (high-chronic-stress) and 9 employed (low-chronic-stress) men were exposed to two erotic videotapes in the laboratory. Acute stress was induced by telling the men that they would have to give a talk on their own sexual behavior and fantasies. Half the men were told about the talk before seeing either erotic tape, the other half were told in between the two erotic tapes. Cardiovascular measures confirmed the stressful nature of this manipulation. Results showed that the unemployed men achieved less penile tumescence than the employed men when stressed prior to erotic stimulation. Presentation of the stressor between the erotic videotapes (after sexual arousal occurred) produced no differences between the employed and unemployed men. These results suggest that impairment of erection occurs as a result of a combination of chronic and acute stress.     

Protein kinase a in major depression: the link between hypothalamic-pituitary-adrenal axis hyperactivity and neurogenesis

The latest and most generative biological theories of major depression center on two major hypotheses. The first focuses on the concept that hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis leads to many of the pathological changes in the brain that accompany major depression. The second posits that neurogenesis leads to the repair of depression-related injuries. These two hypotheses are complementary: the former alludes to the etiology or consequences of depression, while the latter suggests mechanisms of antidepressant action. Significant crosstalk occurs between these two systems at many levels. Protein kinase A (PKA) may play an important role in this crosstalk at the intracellular level of signaling cascades. PKA is involved in the formation of long-term potentiation and fear conditioning in response to stress. Chronic stress leads to the suppression of hippocampal activity, which may cause the hyperactivity of the HPA axis during melancholic depression. PKA is also involved in the stimulation of hippocampal neurogenesis after antidepressant treatment. In theory, neurogenesis may lead to the restoration of hippocampal function, and this may be the mechanism that leads to antidepressant-mediated normalization of HPA hyperactivity. Thus, PKA is active during processes that potentially lead to depression and other processes that lead to the resolution of the illness. These opposing processes may be mediated by separate PKA isozymes that activate two distinct pathways. This review highlights the dual role of this enzyme in two biological hypotheses pertaining to depression and its treatment.