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The physical context of previous stress exposure modifies hypothalamic-pituitary-adrenal responses to a subsequent homotypic stress.

The hypothalamic-pituitary-adrenal (HPA) axis becomes less responsive to some types of repeated stress over time, a process termed habituation. Many facets of the stressful stimulus can modify such HPA responses to stressors, such as predictability and controllability. However, the physical context in which the stressor occurred may also provide a discriminative stimulus that can affect the HPA response to that stressor. In the present study, we examined whether a change in the context in which stress exposure occurs can alter HPA responses to a subsequent [corrected] homotypic stressor. Three separate contexts were produced by manipulating odor cues. Rats housed in the 3 context rooms exhibited similar HPA responses to acute 30-min restraint or repeated (8th) 30-min restraint in their home environments. However, rats that were restrained for 30 min per day for 7 days in a room in one context and then restrained on day 8 in a novel context exhibited attenuated habituation compared to rats restrained on day 8 in the familiar context. These results provide evidence that repeated stress-induced HPA activity depends, in part, on the context in which the stress is experienced.

Adrenocorticotropic Hormone↗

Sex differences in stress responses: social rejection versus achievement stress.

BACKGROUND: Sex differences in stress responses may be one mechanism underlying gender differences in depression. We hypothesized that men and women would show different adrenocortical responses to different stressors. In particular, we predicted that women would show greater responses to social rejection stressors, whereas men would demonstrate greater responses to achievement stressors. METHODS: Following a rest session in which they habituated to the laboratory, 50 healthy volunteers (24 men and 26 women, mean age 19.1, SD = 1.13) were randomly assigned to achievement or rejection stress conditions. The achievement condition involved a mathematical and a verbal challenge; the rejection condition involved two social interaction challenges. Self-reported affect and salivary cortisol were measured throughout each stress session (baseline, stress, and poststress periods). RESULTS: There were no sex differences in mood ratings following the stressors; however, cortisol responses showed the predicted gender by condition by time interaction. Men showed significantly greater cortisol responses to the achievement challenges, but women showed greater cortisol responses to the social rejection challenges. CONCLUSIONS: Women appear more physiologically reactive to social rejection challenges, but men react more to achievement challenges. Women's greater reactivity to rejection stress may contribute to the increased rates of affective disorders in women.

Achievement↗

Chronic stress regulates levels of mRNA transcripts encoding beta subunits of the GABA(A) receptor in the rat stress axis.

Semi-quantitative hybridization histochemical analyses were undertaken to determine expression levels of mRNA transcripts encoding the beta1-3 subunits of the GABA(A)receptor within the rat hypothalamic paraventricular nucleus (PVN) and hippocampal formation following exposure to a chronic non-habituating stress protocol. After delivery of a battery of stressors on a randomized schedule over a 3-week period, expression levels of the beta1 subunit of the GABA(A) receptor were found to be decreased in the medial parvocellular PVN (mpPVN) by 48.3% relative to control animals. Levels of beta2 mRNA following chronic stress were also found to be decreased in the mpPVN (29.8%), but increased in hippocampal subfields CA(1) and CA(3) (33.9 and 23.2%, respectively) and increased (24%) in the dentate gyrus. The results suggest that GABA(A) receptor subunit composition may be altered at a key regulatory site, and may have important implications for studies aimed at understanding GABAergic inhibitory influences upon the hypothalamic-pituitary-adrenocortical (HPA) axis. Hypophysiotropic CRH neurons serve as the origin of the final common pathway for glucocorticoid secretion in response to stressful stimuli, and GABAergic afferents have been implicated in afferent control of these neurons. Regulation of GABA(A) receptors at these sites may alter the efficacy of a major inhibitory influence upon the stress axis, and thereby modulate stress-induced glucocorticoid secretion.

Animals↗

Stress persistently increases NMDA receptor-mediated binding of [3H]PDBu (a marker for protein kinase C) in the amygdala, and re-exposure to the stressful context reactivates the increase.

The long-term consequences of acute stress on [3H]phorbol 12,13-dibutyrate ([3H]PDBu) binding, a marker for protein kinase C (PKC) activity, were investigated. In the first experiment, exposure to acute restraint and intermittent tail-shock increased [3H]PDBu binding in the amygdala but not in the hippocampus or cerebral cortex. The increase was persistent, lasting at least 24 h after stressor cessation. In the second experiment, it was determined that the stress-induced increase in binding in the amygdala was dependent on NMDA receptor activation; rats injected with a competitive NMDA receptor antagonist prior to the stressor did not exhibit the increased binding in the amygdala 24 h later. In the third experiment, re-exposure to the stressful context 96 h after stressor cessation reactivated the stress-induced increase the binding of [3H]PDBu in the amygdala. Re-exposure to the context also increased binding in the thalamus and area CA1 of the hippocampus. [3H]PDBu binds preferentially to PKC in the membrane and, therefore, these results suggest that stress induces the translocation of PKC from its resting compartments in the cytosol to the membrane. Its dependence on NMDA receptor activation implicates isoforms of PKC that are sensitive to intracellular calcium, such as PKC gamma. The results further suggest that a "psychological' manipulation, viz. context re-exposure, can reactivate the persistent increase in [3H]PDBu binding in the amygdala.

2-Amino-5-phosphonovalerate↗

Single restraint stress sensitizes acute chewing movements induced by haloperidol, but not if the 5-HT1A agonist 8-OH-DPAT is given prior to stress.

The objective of this study was two-fold: (i) to analyze behavioral sensitization to haloperidol 2 weeks after single restraint stress, and (ii) to establish the effects of 8-OH-DPAT treatment prior to stress on sensitized behavioral responses. Overall behavior was analyzed and not only catalepsy, but also sedation (immobility), grooming, exploration and vacuous chewing movements were evaluated. Results indicated that single restraint stress induced a long-lasting sensitization of acute vacuous chewing movements induced by haloperidol (0.25, 0.5 mg/kg i.p.). Interestingly, this behavioral sensitization was prevented by 8-OH-DPAT (0.35 mg/kg s.c.) prior to stress. Finally, haloperidol-induced sedation was not disrupted by either restraint stress or 8-OH-DPAT treatment.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Cytokine and hormone profiles in mice subjected to handling combined with rectal temperature measurement stress and handling only stress.

Stress is known to either up or down regulate immunity. In this study, mice were subjected to handling combined with rectal temperature measurement (RTM) stress or handling only stress. We investigated whether there were any significant differences in the effect of handling combined with RTM and handling only on NK cell activity, serum cytokine (IL-1beta, IL-6, and TNF-alpha) and ACTH and beta-endorphin levels, and splenic cytokine (IL-1beta, IL-6, TNF-alpha, IFN-alpha, and IFN-beta) levels. Circulating cytokines and hormones and splenic cytokine mRNA levels were measured in individual mice. NK cell activity was significantly increased in both stress groups when compared to the control group. Handling combined with RTM produced significantly increased serum levels of IL-1beta, IL-6, and beta-endorphin. Serum IL-1beta, ACTH, and beta-endorphin were elevated significantly in the handling only group. Splenic TNFalpha mRNA in both of the stress groups and IL-6 mRNA in handling only group decreased significantly. Our observations are supported by existing literature demonstrating that various stressors have differential effects on immune functions and the neuroendocrine hormones and cytokines, which regulate them.

Adrenocorticotropic Hormone↗

Occupational stress within the paramedic profession: an initial report of stress levels compared to hospital employees.

We report a study of occupational stress in 374 paramedics. Results indicate that this profession experiences a high degree of job-related stress relative to other medical personnel. In a component analysis of this stress the results show that job stress manifests itself as job dissatisfaction, organizational stress, and negative patient attitudes, but not as frequently as somatic distress.

Adult↗

Decreased endothelium-dependent vasoconstriction to noradrenaline in acute-stressed rats is potentiated by previous chronic stress: nitric oxide involvement.

1. The objective was to determine whether nitric oxide participates in stress adaptive responses. Acute stress (AS) decreased endothelium-dependent vasoconstriction to noradrenaline (NA) in rat aorta [control rat (CR) 3.90 +/- 0.18, n = 22; AS 2.76 +/- 0.20, n = 13; P < 0.05]. 2. Chronic stress exposure previous to AS (CS) potentiated this effect [CS 1.93 +/- 0.19; n = 9; P < 0.05 related to CR, P < 0.05 related to AS]. 3. Methylene blue and NG-monomethyl-L-arginine, but not indomethacin, restored the decreased aorta reactivity to NA. 4. No reactivity alteration was observed in aorta without endothelium either in both stress conditions or in the presence of inhibitors. These data show that the nitric oxide participates in stress responses.

Acute Disease↗

Chronic glucocorticoid administration as well as repeated stress affects the subsequent acute immobilization stress-induced expression of immediate early genes but not that of NGFI-A.

We reported that repeated immobilization for six days attenuates the subsequent acute immobilization stress-induced expression of the immediate early genes c-fos, fos B, jun B and nerve growth factor-induced gene-B (NGFI-B), but not of NGFI-A, in the rat paraventricular hypothalamic nucleus. In this study, we confirmed these findings by means of a time-course study, and further investigated whether the elevated plasma basal glucocorticoid level induced by repeated stress underlies the attenuated response of immediate early genes and the preserved reactivity of NGFI-A. Rats implanted with 100, 200 or 400 mg corticosterone or placebo pellets (control), were immobilized for 1 h and decapitated seven days later. In control rats acute immobilization induced c-fos, fos B, jun B, NGFI-A and NGFI-B messenger RNA in the paraventricular hypothalamic nucleus, whereas all of them except NGFI-A, were significantly reduced in rats given 200 and 400 mg corticosterone implants. The similarity of the results from the two procedures suggests that glucocorticoid is involved in regulating immediate early genes in the paraventricular hypothalamic nucleus under repeated stress and that the NGFI-A gene is not regulated by this mechanism. However, the plasma basal corticosterone level in repeatedly stressed rats was lower than that of rats implanted with 100 mg corticosterone, suggesting that a repetitive stress-induced corticosterone surge also contributes to this mechanism.

Animals↗

Activation of the promoters of genes associated with DNA damage, oxidative stress, ER stress and protein malfolding by the bile salt, deoxycholate.

Toxic bile salts, retained within the liver because of impaired biliary excretion, are considered to play a major role in liver injury during cholestasis. Bile salts cause cellular stresses that may result in apoptosis. To better understand such cellular stresses, the effect of the bile salt sodium deoxycholate (NaDOC) on activation of 13 specific gene promoters or response elements associated with different cellular stresses was measured in the transformed human hepatoma line, HepG2. NaDOC was found to activate transcription factors and induce or activate the promoters of genes that respond to protein malfolding (grp78 and hsp70), DNA damage (gadd153, hsp70 and c-fos), oxidative stress (NF-kappaB, c-fos, hsp70 and gadd153), ER stress (grp78) and Ca++ imbalance (grp78).

Bile Acids and Salts↗

Influence of wall stress and left ventricular geometry on the accuracy of dobutamine stress echocardiography.

OBJECTIVE: The goal of this study was to determine whether wall stress at rest and during stress could explain the influence of left ventricular (LV) morphology on the accuracy of dobutamine stress echocardiography (DSE). BACKGROUND: The sensitivity of DSE appears to be reduced in patients with concentric remodeling, but the cause of this finding is unclear. METHODS: We studied 161 patients without resting wall motion abnormalities who underwent DSE and coronary angiography. Patients were classified into four groups according to relative wall thickness (normal <0.45) and LV mass (normal </=131 g/m(2) in men and </=100 g/m(2) in women): normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Significant coronary artery disease was defined as >/=50% stenosis. Circumferential (cESS) and meridional end-systolic wall stress (mESS) were calculated at rest and peak DSE. RESULTS: Both false-negative and false-positive results for DSE were present in 35 patients (22%). The accuracy of DSE in patients with concentric remodeling (61%) was lower than that in patients with normal geometry (85%, p < 0.05) or concentric hypertrophy (86%, p < 0.05), but the accuracy with eccentric hypertrophy (64%, p < 0.05) was lower than with concentric hypertrophy. Patients in lowest quartile of cESS and mESS at peak had significantly lower sensitivity and accuracy than those in the highest quartile. A reduced cESS at peak (p = 0.012), presence of concentric remodeling (p = 0.044), and eccentric hypertrophy (p = 0.012) were significant predictors of both false-negative and false-positive results for DSE. CONCLUSIONS: The accuracy of DSE is influenced by the LV geometric pattern and peak wall stress.

Aged↗

Prenatal experience and postnatal stress modulate the adult neurosteroid and catecholaminergic stress responses.

Allopregnanolone (3 alpha-hydroxy-5 alpha-regnan-20-one) is a neuroactive steroid recently shown to be involved in the neurochemical stress response via its positive modulation of the GABAA receptor complex. This experiment investigated the effects of postnatal stress (daily maternal separation during the first week of life) on the subsequent adult response to a stressor (10 min forced swim) in Long-Evans rats from one of three prenatal treatment groups (alcohol, pair-fed and control). Indices of stress response were allopregnanolone concentrations in plasma, cortex and hippocampus, and dopamine and norepinephrine concentrations in prefrontal cortex, nucleus accumbens and striatum. Females had higher levels of allopregnanolone than males in both plasma and brain. Prenatal alcohol exposure combined with early maternal separation stress resulted in an increase in the endogenous levels of allopregnanolone in the prefrontal cortex and hippocampus of adult offspring in response to a stressor compared to subjects without a prior history of postnatal stress; this effect was greater in females. This increased allopregnanolone was also associated with decreased dopamine and norepinephrine levels in the prefrontal cortex. In the prenatal alcohol-exposed offspring, postnatal maternal separation blunted the increase in dopamine levels in the striatum seen in both control groups. Postnatal maternal separation increased norepinephrine levels in the nucleus accumbens regardless of prenatal experience, while in the prefrontal cortex only prenatal diet condition (pair-feeding and alcohol) resulted in lower norepinephrine levels. The results of this experiment suggest that experience, both pre- and postnatal, can have long-term consequences for the developing neurochemical responses to stressors.

Animals↗

Tibiofemoral contact stress and stress distribution evaluation of total knee arthroplasties.

The Fuji film (Itochu, Los Angeles, CA) area analysis technique demonstrates that a more accurate assessment of tibiofemoral contact stresses is possible when the film is used at 37 degrees C and at the upper end of its sensitivity range (in this case, a 2,000-N load). An AMK with a regular and Hylamer-M insert (DePuy, Warsaw, IN), an MG II (Zimmer, Warsaw, IN), an Omnifit (Osteonics, Allendale, NJ), an Ortholoc III (Dow Corning Wright, Midland, MI), a PCA II (Howmedica, Rutherford, NJ), and a PFC (Johnson & Johnson Orthopaedics, Raynham, MA) had average contact stresses that varied only 12% at 60 degrees flexion. At 0 degrees, 15 degrees and 60 degrees flexion, stresses ranged from 13 to 25 MPa. Contact area distribution ratios, which were smaller at 37 degrees C than at 24 degrees C, provide a quantitative means of grouping implants according to the shape of the tibiofemoral contact area. The Omnifit, MG II, PCA II, and PFC had small ratios (symmetric areas). The AMK and Ortholoc III had large ratios (asymmetric contact areas). If the impression is reflective of wear, it would be expected to be focal in knees with small ratios and contact areas, and uniform in knees with large ratios and contact areas, whereas large ratios and small areas would imply a linear wear pattern. Calibrated electrical resistance contact stress measurements indicated that the Fuji film measurements underestimated the magnitude of contact stresses. They also provided a means of quantifying the rate of area increase during initial loading of the knees, with the highest area increase noted for the knee with the roughest insert (Ortholoc III) and the lowest area increase for the knee with the smoothest insert (PCA II).

Electric Impedance↗

An integrated stress response regulates amino acid metabolism and resistance to oxidative stress.

Eukaryotic cells respond to unfolded proteins in their endoplasmic reticulum (ER stress), amino acid starvation, or oxidants by phosphorylating the alpha subunit of translation initiation factor 2 (eIF2alpha). This adaptation inhibits general protein synthesis while promoting translation and expression of the transcription factor ATF4. Atf4(-/-) cells are impaired in expressing genes involved in amino acid import, glutathione biosynthesis, and resistance to oxidative stress. Perk(-/-) cells, lacking an upstream ER stress-activated eIF2alpha kinase that activates Atf4, accumulate endogenous peroxides during ER stress, whereas interference with the ER oxidase ERO1 abrogates such accumulation. A signaling pathway initiated by eIF2alpha phosphorylation protects cells against metabolic consequences of ER oxidation by promoting the linked processes of amino acid sufficiency and resistance to oxidative stress.

Activating Transcription Factor 4↗

The impact of the homecoming reception on the development of posttraumatic stress disorder. The West Haven Homecoming Stress Scale (WHHSS).

This study reports on the development of a self-report measure of the homecoming experience among Vietnam veterans with posttraumatic stress disorder (PTSD). The West Haven Homecoming Stress Scale (WHHSS), measuring Frequency of Events, Intensity of Feelings, and Level of Support during the first 6 months after return from overseas, and within the past 6 months, was collected from 247 veterans who were receiving inpatient treatment for PTSD. Homecoming Stress was the most significant predictor of current PTSD symptomatology superseding combat exposure, childhood and civilian traumas, and stressful life events. A factor analysis resulted in four orthogonal factors: Shame, Negative Interpersonal Interaction, Social Withdrawal, and Resentment. Homecoming Stress was unchanged over the course of a 4 month inpatient program.

Adult↗

Psychological stress and glucose metabolism in obese and normal-weight subjects: a possible mechanism for differences in stress-induced eating.

Acute psychological stress has been found to impair the handling of a glucose load in normal-weight individuals and to produce a delay in gastrointestinal transit time. The present study utilized the same paradigm to compare 10 obese and 10 normal-weight subjects. All subjects participated in two counterbalanced sessions (stress and nonstress). At each session, subjects were fed a carbohydrate load, and glucose was measured 0, 30, 60, 90, and 120 min after the load. On nonstress days, subjects relaxed after the drink; on stress days, subjects participated in 30 min of competitive tasks. The stressor significantly delayed the glucose response in the normal-weight subjects but did not affect the glucose response in obese subjects. This finding may have implications for differences between obese and normal-weight individuals in stress-induced eating, possibly explaining the decreased consumption of normal-weight individuals during stress.

Anger↗

Juvenile and adult footshock stress modulate later adult gastric pathophysiological reactions to restraint stresses in rats.

Rats were stressed with (a) signaled footshocks, (b) unsignaled footshocks, or (c) handled without footshocks as a prepubertal juvenile (28-36 days old), as an adult (96 days old), or both. This yielded nine treatment groups (3 x 3). Two days after the adult treatment, all animals were challenged by restraint and partial immersion in water (19 degrees C) to assess their relative susceptibility to gastric erosions ("ulcers"). We found that any prior exposure to footshock stress increased the amount of ulcers; juvenile and adult experiences each produced equal increases but the combination of the two was less ulcerogenic than either alone. The predictability of the footshocks did not modulate ulcerogenicity. Adult corticosterone responses to (a) adult stress and (b) ulcer induction were not related to the observed ulcer severity; however, juvenile footshock stress appeared to reduce the corticoid response to the ulcerogenic challenge but not to the adult footshock stress.

Age Factors↗

Dual-earner families: the importance of work stress and family stress for psychological well-being.

Scales of work stress and family stress as well as outcome measures of depression and self-esteem were completed by 94 mothers and 48 fathers in dual-earner families. Working mothers and working fathers reported equivalent levels of family stress, work stress, job-family interference, and psychological well-being, although mothers did report a higher level of lack of task sharing. Self-esteem and depression of dual-earner mothers and fathers were affected by both job and family stress. Insignificance within their work role affected both self-esteem and depression. Lack of task sharing significantly predicted depression among dual-earner mothers. Lack of challenge in their work role appeared to be a positive characteristic for dual-earner fathers.

Adult↗