The role of preterm birth in stress-induced sodium excretion in young adults.

BACKGROUND: Early-life programming due to prematurity and very low birth weight (VLBW, <1500 g) is believed to contribute to development of hypertension, but the mechanisms remain unclear. Experimental data suggest that altered pressure natriuresis (increased renal perfusion pressure promoting sodium excretion) may be a contributing mechanism. We hypothesize that young adults born preterm will have a blunted pressure natriuresis response to mental stress compared with those born term. METHODS: In this prospective cohort study of 190 individuals aged 18-23 years, 156 born preterm with VLBW and 34 controls born term with birth weight at least 2500 g, we measured urine sodium/creatinine before and after a mental stress test and continuous blood pressure before and during the stress test. Participants were stratified into groups by the trajectory at which mean arterial pressure (MAP) increased following the test. The group with the lowest MAP trajectory was the reference group. We used generalized linear models to assess poststress urine sodium/creatinine relative to the change in MAP trajectory and assessed the difference between groups by preterm birth status. RESULTS: Participants' mean age was 19.8 years and 57% were women. Change in urine sodium/creatinine per unit increase in MAP when comparing middle trajectory group against the reference group was greater in those born preterm [ß 5.4%, 95% confidence interval (95% CI) -11.4 to 5.3] than those born term (ß 38.5%, 95% CI -0.04 to 92.0), interaction term P = 0.002. CONCLUSION: We observed that, as blood pressure increased following mental stress, young adults born preterm exhibited decreased sodium excretion relative to term-born individuals.

Psychosocial stress and neuroendocrine biomarker concentrations among women living with or without HIV.

OBJECTIVE: Women living with HIV (WLWH) experience psychosocial stress related to social-structural vulnerabilities. To investigate neuroendocrine pathways linking stress and increased cardiovascular disease risk among WLWH, we evaluated associations between psychosocial stress (i.e., perceived stress, posttraumatic stress, and experiences of race- and gender-based harassment) and a composite neuroendocrine biomarker index among WLWH and women without HIV. METHODS: In 2019-2020, Women's Interagency HIV Study participants in Washington, DC completed a questionnaire and provided blood and 12-hour overnight urine samples for testing of serum dehydroepiandrosterone sulfate (DHEA-S) and urinary free cortisol, epinephrine, and norepinephrine. Psychosocial stress was measured using the Perceived Stress Scale, PTSD Checklist-Civilian Version, and Racialized Sexual Harassment Scale. Latent profile analysis was used to classify participants into low (38%), moderate (44%), and high (18%) stress groups. Composite biomarker index scores between 0-4 were assigned based on participants' number of neuroendocrine biomarkers in high-risk quartiles (≥75th percentile for cortisol, epinephrine, and norepinephrine and ≤25th percentile for DHEA-S). We evaluated associations between latent profile and composite biomarker index values using multivariable linear regression, adjusting for socio-demographic, behavioral, metabolic, and HIV-related factors. RESULTS: Among 90 women, 62% were WLWH, 53% were non-Hispanic Black, and median age was 55 years. In full multivariable models, there was no statistically significant association between psychosocial stress and composite biomarker index values among all women independent of HIV status. High (vs. low) psychosocial stress was positively associated with higher mean composite biomarker index values among all monoracial Black women (adjusted ß = 1.32; 95% CI: 0.20-2.43), Black WLWH (adjusted ß = 1.93; 95% CI: 0.02-3.83) and Black HIV-negative women (adjusted ß = 2.54; 95% CI: 0.41-4.67). CONCLUSIONS: Despite a null association in the overall sample, greater psychosocial stress was positively associated with higher neuroendocrine biomarker concentrations among Black women, highlighting a plausible mechanism by which psychosocial stress could contribute to cardiovascular disease risk.

Is PTSD-Phenotype Associated with HPA-Axis Sensitivity?: The Endocannabinoid System in Modulating Stress Response in Rats.

Endocannabinoids play a role in adaptation to stress and regulate the release of glucocorticoids in stressed and unstressed conditions. We recently found that basal corticosterone pulsatility may significantly impact the vulnerability for developing post-traumatic-stress-disorder (PTSD), suggesting that the endocannabinoid system may contribute to its development. To examine this, we exposed rats to predator scent stress (PSS). Behavioral reactions were recorded seven days post-PSS. Cerebrospinal fluid (CSF) was collected from anesthetized rats shortly after PSS exposure to determine the levels of 2-arachidonoyl glycerol (2-AG) and anandamide (AEA). To correlate between endocannabinoids and corticosterone levels, rats were placed in metabolic cages for urine collection. To assess the levels of endocannabinoids in specific brain regions, rats' brains were harvested one day after behavioral analysis for staining and fluorescence quantification. Moreover, 2-AG was elevated in the CSF of PTSD-phenotype rats as compared with other groups and was inversely correlated with corticosterone urinary secretion. Eight days post-PSS exposure, hippocampal and hypothalamic 2-AG levels and hippocampal AEA levels were significantly more reduced in the PTSD-phenotype group compared to other groups. We posit that maladaptation to stress, which is propagated by an abnormal activation of endocannabinoids, mediates the subsequent stress-induced behavioral disruption, which, later, reduces neuronal the expression of endocannabinoids, contributing to PTSD symptomology.

Time-lag of urinary and salivary cortisol response after a psychological stressor in bonobos (Pan paniscus).

Cortisol is often measured as a marker for stress. Therefore, a profound validation of the time-lag between the stressor and the increase and peak in cortisol levels is needed. No study measured both the urinary and salivary cortisol time-lag after a psychological stressor. In this study, we used a frequent sampling study design to (1) describe the urinary and salivary cortisol pattern during a control day; and (2) characterize the induced excretion pattern of urinary and salivary cortisol after a psychological stressor in six zoo-housed bonobos. Liquid chromatography-tandem mass spectrometry was used to analyze 71 urine and 162 saliva samples collected on a control and a test day. We found that the time-lag between the stressor and the maximal cortisol concentration was similar in urine and saliva (160 min after the stressor). However, salivary cortisol after the stressor did show a faster and steeper increase than urinary cortisol. We also show inter-individual variation in the baseline and stress levels of cortisol, which should be considered in future cortisol studies. Our research highlights the importance of validation studies to confirm relevant sampling windows for cortisol sampling in order to obtain biologically meaningful results.

Urine metabolomic responses to aerobic and resistance training in rats under chronic unpredictable mild stress.

BACKGROUND: It is known that bioenergetics of aerobic and resistance exercise are not the same but both can effectively improve depression. However, it is not clear whether and how different types of exercise can influence depression through the same metabolic regulatory system. Metabolomics provides a way to study the correlation between metabolites and changes in exercise and/or diseases through the quantitative analysis of all metabolites in the organism. The objective of this study was to investigate the effects of aerobic and resistance training on urinary metabolites by metabolomics analysis in a rodent model of depression. METHODS: Male Sprague-Dawley rats were given chronic unpredictable mild stress (CUMS) for eight weeks. The validity of the modeling was assessed by behavioral indices. After four weeks of CUMS, the rats that developed depression were randomly divided into a depression control group, an aerobic training group and a resistance training group. There was also a normal control group. From week 5, the rats in the exercise groups were trained for 30 min per day, five days per week, for four weeks. The urine samples were collected pre and post the training program, and analyzed by proton nuclear magnetic resonance (1H-NMR) spectroscopy. RESULTS: Both types of training improved depression-like behavior in CUMS rats. Compared with normal control, 21 potential biomarkers were identified in the urine of CUMS rats, mainly involved in energy, amino acids and intestinal microbial metabolic pathways. Common responses to the training were found in the two exercise groups that the levels of glutamine, acetone and creatine were significantly recalled (all P<0.05) Aerobic training also resulted in changes in pyruvate and trigonelline, while resistance training modified α-Oxoglutarate, citric acid, and trimethylamine oxide (all P<0.05). CONCLUSIONS: Aerobic and resistance training resulted in common effects on the metabolic pathways of alanine-aspartate-glutamate, TCA cycle, and butyric acid. Aerobic training also had effects on glycolysis or gluconeogenesis and pyruvate metabolism, while resistance training had additional effect on intestinal microbial metabolism.

An investigation into socio-demographic-, health-, and cancer-related factors associated with cortisol and C-reactive protein levels in breast cancer survivors: a longitudinal study.

BACKGROUND: Breast cancer survivors (BCS) may exhibit dysregulated patterns of cortisol and C-reactive protein (CRP). The aims of this study were to describe BCS' cortisol and CRP levels over a 1-year period after treatment, and assess how levels relate to socio-demographic- (age, education level, marital status), health- (body mass index [BMI] category, menopausal status), and cancer-related factors (cancer stage, chemotherapy exposure, time since diagnosis). METHODS: Participants (N = 201) provided data at 3 months post-treatment (T1) and again 3, 6, 9, and 12 months later (T2-T5). At T1, participants completed self-report questionnaires and had their weight and height measured by a trained technician. At T1-T5, they provided five saliva samples at awakening, 30 min after awakening, 2:00 pm, 4:00 pm, and before bedtime on two nonconsecutive days to measure diurnal cortisol, and provided capillary whole blood to measure CRP. Data were analyzed using repeated-measure analyses of variance (ANOVAs) and mixed-design ANOVAs. RESULTS: Diurnal cortisol and CRP levels fluctuated over time. In univariate models, older age and post-menopausal status were associated with higher cortisol and CRP levels, higher cancer stage and chemotherapy were associated with lower cortisol levels, and higher BMI category was associated with higher CRP levels. In adjusted models, age was no longer associated with CRP levels and shorter time since diagnosis was significantly associated with higher CRP levels. CONCLUSIONS: Socio-demographic-, health-, and cancer-related factors may help identify BCS at risk of physiological dysregulation who need intervention. Identifying modifiable factors associated with cortisol and CRP will inform cancer care interventions.

Both objective and paradoxical insomnia elicit a stress response involving mitokine production.

Chronic insomnia is the most common sleep disorder in the elderly population. From 9 to 50% of patients suffer of paradoxical insomnia, with the same symptoms and ailments, though characterized by normal sleep patterns. We have investigated the level of parameters related to stress in a group of post-menopausal female patients (age range 55-70 years) suffering by either objective or paradoxical insomnia, in particular we have measured 24-hours urinary cortisol, allostatic load index, Perceived Stress Scale (PSS) score, and, for the first time, mitokines (mitochondrial stress response molecules) such as FGF21, GDF15 and Humanin (HN). Results show that the two groups are different as far as sleep efficiency score, as expected, but not for stress parameters, that in some cases resulted within the normality range, although quite close to the top threshold (such as cortisol) or much higher with respect to normality ranges (such as PSS). Therefore, the consequences of paradoxical insomnia on the expression of these parameters are the same as objective insomnia. As far as the level of mitokines, we showed that FGF21 and HN in particular resulted altered (decreased and increased, respectively) with respect to control population, however with no difference between the two groups of patients.

[Pharmacological Effects of Yokukansankachimpihange on Urinary Catecholamine in Restraint-stressed Mice].

Herbal medicines, acupuncture and moxibustion are often used for unidentified complaints. It is well known that catecholamine secreted by the sympatho-adrenal medullary system primarily functions to increase cardiac output and raise glucose levels in the blood during acute stress. In the present study, the effects of yokukansankachimpihange (YKSKCH, a Kampo medicine) on urinary catecholamine in mice that were repeatedly stressed by restraining were examined. Restraint stress (240 min/d×3 d×3 cycles, daytime: 12:00-16:00) induced a marked increase in noradrenaline (NA) and adrenaline (A) levels in the urine. Oral administration of YKSKCH (750 mg/kg of body weight) significantly inhibited the increase in urinary NA and A levels in mice after repeated restraint stress. In addition, the NA/dopamine (physical stress) and A/dopamine (mental stress) ratios were lower in the 750 mg/kg YKSKCH-treated group than in the control group. The tail suspension test was also performed and locomotor activity was investigated. Oral administration of YKSKCH at 750 mg/kg significantly reduced the immobility time, which was longer in mice after repeated restraint stress. Furthermore, oral administration of YKSKCH at 750 mg/kg increased locomotor activity, which was lower in mice after repeated restraint stress. These results suggest that YKSKCH has positive effects on mental and physical stress after repeated restraint stress, without reducing locomotor activity.

Preconception Perceived Stress Is Associated with Reproductive Hormone Levels and Longer Time to Pregnancy.

BACKGROUND: Women who experience pregnancy loss are especially prone to high stress, though the effects of stress on reproductive outcomes in this vulnerable population are unknown. We assessed relationships between perceived stress and hormones, anovulation, and fecundability among women with prior loss. METHODS: One thousand two hundred fourteen women with 1-2 prior losses were followed for ≤6 cycles while attempting pregnancy and completed end-of-cycle stress assessments. For cycles 1 and 2, women also collected daily urine and completed daily perceived stress assessments. We assessed anovulation via. an algorithm based on human chorionic gonadotropin (hCG), pregnanediol-3-glucuronide (PdG), luteinizing hormone (LH), and fertility monitor readings. Pregnancy was determined via. hCG. Adjusted weighted linear mixed models estimated the effect of prospective phase-varying (menses, follicular, periovulatory, and luteal) perceived stress quartiles on estrone-1-glucuronide (E1G), PdG, and LH concentrations. Marginal structural models accounted for time-varying confounding by hormones and lifestyle factors affected by prior stress. Poisson and Cox regression estimated risk ratios and fecundability odds ratios of cycle-varying stress quartiles on anovulation and fecundability. Models were adjusted for age, race, body mass index (BMI), parity, and time-varying caffeine, alcohol, smoking, intercourse, and pelvic pain. RESULTS: Women in the highest versus lowest stress quartile had lower E1G and PdG concentrations, a marginally higher risk of anovulation [1.28; 95% confidence interval (CI) = 1.00, 1.63], and lower fecundability (0.71; 95% CI = 0.55, 0.90). CONCLUSION: Preconception perceived stress appears to adversely affect sex steroid synthesis and time to pregnancy. Mechanisms likely include the effects of stress on ovulatory function, but additional mechanisms, potentially during implantation, may also exist.

Urinary catecholamines during stress and ambulatory blood pressure in children born full term but small for gestational age: a pilot study.

OBJECTIVES: Increased sympathetic activity is proposed to be a mechanism of high blood pressure in children born small for gestational age. Ambulatory blood pressure monitoring is a form of blood pressure measurement that can detect high blood pressure outside the hospital in patients with normal office blood pressure. This condition is called masked hypertension. There are limited data on association between ambulatory blood pressure and urinary catecholamines during exposure to stress in children born small for gestational age. METHODS: Nineteen children born small for gestational age and 17 healthy controls ages 6-14 years old were included. Demographic data and office blood pressure were collected. Urinary catecholamines were collected before and after exposure to stress including mathematical test and venipuncture. Afterwards, ambulatory blood pressure monitoring was performed to obtain 24-hour blood pressure profiles. RESULTS: All children had normal office blood pressure but ambulatory blood pressure monitoring revealed masked hypertension in six children born small for gestational age (32%) and two controls (11.7%). After stress, median percentage of increase in urine norepinephrine levels was greater in children born small for gestational age with masked hypertension than that of children born small for gestational age without masked hypertension (9.2 vs. -13.2 µg/g creatinine, P = 0.05). There was no increase in urine norepinephrine levels in controls with masked hypertension. Among children born small for gestational age, awake SBP z-scores had significant positive correlations with pre- and post-stress urinary dopamine levels (r = 0.530, P = 0.02 and r = 0.597, P = 0.007, respectively). CONCLUSION: Masked hypertension is not uncommon in children born small for gestational age. After stress, urinary norepinephrine levels were increased in children born small for gestational age with masked hypertension.

Sex differences in stress and immune responses during confinement in Antarctica.

BACKGROUND: Antarctica challenges human explorers by its extreme environment. The effects of these unique conditions on the human physiology need to be understood to best mitigate health problems in Antarctic expedition crews. Moreover, Antarctica is an adequate Earth-bound analogue for long-term space missions. To date, its effects on human physiology have been studied mainly in male cohorts though more female expeditioners and applicants in astronaut training programs are selected. Therefore, the identification of sex differences in stress and immune reactions are becoming an even more essential aim to provide a more individualized risk management. METHODS: Ten female and 16 male subjects participated in three 1-year expeditions to the German Antarctic Research Station Neumayer III. Blood, saliva, and urine samples were taken 1-2 months prior to departure, subsequently every month during their expedition, and 3-4 months after return from Antarctica. Analyses included cortisol, catecholamine and endocannabinoid measurements; psychological evaluation; differential blood count; and recall antigen- and mitogen-stimulated cytokine profiles. RESULTS: Cortisol showed significantly higher concentrations in females than males during winter whereas no enhanced psychological stress was detected in both sexes. Catecholamine excretion was higher in males than females but never showed significant increases compared to baseline. Endocannabinoids and N-acylethanolamides increased significantly in both sexes and stayed consistently elevated during the confinement. Cytokine profiles after in vitro stimulation revealed no sex differences but resulted in significant time-dependent changes. Hemoglobin and hematocrit were significantly higher in males than females, and hemoglobin increased significantly in both sexes compared to baseline. Platelet counts were significantly higher in females than males. Leukocytes and granulocyte concentrations increased during confinement with a dip for both sexes in winter whereas lymphocytes were significantly elevated in both sexes during the confinement. CONCLUSIONS: The extreme environment of Antarctica seems to trigger some distinct stress and immune responses but-with the exception of cortisol and blood cell counts-without any major relevant sex-specific differences. Stated sex differences were shown to be independent of enhanced psychological stress and seem to be related to the environmental conditions. However, sources and consequences of these sex differences have to be further elucidated.

Home ovulation test use and stress during subfertility evaluation: Subarm of a randomized controlled trial.

OBJECTIVES: A prospective, randomized controlled trial in women seeking to conceive examined the impact of using ovulation tests on self-reported levels of stress, psychological well-being, and quality of life in women with unexplained infertility. METHOD: The test group used a home ovulation test to detect the day of ovulation, whereas the control group were provided with a predicted day of ovulation based on the average length of menstrual cycle reported during study recruitment. Volunteers collected their first morning urine samples to evaluate biochemical levels of stress (urinary cortisol and estrone-3-glucouronide) and completed questionnaires over two complete menstrual cycles. RESULTS: Overall, the use of digital ovulation tests by sub-fertile women under medical care had negligible negative effects and no detectable positive benefit on psychological well-being, according to multiple measurements of stress by questionnaire and biochemical markers. No significant differences were found between groups for all stress measures at the various study time points, except in relation to "couple concordance" where the test group scored much higher than the control group (mean difference at end of study was 21.25 (95% confidence interval: 9.25, 33.25; P = 0.0015)). The maximum difference in log cortisol: creatinine ratio between the test and control groups was -0.28 (95% confidence interval: -0.69, 0.13). CONCLUSIONS: These results do not support propositions that using digital ovulation tests can cause stress in women trying to conceive.

Cortisol and oxytocin show independent activity during chimpanzee intergroup conflict.

The oxytocinergic system is involved in a range of functions, from attachment and social bonding to aggression and stress responses. Whether oxytocin is released in response to a stressor, shows contradictory results across species and potential contexts-dependent differences. To avoid unintended contextual changes due to experimental procedures, we tested this question non-invasively in wild chimpanzees in an ecologically valid context. We collected endogenous hormonal measures during exposure to a known natural stressor, intergroup conflict. Specifically, we tested for potential synchronous activation patterns between urinary oxytocin and cortisol in male and female chimpanzees during stressor exposure. Oxytocinergic system reactivity during chimpanzee intergroup conflict has already been established in this study population. Thus, we first investigated urinary cortisol levels during border patrol and intergroup encounter days, in comparison to another potential stressor, hunting, and control days. We found higher urinary cortisol levels during intergroup encounter days compared with control and hunting days. We then compared secretion patterns of oxytocin and cortisol in relation to increased levels of out-group contact and hostility ('out-group risk') during intergroup conflict. We found that increased 'out-group risk' was associated with higher cortisol levels, especially when involving direct visual or physical contact with rival groups. Although urinary oxytocin levels were high across intergroup conflict contexts, increasing levels of out-group risk showed no significant variation. Taken together, results indicate independent secretion of oxytocin and cortisol during chimpanzee intergroup conflict, emphasizing that stressor exposure in this context is not the main trigger of oxytocin secretion.

Quantitative profiling of cortisol metabolites in human urine by high-resolution accurate-mass MS.

Aim, materials & methods: Urinary cortisol profile has the potential as a diagnostic biomarker. We therefore developed a stable-isotope dilution ultraperformance chromatography multistage MS-based method to quantify cortisol and 16 metabolites in human urines. Results & conclusion: The LOD for cortisol and its metabolites ranges from 0.02 to 5.81 pg/µl urine. The inter- and intraday variations were 3.7-12.9% and 3.5-15.6%, respectively. Among the metabolites analyzed, significant person-to-person heterogeneity was observed, demonstrating the need for comprehensive metabolite profiling in diagnosis. Nevertheless, the glucuronides of dihydrocortisol, dihydrocortisone, tetrahydrocortisol, allo-tetrahydrocortisol and tetrahydrocortisone are the major ones. The sum of the glucuronidated and free forms constitute >93% of the metabolites analyzed, which is termed as total cortisol equivalent. Total cortisol equivalent may serve as a surrogate of cortisol secretion. Clinical trial registration number: NCT02500472.

Trajectory classes of cannabis use and heavy drinking among rural African American adolescents: multi-level predictors of class membership.

AIMS: To inform research on the etiology and prevention of substance use among rural African American youth by (a) identifying developmental trajectory classes of cannabis use and heavy drinking across adolescence and young adulthood and (b) examining associations between trajectory class membership and multi-level assessments of risk factors. DESIGN: A prospective study spanning 9 years with assessments of cannabis use and heavy drinking, the catecholamines epinephrine and norepinephrine, perceived stress and psychosocial risk factors. SETTING: Rural communities in the southeastern United States. PARTICIPANTS: African American youth (n = 518). MEASUREMENTS: Participants were assessed for cannabis use and heavy drinking at seven assessments beginning at 16 years of age and continuing to 25 years of age. At age 19, participants provided overnight urine voids that were assayed for catecholamines, a biological marker of life stress resulting from sympathetic nervous system activation. At ages 16 and 19, participants provided information on malleable psychosocial risk factors. FINDINGS: Latent class growth models revealed three distinct trajectory classes for cannabis use and for heavy drinking. Higher levels of circulating stress hormones and perceived stress were associated with classes reporting greater substance use over time (all Ps < 0.05). A composite of selected risk factors discriminated class membership (all Ps < 0.05). Trajectory classes characterized by rapid usage increases in early adulthood exhibited the greatest increase in deviant peer affiliations between ages 16 and 19 years. CONCLUSIONS: Rural African American youth's cannabis use and heavy drinking across adolescence and young adulthood demonstrate distinct developmental courses; a small number of risk factors and measures of biological and perceived stress differentiate class membership prognostically. Variability over time in these measures, specifically an increase in deviant peer affiliation, may help to account for steep increases in young adulthood.

Metabonomics Approach To Comparing the Antistress Effects of Four Panax ginseng Components in Rats.

Different components of Panax ginseng have different properties and medicinal effects. Metabonomics was a prospective approach to analyze the global response of endogenous metabolites to physiological and pathological processes. In this study, an untargeted metabonomics method using GC/TOFMS combined with multivariate statistical techniques was applied to compare entire metabolite differences and the antistress variations among four components of P. ginseng, namely, total ginsenosides (TG), panaxadiol (PD), panaxatriol (PT), and ginseng polysaccharide (PS), in Wistar rats. The results of metabolite analysis showed that numerous urine metabolites involving neurotransmitters, amino acids, organic acids, and gut microbiota metabolites were changed after administration of the four components of P. ginseng, with TG having the least impact on urinary metabolites. The urinary metabolite profiling of these rats exposed to acute combined stress (forced swimming and behavior restriction) demonstrated that the four ginseng components attenuated urine metabolite changes involving gut microbiota metabolites, tricarboxylic acid (TCA) cycle and energy metabolites, and organic acids to different degrees, with TG improving most of the metabolites altered by stress.

Perceived Stress, Depressive Symptoms, and Oxidative DNA Damage.

OBJECTIVE: Psychosocial stress may influence the risk of disease through its association with oxidative DNA damage. We examined whether perceived stress and depressive symptoms were associated with urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), with mutual interaction on 8-OHdG. METHODS: This cross-sectional study included 6517 individuals aged 45 to 74 years who participated, between 2010 and 2012, in a follow-up survey of an ongoing cohort study. Perceived stress during the past year was measured using a self-report questionnaire. Depressive symptoms were evaluated using the Zung Self-Rating Depression Scale. Urinary 8-OHdG concentrations were measured using a column switching high-pressure liquid chromatography system coupled to an electrochemical detector. RESULTS: Higher perceived stress was significantly associated with higher 8-OHdG (2.1% increase per one-category increase of stress; ptrend = .025), even after adjusting for sex, age, supplement use, psychosocial factors, psychotropic medication use, smoking, and body mass index. This association was modestly attenuated after further adjustment for physical activity, suggesting possible mediation or confounding by this factor. Depressive symptoms were not significantly associated with 8-OHdG. No significant interaction was detected between perceived stress and depressive symptoms on 8-OHdG. CONCLUSIONS: In a general Japanese population, we found a weak positive association between perceived stress and urinary excretion of 8-OHdG, whereas no association was observed between depressive symptoms and 8-OHdG. Further studies are needed to examine whether the association between perceived stress and 8-OHdG is modified by depressive symptoms.

Chronic defensiveness and neuroendocrine dysfunction reflect a novel cardiac troponin T cut point: The SABPA study.

BACKGROUND: Sympatho-adrenal responses are activated as an innate defense coping (DefS) mechanism during emotional stress. Whether these sympatho-adrenal responses drive cardiac troponin T (cTnT) increases are unknown. Therefore, associations between cTnT and sympatho-adrenal responses were assessed. METHODS: A prospective bi-ethnic cohort, excluding atrial fibrillation, myocardial infarction and stroke cases, was followed for 3 years (N=342; 45.6±9.0years). We obtained serum high-sensitive cTnT and exposure measures [Coping-Strategy-Indicator, depression/Patient-Health-Questionnarie-9, 24h BP, 24h heart-rate-variability (HRV) and 24h urinary catecholamines]. RESULTS: Blacks showed moderate depression (45% vs. 16%) and 24h hypertension (67% vs. 42%) prevalence compared to Whites. A receiver-operating-characteristics cTnT cut-point 4.2ng/L predicting hypertension in Blacks was used as binary outcome measure in relation to exposure measures [AUC 0.68 (95% CI 0.60-0.76); sensitivity/specificity 63/70%; P≤0.001]. Bi-ethnic cTnT-incidence was similar (Blacks=27%, Whites=25%) with cTnT-recovery better in Blacks (9%) compared to Whites (5%), P=0.001. In cross-sectional analyses, elevated cTnT was related to DefS [OR 1.08 (95% CI 0.99-1.16); P=0.06]; 24h BP [OR 1.03-1.04 (95% CI 1.01-1.08); P≤0.02] and depressed HRV [OR 2.19 (95% CI 1.09-4.41); P=0.03] in Blacks, but not in Whites. At 3year follow-up, elevated cTnT was related to attenuated urine norepinephrine:creatinine ratio in Blacks [OR 1.46 (95% CI 1.01-2.10); P=0.04]. In Whites, a cut point of 5.6ng/L cTnT predicting hypertension was not associated with exposure measures. CONCLUSION: Central neural control systems exemplified a brain-heart stress pathway. Desensitization of sympatho-adrenal responses occurred with initial neural- (HRV) followed by neuroendocrine dysfunction (norepinephrine:creatinine) in relation to elevated cTnT. Chronic defensiveness may thus drive the desensitization or physiological depression, reflecting ischemic heart disease risk at a novel 4.2ng/L cTnT cut-point in Blacks.

The water avoidance stress induces bladder pain due to a prolonged alpha1A adrenoceptor stimulation.

Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) remains an elusive disease with the cause for the pain unclear. BPS/IC patients present increased sympathetic activity and high levels of urinary noradrenaline. At the experimental level, it has been shown that chronic adrenergic stimulation produces pain and bladder changes through an alpha 1A adrenoceptor mediated mechanism. Water avoidance stress (WAS) in rodents reproduces signs of nociception and bladder changes seen in BPS/IC patients. In this study, we explore the possible role of alpha 1A adrenoceptor in bladder pain and morphological changes. WAS was induced in a group of female Wistar rats. A separate WAS group received 0.2 mg/kg day silodosin (WAS + S). Lower abdominal pain was determined by performing sensitivity to Von Frey filaments. Bladder reflex activity was determined by cystometry in anaesthetised animals. Urine was collected for noradrenaline quantification by HPLC. Bladders were harvested and stained with Haematoxylin-eosin (to analyse urothelial morphology and to determine the disruption of surface umbrella cells) or with Toluidine Blue 0.1% to analyse mast cell infiltration. WAS increased urinary noradrenaline level and bladder frequency and decreased mechanical pain threshold, which was reversed by silodosin. WAS induced lymphocytic and mast cells infiltration in the mucosa and mild urothelial disruption, which was absent in WAS + S group. Alpha 1A adrenoceptor stimulation has an important role in the appearance of bladder pain in rats. Since BPS/IC patients present high levels of noradrenaline, alpha 1A stimulation may be an additional trigger for bladder dysfunction presented by these patients. Further studies will determine the clinical relevance of this finding in the treatment of BPS/IC patients.

Stress-stones-stress-recurrent stones: a self-propagating cycle? Difficulties in solving this dichotomy.

Numerous studies have reported an association between stress and urolithiasis. Although urinary risk factors have been measured in several of these, compelling evidence of a causal relationship has not been established. A shortcoming is that alterations in single urinary parameters rather than ratios and quotients, which provide a more synergistic risk evaluation, have been measured. Recently, we speculated about a possible association between chronic stress and stone recurrence. This presents an intriguing dichotomy of whether stress causes stones or vice versa, or whether they are linked in a self-propagating stress-stones-stress-recurrence cycle. We investigated the latter hypothesis in a retrospective case-control designed study in which we calculated urinary ratios and quotients which are regarded as diagnostic indicators of stone risk. These included Ca/Cr, Ox/Cr, Mg/Cr, Cit/Cr, urate/Cr and citrate-magnesium-calcium ratios, activity product quotient for calcium oxalate (CaOx) and relative supersaturation of CaOx, brushite and uric acid. Overnight urinary data from 128 participants comprising 31 first time (FS), 33 recurrent (RS) CaOx stone formers and 64 controls were used. All subjects had been previously assessed for chronic stress dimensions, as well as for stress caused by their stone episodes per se. Conditional and unconditional logistic regression (with a Bonferroni correction for multiple tests) and simple linear regression were used to analyse various components of the data. Although RS had more stressful life events, with greater intensity of perception than FS, there were no significant differences between the groups regarding any of the urinary risk factors. No significant association between stressful life events and any of the urinary ratios or quotients was observed. A direct causal link between stress and stone recurrence was not indicated. We believe that future studies should shift their focus from traditional urinary risk factors to other stone-forming mechanisms. However, we recognize that there is an inherent problem in attempting to solve the stress-stones dichotomy as it would be impossible to disentangle alterations in risk factors which arise from lifestyle stress and those arising from stone episodes themselves.