Changes in salivary cortisol levels as a prognostic predictor in children with anorexia nervosa

This study investigated the hypothalamus-pituitary-adrenal (HPA) axis activity in children with anorexia nervosa (AN) before and after inpatient treatment. Salivary cortisol levels were measured to ascertain whether changes in the HPA axis activity following therapeutic intervention could be applicable as a prognostic predictor. This study comprised 21 females with AN and 22 control subjects. Saliva was collected at 2-hour intervals from 9 a.m. to 7 p.m. before and after inpatient treatment. The concentrations for areas under the curve (AUC) were compared with physical parameters, eating attitude score, profile of mood states (POMS), and prognostic factors. Mean salivary cortisol levels at all points and mean AUC cortisol levels in subjects with AN before therapy were significantly higher than those in controls, but returned to control levels after inpatient treatment. Higher AUC cortisol levels were associated with lower standard deviation for weight in AN. A significant positive correlation between the AUC cortisol level and POMS subscale of “Fatigue” was apparent in the control group, but not in the AN group. The increased change values of AUC cortisol level before and after inpatient treatment correlated with increased body weight gain ratio just after treatment, but not with the ratio after one year. The present study indicated that HPA axis activity could reflect severity of illness, but did not show an accurate neuroendocrine response for mood states. Changes in HPA axis activity following treatment could therefore be used to predict prognosis and particularly in the short term.     

Individual differences in cortisol levels and performance on a test of executive function in men and women

Despite evidence for a high concentration of corticosteroid receptors in prefrontal cortex, little research has examined the relationship between cortisol and prefrontal cortical function other than working memory. We investigated the association between salivary cortisol levels and performance on the Wisconsin Card Sorting Test (WCST) of executive function and on a test of mental rotation (to test specificity of the relationship between cortisol and cognitive performance) in men and women (n=116, ages 17-22). Higher cortisol levels at the beginning of the test session were associated with more errors in women on the WCST and fewer errors in men. However, men's cortisol levels were lower than women's at this point in time. Cortisol levels were not associated with mental rotation scores. Our results suggest that individual differences in cortisol levels among participants upon arrival to a test situation influence performance on a task involving the prefrontal cortex.     

Investigating the role of perceived stress on bacterial flora activity and salivary cortisol secretion: a possible mechanism underlying susceptibility to illness

This study examined the impact of academic stress on salivary cortisol concentrations and lactic acid bacteria activity. Whole, unstimulated saliva samples and faecal samples were collected from 23 healthy undergraduate students (23.0+/-6.8 years; range 18-44) over two 1-week periods: during the beginning of semester (low-stress baseline condition) and during the first week of exams (high-stress condition). Students also completed a series of questionnaires measuring perceived levels of stress, gastrointestinal symptoms, and nutritional intake. Significant findings indicated that faecal lactic acid bacterial levels were lower during the high-stress condition. Paralleling this, students rated perceived levels of stress as being greater during the exam period compared to the baseline condition. The findings from this study have provided further insight into the link between stress and gastrointestinal flora activity in humans.     

The salivary alpha amylase over cortisol ratio as a marker to assess dysregulations of the stress systems

Different factors have been associated with changes in the regulation of the two major stress response systems of the human body, the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. Changes in these systems have been associated with various (psycho)pathologies across adulthood, and are thus frequently assessed within the context of allostatic load. Early Life Adversity (ELA) has been identified as one such factor. Individuals with histories of ELA show evidence of elevated basal and reactive salivary alpha amylase (sAA) levels (a marker of SNS activity), blunted cortisol levels (a marker of HPA axis activity), and an asymmetrical relationship between the two variables. However, variable methods used in the past to measure each variable, and the relationship between the two systems, prevent us from drawing firm conclusions. This preliminary study investigated whether the ratio of reactive sAA over reactive cortisol would be more informative to investigate the relationship between the two stress systems than the ratio of cortisol over sAA, or either marker alone, and whether there is a systematic link between this marker and subjective indexes of chronic stress and depression. We studied this in a total of 37 subjects (n=20 with signs of early life adversity and n=17 without) exposed to the Trier social stress test. Using a specific formula to determine the ratio of sAA over cortisol, we found a systematically stronger positive relationship with indexes of chronic stress and depression when compared to cortisol over sAA, or either marker alone. Our findings suggest that the ratio of sAA over cortisol might be a better marker of stress systems dysregulation than the ratio of cortisol over sAA, sAA or cortisol alone. The usefulness of this marker for other chronic stress states as found in allostatic load is discussed.     

Increased salivary levels of 8-hydroxydeoxyguanosine may be a marker for disease activity for periodontitis

Background: 8-hydroxydeoxyguanosine (8-OHdG) is commonly used as a marker to evaluate oxidative DNA damage in disorders including chronic inflammatory diseases such as inflammatory periodontal pathologies. In the current study we hypothesized that the level of 8-OHdG in saliva increases by the periodontal destruction severity determined by clinical parameters as clinical attachment level (CAL). Materials and methods: A cross-sectional study was conducted on a sum of 60 age gender balanced; chronic periodontitis (CP) (n = 20), chronic gingivitis (CG) (n = 20) and healthy (H) (n = 20) individuals. Clinical periodontal parameters and salivary 8-OHdG levels were evaluated. Results: The mean 8-OHdG level in the saliva of the CP group was significantly higher than H and CG groups (p < 0.001). Statistically significant correlation was only observed between the salivary levels of 8-OHdG and age (p < 0.05), probing depth (PD) and CAL (p < 0.001) in CP group. However, when CP patients were classified according to their CAL levels (CAL≥ 3 mm (n = 11) and CAL<3 mm (n = 9)) statistically significant correlation was only observed between the salivary levels of 8-OHdG and CAL≥ 3 mm patients (p < 0.001). Conclusion: We suggest that elevated salivary levels of 8-OHdG may be a marker for disease activity and it may reflect indirectly disease severity parameters such as CAL.     

抑郁症患者前扣带回代谢特征与下丘脑-垂体-肾上腺轴活性水平的氢质子波谱研究

目的:用磁共振氢质子波谱的方法探讨抑郁症患者前扣带回(ACC)代谢特征与下丘脑-垂体-肾上腺轴(HPA轴)功能活性的关系.方法:选取68例符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断标准的抑郁症患者及30例正常对照,采用磁共振扫描检测前扣带回氢质子波谱N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)、谷氨酸复合物(Glx)及肌醇(mI)等5种代谢物的含量,计算NAA/Cr、Glx/Cr、Cho/Cr、mI/Cr比值.用皮质醇醒觉反应(CAR)检测HPA轴活性,定义为连续2天醒后30 min觉醒时皮质醇浓度差值的均值.根据抑郁症组HPA轴活性均值将抑郁症组分为HPA轴高活性组35例(＞6.6 nmol/L)及HPA轴低活性组33例(≤6.6nmol/L).结果:与正常对照相比,抑郁症患者两侧ACC的NAA/Cr[左侧(1.6±0.5)vs.(2.0±0.5),右侧(1.7±0.4)vs.(2.2±0.5)]和Glx/Cr[左侧(0.1±0.03) vs.(0.1 ±0.03),右侧(0.1±0.01) vs.(0.2±0.04)]较低(均P＜0.05),右侧Cho/Cr较高[(1.5±0.9)vs.(0.9±0.3),P＜0.01];与低HPA轴活性组相比,高HPA轴活性组左侧NAA/Cr较低[(1.6±0.4)vs.(1.7±0.4),P＜0.05],右侧Cho/Cr较高[(1.7±0.2)vs.(1.2±0.1),P＜0.01].结论:抑郁症患者可能存在双侧前扣带回N-乙酰天门冬氨酸、谷氨酸及胆碱等代谢紊乱,高HPA轴活性可能与部分代谢物质存在相关.     

Hair cortisol as a measure of the stress response to social adversity in young children

Hair cortisol has the potential to provide insight into young children's long-term stress response to social adversity. This study investigated associations between children's exposure to adversity from pregnancy to 2 years of age and their hair cortisol at 2 years, using a longitudinal cohort of children enriched for adversity risk, whose mothers were recruited during pregnancy through the “right@home” trial. Exposures were 18 maternal socioeconomic and psychosocial indicators of adversity, examined as concurrent, cumulative, and longitudinal exposure from pregnancy to 2 years. Hair samples were analyzed from 319/603 (53%) children participating at 2 years. Multivariable regression analyses for concurrent exposure showed three indicators of adversity were associated with higher hair cortisol (housing tenure of public rental, paying board or living rent free; not living in a safe place; higher maternal stress symptoms), one with lower hair cortisol (housing problems), and 14 indicators with no evidence of association. There was no evidence of association for the cumulative adversity count. Longitudinal exposure showed “intermittent” and “persistent” high maternal stress symptoms were associated with higher hair cortisol. The small number of associations identified suggests that hair cortisol is limited as a measure of stress response to social adversity in children at 2 years.     

Diurnal saliva cortisol levels and relations to psychosocial factors in a population sample of middle-aged swedish men and women

Whereas psychosocial risk factors increase the risk for disease, psychosocial resources reduce this risk. To examine a possible pathway for these effects, the relations between saliva cortisol levels and psychosocial factors were studied in a random sample of 257 men and women aged 30 to 64 years. Saliva samples were collected at home on waking, 30 min after waking, and in the evening. A flatter diurnal rhythm of cortisol, that is, lower deviations between awakening and evening cortisol levels, was related to high levels of psychosocial risk factors (cynicism, depression, and vital exhaustion), whereas a steeper diurnal rhythm was related to psychosocial resources (social support and coping), general health, and well-being (all p < .05). Our results support earlier suggestions that the capacity of the hypothalamic-pituitary-adrenal-axis to dynamically respond to stress is 1 pathway for observed effects of psychosocial factors regarding risk for disease development.     

Dehydroepiandrosterone in nails of infants: a potential biomarker of intrauterine responses to maternal stress

Easily accessible biomarkers for fetal stress biology are lacking. We here explore whether quantification of major fetal steroids, dehydroepiandrosterone (DHEA) or DHEA sulfate (DHEAS), with liquid chromatography/tandem mass spectrometry in infant nails is a tool to assess fetal stress biology in response to maternal stressful life events during pregnancy. Sufficient nail (≥1 mg) was available from 80 infants (93% of those providing samples). The concentration of DHEA, but not DHEAS, was increased in infants of mothers with stressful life events during pregnancy (DHEA: F_1,41 = 6.105, P = 0.018; DHEAS: F_1,77 = 0.767, P = 0.384). DHEA concentrations were not related to maternal stress before pregnancy (F_1,41 = 0.010, P = 0.922). Infant nail DHEA may be a fetal biological correlate of intrauterine exposure to maternal stress. The method promises the first non-invasive retrospective biomarker for intrauterine stress biology, opening new ways for research and clinical applications in fetal medicine, endocrinology, obstetrics, gynecology, and for understanding the developmental origins of health and disease.     

Salivary alpha-amylase,cortisol and chromogranin A responses to a lecture: impact of sex

The aim of this study was to (1) examine the presence of stress on professors when they teach in front of 200 students and analyse objectively such stress using biomarkers such as salivary cortisol, chromogranin A (CgA) and alpha-amylase (AA) (2) investigate whether sex affects the reactivity of salivary alpha-amylase (sAA) and cortisol concentrations and the interaction of both hormonal systems. Fifty-two participants (26 women and 26 men) collected nine unstimulated saliva samples on 2 days, (one working day, and one resting day). Cortisol concentrations and AA activity measured on the teaching day were significantly higher than those noted on the resting values. No differences between the resting day and the teaching day were reported for CgA. Our results showed a cortisol response to teaching, which was characterized by an anticipatory rise. The AA level was significantly increased after the end of the lecture, and returned to the pre-lecture level 30 min after the end of the lecture. The awakening cortisol response noted on the teaching day was significantly higher in females than in males. No baseline sex differences in sAA and CgA were observed and men and women seem to have a comparable reactivity in sAA, CgA and cortisol levels on lecture stress. The mechanisms that leads to modify activity of salivary AA and CgA due to stress is not entirely understood and further research is needed to elucidate them.     

Mucin expression in pleomorphic adenoma of salivary gland: a potential role for MUC1 as a marker to predict recurrence

BACKGROUND: Pleomorphic adenoma of the salivary gland (PA) is essentially a benign neoplasm. However, patients with recurrent PA are difficult to manage. There are rare reports on useful immunohistochemical markers to detect a high risk of recurrence when the primary lesions are resected. AIMS: To find a new marker to predict the recurrence of PA. METHODS: Primary lesions of PA were collected from nine patients showing subsequent recurrence and from 40 patients without recurrence during at least 10 years of follow up of the disease. Paraffin wax embedded tumour samples of the two groups were examined for the expression profiles of MUC1 (differentially glycosylated forms), MUC2, MUC4, MUC5AC, and MUC6 using immunohistochemistry. Several clinicopathological factors were also examined. RESULTS: In univariate analysis of the factors examined, MUC1/DF3 high expression (more than 30% of the neoplastic cells stained) in the primary lesions was seen more frequently in patients with recurrence (four of nine) than in those without recurrence (three of 40; p = 0.011). Larger tumour size (more than 3.0 cm) of the primary PA was also a significant (p = 0.035) risk factor for the recurrence of PA. In multivariate analysis, only high expression of MUC1/DF3 was found to be a significant independent risk factor for the recurrence of PA (p = 0.021). CONCLUSIONS: Expression of MUC1/DF3 in PA is a useful marker to predict its recurrence. Those patients with PA showing positive MUC1/DF3 expression should be followed up carefully.     

Neural activity and diurnal variation of cortisol: evidence from brain electrical tomography analysis and relevance to anhedonia

The medial prefrontal cortex (mPFC), hippocampus, and amygdala are implicated in the regulation of affect and physiological processes, including hypothalamic-pituitary-adrenal (HPA) axis function. Anhedonia is likely associated with dysregulation of these processes. Dense-array resting electroencephalographic and cortisol were obtained from healthy and anhedonic groups. Low-resolution electromagnetic tomography was used to compute intracerebral current density. For the control group, voxelwise analyses found a relationship between current density in beta and gamma bands and steeper cortisol slope (indicative of more adaptive HPA axis functioning) in regions of the hippocampus, parahippocampal gyrus, and mPFC. For the anhedonic group, the mPFC finding was absent. Anhedonia may be characterized by disruptions of mPFC-mediated neuroendocrine regulation, which could constitute a vulnerability to the development of stress-related disorders.     

Decrease in the response to ADH of the rat kidney as a result of early postnatal treatment with cortisol

Wistar rats were injected just once, intraperitoneally with cortisol (1 g/g) or saline at the age of 5 days. The cortisol-treated rats did not differ significantly in the (U/P)osm ratio from the saline-treated controls before 15 days of life. Their response to ADH was distinct but weaker than in the saline controls aged 30 days. This reduced response persisted to 60 days of life. In the collecting tubule fragments, (³H)AVP specific binding was lower in the cortisol-treated rats than in the controls at the age of 20 and 60 days. There was no (³H)AVP specific binding in the proximal convoluted tubules in the cortisol-and saline-injected rats of both ages. The ontogenetic patterns of cAMP specific binding in the papillary cytosolic fraction were different: the early increase in cAMP binding was protracted in the cortisol-treated rats, and no peak appeared at the age of 25 days. Cytosolic protein kinase activity was lower, no peak appeared at 30 days, no activation of protein kinase occurred to the end of weaning in the cortisol-treated rats. The difference between the cortisol and saline groups was abolished by day 30. The interference of cortisol with the ontogenetic changes in AVP binding capacity and cAMP-dependent protein kinase appears to be a plausible cause of the altered development of the response to ADH.     

Individual differences in the cortisol response to stress in young healthy men: testing the roles of perceived stress reactivity and threat appraisal using multiphase latent growth curve modeling

Individual differences in stress reactivity and cognitive appraisal processes are thought to explain part of the heterogeneity in stress responses. This study investigated how perceived typical stress reactivity and momentary cognitive appraisal affect salivary cortisol responses to a laboratory performance stressor with social evaluation in 66 male non-smokers. Multiphase latent growth curve models showed positive associations of perceived stress reactivity and primary appraisal with cortisol responses. An age-adjusted path analysis suggested that primary appraisal mediated the effect of perceived reactivity to social evaluation on cortisol responses, and that effects of primary appraisal were attenuated at high levels of perceived reactivity. Our results suggest that individuals who report that they typically show strong perceived emotional, cognitive and autonomic responses to social evaluative stress tend to perceive the prospect of having to perform in front of an audience as more threatening, and that this appraisal then leads to stronger cortisol responses.     

Stable serum levels of relaxin throughout the menstrual cycle: a preliminary comparison of women with premenstrual dysphoria and controls

Summary Serum levels of relaxin in 25 women with premenstrual dysphoria and 25 age-matched controls were determined at three time points during the menstrual cycle. At the same time, levels of estradiol, progesterone, 17-β-OH-progesterone, free testosterone, total testosterone, sex hormone binding hormone, androstenedione, dehydroepiandrosterone sulphate, and 3-α-androstanediol glucuronide were determined. Detectable levels of relaxin were found in all women in both the follicular and luteal phase as well as around ovulation, the inter-individual variations being larger than intra-individual differences. The levels of relaxin were not influenced by the fluctuation of the other reproductive hormones. A significant difference between the two groups of women was observed, subjects with premenstrual dysphoria displaying reduced levels of relaxin (p < 0.05) compared to controls. Also, when analysed with respect to a variable number of tandem repeats polymorphism (CT repeats followed by GT repeats) in the promotor region of the relaxin H2 gene, women with premenstrual dysphoria (n = 29) were found to display significantly longer GT repeats than controls (n = 35).     

Physical activity levels of barbadian youth and comparison to a U.S. sample

This isthe first study toreport on physical activity levels of young people in Barbados. The Self-Administered Physical Activity Checklist was administered to 1,579 children aged 8 to 18 years. The majority of youth (69%) reported at least 60 min of physical activity on the previous school day. Boys and younger students reported greater physical activity than girls and older students (p < .001). Participation in physical education was low among primary (30%) and secondary (18%) school students, and youth reported the majority of their physical activity took place after school (58%). Physical activity levels and patterns were similar to those of U.S. youth. Gender and grade differences in physical activity could put girls and older youth at higher risk for health problems such as obesity. Policy recommendations to support youth physical activity in Barbados include mandatory daily physical education and after-school physical activity programs.     

Luciferase activity as a marker of tumor burden and as an indicator of tumor response to antineoplastic therapyin vivo

The gene encoding firefly luciferase has been used as a reporter gene for the study of gene function. The luciferase catalyzes its substrate and subsequently produces luminescence. In addition, it is not present in mammalian cells. We have therefore explored its use in monitoring the growth of tumorsin vivo. The luciferase gene was transfected into two murine tumor lines, i.e. cl62 melanoma and M109 lung carcinoma, and the luciferase activity associated with the cells was determined by a rapid chemiluminescent reaction. Luciferase activity was well-correlated with the number of tumor cellsin vitro. Luciferase activity also correlated with the tumor burdenin vivo, as well as with the effect of an adoptive T cell transfer therapy in the syngeneic C3H/HeN mice experimental tumor model. This assay offers the advantage of being quantitative, rapid, and reliable for the detection of tumor burden and for the evaluation of the effect of antineoplastic therapy.     

Maternal hair cortisol levels as a novel predictor of neonatal abstinence syndrome severity: A pilot feasibility study

Neonatal abstinence syndrome (NAS) after in-utero opioid exposure remains a poorly understood condition with multiple factors contributing to severity. Exposure to maternal stress may be one contributing factor. Hair cortisol measurement represents a novel technique for assessing prenatal stress. In this pilot study, the association between maternal hair cortisol levels and NAS severity was examined in 70 postpartum women with opioid use disorder within 72 hr of delivery. Infants were monitored for NAS and treated according to institutional protocol. Forty-four (63%) of the infants were pharmacologically treated for NAS, with a mean length of hospital stay (LOS) for all infants of 14.2 (SD 9.0) days. The mean cortisol level in the mothers was 131.8 pg/mg (SD 124.7). In bivariate analysis, higher maternal hair cortisol levels were associated with shorter infant LOS (R = −.26, p = .03) and fewer infant opioid treatment days (R = −.28, p = .02). Results were no longer statistically significant in regression models after adjusting for maternal opioid and smoking. In conclusion, we demonstrated the feasibility of hair cortisol assaying within the first few days after delivery in mothers with opioid use disorder as a novel marker for NAS. The findings suggest that maternal stress may impact the severity of infant opioid withdrawal.