Pain catastrophizing is an important variable in the context of acute and chronic pain. The neurophysiological correlates of pain catastrophizing, however, have not been rigorously evaluated. We examined the relationship between trait pain catastrophizing and morning salivary cortisol levels before and following a 45-minute laboratory pain testing session in healthy, pain-free (n=22) and temporomandibular disorder (TMD) participants (n=39). We also examined whether TMD patients evidenced generalized hyperalgesia and hypercortisolism. Pain catastrophizing was associated with a flattened morning salivary cortisol profile in the context of pain testing, irrespective of pain status. Cortisol profiles did not differ between healthy and TMD participants. TMD was associated with mechanical hyperalgesia only at the masseter. These data are the first to show an association between pain catastrophizing and elevated salivary cortisol profiles in the context of standardized experimental pain testing. These findings in both healthy individuals and those with chronic orofacial pain suggest that aberrant adrenocortical responses to pain may serve as a neurophysiologic pathway by which pain catastrophizing enhances vulnerability for development of chronic pain and maintains and/or exaggerates existing pain and associated morbidity.
Neurophysiological mechanisms by which pain catastrophizing is related to acute and chronic pain recently have come under empirical study. Understanding of these mechanisms has the unique potential to shed light on key central nervous system factors that mediate catastrophizing-pain relations and therapeutic benefits associated with changes in catastrophizing and related cognitive processes.
pain catastrophizing; pain threshold; temporomandibular disorders; HPA; pressure pain; thermal pain
Few studies in healthy subjects have examined the neuroimmune responses associated with specific experimental pain stimuli, while none has measured multiple biomarkers simultaneously. The aim of the present study was to compare the neuro-immune responses following two common experimental pain stimuli: cold pressor test (CPT) and focal heat pain (FHP). Eight adults participated in two counterbalanced experimental sessions of FHP or CPT with continuous pain ratings and blood sampling before and 30 minutes after the sessions. Despite similar pain intensity ratings (FHP = 42.2 ± 15.3; CPT = 44.5 ± 34.1; P = 0.871), CPT and FHP induced different neuro-immune biomarker responses. CPT was accompanied by significant increases in cortisol (P = 0.046) and anti-inflammatory cytokine IL-10 (P = 0.043) with significant decreases in several pro-inflammatory mediators (IL-1β (P = 0.028), IL-12 (P = 0.012), TNF-α (P = 0.039), and MCP-1 (P = 0.038)). There were nonsignificant biomarker changes during the FHP session. There were close to significant differences between the sessions for IL-1β (P = 0.081), IFN-γ (P = 0.072), and IL-12 (P = 0.053) with biomarkers decreasing after CPT and increasing after FHP. There were stronger associations between catastrophizing and most biomarkers after CPT compared to FHP. Our results suggest that CPT is a stressful and painful stimulus, while FHP is mostly a painful stimulus. Thus, each experimental pain stimulus can activate different neuro-immune cascades, which are likely relevant for the interpretation of studies in chronic pain conditions.
Cortisol is a hormone involved in mounting a stress response in humans. The evidence of stress reactivity among young children has been mixed, however. In the present study, the order of two laboratory tasks (i.e., Strange Situation and play) was counterbalanced, and home saliva samples were obtained. Saliva samples were also collected upon the children's arrival at the laboratory and at 40, 65, and 80 min after arrival. The authors examined changes in cortisol using piecewise hierarchical linear modeling, testing whether observed increases reflected a return to baseline or stress reactivity. An interaction between attachment disorganization and task emerged, such that disorganized infants showed increases in cortisol in response to the stressor compared with play, whereas organized infants did not show cortisol reactivity to either task. Implications for the buffering effects of maternal care on stress reactivity are discussed.
cortisol; stress response; HPA system; attachment
This study examined whether the interaction between the serotonin transporter promoter region (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms was associated with hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress. A community sample of 144 preschool-aged children was genotyped and exposed to stress-inducing laboratory tasks. Salivary cortisol was obtained at four time points during a standardized laboratory assessment before and after stressors involving separation from a parent and frustrating tasks. Children homozygous for the short-5-HTTLPR allele and carrying the Met-BDNF allele evidenced a significantly lower initial level of cortisol, followed by a positive increase in cortisol in response to the laboratory stressors. In contrast, children who were homozygous for the short-5-HTTLPR and the Val-BDNF alleles evidenced a greater decline in cortisol in response to the laboratory stressors. Findings indicated that the BDNF gene moderated the association between 5-HTTLPR and children’s biological stress responses, suggesting that epistatic effects play a role in individual differences in stress regulation, and possibly genetic vulnerability to stress-related disorders.
HPA axis reactivity; cortisol; serotonin transporter gene; BDNF; stress; multilevel modeling
This is a descriptive study reporting normative salivary cortisol values and responsivity to a hospital clinic visit and IV procedure in children. The study presented is a sub-project of a primary research study that examined parents coaching their children in the use of distraction for children requiring an IV placement. One measure of child response in the primary study, salivary cortisol, was included to further our understanding of children’s physiologic response to stressful, painful stimuli. Salivary cortisol samples were obtained on 384 children, 4–10 years of age, on arrival to the clinic and 20 minutes after the IV insertion. Baseline samples were collected at home on a typical day for the child. Data from baseline samples were used to establish normative values between the hours of 8:00 am and 3:00 pm on a non-procedural day. Results demonstrated normative cortisol levels in children follow a pattern similar to the circadian pattern in adults, decreasing from early morning to mid-afternoon. Matched samples from control group children were used to evaluate group responsivity. Salivary cortisol levels on the baseline day were lower than levels obtained during the day of the procedure and tapered over time as expected (−8.7% + 6.7%; p=0.43). Cortisol levels on the clinic day were increased from baseline and increased further in response to IV placement (15.7% +6.7%; p=0.023). A location by time interaction was significant (p= 0.019). Findings demonstrate salivary cortisol is a useful measure of stress response that can be used to evaluate intervention effectiveness.
salivary; cortisol; stress; children
Individuals differ widely in cortisol output over the day and cortisol reactivity to challenge, both of which are relevant to disease risk. There is limited evidence concerning the heritability of these differences, so we evaluated the heritability of cortisol levels in the afternoon and cortisol reactivity using a twin design. The study involved 80 monozygotic (MZ) and 70 dizygotic (DZ) same-sex twin pairs aged 11.2 years on average. Salivary cortisol was measured in the afternoon at home before and after playing a computer game. Ratings of excitement and upset were also obtained, and objective task performance was assessed. Salivary cortisol levels averaged 4.08 (S.D. 2.3) nmol/l at pretask baseline, and declined on average over the session to 3.45 (1.9) nmol/l immediately after the tasks and 2.87 (1.6) nmol/l 10 min later. There were, however, marked individual differences, with cortisol reactivity (difference between pretask baseline and post-task 1) ranging from +4.53 to −6.23 nmol/l. Intra-class correlations for all the cortisol parameters were substantially greater for MZ (range 0.41–0.57) than for DZ (0.11–0.29) twin pairs. Quantitative genetic modelling confirmed significant heritability for pretask baseline cortisol (58%), the two post-task values (60 and 56%), and cortisol reactivity (44%). The study lacked power for assessing sex differences. Subjective reports of excitement were also somewhat heritable, but there was little covariation of cortisol and subjective responses, so genetic influences on covariation could not be tested. These findings indicate that individual differences in children’s cortisol levels recorded before tasks and cortisol reactivity to behavioural challenges are influenced by genetic factors.
Cortisol; Genetics; Reactivity; Twins; Children
Catastrophizing exerts its deleterious effects on pain via multiple pathways, and some researchers have reported that high levels of catastrophizing are associated with enhanced physiological reactivity to painful stimulation. In this project, 42 generally healthy adults underwent a series of psychophysical pain testing procedures assessing responses to noxious mechanical, heat, and cold stimuli. Pain-catastrophizing cognitions were assessed prior to and then immediately after the various pain induction procedures. Blood samples were taken at baseline and then at several time points from the end of the procedures to 1 hour post-testing. Samples were assayed for serum levels of cortisol and interleukin-6 (IL-6). Both cortisol and IL-6 increased from baseline during the post-testing period (p’s< .05), with cortisol returning to baseline by 1 hour post-testing and IL-6 remaining elevated. Pain catastrophizing, measured immediately after the pain procedures, was unrelated to cortisol reactivity, but was strongly related to IL-6 reactivity (p< .01), with higher levels of catastrophizing predicting greater IL-6 reactivity. In multivariate analyses, the relationship between catastrophizing and IL-6 reactivity was independent of pain ratings. Collectively, these findings suggest that cognitive and emotional responses during the experience of pain can shape pro-inflammatory immune system responses to noxious stimulation. This pathway may represent one important mechanism by which catastrophizing and other psychosocial factors shape the experience of both acute and chronic pain in a variety of settings.
Experimental Pain; Pro-Inflammatory; Interleukin-6; Cortisol; Catastrophizing
Uncontrollable aversive events are associated with feelings of helplessness and cortisol elevation and are suitable as a model of depression. The high comorbidity of depression and pain symptoms and the importance of controllability in both conditions are clinically well-known but empirical studies are scarce. The study investigated the relationship of pain experience, helplessness, and cortisol secretion after controllable vs. uncontrollable electric skin stimulation in healthy male individuals.
Sixty-four male volunteers were randomly assigned to receive 30 controllable (self-administered) or uncontrollable (experimenter-administered) painful electric skin stimuli. Perceived pain intensity (PPI), subjective helplessness ratings, and salivary cortisol concentrations were assessed. PPI was assessed after stress exposure. For salivary cortisol concentrations and subjective helplessness ratings, areas under the response curve (AUC) were calculated.
After uncontrollable vs. controllable stress exposure significantly higher PPI ratings (P = 0.023), higher subjective helplessness AUC (P < 0.0005) and higher salivary cortisol AUC (P = 0.004, t-tests) were found. Correlation analyses revealed a significant correlation between subjective helplessness AUC and PPI (r = 0.500, P < 0.0005), subjective helplessness AUC and salivary cortisol AUC (r = 0.304, P = 0.015) and between PPI and salivary cortisol AUC (r = 0.298, P = 0.017).
The results confirm the impact of uncontrollability on stress responses in humans; the relationship of PPI with subjective helplessness and salivary cortisol suggests a cognitive-affective sensitization of pain perception, particularly under uncontrollable conditions.
This research examined whether variations in salivary measures of the hypothalamic-pituitary-adrenal axis (cortisol) and autonomic nervous system (alpha amylase [sAA]) contribute to individual differences in the association between peer victimization and aggression. Children (N = 132; M age = 9.46 years, SD = .33) completed a measure of peer victimization, teachers rated children’s aggression, and children’s saliva was collected prior to, and following, participation in a laboratory-based peer-oriented social challenge task. Children rated their level of frustration at the end of the task. Results revealed that victimization interacted with cortisol and sAA measured in anticipation of the task to predict aggression; the victimization × cortisol contribution to aggression was partly mediated by children’s self-reported frustration level. Victimization also was associated with heightened frustration in girls with high task-related sAA reactivity. Task-related sAA reactivity was associated with heightened aggression, but only for girls. These findings suggest that associations between peer victimization and aggression are moderated by variation in the activity of the major components of the psychobiology of stress; results are discussed in relation to theoretical models of individual differences in biological sensitivity to context.
peer victimization; aggression; cortisol; salivary alpha amylase
We examined daytime salivary cortisol and salivary alpha-amylase (sAA) secretion levels and variability in preschool-aged children with autism (AUT) and typically developing children (TYP). Fifty-two subjects (26 AUT and 26 TYP) were enrolled. Salivary samples were obtained at waking, midday, and bedtime on two consecutive days at three phases (baseline, 3 months later, 6 months later). There were modest increases in waking cortisol and sAA levels in AUT relative to TYP, but the increases were not statistically significant. Important differences were observed in cortisol and sAA variability between AUT and TYP. There was also a graded response among AUT by functional status—cortisol and sAA secretion levels were higher when IQ was lower.
Autism; Children; Salivary cortisol; Salivary alpha-amylase; Diurnal; Variability
Most studies on the stress-responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis have focused on glucocorticoids, while few studies have investigated the adrenal secretion of dehydroepiandrosterone-sulfate (DHEAS), which is unique to primates. Monkeys were chair-restrained for two hours per day for seven consecutive days, and blood samples were collected upon placement in the chair, and at 15, 30, 60 and 120 minutes later. Like cortisol, DHEAS concentrations increased throughout the initial session of chair restraint (acute stress). Unlike the cortisol response, which decreased after repeated exposure to the stressor, the DHEAS response was sustained throughout the seventh session of restraint (chronic stress) and response to the seventh session of restraint did not differ from the DHEAS response to the initial session. Like cortisol, DHEAS concentrations showed a diurnal rhythm with higher concentrations in the morning compared to the evening and a decrease in response to dexamethasone (DEX) administration. After repeated exposure to the stressor, the suppression of DHEAS in response to dexamethasone was more complete, suggesting an increase in negative feedback sensitivity. These data show that DHEAS concentrations increase in response to both acute and chronic (repeated) stress and provide another measure of HPA activity that parallels cortisol during acute responses to stress but diverges in chronic or repeated stress.
hypothalamic-pituitary-adrenal (HPA) axis; dehydroepiandrosterone sulfate; DHEAS; cortisol; stress; rhesus monkey; dexamethasone
Physically active individuals have lower rates of morbidity and mortality, and recent evidence indicates that physical activity may be particularly beneficial to those experiencing chronic stress. The tendency to ruminate increases and prolongs physiological stress responses, including hypothalamic-pituitary adrenal (HPA) axis responses as indexed by cortisol reactivity to stressful experiences. We examined the association between ruminating in response to a laboratory stressor task and HPA axis reactivity and recovery, and whether a physically active lifestyle moderates the associations between rumination and cortisol output trajectories.
Forty-six post-menopausal women underwent the Trier Social Stress Test while salivary cortisol was repeatedly measured. Twenty-five minutes after the end of the stressor, participants reported level of rumination in response to the stress.
Findings indicate that physical activity moderated the initial rate (B = −.10, SE = .04, p < .05) and curvature (B = −.03, SE = .01, p = .06) of the relationship between rumination and log-transformed cortisol trajectory. Among sedentary participants, those who responded to the stressor with higher levels of rumination had a more rapid initial increase in cortisol (0.26 vs 0.21, p < .001), a later peak (56 vs. 39 minutes), and a delayed recovery (curvature −0.07 vs. −0.08, p < .001) compared to those with lower levels of rumination. In active participants, cortisol trajectories were equivalent, regardless of level of rumination.
In sum, individuals who maintain a physically active lifestyle may be protected against the effects of rumination on HPA axis reactivity to and recovery from acute stress.
acute stress; rumination; physical activity; mixed modeling; cortisol reactivity
Determine the association between prenatal cocaine exposure and postnatal environmental adversity on salivary cortisol stress reactivity in school aged children.
Subjects included 743 11 year old children (n=320 cocaine exposed; 423 comparison) followed since birth in a longitudinal prospective multisite study. Saliva samples were collected to measure cortisol at baseline and after a standardized procedure to induce psychological stress. Children were divided into those who showed an increase in cortisol from baseline to post stress and those who showed a decrease or blunted cortisol response. Covariates measured included site, birthweight, maternal pre and postnatal use of alcohol, tobacco or marijuana, social class, changes in caretakers, maternal depression and psychological symptoms, domestic and community violence, child abuse and quality of the home.
With adjustment for confounding variables, cortisol reactivity to stress was more likely to be blunted in children with prenatal cocaine exposure. Cocaine exposed children exposed to domestic violence showed the strongest effects.
The combination of prenatal cocaine exposure and an adverse postnatal environment could down regulate the hypothalamic-pituitary-adrenal axis (HPA) resulting in the blunted cortisol response to stress possibly increasing risk for later psychopathology and adult disease.
prenatal cocaine exposure; cortisol reactivity; environmental adversity
Research linking post-traumatic stress disorder (PTSD) to hypercortisolism in laboratory experiments was extended to a natural clinical setting. Mothers of children diagnosed with a life-threatening illness (N = 92) completed standardized measures of PTSD and provided a salivary cortisol sample during their child’s medical check-up (Time 1) and again 24 h later, after the threat of possible negative medical reports was removed (Time 2). Women who met diagnostic criteria for PTSD exhibited significantly higher cortisol levels at Time 1 compared to women who did not meet criteria for a diagnosis. No significant differences were observed for cortisol levels at Time 2 between the women with and without PTSD. These findings extend current laboratory findings linking hypercortisolism and PTSD to a natural, stressful situation. Implications for understanding the etiology of PTSD as well as for possible prevention and intervention options are discussed.
Chronic illness; Cortisol; Hypothalamic–pituitary–adrenal axis; PTSD; Trauma; Women
The normal diurnal cortisol cycle has a peak in the morning, decreasing rapidly over the day, with low levels during the night, then rising rapidly again to the morning peak. A pattern of flatter daytime slopes has been associated with more rapid cancer progression in both animals and humans. We studied the relationship between the daytime slopes and other daytime cortisol responses to both pharmacological and psychosocial challenges of hypothalamic-pituitary-adrenal (HPA) axis function as well as DHEA in a sample of 99 women with metastatic breast cancer, in hopes of elucidating the dysregulatory process.
We found that the different components of HPA regulation: the daytime cortisol slope, the rise in cortisol from waking to 30 minutes later, and cortisol response to various challenges, including dexamethasone (DEX) suppression, corticotrophin releasing factor (CRF) activation, and the Trier Social Stress Task, were at best modestly associated. Escape from suppression stimulated by 1 mg of dexamethasone administered the night before was moderately but significantly associated with flatter daytime cortisol slopes (r=0..28 to .30 at different times of the post dexamethasone administration day, all p<.01) . Daytime cortisol slopes were also moderately but significant associated with the rise in cortisol from waking to 30 minutes after awakening (r=.29, p=.004, N=96), but not with waking cortisol level (r=−0.13, p=.19). However, we could not detect any association between daytime cortisol slope and activation of cortisol secretion by either CRF infusion or the Trier Social Stress Task. The CRF activation test (following 1.5 mg of dexamethasone to assure that the effect was due to exogenous CRF) produced ACTH levels that were correlated (r=0.66 p<.0001, N = 74) with serum cortisol levels, indicating adrenal responsiveness to ACTH stimulation. Daytime cortisol slopes were significantly correlated with the slope of DHEA (r=.21, p=.04, N=95). Our general findings suggest that flatter daytime cortisol slopes among metastatic breast cancer patients may be related to disrupted feedback inhibition rather than hypersensitivity in response to stimulation.
Cortisol; HPA; stress; dexamethasone; CRF; metastatic breast cancer
Accumulated evidence suggests that nicotine induces analgesia, and endogenous pain regulatory mechanisms may be altered by chronic smoking. The extent to which individual differences in pain perception are related to smokers' ability to abstain from smoking has not been directly examined. Seventy-one smokers who were interested in quitting completed a pre-cessation laboratory session which included the cold pressor test (CPT). Pain ratings were collected during and after CPT. Also, mood changes, cardiovascular measures, and salivary cortisol samples were evaluated prior to, during, and after CPT. Participants attended 4 weekly follow-up assessment sessions after their quit day. Cox regression analysis revealed that higher pain ratings during and after CPT predicted greater risk for smoking relapse. These results remained significant after affective and physiological responses to CPT were controlled, suggesting that pain ratings prior to smoking cessation is potentially useful in identifying smokers who are at greater risk of early smoking relapse and may reflect underlying putative risk for nicotine dependence and relapse.
pain; smoking; relapse; cortisol; cold pressor test
Previous studies have reported lower basal cortisol levels and reduced cortisol responses to stress in children and adolescents with conduct disorder (CD). It is not known whether these findings are specific to early-onset CD. This study investigated basal and stress-induced cortisol secretion in male participants with early-onset and adolescence-onset forms of CD.
Forty-two participants with early-onset CD, 28 with adolescence-onset CD, and 95 control subjects participated in the study. They collected saliva across the day to assess their cortisol awakening response and diurnal rhythm. Subsequently, salivary cortisol was measured before, during, and after a psychosocial stress procedure designed to elicit frustration. Cardiovascular activity and subjective mood states were also assessed during stress exposure.
There were no group differences in morning cortisol levels or the size of the cortisol awakening response. Basal cortisol levels in the evening and at 11 am during the laboratory visit were higher in both CD subgroups relative to control subjects. In contrast, cortisol and cardiovascular responses to psychosocial stress were reduced in both CD subgroups compared with control subjects. All groups reported similar increases in negative mood states during stress.
Our findings suggest that group differences in cortisol secretion are most pronounced during stress exposure, when participants with CD show cortisol hyporeactivity compared with control subjects. There was no evidence for reduced basal cortisol secretion in participants with CD, but rather increased secretion at specific time points. The results do not support developmentally sensitive differences in cortisol secretion between CD subtypes.
Antisocial behavior; conduct disorder; cortisol; cortisol awakening response; HPA axis; stress reactivity
Recent studies have found short-term adrenocortical benefits of early interventions for at-risk children. The current study evaluated the effects of the Family Bereavement Program on cortisol levels six years after the program. Parentally bereaved children were randomly assigned to the 12-week preventive intervention (n=78) or a self-study control (n=61) condition. Six years later (mean age 17.5), salivary cortisol levels were measured before and after a conflict discussion task conducted in late afternoon/early evening. The intervention group had significantly higher cortisol levels across the task compared to the control group, and lower cortisol was associated with higher externalizing symptoms. The group effect did not differ by age at the time of death, and the group difference remained significant after adjustment for pre-intervention mental health and current mental health symptoms. Results suggest that a family-focused intervention for parentally-bereaved youth may have prevented the development of attenuated cortisol secretion suggestive of dysregulation and associated with externalizing problems.
parental loss; cortisol; intervention; bereavement; externalizing
Expressed Emotions (EE) are associated with oppositional behavior (OPB) in children with Attention Deficit/Hyperactivity Disorder (ADHD). EE has been linked to altered stress responses in some disorders, but ADHD has not been studied. We test the hypothesis that OPB in ADHD is mediated by altered stress-related cortisol reactivity to EE.
Two groups of children (with/without ADHD) and their respective parents were randomly assigned to two different conditions with/without negative emotion and participated in an emotion provocation task. Parents' EE, their ratings of their children's OPB and their children's salivary cortisol levels were measured.
Low parental warmth was associated with OPB in ADHD. High levels of parental EE elicited a larger cortisol response. Stress-related cortisol reactivity mediated the EE-OPB link for all children. This highlights the general importance of parent-child interactions on externalizing behavior problems.
High EE is a salient stressor for ADHD children that leads to increased levels of cortisol and OPB. The development of OPB might be mediated by the stress-response to high EE.
Levels of the stress-sensitive hormone cortisol increase dramatically in the first 30-40 minutes after waking, an effect known as the cortisol awakening response (CAR). There is considerable cross-sectional evidence that psychosocial stress is associated with an increased CAR, and the CAR has been found to be altered in the presence of stress-related diseases, including Major Depressive Disorder (MDD). To date, no prospective longitudinal studies have examined whether individual differences in the CAR serve as a premorbid risk factor for MDD. In a sample of 230 late adolescents, clinical diagnoses of MDD were predicted from the CAR as well as other indicators of basal cortisol functioning gathered one year earlier, including: waking cortisol levels, bedtime cortisol levels, the size of the CAR, average cortisol, and the slope of the diurnal cortisol rhythm across the waking day. Age and gender, health and health behaviors, baseline neuroticism, exposure to stressful life events and past episodes of mood and anxiety disorders were included as covariates, to help ensure effects are attributable to the CAR rather than related variables. A higher baseline CAR was associated with a significantly increased risk of developing MDD by follow-up, even when excluding individuals with baseline MDD. No other baseline cortisol measures were significant prospective predictors of MDD. In summary, the CAR is a significant prospective risk factor for the development of MDD in young adults, providing some support for the possibility that a heightened CAR may play a role in the etiology of Major Depressive Disorder.
Hypothalamic pituitary adrenal axis; cortisol awakening response; major depressive disorder; life events; prospective; diurnal cortisol rhythms
The present study was carried out to determine day-to-day differences in cortisol levels and the molar cortisol-to-dehydroepiandrosterone (DHEA) ratio (molar C/D ratio) in working subjects.
Materials and Methods
The cortisol and DHEA levels were measured from saliva samples collected 30 minutes after awakening for 7 consecutive days in full-time working subjects that worked Monday through Saturday. To determine the day-to-day differences within subjects, the collected data was analyzed using variance (ANOVA) for a randomized complete block design (RCBD).
The cortisol levels from samples collected 30 minutes after awakening on workdays were similar to each other, but were significantly different from the cortisol levels on Sunday. The DHEA levels were not significantly different between the days of week. The DHEA levels on Monday and Tuesday were relatively lower than the levels on the other weekdays. The DHEA levels on Thursday and Friday were relatively higher than the other days. The molar C/D ratios on Sunday were significantly lower than those on workdays. The molar C/D ratios on Monday and Tuesday were significantly higher than those on Wednesday or other workdays.
The cortisol levels and the molar C/D ratios demonstrate differences in adrenocortical activities between workdays and non-workdays, but the molar C/D ratio additionally represents differences in adrenocortical status between the first two workdays and other workdays. Thus, it is possible that the day-to-day differences in the cortisol levels and the molar C/D ratio represent the adrenal response to upcoming work-related stress.
Salivary cortisol; salivary DHEA; weekly cortisol rhythm; weekly molar cortisol-to-DHEA ratio rhythm; working individuals
To determine if cynical hostility is associated with alterations in diurnal profiles of cortisol. Hostility has been linked to cardiovascular disease but the biological mechanisms mediating this association remain unknown.
Up to 18 measures of salivary cortisol taken over three days were obtained from each of 936 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Cynical hostility was measured using an 8-item subscale of the Cook-Medley Hostility scale. Cortisol profiles were modeled using regression spline models incorporating random parameters for subject-specific effects. Models were adjusted for race, sex, age, socioeconomic position, and lifestyle factors. The association of cynical hostility with key features of the cortisol diurnal profile, both in the full sample and important subsamples, was examined.
Waking cortisol levels as well as the extent of the morning surge in cortisol levels did not differ significantly across tertiles of cynical hostility. However respondents in the lowest tertile of cynical hostility experienced a 22% sharper decline in salivary cortisol (age-and sex-adjusted slope of −.49 μg/dl per hour) than respondents in the highest tertile (−.40 μg/dl per hour, p for difference=.0004). Intertertile differences in these parameters remained unaltered after further adjustment for potential confounders. This pattern of differences in cortisol diurnal profile tended to be related in a dose-response way to level of cynical hostility, and persisted in stratified analyses.
Cynical hostility is associated with the declining phase of the awakening cortisol response. The implications of this for cardiovascular and other health outcomes remain to be determined.
Cortisol rhythms; cynical hostility; regression splines; random effects; cortisol awakening response
Cortisol is an indicator of hypothalamic–pituitary–adrenal axis responsivity to stress, but few twin studies have examined the heritability of cortisol concentrations in adults across the diurnal cycle and in different contexts. Saliva samples were provided by 783 middle-aged male twins on one laboratory and two home days as part of the Vietnam Era Twin Study of Aging. Significant cortisol heritability estimates were found for laboratory measures only: awakening (.56); 30 min after awakening (.48); 1000 h (.42); mean output across the day (.43); and mean cortisol awakening response (.64). Twin correlations at home were low. In the laboratory, they were unchanged for fraternal twins, but increased for identical twins. Greater measurement error at home did not appear to account for home-laboratory differences. The results suggest that genetic factors influence cortisol responses to specific environmental stressors. Thus, cortisol levels are correlated in identical twins only when they undergo similar experiences.
Salivary cortisol; Heritability; Genetics; Twins; HPA axis
Anxiety vulnerability is associated with biases in attention: a tendency to selectively process negative relative to neutral or positive information. It is not clear whether this bias is: 1) related to the physiological response to stressful events, and 2) causally related to the development of anxiety disorders.
We tested the predictive value of both preconscious and conscious attention biases in a prospective study of stress reactivity in a nonclinical sample. One hundred four male participants were assessed at baseline and then again 4 months (n = 82) and 8 months later (n = 70). Salivary cortisol and self-report measures were obtained at the baseline testing session in addition to measures of biased attention. Subsequent emotional reactivity was assessed by means of salivary cortisol and self-reported state-anxiety responses during a laboratory-based stressor (4 months later) as well as during a real-life stressor 8 months later (i.e., examination period).
Regression analyses indicated that a preconscious negative processing bias was the best predictor of the cortisol response to stressful events. Importantly, a measure of selective processing provided a better indicator of subsequent emotional reactivity than self-report measures of neuroticism, trait-anxiety, and extraversion.
These results suggest that preconscious biases toward negative material play a causal role in heightened anxiety vulnerability. Our results illustrate the potential utility of preconscious biases in attention in providing an early marker of anxiety vulnerability and a potential target for treatment intervention.
Anxiety; attention; cortisol response; emotion; processing bias; stress
We examined associations between cognitive function (CF) and the naturally occurring daily cortisol levels using data from the Midlife in the United States survey and the National Study of Daily Experiences.
A national sample of 1,500 (mean age = 57 years; range = 33–84, 56% female) completed a phone-based battery of cognitive tasks and 3–6 months later provided saliva samples upon waking, 30 min after waking, at lunch time, and at bedtime on 4 consecutive days.
Higher CF, particularly executive function, was associated with healthier daily cortisol profiles, including a steeper diurnal cortisol slope, higher morning cortisol levels, and lower afternoon and evening cortisol levels.
The results indicate that better CF is associated with healthier profiles of naturally occurring cortisol and underscore the importance of the timing of cortisol sampling.
Cognitive function; Diurnal cortisol rhythm; Salivary cortisol