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
The cortisol awakening response (CAR) is related with psychosocial factors and health in potentially significant ways, suggesting that it may be a distinctive marker of hypothalamic-pituitary-adrenal (HPA) axis function and dysfunction. This sought to expand upon previous work that examined the association between CAR and ratings of laboratory-evoked acute pain stimulation. In addition to evoked pain ratings, this study also tested whether CAR was prospectively related with salivary cortisol and soluble tumor necrosis factor-α receptor II (sTNFαRII) responses to acute pain stimulation.
This study included 36 healthy, pain-free volunteers of both sexes recruited via posted study flyers. Prior to completion of laboratory pain testing, salivary cortisol samples were obtained at home over the course of a single morning according to the following time frame: upon awakening, and 15, 30, and 60 min after awakening. Following collection of saliva, study participants brought their home saliva samples to the laboratory for assay and subsequently completed acute experimental pain testing procedures.
Cluster analysis of CAR revealed two distinct groups with similar patterns of cortisol response to awakening; increased and flattened. Relative to flattened CAR, increased CAR was associated with greater ratings of pain intensity and unpleasantness. Salivary cortisol was significantly increased and sTNFαRII significantly decreased following pain testing, but neither of these responses differed as a function of increased versus flattened CAR.
CAR may be a marker for stress sensitivity and/or the anticipation of impending stress, which could explain why the increased CAR cohort reported greater acute pain ratings.
Cortisol awakening response; acute pain; inflammation; HPA axis; stress
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
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 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
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
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
Neonatal pain-related stress is associated with elevated salivary cortisol levels to age 18 months in children born very preterm, compared to full-term, suggesting early programming effects. Importantly, interactions between immune/inflammatory and neuroendocrine systems may underlie programming effects. We examined whether cortisol changes persist to school age, and if common genetic variants in the promoter region of the NFKBIA gene involved in regulation of immune and inflammatory responses, modify the association between early experience and later life stress as indexed by hair cortisol levels, which provide an integrated index of endogenous HPA axis activity. Cortisol was assayed in hair samples from 128 children (83 born preterm ≤32 weeks gestation and 45 born full-term) without major sensory, motor or cognitive impairments at age 7 years. We found that hair cortisol levels were lower in preterm compared to term-born children. Downregulation of the HPA axis in preterm children without major impairment, seen years after neonatal stress terminated, suggests persistent alteration of stress system programming. Importantly, the etiology was gender-specific such that in preterm boys but not girls, specifically those with the minor allele for NFKBIA rs2233409, lower hair cortisol was associated with greater neonatal pain (number of skin-breaking procedures from birth to term), independent of medical confounders. Moreover, the minor allele (CT or TT) of NFKBIA rs2233409 was associated with higher secretion of inflammatory cytokines, supporting the hypothesis that neonatal pain-related stress may act as a proinflammatory stimulus that induces long-term immune cell activation. These findings are the first evidence that a long-term association between early pain-related stress and cortisol may be mediated by a genetic variants that regulate the activity of NF-κB, suggesting possible involvement of stress/inflammatory mechanisms in HPA programming in boys born very preterm.
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.
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
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
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
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
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
Most studies on cortisol have focused on smaller, selected samples. We therefore aimed to sex-specifically study the diurnal cortisol pattern and explore its association with abdominal obesity in a large unselected population.
In 2001–2004, 1811 men and women (30–75 years) were randomly selected from the Vara population, south-western Sweden (81% participation rate). Of these, 1671 subjects with full information on basal morning and evening salivary cortisol and anthropometric measurements were included in this cross-sectional study. Differences between groups were examined by general linear model and by logistic and linear regression analyses.
Morning and Δ-cortisol (morning – evening cortisol) were significantly higher in women than men. In both genders older age was significantly associated with higher levels of all cortisol measures, however, most consistently with evening cortisol. In women only, age-adjusted means of WHR were significantly lower in the highest compared to the lowest quartile of morning cortisol (p = 0.036) and Δ-cortisol (p < 0.001), respectively. Furthermore, when comparing WHR above and below the mean, the age-adjusted OR in women for the lowest quartile of cortisol compared to the highest was 1.5 (1.0–2.2, p = 0.058) for morning cortisol and 1.9 (1.3–2.8) for Δ-cortisol. All findings for Δ-cortisol remained after adjustments for multiple covariates and were also seen in a linear regression analysis (p = 0.003).
In summary, our findings of generally higher cortisol levels in women than men of all ages are novel and the stronger results seen for Δ-cortisol as opposed to morning cortisol in the association with WHR emphasise the need of studying cortisol variation intra-individually. To our knowledge, the associations in this study have never before been investigated in such a large population sample of both men and women. Our results therefore offer important knowledge on the descriptive characteristics of cortisol in relation to age and gender, and on the impact that associations previously seen between cortisol and abdominal obesity in smaller, selected samples have on a population level.
Prenatal exposure to inappropriate levels of glucocorticoids and maternal stress are putative mechanisms for the fetal programming of later health outcomes. The current investigation examined the influence of prenatal maternal cortisol and maternal psychosocial stress on infant physiological and behavioral responses to stress.
The study sample comprised 116 women and their full term infants. Maternal plasma cortisol and report of stress, anxiety and depression were assessed at 15, 19, 25, 31 and 36+ weeks’ gestational age. Infant cortisol and behavioral responses to the painful stress of a heel-stick blood draw were evaluated at 24 hours after birth. The association between prenatal maternal measures and infant cortisol and behavioral stress responses was examined using hierarchical linear growth curve modeling.
A larger infant cortisol response to the heel-stick procedure was associated with exposure to elevated concentrations of maternal cortisol during the late second and third trimesters. Additionally, a slower rate of behavioral recovery from the painful stress of a heel-stick blood draw was predicted by elevated levels of maternal cortisol early in pregnancy as well as prenatal maternal psychosocial stress throughout gestation. These associations could not be explained by mode of delivery, prenatal medical history, socioeconomic status or child race, sex or birth order.
These data suggest that exposure to maternal cortisol and psychosocial stress exert programming influences on the developing fetus with consequences for infant stress regulation.
Salivary cortisol is widely used in research but little is known about the typical, or expected, functioning of the HPA-axis in adolescents in naturalistic settings, nor whether the extensive array of confounders documented in the literature is applicable in this situation.
In a school-based study, 2995 15-year-old pupils provided two saliva samples, 30 min apart, in morning sessions timed to capture peak cortisol decline. The collection protocol was a balance between the large sample size obtainable in a school situation and a limited number of samples, constrained by the school timetable. In addition, pupils completed a questionnaire containing items previously shown to be associated with cortisol levels (e.g. time since awakening and life events), and their height and weight were measured. Outcome measures were cortisol levels at Times 1 and 2, and change (per minute) in cortisol between the two time points.
Median (IQR) cortisol levels for males and females were 10.5 (8.1) and 11.6 (9.3) nmol/L at Time 1, and 8.2 (6.0) and 8.1 (6.5) nmol/L at Time 2. 73% had a decline in cortisol level of more than 10% across the two time points, compatible with the expected diurnal pattern. In bivariate analyses, cortisol sampled on Monday, times of measurement and since awakening, prior smoking and several life events were associated with cortisol levels at Times 1 and 2 in both sexes. However, in multivariate analysis, few of these variables remained after controlling for times of measurement and since awakening and, in addition, the final models differed between the sexes. Two events (friend dying and splitting with a boy/girlfriend) predicted cortisol levels in both sexes while age, maturity, recent eating and smoking were predictors only in males. Several factors associated with cortisol change differed from those observed for absolute levels. Further adjustment for school clustering affected some associations, particularly time of measurement.
This study managed many of the problems found in naturalistic research on cortisol and provides norms for morning cortisol levels in 15-year-old adolescents.
Hydrocortisone; Adolescent; Saliva; Stress; Cross-sectional studies; Social environment
Prenatal cocaine exposure (PCE) is associated with blunted stress responsivity within the extrauterine environment. This study investigated the association between PCE and diurnal salivary cortisol levels in preadolescent children characterized by high biological and/or social risk (N = 725). Saliva samples were collected at their home. Analyses revealed no group differences in basal evening or morning cortisol levels; however, children with higher degrees of PCE exhibited blunted overnight increases in cortisol, controlling for additional risk factors. Race and caregiver depression were also associated with diurnal cortisol patterns. While repeated PCE may contribute to alterations in the normal or expected stress response later in life, sociodemographic and environmental factors are likewise important in understanding hormone physiology, especially as more time elapses from the PCE. Anticipating the potential long-term medical, developmental, or behavioral effects of an altered ability to mount a normal protective cortisol stress response is essential in optimizing the outcomes of children with PCE.
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
The hypothalamic-pituitary-adrenal (HPA) axis is posited to play a role in the pathogenesis of depression. We tested the hypothesis that parenting behavior would moderate the relation between parental lifetime depression history and offspring’s cortisol reactivity to a psychosocial stressor. A sample of 160 preschool-aged children was exposed to stress-inducing laboratory tasks, and four salivary cortisol samples were obtained. Parents completed clinical interviews and an observational parent-child interaction task. Parental hostility moderated the relation between parental depression and offspring cortisol reactivity. Only offspring whose parents had a history of depression and demonstrated hostility toward their child evidenced high and increasing cortisol levels. The moderating effect was specific to offspring who were exposed to maternal depression during the first few years of life. Similar to findings in animals, this study underscores the importance of the early rearing environment in the intergenerational transmission of stress sensitivity.
Depression; HPA-axis reactivity; cortisol; risk for depression; offspring; parenting
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
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