Flatter Diurnal Cortisol Slopes Research Articles

Inflammation and inflammatory control in interstitial cystitis/bladder pain syndrome: Associations with painful symptoms

Toll-like receptors (TLR) are known to play a role in chronic pain, from animal models and limited research in humans, but their role in interstitial cystitis/bladder pain syndrome (IC/BPS) is unknown. Similarly, alterations of the hypothalamic–pituitary–adrenal axis have been reported in some pain conditions. Our objectives were to identify inflammatory processes that might distinguish individuals with IC/BPS from healthy controls (HC) and to examine their associations with IC/BPS symptoms. Female participants (58IC/BPS patients and 28HCs) completed pain and urinary symptom questionnaires and collected saliva for cortisol as part of the Multidisciplinary Approach to Pelvic Pain study. Inflammatory cytokines were assayed in plasma, and in TLR-2− and TLR-4–stimulated peripheral blood mononuclear cells. Controlling for BMI and negative affect, between-group differences were analyzed by general linear models, and relationships between symptoms and inflammatory variables were analyzed by regression. Compared to HCs, IC/BPS patients had higher levels of plasma interleukin-6 (P=.040), greater interleukin-1β responsive to TLR-2 stimulation (P=.040), and flatter diurnal cortisol slopes (P=.010), indicating inflammatory dysregulation. In IC/BPS patients, inflammation after TLR-4 stimulation was associated with multiple symptoms, including genitourinary pain (P=.010), sexual pain (P=.002), and marginally with urinary symptoms (P=.068). Genitourinary pain severity (P=.008), frequency (P=.001), and pain with intercourse (P=.002) were strongly associated with TLR-4 inflammatory response. TLR-4 appears to play a central role in painful symptoms of IC/BPS patients, which may be linked to poor endogenous inflammatory control. These findings may help to identify new mechanisms in IC/BPS and lead to new therapeutic approaches.

Associations of ghrelin with eating behaviors, stress, metabolic factors, and telomere length among overweight and obese women: Preliminary evidence of attenuated ghrelin effects in obesity?

Ghrelin regulates homeostatic food intake, hedonic eating, and is a mediator in the stress response. In addition, ghrelin has metabolic, cardiovascular, and anti-aging effects. This cross-sectional study examined associations between total plasma ghrelin, caloric intake based on 3day diet diaries, hedonic eating attitudes, stress-related and metabolic factors, and leukocyte telomere length in overweight (n=25) and obese women (n=22). We hypothesized associations between total plasma ghrelin and eating behaviors, stress, metabolic, cardiovascular, and cell aging factors among overweight women, but not among obese women due to lower circulating ghrelin levels and/or central resistance to ghrelin. Confirming previous studies demonstrating lowered plasma ghrelin in obesity, ghrelin levels were lower in the obese compared with overweight women. Among the overweight, ghrelin was positively correlated with caloric intake, giving in to cravings for highly palatable foods, and a flatter diurnal cortisol slope across 3days. These relationships were non-significant among the obese group. Among overweight women, ghrelin was negatively correlated with insulin resistance, systolic blood pressure, and heart rate, and positively correlated with telomere length. Among the obese subjects, plasma ghrelin concentrations were negatively correlated with insulin resistance, but were not significantly correlated with blood pressure, heart rate or telomere length. Total plasma ghrelin and its associations with food intake, hedonic eating, and stress are decreased in obesity, providing evidence consistent with the theory that central resistance to ghrelin develops in obesity and ghrelin’s function in appetite regulation may have evolved to prevent starvation in food scarcity rather than cope with modern food excess. Furthermore, ghrelin is associated with metabolic and cardiovascular health, and may have anti-aging effects, but these effects may be attenuated in obesity.

The psychophysiological and health corollaries of child problem behaviours in caregivers of children with autism and ADHD

The positive relationship between problem behaviours of children with additional complex needs and psychological distress in their caregivers has been widely evidenced. Fewer studies, however, have assessed the relationship between care recipients' problem behaviours and key physiological processes, relevant for the physical health status of their care providers. This study examined the psychological, endocrine and health corollaries of child problem behaviours in caregivers of children with autism and attention deficit hyperactivity disorder. Caregivers (n = 18) completed self-report measures of psychological distress, child problem behaviours and incidences of commonly occurring ailments. To capture important parameters of the basal diurnal cortisol pattern, caregivers collected saliva samples at waking, 30 min post waking, 1200 h and 2200 h on two consecutive weekdays. Data revealed a positive relationship between caregivers' perceived levels of stress and problems with child conduct behaviours. In addition, caregivers who reported more problems with child emotional and hyperactivity behaviours displayed atypical cortisol patterns characterised by flatter diurnal cortisol slopes and reduced cortisol awakening response magnitude. Subjective reports of commonly occurring ailments were also greater in caregivers experiencing more problems with child emotional behaviours. These findings have implications for interventions that aim to improve the psychophysiological well-being of the caregiver by targeting problem behaviours of the care recipient.

Are flatter diurnal cortisol rhythms associated with major depression and anxiety disorders in late adolescence? The role of life stress and daily negative emotion

Alterations in hypothalamic-pituitary-adrenal (HPA) axis functioning have been associated with major depression disorder (MDD) and some anxiety disorders. Few researchers have tested the possibility that high levels of recent life stress or elevations in negative emotion may partially account for the HPA axis alterations observed in these disorders. In a sample of 300 adolescents from the Youth Emotion Project, we examined associations between MDD and anxiety disorders, dimensional measures of internalizing symptomatology, life stress, mood on the days of cortisol testing, and HPA axis functioning. Adolescents with a past MDD episode and those with a recent MDD episode comorbid with an anxiety disorder had flatter diurnal cortisol slopes than adolescents without a history of internalizing disorders. Higher reports of general distress, a dimension of internalizing symptomatology, were also associated with flatter slopes. Negative emotion, specifically sadness and loneliness, was associated with flatter slopes and partially accounted for the associations between comorbid MDD and anxiety disorders and cortisol. The associations between past MDD and cortisol slopes were not accounted for by negative emotion, dimensional variation in internalizing symptomatology, or levels of life stress, indicating that flatter cortisol slopes may also be a "scar" marker of past experiences of MDD.

The associations between diurnal cortisol patterns, self-perceived social support, and sleep behavior in Chinese breast cancer patients

This study examined the relationships between diurnal cortisol patterns and sleep behavior, social support, psychological factors, and perceived health status in breast cancer patients. One hundred and eighty-one breast cancer patients completed a self-report questionnaire that combined the Hospital Anxiety and Depression Scale, the Yale Social Support Scale, and self-perceived measures of physical health, stress, sleep quality, total sleep hours, and time of awakening. Salivary cortisol was collected upon waking, at 1200h, 1700h, and 2100h on two consecutive days. Multiple regression analysis was performed on the diurnal cortisol slope that was derived from slope analysis of the log-transformed cortisol data. Controlling for the initial cortisol level, a flatter diurnal cortisol slope was significantly associated with a later time of awakening, higher negative social support, poorer perceived health, poorer sleep quality, and shorter total sleep hours. Anxiety and depression were not significantly correlated with the slope. The results indicate a subtle dysregulation in hypothalamic-pituitary-adrenal axis functioning in patients with highly negative social support, poor perceived health, poor sleep quality, a later time of awakening, and insufficient sleep hours.

Dysregulated diurnal cortisol pattern is associated with glucocorticoid resistance in women with major depressive disorder

Dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis is believed to play a role in the pathophysiology of depression. To investigate mechanisms that may underlie this effect, we examined several indices of HPA axis function – specifically, diurnal cortisol slope, cortisol awakening response, and suppression of cortisol release following dexamethasone administration – in 26 pre-menopausal depressed women and 23 never depressed women who were matched for age and body mass index. Salivary cortisol samples were collected at waking, 30min after waking, and at bedtime over three consecutive days. On the third day, immediately after the bedtime sample, participants ingested a 0.5mg dexamethasone tablet; they then collected cortisol samples at waking and 30min after waking the following morning. As predicted, depressed women exhibited flatter diurnal cortisol rhythms and more impaired suppression of cortisol following dexamethasone administration than non-depressed women over the three sampling days. In addition, flatter diurnal cortisol slopes were associated with reduced cortisol response to dexamethasone treatment, both for all women and for depressed women when considered separately. Finally, greater self-reported depression severity was associated with flatter diurnal cortisol slopes and with less dexamethasone-related cortisol suppression for depressed women. Depression in women thus appears to be characterized by altered HPA axis functioning, as indexed by flatter diurnal cortisol slopes and an associated impaired sensitivity of cortisol to dexamethasone. Given that altered HPA axis functioning has been implicated in several somatic conditions, the present findings may be relevant for understanding the pathophysiology of both depression and depression-related physical disease.

Preschoolers' everyday conflict at home and diurnal cortisol patterns.

Early life family conflict is associated with physical health problems later in life, but little is known about the biological pathways through which conflict at home exerts it deleterious effects on health. The goal of this study was to investigate the associations between naturalistically assessed conflict in everyday family environments and diurnal cortisol in preschool-aged children. Forty-four children aged 3-5 from two-parent families provided six saliva samples per day over 2 days from a Saturday morning through Sunday night. For a full day on either Saturday or Sunday, children wore a child version of the Electronically Activated Recorder, a digital voice recorder that records ambient sounds while participants go about their daily lives. Parents provided reports of child externalizing behaviors as well as daily reports of child conflicts. Diurnal salivary cortisol over the two weekend days of the study. Greater Electronically Activated Recorder-assessed child conflict at home was associated with children having lower cortisol at wakeup (p < .009) and flatter diurnal cortisol slopes (p < .007). These associations remained significant even after controlling for parent reports of child externalizing behaviors, parent reports of daily child conflicts, and child age and sex. These findings indicate that taking into consideration everyday conflicts at home may be key to our understanding of stress-health links in young children.

Vagal Regulation, Cortisol, and Sleep Disruption in Women with Metastatic Breast Cancer

To determine the relationship between hypothalamic pituitary axis (HPA) dysregulation, vagal functioning, and sleep problems in women with metastatic breast cancer. Sleep was assessed by means of questionnaires and wrist actigraphy for 3 consecutive nights. The ambulatory, diurnal variation in salivary cortisol levels was measured at 5 time points over 2 days. Vagal regulation was assessed via respiratory sinus arrhythmia (RSA(TF)) during the Trier Social Stress Task. Ninety-nine women (54.6 +/- 9.62 years) with metastatic breast cancer. Longer nocturnal wake episodes (r = 0.21, p = 0.04, N=91) were associated with a flatter diurnal cortisol slope. Sleep disruption was also associated with diminished RSA(TF). Higher RSA baseline scores were significantly correlated with higher sleep efficiency (r = 0.39, p = 0.001, N=68) and correspondingly lower levels of interrupted sleep (waking after sleep onset, WASO; r = -0.38, p = 0.002, N=68), lower average length of nocturnal wake episodes (r = -0.43, p < 0.001, N=68), and a lower self-reported number of hours of sleep during a typical night (r = -0.27, p = 0.02, N=72). Higher RSA AUC was significantly related to higher sleep efficiency (r = 0.45, p < 0.001, N=64), and a correspondingly lower number of wake episodes (r = -0.27, p = 0.04, N=64), lower WASO (r = -0.40, p = 0.001, N=64), and with lower average length of nocturnal wake episodes (r = -0.41, p = 0.001, N=64). While demographics, disease severity, and psychological variables all explained some portion of the development of sleep disruption, 4 of the 6 sleep parameters examined (sleep efficiency, WASO, mean number of waking episodes, average length of waking episode) were best explained by RSA. These data provide preliminary evidence for an association between disrupted nocturnal sleep and reduced RSA the subsequent day, confirming an association between disrupted nocturnal sleep and flattened diurnal cortisol rhythm in women with metastatic breast cancer. They suggest that the stress-buffering effects of sleep may be associated with improved parasympathetic tone and normalized cortisol patterns during the day.

Repression and High Anxiety Are Associated With Aberrant Diurnal Cortisol Rhythms in Women With Metastatic Breast Cancer.

Previous research has provided evidence of autonomic, endocrine, and immunological dysregulation in repressers and a possible association with cancer incidence and progression. Recently published data from the authors' laboratory demonstrated that flatter diurnal cortisol slopes were a risk factor for early mortality in women with metastatic breast cancer. In the current analysis of this same sample (N=91), the authors tested differences at baseline between groups scored using the Weinberger Adjustment Inventory on diurnal cortisol slope and mean cortisol levels. When compared with self-assured and nonextreme groups, the represser and high-anxious groups had a significantly flatter diurnal slope. Diurnal slope was similar for repressers and high-anxious groups. Groups did not differ on mean cortisol levels, nor did they differ on intercept (morning) values.