Diurnal Patterns Of Cortisol Secretion Research Articles

Dysregulated diurnal cortisol patterns are associated with cardiovascular mortality: Findings from the KORA-F3 study

Psychosocial stress has been associated with an increased risk for cardiovascular disease and death. Dysregulated diurnal cortisol slopes, which have also been associated with stress, might mediate this association. However, existing evidence on the cardiovascular health consequences of dysregulated cortisol slopes remains limited and inconclusive. To elucidate whether dysregulated diurnal cortisol slopes are related to cardiovascular mortality, we assessed salivary cortisol and cardiovascular morbidity and mortality in 1090 participants from the KORA-F3 study, a prospective, observational cohort study of a random representative sample from the general population. Eighty-seven deaths were registered during the mean follow-up period of approximately 11 years, 31 of which were classified as cardiovascular deaths. A more pronounced cortisol awakening response was associated with a lower risk of cardiovascular mortality in the adjusted Cox proportional hazards analysis (HR 0.59 [95-%-CI 0.36–0.96], p = 0.03). A greater diurnal cortisol peak-to-bedtime ratio at baseline also predicted a decreased risk of cardiovascular mortality (HR 0.50 [95-%-CI 0.34–0.73], p 0.01) and a decreased risk of stroke (HR 0.71 [95-%-CI 0.55–0.92], p 0.01). Increased levels of late night salivary cortisol predicted a higher risk of cardiovascular mortality (HR 1.49 [95-%-CI 1.13–1.97], p 0.01) and an increased risk of stroke (HR 1.24 [95-%-CI 1.01–1.52], p = 0.04). There was no association between measures of cortisol and non-cardiovascular related mortality. In conclusion, dysregulated diurnal cortisol patterns are associated with cardiovascular mortality, while greater diurnal cortisol variation seems to have a protective effect. This adds evidence to suggest a pathophysiological role of diurnal cortisol secretion patterns in cardiovascular health.

The impact of negative family-work spillover on diurnal cortisol.

Both dimensions of the work-family interface, work-to-family and family-to-work spillover, have important implications for health and well-being. Despite the importance of these associations, very little is known about the physiological mechanisms through which the interplay between family and work experiences are translated into long-lasting consequences for health. This study investigated both positive and negative aspects of each spillover dimension on diurnal cortisol secretion patterns in a large panel study of working adults between the ages of 33 and 80. Greater negative family-to-work (NFW) spillover predicted lower wake-up cortisol values and a flatter (less "healthy") diurnal cortisol slope. This effect was evident even after controlling for the effects of the other spillover dimensions. These findings indicate that not all aspects of the work-family interface might impact stress physiology to the same extent and suggest that diurnal cortisol may be an important pathway through which negative aspects of the work-family interface leave their mark on health. (PsycINFO Database Record

Circadian rhythm of salivary cortisol secretion in female zoo-kept African elephants (Loxodonta africana).

Salivary samples were collected over a 24-hr period from one group of six juvenile (7-12 years) and one group of three adult (24-25 years) African elephant females, Loxodonta africana, and the cortisol concentration was measured in unextracted samples by EIA. Samples were collected during May, June, and November 2012 (n = 147) using cotton swabs at 4-hr intervals from 20:00 to 20:00 of the next day (seven samples per animal in each trial). The animals are kept under standard zoo management: the herd is maintained in their indoor enclosures until 10:00 and then released into the outdoor enclosures until 21:00-21:30 (May/June) and 18:30-19:00 (November). No adult elephant bull was present at the zoo during this time. The results demonstrate a clear diurnal pattern of cortisol secretion with the lowest concentration observed at 20:00 (2.03 ± 0.08 ng/ml saliva) and the peak concentrations at 08:00 (5.26 ± 0.35 ng/ml saliva). Although the cortisol values were higher in the adult cows compared to the juvenile cows in the May-June period, the differences were not significant. However, the values obtained in November from the juvenile group were significantly higher (P < 0.05) than the concentrations measured in this group in June. In conclusion, salivary cortisol in zoo elephants follows a circadian rhythm (sleep-wake cycle) adapted to daily zoo husbandry routines.

Atypical secretion of cortisol in Nursing professionals.

Objective To describe the frequency with which nursing staff in hospitals presents an altered diurnal pattern of cortisol secretion. Method These findings were based on results obtained from 56 randomly selected professional nursing staff working in outpatient clinics, medical clinics, surgical clinics, operating theaters, pediatric and adult emergency units, adult and pediatric intensive care units of a university hospital. The analysis of the diurnal cortisol pattern was based on saliva samples collected over two consecutive working days. Results 42.5% of these nursing staff members presented an atypical pattern of cortisol secretion. Furthermore, the longer the period of exercising this profession, the higher the cortisol concentration (r=0.346; p=0.020). Conclusion Over one-third of nursing staff samples displayed atypical cortisol secretion patterns. This suggests that these professionals are exposed, not only to a mental, but also to a biological, overload and thus, to a risk of contracting stress-related illnesses.

P.1.c.012 Open-label study comparing the efficacy and tolerability of aripiprazole and risperidone in the treatment of children with autism spectrum disorder and ADHD

Research that has assessed the psychophysiological consequences of caregiver stress in young and middle aged caregivers, that is, in populations not contending with age associated decline of the endocrine and immune systems, has been scarce and yielded inconsistent findings. To extend work in this area, this study assessed the psychosocial, endocrine and immune consequences of caregiver stress in a cross sectional sample of young and middle aged caregivers of children with autism and attention deficit hyperactivity disorder (ADHD) compared against parents of typically developing children. Caregivers (n = 56) and parent controls (n = 22) completed measures of psychological distress (perceived stress, anxiety/depression), social support and physical health complaints. To capture important indices of the diurnal cortisol pattern, cortisol was measured at waking, 30 min post waking, 1200 h and 2200 h on two consecutive weekdays. Venous blood was taken to assess systemic concentrations of proinflammatory biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP). Caregivers scored markedly higher on all measures of psychological distress; scores on social support subscales, however, were significantly lower in this group. Diurnal patterns of cortisol secretion did not differentiate between the groups; however, caregivers displayed elevated systemic concentrations of the proinflammatory biomarker, CRP and reported more frequent episodes of physical ill health. The stress of caregiving exacts a significant psychophysiological toll, that is, even in the absence of HPA dysregulation, caregivers demonstrated elevated concentrations of proinflammatory biomarkers and, therefore, might be at greater risk for diseases fostered by disinhibition of the inflammatory response.

Neuromodulation and cognitive rehabilitation: addressing the methodological issue of circadian rhythms.

Most organisms, including humans,exhibit daily rhythms in their biological activities, physiological functions, and homeostatic mechanisms such as cell regeneration, hormone production, cardiac output, blood pressure, blood flow distribution, and body temperature. The physiological system responsible for these rhythms is known as the circadian system. Circadian changes have increasingly become an interesting focus of research, concerning also neurobehavioral functioning of healthy subjects. The impact of factors such as the sleep–wakefulness cycle and biological time-of-day on measures of subjective alertness has been extensively studied (1, 2). Moreover, there is compelling evidence of circadian dependency also for cognitive functions such as attention, memory, and learning (3, 4). Recently, it has been consolidated in different experimental models, including mammalian brain, that the circadian clock has a role in regulating structural synaptic plasticity, opening the new relevant concern of circadian-dependent neural plasticity (5,6). Interestingly, it has been suggested that changes in the electrical properties of the cell membrane (intrinsic plasticity) and in the release of neuromodulatory molecules due to the internal clock can reconfigure circuit dynamics leading individual neurons to switch among different functional networks throughout the day (5). Daily rhythmicity in neural activity has been further elucidated by Blautzik et al. (7) who analyzed the daily course of connectivity patterns. The authors found different degrees of daily modulation across connectivity patterns, ranging from networks characterized by stable activity across the day and networks with highly rhythmic connectivity changes. Based on the reported findings, we can infer that the aforementioned oscillatory processes in connectivity strength and spatial extent would eventually determine highly individual fluctuations of effective connectivity over the course of the day. Circadian rhythms show also to exert influence on the excitability of the cerebral cortex, as found by Lang et al. (8). In this study, the excitability of the primary motor cortex (M1) of healthy subjects was evaluated by transcranial magnetic stimulation (TMS) at different times of the day. Data unveiled that both the intracortical and the corticospinal excitability of M1 exhibited a progressive decrease during the course of the day. In the last years, it has emerged that the effectiveness and reproducibility of several techniques able to induce neuroplastic changes in humans, such as paired associative stimulation (PAS), are influenced by time-of-day of the intervention (9) and subjected to circadian modulation. As demonstrated by Sale et al. (10), who tested 25 subjects twice, at 8:00 a.m. and 8:00 p.m., on separate days, PAS effectiveness is enhanced in the evening,when endogenous cortisol is low; conversely, effects of PAS in the evening are blocked by a single oral dose of hydrocortisone. Additionally, in a large study of humans aged 50–70 years, high salivary levels of cortisol appeared to be related with poor performances on a wide range of cognitive domains, including language, verbal learning, processing speed, memory, and eye–hand coordination (11). Overall, the circadian modulation of several neural properties and structures, at both the microscopic and functional levels, may deeply affect cognitive behavior, responsiveness, and performance within the day. Despite its potential impact, timeof-day is rarely contemplated when brain responses and cognitive functions are studied. As a matter of fact, in order to minimize possible biases related to circadian effects, some neurophysiological studies are conducted with evaluations and/or interventions performed at the same time of the day. Still, these experimental designs do not contemplate another relevant factor, which may strongly affect the reliability of the collected data that is the interindividual variability of the biological clock. This physiological variability of circadian rhythms between subjects has led to the notion of individual chronotypes (12, 13). The chronotype influences the organization of physiological functions, behaviors, and cognitive performances throughout the day (1, 14, 15). Given the differences in circadian rhythmicity between chronotypes, specific individual variations in task performance are likely to occur as a function of time-of-day. In other words, this implies that the scheduled task may not be necessarily synchronized to the most optimal moment in the day for each tested participant (16, 17). The regulation of the endogenous dynamics that characterizes a chronotype is dictated by many factors. The thorough understanding of these mechanisms is critical to gain a comprehensive view on their functional implications and, further, may be considerably useful when addressing the experimental limitations due to diurnal rhythmicity. Among them, cortisol is a main neuromodulator that mediates circadian processes. The normal diurnal pattern of cortisol secretion has been

Cushing syndrome.

Cushing syndrome.

Green Space and Stress: Evidence from Cortisol Measures in Deprived Urban Communities

Contact with green space in the environment has been associated with mental health benefits, but the mechanism underpinning this association is not clear. This study extends an earlier exploratory study showing that more green space in deprived urban neighbourhoods in Scotland is linked to lower levels of perceived stress and improved physiological stress as measured by diurnal patterns of cortisol secretion. Salivary cortisol concentrations were measured at 3, 6 and 9 h post awakening over two consecutive weekdays, together with measures of perceived stress. Participants (n = 106) were men and women not in work aged between 35–55 years, resident in socially disadvantaged districts from the same Scottish, UK, urban context as the earlier study. Results from linear regression analyses showed a significant and negative relationship between higher green space levels and stress levels, indicating living in areas with a higher percentage of green space is associated with lower stress, confirming the earlier study findings. This study further extends the findings by showing significant gender differences in stress patterns by levels of green space, with women in lower green space areas showing higher levels of stress. A significant interaction effect between gender and percentage green space on mean cortisol concentrations showed a positive effect of higher green space in relation to cortisol measures in women, but not in men. Higher levels of neighbourhood green space were associated with healthier mean cortisol levels in women whilst also attenuating higher cortisol levels in men. We conclude that higher levels of green space in residential neighbourhoods, for this deprived urban population of middle-aged men and women not in work, are linked with lower perceived stress and a steeper (healthier) diurnal cortisol decline. However, overall patterns and levels of cortisol secretion in men and women were differentially related to neighbourhood green space and warrant further investigation.

Diurnal cortisol rhythm and cognitive functioning in toddlers: The Generation R Study

Little is known about the relationship between diurnal cortisol secretion patterns and cognitive function early in life. This population-based study examined whether diurnal cortisol rhythms and cognitive functioning in toddlers are related. Within the Generation R Study, parents of 364 infants (median age: 14.2 months) collected saliva samples at five moments during one day. We assessed the diurnal cortisol rhythm by calculating the area under the curve (AUC), the cortisol awakening response (CAR), and the diurnal slope. Verbal cognitive functioning and fine motor development was determined at age 18 months. Nonverbal cognitive functioning was assessed at age 30 months. A more positive CAR was associated with a lower risk of delay in language comprehension (OR per 1-SD CAR: 0.62, 95%CI: 0.40–0.98, p = .04), a lower risk of nonoptimal fine motor development (OR per 1-SD slope: 0.74, 95%CI: 0.57–0.96, p = .03), and a lower risk of delay in nonverbal cognitive development (OR per 1-SD CAR: 0.58, 95%CI: 0.38–0.90, p = .02). Also, children with flatter slopes had a lower risk of delay in nonverbal cognitive development (OR per 1-SD slope: 0.51, 95%CI: 0.34–0.76, p = .001). Higher AUC levels were associated with a higher risk of delay in language production. These results show that variations in diurnal cortisol rhythms are already associated with variations in cognitive functioning at a young age. Infants with a diurnal cortisol pattern indicative of less stress and more cortisol reactivity, that is, lower AUC levels and a more positive CAR, show a lower risk of delay in cognitive functioning as toddlers.

Salivary Cortisol: A Tool for Biobehavioral Research in Children

Measurement of salivary cortisol has been widely used in pediatric research for more than 20 years as a biomarker of hypothalamic pituitary adrenal (HPA) axis activity during normal activity and in response to stress. McCarthy et al. (2010) recently reported cognitive-behavioral interventions that were effective in reducing pain and distress in children undergoing intravenous needle insertion and salivary cortisol measurement was a useful marker of biological response to compare the effect of interventions in conjunction with other physiological and/or behavioral outcome measures. The inclusion of salivary cortisol as an outcome measure would provide a useful biological marker with future research to investigate: stress in children undergoing painful procedures, weight loss, sleep problems, as well as caregiver stress. The use of salivary cortisol in pediatric biobehavioral research has revealed important information about the pattern of cortisol secretion during childhood, the response to stressors in a non-clinical environment, the response to therapeutic interventions, and the identification of dysfunctional patterns of secretion in children. Salivary cortisol is a reliable non-invasive method to assess HPA function, however collection and measurement of specimens with infants and children requires special consideration. This paper will summarize pertinent issues related to salivary cortisol collection to encourage “broader employment” of this method in pediatric biobehavioral research. Various psychological and physical stressors can activate the HPA axis such that corticotrophin releasing hormone (CRH) and adrenocorticotropin hormones (ACTH) are released with subsequent rise in cortisol levels. Once the HPA axis is activated, it takes approximately 15–30 minutes for the cortisol levels to peak. Cortisol secretion has a circadian pattern, peaking in the early morning (approximately 20–30 minutes after awakening) with the nadir around midnight (Stratakis, Gold, & Chrousos, 1995), and short bursts of secretion over the course of the day. The diurnal pattern of cortisol secretion is typically established in early infancy (Price, Close, & Fielding, 1983). HPA axis function and regulation has been shown to have a significant impact on growth and development. Poor regulation of the cortisol response to emotional stress correlates with detrimental effects on cognitive and emotional functioning (Lupien, 2009). Salivary cortisol is a measure of unbound, or “free” cortisol that is biologically relevant with the ease of sampling in clinical and field settings. Saliva sampling is reliable, non-invasive method to measure biologically active, unbound plasma of cortisol in infants and children. Salivary testing offers advantages over venipuncture since it is noninvasive and less likely to confound results. Also, multiple samples can be obtained without increasing ethical concerns. This method is extensively used in psychoneuroendocrinological research (Kirschbaum & Hellhammer, 1994). For example, studies of naturalistic life events that are considered stressful, such as starting school for a child, have incorporated salivary cortisol as an outcome measure to investigate normal versus mal-adaptive responses (Boyce et al., 1995). Also, studies of diurnal salivary cortisol patterns provide insight regarding the role of early environmental factors on cortisol regulation, cognition, and growth (Gutman & Nemeroff, 2003). In addition, salivary cortisol is a useful diagnostic test in the evaluation of suspected cortisol dysregulation (Gafni, Papanicolaou, & Nieman, 2000). For excellent reviews see: Hanrahan, 2006; Jessop & Turner-Cobb, 2006; Kirschbaum & Hellhammer, 1994; and Schmidt, 1997.

More green space is linked to less stress in deprived communities: Evidence from salivary cortisol patterns

Green space has been associated with a wide range of health benefits, including stress reduction, but much pertinent evidence has relied on self-reported health indicators or experiments in artificially controlled environmental conditions. Little research has been reported using ecologically valid objective measures with participants in their everyday, residential settings. This paper describes the results of an exploratory study (n=25) to establish whether salivary cortisol can act as a biomarker for variation in stress levels which may be associated with varying levels of exposure to green spaces, and whether recruitment and adherence to the required, unsupervised, salivary cortisol sampling protocol within the domestic setting could be achieved in a highly deprived urban population. Self-reported measures of stress and general wellbeing were also captured, allowing exploration of relationships between cortisol, wellbeing and exposure to green space close to home. Results indicate significant relationships between self-reported stress (P<0.01), diurnal patterns of cortisol secretion (P<0.05), and quantity of green space in the living environment. Regression analysis indicates percentage of green space in the living environment is a significant (P<0.05) and independent predictor of the circadian cortisol cycle, in addition to self-reported physical activity (P<0.02). Results also show that compliance with the study protocol was good. We conclude that salivary cortisol measurement offers considerable potential for exploring relationships between wellbeing and green space and discuss how this ecologically valid methodology can be developed to confirm and extend findings in deprived city areas to illuminate why provision of green space close to home might enhance health.

Changes in Diurnal Salivary Cortisol Levels in Response to an Acute Stressor in Healthy Young Adults

Knowledge of the diurnal cortisol response to acute stress in healthy individuals can help us better understand the physiological and health effects of chronic stress. To compare the diurnal patterns of cortisol secretion of 15 medical students 2 weeks before a major written examination (control phase) and 2 weeks later at the time of the examination (acute stress phase). Interrupted time series within-subjects. During the acute stress phase, less cortisol was secreted over the course of the day, as demonstrated by a more prolonged and steeper decline in cortisol levels. In addition, higher cortisol levels were present in the evening. Despite these changes in the usual diurnal pattern, overall exposure to cortisol remained the same for both phases. The results of this study suggest that specific adaptations to the diurnal pattern of cortisol are made in the face of acute stress, important information for understanding cortisol regulation in health and illness.

The psychosocial, endocrine and immune consequences of caring for a child with autism or ADHD

Research that has assessed the psychophysiological consequences of caregiver stress in young and middle aged caregivers, that is, in populations not contending with age associated decline of the endocrine and immune systems, has been scarce and yielded inconsistent findings. To extend work in this area, this study assessed the psychosocial, endocrine and immune consequences of caregiver stress in a cross sectional sample of young and middle aged caregivers of children with autism and attention deficit hyperactivity disorder (ADHD) compared against parents of typically developing children. Caregivers (n=56) and parent controls (n=22) completed measures of psychological distress (perceived stress, anxiety/depression), social support and physical health complaints. To capture important indices of the diurnal cortisol pattern, cortisol was measured at waking, 30 min post waking, 1200 h and 2200 h on two consecutive weekdays. Venous blood was taken to assess systemic concentrations of proinflammatory biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP). Caregivers scored markedly higher on all measures of psychological distress; scores on social support subscales, however, were significantly lower in this group. Diurnal patterns of cortisol secretion did not differentiate between the groups; however, caregivers displayed elevated systemic concentrations of the proinflammatory biomarker, CRP and reported more frequent episodes of physical ill health. The stress of caregiving exacts a significant psychophysiological toll, that is, even in the absence of HPA dysregulation, caregivers demonstrated elevated concentrations of proinflammatory biomarkers and, therefore, might be at greater risk for diseases fostered by disinhibition of the inflammatory response.

Perceived stress, common health complaints and diurnal patterns of cortisol secretion in young, otherwise healthy individuals

Research has frequently linked perceived stress with changes in subjective and objective measures of ill health; however, additional assessment should consider the physiological mechanisms mediating these effects. This study investigated whether differential patterns of cortisol secretion might partially mediate perceived stress related disparities in common health complaints in young, otherwise healthy individuals. To capture the kinds of health complaints commonly reported in this population, the Pennebaker Inventory of Limbic Languidness (PILL) was selected. To capture important parameters of the diurnal profile, cortisol was sampled at waking, 30minutes post waking, 1200h and 2200h on three consecutive weekdays. Results revealed flatter diurnal cortisol slopes and elevated mean diurnal output (characterised by HPA hyperactivity in the evening) for participants in the higher stress group. Participants that reported higher perceived levels of stress also reported experiencing common health complaints with markedly greater frequency; however, these disparities were abolished when mean diurnal output of cortisol was statistically controlled. While dysregulation of basal HPA activity has been implicated in the aetiologies of chronic illness, findings reported here implicated hypersecretion of cortisol as one physiological pathway, partially mediating perceived stress related disparities in the kinds of common health complaints that typically affect young, otherwise healthy individuals.

Longitudinal relationships between self‐efficacy, post‐traumatic distress and salivary cortisol among motor vehicle accident survivors

AbstractThe present study tested if post‐traumatic distress following a motor vehicle accident (MVA) and MVA‐related self‐efficacy beliefs were associated with diurnal salivary cortisol in the early post‐traumatic period. Cortisol was collected upon awakening and at 1, 4 and 12 h after waking. Collection days were 1 week, 1 month and 3 months after MVA. A total of 30 participants provided their cortisol samples across all measurement points. Two methods for computing the area under the cortisol curve were used. Higher post‐traumatic distress at 1 month predicted lower cortisol area under the curve (AUC) with respect to increase (AUCI, reflecting changes in cortisol secretions during daytime) at 3 months. AUC with respect to ground (AUCG, reflecting total cortisol release during daytime), measured at 1 month after trauma, predicted higher post‐traumatic distress at 3 months. The results showed that self‐efficacy at 1 week indirectly predicted 3‐month AUCI through 1‐month post‐traumatic distress. These findings highlight the importance of self‐efficacy and post‐traumatic distress in explaining longitudinal diurnal patterns of cortisol secretion after trauma. Copyright © 2011 John Wiley &amp; Sons, Ltd.

Seasonal differences in the diurnal pattern of cortisol secretion in healthy participants and those with self-assessed seasonal affective disorder

This study compared the daily pattern of free salivary cortisol secretion in winter and in summer between two groups; participants with self-assessed seasonal affective disorder (SAD) and age- and sex-matched healthy controls. Fifty-two participants completed the study with an equal number in each group. The diurnal pattern of cortisol secretion was assessed across two consecutive weekdays in summer, and two in winter, with conditions being counterbalanced. On each study day participants collected multiple saliva samples in the domestic setting to capture the cortisol awakening response (CAR) and declining levels across the day. In addition, perceived stress, anxiety, depression, state stress and state arousal were assessed using validated questionnaires. There was no evidence for any seasonal changes in psychological data or cortisol pattern for the healthy control population. In summer, self-assessed SAD and control participants had similar psychological and cortisol profiles. In winter however, SAD participants reported greater depression, stress and anxiety, and lower levels of arousal. Furthermore, the CAR was significantly attenuated in SAD participants during winter months. There was no difference in cortisol levels during the rest of the day between controls and SAD participants in winter. In line with the above findings and previous research, there was an inverse relationship between the increase in cortisol following awakening and a measure of seasonality in winter. Furthermore in winter, a general dysphoria construct correlated inversely with the CAR, indicating that participants reporting greater depression, stress and anxiety and lower arousal, exhibited lower CARs. In conclusion, during the shortened photoperiod in winter, the cortisol response to awakening is attenuated in participants with self-assessed SAD in comparison to controls. These findings contribute to the understanding of the physiology of SAD.

Do social disadvantage and early family adversity affect the diurnal cortisol rhythm in infants? The Generation R Study

Dysregulation of diurnal cortisol secretion patterns may explain the link between adversities early in life and later mental health problems. However, few studies have investigated the influence of social disadvantage and family adversity on the hypothalamic–pituitary–adrenal (HPA) axis early in life. In 366 infants aged 12–20 months from the Generation R Study, a population-based cohort from fetal life onwards, parents collected saliva samples from their infant at 5 moments over the course of 1 day. The area under the curve (AUC), the cortisol awakening response (CAR) and the diurnal cortisol slope were calculated as different composite measures of the diurnal cortisol rhythm. Information about social disadvantage and early adversity was collected using prenatal and postnatal questionnaires. We found that older infants showed lower AUC levels; moreover, infants with a positive CAR were significantly older. Both the AUC and the CAR were related to indicators of social disadvantage and early adversity. Infants of low income families, in comparison to high income families, showed higher AUC levels and a positive CAR. Infants of mothers who smoked during pregnancy were also significantly more likely to show a positive CAR. Furthermore, infants of mothers experiencing parenting stress showed higher AUC levels. The results of our study show that effects of social disadvantage and early adversity on the diurnal cortisol rhythm are already observable in infants. This may reflect the influence of early negative life events on early maturation of the HPA axis.

Amygdala and Ventromedial Prefrontal Cortex Are Inversely Coupled during Regulation of Negative Affect and Predict the Diurnal Pattern of Cortisol Secretion among Older Adults

Among younger adults, the ability to willfully regulate negative affect, enabling effective responses to stressful experiences, engages regions of prefrontal cortex (PFC) and the amygdala. Because regions of PFC and the amygdala are known to influence the hypothalamic-pituitary-adrenal axis, here we test whether PFC and amygdala responses during emotion regulation predict the diurnal pattern of salivary cortisol secretion. We also test whether PFC and amygdala regions are engaged during emotion regulation in older (62- to 64-year-old) rather than younger individuals. We measured brain activity using functional magnetic resonance imaging as participants regulated (increased or decreased) their affective responses or attended to negative picture stimuli. We also collected saliva samples for 1 week at home for cortisol assay. Consistent with previous work in younger samples, increasing negative affect resulted in ventral lateral, dorsolateral, and dorsomedial regions of PFC and amygdala activation. In contrast to previous work, decreasing negative affect did not produce the predicted robust pattern of higher PFC and lower amygdala activation. Individuals demonstrating the predicted effect (decrease < attend in the amygdala), however, exhibited higher signal in ventromedial prefrontal cortex (VMPFC) for the same contrast. Furthermore, participants displaying higher VMPFC and lower amygdala signal when decreasing compared with the attention control condition evidenced steeper, more normative declines in cortisol over the course of the day. Individual differences yielded the predicted link between brain function while reducing negative affect in the laboratory and diurnal regulation of endocrine activity in the home environment.

Blunted hypothalamic–pituitary–adrenocortical axis responsivity to stress in persons with a family history of alcoholism

Abstinent alcoholics show a blunted stress cortisol response that may be a consequence of drinking or a preexisting risk marker. We tested cortisol responses to psychological stress in 186 18–30 year-old, healthy social drinkers having no personal history of alcohol or drug dependence, 91 of whom had one or two alcoholic parents (FH+) and 95 having no family alcoholism for two generations (FH−). We predicted that, similar to alcoholic patients, the FH+ would have reduced stress cortisol responses that would be partially determined by their temperament characteristics, specifically antisocial tendencies as measured by the California Psychological Inventory. On a stress day, subjects performed continuous simulated public speaking and mental arithmetic tasks for 45 min, and on a control day they sat and rested for the same time period. The FH+ who were low in sociability had smaller cortisol responses than FH−, high-sociability persons ( t = 2.27, p = .02). These two groups were not different in diurnal cortisol secretion patterns or affective responses to the stressors. Persons with a familial risk for alcoholism who have more antisocial tendencies may have altered central nervous system responses to emotionally relevant social challenges. Disrupted cortisol stress responses may serve as a risk marker for the development of substance use disorders.

Predicting the failure of disc surgery by a hypofunctional HPA axis: evidence from a prospective study on patients undergoing disc surgery

Patients with postoperative ongoing sciatic pain have been shown to exhibit reduced cortisol levels along with enhanced IL-6 levels. The aim of the present study was to clarify the relationship between a reduced cortisol secretion and enhanced cytokine levels by performing a prospective study on patients with disc herniation. Twenty-two patients were examined before and after their disc surgery. Twelve healthy, pain-free subjects matched for age, education and gender constituted the control group. The preoperative examinations included the assessment of the diurnal pattern of cortisol secretion and the feedback sensitivity of the hypothalamus–pituitary–adrenal (HPA) axis. Patients' subjective stress levels also were assessed during the preoperative examination. The diurnal pattern of cortisol secretion was again assessed during the postoperative examination. Furthermore, blood samples were collected to measure catecholamine, adrenocorticotropic hormone (ACTH)- and interleukin-6 (IL-6) levels before and after measuring the pressure pain thresholds (PPTs). An assessment of the sensitivity of circulating monocytes to the immunosuppressive effects of glucocorticoids was further included in the postoperative examinations. Failed back syndrome (FBS) patients ( n=12) showed a reduced cortisol secretion in the morning hours and enhanced feedback sensitivity of the HPA axis. Furthermore, FBS patients displayed an increased in-vitro production of proinflammatory cytokines and a relative glucocorticoid resistance of pro-inflammatory cytokine producing monocytes as compared to non-FBS patients ( n=10) and controls. After PPT measurement FBS patients exhibited an increased norepinephrine but decreased epinephrine response, together with lower ACTH levels and a four times higher plasma IL-6 response. These findings suggest that chronically stressed patients are at a higher risk for a poor surgical outcome as their reduced cortisol secretion promotes the postoperative ongoing synthesis of proinflammatory cytokines.