Neural Correlates of the Cortisol Awakening Response in Humans.
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SUBMITTER: Boehringer A
PROVIDER: S-EPMC4613622 | biostudies-literature | 2015 Aug
REPOSITORIES: biostudies-literature
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Neural Correlates of the Cortisol Awakening Response in Humans.
Boehringer Andreas A Tost Heike H Haddad Leila L Lederbogen Florian F Wüst Stefan S Schwarz Emanuel E Meyer-Lindenberg Andreas A
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20150317 9
The cortisol rise after awakening (cortisol awakening response, CAR) is a core biomarker of hypothalamic-pituitary-adrenal (HPA) axis regulation related to psychosocial stress and stress-related psychiatric disorders. However, the neural regulation of the CAR has not been examined in humans. Here, we studied neural regulation related to the CAR in a sample of 25 healthy human participants using an established psychosocial stress paradigm together with multimodal functional and structural (voxel- ...[more]
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Project description:BackgroundIn humans, circulating cortisol usually peaks 30-60 min after awakening from nocturnal sleep, this is commonly referred to as the cortisol awakening response (CAR). We examined the extent to which the CAR is influenced by the circadian system, independent of behaviors including sleep.Materials and methodsWe examined the CAR in 34 adults (20 female) using two complementary multiday in-laboratory circadian protocols performed in dim light, throughout which behavioral factors were uniformly distributed across the 24-hour circadian cycle. Protocol 1 consisted of 10 identical consecutive 5-hour 20-minute sleep/wake cycles, and protocol 2 consisted of 5 identical consecutive 18-hour sleep/wake cycles. Salivary melatonin was used as the circadian phase marker (0° = dim light melatonin onset). During each sleep/wake cycle, salivary cortisol was measured upon scheduled awakening and 50-minutes later, with the change in cortisol defined as the CAR. Cosinor analyses were used to detect any significant circadian rhythmicity in the CAR. In secondary analyses, we adjusted the models for time awake before lights on, total sleep time, percent of rapid eye movement (REM) sleep, and percent of non-rapid eye movement (NREM) sleep.ResultsBoth protocols revealed a similar circadian rhythm in the CAR, with peaks occurring at a circadian phase corresponding to 3:40-3:45 a.m., with no detectable CAR during the circadian phases corresponding to the afternoon. In addition to the sinusoidal component of the circadian rhythm, total sleep time was also associated with the CAR for protocol 1. The percent of sleep spent in REM or NREM sleep were not associated with the CAR in either protocol.ConclusionOur results show that the CAR exhibits a robust circadian rhythm that persists even after adjusting for prior sleep. Presuming that the CAR optimizes physiological responses to the anticipated stressors related to awakening, these findings may have implications for shift workers who wake up at unusual circadian phases. A blunted CAR in shift workers upon awakening in the evening may result in diminished responses to stressors.
| S-EPMC9669756 | biostudies-literature
Project description:The cortisol awakening response (CAR), a rapid cortisol rise in the morning after awakening, has been proposed to provide energy to cope with daily demands and suggested to be associated with brain functions. Electroencephalogram (EEG) asymmetry studies have implicated asymmetric cortical activation, especially in frontal cortex, in approach-withdrawal motivation. In this study, we examined the relationship between the CAR and lateralized cortical activity under rest in 55 university male students. Saliva samples were collected at 0, 15, 30 and 60 min after awakening on the two consecutive workdays. The lateralized cortical activity at frontocentral sites was examined by alpha asymmetry score. The results showed that a higher CAR was positively associated with alpha asymmetry score, which indicated that the higher CAR is linked with more left-sided cortical activity at frontocentral sites under resting state. This association still existed even after controlling psychological and sleep quality variables. These results suggested that appropriately mobilizing energy resource storage after awakening revealed as CAR might be associated with goal-directed approach tendencies before any eventual stressful situation, characteristic of more left than right resting-state frontocentral cortical activity.
| S-EPMC6553442 | biostudies-literature
Project description:In older people, less diurnal variability in cortisol levels has been consistently related to worse physical performance, especially to slower walking speed (WS). The cortisol awakening response (CAR) is a discrete component of the hypothalamic-pituitary-adrenal axis that has been related to several health problems, such as cardiovascular disease and/or worse performance on executive function and memory. The relationship between the CAR and physical performance in older people is poorly understood. In this study, in 86 older people (mean age = 64.42, SD = 3.93), we investigated the relationship between the CAR and WS, a commonly used measure of physical performance in the older population that has also been related to health problems, such as cardiovascular disease and executive function performance in older people. Additionally, we studied whether the relationship between the CAR and WS was independent from cortisol levels on awakening and several possible confounders. Results showed that a CAR of reduced magnitude (measured with 3 samples each day, for two consecutive days, and calculated as the area under the curve with respect to the increase), but not cortisol levels on awakening, was related to slower WS. In addition, this relationship was independent from cortisol levels on awakening. It is possible that a CAR of reduced magnitude would contribute to less diurnal cortisol variability, affecting physical performance. Additionally, it is possible that a CAR of reduced magnitude affects WS through a possible negative effect on executive function, or that the association between the CAR and WS is due to the fact that both are related to similar health problems and to changes in cognitive performance in older people.
| S-EPMC4871454 | biostudies-other
Project description:Abnormal hypothalamic-pituitary-adrenal (HPA) axis function, as indexed by elevated diurnal cortisol levels and/or a blunted cortisol awakening response (CAR), has been observed among patients with first episode psychosis and associated with neurocognitive deficits in this population. However, the extent to which these features precede illness onset is unclear. The current study aimed to determine whether children who are at putatively elevated risk for psychosis because they present multiple antecedents of schizophrenia (ASz), and high-risk children with a family history of illness (FHx), are characterized by abnormal cortisol levels when compared with their typically developing (TD) peers. A further aim was to investigate the extent to which cortisol levels are associated with psychosocial stress and neurocognitive function. Thirty-three ASz children, 22 FHx children, and 40 TD children were identified at age 9-12 years using a novel community-based screening procedure or as relatives of individuals with schizophrenia. All participants were antipsychotic-naive and not currently seeking treatment for their symptoms. At age 11-14 years, participants provided salivary cortisol samples and completed psychosocial stress measures and tests of memory and executive function. Results indicated that FHx children, but not ASz children, were characterized by a blunted CAR relative to their TD peers (effect size=-0.73, p=0.01) that was not explained by psychosocial stress exposure or by distress relating to these experiences. Neither FHx nor ASz children were characterized by elevated diurnal cortisol. Among both FHx and ASz children, more pronounced HPA axis function abnormalities (i.e., higher diurnal cortisol levels and greater blunting of the CAR) were associated with poorer performance on tests of verbal memory and executive function. These findings support the notion that at least some HPA axis abnormalities described in psychosis precede illness onset, rather than being a subsequent epiphenomenon. We speculate that the blunted CAR may constitute an early (potentially genetically mediated) marker of psychosis vulnerability, whilst elevated diurnal cortisol levels may emerge only proximally to disease onset.
| S-EPMC4065330 | biostudies-literature
Project description:BACKGROUND:Cognitive impairment, particularly in memory and executive function, is a core feature of psychosis. Moreover, psychosis is characterized by a more prominent history of stress exposure, and by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. In turn, stress exposure and abnormal levels of the main HPA axis hormone cortisol are associated with cognitive impairments in a variety of clinical and experimental samples; however, this association has never been examined in first-episode psychosis (FEP). METHOD:In this study, 30 FEP patients and 26 controls completed assessment of the HPA axis (cortisol awakening response and cortisol levels during the day), perceived stress, recent life events, history of childhood trauma, and cognitive function. The neuropsychological battery comprised general cognitive function, verbal and non-verbal memory, executive function, perception, visuospatial abilities, processing speed, and general knowledge. RESULTS:Patients performed significantly worse on all cognitive domains compared to controls. In patients only, a more blunted cortisol awakening response (that is, more abnormal) was associated with a more severe deficit in verbal memory and processing speed. In controls only, higher levels of perceived stress and more recent life events were associated with a worse performance in executive function and perception and visuospatial abilities. CONCLUSIONS:These data support a role for the HPA axis, as measured by cortisol awakening response, in modulating cognitive function in patients with psychosis; however, this association does not seem to be related to the increased exposure to psychosocial stressors described in these patients.
| S-EPMC3513413 | biostudies-literature
Project description:Background: Internationally deployed humanitarian aid (HA) workers are routinely confronted with potentially traumatic stressors. However, it remains unknown whether HA deployment and related traumatic stress are associated with long-term changes in hypothalamic-pituitary-adrenal (HPA) axis function. Therefore, we investigated whether cortisol awakening response (CAR) decreased upon deployment and whether this was moderated by previous and recent trauma exposure and parallel changes in symptom severity and perceived social support. Methods: In this prospective study, n = 86 HA workers (68% females) completed questionnaires regarding trauma exposure, posttraumatic stress disorder (PTSD), anxiety and depressive symptoms and perceived social support, as well as salivary cortisol assessments at awakening and 30 minutes post-awakening at before, early and 3-6 months post-deployment. Results: Linear mixed models showed significantly decreased CAR (b(SE) = -.036(.011), p = .002) and awakening cortisol over time (b(SE) = -.007(.003), p = .014). The extent of awakening cortisol change was significantly moderated by interactions between previous and recent trauma exposure. Also, a steeper awakening cortisol decrease was significantly associated with higher mean anxiety and PTSD symptoms across assessments. No significant effects were found for social support. Conclusions: We observed attenuated CAR and awakening cortisol upon HA deployment, with a dose-response effect between trauma exposure before and during the recent deployment on awakening cortisol. Awakening cortisol change was associated with PTSD and anxiety symptom levels across assessments. Our findings support the need for organizational awareness that work-related exposures may have long-lasting biological effects. Further research assessing symptoms and biological measures in parallel is needed to translate current findings into guidelines on the individual level.
| S-EPMC7875048 | biostudies-literature
Project description:Background: Anticipation of forthcoming demands is often met with biological up-regulation, for example, levels of the stress hormone cortisol are typically elevated immediately prior to an anticipated event. Similarly, the cortisol awakening response (CAR), a surge in cortisol in the period following waking, is elevated on days of anticipated demand and this is viewed as an adaptive response in the preparation for challenge. This study assessed the effects of competition as an anticipated challenge in elite rowers. Methods: Elite rowers (N = 8) were assessed during two training and two competition weekends. Each assessment involved the measurement of self-reported competitive (cognitive and somatic) anxiety and salivary diurnal cortisol across 2 days representing a preparation day prior to either a training or competition day. Competitive anxiety was measured each morning and saliva samples were provided immediately upon waking and 30 min post waking (CAR) and before bed. Results: Self-reported cognitive and somatic anxiety levels were significantly greater during the competition phase compared with training. Additionally, levels of cognitive anxiety were greater on the day of competition compared with the preparation day. CAR magnitude was significantly reduced during the competition phase compared with training; however, there were no differences between preparation and event days. Conclusions: Reduced or blunted CARs are typically observed in chronically stressed populations and are characteristic of burnout and fatigue. While an increased CAR during competition may represent an adaptive response to challenge, blunted CARs and the concomitant increases in competitive anxiety observed here indicate maladaptive responding during a period where maximized functioning is critical.
| S-EPMC6657667 | biostudies-literature
Project description:Cumulative cortisol burden is known to influence neuropsychiatric and metabolic disorders. To better understand the relationship between daily cortisol exposure and measures of the diurnal circadian cortisol rhythm, we examined the cross-sectional association of the cortisol awakening response (CAR) with wake-up cortisol, bedtime cortisol, diurnal slope, and total cortisol area under the curve (AUC). Up to 18 salivary cortisol samples were collected over 3 days from 935 White, Hispanic, and Black individuals (mean age 65 ± 9.8 years) in the Multi-Ethnic Study of Atherosclerosis. Outcome measures included awakening cortisol, CAR (awakening to 30 min post-awakening), early decline (30 min to 2h post-awakening), late decline (2h post-awakening to bedtime), and the corresponding AUCs. Total cortisol AUC was a summary measure of cumulative cortisol exposure. Higher CAR was associated with significantly lower wake-up cortisol (β=-0.56; 95% CI: -0.59 to -0.53) and a higher early decline AUC (β=0.38; 95% CI: 0.34-0.42) but was not associated with total cortisol AUC (β=0.04; 95% CI: -0.01 to 0.09), or other diurnal cortisol curve components following multivariable adjustment. Total cortisol AUC was significantly and positively associated with wake-up cortisol (β=0.36; 95% CI: 0.32-0.40), bedtime cortisol (β=0.61; 95% CI: 0.58-0.64), and other AUC measures, following multivariable adjustment. Associations were similar by sex, race/ethnicity, and age categories. We conclude that bedtime cortisol showed the strongest correlation with total cortisol AUC, suggesting it may be a marker of daily cortisol exposure.
| S-EPMC3812410 | biostudies-literature
Project description:ObjectivesStudies on hypothalamus-pituitary-adrenal (HPA) axis activity in stress-related exhaustion and burnout have revealed incongruent results, and few longitudinal studies on clinical populations have been performed. This study was designed to investigate differences in HPA axis activity between patients with stress-related exhaustion and healthy controls and to investigate longitudinal changes in HPA axis activity in the patient group as they entered a multimodal treatment programme.DesignHPA axis activity was assessed through the cortisol awakening response (CAR). Salivary cortisol was sampled at awakening and after 15 min. Follow-up measurements were performed in the patient group after 3, 6, 12 and 18 months.SettingAn outpatient clinic specialising in stress-related illness.ParticipantsPatients with clinically diagnosed stress-related exhaustion (n=162) and healthy controls (n=79).Primary and secondary outcome measuresThe primary measure was CAR measured as the difference between the two salivary cortisol samples. Changes in CAR during follow-up were related to changes in symptoms of burnout, depression and anxiety.ResultsPatients showed similar CAR as the controls and their CAR did not change significantly during treatment. No association was found between CAR and symptom development during treatment.ConclusionsThe authors conclude that CAR does not seem to discriminate clinically defined patients with exhaustion from healthy controls and it appears not to change during treatment. CAR, measured as salivary cortisol, at awakening and after 15 min, is thus not a valid marker for stress-related exhaustion.
| S-EPMC3400075 | biostudies-literature
Project description:IntroductionCortisol levels in adults show a sharp decrease from mid-morning to mid-afternoon. Most toddlers take afternoon naps, which is associated with a less mature diurnal pattern characterized by a midday plateau in cortisol secretion. Napping in preschoolers produces a robust cortisol awakening response (CAR), which may account for such maturational differences. This experimental study extends prior work by examining whether the presence and timing of the nap-dependent CAR influences the diurnal cortisol pattern in toddlers.MethodsToddlers (n = 28; 13 females; 30-36 months) followed a strict biphasic sleep schedule (≥ 12.5h time in bed; ≥ 90 min nap) for ≥ 3 days before each of four randomly ordered, in-home cortisol assessments. For each assessment, saliva samples were obtained at morning awakening, ∼ 09:30, pre-nap, 0, 15, 30, 45, 90, and 135 min post-nap awakening (verified with actigraphy), and ∼ 19:30. On one day, children napped at their scheduled time, and parents collected saliva samples. On another day, children missed their nap, and parents collected saliva samples at matched times. On two other days, children napped 4h (morning) and 7h (afternoon) after awakening in the morning, during which time researchers collected pre- and post-nap saliva samples. Saliva was assayed for cortisol (μg/dl).ResultsThree-level multilevel models were used to estimate the CAR and diurnal cortisol patterns in all four conditions. Compared to the no-nap condition (no observed CAR; b = -0.78, p = 0.65), we found a pronounced cortisol rise following the morning nap (b = 11.00, p < 0.001) and both afternoon naps whether samples were collected by parents (b = 5.19, p < 0.01) or experimenters (b = 4.97, p < 0.01). Napping in the morning resulted in the most robust post-nap cortisol rise (b = 10.21, p < 0.001). Diurnal patterns were analyzed using piecewise growth modeling that estimated linear coefficients for five separate periods throughout the day (corresponding to morning decline, noon decline, post-nap rise, post-nap decline, and evening decline). We observed a significant post-nap rise in cortisol values on the parent-collected afternoon nap (b = 3.41, p < 0.01) and the experimenter-collected morning nap (b = 7.50, p < 0.01) days as compared to the no-nap day (b = -0.17, p = 0.82). No other differences in diurnal profiles were observed between the parent-collected nap and no-nap conditions; however, toddlers had a steeper evening decline on the day of the morning nap compared to the parent-collected afternoon nap (b = 0.30, p < 0.05) and no-nap conditions (b = 0.27, p < 0.05).DiscussionThese well-controlled findings suggest that the presence and timing of daytime naps influence the pattern of diurnal cortisol secretion in toddlers. They also provide support for the hypothesis that napping is the primary state driving the immature midday plateau in cortisol secretion, which becomes more adult-like across childhood. Prior studies of the diurnal cortisol pattern have employed a cubic model, and therefore, have not detected all possible variations due to napping. Our experimental data have important methodological implications for researchers examining associations between the slope of the diurnal cortisol pattern and developmental outcomes, as well as those utilizing afternoon cortisol reactivity protocols in napping children.
| S-EPMC4526341 | biostudies-literature