Cortisol Awakening Response Research Articles

Effects of Sleep Fragmentation and Estradiol Decline on Cortisol in a Human Experimental Model of Menopause.

Perturbations to the hypothalamic-pituitary-adrenal (HPA) axis have been hypothesized to increase postmenopausal cardiometabolic risk. Although sleep disturbance, a known risk factor for cardiometabolic disease, is prevalent during the menopause transition, it is unknown whether menopause-related sleep disturbance and estradiol decline disturb the HPA axis. We examined the effect of experimental fragmentation of sleep and suppression of estradiol as a model of menopause on cortisol levels in healthy young women. Twenty-two women completed a 5-night inpatient study during the mid-to-late follicular phase (estrogenized). A subset (n = 14) repeated the protocol after gonadotropin-releasing hormone agonist-induced estradiol suppression. Each inpatient study included 2 unfragmented sleep nights followed by 3 experimental sleep fragmentation nights. This study took place with premenopausal women at an academic medical center. Interventions included sleep fragmentation and pharmacological hypoestrogenism, and main outcome measures were serum bedtime cortisol levels and cortisol awakening response (CAR). Bedtime cortisol increased 27% (P = .03) and CAR decreased 57% (P = .01) following sleep fragmentation compared to unfragmented sleep. Polysomnographic-derived wake after sleep-onset (WASO) was positively associated with bedtime cortisol levels (P = .047) and negatively associated with CAR (P < .01). Bedtime cortisol levels were 22% lower in the hypoestrogenized state compared to the estrogenized state (P = .02), while CAR was similar in both estradiol conditions (P = .38). Estradiol suppression and modifiable menopause-related sleep fragmentation both independently perturb HPA axis activity. Sleep fragmentation, commonly seen in menopausal women, may disrupt the HPA axis, which in turn may lead to adverse health effects as women age.

A Pilot Study of the Biofeedback Training to Reduce Salivary Cortisol Level and Improve Mental Health in Highly-Trained Female Athletes.

Biofeedback (BFB) training can provide a useful resource for athletes to cope with stress. However, the effects of BFB training on acute and chronic endocrine stress responses, parasympathetic activity, and mental health in competitive athletes have not been explored yet. This pilot study examined the effects of a 7-week BFB training on psychophysiological parameters in highly trained female athletes. Six highly trained female volleyball players (mean age: 17.50 ± 1.05 years) volunteered to participate in the study. Athletes individually attended 21-session heart rate variability (HRV)-BFB training consisting of six minutes for 7 weeks. A BFB device (Nexus 10) was used to measure the athletes' physiological responses reflecting HRV. To assess the cortisol awakening response (CAR), saliva samples were collected immediately after awakening and 15min, 30min, and 60min post-awakening. The Depression Anxiety Stress Scale-21 was filled out before and after the intervention to assess mental health. Furthermore, athletes provided saliva samples during eight sessions pre- and immediately post-session. Mid-day cortisol levels decreased significantly after the intervention. No significant change was observed in CAR and physiological responses after the intervention. A significant decrease in cortisol level was observed in BFB sessions in which cortisol level was assessed, except for two sessions. We concluded that short sessions of 7-week HRV-BFB training could be used as an effective method to control autonomic functions and stress of female athletes. Although the present study provides strong evidence for the psychophysiological well-being of athletes, further investigations with larger samples are needed.

High Trait Anxiety Predicts Decreased Cortisol Awakening Response

High Trait Anxiety Predicts Decreased Cortisol Awakening Response

The effect of chronic academic stress on intentional forgetting.

This study investigated whether chronic academic stress could affect the directed forgetting (DF) process. Both the stress group (undergoing preparation for a major academic examination) and the control group performed a DF task. A forgetting cue was presented after a to-be-forgotten (TBF) word, whereas no cue appeared after a to-be-remembered (TBR) item in the study phase. An old/new recognition test was used in the test phase. The results showed that (1) the stress group showed a higher level of self-reported stress, state anxiety, negative affect, and decreased cortisol awakening response (CAR) compared with the control group, suggesting a higher level of stress for the stress group. (2) Both groups showed superior recognition performance of TBR than TBF items, suggesting a DF effect. (3) The stress group showed inferior recognition performance of TBF items and an enhanced DF effect compared with the control group. These results demonstrated that the intentional memory control process might be enhanced under chronic academic stress.

Biopsychological trait markers supporting the stress-diathesis model in functional neurological disorders. (S51.010)

<h3>Objective:</h3> To shed light on the underlying neurobiological mechanisms of functional neurological disorders (FND), we analysed the relationship between potential dysregulation of the Hypothalamic-Pituitary Adrenal (HPA) axis, trauma history, and structural brain abnormalities. <h3>Background:</h3> Stress is a well-known risk factor to develop FND. Only little is known about the biological stress regulation, and what might be the role of predisposing biological and psychosocial risk factors. <h3>Design/Methods:</h3> We set out to study the HPA axis analysing the cortisol awakening response and diurnal baseline cortisol in 86 patients with mixed functional neurological symptoms compared to 76 healthy controls. We then examined the association between cortisol regulation and severity and duration of traumatic life events. Finally, we analysed volumetric brain alterations in brain regions particularly sensitive to psychosocial stress, acting on the assumption of the neurotoxic effect of prolonged cortisol exposure. <h3>Results:</h3> Overall, patients had a significantly flatter cortisol awakening response (<i>P</i> &lt; 0.001) and reported longer (<i>P</i> = 0.01) and more severe (<i>P</i> &lt; 0.001) emotional neglect as compared to heathy controls. Moreover, volumes of bilateral hippocampus and amygdala were found to be reduced in patients. Using a partial least squares correlation, we found that in patients, emotional neglect plays a role in the multivariate pattern between trauma history and HPA axis dysfunction, whilst cortisol did not relate to reduced brain volumes. <h3>Conclusions:</h3> In summary, this study supports a stress-diathesis model for FND and showed an association between different attributes of trauma history and abnormalities in HPA-axis function. Moreover, we suggest that reduced hippocampal- and amygdalar volumes represent a biological ‘trait marker’ for FND patients, which might contribute to a reduced resilience to stress. <b>Disclosure:</b> Mrs. Weber has nothing to disclose. Mrs. Bühler has nothing to disclose. Mr. Loukas has nothing to disclose. Dr. Aybek has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Swiss Movement Disorder Foundation. The institution of Dr. Aybek has received research support from Swiss National Science Foundation.

Exploring role of sleep aids in sleep problems in preschool children

It is well known that children use sleep aids, such as blankets or soft toys, at bedtime. However, there is a lack of understanding regarding the factors associated with their use and role in addressing sleep problems. This study investigated 96 Japanese children aged 40 to 47 months to examine these associations. We measured children’s stress (through a questionnaire and salivary cortisol [cortisol awakening response]), anxiety symptoms, behavioral problems, and temperament, and created a model to predict the status of sleep aid use. Furthermore, we explored the association between sleep aid use and children’s sleep problems as evaluated by their caregivers. We found that children who used sleep aids were more likely to experience anxiety symptoms. Moreover, most children used sleep aids even when they co-slept with their caregivers and/or siblings. Their use was not uniquely associated with sleep problems. These findings suggest that sleep aid serves as a defense against anxiety, including that caused by the absence of a caregiver, rather than as a substitute for a caregiver. Our study sheds light on their role and emphasizes the importance of viewing development within the complex interactive processes of humans and objects.

Changes in cortisol awakening responses (CAR) in menopausal women through short-term marine healing retreat program with specific factors affecting each CAR index.

Recent studies have reported that the cortisol awakening response (CAR) is associated with various health risks. The different indices used to represent the CAR include the average cortisol levels in the morning immediately after waking (AVE); the total area under the curve of cortisol levels with respect to ground (AUCg); and the area under the curve of cortisol levels with respect to increase (AUCi). However, it is unclear which physiological phenomenon each index reflects. This study investigated the factors, such as stress, circadian rhythm, sleep, and obesity, affecting the CAR through a marine retreat-based healing program in which the anticipated stress of the participants could be controlled to some degree. Fifty-one menopausal women in their 50s and 60s were included, who performed beach yoga and Nordic walking for four days at an uncontaminated beach. The baseline CAR indices showed that the AVE and AUCg were significantly higher in the high sleep efficiency group than in the low sleep efficiency group. However, the AUCi decreased substantially with increasing age. The changes in the AVE, AUCg, and AUCi were calculated through the program, and it was found that the AVE and AUCg increased significantly more in the obese group than in the normal and overweight groups. The obese group also showed significantly decreased serum triglyceride and BDNF (brain-derived neurotrophic factor) levels compared to the low BMI group. Thus, it was confirmed that AVE and AUCg reflected physiological phenomena affected by factors such as sleep efficiency and obesity, whereas the AUCi was affected by factors such as age. In addition, the marine retreat program can improve the low levels of CAR associated with obesity and aging.

Pregnancy-specific anxiety and gestational length: The mediating role of diurnal cortisol indices

BackgroundPreterm birth or shorter gestation is a common adverse pregnancy outcome. Pregnancy-specific anxiety is robustly associated with risk for shorter gestation. Hypothalamic-pituitary-adrenal (HPA) dysregulation, indicated by diurnal cortisol index variability [slope, area-under-the-curve (AUC) or cortisol awakening response (CAR)], could mediate associations between pregnancy-specific anxiety and shorter gestation. The purpose of this study was to explore whether diurnal cortisol index variability mediates associations between pregnancy-specific anxiety and gestational length. MethodsA sample of 149 women from the Healthy Babies Before Birth study reported pregnancy-specific anxiety in early pregnancy. Saliva samples were taken at three times during pregnancy, for two days each, at wake, 30 min post wake, noon, and evening. Diurnal cortisol indices were calculated using standard approaches. Pregnancy cortisol index variability was calculated across pregnancy timepoints. Gestational length was derived from medical charts. Covariates were sociodemographics, parity and obstetric risk. Mediation models were tested using SPSS PROCESS. ResultsThere was a significant indirect effect of pregnancy-specific anxiety on gestational length via CAR variability, b(SE)= −0.102(0.057), .95CI [− 0.227,− 0.008]. Higher pregnancy-specific anxiety was associated with lower CAR variability, b(SE)= −0.019(0.008), p = .022, and lower CAR variability was associated with shorter gestation, b(SE)= 5.29(2.64), p = .047. Neither AUC or slope variability mediated associations between pregnancy-specific anxiety and gestational length. ConclusionLower CAR variability during pregnancy mediated the association between higher pregnancy-specific anxiety and shorter gestational length. Pregnancy-specific anxiety could dysregulate HPA axis activity, as indicated by lower CAR variability, demonstrating the importance of the HPA axis system in regulating pregnancy outcomes.

Prenatal depression moderates the relationship between maternal trauma exposure and cortisol production and predicts breastfeeding behavior

ABSTRACT Trauma exposure is associated with many negative outcomes for women during the prenatal and postnatal periods, including increased antenatal depressive symptomatology and dysregulation of the body’s stress responses. Trauma exposure and its consequences are also tied to women’s ability to breastfeed, a crucial component in maternal and infant health. Cortisol is biologically relevant to the breastfeeding process, and is also associated with depressive symptoms, which may interfere with women’s ability to successfully maintain breastfeeding. However, no known studies integrate prenatal cortisol and depressive symptom severity into models of relations between trauma exposure and breastfeeding, particularly while considering trauma timing and type. Therefore, the current study did so using data from a historically understudied sample. Data were drawn from a community sample of 96 women residing in a health professional shortage area for mental health and primary care. Participants provided data during their third trimester of pregnancy and 6 months postpartum. Three moderated mediation models were tested to explore relations among history of trauma, breastfeeding, and related variables. Increased prenatal depressive symptoms were related to elevated prenatal cortisol awakening response, as well as moderated the relationship between interpersonal trauma exposure and greater prenatal cortisol awakening response. A significant positive correlation was also found between trauma and prenatal depressive symptoms, as well as a significant negative correlation between prenatal depressive symptoms and breastfeeding frequency. Results suggest that subclinical prenatal depressive symptoms may interact with trauma symptoms to affect women’s stress responses and breastfeeding behaviors, and that women at risk for breastfeeding difficulty may be identified prenatally.

Effects of left anodal transcranial direct current stimulation on hypothalamic–pituitary–adrenal axis activity in depression: a randomized controlled pilot trial

The main objective of this study was to evaluate the effect of left anodal transcranial direct current stimulation (tDCS) on hypothalamic–pituitary–adrenal axis (HPAA) activity in individuals with depression. We conducted a 3-week, randomized, triple-blind pilot trial with 47 participants (dropout rate: 14.89%) randomly assigned to either the tDCS or control group (sham stimulation). Salivary cortisol was used as an HPAA activity marker since cortisol is the effector hormone of the HPAA. The primary outcome was the effect of tDCS on the diurnal cortisol pattern (DCP and area under the curve with respect to ground -AUCg-). Secondary outcomes included tDCS effects on cortisol awakening response (CAR) and cortisol decline (CD), as well as the variation of cortisol concentrations between the initiation of tDCS and 2 weeks later. Intention-to-treat and per-protocol analyses were conducted. Our primary outcome showed an absent effect of tDCS on DCP and AUCg. Additionally, tDCS had an absent effect on CAR, CD, and cortisol concentration variation before-after stimulation. Our pilot study suggests that anodal tDCS showed an absent effect on HPAA activity in individuals with depression. More studies are needed to confirm these findings.

Hugs and Cortisol Awakening Response the Next Day: An Ecological Momentary Assessment Study

Previous research suggests that affectionate touch such as hugs might downregulate stress systems such as the hypothalamic pituitary adrenal (HPA) axis. However, the current literature lacks in generalizability beyond the laboratory setting and outside the context of romantic relationships. The cortisol awakening response (CAR) is a measure of the HPA axis and is responsive to daily fluctuations in stress and social information. However, associations between affectionate touch and the CAR have never been assessed. This study used ecological momentary assessment (EMA) to measure daily hugging behaviors in 104 first-year college students and salivary cortisol to assess the CAR. Participants who reported more daily hugs in their social interactions had significantly smaller CARs the next morning compared to days they reported fewer hugs. This study contributes to the literature on social interactions and stress responsive systems and emphasizes the importance of assessing affectionate touch behaviors such as hugs that can be exchanged outside the context of romantic relationships.

Lifetime discrimination, habitual and daily everyday discrimination, and diurnal cortisol among older African Americans adults

Experiences of discrimination can be major life events or daily chronic hassles that occur in various social contexts (e.g., housing, education, employment) and have been found to predict adverse health outcomes, including dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. Previous work on daily cortisol dynamics has generally revealed an association between discrimination and flatter cortisol slopes, particularly among racial minorities. However, most of the existing studies have focused on youth and young adults, with little work among older adults. The current study aimed to investigate the relationship between three measures of discrimination (lifetime discrimination, habitual everyday discrimination, and daily everyday discrimination) and diurnal cortisol secretion in a sample of 203 older African Americans. Study results indicated that individuals reporting higher levels of lifetime discrimination experienced morning hypocortisolism and flatter diurnal cortisol slopes. Exploratory analyses also showed that prior daily everyday discrimination was significantly associated with blunted cortisol awakening response (CAR) the next day. Our findings underline the role of discrimination in modulating daily cortisol dynamics among older African American adults and advance knowledge on how social stressors influence healthy aging.

Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial.

Mental contrasting with implementation intentions (MCII) has been successfully applied to improve health-related behaviors (e.g. exercise). We explored its effectiveness to improve sleep outcomes beyond effects of sleep hygiene (SH) information, and investigated associations with stress. Eighty university employees (mean age: 29.6, SD = 4.5) were randomized to either a MCII + SH or a SH-only condition. During a baseline-week and a post-intervention week, sleep duration (Fitbit Alta and self-report), sleep quality, and stress were assessed daily and saliva was collected to assess the cortisol awakening response (CAR). In total, self-reported sleep quality and duration increased, but there was no meaningful condition*week interaction for sleep parameters or CAR. Higher average stress was associated with shorter sleep duration and lower sleep quality. Within-person, days with higher stress were followed by nights with lower sleep quality. Despite overall improvements, effects of MCII were not confirmed. MCII might be less effective to improve behaviors which are less controllable.

Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk.

Coronary heart disease (CHD) and its major risk factor hypertension have both been associated with altered activity of the hypothalamus-pituitary-adrenal (HPA)-axis but the biological mechanisms underlying prospective associations with adverse disease outcomes are unclear. We investigated diurnal HPA-axis activity in CHD-patients, hypertensive (HT) and healthy normotensive men (NT) and tested for prospective associations with biological CHD risk factors. Eighty-three male CHD-patients, 54 HT and 54 NT men repeatedly measured salivary cortisol over two consecutive days. Prospective CHD risk was assessed by changes between baseline and follow-up in the prothrombotic factors D-dimer and fibrinogen, the pro-inflammatory measures interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and acute phase protein C-reactive protein (CRP), as well as blood lipids in terms of total cholesterol (tChol)/high-density-lipoprotein cholesterol (HDL)-ratio. We aggregated coagulation and inflammatory measures to respective indices. The groups differed in repeated daytime cortisol (dayCort) secretion (p=.005,η2 p=.03,f=0.18) and cortisol awakening response (CAR) (p=.006,η2 p=.03,f=0.18), with similarly lower overall dayCort and CAR in CHD-patients and HT, as compared to NT. The groups differed further in cortisol at awakening (p=.015,η2 p=.04,f=0.20) with highest levels in HT (p´s≤.050), and in diurnal slope between waking and evening cortisol (p=.033,η2 p=.04,f=0.20) with steepest slopes in HT (p´s≤.039), although in part not independent of confounders. Lower aggregated dayCort and CAR in terms of area-under-the-curve (AUC) independently predicted increases in future overall CHD risk (AUCdayCort: p=.021,η2 p=.10,f=0.33;AUCCAR: p=.028,η2 p=.09,f=0.31) 3.00 ± 0.06(SEM) years later, with risk prediction most pronounced in fibrinogen (AUCdayCort: p=.017,ΔR 2= 0.12;AUCCAR: p=.082). We found evidence for an HPA-axis hypoactivity in CHD and HT with lower diurnal HPA-axis activity predicting increases in cardiovascular risk as evidenced by increases in circulating levels of biomarkers of atherothrombotic risk. Down-regulation of basal HPA-axis activity may contribute to the pathogenesis of atherosclerosis and thrombosis in CHD via effects on coagulation.

The association between the cortisol and cortisone awakening responses

The cortisol awakening response (CAR) is often assessed in the saliva and considered to be representative of serum cortisol. However, free cortisol is rapidly converted into cortisone as it passes from the serum into the saliva. Because of this enzymatic conversion, the salivary cortisone awakening response (EAR) may be more closely related to serum cortisol dynamics than the salivary CAR. Therefore, the purpose of this study was to measure the EAR and CAR in saliva and compare it to the serum CAR. MethodsMale participants (n = 12) had an intravenous catheter placed for serial serum sampling and completed two overnight laboratory sessions, wherein participants slept in the laboratory and saliva and serum samples were collected every 15 min after volitional awakening the following morning. Serum was assayed for total cortisol and saliva for cortisol and cortisone. The CAR and EAR was assessed in saliva and the CAR in serum via mixed-effects growth models and common awakening response indices (area under the curve [AUC] relative to the ground [AUCG] and relative to the increase [AUCI], and change scores [Δ]). ResultsThere was a distinct rise in salivary cortisone following awakening demonstrating the presence of a discernable EAR (βQuadratic = −41.18, [95%CI = −68.90 to −13.46], p < 0.004, Conditional R2 = 0.641). Two EAR indices (AUCG: p < 0.001 and AUCI: p = 0.030) were associated with the corresponding serum CAR indices. ConclusionWe demonstrate for the first time a distinct cortisone awakening response. The results suggest the EAR may be more closely related to serum cortisol dynamics during the post-awakening period, and thus, may be a biomarker of interest in addition to the CAR for assessing hypothalamic-pituitary-adrenal axis functioning.

Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in patients with psychogenic erectile dysfunction.

Psychological stress and its two stress response systems, the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), are closely related to psychogenic erectile dysfunction (pED). However, the analyses of perceived stress and stress systems in pED patients need to be more in-depth, especially the interactions between them. Our study included 75 patients with pEDs and 75 healthy men. The International Index of Erectile Function-5 (IIEF-5) and the 10-item Perceived Stress Scale (PSS-10) were used for assessing the severity of ED and perceived stress. All participants collected saliva samples on three consecutive days at eight specific times with strict reference to the time of morning awakening for measuring cortisol parameters and wore electrocardiography for 24h to derive heart rate variability (HRV). The PSS-10 scores of pED patients were significantly higher than the control group (p<0.001). Although PSS-10 and IIEF-5 scores were negatively correlated in pED patients, there was no statistical significance between them (r=-0.049, p=0.677). Compared with the control group, the HRV parameters of pED patients were significantly increased in LF/HF ratio (p=0.014) but significantly decreased in LF, HF, and pNN50 (p<0.001). However, the two groups had no statistically significant differences in cortisol variables (all p>0.05). The interaction between sympathovagal modulation (HF, rMSSD) and cortisol awakening response (CAR AUCi) explained significantly greater variance in perceived stress than either stress system alone. Higher parasympathetic activity combined with a higher cortisol awakening response was associated with greater perceived stress. Our results suggested that the interrelation between ANS and HPA axis activity might enhance our comprehension of how stress affected the physical and mental health of pED patients.

Clinical and neuroendocrine correlates of childhood maltreatment history in adults with bipolar disorder

IntroductionChildhood maltreatment (CM) has been associated to an increased risk of developing bipolar disorder (BD). A role of the hypothalamus-pituitary-adrenal (HPA) axis in mediating trauma-related risk for adult psychopathology has been suggested but scarcely investigated in BD.ObjectivesThe aim of this study is to explore the impact of childhood maltreatment on clinical features of BD and on the activity of the HPA axis.MethodsOne hundred and six patients participated in the study. On the basis of their history of childhood trauma, as assessed by the Childhood Trauma Questionnaire (CTQ), they were divided into a group with a history of childhood maltreatment (CM+) and a group without (CM−). Twenty-nine participants (16 with a history of childhood trauma and 13 without) underwent the cortisol awakening response (CAR) test. Saliva cortisol concentrations were determined by an enzyme immunoassay method, using a commercially available ELISA kit.ResultsAccording to CTQ, 62 had a history of childhood maltreatment and 44 had not. CM was significantly more frequent in females than males. CM+ patients showed significant higher body mass index (p = .01), number of suicide attempts (p = .03), and more severe mania symptoms (p = .01) than CM− ones. Significant associations between lifetime suicide attempts and any type of childhood maltreatment (OR = 2.79; CI = 1.01-7.73) and between emotional abuse and the presence of psychotic symptoms (OR = 2.74, CI = 1.11-6.74) or mixed mood episodes were found (OR = 2.62, CI = 1.07-6.43). Moreover, CM+ individuals with BD exhibited a significantly reduced CAR with respect to CM− ones.ConclusionsOur results add to literature findings showing a worse clinical course in BD patients with a history of childhood maltreatment and show for the first time that childhood trauma exposure is associated to impaired CAR in adults with BD.Disclosure of InterestNone Declared

Influences on Stress Load in Young Girls with Major Depression

Based on former empirical studies and theoretical models the present study investigated, whether stress symptoms, stress coping, and activity of HPA axis are different in girls with major depression compared to non-depressed controls. 148 girls with a mean age of 15 years were studied twice with 6 months between the two assessments. 74 fulfilled DSM IV criteria for major depression at first assessment. Stress symptoms and stress coping were measured with validated German questionnaires. The cortisol awakening response was analyzed by collecting saliva samples. Depressed girls showed a greater stress load, which was significantly influenced by stress coping strategies. HPA axis activity was heightened in depressed girls, but does not seem to have an influence on stress load.

CARWatch – A smartphone application for improving the accuracy of cortisol awakening response sampling

BackgroundMany studies investigating the cortisol awakening response (CAR) suffer from low adherence to the study protocol as well as from the lack of precise and objective methods for assessing the awakening and saliva sampling times which leads to measurement bias on CAR quantification. MethodsTo address this issue, we have developed “CARWatch”, a smartphone application that aims to enable low-cost and objective assessment of saliva sampling times as well as to concurrently increase protocol adherence. As proof-of-concept study, we assessed the CAR of N = 117 healthy participants (24.2 ± 8.7 years, 79.5% female) on two consecutive days. During the study, we recorded awakening times (AW) using self-reports, the CARWatch application, and a wrist-worn sensor, and saliva sampling times (ST) using self-reports and the CARWatch application. Using combinations of different AW and ST modalities, we derived different reporting strategies and compared the reported time information to a Naive sampling strategy assuming an ideal sampling schedule. Additionally, we compared the AUCI, computed using information from different reporting strategies, against each other to demonstrate the effect of inaccurate sampling on the CAR. ResultsThe use of CARWatch led to a more consistent sampling behavior and reduced sampling delay compared to self-reported saliva sampling times. Additionally, we observed that inaccurate saliva sampling times, as resulting from self-reports, were associated with an underestimation of CAR measures. Our findings also revealed potential error sources for inaccuracies in self-reported sampling times and showed that CARWatch can help in better identifying, and possibly excluding, sampling outliers that would remain undiscovered by self-reported sampling. ConclusionThe results from our proof-of-concept study demonstrated that CARWatch can be used to objectively record saliva sampling times. Further, it suggests its potential of increasing protocol adherence and sampling accuracy in CAR studies and might help to reduce inconsistencies in CAR literature resulting from inaccurate saliva sampling. For that reason, we published CARWatch and all necessary tools under an open-source license, making it freely accessible to every researcher.

Stress, hypothalamic pituitary adrenal axis activity and autonomic nervous system function in adolescents with insomnia

IntroductionAbnormal stress responses have been linked to the etiology of insomnia. We investigated the relationship between insomnia, stress, hypothalamic-pituitary-adrenal (HPA) axis activity, and autonomic nervous system (ANS) function in adolescence. MethodsForty-seven post-pubertal adolescents (16–20 years old, 28 female) with (N = 16; insomnia group) and without (N = 31; control group) DSM-5 insomnia symptoms were assessed for stress levels and stress reactivity and underwent a standardized stress protocol (Trier Social Stress Test (TSST)), after an overnight laboratory stay. Cortisol was measured upon awakening and 30-minutes later to calculate the cortisol awakening response (CAR). During the TSST, perceived stress, salivary cortisol (HPA activity), heart rate (HR) and blood pressure (BP) measures were collected. ResultsParticipants in the insomnia group reported more stress from school performance and work overload, with insomnia girls experiencing more stress from peer pressure and future uncertainty than control girls (p < 0.05). No group differences were detected in the CAR and pre-TSST stress levels. All participants showed significant increases in perceived stress (~19 %), HR (~33 %), systolic (~13 %), and diastolic (~15 %) BP in response to the TSST (p < 0.05). Overall HR stress response did not differ between groups, but was lower in boys with insomnia than in girls with insomnia (p < 0.05). Cortisol stress responses were inconclusive, possibly due to a masking effect of CAR, as the task was performed shortly after awakening and larger CARs were associated with blunted cortisol stress responses. DiscussionResults mostly show no group difference in physiological stress responses, although some interaction effects suggest a potential sex by insomnia interaction. Larger samples are needed to understand the physiological disturbances of insomnia in adolescence.