The cortisol awakening response (CAR) across the female menstrual cycle

The cortisol awakening response (CAR) has been established as a useful marker of hypothalamus-pituitary-adrenal (HPA) axis activity and has become a standard tool for stress research in ambulatory settings. Although much knowledge has been accumulated on a variety of factors modulating the CAR, the impact of the female menstrual cycle, especially during ovulation, still remains unclear. To the best of our knowledge, this is the first study that measured the CAR during menses, the follicular phase, ovulation and the luteal phase in a repeated measurement design. For this purpose, a final sample of 29 naturally cycling, healthy, non-smoking, and medication-free women collected saliva samples directly after awakening as well as 30, 45, and 60 min later during each of the four different phases. To determine the timing of ovulation, an ambulatory chromatographic ovulation test kit was applied. A repeated measurements ANOVA resulted in a significant interaction effect sample × cycle phase (p=0.04), with the highest awakening response during ovulation. While awakening cortisol levels were comparable across the four cycle phases (p=n.s.), the net increase was significantly elevated during ovulation (p=0.05). Our data also confirmed earlier cross-sectional results reporting no differences in the CAR between the follicular and luteal phase. Finally, a concurrent assessment of mood applying the POMS (Profile of Mood States) yielded no differences across the four cycle phases (all p=n.s.). In sum, the present data points to the idea that the CAR is elevated during ovulation, an effect which is presumably mediated by elevated sex steroid levels during the ovulation period.     

The effect of depression, anxiety and early life trauma on the cortisol awakening response during pregnancy: preliminary results

The purpose of this study was to examine the effects of maternal depression and anxiety on the cortisol awakening response (CAR), a marker of the hypothalamic-pituitary-adrenal (HPA) axis function, during pregnancy. Sixty-six pregnant women were studied between 25 and 33 weeks of gestation and were identified as either Depressed (n=33) or healthy, Control (n=33), based on depression scores and lifetime psychiatric history. Saliva samples were collected (passive drool) upon awakening and at +30 and +60 min thereafter. The CAR was not significantly different between women who were depressed during pregnancy compared to healthy control women. However, women taking antidepressant (AD) medication showed an attenuated CAR (time x AD use interaction, p=0.06). Childhood maltreatment (as measured with the Childhood Trauma Questionnaire) was associated with a lower baseline cortisol concentration explaining 12% of the variance, controlling for wake-up time and AD use. There is a complex interplay of factors involved in the HPA axis regulation of vulnerable women during pregnancy, including depression, anxiety, early life stress and psychotropic medication use, which remain unclear. The CAR may provide important information about the maternal HPA axis during pregnancy and warrants further investigation in larger cohorts.     

The cortisol awakening response: a pilot study on the effects of shift work, morningness and sleep duration

This study concerned the possible influence of experimental shift work, morningness and sleep length on the cortisol awakening response (CAR). Eight morning-oriented (MT) and eight evening-oriented (ET) healthy young men (19-27 years) slept after three consecutive day shifts during the night and after three consecutive night shifts during the day in the laboratory. Salivary cortisol concentrations were ascertained after each sleep period upon awakening and half an hour later, half-hourly during work shifts, and hourly during two 24-h periods, after the three day shift/night sleep sequences and after the three night shift/day sleep sequences. Statistical analyses considered the temporal position of sleep (night, day), the succession of sleep periods, the diurnal type and the polysomnographically verified total sleep time. The CAR was significantly smaller after day than after night sleep and increased significantly with total sleep time in ET. MT had moderately higher cortisol concentrations upon awakening than ET probably because they wake up at a later time of their circadian rhythm. But neither the CARs nor the cortisol concentrations during the following work shifts or during the 24h profiles were different in both diurnal types. The cortisol concentrations during work shifts correlated significantly with the previous post-awakening concentrations in MT but not in ET. Due to the small samples further studies are needed.     

Associations of the cortisol awakening response (CAR) with cortical activation asymmetry during the course of an exam stress period

The cortisol awakening response (CAR) is a cortisol rise which is distinct from the circadian rise in hypothalamus-pituitary-adrenal (HPA) axis activity before awakening. The CAR has been shown to be related to experiences of stress and negative affect, and activation of neocortical networks has been suggested as a mechanism. Right-sided cortical activation has been shown to be correlated with negative affect, and an association of electroencephalogram (EEG) asymmetry measures with cortisol secretion has been demonstrated. Therefore, we investigated for associations of the CAR with lateralised trait-like cortical activation and with changes in EEG asymmetry during a putative stressful period. We examined 37 undergraduate students before, during, and after an academic exam period. CARs were measured five times and EEG was measured both about 6 weeks before the beginning of the exams and 1 day before an exam. Trait-like interindividual differences in posterior cortical asymmetry were differentially associated with CARs at different measurement occasions. Participants with greater right centroparietal cortical trait activation showed an increased CAR in anticipation of the exams, whereas all other participants showed an increased CAR in response to the exams. Furthermore, EEG measures taken directly before the exam revealed that greater right frontal cortical activation was related to higher cortisol levels after awakening. The results suggest that lateralised cortical activation moderates CAR changes during the course of a stressful period. Lateralised cortical activation may be an important link between the CAR and health-related variables like experiences of stress and negative affect.     

The cortisol awakening response: More than a measure of HPA axis function

In most healthy people morning awakening is associated with a burst of cortisol secretion: the cortisol awakening response (CAR). It is argued that the CAR is subject to a range physiological regulatory influences that facilitate this rapid increase in cortisol secretion. Evidence is presented for reduced adrenal sensitivity to rising levels of ACTH in the pre-awakening period, mediated by an extra-pituitary pathway to the adrenal from the suprachiasmatic nucleus (SCN). A role for the hippocampus in this pre-awakening regulation of cortisol secretion is considered. Attainment of consciousness is associated with ‘flip-flop’ switching of regional brain activation, which, it is argued, initiates a combination of processes: (1) activation of the hypothalamic pituitary adrenal (HPA) axis; (2) release of pre-awakening reduced adrenal sensitivity to ACTH; (3) increased post-awakening adrenal sensitivity to ACTH in response to light, mediated by a SCN extra-pituitary pathway. An association between the CAR and the ending of sleep inertia is discussed.     

The effect of repeated virtual nicotine cue exposure therapy on the psychophysiological responses: a preliminary study

Objective

Smoking related cues may elicit smoking urges and psychophysiological responses in subjects with nicotine dependence. This study aimed to investigate the effect of repeated virtual cue exposure therapy using the surround-screen based projection wall system on the psychophysiological responses in nicotine dependence.

Methods

The authors developed 3-dimensional neutral and smoking-related environments using virtual reality (VR) technology. Smoking-related environment was a virtual bar, which comprised both object-related and social situation cues. Ten subjects with nicotine dependence participated in 4-week (one session per week) virtual cue exposure therapy. Psychophysiological responses [electromyography (EMG), skin conductance (SC), and heart rate] and subjective nicotine craving were acquired during each session.

Results

VR nicotine cue elicited greater psychophysiological responses and subjective craving for smoking than did neutral cue, and exposure to social situation cues showed greater psychophysiological responses in SC and EMG than did object-related cues. This responsiveness decreased during the course of repeated therapy.

Conclusion

The present study found that both psychophysiological responses and subjective nicotine craving were greater to nicotine cue exposure via projection wall VR system than to neutral cues and that enhanced cue reactivity decreased gradually over the course of repeated exposure therapy. These results suggest that VR cue exposure therapy combined with psychophysiological response monitoring may be an alternative treatment modality for smoking cessation, although the current findings are preliminary.     

The effect of sleep on the salivary cortisol response to acute stressors: a review and suggestions

There have been steadily increasing studies on the relationship between sleep and stress. However, the findings regarding the effects of sleep on the acute stress response have been inconsistent. Elevated, blunted, or unchanged salivary cortisol stress response have been reported. Therefore, this study conducted a systematic review of previous studies to provide a comprehensive summary of the factors that influence the effects of sleep on the salivary cortisol stress response. We conducted a comprehensive electronic literature search in PubMed, PsycINFO, PsycARTICLES, Web of Science, MEDLINE, and EMBASE for human studies published in English (up to June 2019). Finally, 17 articles with participants aged 6.4–72 years were included in this review. We assessed the following factors: designing factors (sleep measurement, stress induction, cortisol sampling period, and time intervals between sleep measurement and the acute stress task), analyzing factors (cortisol analysis), and participants' characteristics (age, sex, and background stress levels); subsequently, we explained conflicting findings across the current literature. Further, we provide study design, analysis, and report suggestions for optimal assessment of the effects of sleep on the acute stress response. This summary of influencing factors and suggestions for future studies could help elucidate the impact of sleep on stress and advance the field.     

Electroencephalographic sleep profiles and hypothalamic-pituitary-adrenocortical (HPA)-activity in kindergarten children: early indication of poor sleep quality associated with increased cortisol secretion

OBJECTIVES: In children, objective data carried out from sleep EEG monitoring are scarce. Furthermore, results associating the hypothalamic-pituitary-adrenocortical (HPA)-activity with sleep EEG measurements in children are missing. Therefore, our study aimed to investigate in preschool-children the association between sleep patterns and endocrine activity. Furthermore, children's behavioral/emotional difficulties and competences were assessed in order to correlate psychological strain with sleep measures. PARTICIPANTS AND METHODS: Sixty-seven kindergarten children (35 boys and 32 girls) aged 5.34 underwent EEG-monitoring for one night. For baseline HPA-activity assessment, saliva samples were collected immediately after awakening, whereas saliva samples before, while and after a psychological challenge were used to assess the HPA-activity under stress conditions. RESULTS: Compared to girls, boys showed significantly more REM sleep time. After cluster analysis, children labeled as 'poor' sleepers (n=27; 40,30%) showed significantly increased morning cortisol values, as compared to 'good' sleepers (n=22; 32,83%). Furthermore, increased cortisol AUC values under stress conditions were significantly associated with an elevated number of awakenings after sleep onset, and more sleep time in stages 1 and 2. In addition, an increased sleep efficiency was significantly correlated with self-reported emotional/behavioral difficulties, i.e. with low degrees of impulsivity (r=-.31; p<.05) and lower degrees of social inhibition and peer victimiziation (r=-.26, p<.05). CONCLUSIONS: Our results underlined that already in preschool years, associations between objectively examined unfavorable sleep patterns, increased HPA-system activity and more difficult behavioral and psychosocial dimensions may be observed.     

The effects of vagus nerve stimulation on sleep EEG in depression: a preliminary report

OBJECTIVE: The present study evaluated the effects of vagus nerve stimulation (VNS) on sleep in seven treatment-resistant depressed outpatients. METHODS: Sleep studies were conducted in the laboratory at baseline and 10-12 weeks after VNS implantation while the concomitant psychotropic medication regimen was unchanged. Standard sleep macroarchitecture based on visual stage and assessment of ultradian sleep electroencephalographic (EEG) rhythms were measured on all nights. RESULTS: An overall significant treatment effect on sleep macroarchitecture was obtained by MANOVA. Decreased awake time, decreased Stage 1 sleep and increased Stage 2 sleep were evident post-VNS, although univariate analyses did not reach significance. In addition, the strength or amplitude of ultradian sleep EEG rhythms more than doubled on VNS and was restored to within normal range. CONCLUSION: VNS improved the clinical symptoms of depression and sleep architecture. Results suggest that treatment-resistant depressed patients have dampened sleep EEG rhythms that are restored to near-normal amplitudes with VNS treatment.     

Non-linear quantitative electroencephalographic (qEEG) changes during processing of chemo-sensory stimulations: a preliminary study

The present study was to investigate the processing of pleasant smell and taste stimuli by non-linear EEG measures. Point correlation dimension (PD2i) has been used for studying the local, and synchronization likelihood (SL) the global dynamical organization. Nine healthy subjects participated in this study. After a baseline period of 30s the patients were given a perfume cap or a chocolate taste for 30s. The analysis was performed off-line on 16 channels. After smell stimulation an immediate bilateral but short response was seen. First a decrease and afterwards an increase were found in the mean PD2i. In contrast, the taste stimulation resulted in a later reaction mainly on the right side. The SL in the slow alpha band decreased during the first 15s after both stimulations. In the second 15s, however, a remarkable SL increase was seen mainly in the 7-14Hz and in every frequency band. The decreased mean PD2i and SL values could be interpreted by the simplified network preparation to cognitive data processing. The PD2i and SL methods detected subtle dynamical changes during olfactory and gustatory processes suitable for collection normative database to pathological conditions.     

The interactive effects of elevated mid-afternoon cortisol and trauma history on PTSD symptoms in children: A preliminary study

Given the alarming frequency and severity of trauma exposure among children, identifying contextual and biologic factors that increase risk for symptomatic responses to trauma is an essential step toward preventing psychopathology. Basal functioning of the hypothalamic pituitary adrenal axis was evaluated to determine its role in relations between trauma exposure and PTSD symptoms among 66 children (M age = 10.7 years). Exposure to recent trauma (within the past year), previously experienced trauma (more than 1 year ago), and basal mid-afternoon cortisol levels were each positively related to PTSD symptoms. Further, these factors interacted in an additive manner to account for a significant proportion of the variance in PTSD symptoms. Implications for the early identification of children at risk for symptomatic responses to trauma are discussed.     

Effects of prolonged stress on salivary cortisol and dehydroepiandrosterone: a study of a two-week teaching practice

This study investigated variations in salivary levels of cortisol and dehydroepiandrosterone (DHEA) in a prolonged stressful situation (a two-week teaching practice). Thirty-three women for whom a two-week teaching practice at a kindergarten was scheduled were asked to collect saliva samples at awakening, 30 min after awakening, and bedtime at four time points: two weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. In addition, they completed questionnaires for assessing perceived stress and subjective moods on each day. A linear mixed model indicated that cortisol levels significantly increased during the first and second week of the practice compared with those before and after the practice period, and that DHEA levels significantly decreased after the practice period compared with those at the other time points. Further, cortisol awakening response after the practice period significantly reduced compared with that at the other time points. Scores of perceived stress and negative moods were also higher during the practice period. This study showed that prolonged stress affected cortisol and DHEA secretion during as well as after the stress period.     

Mind the social feedback: effects of tDCS applied to the left DLPFC on psychophysiological responses during the anticipation and reception of social evaluations

The left dorsolateral prefrontal cortex (lDLPFC) is implicated in anticipatory (i.e. during anticipation of emotional stimuli) and online (i.e. during confrontation with emotional stimuli) emotion regulatory processes. However, research that investigates the causal role of the lDLPFC in these processes is lacking. In this study, 74 participants received active or sham transcranial direct current stimulation (tDCS) over the lDLPFC. Participants were told strangers evaluated them. These (rigged) social evaluations were presented, and in 50% of the trials, participants could anticipate the valence (positive or negative) of the upcoming social feedback. Pupil dilation (a marker of cognitive resource allocation) and skin conductance responses (a marker of arousal) were measured. The results indicate that active (compared to sham) tDCS reduced arousal during the confrontation with anticipated feedback but only marginally during the confrontation with unanticipated feedback. When participants were given the opportunity to anticipate the social feedback, tDCS reduced arousal, irrespective of whether one was anticipating or being confronted with the anticipated feedback. Moreover, tDCS reduced cognitive resource allocation during anticipation, which was associated with resource allocation increases during the subsequent confrontation. Altogether, results suggest that the lDLPFC is causally implicated in the interplay between anticipatory and online emotion regulatory processes.     

A repeated dose comparison of three benzodiazepine derivative (nitrazepam, flurazepam and flunitrazepam) on subjective appraisals of sleep and measures of psychomotor performance the morning following night-time medication.

Repeated doses of 5 mg nitrazepam, 15 mg flurazepam, and 1 mg flunitrazepam improved subjective assessments of the ease of getting to sleep and the perceived quality of induced sleep in a population of 30 healthy volunteers. The subjective reports of improved sleep inducement were related to a perceived difficulty in awakening from sleep the morning following medication. This subjectively reported "hangover" is also shown in the impairment of mental arithmetic abilities as measured on the serial subtraction of sevens technique. However, complex psychomotor performance is unaffected by repeated administration of these three benzodiazepine derivatives, although these later results are somewhat equivocal. Evidence of a "rebound phenomenon" following 4 nights' withdrawal of active medication is shown in both subjective and objective measures of sleep and early morning behaviour.     

Effects of transcranial direct current stimulation on performance and recovery sleep during acute sleep deprivation: a pilot study

BackgroundPrevious studies claimed that transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) improves cognition in neuropsychiatric patients with cognitive impairment, schizophrenia, organic hypersomnia, etc, but few studies evaluated the effects of tDCS on cognitive improvement following sleep deprivation. The objective of this study was to determine whether tDCS (anode on the left DLPFC and cathode on the right DLPFC with a 2-mA current for 30 min) improves cognition following sleep deprivation.MethodsSeven participants received active tDCS and eight participants received sham tDCS when their cognition declined during at least 30 h of sleep deprivation. All participants completed the psychomotor vigilance task, Trail Making Tests A and B, digit cancellation test, Stroop color word test, the Brief Visuospatial Memory Test-Revised and a procedural game every 2 h during the sleep deprivation and after recovery sleep.ResultsCompared to the sham stimulation, active tDCS (anode on the left DLPFC and cathode on the right DLPFC at a 2-mA current for 30 min) had beneficial effects on attention, memory, executive function, processing speed, and the ability to inhibit cognitive interference, and improved in subjective drowsiness and fatigue following sleep deprivation. The lasting effect of a single tDCS on cognition during sleep deprivation was greater than 2 h. In all participants, tDCS did not disturb recovery sleep, and cognitive performance recovered to the baseline levels after recovery sleep.ConclusionsThe study results indicate that tDCS can improve cognition following sleep deprivation and does not disturb recovery sleep or cognitive performance after recovery sleep. The possible pathophysiological mechanisms might be related to the modulation of the corticothalamic pathway. We believe that tDCS can be applied in the treatment of sleep disorders involving sleepiness.Trial registration numberChiCTR2000029420.Date of registration2020-1-31.