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Objective: Dysregulation of stress‐reactive neuroendocrine measures, as well as subjective stress, have been found to worsen epilepsy. Transcutaneous vagus nerve stimulation (tVNS) is a relatively new treatment option for epilepsy. We were interested in its effect on the activity of the hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS) as well as subjective stress and tiredness in patients with temporal lobe epilepsy (TLE). Methods: Twenty patients (age 44 ± 11 years, 13 women) were enrolled in the study. They were free of seizures for more than 1 year. All took part in two sessions with 4 h of stimulation (tVNS vs. sham) in a randomized order. Saliva samples and subjective stress and tiredness levels were measured at five time points each session (before and after stimulation and three time points every hour in between). Data were analyzed using repeated measures analysis of variance as well as paired t‐tests. Results: There was a dampened salivary cortisol (sCort) decrease during tVNS (time × condition effect: F[2.38, 38.15] = 6.50, P = 0.002, partial η2 = 0.29). Furthermore, we detected a dampened increase in salivary flow rate during tVNS (time × condition effect: F[3.28, 55.67] = 2.82, P = 0.043, partial η2 = 0.14). There was neither a difference in overall sCort or salivary alpha‐amylase (sAA) levels nor in subjective stress or tiredness levels between conditions. sAA levels at the last measurement point were slightly higher during tVNS (t(19) = 2.26, P = 0.035, d = 0.51), but this effect failed to reach significance when controlled for multiple comparisons. Significance: Our results partially support that tVNS influences the regulation of stress‐reactive neuroendocrine systems (namely the HPA axis and ANS) in epilepsy. More research with larger samples is needed on the difference between short‐term and repeated long‐term stimulation. [ABSTRACT FROM AUTHOR]

Highlights • Poor sleep predicts next day's salivary alpha-amylase profile under stress. • The salivary alpha-amylase profile is unrelated to following night's sleep. • Diurnal salivary alpha-amylase profile is not sensitive to everyday occurring sleep variations. • Salivary alpha-amylase profiles indicate autonomic nervous system dysregulation. Abstract Although sleep is linked to physiological stress systems like the autonomic nervous system (ANS), research is still limited regarding night-and-day interactions between nocturnal sleep characteristics, stress, and diurnal parameters of salivary alpha-amylase (sAA) as a surrogate marker of ANS activity. Fifty healthy university students rated their chronic stress burden and completed two five-day periods of ecological momentary assessment – under everyday conditions of both low stress (beginning of semester) and high stress (final examination preparation). Participants collected saliva six times daily and reported on the previous night's sleep (quality, latency, duration, disturbances) immediately after awakening. Additionally, a sub-sample wore actigraphs recording 'time in bed'. In contrast to previous assumptions, poor sleep predicted lower sAA awakening values, more decreased awakening responses, and steeper diurnal slopes the following day only under high stress, but not under low stress. Diurnal sAA parameters did not predict the following night's sleep characteristics. The sAA profile does not seem to be sensitive to everyday occurring sleep variations, but rather seems to be an indicator of more prolonged stress induced ANS dysregulation. [ABSTRACT FROM AUTHOR]

Objective There is limited knowledge about how fatigue develops and worsens and what influences fluctuations in daily fatigue. Stress was found to influence fatigue, and being in a relationship seems to either increase or decrease stress depending on the couple interaction. In this study, co-variation of fatigue, self-reported stress, and biological stress markers in couples’ everyday lives was investigated. Specifically, we examined a) whether momentary couple interactions moderated dyadic outcomes and b) whether and how stress and relationship measures influenced individual momentary fatigue. Methods Forty heterosexual couples (age: 28 ± 5 years) reported subjective fatigue and stress levels 4 times a day for 5 consecutive days (1600 measures). Furthermore, participants reported whether they had interacted with their partner since the last data entry and, if so, they rated the valence of this interaction. Salivary cortisol (a measure of HPA axis activity) and alpha amylase (a measure of ANS activity) were analyzed as biological stress markers from saliva samples obtained at the same time points. Moment-to-moment data were analyzed using dyadic multilevel models to account for the nested design. Results Stress (women and men: p  ≤ 0.001) and fatigue (women: p  = .003, men: p  = .020) showed patterns of co-variation within couples, especially if partners had interacted with each other since the previous data entry. Cortisol was also found to co-vary between partners (women: unstandardized coefficient ( UC)  = 0.12, p  ≤ .001, men: UC  = 0.18, p   ≤  .001), whereas the regulation of alpha-amylase levels depending on the partner’s levels was only present in women ( UC  = 0.11, p  = .002). Valence of couple interaction was negatively associated with fatigue (women: UC  = −0.13, p  ≤ .001, men: UC  = −0.06, p  = .011). There was no momentary association of fatigue with an individual’s own or the partner’s subjective or biological stress markers. Conclusions Fatigue and stress levels during the day seem to co-vary within couples. These associations were particularly strong when the partners had interacted with each other since the last measurement. These data underline the importance of social factors in fatigue and stress in everyday life. [ABSTRACT FROM AUTHOR]

Objective: Fatigue is a core feature of functional somatic syndromes (FSS). Fatigue is also prominent in patients with thyroid diseases, which is unsurprising given the role of the hypothalamic-pituitary-thyroid (HPT) axis in regulating physiological energy demands. Research in healthy women has shown that early life adversity is linked with alterations in the HPT axis. In view of the substantial prevalence of early life adversity in patients with FSS, our aim was to investigate whether HPT functioning is related to (a) fatigue, and (b) early life adversity in these patients. Methods: N = 33 female patients with FSS and n = 30 age-matched controls were recruited. Fasting morning blood samples were taken to determine thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and thyroxine (fT4). General, physical, and mental fatigue were measured via the multidimensional fatigue inventory (MFI). Early life adversity was measured using the childhood trauma questionnaire (CTQ). Results: Patients with FSS did not differ from controls in any thyroid parameters (all p > 0.672). However, the lower the patients' TSH and the higher their fT4, the greater was their general (β = -0.32, p = 0.064; β = 0.35, p = 0.038) and physical (β = 0.47, p = 0.007; β = 0.32, p = 0.077) fatigue. In addition, emotional neglect (β = -0.32, p = 0.057), physical neglect (β = 0.60, p = 0.001), physical abuse (β = -0.47, p = 0.015), and sexual abuse (β = -0.40, p = 0.026) were linked with lower TSH. Conclusion: The lower TSH and the higher fT4, the more fatigue was reported by patients with FSS. In addition, lower TSH was linked with more early life adversity. Larger, prospective studies are warranted to determine whether HPT functioning may be a mediating pathway between early life adversity and fatigue in FSS. [ABSTRACT FROM AUTHOR]

Objective Although fibromyalgia syndrome (FMS) is a chronic condition, its cardinal symptom pain is known to fluctuate over the day. Stress has often been claimed to exacerbate pain; however, there is barely any evidence on whether or not this is true on a day-to-day basis (and, alternatively, on whether pain leads to increased stress levels). Using an ecologically valid measurement design, we tested whether and how stress and pain are intertwined in participants with FMS. We additionally examined the role of the two major stress-responsive systems, the hypothalamic-pituitary-adrenal axis and the autonomic nervous system, as potential mediators of this relationship. Methods An ambulatory assessment study was conducted over the course of 14 days. On each day, 32 females with FMS provided six diary entries on momentary stress and pain levels. Saliva samples were collected at the same time points to determine cortisol and alpha-amylase as indicators of stress-responsive systems. Results Higher stress at a given measurement time point was associated with higher reported pain levels at the subsequent time point (UC = 1.47, p < 0.001), but not vice versa (UC < 0.01, p = 0.179). The stress-pain relationship was neither mediated by momentary cortisol nor by alpha-amylase; however, momentary cortisol was independently associated with momentary pain (UC = 0.27, p = 0.009). Conclusion Stress seems to be a powerful exacerbating factor for pain as experienced by patients with FMS in their everyday lives. Cortisol may be involved in the diurnal fluctuation of pain levels in patients with FMS. Future studies should identify relevant daily stressors in persons with FMS and scrutinize the mechanisms underlying the cortisol-pain relationship. [ABSTRACT FROM AUTHOR]

We investigated whether stress may influence fatigue, or vice versa, as well as factors mediating this relationship. Fifty healthy participants (31 females, 23.6 ± 3.2 years) completed up to 5 momentary assessments of stress and fatigue during 5 days of preparation for their final examinations (exam condition) and 5 days of a regular semester week (control condition). Sleep quality was measured by self-report at awakening. A sub-group of participants ( n = 25) also collected saliva samples. Fatigue was associated with concurrent stress, stress reported at the previous measurement point, and previous-day stress. However, momentary stress was also predicted by concurrent fatigue, fatigue at the previous time point, and previous-day fatigue. Sleep quality mediated the association between stress and next-day fatigue. Cortisol and alpha-amylase did not mediate the stress–fatigue relationship. In conclusion, there is a reciprocal stress–fatigue relationship. Both prevention and intervention programs should comprehensively cover how stress and fatigue might influence one another. [ABSTRACT FROM AUTHOR]

Medically unexplained fatigue is a burdensome, widespread symptom, and a frequent complaint in depressive disorders (DDs) as well as somatic symptom disorder (SSD). Heightened stress levels are a likely cause of fatigue, although the temporal associations, as well as the role of the stress-reactive hypothalamic-pituitary-adrenal (HPA) axis, are not yet completely understood. We were interested in the differences between DD and SSD regarding general, mental, and physical fatigue, as well as associations between psychobiological stress measures (representing different time frames) and fatigue in these groups. Fifty-eight women (29 with DD, 29 with SSD) reported subjective recent fatigue and chronic stress levels, as well as levels of depression and somatic complaints using baseline questionnaires. Furthermore, they completed an ambulatory assessment period comprising measurements of fatigue, subjective stress, and salivary cortisol five times a day for 14 consecutive days. Salivary cortisol was obtained as a measure of within-day HPA axis activity, and hair cortisol concentration was obtained as a measure of accumulated HPA axis activity of the preceding three months. Women with DD reported higher levels of general and mental fatigue than did women with SSD, which was explained by their higher level of depression. Physical fatigue levels did not differ between groups. In both groups, momentary general, mental, and physical fatigue levels were associated with momentary subjective stress but not with chronic stress. Momentary salivary cortisol levels were positively associated with mental fatigue, while hair cortisol concentration was not. There are differences in fatigue profiles between DD and SSD, which should be accounted for in future research and practice (e.g., individualized treatment strategies focusing on mental or physical fatigue, depending on which fatigue dimension is prominent). • Fatigue differs between depressive disorder (DD) and somatic symptom disorder (SSD). • Level of depression is related to everyday life mental, but not physical, fatigue. • Momentary stress is associated with momentary fatigue in DD and SSD. • Salivary cortisol is associated with mental, not physical, fatigue in DD and SSD. • Chronic stress and hair cortisol do not predict momentary fatigue in DD and SSD. [ABSTRACT FROM AUTHOR]

• Healthy women underwent a psychosocial stress and a control session. • Acute psychosocial stress led to an increase in thyroid-stimulating hormone (TSH). • Acute psychosocial stress did not impact triiodothyronine (T3) and thyroxine (T4). The individual set point of the hypothalamic-pituitary-thyroid (HPT) axis is largely genetically determined. Apart from this genetic predisposition, the HPT axis may also be malleable to environmental demands such as psychosocial stress. Indeed, previous research has indicated that critical life events often precede the onset of autoimmune thyroid diseases, and subtle abnormalities in HPT functioning are present in some patients with stress-related disorders such as depression. However, no studies have investigated whether exposure to psychosocial stress leads to an immediate activation of the HPT axis. A total of N = 30 healthy women attended two laboratory appointments in a randomized order. An intravenous catheter was inserted at the beginning of each appointment. In the stress session, this was followed by the Trier Social Stress Test (TSST). Plasma samples to determine thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were taken at baseline and 20, 50, and 110 min after the TSST started. In the control session, participants rested and were instructed to read magazines, while the sampling schedule was maintained. There was a significant rise in TSH concentrations in response to the TSST, with a peak observed 20 min after stressor onset, and a steady decline thereafter. No such response was observed in the control session. The TSST did not increase T3 or T4. The finding that acute psychosocial stress is able to elicit a significant increase in TSH is relevant to our understanding of a number of stress-related illnesses presenting with abnormalities of the HPT axis. [ABSTRACT FROM AUTHOR]