Hair cortisol levels in women with medically unexplained symptoms.

Stress has been demonstrated to be involved in the development of medically unexplained symptoms. A key underlying mechanism could be lower levels of cortisol, which can contribute to symptoms such as fatigue or pain. However, the literature is highly equivocal, which may be due to methodological limitations inherent in short-term cortisol assessment. The aim of this case-control study was to investigate, for the first time, whether individuals with different forms of medically unexplained symptoms show altered hair cortisol concentrations, a long-term marker of hypothalamic-pituitary-adrenal functioning. Two groups of women with medically unexplained symptoms were recruited. The first had a functional somatic syndrome, characterised by specific medically unexplained symptoms (i.e., chronic fatigue syndrome, fibromyalgia, or irritable bowel syndrome, n = 33). The second had somatic symptom disorder, characterised by excessive thoughts, feelings, and behaviours devoted to various medically unexplained symptoms (n = 23). These groups were contrasted with healthy controls (n = 30), and women with depression (n = 27). Cortisol representing the previous three months was extracted from hair. Chronic stress and childhood trauma were assessed (retrospectively). Women with somatic symptom disorder had lower hair cortisol than healthy controls and women with functional somatic syndromes. No differences in hair cortisol were found between healthy controls, functional somatic syndromes, and depression. Neither childhood trauma nor chronic stress was correlated with hair cortisol. Provided that our findings are replicated, they may suggest that hypocortisolism is found in a specific subgroup of individuals with medically unexplained symptoms, and potentially in those characterised by excessive thoughts, feelings, and behaviours about symptoms.

Factors contributing to stability and instability in alpha-amylase activity in diluted saliva samples over time.

For the measurement of salivary alpha-amylase (sAA) activity, saliva samples first have to be diluted. There is some evidence for instability, that is, a decline of sAA activity in diluted samples. It is not clear which factors during dilution may contribute to this phenomenon and how quickly this decline of sAA activity occurs. Several experiments were conducted to investigate whether and how the material of the container (polystyrene (PS), polypropylene (PP), glass; experiment 1) and the diluent (saline (NaCl) solution, phosphate buffer saline (PBS), ultra-pure water; experiment 2) may affect sAA stability in diluted samples over a broad time window of up to 5 h. To study the velocity of the phenomenon in a fine-grained temporal resolution, sAA activity during the dilution process was studied (experiment 3). The results suggest that the (in)stability of sAA activity in diluted samples is determined by the interaction of material, diluent, and time. The sAA activity was relatively stable if saliva samples were diluted with a NaCl solution or PBS in glass tubes. However, sAA activity in diluted samples decreased in plastic containers (PS, PP), or if ultra-pure water was used as the diluent. There was a clear time effect on this decline. However, the decline appears to require some time to evolve and may not occur immediately during the dilution process. To conclude, the dilution of saliva samples should preferably be conducted with NaCl solution or PBS in glass containers. If glass containers are not available, PS and PP containers can be used if the dilution is processed quickly (within 25 min) and the measurement is initiated immediately upon dilution.

Thyroid Functioning and Fatigue in Women With Functional Somatic Syndromes - Role of Early Life Adversity.

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 (ß = -0.32, p = 0.064; ß = 0.35, p = 0.038) and physical (ß = -0.47, p = 0.007; ß = 0.32, p = 0.077) fatigue. In addition, emotional neglect (ß = -0.32, p = 0.057), physical neglect (ß = -0.60, p = 0.001), physical abuse (ß = -0.47, p = 0.015), and sexual abuse (ß = -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.

Hair and salivary cortisol in a cohort of women with chronic fatigue syndrome.

Hypocortisolism has been found in CFS patients in blood, urine, and saliva. It is unclear if hypocortisolism can also be demonstrated using long-term cortisol measurements, such as cortisol in hair. In addition, the interaction between the HPA axis and the immune system, both expected to play an important role in CFS, is unclear. The objective of the current study was to compare hair and salivary cortisol concentrations in a cohort of female CFS patients to those in healthy controls, and to test the effect of an interleukin-1 receptor antagonist (anakinra) on the HPA axis. Salivary cortisol concentrations of 107 CFS patients were compared to 59 healthy controls, with CFS patients showing a decreased cortisol awakening response (4.2 nmol/L ±â€¯5.4 vs 6.1 nmol/L ±â€¯6.3, p = 0.036). Total cortisol output during the day did not differ significantly in saliva, but there was a trend to lower hair cortisol in a subset of 46 patients compared to 46 controls (3.8 pg/mg ±â€¯2.1 vs 4.3 pg/mg ±â€¯1.8, p = 0.062). After four weeks of treatment with either daily anakinra (100 mg/day) or placebo, there was a slight decrease of hair cortisol concentrations in the anakinra group compared to an increase in the placebo group (p = 0.022). This study confirms the altered dynamics of the HPA axis in a group of CFS patients, and for the first time shows that this might also be present for long-term cortisol measures.

Simultaneous measurement of salivary cortisol and alpha-amylase: Application and recommendations.

Salivary cortisol (sCort) and salivary alpha-amylase (sAA) constitute proxy measures of the two major stress response systems, i.e. the hypothalamic-pituitary-adrenal axis and the autonomic nervous system, respectively. Potentially confounding determinants of sCort and sAA may limit a reliable concurrent measurement of both biomarkers, if not adequately considered. We reviewed the most important determinants of sCort and sAA and provide recommendations for handling these potential confounders. We focused on a selection of confounders, resulting in an in-depth consideration of age, sex steroid-related factors, somatic health, acute medication, smoking, consumption of food and drinks, alcohol consumption, physical activity/fitness, and sleep. Our review further highlights the importance of the consideration of potential confounders for a reliable and valid simultaneous measurement of sCort and sAA. We further provide recommendations about which and how to handle relevant confounders in the study design or data analysis.

Long-term stability of diurnal salivary cortisol and alpha-amylase secretion patterns.

This study aimed to investigate long-term stability and variability of diurnal cortisol and alpha-amylase patterns. Diurnal cortisol and alpha-amylase secretion patterns were assessed on a single workday with three waves of measurement across a total time period of 24months in 189 participants. Separate hierarchical linear models were analyzed, with and without a number of potential predictor variables (age, BMI, smoking, chronic stress, stress reactivity). While low long-term stability was found in diurnal cortisol, the stability of diurnal alpha-amylase was moderate across the time period of 24months. Several predictor variables had a positive impact on diurnal cortisol and alpha-amylase secretion patterns averaged across waves. Our findings underpin the notion that long-term stability is not necessarily warranted in longitudinal studies. It is important to choose an appropriate study design when attempting to disentangle clinically and biologically relevant changes from naturally occurring variations in diurnal cortisol and alpha-amylase.

The role of week(end)-day and awakening time on cortisol and alpha-amylase awakening responses.

Awakening responses in salivary cortisol (CAR) and alpha-amylase (AAR) constitute proxies of morning activation patterns of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, respectively. Previous studies suggest that the CAR is decreased at weekends and at late awakening. However, it is insufficiently studied (a) whether this also applies to the AAR and (b) whether week(end)-day and awakening time interact with each other. Using an ecological momentary assessment design, 48 healthy young adults (60% women) were investigated over a 7-d period (Study 1), and 27 chronic pain patients diagnosed with fibromyalgia syndrome were examined over a 14-d period (Study 2). For the assessment of the CAR and AAR, participants provided saliva samples each morning (upon awakening, 30 min after awakening). Preprogrammed electronic diary devices were used to track week(end)-day and exact time of saliva sampling (awakening time). In Study 1, CAR was unrelated to weekend, awakening time, or their interaction, whereas only early awakening time was positively associated with AAR. In Study 2, week-days as well as early awakening times on week-days predicted increased CAR. AARs were not predicted by week(end)-day, awakening times, or their interaction. These findings suggest that time-related factors may influence awakening responses, particularly the impact of week(end)-day on the CAR and the impact of awakening times on the AAR. Since week(end)-day and awakening times may negatively affect awakening responses, these potential confounding factors should be assessed and controlled for, particularly in studies assessing both CAR and AAR.

Introducing a novel method to assess cumulative steroid concentrations: increased hair cortisol concentrations over 6 months in medicated patients with depression.

Depression has been linked to increased cortisol concentrations using point measures taken from urine, blood, or saliva samples. However, with regard to hypercortisolism-induced consequences, long-term cumulative cortisol burden is of relevance. Our objective was to use hair analysis as a new method to assess cortisol exposure over 6 months in depressed patients and healthy controls. We examined 23 depressed patients (8 men and 15 women, mean age: 41.6 years ( ± standard deviation (SD), 13.1 years); mean duration of current depressive episode 9 months ( ± SD, 13 months)) and 64 healthy controls, matched for age and gender. Cortisol concentrations in two 3-cm hair segments from near to the scalp were analyzed, representing cortisol secretion during the 6 months prior to sampling. Compared with healthy individuals, depressed patients had higher hair cortisol concentrations in the first (mean ± SD: 26.7 ± 20.8 vs. 18.7 ± 11.5 pg/mg, p < 0.05) and second hair segment (mean ±  SD: 21.9 ± 23.7 vs. 13.4 ± 9.6 pg/mg, p < 0.05). In conclusion, hair cortisol analysis confirmed enhanced cortisol secretion in depressed patients over a prolonged time period. Because of the retrospective and cumulative nature of cortisol in hair, the assessment of hair cortisol concentration may help in addressing unanswered questions regarding hypothalamic-pituitary-adrenal axis overactivity and associated health consequences in psychiatric disorders.