Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation

The aim of this study was to investigate whether maternal adversities and cortisol levels during pregnancy predict cord blood DNA methylation of the oxytocin receptor (OXTR). We collected cord blood of 39 babies born to mothers participating in a cross-sectional study (N = 100) conducted in Basel, Switzerland (2007-10). Mothers completed the Inventory of Life Events (second trimester: T2), the Edinburgh Postnatal Depression Scale (EPDS, third trimester: T3), the Trier Inventory of Chronic Stress (TICS-K, 1-3 weeks postpartum) and provided saliva samples (T2, T3) for maternal cortisol profiles, as computed by the area under the curve with respect to ground (AUCg) or increase (AUCi) for the cortisol awakening response (CAR) and for diurnal cortisol profiles (DAY). OXTR DNA methylation was quantified using Sequenom EpiTYPER. The number of stressful life events (P = 0.032), EPDS score (P = 0.007) and cortisol AUCgs at T2 (CAR: P = 0.020; DAY: P = 0.024) were negatively associated with OXTR DNA methylation. Our findings suggest that distinct prenatal adversities predict decreased DNA methylation in a gene that is relevant for childbirth, maternal behavior and wellbeing of mother and offspring. If a reduced OXTR methylation increases OXTR expression, our findings could suggest an epigenetic adaptation to an adverse early environment

Stress-Induced Allodynia – Evidence of Increased Pain Sensitivity in Healthy Humans and Patients with Chronic Pain after Experimentally Induced Psychosocial Stress

Background: Experimental stress has been shown to have analgesic as well as allodynic effect in animals. Despite the obvious negative influence of stress in clinical pain conditions, stress-induced alteration of pain sensitivity has not been tested in humans so far. Therefore, we tested changes of pain sensitivity using an experimental stressor in ten female healthy subjects and 13 female patients with fibromyalgia. Methods: Multiple sensory aspects of pain were evaluated in all participants with the help of the quantitative sensory testing protocol before (60 min) and after (10 and 90 min) inducing psychological stress with a standardized psychosocial stress test (“Trier Social Stress Test”). Results: Both healthy subjects and patients with fibromyalgia showed stress-induced enhancement of pain sensitivity in response to thermal stimuli. However, only patients showed increased sensitivity in response to pressure pain. Conclusions: Our results provide evidence for stress-induced allodynia/hyperalgesia in humans for the first time and suggest differential underlying mechanisms determining response to stressors in healthy subjects and patients suffering from chronic pain. Possible mechanisms of the interplay of stress and mediating factors (e.g. cytokines, cortisol) on pain sensitivity are mentioned. Future studies should help understand better how stress impacts on chronic pain conditions

Trait anxiety moderates the impact of performance pressure on salivary cortisol in everyday life.

Stress and negative affective states are associated with cortisol in everyday life. However, it remains unclear what types of stressors and which affective states yield these associations, and the effect of trait anxiety is unknown. This study investigates the associations of specific task-related stressors and negative affective states in everyday life with salivary cortisol, and explores the mediating and moderating role of state negative affect and trait anxiety, respectively.Salivary cortisol, subjective stress, and state negative affect were measured three times a day on 2 days in 71 participants in everyday life, using a handheld computer to collect self-reports and time stamps and an electronic device to monitor saliva sampling compliance. Stress measures comprised the experience of performance pressure and failure during daily tasks; measures of negative affect comprised worn-out, tense, unhappy, and angry. Effects were tested using multilevel fixed-occasion models.Momentary performance under pressure was related to higher momentary cortisol measures, while mean task failure was related to lower daily cortisol concentrations. The association of performance pressure with cortisol varied between subjects, and this variation was explained by trait anxiety, yielding stronger associations in participants scoring high on trait anxiety. No evidence was found for a mediating role of state negative affect.These results describe the well-documented associations of everyday stressors and affect with salivary cortisol more precisely, suggesting that performance pressure is a significant condition related to short-term changes in cortisol. Subjects scoring high on trait anxiety seem to process stress-relevant information in a way that amplifies the association of performance pressure with reactions of the hypothalamus–pituitary–adrenal axis

The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders

Representing a challenge for current concepts of stress research, a number of studies have now provided convincing evidence that the adrenal gland is hypoactive in some stress-related states. The phenomenon of hypocortisolism has mainly been described for patients, who experienced a traumatic event and subsequently developed post-traumatic stress disorder (PTSD). However, as presented in this review, hypocortisolism does nor merely represent a specific correlate of PTSD, since similar findings have been reported for healthy individuals living under conditions of chronic stress as well as for patients with several bodily disorders. These include chronic fatigue syndrome, fibromyalgia, other somatoform disorders, rheumatoid arthritis, and asthma, and many of these disorders have been related to stress. Although hypocortisolism appears to be a frequent and widespread phenomenon, the nature of the underlying mechanisms and the homology of these mechanisms within and across clinical groups remain speculative. Potential mechanisms include dysregulations on several levels of the hypothalamic-pituitary-adrenal axis. In addition, factors such as genetic vulnerability, previous stress experience, coping and personality styles may determine the manifestation of this neuroendocrine abnormality. Several authors proposed theoretical concepts on the development or physiological meaning of hypocortisolism. Based on the reviewed findings, we propose that a persistent lack of cortisol availability in traumatized or chronically stressed individuals may promote an increased vulnerability for the development of stress-related bodily disorders. This pathophysiological model may have important implications for the prevention, diagnosis and treatment of the classical psychosomatic disorders. (C) 1999 Published by Elsevier Science Ltd. All rights reserved

Chronic pelvic pain as a somatoform disorder

BACKGROUND: The purpose of this study was to determine whether psychiatric disturbances, particularly somatization, and an increased number of traumatic and critical life events, which have been found in women with idiopathic chronic pelvic pain (ICPP), can also be observed in women with chronic pelvic pain and abdominal adhesions (ACPP). METHODS: Forty women who underwent diagnostic laparoscopy were subdivided into three groups according to blind rated somatic pathologies: ICPP patients (n = 16), ACPP patients (n = 10), infertile controls without pain (n = 14). Besides the standardized assessment of DSM-III-R diagnosis, questionnaires and semistandardized interviews were used to estimate depression, somatization, pain, the prevalence of sexual and physical abuse, and the number of critical life events. RESULTS: Diagnostic criteria for somatoform pain disorder were fullfilled in 73.3% of the ICPP patients, 60% of the ACPP patients and none of the controls. With respect to the somatization symptom checklist the two pain groups scored significantly higher than the controls (p < 0.05). Referring to perceived pain, ACPP patients differed from the ICPP patients by one out of seven subscales (higher persistence of pain; p < 0.05). No correlation was found between the intensity of pain and the severity of classified adhesions. The two groups of pain patients significantly differed from controls by a higher prevalence of sexual abuse (p < 0.05). Depression was found neither in the pain groups nor in the controls. CONCLUSIONS: Because high somatization and high prevalence rates of abuse were not only found in patients suffering from ICPP but also in ACPP patients, it seems to be doubtful that the somatic pathology may fully explain the psychopathology in patients with ACPP