scholarly journals Protocol for a cross-sectional study: Effects of a Multiple Sclerosis Relapse Therapy with Methylprednisolone on Offspring Neurocognitive Development and Behaviour (MS-Children)

Author(s):  
Valeska Kozik ◽  
Matthias Schwab ◽  
Sandra Thiel ◽  
Kerstin Hellwig ◽  
Florian Rakers ◽  
...  

Introduction: Multiple Sclerosis (MS) is the most common neuroimmunological disease in women of childbearing age. Current MS therapy consists of immunomodulatory relapse prevention with disease-modifying therapies (DMTs) and acute relapse therapy with the synthetic glucocorticoid (GC) methylprednisolone (MP). As most DMTs are not approved for use during pregnancy, treatment is usually discontinued, increasing the risk for relapses. While MP therapy during pregnancy is considered relatively save for the foetus, it may be detrimental for later cognitive and neuropsychiatric function. The underlying mechanism is thought to be an epigenetically mediated desensitisation of GC receptors, the subsequent increase in stress sensitivity, and a GC-mediated impairment of brain development. The aim of this study is to investigate the associations of foetal MP exposure in the context of MS relapse therapy with later cognitive function, brain development, stress sensitivity, and behaviour. Methods and analysis: 80 children aged 8 to 18 years of mothers with MS will be recruited. 40 children, exposed to GC in utero will be compared to 40 children without foetal GC exposure. The intelligence quotient will serve as primary outcome. Secondary outcomes will include attention, motor development, emotional excitability, Attention-Deficit Hyperactivity Disorder-related symptoms, and behavioural difficulties. The Trier Social Stress Test will test stress sensitivity, EEG and MRI will assess functional and structural brain development. To determine underlying mechanisms, DNA methylation of the GC receptor gene and the H19/IGF2 locus and changes in the microbiome and the metabolome will be investigated. Primary and secondary outcomes will be analysed using linear regression models. Time-variant outcomes of the stress test will be analysed in two mixed linear models exploring overall activity and change from baseline. Ethics and dissemination: This study was approved by the participating institutions' ethics committees and results will be presented in accordance with the STROBE 2007 Statement. Trial registration: https://clinicaltrials.gov/ct2/show/NCT04832269?id=ZKSJ0130

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Ahmadreza Askari Ashtiani ◽  
Vahid Shaygannejad ◽  
Foad Ghobadi ◽  
Roozbeh Bathaie ◽  
Shima Shahyad ◽  
...  

Background: It has long been suspected that exposure to stress is a major factor that can increase the risk of Multiple Sclerosis (MS) and exacerbate it, as a stress-related disorder. Therefore, we conducted this study to investigate the response of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal-medullar (SAM) system to acute social stress. Methods: A total of 46 MS patients and 23 age-sex-matched healthy controls were recruited in the study. The Trier Social Stress Test (TSST) was used to induce acute psychosocial stress. We measured salivary cortisol (SC) to evaluate the HPA axis. In addition, electrocardiography (ECG) was recorded to evaluate the SAM system based on the linear and non-linear features of Heart Rate Variation (HRV). Then, SC and HRV were measured before and after the stress exposure. We also used the Depression Anxiety Stress Scale (DASS) and Emotional Visual Analog Scale (EVAS) to conduct the psychometric assessment and evaluate the perceived stress level, respectively. Results: The mean age of the MS group was 35.38 ± 15 years, with a mean disease duration of 7.4 ± 60. Besides, the HC group's mean age was 35.8 ± 9 years. There were no significant differences in demographic features and DASS scores between the two groups. In response to TSST, both MS and healthy individuals showed a significant increase in the SC levels and EVAS scores, as well as changes in the HRV indices. Notably, significant differences were also found between the two groups regarding the basic and post-stress SC levels, EVAS score, and HRV indices. Unlike the HC group, the SC level returned to its baseline after recovery in the MS group, and the sympathetic tone was more sensitive. Conclusions: Our results indicated that both MS and healthy individuals respond to acute stress regarding neuroendocrine assessment; however, patients with multiple sclerosis show some impairments in this response.


2020 ◽  
Vol 68 (4) ◽  
pp. 217-227 ◽  
Author(s):  
Lisanne J. Bulling ◽  
Isabella C. Bertschi ◽  
Céline C. Stadelmann ◽  
Tina Niederer ◽  
Guy Bodenmann

Zusammenfassung. Die vorliegende Arbeit stellt die bisherigen empirischen Befunde zur Sprachgrundfrequenz (f0) in Paargesprächen vor und untersucht, wie sich die f0 nach einer experimentellen Stressinduktion im anschließenden spontanen Gespräch zwischen den Partner_innen verändert, wie die f0 mit der verbalen Stressäußerung zusammenhängt und wie sie zwischen den beiden Partner_innen kovariiert. Von 128 heterosexuellen Paaren nahm jeweils eine Person pro Paar am Trier Social Stress Test (TSST) teil. Die dem TSST vorangehende und anschließende naturalistische Interaktion zwischen den Partner_innen wurde gefilmt und nach Gesprächsthema und Art der Stressäußerung kodiert. Wie vorherige Studien zur f0 im Paargespräch zeigte auch die vorliegende Studie, dass die f0 wichtige Informationen über die Partnerschaft enthält. Während eine Erhöhung der f0 in Gesprächen über einen paarinternen Stressor (d.h. bei Konfliktgesprächen) mit negativen Kommunikationsmustern einherging, zeigte die vorliegende Studie, dass die f0 bei Gesprächen über einen paarexternen Stressor (d.h. beim TSST) mit emotionsorientierten Stressäußerungen einherging, also einer für den Stressbewältigungsprozess förderlichen Art der Kommunikation. Die Oszillatorenmodelle zeigen darüber hinaus, dass eine Kopplung der f0 zwischen den Partner_innen besteht, was darauf hindeutet, dass die nicht gestressten Partner_innen auf die paraverbalen Stressäußerungen der gestressten Partner_innen mit ihren eigenen paraverbalen Stressäußerungen reagieren.


Author(s):  
Yoon Ju Bae ◽  
Alexander Gaudl ◽  
Sonia Jaeger ◽  
Stephanie Stadelmann ◽  
Andreas Hiemisch ◽  
...  

AbstractBackground:Dysregulation of the adrenal cortex has been assessed with measurement of salivary cortisol. So far salivary cortisol is routinely measured with immunoassay (IA). However, liquid chromatography-tandem mass spectrometry (MS) is known to offer better specificity. We compared the concentrations of salivary cortisol measured by MS and IA at basal and stress induced conditions and evaluated reasons for the difference in method-dependent cortisol results.Methods:Saliva samples (n=2703) were collected from 169 children (age range: 8–14 years; 81 healthy children; 55 with internalizing and 33 with externalizing disorders) under circadian conditions and during the Trier Social Stress Test for Children (TSST-C). Biochemical analyses were performed with MS for cortisol and cortisone, IA (IBL, RE62011) for cortisol, and enzyme kinetic assay for α-amylase.Results:MS and IA showed mostly comparable results for circadian activity and TSST-C response with similar statistical power. However, IA measured cortisol concentrations about 2.39-fold higher than MS. We found that this difference in measured values between MS and IA was mainly due to different standardization of IA compared to MS. In addition, at cortisol IA concentration below 5 nmol/L, cross-reactivity with cortisone was found to contribute to the lower concordance between MS and IA.Conclusions:Immunoassay and LC-MS/MS were largely comparable in the interpretation of salivary cortisol dynamics in stress research. But the IA method revealed a restricted accuracy in the measuring range below 5 nmol/L.


Author(s):  
Chuk Ling Julian Lai ◽  
Daryl Yu Heng Lee ◽  
Monique On Yee Leung

Alteration in cortisol response to acute social stressors has been hypothesized to mediate childhood adversities (CA) and increased morbidity in adulthood. However, the evidence supporting an association between CA and cortisol response to social stressors is inconclusive. The present review addressed this issue by reviewing the literature on CA and cortisol response to acute social stressors, with a focus on studies with adolescents or adults, using the Childhood Trauma Questionnaire (CTQ) to assess CA, and examining salivary cortisol response to the Trier Social Stress Test (TSST). Systematic searches of relevant articles in PsycINFO, PubMed, Web of Science and ScienceDirect in February and March 2020 identified 12 articles including 1196 participants with mean ages ranging from 15.3 to 52.3 yrs. across studies. CTQ scores were significantly associated with cortisol response in 2 studies. In addition, the physical abuse and emotional neglect subscales were associated with cortisol response respectively in 2 separate studies. The lack of association between CA and cortisol response calls for more longitudinal studies, and the use of formal records of maltreatment or informant reports in future research to complement information collected by retrospective measures. In addition, increased attention to biological mechanisms other than that associated with the regulation of cortisol in explaining the connection between CA and psychiatry morbidity is warranted.


2011 ◽  
Vol 20 (4) ◽  
pp. 325-336 ◽  
Author(s):  
Mattias Wallergård ◽  
Peter Jönsson ◽  
Gerd Johansson ◽  
Björn Karlson

One of the most common methods of inducing stress in the laboratory in order to examine the stress response in healthy and clinical populations is the Trier Social Stress Test (TSST). Briefly, the participant is asked to deliver a speech and to perform an arithmetic task in front of an evaluating committee. The committee, consisting of three trained actors, does not respond emotionally during the test, which makes the situation very stressful for the participant. One disadvantage of the TSST is that it can be difficult to hold the experimental conditions constant. In particular, it may be difficult for actors to hold their acting constant across all sessions. Furthermore, there are several practical problems and costs associated with hiring professional actors. A computerized version of the TSST using virtual humans could be a way to avoid these problems provided that it is able to induce a stress response similar to the one of the original TSST. The purpose of the present pilot study was therefore to investigate the stress response to a virtual reality (VR) version of the TSST visualized using an immersive VR system (VR-TSST). Seven healthy males with an average age of 24 years (range: 23–26 years) performed the VR-TSST. This included delivering a speech and performing an arithmetic task in front of an evaluating committee consisting of three virtual humans. The VR equipment was a CAVE equipped with stereoscopy and head tracking. ECG and respiration were recorded as well as the participant's behavior and comments. Afterward, a semi-structured interview was carried out. In general, the subjective and physiological data from the experiment indicated that the VR version of the TSST induced a stress response in the seven participants. In particular, the peak increase in heart rate was close to rates observed in studies using the traditional TSST with real actors. These results suggest that virtual humans visualized with an immersive VR system can be used to induce stress under laboratory conditions.


Author(s):  
Sisitha Udara Jayasinghe ◽  
Sarah Janet Hall ◽  
Susan Jane Torres ◽  
Anne Isabella Turner

While the patterns of response within the sympatho-adrenal medullary (SAM) system and hypothalamo-pituitary adrenal (HPA) axis are interesting and important in their own accord, the overall response to acute psychological stress involves reactivity of both pathways We tested the hypothesis that consideration of the integrated response of these pathways may reveal dysregulation of the stress systems that is not evident when considering either system alone. Age matched lean and overweight/obese men were subjected to a Trier Social Stress Test and reactivity of the SAM system (salivary alpha amylase, systolic blood pressure, diastolic blood pressure and heart rate) and the HPA axis (salivary cortisol) were measured. Relative reactivity of SAM system and HPA axis was calculated as the ratio between the measures from each pathway. While analysis of reactivity of individual stress pathways showed no evidence of dysfunction in overweight/obese compared with lean men, analysis of HPA/SAM reactivity revealed significantly lower cortisol over systolic blood pressure (CoSBP) and cortisol over diastolic blood pressure (CoDBP) reactivity in overweight/obese compared with lean men. Other measures of HPA/SAM reactivity and all measures of SAM/HPA reactivity were unaltered in overweight/obese compared with lean men. These findings suggest that the cortisol response per unit of blood pressure response is blunted in men with elevated adiposity. Further, these findings support a notion of a coordinated overall approach to activation of the stress pathways with the degree of activation in one pathway being related to the degree of activation of the other.


1997 ◽  
Author(s):  
Angelika Buske-Kirschbaum ◽  
Silke Jobst ◽  
Andrea Wustmans ◽  
Clemens Kirschbaum ◽  
Wolfgang Rauh ◽  
...  

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