Central stress processing, T-cell responsivity to stress hormones and disease severity in multiple sclerosis

Abstract

Epidemiological, clinical, and neuroscientific studies support a link between psychobiological stress and multiple sclerosis. Neuroimaging suggests that blunted central stress processing goes along with higher multiple sclerosis severity, neuroendocrine studies suggest that blunted immune system sensitivity to stress hormones is linked to stronger neuroinflammation. Until now, however, no effort has been made to elucidate whether central stress processing and immune system sensitivity to stress hormones are related in a disease-specific fashion, and if so, whether this relation is clinically meaningful. Consequently, we conducted two functional MRI analyses based on a total of 39 persons with multiple sclerosis and 25 healthy persons. Motivated by findings of an altered interplay between neuroendocrine stress processing and T cell glucocorticoid sensitivity in multiple sclerosis, we searched for neural networks whose stress task-evoked activity is differentially linked to peripheral T cell glucocorticoid signaling in patients versus healthy persons as a potential indicator of disease-specific CNS-immune crosstalk. Subsequently, we tested whether this activity is simultaneously related to disease severity. We found that activity of a network comprising right anterior insula, right fusiform gyrus, left midcingulate and lingual gyrus was differentially coupled to T cell glucocorticoid signaling across groups. This network’s activity was simultaneously linked to patients’ lesion volume, clinical disability and information processing speed. Complementary analyses revealed that T cell glucocorticoid signaling was not directly linked to disease severity. Our findings show that alterations in the coupling between central stress-processing and T cell stress hormone sensitivity are related to key severity measures of multiple sclerosis.

Similar neural pathways link psychological stress and brain health in health and multiple sclerosis

“…The study integrates data from two study projects conducted by the NeuroCure and the Experimental and Clinical Research Center at Charité – Universitätsmedizin Berlin, Germany. Stress fMRI data acquired in the first project were previously presented in Weygandt et al (2016) and Meyer-Arndt et al (2021; 2020), those in the second in Brasanac et al (2022). Patient inclusion criteria were comparable across projects: Meeting the 2010 McDonald Criteria (Polman et al, 2011) for relapsing-remitting or secondary-progressive MS (first project) or those for relapsing-remitting MS (second project).…”

“…If applicable, these inclusion and exclusion criteria were identical for HPs in both projects. To determine the participants of main analyses 1 - 3, we then proceeded by excluding three participants from the 57 participants in Weygandt et al (2016) and seven of 66 participants in Brasanac et al (2022) who passed the abovementioned criteria but showed pronounced fMRI head motion as indicated by the Framewise Displacement quality assurance metric (Power et al, 2014; see Supplement for details). Prior to data pooling, we finally excluded the data acquired in the first project (the project with slightly lower anatomical MRI resolution) of those 15 persons who participated in both projects to avoid mixing up within- and between-subject variation.…”

“…Despite the high individual sensitivity of FC and brain-PAD, however, these techniques have not yet been combined to identify and compare poorly understood stress-brain health pathways in HPs and neurological patients. Therefore, we employed a well-established Arterial-Spin-Labeling (ASL) fMRI stress paradigm comprising a rest and a socially evaluated mental arithmetic stress condition (e.g., Brasanac et al, 2022; Meyer-Arndt et al, 2021; 2020; Weygandt et al, 2016; Wang et al, 2007; 2005) to compare neurobiological pathways linking stress and brain health in 42 HPs and 56 PwMS. PwMS represent a group of patients well able of dealing with experimental tasks given their comparably moderate average disability and age (Manouchehrinia et al, 2017).…”

Multiple sclerosis with comorbidity depression and its association with vitamin D deficiency in a narrative review of the current literature

“…Increased stress leads to increased inflammatory reactions in the brain and periphery with increased plasma concentrations of proinflammatory cytokines, but also highly sensitive C-reactive protein (hsCRP) and cortisol (also in older people) [24]. VitD deficiency is correlated with an increase in C-reactive protein (CRP) and a sufficient s25(OH)D level can reduce chronic inflammation [25].…”

Neural stress processing, glucocorticoid functioning, and body mass in lean to obese persons with multiple sclerosis

“…The study combines data from two study projects carried out by the Experimental and Clinical Research Center and the NeuroCure Clinical Research Center at Charité -Universitätsmedizin Berlin, which included a clinical and an MRI visit at most two weeks apart. Stress fMRI data from the first project were previously published by (24 -26), those of the second in (23). Comparable inclusion criteria were applied across projects: 2010…”