The role of stress-response systems for the pathogenesis and progression of MS

Gold, Stefan M.; Mohr, David C.; Huitinga, Inge; Flachenecker, Peter; Sternberg, Esther M.; Heesen, Christoph

doi:10.1016/j.it.2005.09.010

Cited by 102 publications

(85 citation statements)

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“…Moreover, MS patients frequently exhibit dysregulated psychobiological stress systems, and these systems interact with the key neurologic characteristics. Neuroendocrine studies revealed a link between MS and altered regulation of both stress systems, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) (4). Specifically, pharmacological challenge tests have shown that glucocorticoid responsivity is elevated in MS patients (5) and that impaired HPA axis feedback control is linked to brain atrophy (6) and subsequent deterioration of clinical disability in MS (7).…”

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confidence: 99%

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

Weygandt

Meyer-Arndt

Behrens

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin-labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was related to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, stress responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to impairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy (i.e., positively to GM volume) in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone.multiple sclerosis | psychological stress | functional magnetic resonance imaging | clinical disability | brain atrophy M ultiple sclerosis (MS) is an autoimmune disease of the central nervous system leading to demyelination, axonal damage. and neuronal degeneration (1). In addition to sensorimotor symptoms, stress-related syndromes such as depression and anxiety disorders are among the most frequent comorbidities in MS (2).A role for psychological stress in the pathobiology of MS was hypothesized as early as the 19th century when Charcot first described the disease, and a link between stress and the risk of MS relapse is now supported by numerous prospective clinical studies (e.g., 3). Moreover, MS patients frequently exhibit dysregulated psychobiological stress systems, and these systems interact with the key neurologic characteristics. Neuroendocrine studies revealed a link between MS and altered regulation of both stress systems, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) (4). Specifically, pharmacological challenge tests have shown that glucocorticoid responsivity is elevated in MS patients (5) and that impaired HPA axis feedback control is linked to brain atrophy (6) and subsequent deterioration of clinical di...

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confidence: 99%

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

Weygandt

Meyer-Arndt

Behrens

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Not all MS patients develop depression and MS itself is associated with altera-tions in stress response systems (Gold et al, 2005). Future studies should also enroll healthy controls as well as patients with idiopathic MDD who do not suffer from inflammatory or autoimmune disorders to determine the specificity of the observed effects for MS depression.…”

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confidence: 99%

Decreased hydrocortisone sensitivity of T cell function in multiple sclerosis-associated major depression

Fischer

Otte

Krieger

et al. 2012

Psychoneuroendocrinology

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Summary Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS with a high prevalence of depression. Both MS and depression have been linked to elevated cortisol levels and inflammation, indicating disturbed endocrine-immune regulation. An imbalance in mineralocorticoid versus glucocorticoid signaling in the CNS has been proposed as a pathogenetic mechanism of depression. Intriguingly, both receptors are also expressed in lymphocytes, but their role for 'escape' of the immune system from endocrine control is unknown. Using steroid sensitivity of T cell function as a read-out system, we here investigate a potential role of mineralocorticoid receptor (MR) versus glucocorticoid receptor (GR) regulation in the immune system as a biological mechanism underlying MS-associated major depression. Twelve female MS patients meeting diagnostic criteria for current major depressive disorder (MDD) were compared to twelve carefully matched MS patients without depression. We performed lymphocyte phenotyping by flow cytometry. In addition, steroid sensitivity of T cell proliferation was tested using hydrocortisone as well as MR (aldosterone) and GR (dexamethasone) agonists. Sensitivity to hydrocortisone was decreased in T cells from depressed MS patients. Experiments with agonists suggested disturbed MR regulation, but intact GR function. Importantly, there were no differences in lymphocyte composition and frequency of T cell subsets, indicating that the differences in steroid sensitivity are unlikely to be secondary to shifts in the immune compartment. To our knowledge, this study provides first evidence for altered steroid sensitivity of T cells from MS patients with comorbid MDD possibly due to MR dysregulation.

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“…cortisol) secretion. In MS this system is commonly hyperactivated [47] . Abnormal functioning of the stress response system as well as abnormal functioning of the immune system are also considered essential in the development of depressive symptoms [48][49][50] , which are frequently present in MS patients and greatly affect quality of life [51] .…”

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confidence: 99%

“…The physiological changes seen in the classic fight-or-flight response to a stressor are the result of activation of neuroendocrine and immune pathways, which includes activation of the hypothalamic-pituitary-adrenal (HPA)-axis. Several studies support a role for the HPA-axis in the development of depression [48,467] , but also in the disease process of multiple sclerosis (MS) [47] , the prototypic inflammatory disease of the central nervous system (CNS). Moreover, there is a high life time prevalence of comorbid depression in MS, which is reported to be up to 50% [51,468] , and which may be related to either CNS inflammation or dysregulation of the HPA-axis [469] .…”

mentioning

confidence: 99%

“…Both in depression and in MS hyperactivation of the HPA-axis is observed [47][48] , as demonstrated by elevated levels of cortisol [386,[470][471][472] and suppression and/or stimulation tests [234,385,[387][388]473] . What underlies this increased activity of the HPA-axis in both disorders, and whether it is a cause or a consequence of depression, is yet unclear.…”

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Mapping the effects of vitamin D in multiple sclerosis

Rolf¹

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Columbus (1451Columbus ( -1506 on one of his four voyages Er zijn verrassend veel parallellen te trekken tussen onderzoek doen en een van mijn favoriete vrijetijdsbestedingen, namelijk koken. Alles begint met een inspiratie, nieuwsgierigheid en een idee. Dan volgt de planning en de uitvoering en na (lang…) wachten kun je het resultaat proeven. Het blijft altijd spannend of het gelukt is en of het wel lekker is. Als het lekker is, dan smaakt het vaak ook naar meer! Zo niet, dan moet je het recept aanpassen, of crucialer, iets heel anders verzinnen...De weg naar een goed gelukt gerecht is, althans voor mij, minstens zo belangrijk: watertandend recepten zoeken en menu's samenstellen, op zoek gaan naar de juiste producten, lekker creatief combineren en (al of niet met succes) uitproberen. Dat kon ook in de voor mij nieuwe keuken van de wetenschap, en wel in een restaurant met een excellente ambiance. Verder is de diversiteit aan smaken, waar ik bij eten zo van houd, zeker ook terug te vinden in de verschillende hoofdstukken.Of kookkunsten gewaardeerd worden is vervolgens een kwestie van smaak, maar ook van kennis. De fijnproevers zullen zich op de details storten en boeren die het niet kennen zullen het niet eten, maar voor iedereen die aan tafel schuift: hopelijk is datgene wat in dit boekje geserveerd wordt smakelijk en levert het gespreksstof op voor het natafelen! Abbreviations and glossary & G L O S S A R Y AB BR EVI ATI ONS 23General IntroductionHistorical explorers discovered new land around the world, and with every journey more details have been added to global maps. For multiple sclerosis research, explorers of the 20 th century put vitamin D on the map, and from 2008 onwards, our research team in Maastricht has tried to add more details to this area. Today, vitamin D in multiple sclerosis is still an active area of research. Many reviews concentrate on the role of vitamin D in multiple sclerosis, illustrated by clinical and immunological studies. Also in this thesis two reviews elaborate on this topic. Therefore, the introduction to this thesis is restricted to the essential players, i.e. multiple sclerosis, its immune pathogenesis, and vitamin D, followed by the outline of the thesis.Multiple sclerosis (MS) is the most common disabling neurological disease among young people. Initial symptoms generally occur in the age of 20-40 years and MS affects women 2-3 times more often compared to men [1][2] . Currently, almost 1 in 1000 people suffers from MS in the Netherlands [3] . MS is characterized by inflammation and neurodegeneration of the central nervous system (CNS; brain and spinal cord). Though, it is still a matter of debate whether it is neurodegenerative or inflammatory from onset [1,4] . Most accepted, however, is the thought that inflammatory processes lead to damage of the fatty myelin sheaths covering the neuronal axons, which normally support fast transduction of signals, and this process is called demyelination. The inflammation can be accompanied by axonal injury and over time this result...

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The role of stress-response systems for the pathogenesis and progression of MS

Cited by 102 publications

References 67 publications

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

Decreased hydrocortisone sensitivity of T cell function in multiple sclerosis-associated major depression

Mapping the effects of vitamin D in multiple sclerosis

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