title: Time matters - acute stress response and glucocorticoid sensitivity in early multiple sclerosis.
abstract: OBJECTIVE
  Psychosocial stress has frequently been associated with disease activity and acute exacerbations in multiple sclerosis (MS). Despite this well established finding, strikingly little is known about the acute hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) stress response in MS.
  
  
  METHODS
  Twenty-six early relapsing-remitting MS (RRMS) patients and seventeen age- and sex-matched healthy control subjects (CS) took part in the Trier Social Stress Test (TSST), a well validated psycho-social laboratory stress protocol. Repeated blood samples were analyzed for stress-related cortisol and catecholamine levels as well as for glucocorticoid sensitivity (GCS) of target immune cells. Chronic and acute stress appraisals were assessed by self-report measures.
  
  
  RESULTS
  RRMS patients and CS did not differ in stress-related cortisol/catecholamine levels, GCS or stress appraisal in response to the TSST. However, cortisol release as well as GCS was strongly correlated with time since diagnosis but not with neurological disability. Patients with shorter disease duration (2-12 months) expressed a significantly higher cortisol stress response while MS patients with longer disease duration (14-36 months) showed a significantly diminished HPA response as well as lower post-stress GCS.
  
  
  CONCLUSIONS
  There is evidence for a time-dependent variability in the HPA stress system with an increased cortisol stress response in the first year after diagnosis along with a more blunted HPA stress response and a diminished GCS in subsequent disease stages. Data underscore the highly dynamic nature of HPA axis regulation in the MS disease process, which could possibly relate to compensatory mechanisms within a cytokine-HPA axis feedback circuit model.
authors.affiliation: Department of Neurology, Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany. Electronic address: Simone.Kern@uniklinikum-dresden.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Kern
authors.affiliation: Department of Psychology & Volen National Center for Complex Systems, Brandeis University, Waltham, MA, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rohleder
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine & Department of Medicine III, Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany.
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
authors.affiliation: Department of Psychiatry & Psychotherapy, Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Lange
authors.affiliation: Department of Neurology, Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany.
authors.forename: Tjalf
authors.initials: T
authors.lastname: Ziemssen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002395:Catecholamines / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis*; D003863:Depression / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D020128:Inhibitory Concentration 50; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008433:Mathematics; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000503:physiopathology* / Q000523:psychology; D015213:Neuroimmunomodulation / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D013060:Speech / Q000502:physiology; D013315:Stress, Psychological / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D002395:Catecholamines; D016207:Cytokines; D008070:Lipopolysaccharides; D003907:Dexamethasone; D006854:Hydrocortisone
keywords: Cortisol; Glucocorticoid sensitivity; Multiple sclerosis; Stress; TSST