title: Endocrine and immune substrates of depressive symptoms and fatigue in multiple sclerosis patients with comorbid major depression.
abstract: OBJECTIVE
  Depression and fatigue are among the most common symptoms of multiple sclerosis (MS). These symptoms frequently co-occur and partially overlap in MS but their underlying biological substrates are unclear. In this study, the relative role of cytokines and hypothalamic-pituitary-adrenal (HPA) axis activity in depression and fatigue were examined in patients with relapsing-remitting MS (RRMS).
  
  
  METHODS
  HPA axis function and frequency of stimulated cytokine (interferon γ (IFNγ) and tumour necrosis factor α (TNFα)) producing T cells was measured cross sectionally in 44 female patients with RRMS. All subjects completed a neurological examination, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and self-report questionnaires.
  
  
  RESULTS
  10 patients met diagnostic criteria for major depressive disorder (MDD). MS patients with comorbid MDD showed normal morning but elevated evening salivary cortisol levels, resulting in a flattened slope. While a higher frequency of cytokine producing CD8+ T cells was also seen in MS patients with MDD, these markers were more closely associated with fatigue than depression.
  
  
  CONCLUSIONS
  This study supports a role for HPA axis hyperactivity in major depression in MS. In addition, inflammatory and neuroendocrine factors may differentially mediate fatigue and depressive symptoms.
authors.affiliation: Institute for Neuroimmunology und Clinical Multiple Sclerosis Research (inims), Falkenried 94, D-20251 Hamburg, Germany. stefan.gold@zmnh.uni-hamburg.de
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Gold
authors.forename: Schulamith
authors.initials: S
authors.lastname: Krüger
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Ziegler
authors.forename: Thorsten
authors.initials: T
authors.lastname: Krieger
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Schulz
authors.forename: Christian
authors.initials: C
authors.lastname: Otte
authors.forename: Christoph
authors.initials: C
authors.lastname: Heesen
mesh_terms: D000328:Adult; D016207:Cytokines / Q000378:metabolism; D003865:Major Depressive Disorder / Q000209:etiology* / Q000503:physiopathology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004702:Endocrine Glands / Q000503:physiopathology*; D005221:Fatigue / Q000209:etiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007107:Immune System / Q000503:physiopathology*; D007371:Interferon-gamma / Q000378:metabolism; D018655:Lymphocyte Count; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications* / Q000503:physiopathology* / Q000523:psychology; D012044:Regression Analysis; D012959:Socioeconomic Factors; D011795:Surveys and Questionnaires; D013601:T-Lymphocytes / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D006854:Hydrocortisone