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Endocrine and immune substrates of depressive symptoms and fatigue in multiple sclerosis patients with comorbid major depression
  1. Stefan M Gold1,2,
  2. Schulamith Krüger1,
  3. Kristin J Ziegler3,
  4. Thorsten Krieger4,
  5. Karl-Heinz Schulz3,
  6. Christian Otte5,
  7. Christoph Heesen1,2
  1. 1Institute for Neuroimmunology and Clinical Multiple Sclerosis Research (inims), University Hospital Hamburg, Germany
  2. 2Department of Neurology, University Hospital Hamburg, Hamburg, Germany
  3. 3Department of Medical Psychology, University Hospital Hamburg, Hamburg, Germany
  4. 4Department of Immunology, University Hospital Hamburg, Hamburg, Germany
  5. 5Department of Psychiatry, University Hospital Hamburg, Hamburg, Germany
  1. Correspondence to Dr S M Gold, Institute for Neuroimmunology und Clinical Multiple Sclerosis Research (inims), Falkenried 94, D-20251 Hamburg, Germany;{at}


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.

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  • See Editorial commentary, p 709

  • Linked article 240507.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the ethics committee of the Medical Board Hamburg.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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