Mood disorders and dysfunction of the hypothalamic-pituitary-adrenal axis in multiple sclerosis: association with cerebral inflammation

Arch Neurol. 1998 Jan;55(1):66-72. doi: 10.1001/archneur.55.1.66.


Objective: To investigate the association between affective and neuroendocrine abnormalities, commonly observed in multiple sclerosis, with inflammatory disease activity.

Design: Cross-sectional design. Twenty-three patients with definite relapsing-remitting multiple sclerosis and age- and sex-matched control subjects were investigated. Depression and anxiety were assessed using structured interviews, self-report measures, and Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria. Neurologic impairment was assessed by the Kurtzke Expanded Disability Status Scale and function of hypothalamic-adrenal-pituitary axis was analyzed using a corticotropin-releasing hormone stimulation test after dexamethasone suppression. Inflammatory disease activity was evaluated first by routine and experimental laboratory tests, and second by magnetic resonance assessment of gadolinium uptake of multiple sclerotic plaques.

Setting: University hospital, a major provider of acute neurologic care.

Results: Compared with controls, patients with multiple sclerosis had higher scores on depression and anxiety scales and exhibited a failure of suppression of cortisol release after dexamethasone pretreatment. Both affective symptoms and neuroendocrine abnormalities were correlated with cerebrospinal fluid white blood cell counts and presence of gadolinium-enhancing lesions on magnetic resonance images; however, no association with the degree of neurologic impairment was observed.

Conclusion: Affective and neuroendocrine disorders were related to inflammatory disease activity but not to degree of disability, supporting the hypothesis that these symptoms are causally associated with brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety
  • Corticotropin-Releasing Hormone / metabolism
  • Cross-Sectional Studies
  • Depression
  • Dexamethasone
  • Encephalitis / complications*
  • Encephalitis / pathology
  • Female
  • Gadolinium
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Inflammation
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mood Disorders / etiology*
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / physiopathology
  • Multiple Sclerosis / psychology*
  • Pituitary-Adrenal System / physiopathology*
  • Psychiatric Status Rating Scales


  • Dexamethasone
  • Corticotropin-Releasing Hormone
  • Gadolinium