Clinical depression and regulation of the inflammatory response during acute stress

Psychosom Med. Sep-Oct 2005;67(5):679-87. doi: 10.1097/01.psy.0000174172.82428.ce.


Objective: This study examined whether clinical depression is associated with a differential inflammatory response to an acute bout of psychological stress.

Methods: A total of 72 women participated in the study; half met diagnostic criteria for clinical depression; the others had no history of psychiatric illness. The groups were matched with respect to age and ethnicity. All subjects were exposed to a 17-minute mock-job interview; blood was drawn to assess secretion and regulation of inflammatory molecules.

Results: The stressor was associated with feelings of shame and anxiety, a mobilization of monocytes, neutrophils, and C-reactive protein into the circulation, and greater endotoxin-stimulated production of interleukin-6 and tumor necrosis factor-alpha by white blood cells in vitro. Depressed subjects began the session with greater sensitivity to the antiinflammatory properties of glucocorticoids than control subjects. Following exposure to the stressor protocol, however, sensitivity decreased among depressed subjects and increased among controls. This was manifest by disparities in interleukin-6 and tumor necrosis factor-alpha production in the presence of dexamethasone.

Conclusions: These findings suggest that under acutely challenging conditions, depression is associated with greater resistance to molecules that normally terminate the inflammatory cascade. An impaired capacity to regulate inflammation could underlie some of the excess morbidity and mortality that has been associated with depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • C-Reactive Protein / analysis
  • Cytokines / blood
  • Depressive Disorder, Major / blood
  • Depressive Disorder, Major / immunology
  • Depressive Disorder, Major / physiopathology*
  • Endotoxins / blood
  • Endotoxins / physiology
  • Female
  • Glucocorticoids / pharmacology
  • Humans
  • Hydrocortisone / blood
  • In Vitro Techniques
  • Inflammation / blood
  • Inflammation / immunology
  • Inflammation / physiopathology*
  • Interleukin-6 / blood
  • Monocytes / chemistry
  • Monocytes / immunology
  • Stress, Psychological / blood
  • Stress, Psychological / physiopathology*
  • Tumor Necrosis Factor-alpha / analysis


  • Cytokines
  • Endotoxins
  • Glucocorticoids
  • Interleukin-6
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Hydrocortisone