Cytokines and psychopathology: lessons from interferon-alpha

Biol Psychiatry. 2004 Dec 1;56(11):819-24. doi: 10.1016/j.biopsych.2004.02.009.


Interferon-alpha is a potent inducer of the cytokine network and is notorious for causing behavioral alterations. Studies on interferon-alpha-treated patients reveal at least two distinct syndromes: 1) a mood/cognitive syndrome that appears late during interferon-alpha therapy is responsive to antidepressants and is associated with activation of neuroendocrine pathways and altered serotonin metabolism; and 2) a neurovegetative syndrome characterized by psychomotor slowing, and fatigue that appears early during interferon-alpha treatment is antidepressant nonresponsive and may be mediated by alterations in basal ganglia dopamine metabolism. Findings from interferon-alpha may provide important clues regarding the pathophysiology and treatment of cytokine-induced behavioral changes in medically ill patients, while also potentially modeling the development of neuropsychiatric symptoms in patients without medical disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adrenocorticotropic Hormone / metabolism
  • Animals
  • Basal Ganglia / metabolism
  • Behavioral Symptoms / chemically induced*
  • Behavioral Symptoms / immunology
  • Cognition Disorders / complications
  • Cytokines / physiology
  • Humans
  • Hydrocortisone / metabolism
  • Interferon-alpha / adverse effects*
  • Models, Immunological
  • Psychopathology*
  • Serotonin / metabolism


  • Cytokines
  • Interferon-alpha
  • Serotonin
  • Adrenocorticotropic Hormone
  • Hydrocortisone