Cytokines and psychopathology: Lessons from interferon-α

Interferon-α is a potent inducer of the cytokine network and is notorious for causing behavioral alterations. Studies on interferon-α-treated patients reveal at least two distinct syndromes: 1) a mood/cognitive syndrome that appears late during interferon-α 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-α treatment is antidepressant nonresponsive and may be mediated by alterations in basal ganglia dopamine metabolism. Findings from interferon-α 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.