Basal ganglia hypermetabolism and symptoms of fatigue during interferon-α therapy

Lucile Capuron, Giuseppe Pagnoni, Marina F. Demetrashvili, David H. Lawson, Fiona B. Fornwalt, Bobbi Woolwine, Gregory S. Berns, Charles B. Nemeroff, Andrew H. Miller

Research output: Contribution to journalArticlepeer-review

174 Scopus citations


Interferon (IFN)-α is a cytokine of the innate immune response that is well known for inducing behavioral alterations and has been used to study effects of cytokines on the nervous system. Limited data, however, are available on the sites of action of IFN-α within the brain and their relationship with specific IFN-α-induced symptoms. Using a longitudinal design, whole-brain metabolic activity as assessed by fluorine-18-labeled fluorodeoxyglucose uptake and positron emission tomography was examined before and 4 weeks after IFN-α administration in patients with malignant melanoma. Changes in metabolic activity in relevant brain regions were then correlated with IFN-α-induced behavioral changes. IFN-α administration was associated with widespread bilateral increases in glucose metabolism in subcortical regions including the basal ganglia and cerebellum. Decreases in dorsal prefrontal cortex glucose metabolism were also observed. Prominent IFN-α-induced behavioral changes included lassitude, inability to feel, and fatigue. Correlational analyses revealed that self-reported fatigue (specifically as assessed by the 'energy' subscale of the Visual Analog Scale of Fatigue) was associated with increased glucose metabolism in the left nucleus accumbens and putamen. These data indicate that IFN-α as well as other cytokines of the innate immune response may target basal ganglia nuclei, thereby contributing to fatigue-related symptoms in medically ill patients.

Original languageEnglish (US)
Pages (from-to)2384-2392
Number of pages9
Issue number11
StatePublished - Nov 2007
Externally publishedYes


  • Basal ganglia
  • Cytokines
  • Dopamine
  • Fatigue
  • Positron emission tomography

ASJC Scopus subject areas

  • Pharmacology


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