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 Nemeroff, Andrew H. Miller

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

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
Pages (from-to)2384-2392
Number of pages9
JournalNeuropsychopharmacology
Volume32
Issue number11
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

Fingerprint

Basal Ganglia
Interferons
Fatigue
Therapeutics
Cytokines
Innate Immunity
Glucose
Brain
Putamen
Fluorodeoxyglucose F18
Nucleus Accumbens
Prefrontal Cortex
Visual Analog Scale
Positron-Emission Tomography
Cerebellum
Nervous System
Melanoma

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Capuron, L., Pagnoni, G., Demetrashvili, M. F., Lawson, D. H., Fornwalt, F. B., Woolwine, B., ... Miller, A. H. (2007). Basal ganglia hypermetabolism and symptoms of fatigue during interferon-α therapy. Neuropsychopharmacology, 32(11), 2384-2392. https://doi.org/10.1038/sj.npp.1301362

Basal ganglia hypermetabolism and symptoms of fatigue during interferon-α therapy. / Capuron, Lucile; Pagnoni, Giuseppe; Demetrashvili, Marina F.; Lawson, David H.; Fornwalt, Fiona B.; Woolwine, Bobbi; Berns, Gregory S.; Nemeroff, Charles; Miller, Andrew H.

In: Neuropsychopharmacology, Vol. 32, No. 11, 01.11.2007, p. 2384-2392.

Research output: Contribution to journalArticle

Capuron, L, Pagnoni, G, Demetrashvili, MF, Lawson, DH, Fornwalt, FB, Woolwine, B, Berns, GS, Nemeroff, C & Miller, AH 2007, 'Basal ganglia hypermetabolism and symptoms of fatigue during interferon-α therapy', Neuropsychopharmacology, vol. 32, no. 11, pp. 2384-2392. https://doi.org/10.1038/sj.npp.1301362
Capuron L, Pagnoni G, Demetrashvili MF, Lawson DH, Fornwalt FB, Woolwine B et al. Basal ganglia hypermetabolism and symptoms of fatigue during interferon-α therapy. Neuropsychopharmacology. 2007 Nov 1;32(11):2384-2392. https://doi.org/10.1038/sj.npp.1301362
Capuron, Lucile ; Pagnoni, Giuseppe ; Demetrashvili, Marina F. ; Lawson, David H. ; Fornwalt, Fiona B. ; Woolwine, Bobbi ; Berns, Gregory S. ; Nemeroff, Charles ; Miller, Andrew H. / Basal ganglia hypermetabolism and symptoms of fatigue during interferon-α therapy. In: Neuropsychopharmacology. 2007 ; Vol. 32, No. 11. pp. 2384-2392.
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