Basal ganglia hypermetabolism and symptoms of fatigue during interferon-alpha therapy.
Neuropsychopharmacol. 2007-02-28; 32(11): 2384-2392
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1. Neuropsychopharmacology. 2007 Nov;32(11):2384-92. Epub 2007 Feb 28.
Basal ganglia hypermetabolism and symptoms of fatigue during interferon-alpha
Capuron L(1), Pagnoni G, Demetrashvili MF, Lawson DH, Fornwalt FB, Woolwine B,
Berns GS, Nemeroff CB, Miller AH.
(1)Department of Psychiatry and Behavioral Sciences, Emory University School of
Medicine, Atlanta, GA 30322, USA.
Interferon (IFN)-alpha 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-alpha within the brain and their relationship with
specific IFN-alpha-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-alpha
administration in patients with malignant melanoma. Changes in metabolic activity
in relevant brain regions were then correlated with IFN-alpha-induced behavioral
changes. IFN-alpha 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-alpha-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-alpha as
well as other cytokines of the innate immune response may target basal ganglia
nuclei, thereby contributing to fatigue-related symptoms in medically ill
PMID: 17327884 [Indexed for MEDLINE]