Basal ganglia hypermetabolism and symptoms of fatigue during interferon-alpha therapy.
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 patients.
Capuron
Lucile
L
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Pagnoni
Giuseppe
G
Demetrashvili
Marina F
MF
Lawson
David H
DH
Fornwalt
Fiona B
FB
Woolwine
Bobbi
B
Berns
Gregory S
GS
Nemeroff
Charles B
CB
Miller
Andrew H
AH
D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D001526:Behavioral Symptoms / Q000188:drug therapy / Q000209:etiology; D001931:Brain Mapping; D015673:Fatigue Syndrome, Chronic / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
D007155:Immunologic Factors; D016898:Interferon-alpha; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18