title: HCV patients, psychopathology and tryptophan metabolism: analysis of the effects of pegylated interferon plus ribavirin treatment.
abstract: OBJECTIVE
  Depression and other psychiatric disorders are frequent in HCV-infected patients, especially during interferon treatment. The molecular mechanism(s) underlying this finding is still unknown but it has been suggested that HCV and/or interferon administration may increase indoleamine 2,3-dioxygenase (IDO) activity, and reduce plasma tryptophan (TRP) levels and brain serotonin synthesis thus leading to psychopathological disorders.
  
  
  METHODS
  We studied 89 subjects: (a) 39 patients with chronic hepatitis C virus (HCV) infection and mild liver damage; (b) 39 healthy controls; and (c) 10 patients with chronic hepatitis B virus (HBV) infection. 15 of the patients with HCV infection were re-evaluated after antiviral treatment with pegylated interferon alpha-2a plus ribavirin leading to viral eradication. We measured serum TRP and kynurenine levels and IDO activity in macrophages. Furthermore, each patient had an accurate psychopathological evaluation.
  
  
  RESULTS
  HCV-infected patients had lower (-28%) serum TRP and kynurenine levels than healthy volunteers or HBV-infected patients with comparable liver damage. Depression and anxiety symptoms were particularly common in HCV patients. After viral clearance, macrophage IDO activity, plasma TRP and kynurenine levels returned toward normal values and psychopathology improved.
  
  
  CONCLUSIONS
  Our study shows that HCV patients have reduced serum TRP levels and confirms that they frequently suffer from anxiety and depression-related symptoms. The reduced IDO activity found in the macrophages of these patients suggests that HCV infection may hamper macrophage functions. After successful antiviral treatment, in spite of the expected increase of IDO activity in macrophages, we noticed that TRP and kynurenine plasma levels returned toward physiological levels and psychopathology decreased significantly.
authors.affiliation: Department of Internal Medicine, Center for Research and Higher Education MCTDNENT, University of Florence, Florence, Italy.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Zignego
authors.forename: Andrea
authors.initials: A
authors.lastname: Cozzi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Carpenedo
authors.forename: Carlo
authors.initials: C
authors.lastname: Giannini
authors.forename: Massimo
authors.initials: M
authors.lastname: Rosselli
authors.forename: Tiziana
authors.initials: T
authors.lastname: Biagioli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Aldinucci
authors.forename: Giacomo
authors.initials: G
authors.lastname: Laffi
authors.forename: Flavio
authors.initials: F
authors.lastname: Moroni
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007737:Kynurenine / Q000097:blood; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D014364:Tryptophan / Q000097:blood*
chemical_list: D000998:Antiviral Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D007737:Kynurenine; D011092:Polyethylene Glycols; D012254:Ribavirin; D014364:Tryptophan; C100416:peginterferon alfa-2a