title: Psychiatric side effects and fluctuations in serotonergic parameters in the treatment of chronic hepatitis C infection.
abstract: BACKGROUND
  Treatment of hepatitis C with peginterferon induces psychiatric side effects. These might include changes in serotonergic function.
  
  
  METHODS
  Twenty-two hepatitis C patients were treated with peginterferon. At different time points, psychometric assessment was performed using the profile of mood states. Plasma samples were taken to study serotonergic parameters.
  
  
  RESULTS
  Anger and depression increased compared to baseline, starting with anger (from week 3 onwards), followed by depression (from week 7 onwards). Other scores did not show consistent changes. No consistent changes were observed in tryptophan, tryptophan/large neutral amino acids ratio, biopterin and 5-hydroxyindoleacetic acid. The tyrosine/large neutral amino acids ratio, neopterin, phenylalanine/tyrosine ratio, and prolactin concentrations increased compared to baseline. Prolactin levels were associated with the occurrence of depression and anger.
  
  
  CONCLUSIONS
  Particularly anger and depression increased during treatment. Neither a decrease in tryptophan and tryptophan availability was seen, nor a relationship between these parameters and the development of psychopathology. Therefore, other mechanisms in the induction of psychopathology should be considered. The observed increases in neopterin and phenylalanine/tyrosine ratio are indicative of changes in tetrahydrobiopterin, which is involved in the metabolism of serotonin, noradrenaline and dopamine, and possibly mediating the increase in prolactin. The increase in prolactin levels and its relationship with depression and anger needs further exploration.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Bezemer
authors.forename: A R
authors.initials: AR
authors.lastname: Van Gool
authors.forename: D
authors.initials: D
authors.lastname: Fekkes
authors.forename: J M
authors.initials: JM
authors.lastname: Vrolijk
authors.forename: B E
authors.initials: BE
authors.lastname: Hansen
authors.forename: H L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: R J
authors.initials: RJ
authors.lastname: de Knegt
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000139:chemically induced*; D019798:Neopterin / Q000097:blood; D010649:Phenylalanine; D011092:Polyethylene Glycols / Q000009:adverse effects*; D011388:Prolactin / Q000097:blood; D011594:Psychometrics; D011994:Recombinant Proteins / Q000009:adverse effects; D012701:Serotonin / Q000097:blood*; D018709:Statistics, Nonparametric; D013997:Time Factors; D014443:Tyrosine / Q000097:blood
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012701:Serotonin; D011092:Polyethylene Glycols; D014443:Tyrosine; D010649:Phenylalanine; D019798:Neopterin; D011388:Prolactin; C100416:peginterferon alfa-2a