title: Quantifying serotonin transporters by PET with [11C]-DASB before and after interferon-α treatment.
abstract: BACKGROUND
  Interferon-α (IFN-α) therapy is frequently associated with disabling depression, fatigue, and related neuropsychiatric effects. Although depression in major depressive disorder is associated with low serotonin transporter binding, animal models suggest that IFN-associated mood effects are linked to increased presynaptic serotonin transporter binding. This study tested the hypotheses that IFN administration to human subjects increases presynaptic serotonin binding activity, and that this effect correlates with incident depression symptoms.
  
  
  METHODS
  Positron emission tomography (PET) scans using [11C]-DASB were obtained for nine hepatitis C patients before and after IFN-α treatment for 8 weeks. Serotonin transporter binding was estimated using the likelihood estimation in graphical analysis (LEGA) model and measured as the volume of distribution (VT) divided by the free fraction of ligand (fP). Depression was measured with the Structured Clinical Interview for DSM-IV Diagnosis (SCID) and the Hamilton Rating Scale for Depression (HAM-D).
  
  
  RESULTS
  Compared to pre-IFN treatment values, changes in serotonin transporter binding and depression symptoms were not significant. There was no correlation between changes in serotonin transporter binding and depression symptoms.
  
  
  CONCLUSIONS
  The study is limited by small sample size, minimal effect on observed mood symptoms within the sample, and brief duration of follow-up.
  
  
  CONCLUSIONS
  These findings do not support the hypothesis of an IFN-induced change in serotonin transporter function as the cause of incident depressive symptoms in patients treated with IFN-α. Additional study of these possible relationships should be of longer duration and include more subjects with more pronounced changes in mood.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Shapiro
authors.forename: Richard P
authors.initials: RP
authors.lastname: Sloan
authors.forename: Chetram
authors.initials: C
authors.lastname: Deochand
authors.forename: Ana M
authors.initials: AM
authors.lastname: Franceschi
authors.forename: Christine
authors.initials: C
authors.lastname: Delorenzo
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000814:Aniline Compounds / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging; D003863:Depression / Q000000981:diagnostic imaging / Q000209:etiology; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013440:Sulfides / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D016898:Interferon-alpha; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; D012701:Serotonin
keywords: binding; depression; imaging; interferon; serotonin; transporter