Quantifying serotonin transporters by PET with [¹¹C]-DASB before and after interferon-α treatment

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 (V_T) divided by the free fraction of ligand (f_P). 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. Limitations: The study is limited by small sample size, minimal effect on observed mood symptoms within the sample, and brief duration of follow-up. Conclusion: 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.