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. 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.
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 Cpatients 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. 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.
Authors: Robert B Innis; Vincent J Cunningham; Jacques Delforge; Masahiro Fujita; Albert Gjedde; Roger N Gunn; James Holden; Sylvain Houle; Sung-Cheng Huang; Masanori Ichise; Hidehiro Iida; Hiroshi Ito; Yuichi Kimura; Robert A Koeppe; Gitte M Knudsen; Juhani Knuuti; Adriaan A Lammertsma; Marc Laruelle; Jean Logan; Ralph Paul Maguire; Mark A Mintun; Evan D Morris; Ramin Parsey; Julie C Price; Mark Slifstein; Vesna Sossi; Tetsuya Suhara; John R Votaw; Dean F Wong; Richard E Carson Journal: J Cereb Blood Flow Metab Date: 2007-05-09 Impact factor: 6.200
Authors: Charles L Raison; Andrey S Borisov; Sherry D Broadwell; Lucile Capuron; Bobbi J Woolwine; Ira M Jacobson; Charles B Nemeroff; Andrew H Miller Journal: J Clin Psychiatry Date: 2005-01 Impact factor: 4.384
Authors: S J Bull; P Huezo-Diaz; E B Binder; J F Cubells; G Ranjith; C Maddock; C Miyazaki; N Alexander; M Hotopf; A J Cleare; S Norris; E Cassidy; K J Aitchison; A H Miller; C M Pariante Journal: Mol Psychiatry Date: 2008-05-06 Impact factor: 15.992
Authors: Maria A Oquendo; Ramin S Hastings; Yung-Yu Huang; Norman Simpson; R Todd Ogden; Xian-Zhang Hu; David Goldman; Victoria Arango; Ronald L Van Heertum; J John Mann; Ramin V Parsey Journal: Arch Gen Psychiatry Date: 2007-02