TY - JOUR
T1 - Interferon-alpha-induced changes in tryptophan metabolism
T2 - Relationship to depression and paroxetine treatment
AU - Capuron, Lucile
AU - Neurauter, Gabriele
AU - Musselman, Dominique L.
AU - Lawson, David H.
AU - Nemeroff, Charles B.
AU - Fuchs, Dietmar
AU - Miller, Andrew H.
PY - 2003/11/1
Y1 - 2003/11/1
N2 - Background: Tryptophan (TRP) degradation into kynurenine (KYN) by the enzyme, indoleamine-2,3-dioxygenase, during immune activation may contribute to development of depressive symptoms during interferon (IFN)-α therapy. Methods: Twenty-six patients with malignant melanoma were randomly assigned in double-blind fashion to receive either placebo or paroxetine, beginning 2 weeks before IFN-α treatment and continuing for the first 12 weeks of IFN-α therapy. At treatment initiation and at 2, 4, and 12 weeks of IFN-α treatment, measurements of TRP, KYN, and neopterin (a marker of immune activation), were obtained, along with structured assessments of depression, anxiety, and neurotoxicity. Results: Regardless of antidepressant treatment status, all patients exhibited significant increases in KYN, neopterin, and the KYN/TRP ratio during IFN-α therapy. Among antidepressant-free patients, patients who developed major depression exhibited significantly greater increases in KYN and neopterin concentrations and more prolonged decreases in TRP concentrations than did nondepressed, antidepressant-free patients. Moreover, in antidepressant-free patients, decreases in TRP correlated with depressive, anxious, and cognitive symptoms, but not neurovegetative or somatic symptoms. No correlations were found between clinical and biological variables in antidepressant-treated patients. Conclusions: The results suggest that reduced TRP availability plays a role in IFN-α-induced depressive symptoms, and paroxetine, although not altering the KYN or neopterin response to IFN-α, attenuates the behavioral consequences of IFN-α-mediated TRP depletion.
AB - Background: Tryptophan (TRP) degradation into kynurenine (KYN) by the enzyme, indoleamine-2,3-dioxygenase, during immune activation may contribute to development of depressive symptoms during interferon (IFN)-α therapy. Methods: Twenty-six patients with malignant melanoma were randomly assigned in double-blind fashion to receive either placebo or paroxetine, beginning 2 weeks before IFN-α treatment and continuing for the first 12 weeks of IFN-α therapy. At treatment initiation and at 2, 4, and 12 weeks of IFN-α treatment, measurements of TRP, KYN, and neopterin (a marker of immune activation), were obtained, along with structured assessments of depression, anxiety, and neurotoxicity. Results: Regardless of antidepressant treatment status, all patients exhibited significant increases in KYN, neopterin, and the KYN/TRP ratio during IFN-α therapy. Among antidepressant-free patients, patients who developed major depression exhibited significantly greater increases in KYN and neopterin concentrations and more prolonged decreases in TRP concentrations than did nondepressed, antidepressant-free patients. Moreover, in antidepressant-free patients, decreases in TRP correlated with depressive, anxious, and cognitive symptoms, but not neurovegetative or somatic symptoms. No correlations were found between clinical and biological variables in antidepressant-treated patients. Conclusions: The results suggest that reduced TRP availability plays a role in IFN-α-induced depressive symptoms, and paroxetine, although not altering the KYN or neopterin response to IFN-α, attenuates the behavioral consequences of IFN-α-mediated TRP depletion.
KW - Depressive symptoms
KW - Indoleamine-2,3- dioxygenase
KW - Interferon-alpha
KW - Kynurenine
KW - Neopterin
KW - Tryptophan
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U2 - 10.1016/S0006-3223(03)00173-2
DO - 10.1016/S0006-3223(03)00173-2
M3 - Article
C2 - 14573318
AN - SCOPUS:0142250797
VL - 54
SP - 906
EP - 914
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 9
ER -