Kynurenine metabolites and inflammation markers in depressed patients treated with fluoxetine or counselling.
1. Depression could result from changes in tryptophan availability caused by activation of the kynurenine pathway as a result of inflammation. In the present study, we examined patients newly diagnosed with depression to determine whether kynurenines and related factors change in parallel with improvements in mood. 2. Concentrations of 5-hydroxytryptamine (5-HT; serotonin), 5-hydroxyindoleacetic acid (5-HIAA), oxidized tryptophan metabolites, brain-derived neurotrophic factor (BDNF) and inflammatory mediators (interleukin (IL)-2, C-reactive protein (CRP), neopterin) were measured in peripheral blood during an 18 week period of treatment with fluoxetine, fluoxetine plus tri-iodothyronine (T(3)) or psychiatric counselling. 3. The results showed significant improvements in mood, with reduced 5-HT concentrations in patients given fluoxetine and a rise in plasma tryptophan in patients given counselling or fluoxetine and T(3). The addition of T(3) to the fluoxetine regimen appeared to slow recovery from depression, although the use of T(3) was associated with a fall in thyroxine concentrations. Changes in 5-HT concentrations did not correlate with psychiatric scores and were seen only in drug-treated groups, not those given counselling. There were no associated changes in absolute concentrations of kynurenines, BDNF, CRP, neopterin or IL-2. With fluoxetine treatment, there were correlations between the concentrations of kynurenine metabolites and the psychiatric rating scores, whereas no correlations were found with BDNF or inflammatory markers. 4. It is concluded that depression scores are largely independent of inflammatory status, but kynurenine metabolism may be related to the degree of depression after fluoxetine treatment.
Mackay
Gillian M
GM
Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.
Forrest
Caroline M
CM
Christofides
John
J
Bridel
Michala A
MA
Mitchell
Susan
S
Cowlard
Richard
R
Stone
Trevor W
TW
Darlington
L Gail
LG
D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D003376:Counseling; D003863:Depression / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000032:analysis / Q000097:blood; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000378:metabolism*; D007737:Kynurenine / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011613:Psychotherapy / Q000379:methods; D012701:Serotonin / Q000032:analysis / Q000097:blood; D014284:Triiodothyronine / Q000008:administration & dosage / Q000494:pharmacology
D000928:Antidepressive Agents; D015415:Biomarkers; D005473:Fluoxetine; D014284:Triiodothyronine; D012701:Serotonin; D007737:Kynurenine; D006897:Hydroxyindoleacetic Acid