Kynurenine Metabolites and Inflammation Markers in Depressed Patients Treated With Fluoxetine or Counselling

Abstract

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.

Stress-Induced Increase in Kynurenic Acid as a Potential Biomarker for Patients With Schizophrenia and Distress Intolerance

“…47 Rodents treated with antipsychotics or antidepressants also failed to show a substantial effect on peripheral KYNA. 1,48,49 We did not find a clear relationship between dose of antipsychotics and salivary KYNA level, nor did salivary KYNA level differ between patients treated vs not treated with antipsychotics. It is therefore unlikely that the pattern of increased KYNA levels in patients with distress intolerance can be explained by effects of antipsychotics.…”

Effect of antidepressant treatment on peripheral inflammation markers – A meta-analysis

“…Longitudinal studies with multiple blood draws indicated that the levels of cytokines may significantly fluctuate over the time of treatment which may partially explain the inconsistency of results among presented studies [Hernandez et al, 2013;Mackay et al, 2009]. …”

“…We did not include studies measuring the effect of non-pharmacological depression treatments or studies with the use of ketamine or pharmacological agents not registered as antidepressants. We did however partially include some studies (Brunoni et al 2014, Ranjbar et al 2014, Hernandez et al 2014, Abbasi et al 2012, Mackay et al 2009, Jazayeri et al 2010) examining the effect of other than antidepressant therapies with the control group (e.g. treated with an SSRI) meeting our inclusion criteria.…”

A review of peripheral biomarkers in major depression: The potential of inflammatory and oxidative stress biomarkers

“…TRYCATs -Little or no change was observed in the concentrations of any of the TRYCATs following treatment with fluoxetine, fluoxetine plus the thyroid hormone triiodothyronine (T3), or counselling (Mackay et al, 2009). Despite this, in a correlation analysis at weeks 6 and 18, highly significant relationships between several of the TRYCATs and psychiatric inventory scores were revealed.…”