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High Kynurenine (a Tryptophan Metabolite) Predicts Remission in Patients with Major Depression to Add-on Treatment with Celecoxib

View Article: PubMed Central - PubMed

ABSTRACT

Background: Signs of an inflammatory process have been described in major depression.

Methods: In a double-blind, randomized study of celecoxib or placebo add-on to reboxetine in 40 depressed patients, celecoxib treatment has beneficial effects. In order to evaluate the tryptophan/kynurenine metabolism and to identify predictors for remission, tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were estimated in the serum of 32 patients before and after treatment and in a group of 20 healthy controls.

Results: KYN levels were significantly lower in patients (p = 0.008), and the QUIN/KYN ratios were significantly higher (p = 0.028). At baseline, the higher KYN/TRP ratio was predictive for remission during celecoxib add-on treatment (p = 0.04) as well as for remission in the overall patient group (p = 0.01). In the placebo group, remitters showed a higher KYNA/QUIN ratio (p = 0.032). In the overall group, remitters showed lower KYNA/KYN (p = 0.035) and QUIN/KYN (p = 0.011) ratios. The lower the formation of downstream metabolites, especially QUIN, the better the treatment outcome.

Conclusion: The high KYN/TRP ratio predicted remission after treatment with celecoxib in this small sample of depressed patients. Eventually, the KYN/TRP ratio might be a marker for those patients, which benefit from an additional anti-inflammatory treatment.

No MeSH data available.


Related in: MedlinePlus

Comparison of QUIN/KYN ratio at baseline (QUIN/KYN V0) between remitters (n = 9) and non-remitters (n = 23) from the overall group of patients with major depression.
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Figure 3: Comparison of QUIN/KYN ratio at baseline (QUIN/KYN V0) between remitters (n = 9) and non-remitters (n = 23) from the overall group of patients with major depression.

Mentions: In the overall group (celecoxib and placebo add-on to reboxetine), remitters (n = 9) showed a higher KYN/TRP ratio (11.51 ± 1.81 vs 9.31 ± 1.99; t = −2.72, p = 0.011) (Figure 2) and lower KYNA/KYN (0.163 ± 0.017 vs 0.19 ± 0.051; t = −2.22, p = 0.035) (Figure 3) and lower QUIN/KYN (0.139 ± 0.022 vs 0.179 ± 0.057; t = −2.74, p = 0.011) ratios. When age and gender were controlled for, higher KYN/TRP was predictive for remission to antidepressant treatment with or without celecoxib add-on in terms of reduction of HAMD score to 7 or below (B = 33.012, F = 10.312, p = 0.004).


High Kynurenine (a Tryptophan Metabolite) Predicts Remission in Patients with Major Depression to Add-on Treatment with Celecoxib
Comparison of QUIN/KYN ratio at baseline (QUIN/KYN V0) between remitters (n = 9) and non-remitters (n = 23) from the overall group of patients with major depression.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5304105&req=5

Figure 3: Comparison of QUIN/KYN ratio at baseline (QUIN/KYN V0) between remitters (n = 9) and non-remitters (n = 23) from the overall group of patients with major depression.
Mentions: In the overall group (celecoxib and placebo add-on to reboxetine), remitters (n = 9) showed a higher KYN/TRP ratio (11.51 ± 1.81 vs 9.31 ± 1.99; t = −2.72, p = 0.011) (Figure 2) and lower KYNA/KYN (0.163 ± 0.017 vs 0.19 ± 0.051; t = −2.22, p = 0.035) (Figure 3) and lower QUIN/KYN (0.139 ± 0.022 vs 0.179 ± 0.057; t = −2.74, p = 0.011) ratios. When age and gender were controlled for, higher KYN/TRP was predictive for remission to antidepressant treatment with or without celecoxib add-on in terms of reduction of HAMD score to 7 or below (B = 33.012, F = 10.312, p = 0.004).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Signs of an inflammatory process have been described in major depression.

Methods: In a double-blind, randomized study of celecoxib or placebo add-on to reboxetine in 40 depressed patients, celecoxib treatment has beneficial effects. In order to evaluate the tryptophan/kynurenine metabolism and to identify predictors for remission, tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were estimated in the serum of 32 patients before and after treatment and in a group of 20 healthy controls.

Results: KYN levels were significantly lower in patients (p = 0.008), and the QUIN/KYN ratios were significantly higher (p = 0.028). At baseline, the higher KYN/TRP ratio was predictive for remission during celecoxib add-on treatment (p = 0.04) as well as for remission in the overall patient group (p = 0.01). In the placebo group, remitters showed a higher KYNA/QUIN ratio (p = 0.032). In the overall group, remitters showed lower KYNA/KYN (p = 0.035) and QUIN/KYN (p = 0.011) ratios. The lower the formation of downstream metabolites, especially QUIN, the better the treatment outcome.

Conclusion: The high KYN/TRP ratio predicted remission after treatment with celecoxib in this small sample of depressed patients. Eventually, the KYN/TRP ratio might be a marker for those patients, which benefit from an additional anti-inflammatory treatment.

No MeSH data available.


Related in: MedlinePlus