Does tryptophan degradation along the kynurenine pathway mediate the association between pro-inflammatory immune activity and depressive symptoms?

J. Quak, B. Doornbos, A.M. Roest, H.E. Duivis, N. Vogelzangs, W.A. Nolen, B.W.J.H. Penninx, I.P. Kema, P. de Jonge

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Background
Several studies have suggested that induced tryptophan (TRP) degradation through the kynurenine (KYN) pathway by the enzyme indoleamine 2,3-dioxygenase (IDO) is implicated in the relation between depression and inflammation. We investigated the role of tryptophan degradation in the relationship between inflammatory markers and depressive symptoms in the Netherlands Study of Depression and Anxiety (NESDA) and hypothesized that tryptophan degradation would mediate (part of) this association.
Methods
2812 Participants of NESDA were included in this study including 1042 persons with current major depressive disorder (MDD). Assessments of C-reactive protein (CRP), interleukin (IL)-6, tumor-necrosis factor (TNF)-α, KYN and TRP were obtained from fasting blood samples at the baseline assessment. Tryptophan degradation was estimated by calculating the ratio [KYN/TRP]. Depressive symptoms were measured with the Inventory of Depressive Symptomatology.
Results
Significant associations between inflammation and depressive symptoms were found for CRP and IL-6, for the total group and the subgroup of patients with current MDD. Adjustment for KYN/TRP did not attenuate these associations. There were no significant indirect effects for CRP on depressive symptoms mediated by KYN/TRP for the whole group (B = −0.032; 95% CI: −0.103 to 0.028) and for the subgroup of patients with current MDD (B = 0.059; 95% CI: −0.037 to 0.165). Also IL-6 did not indirectly affect depressive symptoms through KYN/TRP in the total group (B = −0.023; 95% CI: −0.093 to 0.045) and in the MDD subgroup B = 0.052; 95% CI: −0.019 to 0.144). Finally, no significant relation between depressive symptoms and KYN/TRP was found in the whole group (β = −0.019, p = 0.311) nor in the subgroup with MDD (β = 0.025, p = 0.424).
Conclusions
We did not find indications for tryptophan degradation, measured by KYN/TRP, to mediate the relationship between inflammation and depressive symptoms.
Keywords: Indoleamine 2,3-dioxygenase, Depressive symptoms, Depression, Tryptophan, Kynurenine, Inflammation
Original languageEnglish
Pages (from-to)202-210
JournalPsychoneuroendocrinology
Volume45
DOIs
Publication statusPublished - 2014

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Kynurenine
Depression
Major Depressive Disorder
Indoleamine-Pyrrole 2,3,-Dioxygenase
Interleukin-6
Netherlands

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Quak, J. ; Doornbos, B. ; Roest, A.M. ; Duivis, H.E. ; Vogelzangs, N. ; Nolen, W.A. ; Penninx, B.W.J.H. ; Kema, I.P. ; de Jonge, P. / Does tryptophan degradation along the kynurenine pathway mediate the association between pro-inflammatory immune activity and depressive symptoms?. In: Psychoneuroendocrinology. 2014 ; Vol. 45. pp. 202-210.
@article{8002231f519e48488e662b1822d8f72c,
title = "Does tryptophan degradation along the kynurenine pathway mediate the association between pro-inflammatory immune activity and depressive symptoms?",
abstract = "BackgroundSeveral studies have suggested that induced tryptophan (TRP) degradation through the kynurenine (KYN) pathway by the enzyme indoleamine 2,3-dioxygenase (IDO) is implicated in the relation between depression and inflammation. We investigated the role of tryptophan degradation in the relationship between inflammatory markers and depressive symptoms in the Netherlands Study of Depression and Anxiety (NESDA) and hypothesized that tryptophan degradation would mediate (part of) this association.Methods2812 Participants of NESDA were included in this study including 1042 persons with current major depressive disorder (MDD). Assessments of C-reactive protein (CRP), interleukin (IL)-6, tumor-necrosis factor (TNF)-α, KYN and TRP were obtained from fasting blood samples at the baseline assessment. Tryptophan degradation was estimated by calculating the ratio [KYN/TRP]. Depressive symptoms were measured with the Inventory of Depressive Symptomatology.ResultsSignificant associations between inflammation and depressive symptoms were found for CRP and IL-6, for the total group and the subgroup of patients with current MDD. Adjustment for KYN/TRP did not attenuate these associations. There were no significant indirect effects for CRP on depressive symptoms mediated by KYN/TRP for the whole group (B = −0.032; 95{\%} CI: −0.103 to 0.028) and for the subgroup of patients with current MDD (B = 0.059; 95{\%} CI: −0.037 to 0.165). Also IL-6 did not indirectly affect depressive symptoms through KYN/TRP in the total group (B = −0.023; 95{\%} CI: −0.093 to 0.045) and in the MDD subgroup B = 0.052; 95{\%} CI: −0.019 to 0.144). Finally, no significant relation between depressive symptoms and KYN/TRP was found in the whole group (β = −0.019, p = 0.311) nor in the subgroup with MDD (β = 0.025, p = 0.424).ConclusionsWe did not find indications for tryptophan degradation, measured by KYN/TRP, to mediate the relationship between inflammation and depressive symptoms.Keywords: Indoleamine 2,3-dioxygenase, Depressive symptoms, Depression, Tryptophan, Kynurenine, Inflammation",
author = "J. Quak and B. Doornbos and A.M. Roest and H.E. Duivis and N. Vogelzangs and W.A. Nolen and B.W.J.H. Penninx and I.P. Kema and {de Jonge}, P.",
year = "2014",
doi = "10.1016/j.psyneuen.2014.03.013",
language = "English",
volume = "45",
pages = "202--210",
journal = "Psychoneuroendocrinology",
issn = "0306-4530",
publisher = "PERGAMON-ELSEVIER SCIENCE LTD",

}

Does tryptophan degradation along the kynurenine pathway mediate the association between pro-inflammatory immune activity and depressive symptoms? / Quak, J.; Doornbos, B.; Roest, A.M.; Duivis, H.E.; Vogelzangs, N.; Nolen, W.A.; Penninx, B.W.J.H.; Kema, I.P.; de Jonge, P.

In: Psychoneuroendocrinology, Vol. 45, 2014, p. 202-210.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Does tryptophan degradation along the kynurenine pathway mediate the association between pro-inflammatory immune activity and depressive symptoms?

AU - Quak, J.

AU - Doornbos, B.

AU - Roest, A.M.

AU - Duivis, H.E.

AU - Vogelzangs, N.

AU - Nolen, W.A.

AU - Penninx, B.W.J.H.

AU - Kema, I.P.

AU - de Jonge, P.

PY - 2014

Y1 - 2014

N2 - BackgroundSeveral studies have suggested that induced tryptophan (TRP) degradation through the kynurenine (KYN) pathway by the enzyme indoleamine 2,3-dioxygenase (IDO) is implicated in the relation between depression and inflammation. We investigated the role of tryptophan degradation in the relationship between inflammatory markers and depressive symptoms in the Netherlands Study of Depression and Anxiety (NESDA) and hypothesized that tryptophan degradation would mediate (part of) this association.Methods2812 Participants of NESDA were included in this study including 1042 persons with current major depressive disorder (MDD). Assessments of C-reactive protein (CRP), interleukin (IL)-6, tumor-necrosis factor (TNF)-α, KYN and TRP were obtained from fasting blood samples at the baseline assessment. Tryptophan degradation was estimated by calculating the ratio [KYN/TRP]. Depressive symptoms were measured with the Inventory of Depressive Symptomatology.ResultsSignificant associations between inflammation and depressive symptoms were found for CRP and IL-6, for the total group and the subgroup of patients with current MDD. Adjustment for KYN/TRP did not attenuate these associations. There were no significant indirect effects for CRP on depressive symptoms mediated by KYN/TRP for the whole group (B = −0.032; 95% CI: −0.103 to 0.028) and for the subgroup of patients with current MDD (B = 0.059; 95% CI: −0.037 to 0.165). Also IL-6 did not indirectly affect depressive symptoms through KYN/TRP in the total group (B = −0.023; 95% CI: −0.093 to 0.045) and in the MDD subgroup B = 0.052; 95% CI: −0.019 to 0.144). Finally, no significant relation between depressive symptoms and KYN/TRP was found in the whole group (β = −0.019, p = 0.311) nor in the subgroup with MDD (β = 0.025, p = 0.424).ConclusionsWe did not find indications for tryptophan degradation, measured by KYN/TRP, to mediate the relationship between inflammation and depressive symptoms.Keywords: Indoleamine 2,3-dioxygenase, Depressive symptoms, Depression, Tryptophan, Kynurenine, Inflammation

AB - BackgroundSeveral studies have suggested that induced tryptophan (TRP) degradation through the kynurenine (KYN) pathway by the enzyme indoleamine 2,3-dioxygenase (IDO) is implicated in the relation between depression and inflammation. We investigated the role of tryptophan degradation in the relationship between inflammatory markers and depressive symptoms in the Netherlands Study of Depression and Anxiety (NESDA) and hypothesized that tryptophan degradation would mediate (part of) this association.Methods2812 Participants of NESDA were included in this study including 1042 persons with current major depressive disorder (MDD). Assessments of C-reactive protein (CRP), interleukin (IL)-6, tumor-necrosis factor (TNF)-α, KYN and TRP were obtained from fasting blood samples at the baseline assessment. Tryptophan degradation was estimated by calculating the ratio [KYN/TRP]. Depressive symptoms were measured with the Inventory of Depressive Symptomatology.ResultsSignificant associations between inflammation and depressive symptoms were found for CRP and IL-6, for the total group and the subgroup of patients with current MDD. Adjustment for KYN/TRP did not attenuate these associations. There were no significant indirect effects for CRP on depressive symptoms mediated by KYN/TRP for the whole group (B = −0.032; 95% CI: −0.103 to 0.028) and for the subgroup of patients with current MDD (B = 0.059; 95% CI: −0.037 to 0.165). Also IL-6 did not indirectly affect depressive symptoms through KYN/TRP in the total group (B = −0.023; 95% CI: −0.093 to 0.045) and in the MDD subgroup B = 0.052; 95% CI: −0.019 to 0.144). Finally, no significant relation between depressive symptoms and KYN/TRP was found in the whole group (β = −0.019, p = 0.311) nor in the subgroup with MDD (β = 0.025, p = 0.424).ConclusionsWe did not find indications for tryptophan degradation, measured by KYN/TRP, to mediate the relationship between inflammation and depressive symptoms.Keywords: Indoleamine 2,3-dioxygenase, Depressive symptoms, Depression, Tryptophan, Kynurenine, Inflammation

U2 - 10.1016/j.psyneuen.2014.03.013

DO - 10.1016/j.psyneuen.2014.03.013

M3 - Article

VL - 45

SP - 202

EP - 210

JO - Psychoneuroendocrinology

JF - Psychoneuroendocrinology

SN - 0306-4530

ER -