Does tryptophan degradation along the kynurenine pathway mediate the association between pro-inflammatory immune activity and depressive symptoms?
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.
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Jacqueline
J
Quak
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: b.doornbos@umcg.nl.
Bennard
B
Doornbos
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Annelieke M
AM
Roest
Center of Research on Psychology in Somatic Diseases, Tilburg University, The Netherlands.
Hester E
HE
Duivis
Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Nicole
N
Vogelzangs
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Willem A
WA
Nolen
Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Brenda W J H
BW
Penninx
Department of Laboratory Medicine, University Medical Center, University of Groningen, Groningen, The Netherlands.
Ido P
IP
Kema
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Peter
P
de Jonge
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003863:Depression / Q000276:immunology* / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007107:Immune System / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D009426:Netherlands; D059748:Proteolysis; D014364:Tryptophan / Q000378:metabolism*; D055815:Young Adult
D018836:Inflammation Mediators; D007737:Kynurenine; D014364:Tryptophan
Depression; Depressive symptoms; Indoleamine 2,3-dioxygenase; Inflammation; Kynurenine; Tryptophan