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Activation and deactivation steps in the tryptophan breakdown pathway in major depressive disorder: A link to the monocyte inflammatory state of patients

Authors :
Arteaga-Henriquez, G
Burger, B
Weidinger, E
Grosse, L
Moll, N
Schuetze, G
Schwarz, M
Wijkhuijs, Annemarie
Op de Beeck, G
Berghmans, R
Versnel, Marjan
Arolt, V
Müller, N
Drexhage, Hemmo
Arteaga-Henriquez, G
Burger, B
Weidinger, E
Grosse, L
Moll, N
Schuetze, G
Schwarz, M
Wijkhuijs, Annemarie
Op de Beeck, G
Berghmans, R
Versnel, Marjan
Arolt, V
Müller, N
Drexhage, Hemmo
Source :
Arteaga-Henriquez , G , Burger , B , Weidinger , E , Grosse , L , Moll , N , Schuetze , G , Schwarz , M , Wijkhuijs , A , Op de Beeck , G , Berghmans , R , Versnel , M , Arolt , V , Müller , N & Drexhage , H 2021 , ' Activation and deactivation steps in the tryptophan breakdown pathway in major depressive disorder: A link to the monocyte inflammatory state of patients ' , Progress in Neuro-Psychopharmacology and Biological Psychiatry , vol. 107 , 110226 .
Publication Year :
2021

Abstract

It is unclear how the tryptophan (TRP) breakdown pathway relates to the activated inflammatory state of patients with major depressive disorder (MDD). We determined in two different cohorts of patients with MDD (n = 281) and healthy controls (HCs) (n = 206) collected for the EU-MOODINFLAME project: a.) the monocyte expression levels of 5 key pro-inflammatory cytokine/chemokine genes (ICCGs), 5 type I interferon stimulated genes (ISGs), and 4 kynurenine pathway (KP) enzyme genes (i.e. IDO-1, KMO, CCBL1/KAT II and CCBL2/KAT III) by standard q-PCR, b.) serum levels of TRP, 5-HTrp, 5-HIAA, KYN, KYNA, 3-HK, XA, PIC, and QUIN by LC-MS/MS and/or HPLC, and calculated various TRP/KP metabolism ratios. We then correlated outcomes to each other, and to the clinical characteristics of patients. Both cohorts of patients differed clinically; patients of the Munich cohort (n = 50) were less overweight, less medicated, were less in the current episode and showed a higher HAM-D 17 score as compared with patients of the Muenster cohort (n = 231). An increased expression of ICCGs was found in the circulating monocytes of patients of both cohorts; this was in particular evident in the Munich cohort. In contrast, ISGs monocyte expression levels tended to be reduced (both cohorts). TRP serum levels were linked to the pro-inflammatory (ICCGs) monocyte state of patients; a decrease in TRP serum levels was found in the Munich cohort; TRP levels correlated negatively to patient's HAM-D 17 score. Contrary to what expected, KYN serum levels were not increased in patients (both cohorts); and an increased KYN/TRP ratio was only found in the Munich patients (who showed the lowest TRP serum levels). IDO-1 monocyte expression levels were decreased in patients (both cohorts) and negatively associated to their pro-inflammatory (ICCGs) monocyte state. Thus, a depletion of TRP via an ICCGs-inflammatory IDO activation is not likely in MDD. Downstream from KYN, and regarding compounds influencing glut

Details

Database :
OAIster
Journal :
Arteaga-Henriquez , G , Burger , B , Weidinger , E , Grosse , L , Moll , N , Schuetze , G , Schwarz , M , Wijkhuijs , A , Op de Beeck , G , Berghmans , R , Versnel , M , Arolt , V , Müller , N & Drexhage , H 2021 , ' Activation and deactivation steps in the tryptophan breakdown pathway in major depressive disorder: A link to the monocyte inflammatory state of patients ' , Progress in Neuro-Psychopharmacology and Biological Psychiatry , vol. 107 , 110226 .
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1313630777
Document Type :
Electronic Resource