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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Neuroinflammation
2016 ; 13
(1
): 51
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Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine
pathway in treatment-resistant depressed patients
#MMPMID26925576
Schwieler L
; Samuelsson M
; Frye MA
; Bhat M
; Schuppe-Koistinen I
; Jungholm O
; Johansson AG
; Landén M
; Sellgren CM
; Erhardt S
J Neuroinflammation
2016[Feb]; 13
(1
): 51
PMID26925576
show ga
BACKGROUND: Neuroinflammation is increasingly recognized as contributing to the
pathogenesis of depression. Key inflammatory markers as well as kynurenic acid
(KYNA) and quinolinic acid (QUIN), both tryptophan metabolites, have been
associated with depressive symptoms and suicidality. The aim of the present study
is to investigate the peripheral concentration of cytokines and tryptophan and
kynurenine metabolites in patients with unipolar treatment-resistant depression
before and after electroconvulsive therapy (ECT), the most effective treatment
for depression. METHODS: Cytokines in plasma from patients with major depressive
disorder (MDD; n?=?19) and healthy volunteers (n?=?14) were analyzed with
electrochemiluminescence detection. Tryptophan and kynurenine metabolites were
detected with high-performance liquid chromatography (HPLC) and LC/MS. KYNA was
analyzed in a second healthy control cohort (n?=?22). RESULTS: Patients with MDD
had increased plasma levels of interleukin (IL)-6 compared to healthy volunteers
(P?0.05). We also found an altered kynurenine metabolism in these patients
displayed by decreased plasma levels of KYNA (P?0.0001) as well as a
significantly increased QUIN/KYNA ratio (P?0.001). Plasma levels of tryptophan,
kynurenine, and QUIN did not differ between patients and controls. Treatment with
ECT was associated with a significant decrease in the plasma levels of tryptophan
(P?0.05), kynurenine (P?0.01), and QUIN (P?0.001), whereas plasma levels of
KYNA did not change. The QUIN/KYNA ratio was found to significantly decrease in
ECT-treated patients (P?0.05). There was a significant inverse correlation
between symptom severity and kynurenine levels at baseline (r?=?-0.67,
P?=?0.002). CONCLUSIONS: This study confirms an imbalanced kynurenine pathway in
MDD supporting the hypothesis of a netstimulation of N-methyl-D-aspartic acid
(NMDA) receptors in the disorder. Treatment with ECT profoundly decreased QUIN,
an NMDA-receptor agonist previously suggested to be implicated in the
pathogenesis of depression, an effect that might have bearing for the good
clinical outcome of ECT.