Abstract | BACKGROUND: 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.
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Authors | Lilly Schwieler, Martin Samuelsson, Mark A Frye, Maria Bhat, Ina Schuppe-Koistinen, Oscar Jungholm, Anette G Johansson, Mikael Landén, Carl M Sellgren, Sophie Erhardt |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 13
Issue 1
Pg. 51
(Feb 29 2016)
ISSN: 1742-2094 [Electronic] England |
PMID | 26925576
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cytokines
- IL6 protein, human
- Interleukin-6
- Kynurenine
- Tryptophan
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Topics |
- Adult
- Chromatography, High Pressure Liquid
- Cohort Studies
- Cytokines
(blood)
- Depressive Disorder, Major
(metabolism, psychology, therapy)
- Depressive Disorder, Treatment-Resistant
(metabolism, psychology, therapy)
- Diagnostic and Statistical Manual of Mental Disorders
- Electroconvulsive Therapy
- Female
- Humans
- Interleukin-6
(blood)
- Kynurenine
(metabolism)
- Luminescence
- Male
- Metabolic Networks and Pathways
- Middle Aged
- Psychiatric Status Rating Scales
- Treatment Outcome
- Tryptophan
(blood)
- Young Adult
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