Changes in the levels of kynurenic acid and selected proinflammatory cytokines after pharmacological treatment and electroconvulsive therapy (ECT) in patients with depressive disorder

Abstract

The aim of the present study was to compare the concentrations of KYNA, 3-OH-KYN and the cytokines TNF-α and IL-6 in patients with depression vs. healthy controls as well as in patients with depression treated pharmacologically vs. those treated using ECT. We also evaluated the relationship between the concentrations of KYNA, 3-OH-KYN and the cytokines TNF-α and IL-6 and clinical improvement measured on the MADRS scale in patients treated pharmacologically and those treated with ECT.Subjects and methods: The study group comprised 29 patients aged 28 to 60 years with a diagnosis of a major depressive episode. Eleven of the patients received pharmacological treatment and 18 were treated with ECT.Patients were assayed for serum levels of KYNA and the cytokines IL-6 and TNF-α. Clinical improvement was measured on the MADRS depression rating scale and the clinical global impression (CGI) scale.Results: Significant differences were found in KYNA levels between depressive patients and healthy controls. Pharmacological treatment significantly contributed to the increase in KYNA levels and ECT – to the increase in TNF-α levels in depressive patients.Conclusions: Depressive patients have significantly lower concentrations of KYNA than healthy individualsDepressive patients who have undergone pharmacological treatment have significantly higher KYNA concentrations than before treatment.Depressive patients who have undergone ECT treatment have significantly lower TNF-α concentrations than before treatment.High pre-treatment levels of IL-6 are associated with a lower MADRS improvement index in pharmacologically treated patients with depression.

Chromatographic analysis of tryptophan metabolites

“…The increased Kyna concentration is associated also with other neurological conditions and was found elevated in Alzheimerʼs dementia (in brain) or in schizophrenia (in CSF) . Interestingly, the lower concentrations of Kyna have been recorded in CSF of Huntington's disease and depressive patients compared to control individuals. Important contribution to Kyna level has ᴅ‐amino acid oxidase (DAAO, a susceptibility gene of schizophrenia) converting ᴅ‐Kyn to Kyna .…”

“…Some of psychiatric/neurologic symptoms have been also found to correlate with Trp metabolites produced through kynurenine pathway in brain, CSF, astrocytes, plasma, and serum. The imbalance between neurodegenerative and neuroprotective Trp metabolites might explain the cause of major depression while the increased Trp degradation is involved in neuropathogenesis of Alzheimerʼs disease , Huntington's disease , Parkinson's disease , brain injury , AIDS dementia complex , meningitis , chronic migraine , and amyotrophic lateral sclerosis . In patients with schizophrenia an enhancement of TDO expression has been demonstrated .…”