A kynurenine pathway enzyme aminocarboxymuconate-semialdehyde decarboxylase may be involved in treatment-resistant depression, and baseline inflammation status of patients predicts treatment response: a pilot study

The kynurenine pathway (KP) and inflammation are substantial in depression pathogenesis. Although there is a crosstalk between the KP, inflammation, and neurotrophic factors, few studies examine these topics together. Novel medications may be developed by clarifying dysregulations related to inflammation, KP, and neurotrophic factors in treatment-resistant depression (TRD). We aimed to evaluate the serum levels of KP metabolites, proinflammatory biomarkers, and brain-derived neurotrophic factor (BDNF) in healthy controls (HC) and the patients with TRD whose followed up with three different treatments. Moreover, the effect of electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) on biomarkers was investigated. Study groups comprised a total of 30 unipolar TRD patients consisting of three separate patient groups (ECT = 8, rTMS = 10, pharmacotherapy = 12), and 9 HC. The decision to administer only pharmacotherapy or ECT/rTMS besides pharmacotherapy was given independently of this research by psychiatrists. Blood samples and symptom scores were obtained three times for patients. At baseline, quinolinic acid (QUIN) was higher in the patients with TRD compared to HC, whereas picolinic acid (PIC), PIC/QUIN, and PIC/3-hydroxykynurenine were lower. Baseline interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were higher in nonresponders and non-remitters. ECT had an acute effect on cytokines. In the rTMS group, tumor necrosis factor-α (TNF-α) decreased in time. PIC, QUIN, and aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) enzyme may play a role in TRD pathogenesis, and have diagnostic potential. rTMS and ECT have modulatory effects on low-grade inflammation seen in TRD. Baseline inflammation severity is predictive in terms of response and remission in depression.