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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

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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A Correction to this article was published on 14 December 2022

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Abstract

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.

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The data that support the findings of this study are available on request from the corresponding author.

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Acknowledgements

We would like to thank all the participants who attended our study. We also thank Reyhan Canbay, Aycan Kayalar, and all nurses from the psychiatry departments in GUFM, and HSU GTRH, biochemistry and psychiatry doctors in GUFM, Prof. Dr. Behcet Cosar from GUFM, and Prof.Dr. Kamil Nahit Ozmenler from HSU GTRH.

Funding

The research was supported by Gazi University Scientific Research Projects with project number 01/2018—30.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey

    Niyazi Samet Yilmaz, Bayram Sen, Cemal Cevik & Neslihan Bukan

  2. Department of Psychiatry, Faculty of Medicine, Gazi University, Ankara, Turkey

    Rukiye Filiz Karadag, Selcuk Aslan, Irem Ekmekci Ertek, Aruz Bozkurt & Saba Cicek

  3. Department of Psychiatry, Health Sciences University Gulhane Training and Research Hospital, Ankara, Turkey

    Abdullah Bolu & Huseyin Ucar

  4. Republic of Turkey Ministry of Health, General Directorate of Public Health, Ankara, Turkey

    Cemal Kocak

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  1. Niyazi Samet Yilmaz
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Contributions

NSY: conceptualization, data curation, ınvestigation, methodology, project administration, resources, supervision, visualization, writing—original draft, and writing—review and editing. BS: conceptualization, data curation, ınvestigation, methodology, visualization, and writing—review and editing. RFK: conceptualization, methodology, project administration, and supervision. SA: conceptualization, methodology, project administration, and supervision. IEE: conceptualization, ınvestigation, and methodology ab: ınvestigation, methodology, and resources. SC: ınvestigation, methodology, and resources. AB: conceptualization and methodology. HU: ınvestigation, methodology, and resources. CK: data curation, formal analysis, and visualization. CC: conceptualization, methodology, funding acquisition, project administration, and supervision. NB: conceptualization, funding acquisition, ınvestigation, methodology, project administration, supervision, and writing—review and editing.

Corresponding author

Correspondence to Niyazi Samet Yilmaz.

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Conflict of Interest

The authors have no relevant financial or non-financial interest to disclose.

Ethical approval

The study began and performed with the approval of GUFM Clinical Research Ethics Committee (Date/Number: 12.02.2018/99, and 24.09.2018/688).

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Yilmaz, N.S., Sen, B., Karadag, R.F. et al. 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. J Neural Transm 129, 1513–1526 (2022). https://doi.org/10.1007/s00702-022-02553-x

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