Serum neuroactive metabolites of the tryptophan pathway in patients with acute phase of affective disorders

Yanli Li; Leilei Wang; Junchao Huang; Ping Zhang; Yanfang Zhou; Jinghui Tong; Wenjin Chen; Mengzhuang Gou; Baopeng Tian; Wei Li; Xingguang Luo; Li Tian; L Elliot Hong; Chiang-Shan R Li; Yunlong Tan

doi:10.3389/fpsyt.2024.1357293

Serum neuroactive metabolites of the tryptophan pathway in patients with acute phase of affective disorders

Front Psychiatry. 2024 Apr 12:15:1357293. doi: 10.3389/fpsyt.2024.1357293. eCollection 2024.

Authors

Affiliations

¹ Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan, Hospital, Beijing, China.
² Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States.
³ Institute of Biomedicine and Translational Medicine, Department of Physiology, Faculty of Medicine, University of Tartu, Tartu, Estonia.
⁴ Louis A. Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States.

^# Contributed equally.

Abstract

Background: Many studies showed disrupted tryptophan metabolism in patients with affective disorders. The aims of this study were to explore the differences in the metabolites of tryptophan pathway (TP) and the relationships between TP metabolites and clinical symptoms, therapeutic effect in patients with bipolar disorder with acute manic episode (BD-M), depressive episode (BD-D) and major depressive disorder (MDD).

Methods: Patients with BD-M (n=52) and BD-D (n=39), MDD (n=48) and healthy controls (HCs, n=49) were enrolled. The serum neuroactive metabolites levels of the TP were measured by liquid chromatography-tandem mass spectrometry. Hamilton Depression Scale-17 item (HAMD-17) and Young Mania Rating Scale (YMRS) were used to evaluate depressive and manic symptoms at baseline and after 8 weeks of antidepressants, mood stabilizers, some also received antipsychotic medication.

Results: The levels of tryptophan (TRP) and kynurenic acid (KYNA) were significantly lower and the ratios of tryptophan/kynurenine (TRP/KYN), 5-hydroxytryptamine/tryptophan (5-HT/TRP), quinolinic acid/kynurenic acid (QUIN/KYNA) were higher in BD-M, BD-D, MDD vs. HC. The levels of QUIN and the ratios of QUIN/KYNA were higher in BD-M than in BD-D, MDD, and HCs. The 5-hydroxyindoleacetic acid (5-HIAA) levels of patients with MDD were significantly higher than those in BD-M and BD-D. Binary logistic regression analysis showed the lower peripheral KYNA, the higher the QUIN level, and the higher the risk of BD-M; the lower peripheral KYNA and the higher KYN/TRP and 5-HT/TRP, the higher the risk of BD-D; and the lower the peripheral KYNA level and the higher the KYN/TRP and 5-HT/TRP, the higher the risk of MDD. Correlation analysis, showing a significant association between tryptophan metabolites and improvement of clinical symptoms, especially depression symptoms.

Conclusions: Patients with affective disorders had abnormal tryptophan metabolism, which involved in 5-HT and kynurenine pathway (KP) sub-pathway. Tryptophan metabolites might be potential biomarkers for affective disorders and some metabolites have been associated with remission of depressive symptoms.

Keywords: 5-hydroxytryptamine pathway; bipolar disorder; kynurenine pathway; major depressive disorder; tryptophan metabolism.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Support was received from the Capital’s Funds for Health Improvement and Research (CFH2020-2-2134).