Changes in tryptophan breakdown associated with response to multimodal treatment in depression

Eva Z Reininghaus; Melanie Lenger; Elena M D Schönthaler; Frederike T Fellendorf; Tatjana Stross; Markus Schwarz; Natalie Moll; Bernd Reininghaus; Nina Dalkner

doi:10.3389/fpsyt.2024.1380620

Changes in tryptophan breakdown associated with response to multimodal treatment in depression

Front Psychiatry. 2024 Jun 21:15:1380620. doi: 10.3389/fpsyt.2024.1380620. eCollection 2024.

Authors

Eva Z Reininghaus¹, Melanie Lenger¹, Elena M D Schönthaler¹, Frederike T Fellendorf¹, Tatjana Stross¹, Markus Schwarz², Natalie Moll², Bernd Reininghaus¹, Nina Dalkner¹

Affiliations

¹ Clinical Division of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.
² Institute of Laboratory Medicine, University Hospital, Ludwig-Maximilian University (LMU), Munich, Munich, Germany.

Abstract

Background: Research on depression showed that dysregulations in tryptophan (TRP), kynurenine (KYN), and its KYN pathway metabolites are key aspects in the development and maintenance of depressive symptoms. In our previous reports, we described sex-specific changes in TRP breakdown as well as changes in KYN and KYN/TRP in association with treatment response and inflammatory and metabolic parameters. However, results of treatment effects on KYN pathway metabolites as well as how pathway changes are related to treatment response remain sparse.

Objective: We investigated potential changes of KYN and KYN pathway metabolites in association with therapeutic response of individuals with depression during a six-week multimodal psychiatric rehabilitation program.

Methods: 87 participants were divided into treatment responders and non-responders (48 responders, 39 non-responders; 38 male, 49 female; M _age = 51.09; SD _age = 7.70) using scores of psychological questionnaires. KYN pathway metabolites serum concentrations as well as their ratios were collected using high performance liquid chromatography. Changes over time (time of admission (t1) vs. time of discharge (t2)) were calculated using repeated measure analyses of (co)variance.

Results: Non-responders exhibited higher levels of 3-Hydroxyanthralinic acid (3-HAA), nicotinic acid (NA), and 3-HAA/KYN, independently of measurement time. NA levels decreased, while 3-HAA levels increased over time in both groups, independently of treatment response. 3-HK/KYN levels decreased, while KYN levels increased in non-responders, but not in responders over time.

Discussion: The results indicate that some compounds of the KYN pathway metabolites can be altered through multimodal long-term interventions in association with treatment response. Especially the pathway degrading KYN further down to 3-HAA and 3-HK/KYN might be decisive for treatment response in depression.

Keywords: affective disorder; depression; kynurenine; kynurenine pathway; multimodal treatment.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Open Acces was funded by “Das Land Steiermark, Economy, Tourism, Science and Research”.