The effect of inflammation, SARS-CoV-2 infection, age and mental health on serotonin, and kynurenine and catecholamine pathway metabolites

Katharina Hüfner; Sophia Vedova; Piotr Tymoszuk; Philipp Nelles; Tobias Bruckner; Eberhard A Deisenhammer; Jonas Egeter; Matyas Galffy; Johannes M Giesinger; Jens Lehmann; Maria Oberhammer; Joachim Rockenschaub; Magdalena Sacher; Bernhard Holzner; Johanna M Gostner; Barbara Sperner-Unterweger

doi:10.1016/j.psyneuen.2023.106334

The effect of inflammation, SARS-CoV-2 infection, age and mental health on serotonin, and kynurenine and catecholamine pathway metabolites

Psychoneuroendocrinology. 2023 Oct:156:106334. doi: 10.1016/j.psyneuen.2023.106334. Epub 2023 Jul 14.

Authors

Katharina Hüfner¹, Sophia Vedova², Piotr Tymoszuk³, Philipp Nelles², Tobias Bruckner², Eberhard A Deisenhammer⁴, Jonas Egeter², Matyas Galffy², Johannes M Giesinger², Jens Lehmann², Maria Oberhammer⁵, Joachim Rockenschaub², Magdalena Sacher⁶, Bernhard Holzner², Johanna M Gostner⁷, Barbara Sperner-Unterweger²

Affiliations

¹ University Hospital of Psychiatry II, Department of Psychiatry, Psychotherapy, Psychosomatics and Medical Psychology, Medical University Innsbruck, Innsbruck, Austria. Electronic address: katharina.huefner@tirol-kliniken.at.
² University Hospital of Psychiatry II, Department of Psychiatry, Psychotherapy, Psychosomatics and Medical Psychology, Medical University Innsbruck, Innsbruck, Austria.
³ Data Analytics As a Service Tirol, Innsbruck, Austria.
⁴ University Hospital of Psychiatry II, Department of Psychiatry, Psychotherapy, Psychosomatics and Medical Psychology, Medical University Innsbruck, Innsbruck, Austria; University Hospital of Psychiatry I, Department of Psychiatry, Psychotherapy, Psychosomatics and Medical Psychology, Medical University Innsbruck, Innsbruck, Austria.
⁵ University Hospital of Psychiatry I, Department of Psychiatry, Psychotherapy, Psychosomatics and Medical Psychology, Medical University Innsbruck, Innsbruck, Austria.
⁶ Department of Visceral, Transplant and Thoracic Surgery (VTT), Medical University Innsbruck, Innsbruck, Austria.
⁷ Institute of Medical Biochemistry, Medical University Innsbruck, Innsbruck, Austria.

PMID: 37481962
DOI: 10.1016/j.psyneuen.2023.106334

Abstract

Background: A high prevalence of mental disorders following COVID-19 has been described. It is therefore essential to elucidate underlying biological mechanisms linking SARS-CoV-2 infection and mental health. The kynurenine and catecholamine metabolic pathways are modulated by inflammation and can affect systemic levels of serotonin and dopamine. Their activity may hence link physical disorders with mental health. We investigated factors that affect kynurenine and catecholamine pathway activity in SARS-CoV-2 infection and recovery.

Methods: The cross-sectional SIMMUN (n = 165) and longitudinal INCOV cohort (n = 167, Su et al. 2022) were analyzed. Demographic and clinical characteristic, inflammatory markers, SARS-CoV-2 infection, symptoms of depression and anxiety (HADS), and mental stress (PSS-4) served as explanatory variables. Blood serotonin and markers of kynurenine (kynurenine/tryptophan ratio), and catecholamine pathway activity (dopamine 3-O-sulfate, phenylalanine/tyrosine ratio) were modeled by multi-parameter linear regression.

Results: In the SIMMUN cohort, the inflammatory marker neopterin (β = 0.47 [95% CI: 0.34-0.61]), SARS-CoV-2-positivity (0.42 [0.16-0.68]), mental stress (0.18 [0.055-0.31]), and age (0.26 [0.12-0.39]) were positively associated with the kynurenine/tryptophan ratio. The phenylalanine/tyrosine ratio was lower in SARS-CoV-2-positive than uninfected participants (-0.38 [-0.68 to -0.08]). In the INCOV cohort, markers of inflammation were associated with lower serotonin (IL6: -0.22 [-0.38 to -0.053]) and dopamine 3-O-sulfate levels (interferon-gamma: -0.15 [-0.26 to -0.036]). Serotonin (0.76 [0.34-1.2]) and dopamine 3-O-sulfate levels (0.63 [0.28-0.99]) were higher during recovery than in acute SARS-CoV-2 infection.

Conclusion: SARS-CoV-2 infection, inflammation, age and mental stress are key independent predictors of kynurenine pathway activity, which may influence serotonin availability. The catecholamine pathway was also affected in SARS-CoV-2 infection. Altered activity of these pathways may contribute to impaired mental health following COVID-19.

Keywords: COVID-19; Inflammation; Kynurenine; Mental health; Serotonin and dopamine availability; Tryptophan.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Cross-Sectional Studies
Dopamine
Humans
Inflammation
Kynurenine* / metabolism
Mental Health
Phenylalanine
SARS-CoV-2
Serotonin / metabolism
Tryptophan / metabolism
Tyrosine

Substances

Kynurenine
Tryptophan
Serotonin
dopamine 3-O-sulfate
Dopamine
Phenylalanine
Tyrosine