The Metabolic Factor Kynurenic Acid of Kynurenine Pathway Predicts Major Depressive Disorder

Abstract

Background: Metabolic factors in the kynurenine pathway (KP) have been widely accepted as being a major mechanism in Major Depressive Disorder (MDD). However, the effects of these metabolites on the degree and pattern of MDD are still poorly understood, partly due to the elusiveness of the level of metabolites when diagnosing depression. This study aimed to explore a novel diagnostic method analyzing peripheral blood with mass spectrometry to assess metabolites from KP in patients with MDD and Bipolar Depression (BD).Methods: Thirty-three patients with MDD, 20 patients with BD, and 23 healthy control participants were enrolled Metabolic factors of KP from plasma including tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were analyzed by UPLC-3Q-MS, and levels compared across three groups. Correlation between HAMD scores and metabolite levels conducted. Receiver operating characteristic (ROC) curve was used to determine the diagnostic value of metabolic factors in MDD.Results: Levels of KYNA, QUIN, KYNA/QUIN, and KYNA/KYN were statistically different across the three groups (P < 0.05); HAMD scores and TRP, KYN, KYNA/QUIN levels were negatively correlated in the MDD group (r = −0.633, −0.477, −0.418, P < 0.05); Accuracy of KYNA diagnosing MDD was 82.5% with the optimal diagnostic value being 15.48 ng/ml. Diagnostic accuracy was increased to 83.6% when KYNA and QUIN levels were used in combination.Conclusion: This results indicate that metabolic factors of KP play a crucial role in the occurrence and development of MDD, supporting the metabolic imbalance hypothesis of MDD. Furthermore, our study also provides a new diagnostic method to study MDD based on plasma KYNA level, and suggests that KYNA would be a potential biomarker in diagnosing depression patients.

Kynurenic acid is a potential overlapped biomarker between diagnosis and treatment response for depression from metabolome analysis

“…A meta-analysis of these findings suggested that KYNA levels were decreased in patients with depression 27 . Another recent study also suggested that KYNA would be a potential biomarker in diagnosing depression patients 28 . In addition to reduced KYNA levels in MDD, a recent study demonstrated that the administration of KYNA induced antidepressant-like effects in an animal model of depression 29 .…”

Kynurenic acid underlies sex-specific immune responses to COVID-19

“…Of note, tryptophan was inversely associated with COVID-19 disease, as noted in Extended Data Table 3 . We examined the ratio of KA:K in patients with COVID-19 as a surrogate for KAT-mediated production of KA from K 7 . In males, we observed that a high KA:K was positively correlated with IL6, CCL1, CCL21, TNFα, M-CSF, NK cells, and CD8 terminally differentiated effector memory (Temra) T cells ( Fig.…”

Kynurenine Pathway Metabolites as Biomarkers for Amyotrophic Lateral Sclerosis

“…Using these modern techniques, the KP has been investigated as a marker for progression, severity, and prognostic for diseases such as systemic lupus erythematosus (Perl, 2015; Åkesson et al, 2018), cancers (Jin et al, 2015; Zuo et al, 2016; Xie et al, 2017; Huang et al, 2018; Liu et al, 2018; Khan et al, 2019), cardiovascular disease (Sun et al, 2013; Zuo et al, 2016), lung cancer and chronic obstructive pulmonary disease (Chuang et al, 2014; Zinellu et al, 2018), chronic kidney disease and diabetes (Hirayama et al, 2012; Zhao, 2013), acquired immunodeficiency syndrome (AIDS) and HIV-dementia (Fuchs et al, 1990; Heyes et al, 1991; Sardar et al, 2002; Guillemin et al, 2005b; Favre et al, 2010; Lee et al, 2016; Wang et al, 2019), pancreatic cysts (Park et al, 2013), acute myeloid leukemia and lymphomas (Giusti et al, 1996; Finger et al, 2017), vitamin levels (Midttun et al, 2014), tuberculosis (Weiner et al, 2012; Feng et al, 2015), malaria (Medana et al, 2003), irritable bowel syndrome (IBS) (Clarke et al, 2012; Gupta et al, 2012), rheumatoid arthritis (Spiera and Vallarino, 1969; Schroecksnadel et al, 2003), growth deficits (Kosek et al, 2016), obesity (Mangge et al, 2014), and preeclampsia (Nilsen et al, 2012). In the nervous system, the KP has been shown to associate with pathologies such as stroke (Darlington et al, 2007), schizophrenia (Müller and Schwarz, 2006; Kegel et al, 2014; Oxenkrug et al, 2016), Parkinson’s (Ogawa et al, 1992; Widner et al, 2002; Lewitt et al, 2013; Havelund et al, 2017), neuropsychiatric disorders such as depression and stress (Mackay et al, 2009; Gabbay et al, 2010; Olsson et al, 2010; Steiner et al, 2011; Kocki et al, 2012; Erhardt et al, 2013; Comai et al, 2016; Küster et al, 2017; Huang et al, 2018; Kuwano et al, 2018), suicide (Erhardt et al, 2013; Bay-Richter et al, 2015; Brundin et al, 2016), multiple sclerosis (Rejdak et al, 2002; Lim et al, 2017)...…”