Blood and urinary metabolomic evidence validating traditional Chinese medicine diagnostic classification of major depressive disorder

Abstract

BackgroundMajor depressive disorder (MDD) is a highly heterogeneous disease. Further classification may characterize its heterogeneity. The purpose of this study was to examine whether metabolomic variables could differentiate traditional Chinese medicine (TCM) diagnostic subtypes of MDD.MethodsFifty medication-free patients who were experiencing a recurrent depressive episode were classified into Liver Qi Stagnation (LQS, n = 30) and Heart and Spleen Deficiency (HSD, n = 20) subtypes according to TCM diagnosis. Healthy volunteers (n = 28) were included as controls. Gas chromatography-mass spectrometry (GC–MS) was used to examine serum and urinary metabolomic profiles.ResultsTwenty-eight metabolites were identified for good separations between TCM subtypes and healthy controls in serum samples. Both TCM subtypes had similar profiles in proteinogenic branched-chain amino acids (BCAAs) (valine, leucine, and isoleucine) and energy metabolism-related metabolites that were differentiated from healthy controls. The LQS subtype additionally differed from healthy controls in multiple amino acid metabolites that are involved in biosynthesis of monoamine and amino acid neurotransmitters, including phenylalanine, 3-hydroxybutric acid, o-tyrosine, glycine, l-tryptophan, and N-acetyl-l-aspartic acid. Threonic acid, methionine, stearic acid, and isobutyric acid are differentially associated with the two subtypes.ConclusionsWhile both TCM subtypes are associated with aberrant BCAA and energy metabolism, the LQS subtype may represent an MDD subpopulation characterized by abnormalities in the biosynthesis of monoamine and amino acid neurotransmitters and closer associations with stress-related pathophysiology. The metabolites differentially associated with the two subtypes are promising biomarkers for predicting TCM subtype-specific antidepressant response [registered at http://www.clinicaltrials.gov (NCT02346682) on January 27, 2015].Electronic supplementary materialThe online version of this article (10.1186/s13020-018-0211-z) contains supplementary material, which is available to authorized users.

Metabolomics in Psychiatric Disorders: What We Learn from Animal Models

“…Thus, perturbations in SCFA and AA in the central, as well as peripheral system, seem to be involved in the pathogenesis of depression. Studies conducted on human cerebral fluid or plasma samples, also observed pronounced differences in AA concentrations between healthy and depressed individuals [22,29]. Moreover, alterations of five metabolites involved in the ABC transport system were observed in depressed monkeys compared to their healthy counterparts.…”

“…More specifically, animal depression studies revealed that amino acid (AA) metabolism is disturbed in various brain regions, but also in the plasma of depressed individuals. Especially the glutamate-γ-aminobutyric acid (GABA)-glutamine cycle, which has been implicated to be related to the pathogenesis of MDD, due to its key role in maintaining the supply of neurotransmitters [22]. Overall, the glutamatergic system plays an important role in the pathophysiology of mood disorders, such as depression, where glutamate disturbances in the brain have been linked to the neuroplasticity hypothesis of MDD [23].…”

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“…Tai Chi Chuan is often viewed by Chinese people as physical exercise to improve mind–body health, therefore, making it an interesting research target in the field of cardiovascular health and anxiety symptoms. Thus, a randomized-controlled trial was conducted to evaluate the effect of a Tai Chi Chuan exercise program on anxiety status and blood lipid profile in individuals with hypertension as compared to healthy subjects [ 132 ]. As an increase in HDL and a decrease in total cholesterol, LDL, and triglycerides went along with decreases in trait and state anxiety, it was suggested that Tai Chi might be used as an alternative treatment in patients with anxiety disorders.…”

Self-Designed Ningxin Anshen Formula for Treatment of Post-ischemic Stroke Insomnia: A Randomized Controlled Trial

“…TCM is an ancient medical practice with a unique diagnostic system. A key method of diagnosis is to differentiate the etiology and pathogenesis, which are usually determined by the comprehensive analysis of clinical symptoms and signs collected through inspection, auscultation, olfaction, interrogation and pulse palpation (13). These are also known as TCM Syndromes according to which clinicians choose suitable treatments.…”