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].
Highlights
Major depressive disorder (MDD) is a highly heterogeneous disease
These metabolites mainly included amino acid metabolites involved in the synthesis of monoamine and amino acid neurotransmitters (l-tryptophan, phenylalanine, o-tyrosine, glycine, 3-hydroxybutric acid, and N-acetyll-aspartic acid), proteinogenic branched-chain amino acids (BCAAs), oxaloacetate-derived amino acids (l-lysine, l-threonine and l-methionine) which are mainly involved in the biosynthesis of proteins and energy production via gluconeogenesis, and energy metabolism-related metabolites (l-lactic acid, palmitic acid, citric acid, stearic acid, pyruvic acid, and α-lactose) [24]
Plasma level of β-amino-isobutyric acid of autistic children has been shown to be significantly higher than that of healthy children [35]. These results suggest that threonic acid, methionine, stearic acid, and isobutyric acid are differentially associated with the two traditional Chinese medicine (TCM) subtypes and may be promising biomarkers for TCM classification of MDD
Summary
Major depressive disorder (MDD) is a highly heterogeneous disease. The purpose of this study was to examine whether metabolomic variables could differentiate traditional Chinese medicine (TCM) diagnostic subtypes of MDD. Major depressive disorder (MDD) is a highly heterogeneous mental illness with a wide range of clinical manifestations and multi-system etiopathogenesis. A great attempt has been made to characterize its heterogeneity by subdividing MDD based on its clinical features, severity, and polygenic features, convincing evidence for the existence of depressive symptom dimensions and symptomatic subtypes is lacking, mainly due to symptomatic diversity and the absence of patterns [2,3,4,5]. Several large-scale studies have revealed 12 different TCM patterns of MDD on the basis of the modern psychiatric diagnostic instruments and analysis tools, such as latent tree model analysis [7,8,9,10,11,12]. Despite disagreements on some patterns, a consensus on clinical diagnostic criteria for the two most common and opposing patterns, Liver Qi Stagnation (LQS) and Heart and Spleen Deficiency (HSD), which account for approximately 2/3 of depressed patients, have been reached as shown in Table 1 [7, 9, 10]
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