Table 3.

Differential metabolites identified from MDD patients with TCM subtypes and healthy controls ^a

Group samples	Metabolites	Formula	r b	p-valuec	FC (MDD/HC)a	Pathway
Serum: LQS vs. HC a
1d	l-Valine	C5H11NO2	0.236	0.009	0.930	Aminoacyl-tRNA biosynthesis
2d	l-Phenylalanine	C9H11NO2	0.199	0.237	0.350	Aminoacyl-tRNA biosynthesis
3d	l-Lysine	C6H14N2O2	0.150	0.761	0.459	Aminoacyl-tRNA biosynthesis
4	l-Proline	C5H9NO2	0.143	0.447	0.182	Aminoacyl-tRNA biosynthesis
5d	l-Leucine	C6H13NO2	0.124	0.000	1.047	Aminoacyl-tRNA biosynthesis
6e	Isobutyric acid	C4H8O2	0.103	0.565	0.702	Protein digestion and absorption
7	l-Lactic acid	C3H6O3	− 0.147	0.370	0.013	Propanoate metabolism
8	Glycine	C2H5NO2	− 0.151	0.279	− 0.954	Aminoacyl-tRNA biosynthesis
9	Threonic acid	C4H8O5	− 0.175	0.250	− 1.080	Ascorbate and aldarate metabolism
Urine: LQS vs. HC a
1	l-Sorbose	C6H12O6	0.149	0.624	0.661	Unknown
2	Diacetyl	C4H6O2	0.147	0.120	0.825	Butanoate metabolism
3	N-Acetyl-d-glucosamine	C8H15NO6	0.146	0.748	0.304	Amino sugar and nucleotide sugar metabolism
4d	l-Methionine	C5H11NO2S	0.144	0.417	0.546	Cysteine and methionine metabolism
5d	3-Hydroxybutyric acid	C4H8O3	0.139	0.088	0.819	Butanoate metabolism
6d	Pyruvic acid	C3H4O3	0.125	0.116	1.085	Citrate cycle (TCA cycle)
7d	Stearic acid	C18H36O2	0.117	0.327	0.490	Fatty acid biosynthesis
8	trans-Aconitic acid	C6H6O6	0.115	0.648	0.444	C5-Branched dibasic acid metabolism
9d	Glycine	C2H5NO2	0.111	0.685	0.441	Aminoacyl-tRNA biosynthesis
10d	N-Acetyl-l-aspartic acid	C6H9NO5	0.107	0.176	0.680	Alanine, aspartate and glutamate metabolism
11	Threonic acid	C4H8O5	0.101	0.906	0.428	Ascorbate and aldarate metabolism
12d	l-Tryptophan	C11H12N2O2	− 0.108	0.054	0.186	Glycine, serine and threonine metabolism
13	α-Lactose	C12H22O11	− 0.114	0.116	0.259	Galactose metabolism
14d	l-Lactic acid	C3H6O3	− 0.129	0.735	0.263	Propanoate metabolism
15d	Palmitic acid	C16H32O2	− 0.149	0.005	0.303	Fatty acid metabolism
16	Indoxyl sulfate	C8H7NO4S	− 0.164	0.673	0.583	Unknown
17d	o-Tyrosine	C9H11NO3	− 0.203	0.217	0.080	Unknown
18	p-Hydroxyphenylacetic acid	C9H8O3	− 0.122	0.673	− 0.120	Tyrosine metabolism
19d	Citric acid	C6H8O7	− 0.156	0.015	− 0.265	Citrate cycle (TCA cycle)
Serum: HSD vs. HC a
1d	l-Valine	C5H11NO2	0.226	0.079	0.689	Aminoacyl-tRNA biosynthesis
2d	l-Leucine	C6H13NO2	0.161	0.000	1.120	Aminoacyl-tRNA biosynthesis
3d	l-Lysine	C6H14N2O2	0.148	0.337	0.722	Aminoacyl-tRNA biosynthesis
4	l-Threonine	C4H9NO3	− 0.105	0.000	− 0.191	Glycine, serine and threonine metabolism
5	d-chiro-Inositol	C6H12O6	− 0.135	0.138	− 0.200	Inositol phosphate metabolism
6d	l-Methionine	C5H11NO2S	− 0.140	0.009	− 0.299	Cysteine and methionine metabolism
7	l-Lactic acid	C3H6O3	− 0.170	0.253	− 0.183	Propanoate metabolism
Urine: HSD vs. HC a
1d	l-Isoleucine	C6H13NO2	0.161	0.007	0.681	Valine, leucine and isoleucine degradation
2	Threonic acid	C4H8O5	0.113	0.349	0.687	Ascorbate and aldarate metabolism
3	N-Acetyl-d-glucosamine	C8H15NO6	0.109	0.283	0.432	Amino sugar and nucleotide sugar metabolism
4d	Stearic acid	C18H36O2	− 0.104	0.002	0.019	Fatty acid biosynthesis
5	α-Lactose	C12H22O11	− 0.116	0.000	− 0.126	Galactose metabolism
Urine: LQS vs. HSD a
1	Isobutyric acid	C4H8O2	0.127	0.304	1.114e	Protein digestion and absorption

^a FC fold change, MDD major depressive disorder, HC healthy controls, LQS Liver Qi Stagnation, HSD Heart and Spleen Deficiency

^b Correlation coefficients (r) were obtained from OPLC-DA with a threshold of 3.010. Positive and negative coefficients respectively indicate higher and lower levels of metabolites compared to healthy controls

^c p-values were obtained from Wilcoxon-Mann–Whitney test between TCM subtypes and healthy controls

^d Metabolites were determined using standard samples

^e FC value represents LQS/HSD