Background
Liver Qi Stagnation (LQS) | Heart and Spleen Deficiency (HSD) | |
---|---|---|
Mood symptom characters | Depressed mood with frustration, nervousness, and/or irritability | Depressed mood with excessive pensiveness, suspicion, and/or timorousness |
Somatic symptoms | A. Frequently sighing (0 = absent, 1 = slight, 2 = mild, 3 = moderate, 4 = severe) B. Chest distension and/or hypochondriac pain (0 = absent, 1 = slight, 2 = mild, 3 = moderate, 4 = severe) C. Abdominal bloating (0 = absent, 1 = slight, 2 = mild, 3 = moderate, 4 = severe) D. Decreased appetite (0 = absent, 1 = mild, 2 = moderate, 3 = severe) E. Loose stool (0 = absent, 1 = mild, 2 = moderate, 3 = severe) F. Breast tenderness (0 = absent, 1 = slight, 2 = mild, 3 = moderate, 4 = severe) G. Irregular menstruation (0 = normal, 1 = seldom, 2 = sometimes, 3 = frequent)a H. Menstrual pain (0 = absent, 1 = mild, 2 = moderate, 3 = severe)a | A. Palpitation (0 = normal, 1 = seldom, 2 = sometimes, 3 = most times, 4 = all times) B. Forgetfulness (0 = absent, 1 = slight, 2 = mild, 3 = moderate, 4 = severe) C. Insomnia or dream-disturbed sleep (0 = absent, 1 = sometimes, 3 = most times) D. Decreased appetite (0 = absent, 1 = slight, 2 = mild, 3 = moderate, 4 = severe) E. Abdominal fullness (0 = absent, 1 = sometimes, 3 = most times) F. Loose stool or dysfunctional diarrhea (0 = absent, 1 = slight, 2 = mild, 3 = moderate, 4 = severe) G. Pale and sallow complexion (0 = normal, 1 = slightly apparent, 2 = mildly apparent; 3 = moderately apparent, 4 = very apparent) H. Tiredness (0 = absent, 1 = mild, 2 = moderate, 3 = severe) |
Tongue and pulse | I. Red tongue body with thin and white coating (0 = normal, 1 = mildly apparent, 2 = moderately apparent, 3 = very apparent) J. Wiry pulse (0 = normal, 1 = slightly apparent, 2 = mildly apparent; 3 = moderately apparent, 4 = very apparent) | I. Pale and tender or watery tongue body with white coating (0 = normal, 1 = slightly apparent, 2 = mildly apparent; 3 = moderately apparent, 4 = very apparent) J. Weak and thin pulse (0 = normal, 1 = slightly apparent, 2 = mildly apparent; 3 = moderately apparent, 4 = very apparent) |
Diagnostic criteriab | [1]. Must have A, B, I, and J; at least one of D and E; and at least one of F, G, and H for women [2]. Total score of physical symptoms and tongue and pulse signs is not less than 10 | [1]. Must have at least two of A, B and C; at least two of D, E and F; at least one of G and H; I and J [2]. Total score of physical symptoms and tongue and pulse signs is not less than 10 |
Materials and methods
Setting and participants
Screening, assessment, and TCM diagnosis
Collection and preparation of serum and urine samples
GC–MS acquisition
Statistical analysis
Results
Participant characteristics
Variables | Healthy controls (n = 28) | LQS subtypea (n = 30) | HSD subtypea (n = 20) | p valueb,c |
---|---|---|---|---|
Female, n (%)b | 17 (60.7) | 25 (83.3) | 10 (50.0) | 0.035 |
Age (y)c | 34.1 ± 8.1 | 38.1 ± 13.4 | 41.5 ± 13.7 | 0.107 |
Educational level, n (%)b | 0.331 | |||
Primary | 2 (7.1) | 6 (20.0) | 5 (25.0) | |
Middle | 5 (17.9) | 4 (13.3) | 5 (25.0) | |
Highd | 21 (75.0) | 20 (66.7) | 10 (50.0) | |
Marital status, n (%)b | 0.734 | |||
Married | 23 (82.1) | 26 (86.7) | 18 (90.0) | |
Single/divorced/widowed | 5 (17.9) | 4 (13.3) | 2 (10.0) | |
Income level, n (%)b,e | 0.775 | |||
Low | 4 (14.3) | 7 (23.3) | 3 (15.0) | |
Middle | 17 (60.7) | 18 (60.0) | 14 (70.0) | |
High | 7 (25.0) | 5 (16.7) | 3 (15.0) | |
Family history with severe mental diseases, n (%)b,f | 3 (10.7) | 4 (13.3) | 0 | 0.250 |
Comorbid conditions, n (%)b,g | 3 (10) | 4 (20) | 0.560 | |
Medication history, n (%)b,h | 0.803 | |||
SSRIs/SNRIsa | 25 (83.3) | 18 (90.0) | ||
Antipsychotics | 5 (16.7) | 2 (10.0) | ||
Previous depressive episode, n (%)b | 0.684 | |||
Single | 18 (60.0) | 10 (50.0) | ||
Multiple | 12 (40.0) | 10 (50.0) | ||
Duration of the illness (months)c,i | 39.5 ± 60.9 | 33.6 ± 47.8 | 0.716 | |
HAMD-24 scorea,c | 32.5 ± 8.5 | 30.1 ± 6.5 | 0.286 |
Clustering patterns of differential metabolite profiles
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 |