Alterations of serum metabolic profile in major depressive disorder: A case-control study in the Chinese population

Table 1 Basic information of included participants

Variable	MDD patients (n = 100)	HCs (n = 97)	P value
Age (years), mean ± SD	39.07 ± 15.23	40.33 ± 6.61	0.238
Sex, n (%)			0.027
Male	44 (44.0)	28 (28.9)
Female	56 (56.0)	69 (71.1)
Education level, n (%)			0.751
Primary school	19 (19.0)	22 (22.7)
Secondary school	48 (48.0)	41 (42.3)
High school	23 (23.0)	21 (21.6)
Undergraduate or above	10 (10.0)	13 (13.4)
Drinker, n (%)	11 (11.0)	16 (16.5)	0.262
Smoker, n (%)	8 (8.0)	15 (15.5)	0.103
BMI (kg/m2), mean ± SD	22.21 ± 4.25	23.91 ± 2.14	0.001
HAMD-24, mean ± SD	27.14 ± 6.10	2.08 ± 1.63	< 0.001
SHAPS, mean ± SD	37.71 ± 4.97	18.33 ± 3.51	< 0.001
GAD-7, mean ± SD	19.76 ± 3.28	7.54 ± 0.93	< 0.001

HCs: Healthy controls; MDD: Major depressive disorder; BMI: Body mass index; HAMD-24: Hamilton Depression Rating Scale-24 items; SHAPS: Snaith-Hamilton Pleasure Scale; GAD-7: Generalized Anxiety Disorder 7-item scale.

Table 2 Differential metabolites between major depressive disorder and healthy control groups identified from metabolomic data

Adduct type	Metabolite	Reference m/z	FC	log2 (FC)	FDR	VIP	Ontology	Trend
POS	Phytosphingosine	318.30	2.33	2.43	3.34E-16	2.42	1,3-aminoalcohols	↑
	Cortisol	363.22	2.14	-1.45	1.00E+00	3.23	21-hydroxysteroids	↑
	Estriol	289.18	1.97	1.89	2.38E-18	2.55	Estrogens and derivatives	↑
	D-pantothenic acid	220.12	1.72	2.50	4.40E-06	1.50	Secondary alcohols	↑
	Niacinamide	123.06	1.54	1.66	3.13E-07	1.64	Nicotinamides	↑
	Palmitoylcarnitine	400.34	1.51	0.40	1.74E-10	1.98	Acyl carnitines	↑
	Oleoyl-L-carnitine	426.36	1.50	-0.28	7.24E-07	1.60	Acyl carnitines	↑
	L-glutamic acid	146.05	1.41	-2.15	3.19E-11	2.05	Glutamic acid and derivatives	↑
	S1P (d18:1)	380.26	1.35	-0.46	2.32E-16	2.43	Phosphosphingolipids	↑
	Viridiflorine	286.20	0.65	1.95	4.77E-18	2.53	Pyrrolizidines	↓
	Cyclo(Leu-Pro)	211.14	0.58	2.76	6.45E-09	1.83	Alpha amino acids and derivatives	↓
	Sebacic acid	225.11	0.52	-1.80	9.56E-09	1.81	Medium-chain fatty acids	↓
	Piperine	286.14	0.30	1.10	7.26E-09	1.82	Alkaloids and derivatives	↓
	Theobromine	181.02	0.29	-0.78	3.13E-07	1.64	Xanthines	↓
	3-indoleacetic acid	176.07	0.23	0.22	1.44E-07	1.68	Indole-3-acetic acid derivatives	↓
NEG	8-HETE	279.20	6.77	0.89	1.71E-26	2.96	Long-chain fatty acids	↑
	12-HHTrE	319.23	5.67	1.45	8.90E-22	2.74	Hydroxyeicosatetraenoic acids	↑
	10-HDoHE	343.23	5.38	0.78	3.68E-21	2.71	Very long-chain fatty acids	↑
	5,12-DiHETE	335.22	3.86	0.98	5.46E-16	2.40	Leukotrienes	↑
	12-HEPE	317.21	3.70	-1.20	7.26E-09	1.83	Hydroxyeicosapentaenoic acids	↑
	Hexanedioic acid	145.05	3.21	-1.27	3.54E-08	1.75	Medium-chain fatty acids	↑
	12-hydroxydodecanoic acid	215.17	3.17	-1.32	3.13E-07	1.64	Medium-chain hydroxy acids and derivatives	↑
	Dodecanedioic acid	229.14	2.73	1.68	7.04E-15	2.33	Medium-chain fatty acids	↑
	Methylsuccinic acid	131.03	2.59	0.49	6.38E-11	2.02	Methyl-branched fatty acids	↑
	Pregnenolone sulfate	395.19	2.06	1.37	3.07E-08	1.76	Sulfated steroids	↑
	Dehydroisoandrosterone sulfate	367.16	1.85	0.63	6.90E-08	1.72	Sulfated steroids	↑
	D-(+)-malic acid	133.01	1.54	0.59	1.02E-12	2.17	Beta hydroxy acids and derivatives	↑
	2-hydroxyisocaproic acid	131.07	1.32	0.60	5.57E-14	2.27	Hydroxy fatty acids	↑
	3-hydroxyanthranilic acid	152.03	0.82	1.22	1.63E-18	2.57	Hydroxybenzoic acid derivatives	↓
	4-nitrophenol	138.02	0.73	-1.74	1.57E-09	1.90	Nitrophenols	↓
	FA 18:1 + 2O	313.24	0.43	1.04	2.34E-11	2.06	Long-chain fatty acids	↓
	FA 18:1 + 3O	329.23	0.42	-0.95	1.38E-07	1.68	Long-chain fatty acids	↓
	FA 18:3 + 1O	297.24	0.40	0.43	6.45E-09	1.83	Lineolic acids and derivatives	↓
	10-hydroxydecanoic acid	187.14	0.37	-1.77	1.93E-09	1.89	Medium-chain hydroxy acids and derivatives	↓
	CMPF	239.09	0.29	-0.62	1.67E-08	1.79	Furanoid fatty acids	↓

FC: Fold change; FDR: False discovery rate; VIP: Variable importance projection; CMPF: 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid; FA: Fatty acid; S1P: Sphingosine-1-phosphate.