Metabolic pathway modulation by olanzapine: Multitarget approach for treating violent aggression in patients with schizophrenia

Table 1 Differentially abundant metabolites in patients with schizophrenia with violent aggression

No.	Metabolites	Retention time/minute	m/z	Formula	VIP	P value	Trend	Scan mode
1	Platelet-activating factor	9.44	524.36951	C26 H54 N O7 P	2.09169	0.000	↓	+
2	2-amino-1,3,4-octadecanetriol	6.441	318.29908	C18 H39 N O3	1.88102	0.000	↑	+
3	Palmitic acid	6.402	274.27291	C16 H32 O2	1.86839	0.000	↑	+
4	Cortisol	5.742	363.21555	C21 H30 O5	1.91193	0.000	↑	+
5	Stearic acid	6.99	302.30423	C18 H36 O2	1.59533	0.000	↑	+
6	Hexadecanamide	10.073	256.26277	C16 H33 N O	1.47424	0.000	↑	+
7	Arachidic acid	7.54	330.33567	C20 H40 O2	1.17354	0.000	↑	+
8	N-undecanoylglycine	6.134	266.17185	C13 H25 N O3	1.97952	0.000	↑	+
9	Dihydrosphingosine 1-phosphate	7.693	382.27068	C18 H40 N O5 P	1.37863	0.000	↑	+
10	Palmitoyl ethanolamide	9.734	300.28892	C18 H37 N O2	1.70707	0.000	↑	+
11	D-(+)-pyroglutamic acid	1.01	130.04979	C5 H7 N O3	1.21094	0.000	↓	+
12	Oleoylethanolamide	9.932	326.30444	C20 H39 N O2	1.45824	0.000	↑	+
13	D-erythro-sphingosine 1-phosphate	7.519	380.25492	C18 H38 N O5 P	1.36048	0.000	↑	+
14	Hypoxanthine	1.111	137.04556	C5 H4 N4 O	1.33242	0.000	↓	+
15	Glutamine	0.96	147.07623	C5 H10 N2 O3	1.24123	0.000	↑	+
16	N-undecanoylglycine	6.181	242.17601	C13 H25 N O3	2.20108	0.000	↑	-
17	L-glutamic acid	0.893	146.0449	C5 H9 N O4	1.9134	0.000	↓	-
18	Sphingosine 1-phosphate	7.587	378.24163	C18 H38 N O5 P	1.81005	0.000	↑	-
19	N-phenylacetylglutamine	4.125	263.10371	C13 H16 N2 O4	1.68847	0.000	↑	-
20	D-(-)-fructose	0.853	179.05538	C6 H12 O6	1.63729	0.000	↑	-
21	4-oxoproline	0.968	128.03417	C5 H7 N O3	1.54629	0.000	↓	-
22	L-(+)-lactic acid	1.093	89.02311	C3 H6 O3	1.16621	0.000	↓	-
23	Levothyroxine	6.053	775.68055	C15 H11 I4 N O4	1.51385	0.000	↑	-
24	3-hydroxybutyric acid	1.784	103.03886	C4 H8 O3	1.43635	0.000	↑	-
25	Arachidonic acid	10.197	303.23285	C20 H32 O2	1.12287	0.000	↓	-
26	Cis-5,8,11,14,17-eicosapentaenoic acid	9.785	301.21728	C20 H30 O2	1.09833	0.000	↓	-

“↑” or ”↓” indicates that the metabolite significantly increased or decreased, respectively, in the disease group compared with the control group. VIP: Variable importance in projection.

Table 2 Differentially abundant metabolites in patients with schizophrenia treated with olanzapine

No.	Formula	Metabolites	Control group vs pretherapy in the disease group			Control group vs post therapy in the disease group			Adjust
			VIP	Fold change	P value	VIP	Fold change	P value
1	C26 H54 N O7 P	Platelet-activating factor	2.09169	0.620166	1.64E-21	1.79868	0.645408	7.75E-19	Reverse
2	C21 H30 O5	Cortisol	1.91193	2.14094	1.21E-17	1.63334	1.72288	2.07E-13	Reverse
3	C18 H40 N O5 P	Dihydrosphingosine 1-phosphate	1.37863	1.79149	1.55E-08	1.11856	1.4172	9.58E-06	Reverse
4	C18 H37 N O2	Palmitoyl ethanolamide	1.70707	1.6449	6.51E-14	1.00437	1.27934	7.33E-06	Reverse
5	C5 H7 N O3	D-(+)-pyroglutamic acid	1.21094	0.586656	9.25E-07	1.06578	0.591467	8.40E-06	Reverse
6	C13 H25 N O3	N-undecanoylglycine	2.20108	4.90093	2.62E-15	1.58901	4.27589	1.64E-09	Reverse
7	C5 H9 N O4	L-glutamic acid	1.9134	0.630722	1.87E-11	1.41269	0.712935	9.56E-08	Reverse
8	C18 H38 N O5 P	Sphingosine 1-phosphate	1.81005	1.38203	4.22E-11	1.45196	1.27835	1.04E-06	Reverse
9	C6 H12 O6	D-(-)-fructose	1.63729	1.77875	6.54E-09	1.25196	1.61936	9.64E-06	Reverse
10	C5 H7 N O3	4-oxoproline	1.54629	0.592293	1.21E-07	1.33034	0.615205	3.25E-06	Reverse

VIP: Variable importance in projection.