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Alterations of eicosanoids and related mediators in patients with schizophrenia
Dongfang Wanga, Xiaoyu Suna, Jingjing Yana, Biao Renb, Bing Caoa, Lailai Yana,c,d,
Qingbin Lua,c,d, Yaqiong Liua,c,d, Jing Zenga,c,d, Ninghua Huanga,c,d, Qing Xiea,c,d, Haiwei
Gue*, and Jingyu Wanga,c,d*
a Department of Laboratorial Science and Technology, School of Public Health,
Peking University, Beijing 100191, P. R. Chinab Shimadzu (China) Co., LTD Beijing Branch, Beijing 100020, P. R. China.c Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food
Safety, Beijing 100191, P.R. Chinad Peking University Medical and Health Analysis Center, Peking University, Beijing
100191, P.R. Chinae Center for Metabolic and Vascular Biology, School of Nutrition and Health
Promotion, College of Health Solutions, Arizona State University, Phoenix, AZ
85004, USA
* Corresponding Authors:Haiwei Gu, Ph.D. Center for Metabolic and Vascular BiologySchool of Nutrition and Health PromotionCollege of Health SolutionsArizona State University13208 E. Shea Blvd, CRB 2-221Scottsdale, AZ 85259Tel: 480-301-6016Fax: 480-301-7017Email: [email protected] Jingyu Wang, Ph.D. School of Public Health, Peking UniversityNo.38 Xueyuan Road, Haidian DistrictBeijing 100191, P.R. ChinaTel/Fax: +86-10-82801107Email: [email protected]
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Table S1. The spiked concentrations of 14 internal standards.
A Separate Excel Table: Table S2. The LC-MS/MS parameters of the 158
metabolites and 14 internal standards used in this study.
Table S3. The gradient conditions for reversed phase C8 separation.
Table S4. Demographic and clinical characteristics of first episode and recurrent
patients at baseline.
Table S5. Antipsychotic use for patients during 8-week treatment.
Table S6. The AUROCs of individual significant metabolites for the comparison
between SCZ patients and healthy controls at baseline.
Table S7. The AUROCs of individual significant metabolites for the comparison
between pretreatment and posttreatment patients.
Fig. S1. Distribution of coefficients of variation (CVs) of all measured metabolites in
this study.
Fig. S2. Top 10 metabolites with highest VIP values from OPLS-DA models for
separation between (a) SCZ patients and healthy controls, (b) pretreatment patients
and posttreatment patients.
Fig. S3. Partial correlation coefficients among changes of eicosanoids and related
metabolites, and among changes of eicosanoid metabolites and clinical characteristics,
after adjusting for age, sex, BMI, current smoking, current drinking and
psychiatric family history.
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Table S1
The spiked concentrations of 14 internal standards.
Group
Internal standardSpiked concentration
(ng/mL)
1 Tetranor-PGEM-d6 1.1252 6-keto-Prostaglandin F1α-d4 1.1253 Thromboxane B2-d4 1.1254 Prostaglandin F2α-d4 2.3755 Prostaglandin E2-d4 2.3756 Prostaglandin D2-d4 1.1257 Leukotriene C4-d5 1.1258 Leukotriene B4-d4 1.1259 15(S) HETE-d8 1.12510 12(S) HETE-d8 1.12511 5(S) HETE-d8 1.12512 PAF C-16-d4 2.00013 Oleoyl Ethanolamide-d4 2.00014 Arachidonic Acid-d8 25.000
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Table S3
The gradient conditions for reversed phase C8 separation.
Time(min) A (v%) B (v%)0.0 90 105.0 75 2510.0 65 3520.0 25 7520.1 5 9525.0 5 9525.1 90 1030.0 90 10
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Table S4
Demographic and clinical characteristics of first episode and recurrent patients.
VariableFirst episode patients
(N=27)Recurrent patients
(N=88)p
Age (years); median (IQR) 29.0 (22.0, 34.0) 29.0 (25.0, 33.0) 0.807a
Gender; male n (%) 11 (40.7) 40 (45.5) 0.666b
BMI (kg/m2); median (IQR) 22.8 (20.4, 27.2) 24.0 (20.9, 25.9) 0.838a
Current smoker; n (%) 1 (3.7) 13 (14.8) 0.254b
Current drinker; n (%) 1 (3.7) 7 (8.0) 0.066b
Psychiatric family history; n (%) 7 (25.9) 12 (13.6) 0.146b
FBG (mmol/L); median (IQR) 5.4 (4.8, 5.6) 5.2 (4.7, 5.4) 0.268c
TG (mmol/L); median (IQR) 1.1 (0.6, 1.3) 0.9 (0.7, 1.4) 0.717c
TC (mmol/L); median (IQR) 4.2 (3.7, 5.4) 4.5 (3.9, 5.0) 0.380c
VLDL (mmol/L); median (IQR) 0.5 (0.3, 0.6) 0.4 (0.3, 0.7) 0.680c
Age of onset (years); median (IQR) 21.0 (18.0, 29.0) 21.5 (19.0, 26.0) 0.900a
Duration of illness (years); median (IQR) 4.2 (1.0, 8.3) 6.0 (2.4, 10.1) 0.119a
PANSS scores; median (IQR)Total score 80.0 (72.0, 93.0) 82.5 (73.3, 101.0) 0.273a
Positive symptoms 22.0 (16.0, 28.0) 21.0 (16.0, 25.0) 0.548a
Negative symptoms 20.0 (11.0, 23.0) 20.5 (15.0, 24.8) 0.249a
General psychopathology 42.0 (34.0, 54.0) 42.0 (37.0, 50.0) 0.995a
ap values were calculated by two-tailed Mann-Whitney U-tests. bp values were calculated by
chi-square tests. cP values were calculated by general linear models (GLM) after adjustment
for age, sex, BMI, smoking, drinking, and psychiatric family history. BMI, body mass
index; FBG, fasting blood glucose; TG, triglyceride; TC, total cholesterol; VLDL, very low
density lipoprotein; IQR, interquartile range.
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Table S5
Clinical treatment therapies of Study Participants.
Categories DrugsNo. of Patients (n, %)
First generation antipsychotics Haloperidol 9 (8.26)Chlorpromazine 1 (0.92)Promethazine 4 (3.67)
Second generation antipsychotics
Olanzapine 20 (18.35)Risperidone 34 (31.19)Clozapine 30 (27.52)Quetiapine 42 (38.53)Ziprasidone 25 (22.94)Aripiprazole 17 (15.60)Perphenazine 4 (3.67)Sulpiride 2 (1.83)
AnxiolyticsLorazepam 31 (28.44)Clonazepam 6 (5.50)Alprazolam 8 (7.34)
Anticonvulsants Magnesium valproate
20 (18.35)
Sodium valproate 18 (16.51)Anti-Tremor Medications Benzhexol 30 (27.52)
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Table S6
The AUROCs of individual significant metabolites for the comparison between SCZ
patients and healthy controls at baseline.
Metabolites AUROC 95% CIAA 0.682 0.612-0.751PGE2 0.537 0.458-0.615PGA2 0.539 0.461-0.616PGF2α 0.541 0.462-0.620PGJ2 0.548 0.471-0.625TXB2 0.585 0.508-0.66211-dehydro-TXB2 0.550 0.473-0.62711,12-DHET 0.604 0.528-0.67914,15-DHET 0.632 0.559-0.70520-carboxy-AA 0.643 0.571-0.716LTB4 0.543 0.466-0.62012-HpETE 0.604 0.529-0.67912-HETE 0.534 0.455-0.61315-HETE 0.512 0.432-0.5928-HETE 0.518 0.440-0.59611-HETE 0.544 0.466-0.622DHA 0.622 0.548-0.69513-HDoHE 0.587 0.512-0.662EPA 0.625 0.552-0.69812-HEPE 0.510 0.432-0.587AEA 0.810 0.754-0.867OEA 0.834 0.780-0.88915-KEDE 0.629 0.556-0.702
AUROC, area under the receiver-operating characteristic curve; CI, confidence interval.
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Table S7
The AUROCs of individual significant metabolites for the comparison between
pretreatment and posttreatment patients.
Metabolites AUROC 95% CIPGE2 0.585 0.509-0.660PGF2α 0.624 0.550-0.698TXB2 0.639 0.566-0.71211-dehydro-TXB2 0.615 0.540-0.68911,12-DHET 0.721 0.655-0.78814,15-DHET 0.662 0.591-0.73420-carboxy-AA 0.711 0.643-0.7795-KETE 0.577 0.501-0.65212-HETE 0.595 0.520-0.6704-HDoHE 0.636 0.563-0.7097-HDoHE 0.654 0.582-0.72612-HEPE 0.573 0.497-0.649AEA 0.699 0.630-0.769OEA 0.716 0.647-0.78415-KEDE 0.642 0.569-0.71513-HpODE 0.611 0.537-0.68613-KODE 0.633 0.560-0.7079,10-DiHOME 0.635 0.561-0.7089-HpODE 0.609 0.534-0.68313-HODE 0.622 0.548-0.6969-HODE 0.626 0.552-0.6999-KODE 0.638 0.565-0.711
AUROC, area under the receiver-operating characteristic curve; CI, confidence interval.
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<5% 5-10% 10-15% 15-20% 20-25%0
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CV distribution
% o
f met
abol
ites
Fig. S1
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0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0
PGE2
12-HpETE
15-KEDE
AA
12-HETE
EPA
11-dehydro-TXB2
AEA
OEA
TXB2
VIP values
Lipi
d m
etab
olite
s
0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8
13-HODE
9-HODE
9-HpODE
13-KODE
AEA
14,15-DHET
15-KEDE
11,12-DHET
20-carboxy-AA
OEA
VIP values
Lipi
d m
etab
olite
s
a b
Fig. S2
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Fig. S3
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