TY - JOUR
T1 - Alterations of eicosanoids and related mediators in patients with schizophrenia
AU - Wang, Dongfang
AU - Sun, Xiaoyu
AU - Yan, Jingjing
AU - Ren, Biao
AU - Cao, Bing
AU - Lu, Qingbin
AU - Liu, Yaqiong
AU - Zeng, Jing
AU - Huang, Ninghua
AU - Xie, Qing
AU - Gu, Haiwei
AU - Wang, Jingyu
N1 - Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/7
Y1 - 2018/7
N2 - Schizophrenia (SCZ) is a multifactorial psychiatric disorder. Currently, its molecular pathogenesis remains largely unknown, and no reliable test for diagnosis and therapy monitoring is available. Polyunsaturated fatty acids (PUFAs) and their derived eicosanoid signaling abnormalities are relevant to the pathophysiology of schizophrenia. However, comprehensive analysis of eicosanoids and related mediators for schizophrenia is very rare. In this study, we applied a targeted liquid chromatography-mass spectrometry based method to monitor 158 PUFAs, eicosanoids and related mediators from enzyme-dependent or independent pathways, in the serum samples of 109 healthy controls, and 115 schizophrenia patients at baseline and after an 8-week period of antipsychotic therapy. Twenty-three metabolites were identified to be significantly altered in SCZ patients at baseline compared to healthy controls, especially arachidonic acid (AA) derived eicosanoids. These disturbances may be related to altered immunological reactions and neurotransmitter signaling. After 8-week antipsychotic treatment, there were 22 metabolites, especially AA and linoleic acid derived eicosanoids, significantly altered in posttreatment patients. Some metabolites, such as several AA derived prostaglandins, thromboxanes, and di-hydroxy-eicosatrienoic acids were reversed toward normal levels after treatment. Based on univariate analysis and orthogonal partial least-squares discriminant analysis, anandamide, oleoylethanolamine, and AA were selected as a panel of potential biomarkers for differentiating baseline SCZ patients from controls, which showed a high sensitivity (0.907), good specificity (0.843) and excellent area under the receiver operating characteristic curve (0.940). This study provided a new perspective to understand the pathophysiological mechanism and identify potential biomarkers of SCZ.
AB - Schizophrenia (SCZ) is a multifactorial psychiatric disorder. Currently, its molecular pathogenesis remains largely unknown, and no reliable test for diagnosis and therapy monitoring is available. Polyunsaturated fatty acids (PUFAs) and their derived eicosanoid signaling abnormalities are relevant to the pathophysiology of schizophrenia. However, comprehensive analysis of eicosanoids and related mediators for schizophrenia is very rare. In this study, we applied a targeted liquid chromatography-mass spectrometry based method to monitor 158 PUFAs, eicosanoids and related mediators from enzyme-dependent or independent pathways, in the serum samples of 109 healthy controls, and 115 schizophrenia patients at baseline and after an 8-week period of antipsychotic therapy. Twenty-three metabolites were identified to be significantly altered in SCZ patients at baseline compared to healthy controls, especially arachidonic acid (AA) derived eicosanoids. These disturbances may be related to altered immunological reactions and neurotransmitter signaling. After 8-week antipsychotic treatment, there were 22 metabolites, especially AA and linoleic acid derived eicosanoids, significantly altered in posttreatment patients. Some metabolites, such as several AA derived prostaglandins, thromboxanes, and di-hydroxy-eicosatrienoic acids were reversed toward normal levels after treatment. Based on univariate analysis and orthogonal partial least-squares discriminant analysis, anandamide, oleoylethanolamine, and AA were selected as a panel of potential biomarkers for differentiating baseline SCZ patients from controls, which showed a high sensitivity (0.907), good specificity (0.843) and excellent area under the receiver operating characteristic curve (0.940). This study provided a new perspective to understand the pathophysiological mechanism and identify potential biomarkers of SCZ.
KW - Biomarker
KW - Eicosanoids
KW - Liquid chromatography-mass spectrometry
KW - Metabolomics
KW - Polyunsaturated fatty acids
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85045548778&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045548778&partnerID=8YFLogxK
U2 - 10.1016/j.jpsychires.2018.04.002
DO - 10.1016/j.jpsychires.2018.04.002
M3 - Article
C2 - 29674269
AN - SCOPUS:85045548778
SN - 0022-3956
VL - 102
SP - 168
EP - 178
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
ER -