Metabolomic analysis of biochemical changes in the plasma and urine of first-episode neuroleptic-naïve schizophrenia patients after treatment with risperidone.
Early findings propose that impaired neurotransmission in the brain plays a key role in the pathophysiology of schizophrenia. Recent advances in understanding its multiple etiologies and pathogenetic mechanisms provide more speculative hypotheses focused on even broader somatic systems. Using a targeted tandem mass spectrometry (MS/MS)-based metabolomic platform, we compared metabolic signatures consisting of monoamine and amino acid neurotransmitter (NT) metabolites in plasma/urine simultaneously between first-episode neuroleptic-naïve schizophrenia patients (FENNS) and healthy controls before and after a 6-week risperidone monotherapy, which suggest that the patient NT profiles are restoring during treatment. To detect and identify potential biomarkers associated with schizophrenia and risperidone treatment, we also performed a combined ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) and 1H nuclear magnetic resonance (NMR)-based metabolomic profiling of the same samples, indicating a further deviation of the patients' global metabolic profile from that of controls. The NTs and their metabolites together with the 32 identified biomarkers underpin that metabolic pathways including NT metabolism, amino acid metabolism, glucose metabolism, lipid metabolism, energy metabolism, antioxidant defense system, bowel microflora and endocrine system are disturbed in FENNS. Among them, pregnanediol, citrate and α-ketoglutarate (α-KG) were significantly associated with symptomatology of schizophrenia after Bonferroni correction and may be useful biomarkers for monitoring therapeutic efficacy. These findings promise to yield valuable insights into the pathophysiology of schizophrenia and may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.
Clinical Pharmacy and Pharmacology Research Institute, the Second Xiangya Hospital of Central South University, and School of Pharmaceutical Sciences, Central South University, Changsha, China.
Hua-Lin
HL
Cai
Huan-De
HD
Li
Xian-Zhong
XZ
Yan
Bo
B
Sun
Qi
Q
Zhang
Miao
M
Yan
Wen-Yuan
WY
Zhang
Pei
P
Jiang
Rong-Hua
RH
Zhu
Yi-Ping
YP
Liu
Ping-Fei
PF
Fang
Ping
P
Xu
Hai-Yan
HY
Yuan
Xiang-Hui
XH
Zhang
Li
L
Hu
Wen
W
Yang
Hai-Sen
HS
Ye
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D055442:Metabolome / Q000187:drug effects; D015999:Multivariate Analysis; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy / Q000652:urine*; D055815:Young Adult
D014150:Antipsychotic Agents; D015415:Biomarkers; D018967:Risperidone