OBJECTIVE: To investigate the effect of ziprasidone and olanzapine on glucose and lipid metabolism in first-episode schizophrenia. METHODS: A total of 260 schizophrenics were assigned randomly to receive ziprasidone or olanzapine for 6 weeks. The weight was measured at baseline, week 2, 4 and 6. Fasting blood glucose (FBS), fasting insulin, high-density lipoprotein (HDL), total-cholesterol (TC) and triglycerides (TG) were measured at baseline and the end of 6-week treatment. Low-density lipoprotein (LDL) was measured in some patients at baseline and the end of 6-week treatment. Body mass index (BMI) and insulin resistance index (IRI) were counted. RESULTS: A total of 245 patients completed the trial, including 121 ziprasidone patients and 124 olanzapine patients. The average dose was 137.5 mg/d for ziprasidone and 19.5 mg/d for olanzapine. Patients treated with olanzapine had higher weight gain than those treated with ziprasidone [(4.55±3.37) kg vs (-0.83±2.05) kg, P<0.001]. After the treatment, FBS, fasting insulin, HDL, TC, TG, LDL and IRI levels were significantly increased in the olanzapine group (all P values<0.001 ). However, in the ziprasidone group, FBS decreased significantly and HDL and TG levels increased significantly after the 6-week treatment (all P values<0.05). The mean changes of FBS, fasting insulin, TC, TG, LDL and IRI were significantly different in the two groups (all P values<0.001). CONCLUSION Ziprasidone has less glucose and lipid metabolic effect for first-episode schizophrenia patients in short-term treatment. However, olanzapine induces weight gain and dysfunction of glucose and lipid metabolism significantly, which is associated with increased risk of complications. When the doctors choose antipsychotics in the clinic, they should consider the side effects of the medication.
Adolescent ; Adult ; Benzodiazepines ; adverse effects ; therapeutic use ; Blood Glucose ; drug effects ; Female ; Humans ; Lipid Metabolism ; drug effects ; Male ; Middle Aged ; Olanzapine ; Piperazines ; adverse effects ; therapeutic use ; Schizophrenia ; drug therapy ; Thiazoles ; adverse effects ; therapeutic use ; Young Adult

OBJECTIVE: To analyze the differentially expressed proteins in the dorsal raphe nucleus of rats treated with olanzapine and explore the possible mechanism of metabolic disorders in the early stage of olanzapine treatment. METHODS: Twenty male and 20 female SD rats were both randomized equally into olanzapine group and control group for daily treatment with olanzapine and saline for 4 weeks, respectively. One hour after the last treatment, the dorsal raphe nucleus of the rats was dissected for proteomic analysis using iTRAQ combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). GO, KEGG pathway, COG, pathways and protein interaction network analyses of the differentially expressed proteins were performed. Several target genes were selected from the proteomic list, and their expression levels in the dorsal raphe nucleus of another 24 mice with identical grouping and treatment using real time real-time quantitative PCR and Western blotting. RESULTS: A total of 214 differentially expressed proteins were identified in the dorsal raphe nucleus of olanzapine-treated mice, including 72 unregulated and 142 downregulated proteins. GO analyses showed that the differentially expressed proteins were enriched in cellular process, biological regulation, metabolic process, response to stimulus, multicellular organismal process, bindings, catalytic activity, molecular function regulator and transcription regulator activity. KEGG analysis suggested that these proteins were enriched in fluid shear stress and atherosclerosis, serotonergic synapse, butanoate metabolism, thyroid hormone synthesis and IL-17 signaling pathway. The differentially expressed proteins Cav1, Hsp90b1, Canx, Gnai1, MAPK9, and LOC685513 were located at the nodes of the protein-protein interaction network in close relation with metabolic disorders. In olanzapine-treated mice, the expression of Hmgcs2, a negative regulator of apoptosis, was significantly down-regulated in the dorsal raphe nucleus, where the expressions of Pla2g4e, Slc6a4 and Gnai1 involved in serotonergic synapse were significantly upregulated. CONCLUSION In the early stage of treatment, olanzapine may contribute to the occurrence of metabolic disorders in rats by regulating the expressions of Cav1, Hsp90b1, Canx, Gnai1, MAPK9, LOC685513 (Gng14) and 5-HTR2 synapse-related proteins in the dorsal raphe nucleus.
Animals ; Chromatography, Liquid ; Computational Biology ; Dorsal Raphe Nucleus ; Female ; GTP-Binding Protein alpha Subunits, Gi-Go ; Male ; Mice ; Olanzapine/adverse effects* ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry