Metabolic Syndrome And Its Association With Leptin And5-HT2C Receptor Gene Polymorphisms In First-episode, Drug-naive Patients With Schizophrenia

Objective:Researches investigating the metabolic syndrome in patients with schizophrenia have mainly focused on antipsychotic-induced metabolic impairments. However, recent studies also suggest schizophrenic patients even without treatment are at increased risk for metabolic abnormalities. The purpose of the present study was to explore whether first-episode, drug-naive schizophrenic patients are associated with increased incidence of metabolic syndrome and the influence of leptin and5-HT2C receptor gene polymorphisms on metabolic disturbances in those individuals..Methods:First-episode, drug-naive patients with schizophrenia (n=100) and healthy comparison individuals (n=118) were assessed for measures of metabolic syndrome including blood pressure, waist circumference, hip circumference, weight, hight, levels of fasting glucoselipids, insulin and glucose levels2-hours after glucose load (75g). The body mass index, waist-to-hip ratio and insulin resistant index were calculated for each subject. Two genetic polymorphisms (leptin-2458A/G and5-HT2C receptor-759C/T) were genotyped in schizophrenic patients (n=137) and healthy controls (n=165). Results:About6%of the drug-naive first-episode patients with schizophrenia fulfilled the criteria for metabolic syndrome, significantly higher than0.83%of the healthy volunteers. The patient group also demonstrated higher rate of impaired fasting glycaemia, impaired glucose tolerance, diabetes mellitus and the total rate of glucose metabolism abnormalities (4%,11%,7%,22%) for the patient group versus0%,2.54%,0%,2.54%for the healthy control group respectively, p<0.05). Compared with the healthy subjects, patients with schizophrenia had a significantly higher mean fasting levels of glucose, insulin, glucose levels2-hours after glucose load and were more insulin resistant, as measured with homeostasis model assessment. Levels of serum high density lipoprotein in the patient group were significantly lower than the healthy control group. Comparison of the genotypes or allele frequencies of leptin-2548G/A and5-HT2C receptor-759C/T polymorphism showed no significant differences between the patient and the control groups. There was no significant association between of the division of these two genetic genotype with any of the metabolic measures tested above.Conclusions:(1) The high point prevalence of metabolic syndrome in never-treated first-episode patients supports either shared environmental or genetic predisposition to metabolic impairment. (2) First-episode, drug-naive patients with schizophrenia have impaired glucose and lipid metabolism.(3) Thepolymorphisms of leptin-2548G/A and5-HT2C receptor-759C/T may not be linked with susceptibility to schizophrenia or metabolisms of glucose and lipids.