CSF levels of synaptosomal-associated protein 25 and synaptotagmin-1 in first-episode psychosis subjects.

Post-mortem studies consistently show evidence of reduced synaptic protein levels in patients with schizophrenia. Clinically high-risk subjects show a steeper decrease in grey matter thickness and in vitro modeling using patient-derived cells implicate excessive synaptic pruning during neurodevelopment as a part of the schizophrenia pathophysiology. However, it is unclear to what extent synapse elimination is present during various stages of the disease, which is of clinical importance as in a real-world setting most subjects received their first-episode psychosis (FEP) diagnosis not until their mid-twenties. In the present study, we measured cerebrospinal fluid (CSF) concentrations of the two pre-synaptic proteins synaptosomal-associated protein 25 (SNAP-25) and synaptotagmin-1 (SYT-1), both of which are increased in conditions of ongoing synaptic degeneration, in 44 FEP subjects (mean age 29.9 years) and 21 healthy controls (25.9 years) using immunoprecipitation mass spectrometry. Neither protein was found to differ between healthy controls and patients, and they showed no correlation with symptom ratings, cognitive performance or antipsychotic medication. Additional studies in high-risk subjects in the early prodromal phase will be needed to address if excessive synapse destruction occurs before the development of overt psychotic symptoms.

T4 and waist:hip ratio as biomarkers of antipsychotic-induced weight gain in Han Chinese inpatients with schizophrenia.

Second-generation antipsychotic agents (SGAs) cause serious metabolic side effects, including weight gain, dyslipidemia, and glucose metabolism abnormalities, which occur by unknown mechanisms. Therefore, the search for prospective markers for antipsychotic-induced weight gain (AIWG) has been of major interest. So far, predictive factors predisposing patients to the develop obesity and related metabolic disturbances induced by SGAs have been relatively less studied among large samples of Chinese schizophrenic patients. In this study, 264 Han Chinese inpatients diagnosed with schizophrenia or schizoaffective disorder initiated treatment with olanzapine (n=131) or risperidone (n=133) and were followed for 12weeks. Anthropometric measurements and laboratory analyses of thyroid hormone, fasting plasma glucose (FPG), and lipid levels were conducted as part of routine medical care. The results showed baseline thyroxine (T4) and waist:hip ratio (WHR)were negatively correlated to AIWG (T4: rs=-0.154, P=0.014; WHR: rs=-0.199, P=0.008). Correlations remained significant after multiple regression analyses. The two treatment groups statistically differed for changes in body mass index, WHR, LDL cholesterol, and FPG; in both groups FPG decreased at first and then increased. Our findings suggest basal T4 and WHR may serve as early biomarkers for weight gain as a side effect of single-SGA treatment.

TOX and ADIPOQ Gene Polymorphisms Are Associated with Antipsychotic-Induced Weight Gain in Han Chinese.

To find the genetic markers related to the antipsychotic-induced weight gain (AIWG), we analyzed associations among candidate gene single-nucleotide polymorphisms (SNPs) and quantitative traits of weight changes and lipid profiles in a Chinese Han population. A total of 339 schizophrenic patients, including 86 first-episode patients (FEPs), meeting the entry criteria were collected. All patients received atypical antipsychotic drug monotherapy and hospitalization and were followed for 12 weeks. Forty-three SNPs in 23 candidate genes were calculated for quantitative genetic association with AIWG, performed by PLINK. The TOX gene SNP rs11777927 (P = 0.009) and the ADIPOQ gene SNP rs182052 (P = 0.019) were associated with AIWG (in body mass index, BMI). In addition, the BDNF SNP rs6265 (P = 0.002), BDAF SNP rs11030104 SNP (P = 0.001), and ADIPOQ SNPs rs822396 (P = 0.003) were significantly associated with the change of waist-to-hip ratio (WHR) induced by atypical antipsychotics. These results were still significant after age and gender adjustments. These findings provide preliminary evidence supporting the role of TOX, ADIPOQ and BDNF in weight and WHR gain induced by atypical antipsychotics.