Metformin Attenuates Liver Fat Content: Finding from Schizophrenia Patients with Olanzapine-induced Weight Gain.

OBJECTIVE: This study was performed to evaluate the efficacy of metformin on liver fat content (LFC) in first episode schizophrenia patients with olanzapine-induced weight gain, and the relationship between the change of LFC and the other metabolic indices. METHODS: In a double-blind study, the clinically stable inpatients with first-episode schizophrenia under olanzapine monotherapy who gained more than 7% of their baseline weight were randomly assigned to two groups; one with olanzapine plus metformin (1,000 mg/day) (metformin group) and the other with olanzapine plus placebo (placebo group) for 16 weeks. All patients continued to maintain the original olanzapine dosage. LFC was measured by magnetic resonance imaging at baseline and at the end of 16 weeks, respectively. At the same time, glucose and lipid metabolism, homeostasis model assessment of insulin resistance index (HOMA-IR) were measured respectively, analyzing the correlation between the change value of LFC and other indicators. RESULTS: Over the 16-week study period, LFC value in metformin group decreased compared with baseline. LFC change across the 16-week treatment period was -2.91% for the metformin group and 0.59% for the placebo group, with a between-group difference of -3.5% (95% confidence interval, -6.08 to -0.93; p = 0.009). Compared to baseline, in the metformin group, triglyceride and HOMA-IR reduced significantly, while high density lipoprotein cholesterol increased significantly at weeks 16. There was positive correlation between LFC changes and triglycerides, HOMA-IR changes significantly. CONCLUSION: Metformin can significantly attenuate LFC in schizophrenia patients with olanzapine-induced weight gain. It may be related to the improvement of the part of the glucolipid metabolic indices.

Function of Ca2+ -/calmodulin-dependent protein kinase IV in Ca2+ -stimulated neuronal signaling and behavior.

The activity of Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) is sensitive to activity-dependent changes in the level of intracellular Ca(2+). Following neuronal stimulation, the activation of CaMKIV may trigger synaptic modifications and transcriptional responses, both of which are involved in regulating cognitive and emotional behavior. Here, we used CaMKIV knockout (KO) neurons and mice to examine the function of CaMKIV in Ca(2+)-stimulated intracellular signaling and animal behavior, respectively. Following NMDA receptor activation or membrane depolarization, the up-regulation of CREB (cAMP responsive element binding protein) and its target gene Bdnf (brain-derived neurotrophic factor) was intact in cortical neurons obtained from CaMKIV KO mice. CaMKIV KO mice displayed severe impairment in contextual fear memory but normal locomotor activity and anxiety level in the contextual training chamber. Although CaMKIV KO mice showed normal memory in the standard passive avoidance task, they were defective in learning the temporal dissociative passive avoidance task. As indicated by the light/dark test and marble-burying test data, CaMKIV KO mice showed less anxiety and normal perseveration. In the voluntary wheel-running test, CaMKIV KO mice showed normal running time and distance but higher maximal running speed. Our results demonstrate the function of CaMKIV in regulating different forms of fear memory, anxiety, and certain aspect of motor function.

Abnormal glycosylated hemoglobin as a predictive factor for glucose metabolism disorders in antipsychotic treatment.

The aim of this study was to observe the changes in glucose metabolism after antipsychotic (APS) therapy, to note the influencing factors, as well as to discuss the relationship between the occurrence of glucose metabolism disorders of APS origin and abnormal glycosylated hemoglobin (HbA1c) levels. One hundred and fifty-two patients with schizophrenia, whose fasting plasma glucose (FPG) and 2-h plasma glucose (2hPG) in the oral glucose tolerance test (2HPG) were normal, were grouped according to the HbA1c levels, one normal and the other abnormal, and were randomly enrolled into risperidone, clozapine and chlorpromazine treatment for six weeks. The FPG and 2hPG were measured at the baseline and at the end of the study. In the group with abnormal HbA1c and clozapine therapy, 2HPG was higher after the study [(9.5 ± 1.8) mmol/L] than that before the study [(7.2 ± 1.4) mmol/L] and the difference was statistically significant (P < 0.01). FPG had no statistically significant difference before and after the study in any group (P > 0.05). HbA1c levels and drugs contributing to 2HPG at the end of study had statistical cross-action (P < 0.01). In the abnormal HbA1c group, 2HPG after the study was higher in the clozapine treatment group [(9.5 ± 1.8) mmol/L] than in the risperidone treatment group [(7.4 ± 1.7) mmol/L] and the chlorpromazine treatment group [(7.3 ± 1.6) mmol/L]. The differences were statistically significant (P < 0.01). In the normal HbA1c group there was no statistically significant difference before and after the study in any group (P > 0.05). 2HPG before [(7.1 ± 1.6) mmol/L] and after the study [(8.1 ± 1.9) mmol/L] was higher in the abnormal HbA1c group than in the normal HbA1c group [(6.2 ± 1.4) mmol/L vs (6.5 ± 1.4) mmol/L] with the difference being statistically significant (P < 0.01 vs P < 0.001). As compared with normal HbA1c group, the relative risk (RR) of glucose metabolism disease occurrence was 4.7 in the abnormal HbA1c group with the difference being statistically significant (P < 0.001). Patients with abnormal HbA1c are more likely to have a higher risk of having glucose metabolism disorders after APS treatment.