Successful treatment of hyperglycemia with liraglutide in a hospitalized 27-year-old patient with schizophrenia: A case report.

BACKGROUND: Antipsychotics are associated with abnormalities in glucose metabolism in patients with schizophrenia. Liraglutide, a GLP-1 receptor agonist, is Food and Drug Administration approved for the treatment of type 2 diabetes mellitus. However, ways to maintain the long-term stability of psychotic symptoms and balance the disadvantages of obesity, diabetes, and other metabolic disorders caused by antipsychotic medications remain unclear. In this study, we present a case of weight gain and hyperglycemia in a schizophrenia patient who received antipsychotic polypharmacy for 6 years. CASE SUMMARY: A 27-year-old man with olanzapine and sodium valproate-treated disorganized schizophrenia was admitted to a diabetes outpatient clinic. He was diagnosed with type 2 diabetes (fasting blood glucose, 20 mmol/L) and obesity (body mass index, 38.58 kg/m2). The patient had been treated with glargine (40 IU/d) and metformin (1.5 g/d) and showed a poor response for 2 mo. Two years of liraglutide treatment resulted in stable blood glucose levels and weight loss in addition to a maintained stable mental status for a long time. The biological activities of GLP-1 significantly improved glucose levels and body weight in the schizophrenia patient treated with antipsychotic medications. CONCLUSION: Liraglutide administration can be considered an effective alternative treatment for abnormalities in glucose metabolism in schizophrenia patients receiving antipsychotics.

Association Study of Polymorphisms in Neuronal Nicotinic Acetylcholine Receptor Subunit Genes With Schizophrenia in the Han Chinese Population.

OBJECTIVE: To investigate the relation between nicotinic acetylcholine receptor subunit (nAChR) genes and schizophrenia, and the relation between tag single nucleotide polymorphism (rs1317286, rs1044396, rs6494212, rs16969968, and rs684513) and schizophrenia in Han Chinese people. METHODS: The protein-protein interaction (PPI) network among nAChR protein and 350 proteins encoded by schizophrenia-related susceptibility genes was constructed through the String database to explore whether nAChR genes were associated with schizophrenia in these known databases. Then, five single nucleotide polymorphisms (SNPs) of CHRNA3 (rs1317286), CHRNA4 (rs1044396), CHRNA7 (rs6494212), and CHRNA5 (rs16969968, rs684513) were analyzed in a sample of 1,035 schizophrenic patients and 816 healthy controls. The interaction between the markers was analyzed using multifactor dimensionality reduction (MDR) software. Power analysis was performed using the Quanto program. RESULTS: There are no significant differences in genotype or allele distribution were identified between the patients and controls (p>0.05). The haplotypes constructed by four markers rs1317286, rs6494212, rs16969968, and rs684513 were not associated with schizophrenia either. However, a significant association between models made of rs1317286, rs1044396, rs6494212, and rs684513 and schizophrenia was revealed in interaction analysis (p<0.05). CONCLUSION: The nAChR protein may have effects on the development of schizophrenia through the interaction with proteins encoded by schizophrenia-related susceptibility genes, but no relation was found between selected polymorphisms and schizophrenia in the collected Han Chinese people. However, interaction analysis suggested four-SNP model has an important effect on schizophrenia.

Identifying Modifiable Risk Factors for Relapse in Patients With Schizophrenia in China.

BACKGROUND: Preventing relapse of schizophrenic patients is really a challenge. The present study sought to provide more explicit evidence and factors of different grades and weights by a series of step-by-step analysis through χ2 test, logistic regression analysis and decision-tree model. The results of this study may contribute to controlling relapse of schizophrenic patients. METHODS: A total of 1,487 schizophrenia patients were included who were 18-65 years of age and discharged from 10 hospitals in China from January 2009 to August 2009 and from September 2011 to February 2012 with improvements or recovery of treatment effect. We used a questionnaire to collect information about relapse and correlative factors during one year after discharge by medical record collection and telephone interview. The χ2 test and logistic regression analysis were used to identify risk factors and high-risk factors firstly, and then a decision-tree model was used to find predictive factors. RESULTS: The χ2 test found nine risk factors which were associated with relapse. Logistic regression analysis also showed four high-risk factors further (medication adherence, occupational status, ability of daily living, payment method of medical costs). At last, a decision-tree model revealed four predictors of relapse; it showed that medication adherence was the first grade and the most powerful predictor of relapse (relapse rate for adherence vs. nonadherence: 22.9 vs. 55.7%, χ2 = 116.36, p < 0.001). The second grade factor was occupational status (employment vs. unemployment: 19.7 vs. 42.7%, χ2 = 17.72, p < 0.001); the third grade factors were ability of daily living (normal vs. difficult: 28.4 vs. 54.3%, χ2 = 8.61, p = 0.010) and household income (household income ≥ 3000 RMB vs. <3000 RMB: 28.6 vs. 42.4%, χ2 = 6.30, p = 0.036). The overall positive predictive value (PPV) of the logistic regression was 0.740, and the decision-tree model was 0.726. Both models were reliable. CONCLUSIONS: For schizophrenic patients discharged from hospital, who had good medication adherence, more higher household income, be employed and normal ability of daily living, would be less likely to relapse. Decision tree provides a new path for doctors to find the schizophrenic inpatient's relapse risk and give them reasonable treatment suggestions after discharge.

Insight into role and mechanism of Li on the key aspects of biodegradable ZnLi alloys: Microstructure evolution, mechanical properties, corrosion behavior and cytotoxicity.

ZnLi based alloys have been proved as desirable candidates for biodegradable materials accounting for its high mechanical performance and great biocompatibility. However, effects of Li on microstructure and comprehensive properties of Zn alloys are seldom investigated and need to be addressed. Herein, Zn-(0.1-1.4 wt%)Li alloys are fabricated and systematically analyzed. Lath-like Zn precipitates are observed in the primary ß-LiZn4 (ß) phase of Zn-(0.5-1.4 wt%)Li alloys, leading to the formation of dense ß/Zn lamellar structure with an inter-spacing of 0.8 µm. Mechanical tests show that the strengths of the ZnLi alloys have at least tripled due to the formation of dense ß/Zn lamellar structure. Early degradation behaviors of the ZnLi alloys in simulated body fluid (SBF) reveal a competitive releasing of Li+ and Zn2+. As the priority of Li+ releasing becomes more obvious with increasing Li content in the alloys, aqueous insoluble Li-rich corrosion products containing LiOH and Li2CO3 form a passivation film on Zn-(0.5-1.4 wt%)Li alloys. Consequently, corrosion rate decreases significantly from 45.76 µm/y of pure Zn to 14.26 µm/y of Zn-1.4Li alloy. Importantly, observations of white light interferometer microscope and transmission electron microscope demonstrate that ß phase degrades prior to Zn in the alloys, suggesting that biomedical implants made of ZnLi alloys are likely to degrade completely in human body. Cytotoxicity tests of the alloys exhibit no cytotoxicity in 10% extracts. The most tolerated Zn2+/Li+ concentrations of the alloy extracts to L-929 cells are calculated, which provides guidance for future design of Zn alloys containing Li.

Efficacy of low-dose D2/D3 partial agonist pramipexole on neuroleptic-induced extrapyramidal symptoms and symptoms of schizophrenia: a stage-1 open-label pilot study.

Objective: Some lines of evidence show that D2/D3 receptor partial agonist pramipexole may be effective in the treatment of extrapyramidal symptoms (EPS) and psychiatric symptoms of schizophrenia. Therefore, we analyzed whether a low dose of pramipexole (0.375-0.75 mg/day) has efficacy on EPS and symptoms of schizophrenia while maintaining tolerability. Methods: Ten subjects with EPS [including drug-induced parkinsonism (DIP) and akathisia] were recruited in a stage-1, open-label pilot study. All the subjects were treated with a low dose of pramipexole. The evaluations were performed at baseline, day 3, week 1, week 2, week 4, week 6, and week 8. The ratings of SAS, BARS, PANSS, CDSS, and CGI-S and adverse effects (AE) were recorded in every visit. Results: SAS total scores decreased significantly during the study in patients with DIP (P<0.001), and mild AEs were detected. Treatments with pramipexole did not show an anti-akathisia effect during the study, while 2 subjects experienced deterioration of akathisia and mood symptoms. The psychiatric symptoms of schizophrenia showed a trend of improvement during the study, but there was no improvement in depressive mood. Conclusion: A low dose of pramipexole can significantly relieve antipsychotic-induced parkinsonism, but not akathisia. Improvements in psychiatric symptoms of schizophrenia were found, but the results of this study need to be validated in a larger sample. No improvement of mood disorder was detected.

Long-term in vivo study of biodegradable Zn-Cu stent: A 2-year implantation evaluation in porcine coronary artery.

In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ±â€¯13 vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications. STATEMENT OF SIGNIFICANCE: Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research.

Quantitative efficacy of three antipsychotic drugs for schizophrenia based on a real-world study in China.

Atypical antipsychotics exert remarkable long-term efficacy on the personal and social functions of schizophrenic patients. However, quantitative information on the social function of schizophrenic patients treated with atypical antipsychotics is scarce in the current clinical guidelines. In this study, we established pharmacodynamic models to quantify the time-efficacy relationship of three antipsychotic drugs based on the data from a real-world study conducted in China. A total of 373 schizophrenic patients who received antipsychotic monotherapy with olanzapine (n = 144), risperidone (n = 160), or aripiprazole (n = 69) were selected from a three-year prospective, multicenter study. The follow-up times were 13, 26, 52, 78, 104, 130, and 156 weeks after baseline. A time-efficacy model was developed with nonlinear mixed effect method based on changes in Personal and Social Performance (PSP) score compared with the baseline level. Crucial pharmacodynamic parameters, including maximum efficacy and drug onset time, were used to distinguish the efficacy of the three drugs. We quantified the time course of PSP improvement in patients after treatment with these three antipsychotics: olanzapine, risperidone, and aripiprazole reached an Emax value of 80.3%, 68.2%, and 23.9% at weeks 56.7, 29.2, and 36.8, respectively. General psychotic symptoms, onset frequency, and illness course were identified as significant factors affecting the efficacy of these drugs. The newly constructed models provide an evidence of the benefit of long-term maintenance therapy with atypical antipsychotics in individualized schizophrenia treatment in China.

Efficacy and Safety of Agomelatine vs Paroxetine Hydrochloride in Chinese Han Patients with Major Depressive Disorder: A Multicentre, Double-Blind, Noninferiority, Randomized Controlled Trial.

PURPOSE: The purpose of this study is to investigate the efficacy, safety, and tolerability of agomelatine and paroxetine in Chinese Han patients with major depressive disorder (MDD). METHODS: A 8-week, double-blind, randomized, parallel study was conducted in 14 medical centers in mainland China from December 2011 to September 2012. A total of 264 subjects with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD were randomly assigned to receive agomelatine 25-50 mg/d (n = 132) or paroxetine 20-40 mg/d (n = 132). The primary efficacy was evaluated by the decrease of Hamilton Depression Rating Scale (HAM-D17) scores. The secondary measurements of efficacy included Hamilton Anxiety Rating Scale, Montgomery-Asberg Depression Rating Scale, Sheehan Disability Scale, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. The laboratory test abnormity, and observed and self-reported adverse events were all assessed as the measurements of safety and tolerability. RESULTS: Both the agomelatine and paroxetine groups showed significant improvement from baseline to the end point (P < 0.05) without between-group differences (P > 0.05). The mean decrease of HAM-D17 of agomelatine group was not inferior to the paroxetine group over the 8-week treatment (agomelatine 15.26 ± 6.44 vs paroxetine 14.87 ± 5.89, δ = 2.0; µA-µB 95% confidence interval, -1.13 to 1.91). The percentage of responders at the last postbaseline assessment was similar in the 2 groups on both HAM-D17 (agomelatine 66.15% vs paroxetine 63.49%) and Clinical Global Impressions-Improvement (agomelatine 79.09% vs paroxetine 80.36%). The anxiety (Hamilton Anxiety Rating Scale) and sleep symptoms (sleep items of HAM-D17) of the patients were improved significantly in the 2 groups at week 8 without between-group differences (P > 0.05). The incidence of overall adverse events was similar in the 2 groups (agomelatine 49.62% vs paroxetine 56.15%, P > 0.05). The incidence of adverse events in skin and subcutaneous tissue was higher in the paroxetine group than in the agomelatine group (none in agomelatine and 4.62% in paroxetine, P = 0.0144). CONCLUSIONS: Agomelatine showed equivalent antidepressant efficacy to paroxetine in treating MDD patients after 8 weeks of treatment with an acceptable safety.

Applicability of the Chinese version of the Personal and Social Performance scale in patients with severe mental disorders.

INTRODUCTION: This study was designed to determine the reliability and validity of the Chinese version of the Personal and Social Performance scale (PSP-CHN) and assess the applicability of using the PSP-CHN in patients with severe mental disorders. METHODS: A total of 285 outpatients with severe mental disorders, 220 with schizophrenia and 65 with major depressive disorder, were enrolled into the study. Both diagnoses were made using the DSM-IV. All the patients were assessed with the PSP-CHN, the GAF, and the CGI-S. In addition, the PANSS and the MADRS were used to assess the patients with schizophrenia and major depressive disorder, respectively. RESULTS: The PSP-CHN showed good internal consistency (Cronbach α = 0.839, n = 285), high interrater reliability for total scores (intraclass correlation coefficient, ICC = 0.865, n = 48), and good test-retest reliability (ICC = 0.892, n = 130). The PSP-CHN total score showed a statistically significant positive correlation with the GAF score (r = 0.927, P < .01, n = 285), as well as a significant negative correlation with the CGI-S total score (r = -0.793, P < .01, n = 285), the PANSS total score (r = -0.694, P < .01, n = 220), and the MADRS total score (r = -0.721, P < .01, n = 65). DISCUSSION: We were able to demonstrate that the PSP-CHN is a reliable and valid measurement tool to assess the personal and social functioning in patients with severe mental disorders.

Plasma metabonomics study of first-Episode schizophrenia treated with olanzapine in female patients.

Schizophrenia is a persistent chronic mental illness with an unknown pathogenic mechanism; no empirical laboratory-based tests are available to support the diagnosis of schizophrenia or to identify biomarkers correlated with the therapeutic effect of olanzapine. For this study, 15 female first-episode, drug-naïve patients with schizophrenia and 15 healthy female volunteers were recruited. Tests for blood glucose and lipids were conducted at baseline and after 4 weeks of treatment with olanzapine. UPLC-MS based metabonomic analysis was performed on both case and control groups to identify biomarkers of schizophrenia at baseline and to explore which biomarkers correlated with the therapeutic effect of olanzapine after a 4-week treatment. Compared with the control group, the case group showed significant changes in plasma metabolites. Thirteen distinct metabolites were identified. Among all the therapeutically effective cases, levels of these metabolites appeared to shift towards the normal trend; 8 of the identified 13 metabolites changed dramatically. The metabolites that we found are potential biomarkers for the diagnosis and treatment of schizophrenia.

Antidepressant desipramine leads to C6 glioma cell autophagy: implication for the adjuvant therapy of cancer.

Depression is the most common psychiatric syndrome in cancer patients and adversely affects anti-cancer immune system and life quality of patients. Antidepressant desipramine (DMI) is clinically prescribed in the auxiliary treatment of cancer patients. Increasing evidences suggest that DMI has a broad spectrum of target-off biological effects, such as anticancer properties. Our previous study revealed that DMI at the clinical relevant concentrations could induce CHOP-dependent apoptotic death in C6 glioma cells. In this study, we further explored the pro-autophagic effect of DMI in C6 glioma cells and its underlying mechanism. Treatment with DMI could induce autophagic cell death characterized by the formation of autophagosome and the elevated level of autophagic protein Beclin-1 and cellular redistribution of marker LC3. Meanwhile, DMI inhibited the activation of PI3K-AKT-mTOR pathway which is considered as a negative regulator of autophagy. Furthermore, DMI activated PERK-eIF2α and ATF6 of endoplasmic reticulum (ER) stress pathway, while knockdown of PERK with the PERK-specific short interfering RNA (siRNA) could obviously attenuate the autophagy. The results strongly suggested that DMI could induce autophagy through the PERK-ER stress pathway in C6 glioma cells. Our findings provided new insights into another beneficial potential of antidepressant DMI in the adjuvant therapy of cancer.

[Fracture analyses of casting framework removable partial dentures].

OBJECTIVE: To compare the clinical fracture rates of removable partial denture (RPD) made of titanium with that of Co-Cr alloy, to analyze the fracture modes and reasons of two kinds of metal frameworks, and to explore the effect of defects on the fracture process. METHODS: Following totally 30 618 RPDs made by titanium and by Co-Cr alloy, the fracture rates in 18-month were calculated individually. The fractured surfaces of failed RPDs were examined by fractography investigations using a field emission scanning electron microscope to disclose the fracture mode and damage character. The energy-dispersive X-ray spectroscopy analysis was performed to examine the chemical compositions. RESULTS: The fracture rate of titanium framework was 1.75%, comparing with 0.57% of Co-Cr alloy framework. The reasons included teeth preparing, framework design, and defects during casting. The fracture modes of titanium and Co-Cr alloy framework performed toughness fracture character. The fissures were found in both titanium and Co-Cr alloy frameworks, and pores were detected in titanium frameworks. CONCLUSION: The higher fracture rate of titanium framework is related to the defects during casting.

Randomized double-blind multicentre placebo-controlled clinical trial of the clonidine adhesive patch for the treatment of tic disorders.

OBJECTIVE: The aim of the present study was to evaluate the therapeutic effectiveness and safety of the clonidine adhesive patch in treating tic disorders. METHOD: A total of 437 patients, who met Chinese Classification of Mental Disorders-third edition diagnostic criteria for transient tic disorder (5%), chronic motor or vocal tic disorder (40%) or Tourette disorder (55%), aged 6-18 years, were divided randomly into an active treatment group and a clinical control group. Participants in the active treatment group were treated with a clonidine adhesive patch and participants in the clinical control group with a placebo adhesive patch for 4 weeks. The dosage of the clonidine adhesive patch was 1.0mg, 1.5mg or 2.0mg per week, depending on each participant's bodyweight. Participants whose Yale Global Tic Severity Scale (YGTSS) score decreased <30% and Clinical Global Impression score was > or =4 by the end of week 3 were withdrawn from the trial. RESULTS: After 4 weeks of treatment the active treatment group participants' YGTSS score was significantly lower than that of the clinical control group (F=4.63, p=0.03). Further, the active treatment group had a significantly better therapeutic response than the clinical control group (chi(2)=9.15, p=0.003). The response rate in the active treatment group was 68.85% compared to 46.85% in the clinical control group (chi(2)=16.98, p=0.0001). The rate of adverse events was low (active treatment group, 3.08%; clinical control group, 7.21%) and did not differ between the two groups. CONCLUSIONS: The clonidine adhesive patch is effective and safe for tic disorders.

Association between a polymorphism of the HTR3A gene and therapeutic response to risperidone treatment in drug-naive Chinese schizophrenia patients.

OBJECTIVES: Certain components of the serotonin system have been known for some time to be risk factors for schizophrenia. Few studies have, however, focused on the association between the therapeutic responses to atypical antipsychotics, such as risperidone, and polymorphisms of the 5-HT3 receptor, the only ionotropic ligand-gated serotonin receptor, even though there have been some genetic clues linking HTR3A and schizophrenia. We therefore postulated that such a polymorphism might be an explanatory factor in the diversity of response to risperidone treatment. METHODS: The study recruited 107 drug-naive Chinese schizophrenia patients who were given 8 weeks of risperidone monotherapy and it explored three of four single nucleotide polymorphisms spanning HTR3A for possible association with therapeutic improvement, using the Positive and Negative Symptom Scale. RESULTS: Significant correlation between the baseline score and therapeutic improvement was observed in each subscale (P<0.001). Statistical analysis revealed association between genotypes of g.14396A>G polymorphism (rs1176713) and score reductions of negative and general subscales after adjusting for the influence of the baseline scores of each subscale [P (F, d.f.)=0.026 (3.763, 2), 0.023 (3.937, 2) respectively]. One haplotype, C-A-G, contributed to an effective response in general symptoms (chi(2)=7.3, P=0.007, odds ratio=3.371). CONCLUSION: The results of this study are the first to suggest that the polymorphism of HTR3A may be a useful predictor of therapeutic response to risperidone treatment in Chinese schizophrenic patients, although these conclusions should be treated with caution because of the intricacy of the variety of the therapeutic effects to risperidone.

Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients.

AIM: Extrapyramidal syndrome (EPS) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor. Recently, many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression. In this study, we evaluate the role DRD2 plays in chlorpromazine-induced EPS in schizophrenic patients. METHODS: We identified seven SNP(single nucleotide polymorphism) (-141Cins>del, TaqIB, TaqID, Ser311Cys, rs6275, rs6277 and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87 without EPS according to the Simpson-Angus Scale) treated with chlorpromazine after 8 weeks. The alleles of all loci were determined by PCR (polymerase chain reaction). RESULTS: Polymorphisms TaqID, Ser311Cys and rs6277 were not polymorphic in the population recruited in the present study. No statistical significance was found in the allele distribution of -141Cins>del, TaqIB, rs6275 and TaqIA or in the estimated haplotypes (constituted by TaqIB, rs6275 and TaqIA) in linkage disequilibrium between the two groups. CONCLUSION: Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine, at least in Chinese patients with schizophrenia. Our results confirmed a previous study on the relationship between DRD2 and EPS in Caucasians.

Association analysis of polymorphisms in the upstream region of the human dopamine D4 receptor gene in schizophrenia.

Several studies have suggested that the transcriptional activity of the DRD4 gene may exert an important role in susceptibility to schizophrenia. To address this issue, we studied the association of schizophrenia and polymorphisms including -616C>G, -603T>del, -602G>del, 600G>C, -521C>T, -376C>T and a 120 bp tandem duplication polymorphism (120 bp repeat) in 1.2 kb upstream from the initiation codon in the promoter region of the DRD4 gene with 210 schizophrenic cases and 206 healthy controls. The results showed a significant excess of allele L of the 120 bp repeat in the schizophrenic patients compared to the controls (X(2)=8.585, df=1, P=0.003, OR=1.546, 95% CI=1.154-2.070). No significant difference was detected in the frequencies of genotype and allele of six other polymorphisms between the two groups. However, haplotypic distribution of 120 bp repeat, -616C>G, -602G>del, -521C>T and -376C>T was significantly different between case and control groups (P=0.005). This might cause the alteration of the transcriptional regulation of the DRD4 gene, as the consensus sequences of binding sites for several known transcription factors are involved in this region.