Research advances in add-on treatment for negative symptoms and cognitive dysfunction in schizophrenia / 中南大学学报(医学版)

Antipsychotic medication is the primary treatment for schizophrenia, which is effective on ameliorating positive symptoms and can reduce the risk of recurrence, but it has limited efficacy for negative symptoms and cognitive dysfunction. The negative symptoms and cognitive dysfunction seriously affects the life quality and social function for the patients with schizophrenia. Currently, there is plenty evidence that antipsychotic drugs combined with adjuvant therapy drugs can effectively improve the negative symptoms and cognitive dysfunction. These drugs include anti-oxidants, nicotinic acetylcholine receptors and neuro-inflammatory drugs (anti-inflammatory drugs, minocycline), which show potential clinical effects.

Cognitive function in patients with early onset and adult onset schizophrenia / 中国心理卫生杂志

Objective:To explore the characteristics of cognitive function in patients with early onset and adult onset schizophrenia.Methods:In this cross-sectional study, 546 patients with schizophrenia who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-Ⅳ) were selected.Among them, 62 cases were defined as early onset schizophrenia (EOS, age of onset＜18 years) and 175 patients were defined as adult onset schizophrenia (AOS, age of onset≥25 years).Patients underwent clinical assessments with the Positive and Negative Symptom Scale (PANSS) and the Personal and Social Performance Scale (PSP), and comprehensive neuropsychological assessments.Results:The EOS patients got lower scores in motor function-PEGDOM T score [ (26±12) vs. (30±11), P＜0.01], working memory-average T score of PASAT and WMSSP[ (34±12) vs. (38±10), P＜0.05]and executive function (inhibition) -Stroop T score [ (35±12) vs. (39±10), P＜0.05]than AOS patients.No differences were fund in processing speed, verbal memory and learning, visual memory and learning (Ps＞0.05) between the two groups.Conclusion:It suggests that the EOS patients have worse motor function, working memory and inhibition.

Metformin treatment of antipsychotic-induced dyslipidemia: analysis of two randomized, placebo-controlled trials / 中南大学学报(医学版)

To examine the efficacy and safety for metformin in treating antipsychotic-induced dyslipidemia.
 Methods: Two randomized placebo-controlled trials were included in the analysis. A total of 201 schizophrenia patients with dyslipidemia after treatment with an antipsychotic were collected, and the patients were divided into two groups: a 1 000 mg/d metformin group (n=103) and a placebo group (n=98). The clinical symptoms and metabolic indicators such as body weight, blood glucose, and blood lipids were assessed at baseline, the 12th week and the 24th week after treatment respectively.
 Results: After metformin treatment, the mean difference in the low-density lipoprotein cholesterol (LDL-C) value between the metformin group and the placebo group was from 0.16 mmol/L at baseline to -0.86 mmol/L at the end of the 24th week, which was decreased by 1.02 mmol/L 
(P<0.01). At the 24th week, the LDL-C was more than 3.37 mmol/L in 25.3% patients in the metformin group, which was significantly lower than that in the placebo group (64.8%) (P<0.01). Compared with the placebo group, there were significant changes in the weight, body mass index (BMI), insulin, insulin resistance index, total cholesterol and triglyceride, and high-density lipoprotein cholesterol (HDL-C) in the metformin group (all P<0.05). The treatment effects on weight and insulin resistance appeared at the 12th week and further improved at the 24th week, but the effects on improving dyslipidemia only significantly occurred at the end of the 24th week.
 Conclusion: The metformin treatment is effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effect to reduce the antipsychotic-induced insulin resistance appears earlier than the effect to improve dyslipidemia.

Expert advice on practical use of amisulpride in treatment of schizophrenia / 中国心理卫生杂志

Amisulpride,a kind of the second generation antipsychotics,was marketed in China in 2010.A series of clinical research and experience before and after listed,especially the data based on Chinese population,provided evidence for the generalization and application of amisulpride.In order to optimize the clinical application of amisulpride,and improve the prognosis of patients,Expert Advice on the Practical Use of Amisulpride in the Treatment of Schizophrenia is presented here.This advice is based on the recent evidence and clinical experience,for guiding the clinical medication of amisulpride.

Progress in study on the role of exosome-derived microRNA in diagnosis and treatment of diseases / 中南大学学报(医学版)

Exosome is a kind of biological membrane structure at nanometer level. It is secreted by various cells in the body and widely distributed in most body fluids, such as saliva, blood, and milk. Biological active substances, including mRNAs, microRNAs, cytokines, and transcription factor, have been identified in the exosomes. MiRNAs are short and non-coding RNAs that modulate gene expression at the posttranscriptional level. MiRNAs extensively involves in henogenesis, cell proliferation and apoptosis. With various biological functions, exosome-derived miRNAs can not only be served as biomarkers to diagnose tumor, neurological diseases and mental disorders, but also possess potential as therapeutic targets.

Association study of disrupted in schizophrenia 1 gene polymorphisms with autism in Chinese Han children / 中华实用儿科临床杂志

Objective To investigate the relationship between the single nucleotide polymorphisms(SNPs) of disrupted in schizophrenia 1 (DISC1) gene and autism in Chinese Han children.Methods Genome-wide SNP genotyping was performed by using Illumina HumanHap CNV370-Duo Chip in 278 autistic trios,157 autistic individuals and 435 healthy controls.Genotype data of SNPs within DISC1 gene were selected.The association between these SNPs loci and autism was analyzed through case-control association analysis and family-based transmission disequilibrium test.Results Fifty-two SNPs were involved for further analysis.1.Case-control association analysis showed that 6 SNPs (rs4658939,rs2793093,rs10495309,rs2492367,rs1 1122362,rs1073179) and 7 haplotypes (AGAAAG constructed with rs823163-rs823161-rs4658933-rs1417585-rs10864693-rs6541281,GGG and AAA constructed with rs4658939-rs2793093-rs10495309,GG and AG constructed with rs2492367-rs12046794,GAA constructed with rs9432040-rs2356606-rs1 1122362 and GG constructed with rs9431714-rs1073179) had significant differences between autistic patients and controls(x2 =4.704,4.915,5.568,8.087,4.043,5.183,5.369,5.295,4.440,5.304,7.615,4.018,4.811,P =0.030,0.027,0.018,0.005,0.044,0.023,0.021,0.021,0.035,0.021,0.006,0.045,0.028).2.In the transmission disequilibrium test analysis,2 SNPs (rs4658945,rs11122362) and 2 haplotypes (AG constructed with rs10495310-rs4658945,GAA constructed with rs9432040-rs2356606-rs11122362) showed significant transmission disequilibrium(x2=4.445,5.400,3.973,5.126,P =0.035,0.020,0.046,0.024).Conclusions The polymorphism of rs11122362 and GAA haplotype constructed with rs9432040-rs2356606-rs11122362 are associated with autism,and DISC1 gene is a susceptibility gene for autism in Chinese Han children.

Effects of ziprasidone and olanzapine on glucose and lipid metabolism in first-episode schizophrenia / 中南大学学报(医学版)

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.

Brain-derived neurotrophic factor gene G196A polymorphisms and the cognitive function of schizophrenia: a case-control study / 中华行为医学与脑科学杂志

Objective To explore the relationships between brain-derived neurotrophic factor gene G196A polymorphisms and psychopathology and the cognitive function in schizophrenic patients.Methods 224 patients and 220 normal controls were examined with polymerase chain reaction(PCR),denaturing polyacrylamide gel electrophoresis and silver staining to determine genotype and allele of G196A.Clinical symptoms were assessed with the Positive and Negative Symptom Scale (PANSS).Cognitive function was assessed with Wisconsin card sorting test (WCST) and Trail Making Test(CPT).To analyse the differences of the scores of Scale for the Assessment of Positive Symptoms(SAPS) and Scale for the Assessment of Negative Symptoms (SANS) among the patients with the genotype G/G,G/A and A/A.At the same time,the differences of the performance of WCST and CPT were analyzed.Results ①There were no significant differences of the genotypes G/G,G/A and A/A and allele G and A between patients and controls.②There were significant differences of the genotypes A/A between patients with Positive Symptoms and patients with Negative Symptoms (x2 =4.558,P ＜ 0.05).③There were no significant differences in the performances of complete categorizations and persistent wrong numbers of WCST and the performances of CPT among three groups of patients with genotype G/G,G/A and A/A (One-Way ANOVA,all P ＞ 0.05).Conclusion BDNF gene G196A polymorphisms are not associated with schizophrenia and the cognitive function but are associated with positive symptoms of schizophrenia.

Effect of Shuganjieyu capsules on neuronal apoptosis in hippocampal CA3 area and the expression of caspase-3 in the brain of rat depression model / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the effect of "Shuganjieyu" (SGJY) capsules on neuronal apoptosis in hippocampal CA3 area and the expression of caspase-3 in the brain of rat depression model, and to investigate its pharmacological mechanisms in depression treatment.@*METHODS@#Adult male SD rats were randomly divided into 4 groups: a control, a model, a SGJY and a fluoxetine group. The rat depression model was established under chronic unpredictable mild stress (CUMS) and separate feeding. The behaviors were measured by open-field test, sucrose consumption and forced swimming test. We observed the neuronal morphology structure and neuronal apoptosis in the hippocampal CA3 area. We detected the rat caspase-3 expression level of medial prefrontal cortex ( mPFC) and hippocampal CA3 area by Western blot.@*RESULTS@#After 21-day stress, compared with the model group, spontaneous activity and sucrose consumption and preference percentage of the rats in the SGJY group significantly increased, while the immobility time in forced swimming test, the number of apoptotic cells and the protein levels of caspase-3 significantly reduced (P0.05).@*CONCLUSION@#SGJY capsules can reduce the depression symptoms of CUMS and help to increase hippocampal neuron generation, survival and neogenesis, reduce the protein levels of caspase-3, and reverse neurocyte apoptosis in the rat depression model with the same efficacy as fluoxetine.

Genetics of autism spectrum disorders / 中南大学学报(医学版)

Autism is a group of etiology and clinical heterogeneous neurodevelopmental disorders with an onset before 3 years old. It has 3 core characteristics: deficits in verbal communication; impairment of social interaction; restricted interests and repetitive behaviors. The incidence is increasing over time worldwide. Twin and family studies have demonstrated that autism has a high heritability (>90%). Although certain progress of autism genetic study has been made in the last decades and several autism susceptibility genes and loci have been identified, there are still about 70%-80% of patients for whom an autism-related genetic change cannot be identified.

Genetics of autism spectrum disorders / 中南大学学报(医学版)

Autism is a group of etiology and clinical heterogeneous neurodevelopmental disorders with an onset before 3 years old.It has 3 core characteristics:deficits in verbal communication;impairment of social interaction; restricted interests and repetitive behaviors.The incidence is increasing over time worldwide.Twin and family studies have demonstrated that autism has a high heritability ( ＞ 90％ ).Although certain progress of autism genetic study has been made in the last decades and several autism susceptibility genes and loci have been identified,there are still about 70％ -80％ of patients for whom an autism-related genetic change cannot be identified.

Concentration change of DA, DOPAC, Glu and GABA in brain tissues in schizophrenia developmental model rats induced by MK-801 / 中南大学学报(医学版)

Objective To explore the related neurobiochemical mechanism by comparing the concentration change of dopamine (DA),dihydroxy-phenyl acetic acid (DOPAC),glutamate (Glu),and γ-aminobutyric acid (GABA) in the brain tissues in schizophrenia (SZ) developmental model rats and chronic medication model rats.Methods A total of 60 neonatal male Spragur-Dawley (SD) rats were randomly assigned to 3 groups at the postnatal day 6:an SZ developmental rat model group (subcutaneous injection with MK-801 at the postnatal day 7-10,0.1 mg/kg,Bid),a chronic medication model group (intraperitoneal injection at the postnatal day 47-60,0.2 mg/kg,Qd),and a normal control group (injection with O.9％ normal saline during the corresponding periods).DA,DOPAC,Glu,and GABA of the tissue homogenate from the medial prefrontal cortex (mPFC) and hippocampus were examined with Coularray electrochemic detection by high performance liquid chromatogram technique.The utilization rate of DA and Glu was calculated.Results Compared with the normal control group,the concentration of DA and DOPAC in the mPFC and the hippocampus in the SZ developmental model group significantly decreased ( P ＜ 0.05 ),and the GABA concentration and Glu utilization rate in the mPFC also decreased (P ＜ 0.05 ).Compared with the chronic medication model group,the DA concentration of the mPFC in the SZ developmental group decreased ( P ＜ 0.05 ),and the DOPAC concentration and the utility rate of DA in the hippocampus also decreased (P ＜0.01,P ＜0.05,respectively).Conclusion The activities of DA,Glu and GABA system decrease in the mPFC and the DA system function reduces in the hippocampus of SZ developmental rats.

Genetic predictors of antipsychotic-induced weight gain: a case-matched multi-gene study / 中南大学学报(医学版)

Objective To determine associations between weight gain induced by antipsychotic and the polymorphisms of HTR2C gene -759C/T and -697G/C,histamine-1 receptor gene,leptine gene -2548G/A,and adiponectin gene +276G/T and +45T/G.Methods In the casematched study,85 patients who gained more than 7％ of their pre-drug body weight served as the study group and another 85 patients who gained less than 7％ of their pre-drug body weight served as the control group.The ligation diction reaction technique was used to analyze the frequencies of the -759C/T and -697G/C polymorphism of the HTR2C gene,-2548A/G polymorphism of leptin gene,+ 276G/T and + 45T/G polymorphism of adiponectin gene and glu349asp polymorphism of H1 receptor gene.Results The presence of the -759C allele,-697G allele,-2548A allele and + 276G allele was significantly higher in the study group than that in the control group (P ＜ 0.05 ).Conclusion The -759C/T and -697G/C polymorphisms of the promoter region of 5HT2C receptor gene,-2548A/G polymorphisms of leptin gene and + 276G/T polymorphisms of adiponectin gene may be associated with the antipsychotic induced weight gain.The glu349asp polymorphisms of histamine-1 receptor gene is not associated with antipsychotic induced weight gain.

Cognitive functioning in schizophrenia with or without diabetes / 中南大学学报(医学版)

Objective To determine the influence of schizophrenia patients with diabetes on cognitive function.Methods Altogether 78 schizophrenia patients with diabetes and 118 patients with schizophrenia were enrolled and Negative and Positive Syndrome Scale,Wechsler Memory Scale-Revised Visual Reproduction Test,Wechsler Adult Intelligence Scale-Revised Digit Symbol Test,Computerized Wisconsin Card Sorting Test,Trail Making Tests,Part A and B,and Wechsler Adult Intelligence Scale-Revised Digit Span Test were used to assess the clinical syndrome and to test the cognitive function.ResultsImpairment of Processing Speed,Attention/Working Memory,Executive Functioning and Visual Memory in schizophrenia patients with diabetes was significantly poorer than that of the schizophrenia patients ( all P ＜ 0.05 ).WAIS-R Digit Symbol Test score and Trail Making Test A and B scores were associated with diabetes duration and age at diabetes onset (P ＜0.01 ).Conclusion The impairment of cognitive function in schizophrenia patients with diabetes is severer than schizophrenia patients,suggesting that the prevention and management of diabetes may improve cognitive outcome in schizophrenia patients.

Effect of antipsychotic drugs on life quality of schizophrenic patients: one year follow-up study / 中南大学学报(医学版)

OBJECTIVE@#To compare the effect of 7 antipsychotic drugs on the life quality of schizophrenia patients including chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine, and aripiprazole.@*METHODS@#A total of 1,227 stable schizophrenic patients within 5 years onset who took 1 of the 7 study medications as maintenance treatment were followed up for 1 year at 10 China sites. Patients were evaluated by the short form-36 health survey (SF-36) at the baseline and at the end of 1 year.@*RESULTS@#The life quality was improved obviously at the end of the follow-up. There was significant difference in body pain, vitality, and mental health (P<0.05) among these antipsychotic drugs.@*CONCLUSION@#All 7 antipsychotic drugs can improve the life quality of schizophrenia patients. Atypical antipsychotic drugs, especially olazapine and quetiapine, are superior to typical antipsychotic drugs in improving life quality.

Adiponectine gene +45T/G and +276G/T polymorphism and antipsychotic-induced weight gain / 中南大学学报(医学版)

ts The presence of +276G allele was significantly higher in the study group as compared with the control group.Conclusion Subjects with the +276G variant alleles may have a greater risk for weight gain after antipsychotic treatment.

Efficacy and Safety of Zaleplon in Treatment of Insomnia / 中国药房

OBJECTIVE:To evaluate the efficacy and safety of new agent zaleplon in treatment of insomnia.METHODS:A randomized,double-blind,controlled and dosage-adjusted clinical trial was conducted.The subjects had been treated with zaleplon5～10mg/d and zopicolone7.5～15mg/d for14days,respectively.RESULTS:The scores of sleep dysfunction rating scale at endpoint were significantly reduced as compared with the baseline in both groups(P

Association of schizophrenia and the C270T polymorphism of brain-derived neurotrophic factor gene / 中国组织工程研究

BACKGROUND: The study on the candidate gene of schizophrenia was one of the major ways of exploring its etiology. One of important candidate genes associated with schizophrenia is the brain-derived neurotrophic factor gene(BDNF)OBJECTIVE: To explore the association between schizophrenia and C270T polymorphism of BDNF gene.DESIGN: Case-control and comparative observation SETTING: Institute of Mental Health of Central South University PARTICIPANTS: Totally 194 patients with schizophrenia, including 95 males and 99 females aged from 15 to 59 years, hospitalized in man and women wards in the Institute of Mental Health, Xiangya Second Hospital of Central South University from March to October 2003 were set as patients group. Controls were selected among the healthy volunteers of Xiangya Medical College was included in terms of age and gender comparable with patients group. Altogether 187 cases of controls, of whom 88 males and 99 females were studied. Their age ranged from 18 to 42 years old with the average of (26±7) years old.Those with psychosies and severe somatopathy were excluded. The patients and their family member have no history of psychosis .All the subjects were of Hunan Han nationality. Either the patient or his or her family members signed the written consent form. Individuals in the control group also signed the written consent form.positive symptom scale (PANSS-P) (7 items), negative symptom scale (PANSS-N) (7 items) and General Symptom Scale (PANSS-G) (16 items),altogether 30 items, as well as 3 additional items to evaluate the attack fatalness were used to evaluate whether the psychic symptom existed or not and the degree of severity of each symptom(7-item scoring: 1 was without,7 was very severe) . The patients were evaluated on the day of hospitalizing was used to compare the frequency among groups.polymorphism of BDNF gene between patients group and healthy control RESULTS: Totally 194 patients with schizophrenia and 187 healthy genotype (26.8%) in patients was much higher than that of the healthy controls (5.9%) (x2=32.71, df=1, P ＜ 0.01).The distribution frequency of T allele in patients' group (14.4%) was much higher than that in the scores, PANSS-P, PANSS-N and PANSS-G scores in patients with the genotype of C/T were 59-121 ;9-42( average 20.08±6.16);8-41 (average 19.02±9.13);22-68 (average 36±8.02)respectively. And the total PANSS scores, PANSS-P, PANSS-N and PANSS-G scores in patients with the genotype of C/C were 58-121 ;7-39, (average 19.2±5.88);8-40scores, (average19.02 ±8.98); 22 -68 (average36.4 ±8.32)respectively.There were no significant differences in positive and negative symptom scale (PANSS)items as well as PANSS-G between the patients with C/C and C/T genotype(P ＞ 0.05).CONCLUSION: BDNF gene C270T polymorphism was associated with the susceptibility of schizophrenia. The distribution frequency of T/C genotype and T allele in schizophreniac was significantly higher than those of the normal healthy controls. And no significant difference was obtained between patients with the genotype of T/C or C/C in terms of negative,positive symptoms and psychosocial function as well.

Study on the NF-?B activation and mRNA expression of NF-?B,IL-1?,TNF-? and IL-6 in PBMCs of first-episode schizophrenia / 中国免疫学杂志

Objective:To measure the nuclear factor kappa B(NF-?B) activation and its mRNA expression in the PBMC,and to analyze the interaction between NF-?B activation and IL-1?,IL-6,TNF-? mRNA expression for exploration the role of NF-?B in production of cytokine in schizophrenia.Methods:Transcription Factor Assay Kits were used to measure NF-?B activation.RT-PCR technique was perftormed to analyze semiquantitatively NF-?B,IL-1?,IL-6 and TNF-? mRNA expression in the PBMC in both schizophrenia and control group.Results:NF-?B activation and its mRNA expression in the schizophrenia group were significantly higher than in the control group(P0.05).IL-1?,IL-6 and TNF-? mRNA expressions in the PBMCs from the schizophrenia group were significantly higher than those from the control subjects(P0.05).Conclusion:It is of significance to measure NF-?B activation in evaluating the regulation function of NF-?B.Activated NF-?B plays an important role in mediating the expression of IL-1? and TNF-? gene in schizophrenia.