Developments in Biological Mechanisms and Treatments for Negative Symptoms and Cognitive Dysfunction of Schizophrenia / 神经科学通报·英文版

The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade. The first part of this review summarizes the pathogenesis of schizophrenia, especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and epigenetics. The second part describes the novel medications and several advanced physical therapies (e.g., transcranial magnetic stimulation and transcranial direct current stimulation) for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.

Developments in Biological Mechanisms and Treatments for Negative Symptoms and Cognitive Dysfunction of Schizophrenia / 神经科学通报·英文版

The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade. The first part of this review summarizes the pathogenesis of schizophrenia, especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and epigenetics. The second part describes the novel medications and several advanced physical therapies (e.g., transcranial magnetic stimulation and transcranial direct current stimulation) for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.

Analysis about risk factors of autism disorder in 278 children / 中华实用儿科临床杂志

Objective To explore the high risk factors of the etiology of autism disorder.Methods Two hundred and seventy-eight children with autism disorder and 200 healthy children were investigated with self-designed questionnaire to obtain their demographic information,pre-and perinatal information,developmental information in toddler period.All the data were compared between autism group and healthy controls.Results 1.There were significant dif ferences in maternal prenatal data and perinatal data between autism group and healthy controls.Logistic regression analysis found that maternal/paternal reproductive age,family burden,caregiver,pregnancy reaction,drug administration in prenatal period,mode of delivery,chief instructor entered the regression equation.2.The 6 items in regression equation which had clinical significance consisted of maternal reproductive age above 30 years old [odds ratio (OR) =6.72],family history of mental disorders (OR =5.80),drug administration in prenatal period (OR =4.65),non-natural childbirth (OR =4.15),paternal reproductive age above 30 years old (OR =1.27),moderate or serious pregnancy reaction (OR =1.04).Conclusions The main risk factors of autism disorder in pre-and perinatal period consists of maternal reproductive age above 30 years old,positive family history of mental disorders,drug administration in prenatal period and non-natural childbirth.Avoiding these risk factors might contribute to reduce the incidence of autism.

MiRNA-365 and miRNA-520c-3p respond to risperidone treatment in first-episode schizophrenia after a 1 year remission / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>MicroRNAs (miRNAs) control gene expression by destabilizing target transcripts and inhibiting their translation. Aberrant expression of miRNAs has been described in many human diseases, including schizophrenia. However, the effects on miRNA expression in response to antipsychotic treatment in peripheral circulation have not been thoroughly examined.</p><p><b>METHODS</b>Using quantitative real-time PCR (qRT-PCR), We quantified the expression of seven candidate miRNAs in plasma samples of 40 first-episode schizophrenics before and after antipsychotic treatment. The patients were all treated with risperidone and achieved remission in 1 year.</p><p><b>RESULTS</b>Compared with the baseline, the expression levels of miR-365 and miR-520c-3p were significantly down-regulated after 1 year of risperidone treatment (P < 0.001). There were no significant correlations between the clinical symptoms and the expression levels of these two miRNAs (P > 0.05).</p><p><b>CONCLUSIONS</b>This study analyzed possible circulating miRNAs in response to antipsychotic monotherapy for schizophrenia, the further mechanism need to be confirmed.</p>

Changes in expression levels of PV, GAD67 and KCC2 in the brain tissue of rats with schizophrenia induced by MK-801 / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study changes in the expression levels of parvalbumin (PV), glutamate decarboxylase 67 (GAD67) and K+-Cl- cotransporter 2 (KCC2) in the brain tissue of rats with schizophrenia (SZ) induced by dizocilpine (MK-801), and to investigate the mechanism involving gamma-aminobutyric acid (GABA) by which NMDA receptor blocker induces SZ in the perinatal period.</p><p><b>METHODS</b>Thirty-six neonatal male Sprague-Dawley rats were randomly assigned to two batches on postnatal day 6. Each batch was divided into normal control (treated by 0.9% normal saline), SZ-development model (treated by subcutaneous injection of 0.1 mg/kg MK-801 on postnatal days 7-10; bid), and SZ-chronic medication model groups (treated by intraperitoneal injection of 0.2 mg/kg MK-801 on postnatal days 47-60; qd). On postnatal day 63, the brain tissue of the first batch of rats was obtained and then fixed with paraform for histological sections; expression levels of PV and GAD67 in the medial prefrontal cortex (mPFC) and hippocampus CA1 were measured by immunohistochemistry. Simultaneously, the second batch of rats was sacrificed and the mPFC and hippocampus were obtained and homogenized; expression levels of KCC2 in the mPFC and hippocampus were measured by Western blot.</p><p><b>RESULTS</b>Expression levels of PV and GAD67 in the mPFC and hippocampus CA1 were significantly lower in the SZ-development and chronic medication model groups than in the normal control group (P<0.05). Expression levels of KCC2 in the mPFC and hippocampus were significantly lower in the SZ-development model group than in the SZ-chronic medication model and normal control groups (P<0.05).</p><p><b>CONCLUSIONS</b>The expression changes of PV and GAD67 in SZ can be simulated using the SZ development model induced by MK-801, which might affect the development of the GABA system in the PFC and hippocampus by downregulating KCC2 expression.</p>

Linkage analysis of susceptibility loci in 2 target chromosomes in pedigrees with paranoid schizophrenia and undifferentiated schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship of susceptibility loci in chromosomes 1q21-25 and 6p21-25 and schizophrenia subtypes in Chinese population.</p><p><b>METHODS</b>A genomic scan and parametric and non-parametric analyses were performed on 242 individuals from 36 schizophrenia pedigrees, including 19 paranoid schizophrenia and 17 undifferentiated schizophrenia pedigrees, from Henan province of China using 5 microsatellite markers in the chromosome region 1q21-25 and 8 microsatellite markers in the chromosome region 6p21-25, which were the candidates of previous studies. All affected subjects were diagnosed and typed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised (DSM-IV-TR; American Psychiatric Association, 2000). All subjects signed informed consent.</p><p><b>RESULTS</b>In chromosome 1, parametric analysis under the dominant inheritance mode of all 36 pedigrees showed that the maximum multi-point heterogeneity Log of odds score method (HLOD) score was 1.33 (α = 0.38). The non-parametric analysis and the single point and multi-point nonparametric linkage (NPL) scores suggested linkage at D1S484, D1S2878, and D1S196. In the 19 paranoid schizophrenias pedigrees, linkage was not observed for any of the 5 markers. In the 17 undifferentiated schizophrenia pedigrees, the multi-point NPL score was 1.60 (P= 0.0367) at D1S484. The single point NPL score was 1.95(P= 0.0145) and the multi-point NPL score was 2.39 (P= 0.0041) at D1S2878. Additionally, the multi-point NPL score was 1.74 (P= 0.0255) at D1S196. These same three loci showed suggestive linkage during the integrative analysis of all 36 pedigrees. In chromosome 6, parametric linkage analysis under the dominant and recessive inheritance and the non-parametric linkage analysis of all 36 pedigrees and the 17 undifferentiated schizophrenia pedigrees, linkage was not observed for any of the 8 markers. In the 19 paranoid schizophrenias pedigrees, parametric analysis showed that under recessive inheritance mode the maximum single-point HLOD score was 1.26 (α = 0.40) and the multi-point HLOD was 1.12 (α = 0.38) at D6S289 in the chromosome 6p23. In nonparametric analysis, the single-point NPL score was 1.52 (P= 0.0402) and the multi-point NPL score was 1.92 (P= 0.0206) at D6S289.</p><p><b>CONCLUSION</b>Susceptibility genes correlated with undifferentiated schizophrenia pedigrees from D1S484, D1S2878, D1S196 loci, and those correlated with paranoid schizophrenia pedigrees from D6S289 locus are likely present in chromosome regions 1q23.3 and 1q24.2, and chromosome region 6p23, respectively.</p>

Expressional changes of neuregulin-1 gene mRNA in peripheral blood from schizophrenia patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the effect of anti-psychotic treatment on the expression of Neuregulin-1 (NRG1) mRNA in the peripheral blood lymphocytes of schizophrenia patients.</p><p><b>METHODS</b>The NRG1 mRNA in peripheral blood lymphocytes was measured using semi-quantitative reverse transcription (RT)-PCR in 80 first-onset schizophrenia patients, 37 sibling controls and 83 non-related controls. The patients were treated with risperdone and quetiapine for 4 weeks. Positive and negative symptom scale (PANSS) was used to evaluate the severity and clinical efficacy.</p><p><b>RESULTS</b>Prior to the treatment, the expression of NRG1 mRNA expression was significantly lower in patients than other two groups (F=73.004, P=0.000). From the second week on, the level of NRG1 mRNA expression in patients became significantly higher than before and gradually increased, whilst no significant difference between sib and non-sib controls. Prior to the treatment, there was significant correlation (r=-0.232, P=0.038) between the level of NRG1 mRNA and PANSS scores. Four weeks after the treatment, a significant correlation between the reduction rate of PANSS and the change of NRG1 mRNA (r=0.27, P=0.016).</p><p><b>CONCLUSION</b>The expression of NRG1 gene mRNA is associated with schizophrenia. Decreased expression of NRG1 may play a role in the development of schizophrenia, which can be improved by anti-psychotic drugs.</p>

Association analysis of neuregulin 1 gene polymorphism with schizophrenia in Chinese Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of the Neuregulin 1(NRG1) gene polymorphism with schizophrenia by analyzing allele transmission in schizophrenic parent-proband trios.</p><p><b>METHODS</b>Quantitative real-time PCR was used to check the genotypes of four SNPs-rs221533(C/T), rs7820838(C/T), 433E1006(A/G) and rs3924999(C/T), located at the 5o terminus of the Nrg1 gene, in 258 Chinese Han schizophrenic parent-proband trios. The transmission disequilibrium test (TDT) program (Genehunter software 2.0) was used to evaluate the association of the NRG1 gene with schizophrenia.</p><p><b>RESULTS</b>For all the subjects, the genotypes of the 4 SNPs were in Hardy-Weinberg equilibrium. In all the 258 parent-proband trios, there were significant transmission disequilibrium in allelic transmission of C, A, T from rs221533, 433E1006, rs3924999 loci respectively (rs221533: chi-square was 27.45, P was 0.000; 433E1006: chi-square was 56.08, P was 0.000; rs3924999: chi-square was 10.53, P was 0.001). Haplotype was analyzed at frequency exceeding 1%. In three-marker-haplotype, C/C/G and C/C/A (marker order: rs221533, rs7820838, 433E1006) transmitted predominantly(C/C/G: chi-square was 5.26, P was 45.08; C/C/A: chi-square was 0.026, P was 0.000). In four-marker-haplotype (marker order: rs221533, rs7820838, 433E1006, rs3924999), C/C/G/T, C/C/A/C and C/C/A/T showed transmission disequilibrium (C/C/G/T: chi-square was 10.71, P was 0.001; C/C/A/C: chi-square was 8.83, P was 0.006, C/C/A/T: chi-square was 27.00, P was 0.000). In the positive subtype of parent-proband trios, C/T/G/C hapoltype transmission was not observed.</p><p><b>CONCLUSION</b>The NRG1 gene polymorphism is significantly associated with schizophrenia in Chinese Han, especially in the positive subtype of schizophrenia.</p>

Association of HTR2C-759C/T and -697G/C polymorphisms with antipsychotic agent-induced weight gain / 中南大学学报(医学版)

OBJECTIVE@#To determine whether antipsychotic agent-induced weight gain was associated with 5-hydroxytryptamine 2C receptor (HTR2C) gene-759C/T and -697G/C polymorphisms.@*METHODS@#A case-matching controlled study was done. Eighty-five patients who had gained more than 7% of their pre-drug body weight served as a study group, and 85 patients who had gained less than 7% of their pre-drug body weight served as a control group. The control group were matched with the study group in the kinds of antipsychotic agents and the course of antipsychotic treatment. The ligation diction reaction technique was used to analyse the frequencies of HTR2C gene-759C/T and -697G/C polymorphisms.@*RESULTS@#The study group were more likely to be hemizygous for the -759C (for male) and the -759CC genotype (for female) than the control group. The study group were more likely to be hemizygous for the -697G (for male) and the -697CG/GG genotype (for female) (all P<0.05) than the control group.@*CONCLUSION@#The -759C/T and -697G/C polymorphisms of the promoter region of HTR2C gene may be associated with antipsychotic agent-induced weight gain.

Distribution of genotype and allele frequencies of dopamine D4 receptor gene 48 bp variable number tandem repeat polymorphism in Chinese Han population in Hunan / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the distribution of genotype and allele frequencies of the dopamine D4 receptor(DRD4) gene exon 3 48 bp variable number of tandem repeats polymorphism in Hunan Han population.</p><p><b>METHODS</b>The genotype and alleles of 304 healthy persons were examined with polymerase chain reaction, denaturing polyacrylamide gel electrophoresis and silver staining.</p><p><b>RESULTS</b>Seven alleles and twelve genotypes were found. The most common allele was allele 5 with a frequency of 70.6%. There was statistically significant difference in allele distribution between the Hunan Han population and the Han population of other regions such as Shanghai, Beijing and Sichuan in China (P< 0.05). Different allele frequency distributions were observed when compared to other ethnic populations such as Japanese, American, Mexican, and Italian (P< 0.05).</p><p><b>CONCLUSION</b>The distributions of allele of DRD4 gene exhibit regional and ethnic heterogeneity.</p>

Changes and Significances of Serum Leptin and Interleukin-1? before and after Treatment with Risperidone in Children with Schizophrenics / 实用儿科临床杂志

Objective To explore the changes and significances of serum leptin and interleukin-1?(IL-1?)before and after treatment with risperidone in children with schizophrenics.Methods Thirty-one cases with first-episode children with schizophrenia were chosen in patient group.Their body weight and height were measured before and 8 weeks after treatment with risperidone to calculate the body mass index(BMI),and their fasting serum leptin and IL-1? were assayed radio-immunity method.Thirty-one healthy controls were measured at the same time.Results BMI and the level of serum leptin in patients of post-treatment increased significantly compared with those of pre-treatment(all P