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Objective:To evaluate association of peripheral blood brain-derived neurotrophic factor (BDNF) with Alzheimer's disease (AD) .Methods:Databases including Pubmed, Cochrane library, Web of science, Embase, China National Knowledge Infrastructure, CBM disc, VIP-CSTJ and Wanfang Data were used to collect case-control studies related to the concentration of BDNF in peripheral blood of dementia patients with Alzheimer's type(DAT) and mild cognitive impairment(MCI). After extracting data and appraising the quality of the included studies, meta-analysis were conducted using Review Manager 5.3 and CMA 3.0.Results:A total of 51 articles were included in the analysis, with a total subjects of 7 182, including 2 673 subjects in DAT group, 1 506 subjects in MCI group, and 3 003 subjects in control group.The Meta-analysis showed that the levels of peripheral blood BDNF in patients with DAT were significantly lower than normal control group(SMD=-0.71, 95% CI : -0.99--0.43, P<0.001) ( n=5 111), and there were no statistical differences in peripheral blood BDNF levels between MCI group and control group and between DAT group and MCI group.The subgroup analysis showed that the level of serum BDNF in patients with DAT (SMD=-0.85, 95% CI: -1.15--0.55, P<0.001)( n=4 425) and MCI(SMD=-0.38, 95% CI: -0.62--0.14, P=0.002)( n=2 476) was significantly lower than that in normal control group, and the level of serum BDNF (SMD=-0.76, 95% CI: -1.37--0.16), P=0.01)( n=1 630) in patients with DAT was lower than that in MCI; However, there were no statistical difference among DAT, MCI and control groups in the level of plasma BDNF( P>0.05). Conclusion:The patients with DAT and mild cognitive impairment have lower level of serum BDNF, which suggesting that serum BDNF level may be a potential biomarker for early diagnosis of AD.
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Objective To investigate the differential expression of microRNA (miRNA) in schizophrenia (SZ) patients,and explore the comorbidity of SZ and depression disorder based upon miRNA expression.Methods Affymetrix array analysis was used to investigate the differentially expressed miRNA in SZ patients firstly,and then quantitative real-time polymerase chain reaction (qRT-PCR) was further carried out to confirm the selected miRNA in peripheral blood mononuclear cells of 40 SZ patients,whom were administered by Positive and Negative Syndrome Scale (PANSS) and the selected miRNAs in depression disorder patients has also been confirmed by Affymetrix array analysis and qRT-PCR in our previous studies.Results Affymetrix array analysis indicated that there existed 33 miRNAs which differentially expressed (32 up-regulated and 1 down-regulated) compared with normal controls.qRT-PCR results suggested that the expression of 8 miRNAs (miR-1273d,miR-1303,miR-3064-5p,miR3131,miR-3687,miR-4428,miR-4725-3p and miR-5096) were significantly up-regulated in SZ;the miRNA differentially expressed in depression disorder patients also had differential expression in SZ patients (P＜0.05).There were significant correlation between the miRNAs differentially expressed in depression disorder patients and in SZ patients (P＜0.01).MiR-1972 differentially expressed in depression disorder patients had significant positive correlation with the positive symptoms of PANSS (P＜0.05),and miR-26b was positively correlated with composite factor (P＜0.05).Conclusion Comorbidity of SZ and depression disorder is observed not only on the clinical symptoms,but on the molecular genetic basis.
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OBJECTIVE To identify differentially expressed microRNA (miRNA) in peripheral blood mononuclear cells (PBMCs) of anxiety patients and predict their target genes and function by bioinformatics analysis. METHODS The miRNA expression profiles were determined using an Affymetrix array. To validate the results, real-time quantitative polymerase chain reaction (qRT-PCR) analysis in a larger cohort was employed. The targets of the differentially expressed miRNAs were predicted by Target Scan, miRBD, and DIANA-microT-CDS, and the results were analyzed by gene ontology (GO) and KEGG pathway analysis using FunNet. RESULTS MicroRNA microarray chip analysis has identified 7 miRNAs were detected with significant changes in expression in PBMCs of anxiety patients. qRT-PCR analysis has confirmed that the expression levels of 5 miRNAs (has-miR-4484, has-miR-4505, has-miR-4674, has-miR-501-3p and has-miR-663) were up-regulated. Intersecting the genes by Target Scan, miRBD, and DIANA-microT-CDS has predicted 195 targets. GO analysis showed that biological processes regulated by the predicted target genes have included diverse terms. Some terms, e.g., nervous system development, nerve growth factor receptor signaling pathway, neuron migration, dendrite development, regulation of neuron projection development, midbrain development, regulation of excitatory postsynaptic membrane potential, gliogenesis, dendrite morphogenesis, etc. have direct relationship with the central nervous system and brain functions. Pathway analysis showed that a significant enrichment in several pathways related to neuronal brain functions such as glutamatergic synapse, axon guidance, calcium signaling pathway, MAPK signaling pathway, GnRH signaling pathway, Wnt signaling pathway, gap junction, long-term potentiation and VEGF signaling pathway, etc. Among the five microRNAs, has-miR-4484, has-miR-4505, has-miR-4674 and has-miR-501-3p may have more important regulatory functions. CONCLUSION Five miRNAs (has-miR-4484, has-miR-4505, has-miR-4674, has-miR-501-3p and has-miR-663) are up-regulated in PBMCs of anxiety patients and may be closely involved in the pathogenesis of anxiety disorder.
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Humans , Anxiety Disorders , Genetics , Computational Biology , Methods , Gene Expression Regulation , MicroRNAs , Real-Time Polymerase Chain ReactionABSTRACT
Objective To predict the target genes and function of has-miR-26b,has-miR-1972,has-miR4485,has-miR-4498,and has-miR-4743 by bioinformatics analysis,and provide the theoretical basis for the further research.Methods The targets of the five microRNAs were predicted by Target Scan,miRBD,and DIANA-microT-CDS,and the result were analyzed by gene ontology and pathway analysis using FunNet.Results 734 predicted targets were obtained by finding the intersected genes of Target Scan,miRBD,and DIANA-microT-CDS.GO analysis showed that biological processes regulated by the differentially expressed microRNAs included diverse terms,among which some terms (e.g.,central nervous system development,neuron differentiation,axonogenesis,synaptic transmission,learning,and memory,etc.) had direct relationship with the central nervous system and brain functions.The pathway analysis showed that a significant enrichment in several pathways related to neuronal brain function,such as axon guidance,glutamatergic synapse,Wnt signaling pathway,mTOR signaling pathway,VEGF signaling pathway,etc.Among the five microRNAs,has-miR-26b,has-miR-1972,has-miR-4498 might have more important regulatory functions.Conclusion Bioinformatic analysis indicates that has-miR-26b,has-miR-1972,has-miR-4485,has-miR-4498,and has-miR-4743 are closely related to the mechanism and pathogenesis of major depressive disorder.
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Objective To investigate the diagnostic value of microRNA (miRNA) in peripheral venous blood for depressive disorder.Methods Real-time fluorescence quantitative PCR (RT-qPCR) was used to verify expression level of miRNAs in peripheral blood of non-specific mental retardation children,which were aberrantly expressed in depressive disorder patients,and then Receiver Operating Characteristics (ROC)curve was employed to confirm the sensitivity and specificity of abnormal miRNA expression in depressive disorder and non-specific mental retardation.Results MiR-1972,miR-26b,miR-4485,miR-4498 and miR-4743 were upregulated significantly in case group of depressive disorder(P＜0.05),meanwhile miR-4485 and miR-4743 in aforementioned 5 miRNAs also upregulated significandy in patients of non-specific mental retardation(P＜0.05),but miR-26b showed no significant difference between case group of non-specific mental retardation and the control group (P＞0.05).The ROC curve of miR-26b in depressive disorder patients and their control group showed that the sensitivity and specificity were 0.609,0.664 respectively,and the area square under the curve was 0.614(P=0.021).The ROC curve of miR-26b in patients of depressive disorder and non-specific mental retardation indicated that the sensitivity and specificity were 0.784 and 0.471,and area square under the curve was 0.643 (P=0.003).Conclusion miR-26b probably have diagnostic value for depressive disorder,which may comorbidity with non-specific mental retardation.But genetic and psychosocial mechanism of comorbidity still needs further exploration.
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Objective To explore the effect of repetitive transcranial magnetic stimulation(rTMS) treatment on the brain derived neurotrophic factor(BDNF) serum levels in depressive patients.Methods Sixty-eight unipolar depressions treated with venlafaxine were randomly assigned to the real rTMS group(n =34)and the sham rTMS group(n =34),which were accepted the real or the shame rTMS treatment on the left dorsolateral prefrontal lobes respectively.The Hamilton Rating Scale for Depression (HAMD) and BDNF serum was assayed before and after 4 weeks' treatment.Results 1) A significant increase of serum BDNF((12.2 ± 1.3) μg/L vs (5.6 ± 0.8) μg/L,t=-9.167,P=0.000;(11.4 ± 1.5)μg/L vs (6.0± 1.0)μg/L,t=-7.421,P=0.000)and a significant decline of HAMD((11.6 ± 1.7) score vs (32.6 ± 2.5) score,t =14.654,P =0.000 ; (4.2 ± 2.8) score vs (31.8 ± 3.2)score,t=12.089,P =0.000) were found after the treatment in the real and the shame group,and the real group changed more significantly than the shame group ((6.7 ± 0.8) μg/L vs (5.1 ± l.2) μg/L,t =2.690,P =0.009 ; (21.0 ± 2.1) score vs (17.6 ± 2.6) score,t =2.693,P =0.000).2) A negative correlation was found between the serum BDNF levels and the HAM D scores before the treatment(r =-0.530,P=0.003; r =-0.490,P =0.004),and a positive correlation between changes of BDNF levels and HAMD scores changes(r =0.439,P =0.006 ; r =0.454,P =0.005).Conclusion The rTMS treatment can increase serum BDNF levels in depressive patients.
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Objective To investigate the possible role of plasma leptin and total cholesterol in the pathophysiology of attempted suicide in depressive episode patients. Methods The subjects were 25 depressive episode patients who had recently attempted suicide and 30 depressive episode patients without suicide attempt. The Hamilton Depression Rating Scale-24 items ( HAMD24 ), Beck Helpless Rating Scale (BHS) and Self-rating Idea of Suicide Scale (SIOSS) were used to evaluate the severity of symptoms. In addition, 32 individuals who took part in health examination were selected as health control group. Body height and weight were measured to get body mass index (BMI) of all objects, and plasma leptin and total cholesterol were measured by venous blood before taking pill. Results (1)HAMD score , BHS score and SIOSS score in patients with attempted suicide were higher than patients without suicide (P ＜ 0.01 ). (2) The total cholesterol and plasma leptin in patients with attempted suicide ( (3.3 ±0.9)mmol/L, (6.1 ±3.7)μg/L)were lower than that in patients without suicide( (3.6± 1.2)mmol/L, (9.4 ± 4.4)μg/L; P ＜ 0.05 ～ 0. 0l ), while total cholesterol and leptin in patients without suicide attempt ( (3.6 ± 1.2 ) mmol/L, ( 9.4 ± 4.4 ) μg/L) were lower than that in normal controls ( ( 4.8 ± 0.9 )mmol/L, ( 13.4 ± 6.7 ) μg/L; P ＜ 0.05 ～ 0.01 ). (3) Plasma leptin and total cholesterol of all patients were positively correlated with BMI(P＜0.01 ). Moreover, plasma leptin and total cholesterol in patients with attempted suicide and patients without attempted suicide were inversely positively correlated with HAMD score , BHS score and SIOSS score. Plasma leptin was significantly positively correlated with total cholesterol in patients with attempted suicide and patients without suicide, but there was no significant difference in normal controls(P＞ 0. 05). Conclusion The results suggest that decreased plasma leptin is related to the pathophysiology of attempted suicide in depressive episode patients.
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BACKGROUND:Now researches on psychiatric disease and molecular heredity are becoming more and more gradually because of the development of molecular genetics,but conclusions are controversial,and for the time being there are no reports about whether there are regional differences and ethnical differences in the distribution of genotype frequency of 5-hydroxytryptamine 2A receptor gene T102C.OBJECTIVE:Researches on the geographic distribution of genotype frequency of 5-hydroxytryptamine 2A receptor gene T102C of schizophrenics people.DESIGN:Sample survey and observation with schizophrenics selected as subjects.SETTING: Mental Department, Changzhou Peace Hospital.PARTICIPANTS: The experiment was completed in The No.102 Hospital of PLA from January 1999 to August 2003.Totally 177 people of Han nationality (Age: 18-45; Duration of illness: 1 month-20 years) from different provinces and autonomous regions of China in compliance with diagnostic standards of Psychiatric Disease Classification and Diagnosis Standards of China (The 3rd version) were selected as the subjects.METHODS:The blood samples from 117 schizophrenics were given test of polymerase chain reaction(PCR),and the distribution differences of genotype frequency of 5-hydroxytryptamine receptor gene of normal control population from different provinces and autonomous regions were compared. DNA were abstracted by means of phenol chloroform, amplification and cataphoresis test of polymerase chain reaction of target DNA,primer sequence of gene segment amplification of 5-hydroxytryptamine (5-HT) 2A receptor gene T102C: 5'-TCT GCT ACA AGT TCT GGC TT-3', 5 '-CTG CAG CTT TTT CTC TAG GG-3'; Reaction system of 50 μL, DNA 0.5 μg,Primer 50 pmol,TagDNA enzyme 2U were added with dNTP to the final concentration of 200 μmol/L.MAINOUTCOMEMEASURES: DNA cataphores is test of schiophrenicanddistributionofgenotypefrequencyof5-hydroxytryptamine 2A receptor gene.RESULTS: The distribution of genotype frequency of 5-hydroxytryptamine(5-HT) 2A receptor gene: A1A1, 0.07-0.03; A1A2, 0.50-0.72; A2A2,0.17-0.29. Correlation analysis of genotype frequency in different regions:A1A1, x2=4.44, P=0.617 1, P ＞ 0.05;A1A2, x2=1.14, P=0.942 2, P ＞ 0.05;A2A2, x2=0.93, P=0.985 7, P ＞ 0.05.CONCLUSION: The geographic distributions of genotype frequency of 5-hydroxytryptamine 2A receptor gene T102C of schizophrenics of the Chinese Han nationality people were comparatively even.
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Objective To investigate the geographic distribution of 5-HT2A T102C genotypes frequency in the PLA schizophrenia patients. Methods The 5-HT2A receptor gene T102C polymorphism was analyzed for genotyping by the method of polymerase chain reaction(PCR)in 177 male PLA schizophrenia patients. Results The distribution of 5-HT2A genotypic frequencies in 177 male PLA schizophrenia patients were 0.07~0.33(? 2=4.44,P=0.617 1) for A1A1, 0.50~0.72 for A1A2 (? 2=1.14, P=0.942 2), and 0.17~0.29 for A2A2 (? 2=0.93, P=0.985 7), respectively. There was no significant correlation between 5-HT2A frequencies and different populations. Conclusion The frequencies of 5-HT2A T102C genotypes in the PLA schizophrenia patients were uniform in different populations.