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Objective@#Schizophrenia (SCZ) is one of the most common and severe mental disorders. Modified electroconvulsive therapy (MECT) is the most effective therapy for all kinds of SCZ, and the underlying molecular mechanism remains unclear. This study is aim to detect the molecule mechanism by constructing the transcriptome dataset from SCZ patients treated with MECT and health controls (HCs). @*Methods@#Transcriptome sequencing was performed on blood samples of 8 SCZ (BECT: before MECT; AECT: after MECT) and 8 HCs, weighted gene co-expression network analysis (WGCNA) was used to cluster the different expression genes, enrichment and protein-protein interaction (PPI) enrichment analysis were used to detect the related pathways. @*Results@#Three gene modules (black, blue and turquoise) were significantly associated with MECT, enrichment analysis found that the long-term potentiation pathway was associated with MECT. PPI enrichment p-value of black, blue, turquoise module are 0.00127, <1×10-16 and 1.09×10-13, respectively. At the same time, EP300 is a key node in the PPI for genes in black module, which got from the transcriptome sequencing data. @*Conclusion@#It is suggested that the long-term potentiation pathways were associated with biological mechanism of MECT.
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Objective@#Schizophrenia (SCZ) is one of the most common and severe mental disorders. Modified electroconvulsive therapy (MECT) is the most effective therapy for all kinds of SCZ, and the underlying molecular mechanism remains unclear. This study is aim to detect the molecule mechanism by constructing the transcriptome dataset from SCZ patients treated with MECT and health controls (HCs). @*Methods@#Transcriptome sequencing was performed on blood samples of 8 SCZ (BECT: before MECT; AECT: after MECT) and 8 HCs, weighted gene co-expression network analysis (WGCNA) was used to cluster the different expression genes, enrichment and protein-protein interaction (PPI) enrichment analysis were used to detect the related pathways. @*Results@#Three gene modules (black, blue and turquoise) were significantly associated with MECT, enrichment analysis found that the long-term potentiation pathway was associated with MECT. PPI enrichment p-value of black, blue, turquoise module are 0.00127, <1×10-16 and 1.09×10-13, respectively. At the same time, EP300 is a key node in the PPI for genes in black module, which got from the transcriptome sequencing data. @*Conclusion@#It is suggested that the long-term potentiation pathways were associated with biological mechanism of MECT.
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<p><b>OBJECTIVE</b>To explore common biological pathways for attention deficit hyperactivity disorder (ADHD) and low birth weight (LBW).</p><p><b>METHODS</b>Thei-Gsea4GwasV2 software was used to analyze the result of genome-wide association analysis (GWAS) for LBW (pathways were derived from Reactome), and nominally significant (P< 0.05, FDR< 0.25) pathways were tested for replication in ADHD.Significant pathways were analyzed with DAPPLE and Reatome FI software to identify genes involved in such pathways, with each cluster enriched with the gene ontology (GO). The Centiscape2.0 software was used to calculate the degree of genetic networks and the betweenness value to explore the core node (gene). Weighed gene co-expression network analysis (WGCNA) was then used to explore the co-expression of genes in these pathways.With gene expression data derived from BrainSpan, GO enrichment was carried out for each gene module.</p><p><b>RESULTS</b>Eleven significant biological pathways was identified in association with LBW, among which two (Selenoamino acid metabolism and Diseases associated with glycosaminoglycan metabolism) were replicated during subsequent ADHD analysis. Network analysis of 130 genes in these pathways revealed that some of the sub-networksare related with morphology of cerebellum, development of hippocampus, and plasticity of synaptic structure. Upon co-expression network analysis, 120 genes passed the quality control and were found to express in 3 gene modules. These modules are mainly related to the regulation of synaptic structure and activity regulation.</p><p><b>CONCLUSION</b>ADHD and LBW share some biological regulation processes. Anomalies of such proces sesmay predispose to ADHD.</p>
Subject(s)
Humans , Attention Deficit Disorder with Hyperactivity , Genetics , Gene Ontology , Gene Regulatory Networks , Genome-Wide Association Study , Infant, Low Birth WeightABSTRACT
<p><b>OBJECTIVE</b>To explore the association of a functional polymorphism Val158Met of COMT gene and attention and executive function in first-episode treatment-naive patients with schizophrenia and healthy controls.</p><p><b>METHODS</b>Trail making test (TMT) and clinical performances were evaluated in 103 first-episode treatment-naive patients with schizophrenia and 99 healthy controls. Polymorphism of COMT Val158Met was analyzed using polymerase chain reaction-restriction fragment length polymorphism method. A general linear model was used to investigate the effect of genotype subgroups on the attention and executive function.</p><p><b>RESULTS</b>There was a significant difference between control subjects and patients with schizophrenia on the TMT-A and B. However, no significant difference among Val/Val, Val/Met and Met/Met on the TMT-A and B in control subjects and patients with schizophrenia was detected.</p><p><b>CONCLUSION</b>The association among COMT Met variant and trail making testing (attention and executive function) has been replicated. However, no association of COMT Met variant with disruption of dopaminergic influence on neurocognitive function was detected. This may be due to the heterogeneity of population.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Young Adult , Amino Acid Substitution , Attention , Physiology , Catechol O-Methyltransferase , Genetics , Executive Function , Physiology , Gene Frequency , Genotype , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Schizophrenia , Genetics , Schizophrenic Psychology , Trail Making TestABSTRACT
Objective To investigate gray matter structural damage in first-episode antipsychotic-na?ve patients with adolescent-onset schizophrenia. Methods Twenty-six patients with schizophrenia and 26 healthy controls were scanned by using GE 3.0T magnetic resonance imaging in order to explore brain gray matter volume (GMV) changes with registration techniques based on the latest morphological deformation field theory. The correlation of gray matter volume abnormalities with clinical severity was also analyzed. Results Compared with healthy controls, patients with adoles-cent-onset schizophrenia showed significant reduction in GMV in the left parietal lobe, parahippocampal gyrus and right cerebellar pyramis. GMV of the left parahippocampal gyrus is significantly correlated with PANSS paranoid scores (r=-0.49, P=0.02). Conclusions There is structural abnormality in GM in parahippocampal-parietal-cerebellar in pa-tients with adolescent-onset schizophrenia and the severity of paranoid symptoms is related to the reduced GMV in the left parahippocampal gyrus.
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ObjectiveTo identify the metabolic alterations on prefrontal lobes and hippocampus in male patients with the first-episode mania using proton magnetic resonance spectroscopy(H-MRS).Method 18 male patients with the first-episode mania and 27 healthy subjects matched for age,gender,and years of education were included in the study.1 H-MRS was performed in two sides of the hippocampus and frontal lobes regions.The ratios of N-acetylaspartate (NAA),choline (Cho) to creatine (Cr) were measured.One-sample t test and paired-samples t test were used for statistic process.ResultsMale patients with the first-episode mania presented decreased NAA/Cr in left frontal lobe and hippocampus regions when compared to normal controls( left frontal lobe (1.68 ±0.19 vs 1.86 ± 0.19),hippocampus ( 1.32 ± 0.10 vs 1.43 ± 0.16 ),P ＜ 0.01 ),but there were no significant difference in NAA/Cr for right frontal lobe and hippocampus regions between groups ( all P ＞ 0.05 ).Two groups also showcd no significant difference for Cho/Cr in bilateral frontal lobe and hippocampus (P ＞ 0.05 ).Conclusion There is significant difference of manifestation of 1H-MRS between male patients with mania and normal controls,which reflects neuronal dysfunction in the prefrontal lobes and hippocampus.
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ObjectiveTo examine biochemical characteristics of the frontal lobe and hippocampus in unaffected parentsof schizophreniaprohandsusingprotonmagneticresonancespectroscopy(1H-MRS).Method 19 unaffected fathers of schizophrenia probands with matched 19 male healthy control subjects and 24 unaffected mothers of schizophrenia probands with matched 24 female healthy control subjects were included in the study.1 H-MRS was performed in two sides of the hippocampus and frontal lobes regions.The ratios of N-Acetylaspartate ( NAA ),choline (Cho) to creatine (Cr) were measured.One-sample T test and paired-samples t test were used for statistic process.ResultsUnaffected mothers of schizophrenia probands had a higher Cho/Cr ratio ( left ( 1.10 ± 0.13,right ( 1.08 ± 0.12 ) ) in the frontal white matter compared with matched female health control subjects(left( 1.03 ± 0.10),right( 1.02 ± 0.09 )).The NAA/Cr ratio was significantly reduced in the left frontal white matter of female health control subjects compared to right( 1.64 ± 0.12 vs 1.74 ± 0.13 ),but this difference was not observed in unaffected mothers of schizophrenia probands.There were no significant differences in metabolites for frontal lobe and hippocampus regions between unaffected fathers of schizophrenia probands and male healthy control subjects groups( all P＞0.05 ).ConclusionThe results implicate that the metabolic abnormalities and disappeared asymmetry of NAA/Cr might exist in the frontal white matter among unaffected mothers of schizophrenia probands.
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Objective To detect the patterns of cognitive impairment between patients with paranoid schizophrenia and patients with bipolar mania by using the Cambridge Neuropsychological Test Automated Battery (CANTAB) ,and to explore research clues for finding of cognitive endophenotype in patients with paranoid schizophrenia or bipolar mania. Methods Six CANTAB subtests and the seven subtests of the Wechsler Abbreviated Scale of Intelligence (WAIS short form) were administered to 35 patients with paranoid schizophrenia and 33 patients with bipolar mania who were drug naive experiencing an acute episode, as well as 30 healthy controls. Results Patients with paranoid schizophrenia and bipolar mania demonstrated impairments in 13 of the 15 cognitive indicators in CANTAB. After controlling IQ, both patient groups remained as significantly different from normal controls in terms of search strategy(36. 8 ±3.56,37.24 ±4. 21,30. 33 ±6.24) ,between-search errors(40. 86 ± 19.97,40.24 ± 18.92,15.4 ±17.22) on the SWM test,the proportion of hits(0.54 ±0. 18,0.56 ±0.15,0.78 ± 0.17) on the RVIP test,total errors(45.26 ±36.36,46.61 ±33.32,14 ± 11.7) and EDS errors (12.43 ±9.96, 13.18 ±8.98,4.97 ±6.09)on the IED test. Between search error in the SWM test was positively correlation with YMRS scores ( r=0.38, P=0.039) in bipolar patients. Conclusion Both patient groups demonstrated a comparable profile of cognitive impairments during active periods of their condition. The cognitive impairment index may be a discreet cognitive endophenotype overlapping the disorders.