Zaohuo Cheng

An event‐related potential investigation of deficient inhibitory control in individuals with pathological Internet use

UNLABELLED Zhou Z-H, Yuan G-Z, Yao J-J, Li C, Cheng Z-H. An event-related potential investigation of deficient inhibitory control in individuals with pathological Internet use. OBJECTIVE The purpose of this study was to investigate deficient inhibitory control in individuals with pathological Internet use (PIU) using a visual go/no-go task by event-related potentials (ERPs). METHODS Subjects were 26 individuals with PIU and 26 controls. Barratt Impulsiveness Scale-11 (BIS-11) was used for measures of impulsivity. A go/no-go task involved eight different two-digit numerical stimuli. The response window was 1000 ms and the inter-trial-interval (ITI) was 1500 ms. Electroencephalography (EEG) was recorded when participants performed the task. Brain electrical source analysis (BESA) 5.2.0 was used to perform data analysis and the no-go N2 amplitude was analysed for investigation of inhibitory control. RESULTS BIS-11 total scores, attentional key and motor key scores in PIU group were higher than that of the control group. In the go/no-go task, false alarm rate of PIU group was higher, and hit rate was lower than that of the control group. A repeated measure ANOVA revealed a significant group, frontal electrode sites and group × frontal electrode sites main effect for N2 amplitudes of no-go conditions (for group: F = 3953, df = 1, p = 0.000; for frontal electrode sites: F = 541, df = 9, p = 0.000; for group × frontal electrode sites: F = 306, df = 9, p = 0.000), and a significant group, central electrode sites and group × central electrode sites main effect for N2 amplitudes of no-go conditions (for group: F = 9074, df = 1, p = 0.000; for central electrode sites: F = 163, df = 2, p = 0.000; for group × central electrode sites: F = 73, df = 2, p = 0.000). N2 amplitudes of no-go conditions were lower than those at control group. CONCLUSIONS Individuals with PIU were more impulsive than controls and shared neuropsychological and ERPs characteristics of compulsive-impulsive spectrum disorder, which supports that PIU is an impulse disorder or at least related to impulse control disorder.

Effect of Tryptophan Hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression

BackgroundSuicide and major depressive disorders (MDD) are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene rs7305115 SNP may predispose to suicide attempts in MDD.MethodsWe genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis.ResultsThere were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG) frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p < 0.001). The G-allele frequency was significantly higher in cases than control group (58.1% vs.45.6%, p < 0.001), but the A-allele carrier indicated a decreased trend in MDD with suicide behaviors than control group (41.9% vs.54.4%, p < 0.001). The multivariate logistic regression analysis indicated that TPH2 rs7305115 AA (OR 0.33, 95% CI 0.22-0.99), family history of suicide (OR 2.98, 95% CI 1.17-5.04), negative life events half year ago (OR 6.64, 95% CI 2.48-11.04) and hopelessness (OR 7.68, 95% CI 5.79-13.74) were significantly associated with the suicide behaviors in MDD patients.ConclusionsThe study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.

Meta-analysis of association between the -1438A/G (rs6311) polymorphism of the serotonin 2A receptor gene and major depressive disorder

Abstract Objectives: Major depressive disorder (MDD) is a severe psychiatric disorder with a lifetime prevalence of approximately 10–15%. Previous pharmacological studies suggested that the serotonin 2A receptor (5-HTR2A) was one of the major pharmacological therapeutic targets for MDD. Recently, genetic studies investigated the association between the polymorphism rs6311 of the 5-HTR2A gene and MDD. However, the results of these studies were inconsistent. To evaluate these conflicting findings, we performed the current meta-analysis. Methods: Eleven articles form PubMed and Chinese National Knowledge Infrastructure databases were selected including 1491 patients and 2937 controls for the meta-analysis through assessing in detail. All statistical analyses were performed by RevMan (v.5·1) program. Results: No significant association between the 5-HTR2A gene SNP rs6311 and the risk of MDD was observed by four genetic models in the current meta-analysis (P = 0·12 for A versus G; P = 0·11 for AA versus GG; P = 0·06 for AA+AG versus GG; P = 0·24 for AG+GG versus AA). The calculated generalized odds ratio also revealed that the SNP rs6311 did not confer an increased risk to MDD. Moreover, the sensitivity analysis indicated that the result of meta-analysis is instable. Conclusions: Although the current meta-analysis indicated that the SNP rs6311 within the 5-HTR2A gene may be not associated with an increased risk for MDD, the results require further study to acquire more direct evidence.

Association of the CR1 polymorphism with late-onset Alzheimer's disease in Chinese Han populations: A meta-analysis

It is well known that genetic variants play a critical role in the pathogenesis of Alzheimers disease (AD). In 2009, a genome-wide association study (GWAS) demonstrated that a single nucleotide polymorphism (SNP), rs6656401, in complement receptor 1 (CR1) is significantly associated with late-onset Alzheimers disease (LOAD) in Caucasian population. Subsequently, other researchers have attempted to validate this finding in Chinese Han populations. However, these findings in Chinese Han populations have produced both negative and positive results. To derive a more precise estimation for the relationship, we performed the present meta-analysis by analyzing three published association studies involving CR1 SNP rs6656401 through the use of the RevMan (v.5.1) program. Pooled odds ratios (ORs) were calculated for allele contrasts (A vs. G) and a dominant model [(AA+AG) vs. GG] in three studies that included 1019 cases and 1080 controls, respectively. The statistical results showed a significant difference between patients and controls for the A allele of CR1 SNP rs6656401 (P=0.005). In addition, carriers of the A allele (AA+AG) of rs6656401 had a 1.69-fold increased risk for LOAD compared with non-carriers (GG) (P=0.01). In conclusion, despite there are some limitations, this meta-analysis indicates that the A allele of the CR1 SNP rs6656401 is significantly associated with LOAD susceptibility in Chinese Han populations.

An Updated Meta-Analysis of the Association between SORL1 Variants and the Risk for Sporadic Alzheimer's Disease

The pathogenetic mechanism of Alzheimers disease (AD) is still unknown; however, genetic variants play a critical role in the pathogenesis of AD. It has been reported that single nucleotide polymorphisms (SNPs) of the sortilin-related receptor with A-type repeats (SORL1, also called LR11 or sorLA) are associated with late-onset AD in Caucasian populations. Subsequently, other researchers have attempted to validate this finding in different ethnic populations. However, these findings have produced both negative and positive results. To derive a more precise estimation of whether SORL1 variants are associated with sporadic AD (SAD), we performed the meta-analysis presented in this manuscript. Databases including PubMed, AlzGene, the China National Knowledge Infrastructure (CNKI), and Wan Fang were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association studies. A total of twenty-three case-control studies involving 11,837 cases and 20,022 controls were included. Among the eleven candidate SNPs highlighted in the previous study, four SNPs (SNP 4, SNP 5, SNP 8 and SNP 10) showed a significant association with SAD using a generalized odds ratio (ORG, a model-free approach) and linkage disequilibrium structure analysis. Meanwhile, no significant heterogeneity between the Caucasian and Asian populations for the associated SNPs was observed in the current meta-analysis. Moreover, we further confirmed that the SORL1 three-marker haplotype C-G-C at SNP 8-SNP 9-SNP 10 was significantly associated with SAD (OR = 1.37, 95% CI = 1.12-1.66, padj = 0.008). The current meta-analysis further supports the previous findings that the SORL1 gene may be associated with SAD risk.

Exploring Transcription Factors-microRNAs Co-regulation Networks in Schizophrenia

BACKGROUND Transcriptional factors (TFs) and microRNAs (miRNAs) have been recognized as 2 classes of principal gene regulators that may be responsible for genome coexpression changes observed in schizophrenia (SZ). METHODS This study aims to (1) identify differentially coexpressed genes (DCGs) in 3 mRNA expression microarray datasets; (2) explore potential interactions among the DCGs, and differentially expressed miRNAs identified in our dataset composed of early-onset SZ patients and healthy controls; (3) validate expression levels of some key transcripts; and (4) explore the druggability of DCGs using the curated database. RESULTS We detected a differential coexpression network associated with SZ and found that 9 out of the 12 regulators were replicated in either of the 2 other datasets. Leveraging the differentially expressed miRNAs identified in our previous dataset, we constructed a miRNA-TF-gene network relevant to SZ, including an EGR1-miR-124-3p-SKIL feed-forward loop. Our real-time quantitative PCR analysis indicated the overexpression of miR-124-3p, the under expression of SKIL and EGR1 in the blood of SZ patients compared with controls, and the direction of change of miR-124-3p and SKIL mRNA levels in SZ cases were reversed after a 12-week treatment cycle. Our druggability analysis revealed that many of these genes have the potential to be drug targets. CONCLUSIONS Together, our results suggest that coexpression network abnormalities driven by combinatorial and interactive action from TFs and miRNAs may contribute to the development of SZ and be relevant to the clinical treatment of the disease.

Altered expression of mRNA profiles in blood of early-onset schizophrenia

To identify gene expression abnormalities in schizophrenia (SZ), we generated whole-genome gene expression profiles using microarrays on peripheral blood mononuclear cells (PBMCs) from 18 early-onset SZ cases and 12 controls. We detected 84 transcripts differentially expressed by diagnostic status, with 82 genes being upregulated and 2 downregulated. We identified two SZ associated gene coexpression modules (green and red), including 446 genes . The green module is positively correlated with SZ, encompassing predominantly up-regulated genes in SZ; while the red module was negatively correlated with disease status, involving mostly nominally down-regulated genes in SZ. The olfactory transduction pathway was the most enriched pathways for the genes within the two modules. The expression levels of several hub genes, including AKT1, BRCA1, CCDC134, UBD, and ZIC2 were validated using real-time quantitative PCR. Our findings indicate that mRNA coexpression abnormalities may serve as a promising mechanism underlying the development of SZ.

Increased Variability of Genomic Transcription in Schizophrenia

Schizophrenia (SZ) is a severe chronic mental disorder with a high heritability. Current microarray analyses typically focus on identifying differentially expressed genes or enriched pathways relevant to phenotypes. Whether there is a variability change of the genomic transcription in diseases has rarely been explored. In this study, we compared coefficient of variation (CV, the ratio of the standard deviation to the mean) of genome transcription of early-onset SZ (EOS) patients with controls in a blood mRNA microarray dataset and a blood microRNA (miRNA) microarray dataset. Furthermore, we compared CV of the expression levels of 17 genes in blood of the 30 patients before and after the 12-week treatment using real-time quantitative PCR (RT-qPCR) analysis. Our results indicated a significant increase of CV of genome transcription in patients compared with controls in both the mRNA and the miRNA datasets. The 30 after-treatment patients showed a significant decrease of CV of gene expression compared with the before-treatment patients. Our study may implicate the blood gene expression variability in SZ, providing further evidence supporting the abnormality of peripheral blood transcriptome in SZ. Given that peripheral blood can be easily collected from patients and followed longitudinally, our results may indicate a new way to facilitate the identification of the signatures of clinical subtypes, their prognosis and treatment response.

No association between ZNF804A rs1344706 and schizophrenia in a case-control study of Han Chinese

Previous studies indicated that the single nucleotide polymorphism (SNP) rs1344706 within the gene ZNF804A was a promising risk variant for schizophrenia in European populations. However, existing results are inconsistent in Han Chinese. Hoping to validate the association of rs1344706 with schizophrenia susceptibility in Han Chinese, we conducted a case-control study in 1284 cases and 990 healthy controls from Jiangsu Province, China. We did not detect any significant between-group difference (all P>0.05) in either allele or genotype frequency under any genetic model between cases and controls. Stratified analysis by sex also failed to find any significant association. Our results did not support the association of rs1344706 with schizophrenia in Han Chinese, and further association studies with large samples from other ethnic backgrounds and focus on more SNPs of ZNF804A are warranted.

Association analysis of a functional variant in ATXN2 with schizophrenia

Schizophrenia (SZ) is a severe mental disorder characterized by multiple neurodevelopmental dysfunctions including a breakdown of thinking process and a deficit of typical emotional responses. Ataxin-2 (ATXN2) plays vital roles in cell proliferation and growth, and functional mutations of ATXN2 cause neurodegenerative phenotypes, including spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS). To explore the possible role of ATXN2 in SZ, we conducted a two-stage study to examine the association of ATXN2 polymorphisms with SZ in the Han Chinese population. Association analysis of seven SNPs in 768 patients and 1348 controls revealed two associated SNPs, including rs630511 (P=1.76E-4) and rs7969300 (P=5.08E-4). We examined these two SNPs in a validation sample of 1957 patients and 1509 controls, and observed an association of rs7969300 with SZ (P=5.03E-3). The SNP rs7969300 is a non-synonymous SNP causing a Ser to Asn substitution, which is predicted to increase the protein stability of ATXN2. Our data suggest that the ATXN2 gene may confer vulnerability for SZ, adding further evidence for the genetic variants within the developmental pathway in the illness.