Zhenhe Zhou

Cognitive biases toward Internet game-related pictures and executive deficits in individuals with an Internet game addiction.

Background The cue-related go/no-go switching task provides an experimental approach to study individual’s flexibility in changing situations. Because Internet addiction disorder (IAD) belongs to the compulsive-impulsive spectrum of disorders, it should present cognitive bias and executive functioning deficit characteristics of some of these types of disorders. Until now, no studies have been reported on cognitive bias and executive function involving mental flexibility and response inhibition in IAD. Methodology/Principal Findings A total of 46 subjects who met the criteria of the modified Young’s Diagnostic Questionnaire for Internet addiction (YDQ) were recruited as an Internet game addiction (IGA) group, along with 46 healthy control individuals. All participants performed the Internet game-shifting task. Using hit rate, RT, d′ and C as the dependent measures, a three-way ANOVA (group × target × condition) was performed. For hit rate, a significant effect of group, type of target and condition were found. The group–target interaction effect was significant. For RT, significant effects were revealed for group and type of target. The group–target interaction effect was significant. Comparisons of the means revealed that the slowing down of IGA relative to NIA was more pronounced when the target stimuli were neutral as opposed to Internet game-related pictures. In addition, the group–condition interaction effect was significant. For d′, significant effects of group, type of target and condition were found. The group–target interaction effect was significant. For C, the type of target produced a significant effect. There was a positive correlation between the length of the addiction (number of years) and the severity of the cognitive bias. Conclusions IGA present cognitive biases towards information related to Internet gaming. These biases, as well as poor executive functioning skills (lower mental flexibility and response inhibition), might be responsible for Internet game addiction. The assessment of cognitive biases in IGA might provide a methodology for evaluation of therapeutic effects.

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 Aripiprazole on Mismatch Negativity (MMN) in Schizophrenia

Background Cognitive deficits are considered core symptoms of the schizophrenia. Cognitive function has been found to be a better predictor of functional outcome than symptom levels. Changed mismatch negativity (MMN) reflects abnormalities of early auditory processing in schizophrenia. Up to now, no studies for the effects of aripiprazole on MMN in schizophrenia have been reported. Methodology/Principal Findings Subjects included 26 patients with schizophrenia, and 26 controls. Psychopathology was rated in patients with the Positive and Negative Syndrome Scale (PANSS) at baseline, after 4- and 8-week treatments with aripiprazole. Auditory stimuli for ERP consisted of 100 millisecond/1000 Hz standards, intermixed with 100 millisecond/1500 Hz frequency deviants and 250 millisecond/1000 Hz duration deviants. EEG was recorded at Fz. BESA 5.1.8 was used to perform data analysis. MMN waveforms were obtained by subtracting waveforms elicited by standards from waveforms elicited by frequency- or duration-deviant stimuli. Aripiprazole decreased all PANSS. Patients showed smaller mean amplitudes of frequency and duration MMN at baseline than did controls. A repeated measure ANOVA with sessions (i.e., baseline, 4- and 8-week treatments) and MMN type (frequency vs. duration) as within-subject factors revealed no significant MMN type or MMN type × session main effect for MMN amplitudes. Session main effect was significant. LSD tests demonstrated significant differences between MMN amplitudes at 8 weeks and those at both baseline and 4 weeks. There was significant negative correlation between changes in amplitudes of frequency and duration MMN and changes in PANSS total scores at baseline and follow-up periods. Conclusions Aripiprazole improved the amplitudes of MMN. MMN offers objective evidence that treatment with the aripiprazole may ameliorate preattentive deficits in schizophrenia.

Working memory, executive function and impulsivity in Internet-addictive disorders: a comparison with pathological gambling

Objective The purpose of the present study was to test whether individuals with Internet addiction disorder (IAD) presented analogous characteristics of working memory, executive function and impulsivity compared with pathological gambling (PG) patients. Methods The subjects included 23 individuals with IAD, 23 PG patients and 23 controls. All of the participants were measured with the digit span task, Wisconsin Card Sorting Test, go/no-go task and Barratt Impulsiveness Scale-11 (BIS-11) under the same experimental conditions. Results The results of this study showed that the false alarm rate, total response errors, perseverative errors, failure to maintain set and BIS-11 scores of both the IAD and PG groups were significantly higher than that of the control group. In addition, the forward scores and backwards scores, percentage of conceptual level responses, number of categories completed and hit rate of the IAD and PG groups were significantly lower than that of the control group. Furthermore, the false alarm rate and BIS-11 scores of the IAD group were significantly higher than those of PG patients, and the hit rate was significantly lower than that of the PG patients. Conclusions Individuals with IAD and PG patients present deficiencies in working memory, executive dysfunction and impulsivity, and individuals with IAD are more impulsive than PG patients.

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.

A competitive PCR assay confirms the association of a copy number variation in the VIPR2 gene with schizophrenia in Han Chinese

Evidence from genetic studies has revealed that genome-wide rare copy number variations (CNVs) are risk factors for neurodevelopmental disorders and this evidence has given rise to a new understanding of disease etiology, including that of schizophrenia (SCZ). Recent studies have indicated that duplication in the vasoactive intestinal peptide receptor-2 (VIPR2) gene confers the susceptibility to SCZ in Caucasians, but so far this finding has still not been confirmed in Chinese populations. In this study, we investigated the association between CNVs in VIPR2 and SCZ risk in an independent case-control study of Han Chinese using 1035 cases and 1535 controls. The CNVs were genotyped using the multiplex fluorescence competitive PCR method. In contrast with a common genotype (2-copy), a microduplication variant genotype (3-copy) was only carried by SCZ patients (4/1035). This finding indicated that CNVs in VIPR2 may impose a significantly increased risk of SCZ in Han Chinese (P=0.02646, OR=infinity, 95% CI=1.327-infinity). Thus, our results suggest that carriers of microduplication genotypes of VIPR2 are predisposed to SCZ in Han Chinese.

Lack of association between MPC2 variants and schizophrenia in a replication study of Han Chinese

Schizophrenia (SCZ) is a common, complex and severe psychiatric disorder associated with many different risk factors, both genetic and environmental. A recent genome-wide association study (GWAS) of Han Chinese identified a single-nucleotide polymorphism (SNP, rs10489202) in the mitochondrial pyruvate carrier 2 gene (MPC2, also known as BRP44) as a possible susceptibility locus for schizophrenia. Hoping to validate this finding, we conducted a case-control study of Han Chinese with 1093 schizophrenia cases and 1022 healthy controls, using the LDR-PCR method to genotype polymorphisms (rs10489202 and a TagSNP rs203861) in the MPC2 gene. However, we found no significant difference (P>0.05) in either allele or genotype frequency in the SNPs between patients and controls. These results did not support the previous finding suggesting the further study by using a large-scale association analysis in the future should be warranted in Han Chinese populations.

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.

Olanzapine-induced weight gain plays a key role in the potential cardiovascular risk: evidence from heart rate variability analysis

Patients with schizophrenia have a higher risk for cardiovascular disease (CVD) than the general population. Research has suggested that autonomic imbalance is a common pathway to increased morbidity and mortality for CVD. Heart rate variability (HRV) analysis is a non-invasive method that assesses autonomic imbalance, and low HRV is correlated with high cardiovascular risk. Olanzapine, a widely used antipsychotic drug, is considered to have good cardiac safety because of not causing significant corrected QT-interval (QTc) prolongation; however, it is still unclear whether olanzapine affects HRV. We recruited 83 patients with schizophrenia who were medication-free for at least 1 month and tested their HRV at the baseline and 4 weeks after treatment with olanzapine. We found that patients who had substantial weight gain (EWG) manifested significantly lower HRV than those who had non-substantial weight gain (NWG) and that HRV decrease was positively correlated to an increase in body mass index (BMI) and weight gain. Our results indicate that olanzapine-induced weight gain may play an important role in its potential cardiovascular risk. Since olanzapine has a very high potential for weight gain compared with other antipsychotics, further research is needed to explore its cardiovascular safety profile, specifically long-term cardiac safety.