ZNF804A Variation May Affect Hippocampal-Prefrontal Resting-State Functional Connectivity in Schizophrenic and Healthy Individuals / 神经科学通报·英文版

The ZNF804A variant rs1344706 has consistently been associated with schizophrenia and plays a role in hippocampal-prefrontal functional connectivity during working memory. Whether the effect exists in the resting state and in patients with schizophrenia remains unclear. In this study, we investigated the ZNF804A polymorphism at rs1344706 in 92 schizophrenic patients and 99 healthy controls of Han Chinese descent, and used resting-state functional magnetic resonance imaging to explore the functional connectivity in the participants. We found a significant main effect of genotype on the resting-state functional connectivity (RSFC) between the hippocampus and the dorsolateral prefrontal cortex (DLPFC) in both schizophrenic patients and healthy controls. The homozygous ZNF804A rs1344706 genotype (AA) conferred a high risk of schizophrenia, and also exhibited significantly decreased resting functional coupling between the left hippocampus and right DLPFC (F(2,165) = 13.43, P < 0.001). The RSFC strength was also correlated with cognitive performance and the severity of psychosis in schizophrenia. The current findings identified the neural impact of the ZNF804A rs1344706 on hippocampal-prefrontal RSFC associated with schizophrenia.

Function of Znf804a in neuronal migration, proliferation and differentiation during mice brain development / 中国心理卫生杂志

Objective:To explore the function of Znf804a during brain development by using mouse model.Methods:The shRNA of Znf804a (shZnf804a) and control (pSUPER) plasmids were introduced into ventricular zone of ICR (Institute of Cancer Research) mice at E14.5 (three mice in each group) by using in utero electroporation.The speed of migration was evaluated by comparing the proportions of neuron in cortical plate (CP) zone.The proliferation speed was evaluated by comparing the diameters of neurospheres formed by neuron progenitor cells.The differentiation speed was evaluated by comparing the proportions of Nestin staining positive cells in neuron progenitor cells.Results:The proportion of neurons in CP zone was lower in shZnf804a group than in controls(11.8％ vs.75.4％,P ＜ 0.001).The diameter of neurospheres formed by neuron progenitor cells was bigger in shZnf804a group than in controls (295μm vs.172μm,P ＜0.01).The proportion of Nest in staining positive cells in neuron progenitor cells was larger in shZnf804a group than in controls (31.5％ vs.9.6％,P ＜0.01).Conclusion:It suggests that the migration speed of neurons in shZnf804a is lower than that in controls,the proliferation speed is higher than that in controls,and the differentiation speed is lower than that in controls.These results indicate that Znf804a may play an important role in the development of mouse brain.

Association study of ZNF804A gene polymorphism rs7597593 with schizophrenia and working memory / 中华行为医学与脑科学杂志

Objective To assess the association between rs7597593 polymorphism of ZNF804A gene and schizophrenia,and to assess the relationship between rs7597593 polymorphism and working memory.Methods Schizophrenia patients and healthy controls were diagnosed in accordance with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-Ⅳ) ; 767 schizophrenia patients and 690 healthy controls were involved.Restriction fragment length polymorphism (RFLP) was carried out to genotype rs7597593 polymorphism.The cognitive function of working memory was assessed by the N-back task.Statistical analyses were carried out with SPSS19.0 software.Results The study found no significantly different genotype frequencies (x2=1.519,P=0.468) and allele frequencies(x2=1.263,P=0.261) of rs7597593 polymorphism between schizophrenia patients and healthy controls,however in the subgroup of higher IQ (IQ ≥ 110),there were significant different distributions of both genotype and allele (x2 =9.411 and 6.529; P=0.009 and 0.011 respectively).It was also found in this subgroup that risk T allele was associated with more error at 1-back task (F=6.854,P=0.009).Conclusion These results indicated that rs7597593 polymorphism was associated with individuals having spared cognitive function; carriers of T allele had worse cognitive function,which maybe a pathway that it contributes to schizophrenia.

A family-based transmission disequilibrium test of single nucleotide polymorphisms in exon 4 of ZNF804A gene in Han Chinese patients with schizophrenia / 第二军医大学学报

Objective To investigate the association of the single nucleotide polymorphisms (SNPs) in exon 4 of ZNF804A gene with schizophrenia in a family-trios sample. Methods MassARRAY genotyping technique and the transmission disequilibrium test (TDT) were employed to study the association of SNPs (seven nonsynonymous and two intronic) encompassing exon 4 of ZNF804A gene with schizophrenia in 69 nuclear families. Results (1) Four SNPs (rs79776875, rs78816540, rs79082132 and rs62198467) in this study were found to be rare variants (0

The relationship between genetic polymorphism of ZNF804A and drug efficacy to schizophrenia: a meta-analysis / 中华行为医学与脑科学杂志

ObjectiveTo assess the association of rs1344706 and rs4667001 polymorphism of ZNF804A gene with schizophrenia,and the relationship between rs1344706 polymorphism and antipsychotic drug efficacy.MethodsThe studies concerning association of ZNF804A gene polymorphism with schizophrenia and its drug efficacy were retrieved in databases such as Medline and CNKI,and then screened according to the inclusion and exclusion criteria.Meta-analysis was performed by RevMan 5.1 following quality assessment and data extraction.ResultsEleven high-quality studies under the criteria were included.For rs1344706,T allele frequency was significant higher in the schizophrenia group than control group ( OR=1.13,95％ CI (1.06-1.21 ),P=0.0003).Moreover,for rs4667001,G allele frequency was significant higher in the schizophrenia group ( OR =1.14,95％ CI( 1.04-1.26),P =0.005 ).In addition,the difference of PANSS scores reduction between T allele and GG genotype carriers was not significant in both positive and negative symptoms after four-week treatment,and the same trend of difference was in the comparison between TT genotype and G allele carriers.ConclusionThe data supports that T allele of rs1344706 and G allele of rs4667001 in ZNF804A gene are associated with the susceptibility of schizophrenia,but rs1344706 polymorphism is not related to antipsychotic drug efficacy.