The Characteristics Of CXCL1 Gene Methylation And Default Network Activity And Their Association In Defective Schizophrenia

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DNA methylation and gene expression of the chemokine(C-X-C motif)ligand 1 in patients with Deficit and Non-Deficit SchizophreniaObjective: The conception of Deficit schizophrenia(DS)had been proposed for years.However,the biological pathology underlying DS remains unknown.Chemokine(C-X-C motif)ligand 1(CXCL1)as a chemoattractant for neutrophils associates with neuroinflammation and may involve in the pathogenesis of schizophrenia.This study detects gene expression and DNA methylation of CXCL1 and discuss their association with clinical symptoms in DS and non-deficit schizophrenia(NDS).Methods: Pyrosequencing and RT-q PCR were separately used to determine DNA methylation at Cp G site and m RNA expression of CXCL1 gene in 53 DS patients,55 NDS patients and 63 healthy controls(HCs).BPRS,SANS and SAPS scales were rated for all patients to assess clinical symptoms.Results: Post hoc comparisons showed significantly increased CXCL1 expression in PBMCs of DS patients and NDS patients relative to HC group,particularly,DS patients exhibited the highest gene expression.The DNA methylation of Cp G1 and Cp G2 was significantly lower in DS compared to NDS and HCs.Correlation analysis revealed a negative correlation between average methylation in exon and gene expression in DS patients.CXCL1 gene expression was positively associated with negative symptoms in total schizophrenic patients.Positive correlation was found between CXCL1 gene expression and negative syndrome of BPRS,and between DNA methylation of Cp G3 and affect syndrome of BPRS in NDS patients but not in DS patients.Conclusion: The results suggest that DS may be a specific subgroup of schizophrenia with the characteristic abnormality of peripheral CXCL1 gene expression and DNA methylation.Part ? Convergent and divergent altered patterns of default mode network in deficit and non-deficit schizophreniaObjective: Previous studies suggested likely mechanisms underlying the dysfunction of the default mode network(DMN)in schizophrenia.However,altered patterns of the intrinsic activity of the DMN in both deficit schizophrenia(DS)and non-deficit schizophrenia(NDS)patients,as well as the neurocognitive relationships among them,remain unknown.This study explores the resting-state characteristics of the DMN activity in both DS and NDS patients,and further investigates correlations with neurocognitive features.Methods: Demographic,resting-state functional MRI,and neurocognitive data were collected in 37 DS and 38 NDS patients,as well as in 38 matched healthy control controls(HCs).Independent component analysis was conducted to investigate the characteristics of DMN activity and to further distinguish between common and specific altered regions.In addition,partial correlation analysis was conducted to examine associations between the activity of altered regions and neurocognitive assessments.Results: Overlapping altered brain activity was observed in both DS and NDS patients in the left middle frontal gyrus(MFG),the left angular gyrus(ANG),and the calcarine sulcus(CAL)region.Furthermore,compared to HCs,DS patients showed less activity in the right inferior temporal gyrus,the right para-hippocampal gyrus /hippocampus(PHP / HIP),and the left precuneus(PCUN),while they showed increased activity in the posterior cingulate cortex(PCC).Notably,NDS patients showed less activity in the bilateral middle occipital gyrus.Correlation analysis indicated that,in the DS group,both Trail Making Test(TMT)-B and spatial processing scores were positively associated with the activities of the left PCUN and the right PHP / HIP,while the Stroop color scores were negatively associated with PCC activity.In the NDS group,the TMT-B scores were associated with activities of the left MFG and CAL regions,while the scores of the Wechsler adult intelligence scale(Chinese revision)were negatively associated with CAL region activity.Conclusion: The present study demonstrates convergent and divergent altered patterns of the DMN in both DS and NDS patients.Importantly,the specific altered regions of the DMN in DS patients may be associated with extensive deficient neurocognition,indicating novel insights into the pathogenesis of cognitive impairment in schizophrenia.Part ? Associations between CXCL1,default mode network activity and cognitive function in patients with deficit schizophreniaObjective: Deficit schizophrenia(DS)characterized by primary,persistence,negative symptoms,is considered to be a high homogeneous subtype of schizophrenia.Previous studies have suggested that genetic changes in patients with schizophrenia are associated with altered brain function.However,studies related to DS are relatively lacking.Based on our previous genetic and imaging data,this study explored the correlation between CXCL1,default mode network(DMN)activity and cognitive function in DS.Methods: A total of 75 male subjects were recruited,including 37 DS patients and 38non-deficit schizophrenia(NDS)patients.Demographic,genetic,brain functional,and neurocognitive data of all subjects were collected.Correlation analysis was used to explore the correlation between genetic changes of CXCL1,default network activity,and neurocognitive function.Results: Correlation analysis showed that in DS group,the DNA methylation of Cp G2 was negatively correlated with the score of spatial processing test;in NDS group,the DNA methylation of Cp G2 was negatively correlated with the activity of calcarine sulcus and was positively correlated the activity of right middle occipital gyrus.Additionally,in NDS group,CXCL1 gene expression was positively correlated with the activity of calcarine sulcus and was negatively correlated the activity of right middle occipital gyrus.Conclusion: The changes of CXCL1 gene may be related to the altered activity of DMN and neurocognitive impairments in DS and NDS,providing multidimensional evidence for the pathogenesis of neurocognitive function in schizophrenia.