Dataset Information

Transcriptome alterations of mitochondrial and coagulation function in schizophrenia by cortical sequencing analysis.

ABSTRACT: BACKGROUND: Transcriptome sequencing of brain samples provides detailed enrichment analysis of differential expression and genetic interactions for evaluation of mitochondrial and coagulation function of schizophrenia. It is implicated that schizophrenia genetic and protein interactions may give rise to biological dysfunction of energy metabolism and hemostasis. These findings may explain the biological mechanisms responsible for negative and withdraw symptoms of schizophrenia and antipsychotic-induced venous thromboembolism. RESULTS: Published BA22 RNA-Seq brain data of 9 schizophrenic patients and 9 controls samples were analyzed. The differentially expressed genes in the BA22 brain samples of schizophrenia are proposed as schizophrenia candidate marker genes (SCZCGs). The genetic interactions between mitochondrial genes and many under-expressed SCZCGs indicate the genetic predisposition of mitochondria dysfunction in schizophrenia. The biological functions of SCZCGs, as listed in the Pathway Interaction Database (PID), indicate that these genes have roles in DNA binding transcription factor, signal and cancer-related pathways, coagulation and cell cycle regulation and differentiation pathways. CONCLUSIONS: It is implicated that the energy metabolism and hemostatic process have important roles in the pathogenesis for schizophrenia. The cross-talk of genetic interaction by these co-expressed genes and reached candidate genes may address the key network in disease pathology. The accuracy of candidate genes evaluated from different quantification tools could be improved by crosstalk analysis of overlapping genes in genetic networks.

SUBMITTER: Huang KC

PROVIDER: S-EPMC4290619 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Transcriptome alterations of mitochondrial and coagulation function in schizophrenia by cortical sequencing analysis.

Huang Kuo-Chuan KC Yang Ko-Chun KC Lin Han H Tsao Theresa Tsun-Hui TT Lee Sheng-An SA

BMC genomics 20141208

<h4>Background</h4>Transcriptome sequencing of brain samples provides detailed enrichment analysis of differential expression and genetic interactions for evaluation of mitochondrial and coagulation function of schizophrenia. It is implicated that schizophrenia genetic and protein interactions may give rise to biological dysfunction of energy metabolism and hemostasis. These findings may explain the biological mechanisms responsible for negative and withdraw symptoms of schizophrenia and antipsy ...[more]

PMID: 25522158

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Project description:Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia's alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.

Dataset Information

Transcriptome alterations of mitochondrial and coagulation function in schizophrenia by cortical sequencing analysis.

Publications

Transcriptome alterations of mitochondrial and coagulation function in schizophrenia by cortical sequencing analysis.

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