Dataset Information

Network Analysis of Language Disorganization in Patients with Schizophrenia.

ABSTRACT: Language disorganization, an objective component of formal thought process abnormality, has been regarded as a core symptom of schizophrenia from an evolutionary psychopathology perspective. However, to the best of our knowledge, the network structure of language disorganization has rarely been examined in patients with schizophrenia. Thus, our preliminary study aimed to evaluate the network structure using the Clinical Language Disorder Rating Scale (CLANG) in 167 inpatients with schizophrenia. All 17 of the CLANG items were considered to be ordered categorical variables ranging from 0 to 3. Our results indicated that disclosure failure, excess syntactic constraints, abnormal prosody, and aprosodic speech rank among the top five central domains within the network structure. We deemed that disclosure failure and prosody problems are the most important symptoms of language disorder in schizophrenia. Thus, reduced top-down processing of linguistic information may be a core neurobiological underpinning of language disorganization in schizophrenia. Further studies controlling for the potential effects of confounding factors (i.e., duration of illness) on network analyses of language disorder and formal thought disorder are warranted in patients with schizophrenia.

SUBMITTER: Park SC

PROVIDER: S-EPMC7393296 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Network Analysis of Language Disorganization in Patients with Schizophrenia.

Park Seon Cheol SC Kim Kiwon K Jang Ok Jin OJ Yoon Hyung Jun HJ Jang Seung Ho SH Kim Sung Wan SW Lee Bong Ju BJ Park Jae Hong JH Lee Kang Uk KU Choi Joonho J

Yonsei medical journal 20200801 8

Language disorganization, an objective component of formal thought process abnormality, has been regarded as a core symptom of schizophrenia from an evolutionary psychopathology perspective. However, to the best of our knowledge, the network structure of language disorganization has rarely been examined in patients with schizophrenia. Thus, our preliminary study aimed to evaluate the network structure using the Clinical Language Disorder Rating Scale (CLANG) in 167 inpatients with schizophrenia. ...[more]

PMID: 32734737

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Project description:Individuals with 22q11.2 Deletion Syndrome (22q11.2 DS) are a specific high-risk group for developing schizophrenia (SZ), schizoaffective disorder (SAD) and autism spectrum disorders (ASD). Several genes in the deleted region have been implicated in the development of SZ, e.g., PRODH and DGCR8. However, the mechanistic connection between these genes and the neuropsychiatric phenotype remains unclear. To elucidate the molecular consequences of 22q11.2 deletion in early neural development, we carried out RNA-seq analysis to investigate gene expression in early differentiating human neurons derived from induced pluripotent stem cells (iPSCs) of 22q11.2 DS SZ and SAD patients.Eight cases (ten iPSC-neuron samples in total including duplicate clones) and seven controls (nine in total including duplicate clones) were subjected to RNA sequencing. Using a systems level analysis, differentially expressed genes/gene-modules and pathway of interests were identified. Lastly, we related our findings from in vitro neuronal cultures to brain development by mapping differentially expressed genes to BrainSpan transcriptomes.We observed ~2-fold reduction in expression of almost all genes in the 22q11.2 region in SZ (37 genes reached p-value?<?0.05, 36 of which reached a false discovery rate?<?0.05). Outside of the deleted region, 745 genes showed significant differences in expression between SZ and control neurons (p?<?0.05). Function enrichment and network analysis of the differentially expressed genes uncovered converging evidence on abnormal expression in key functional pathways, such as apoptosis, cell cycle and survival, and MAPK signaling in the SZ and SAD samples. By leveraging transcriptome profiles of normal human brain tissues across human development into adulthood, we showed that the differentially expressed genes converge on a sub-network mediated by CDC45 and the cell cycle, which would be disrupted by the 22q11.2 deletion during embryonic brain development, and another sub-network modulated by PRODH, which could contribute to disruption of brain function during adolescence.This study has provided evidence for disruption of potential molecular events in SZ patient with 22q11.2 deletion and related our findings from in vitro neuronal cultures to functional perturbations that can occur during brain development in SZ.

Dataset Information

Network Analysis of Language Disorganization in Patients with Schizophrenia.

Publications

Network Analysis of Language Disorganization in Patients with Schizophrenia.

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