Association analysis of the DISC1 gene with schizophrenia in the Japanese population and DISC1 immunoreactivity in the postmortem brain

Ratta‐apha, Woraphat; Hishimoto, Akitoyo; Mouri, Kentaro; Shiroiwa, Kyoichi; Sasada, Toru; Yoshida, Masakuni; Supriyanto, Irwan; Ueno, Yoshio; Asano, Masaharu; Sato, Osamu; Togashi, Hiroyuki; Takai, Yoshimi; Sora, Ichiro

doi:10.1016/j.neures.2013.08.010

Cited by 17 publications

(8 citation statements)

References 28 publications

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“…Our data demonstrating increased numerical density of DISCimmunopositive white matter OLs in paranoid schizophrenia indicate that DISC might belong to the latter group. However, contradictory results have yet been obtained with regard to DISC1 transcript expression patterns in cerebral and extra-cerebral tissues in schizophrenia: reduced DISC1 immunoreactivities in the prefrontal cortex [58], in pinealocytes in the same brains as studied here (Bernstein et al [59] in preparation), and in lymphocytes, but elevated DISC1 transcript levels in hippocampal tissue of schizophrenia patients [59,60] as well as in blood mononuclear cells of schizophrenia patients with positive symptoms during acute psychosis [61] and chronic schizophrenia [61,62]. Interestingly, in the latter study, it was found that treatment with antipsychotics (which considerably reduced patients' positive symptoms) also decreased DISC1 expression.…”

Section: Discussionmentioning

confidence: 99%

Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia

Bernstein

Jauch

Dobrowolny

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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Profound white matter abnormalities have repeatedly been described in schizophrenia, which involve the altered expression of numerous oligodendrocyte-associated genes. Transcripts of the disrupted-in-schizophrenia 1 (DISC1) gene, a key susceptibility factor in schizophrenia, have recently been shown to be expressed by oligodendroglial cells and to negatively regulate oligodendrocyte differentiation and maturation. To learn more about the putative role(s) of oligodendroglia-associated DISC1 in schizophrenia, we analyzed the density of DISC1-immunoreactive oligodendrocytes in the fronto-parietal white matter in postmortem brains of patients with schizophrenia. Compared with controls (N = 12) and cases with undifferentiated/residual schizophrenia (N = 6), there was a significantly increased density of DISC1-expressing glial cells in paranoid schizophrenia (N = 12), which unlikely resulted from neuroleptic treatment. Pathophysiologically, over-expression of DISC1 protein(s) in white matter oligodendrocytes might add to the reduced levels of two myelin markers, 2',3'-cyclic-nucleotide 3'-phosphodiesterase and myelin basic protein in schizophrenia. Moreover, it might significantly contribute to cell cycle abnormalities as well as to deficits in oligodendroglial cell differentiation and maturation found in schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia

Bernstein

Jauch

Dobrowolny

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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“…Venous blood was collected and extracted for genomic DNA using a commercially available genomic DNA kit (Omega Bio-tek, Norcross, GA, USA). Six SNPs (rs1261085, rs1261084, rs8766, rs9960767, rs2958182, and rs12966547) of the TCF4 gene were detected based on their likely involvement in SCZ [2,18,19]. As previously described, genotyping was performed by SNPscan Genotyping Assays on an ABI 7900HT Fast Real-Time PCR System (Genesky Biotechnologies Inc., Shanghai, China) according to the manufacturer's instructions [20].…”

Section: Snp Selection and Genotypingmentioning

confidence: 99%

Association between a TCF4 Polymorphism and Susceptibility to Schizophrenia

Gao

Liu

et al. 2020

BioMed Research International

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The basic helix-loop-helix (bHLH) transcription factor 4 (TCF4) had been identified as a susceptibility gene associated with schizophrenia (SCZ) by GWAS, but inconsistent results have been found in other studies. To validate these findings and to reveal the effects of different inheritance models, rs2958182, rs1261085, rs8766, and rs12966547 of the TCF4 gene were genotyped in the Northwest Han Chinese population (448 cases and 628 controls) via a multiplex polymerase chain reaction SNPscan assay. Single SNP, genotype, and association analyses with three different models were performed. We observed genotype and allele distributions of four SNPs that showed nonsignificant associations in the Northwest Han Chinese population. However, published datasets (51,892 cases and 68,498 controls) were collected and combined with our experimental results to ascertain the association of the TCF4 gene SNPs and SCZ, which demonstrated that rs2958182 (P=0.003) was a significant signal based on a systematic meta-analysis. To clarify the biological role of rs2958182, it is important to improve the understanding of the pathophysiology of SCZ.

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“…In contrast, ∼75 kDa DISC1 hippocampal protein expression was found to be increased in schizophrenic patients [15]. A recent study identified decreased 91 kDa DISC1 immunoreactivity in the dorsolateral prefrontal cortex (DLPFC) in schizophrenic patients [36], while studies of DISC1 mRNA expression in this region have found no differences between schizophrenic patients and controls [15], [37]. There are several possible explanations for the apparent discrepancies between these studies: schizophrenia-associated changes in gene expression might be isoform, tissue- and/or brain region- specific; and/or aetiological heterogeneity might have resulted in systematic between-study sample differences.…”

Section: Discussionmentioning

confidence: 95%

Expression of DISC1-Interactome Members Correlates with Cognitive Phenotypes Related to Schizophrenia

et al. 2014

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Cognitive dysfunction is central to the schizophrenia phenotype. Genetic and functional studies have implicated Disrupted-in-Schizophrenia 1 (DISC1), a leading candidate gene for schizophrenia and related psychiatric conditions, in cognitive function. Altered expression of DISC1 and DISC1-interactors has been identified in schizophrenia. Dysregulated expression of DISC1-interactome genes might, therefore, contribute to schizophrenia susceptibility via disruption of molecular systems required for normal cognitive function. Here, the blood RNA expression levels of DISC1 and DISC1-interacting proteins were measured in 63 control subjects. Cognitive function was assessed using neuropsychiatric tests and functional magnetic resonance imaging was used to assess the activity of prefrontal cortical regions during the N-back working memory task, which is abnormal in schizophrenia. Pairwise correlations between gene expression levels and the relationship between gene expression levels and cognitive function and N-back-elicited brain activity were assessed. Finally, the expression levels of DISC1, AKAP9, FEZ1, NDEL1 and PCM1 were compared between 63 controls and 69 schizophrenic subjects. We found that DISC1-interactome genes showed correlated expression in the blood of healthy individuals. The expression levels of several interactome members were correlated with cognitive performance and N-back-elicited activity in the prefrontal cortex. In addition, DISC1 and NDEL1 showed decreased expression in schizophrenic subjects compared to healthy controls. Our findings highlight the importance of the coordinated expression of DISC1-interactome genes for normal cognitive function and suggest that dysregulated DISC1 and NDEL1 expression might, in part, contribute to susceptibility for schizophrenia via disruption of prefrontal cortex-dependent cognitive functions.

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Association analysis of the DISC1 gene with schizophrenia in the Japanese population and DISC1 immunoreactivity in the postmortem brain

Cited by 17 publications

References 28 publications

Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia

Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia

Association between a TCF4 Polymorphism and Susceptibility to Schizophrenia

Expression of DISC1-Interactome Members Correlates with Cognitive Phenotypes Related to Schizophrenia

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