Comprehensive DNA methylation analysis of human neuroblastoma cells treated with blonanserin

Murata, Y.; Nishioka, M.; Bundo, Miki; Sunaga, Fumiko; Kasai, Kiyoto; Iwamoto, Kazuya

doi:10.1016/j.neulet.2014.01.038

Cited by 20 publications

(20 citation statements)

References 18 publications

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“…We also found that decreased DNA methylation following clozapine treatment was more likely to occur at CpG sites located in CGIs in gene promoter regions. This trend is consistent with results reported in a previous study of the effects of blonanserin, another atypical antipsychotic [22]. …”

Section: Discussionsupporting

confidence: 93%

“…Fifth, it is also unclear whether the DNA methylation changes following the treatment are specific to clozapine or are common among other antipsychotics. Direct comparisons to previous studies that examined the effects of antipsychotics on DNA methylation are hampered by the use of different study designs and analysis of different tissues [19,20,21,22,23,24]. Further blood studies using other antipsychotics are needed to reveal differences between clozapine and other antipsychotics.…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies have demonstrated aberrant DNA methylation in SCZ [10,11,12,13,14,15,16,17,18]. Furthermore, growing evidence suggests that DNA methylation may be involved in the therapeutic efficacy of atypical antipsychotic drugs [19,20,21,22,23,24]. With respect to clozapine, two animal studies have demonstrated that acute clozapine treatment induces DNA demethylation in the promoters of specific GABAergic and glutamatergic genes [25,26].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

Kinoshita

Numata

Tajima

et al. 2017

IJMS

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Abstract:Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for "cell substrate adhesion" and "cell matrix adhesion" gene ontology (GO) terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein) gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

Kinoshita

Numata

Tajima

et al. 2017

IJMS

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“…Second, cell-type specific studies will be needed even though we adjusted for estimated cellular proportions in the present study. Third, medication might affect our results because antipsychotic drugs are known to influence DNA methylation status (Dong et al 2008;Melas et al 2012;Murata et al 2014). Fourth, the number of CpG sites that we analyzed in the present study was limited, although the 450 K microarray is one of the highest resolution tools currently available for assessing DNA methylation changes.…”

Section: Discussionmentioning

confidence: 98%

Aberrant DNA Methylation of Blood in Schizophrenia by Adjusting for Estimated Cellular Proportions

et al. 2014

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DNA methylation, which is the transference of a methyl group to the 5'-carbon position of the cytosine in a CpG dinucleotide, is one of the major mechanisms of epigenetic modifications. A number of studies have demonstrated altered DNA methylation of peripheral blood cells in schizophrenia (SCZ) in previous studies. However, most of these studies have been limited to the analysis of the CpG sites in CpG islands in gene promoter regions, and cell-type proportions of peripheral leukocytes, which may be one of the potential confounding factors for DNA methylation, have not been adjusted in these studies. In this study, we performed a genome-wide DNA methylation profiling of the peripheral leukocytes from patients with SCZ and from non-psychiatric controls (N = 105; 63 SCZ and 42 control subjects) using a quantitative high-resolution DNA methylation microarray which covered across the whole gene region (485,764 CpG dinucleotides). In the DNA methylation data analysis, we first estimated the cell-type proportions of each sample with a published algorithm. Next, we performed a surrogate variable analysis to identify potential confounding factors in our microarray data. Finally, we conducted a multiple linear regression analysis in consideration of these factors, including estimated cell-type proportions, and identified aberrant DNA methylation in SCZ at 2,552 CpG loci at a 5% false discovery rate correction. Our results suggest that altered DNA methylation may be involved in the pathophysiology of SCZ, and cell heterogeneity adjustments may be necessary for DNA methylation analysis.

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“…Other studies point to the effects of blonanserin, an antipsychotic drug, in inducing genome-wide DNAM as well as hypermethylation of CpG sites located within DRD2 and HTR2A genes in neuroblastoma cells [62]. However, in a postmortem brain studies the use of antipsychotic drugs were linked to decrease DNAM of HTR2A as well as 5-HTT promoter regions [33,63].…”

Section: Current Therapeutic Modalities In Psychiatry Targeting Dnammentioning

confidence: 99%

An Update on the Epigenetics of Psychotic Diseases and Autism

2015

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The examination of potential roles of epigenetic alterations in the pathogenesis of psychotic diseases have become an essential alternative in recent years as genetic studies alone are yet to uncover major gene(s) for psychosis. Here, we describe the current state of knowledge from the gene-specific and genome-wide studies of postmortem brain and blood cells indicating that aberrant DNA methylation, histone modifications and dysregulation of micro-RNAs are linked to the pathogenesis of mental diseases. There is also strong evidence supporting that all classes of psychiatric drugs modulate diverse features of the epigenome. While comprehensive environmental and genetic/epigenetic studies are uncovering the origins, and the key genes/pathways affected in psychotic diseases, characterizing the epigenetic effects of psychiatric drugs may help to design novel therapies in psychiatry.

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Comprehensive DNA methylation analysis of human neuroblastoma cells treated with blonanserin

Cited by 20 publications

References 18 publications

Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

Aberrant DNA Methylation of Blood in Schizophrenia by Adjusting for Estimated Cellular Proportions

An Update on the Epigenetics of Psychotic Diseases and Autism

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