Effects of quetiapine on DNA methylation in neuroblastoma cells

Sugawara, Hiroko; Bundo, Miki; Asai, Tatsuro; Sunaga, Fumiko; Ueda, Junko; Ishigooka, Jun; Kasai, Kiyoto; Kato, Takeshi; Iwamoto, Kazuya

doi:10.1016/j.pnpbp.2014.08.010

Cited by 26 publications

(17 citation statements)

References 29 publications

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“…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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…Antipsychotic such as quetiapine decreased the DNA methylation level of the promoter region of SLC6A4. Mood stabilizers could also reverse the hypermethylation process of CpG sites of SLC6A4 to be hypomethylated in bipolar disorder [106, 107]. However, SLC6A9 was under-expressed gene in Huang et al [2].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic profiling of human brain differential DNA methylation networks in schizophrenia

Lee

Huang

2016

BMC Med Genomics

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BackgroundEpigenetics of schizophrenia provides important information on how the environmental factors affect the genetic architecture of the disease. DNA methylation plays a pivotal role in etiology for schizophrenia. Previous studies have focused mostly on the discovery of schizophrenia-associated SNPs or genetic variants. As postmortem brain samples became available, more and more recent studies surveyed transcriptomics of the diseases. In this study, we constructed protein-protein interaction (PPI) network using the disease associated SNP (or genetic variants), differentially expressed disease genes and differentially methylated disease genes (or promoters). By combining the different datasets and topological analyses of the PPI network, we established a more comprehensive understanding of the development and genetics of this devastating mental illness.ResultsWe analyzed the previously published DNA methylation profiles of prefrontal cortex from 335 healthy controls and 191 schizophrenic patients. These datasets revealed 2014 CpGs identified as GWAS risk loci with the differential methylation profile in schizophrenia, and 1689 schizophrenic differential methylated genes (SDMGs) identified with predominant hypomethylation. These SDMGs, combined with the PPIs of these genes, were constructed into the schizophrenic differential methylation network (SDMN). On the SDMN, there are 10 hypermethylated SDMGs, including GNA13, CAPNS1, GABPB2, GIT2, LEFTY1, NDUFA10, MIOS, MPHOSPH6, PRDM14 and RFWD2. The hypermethylation to differential expression network (HyDEN) were constructed to determine how the hypermethylated promoters regulate gene expression. The enrichment analyses of biochemical pathways in HyDEN, including TNF alpha, PDGFR-beta signaling, TGF beta Receptor, VEGFR1 and VEGFR2 signaling, regulation of telomerase, hepatocyte growth factor receptor signaling, ErbB1 downstream signaling and mTOR signaling pathway, suggested that the malfunctioning of these pathways contribute to the symptoms of schizophrenia.ConclusionsThe epigenetic profiles of DNA differential methylation from schizophrenic brain samples were investigated to understand the regulatory roles of SDMGs. The SDMGs interplays with SCZCGs in a coordinated fashion in the disease mechanism of schizophrenia. The protein complexes and pathways involved in SDMN may be responsible for the etiology and potential treatment targets. The SDMG promoters are predominantly hypomethylated. Increasing methylation on these promoters is proposed as a novel therapeutic approach for schizophrenia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-016-0229-y) contains supplementary material, which is available to authorized users.

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“…Previous studies have reported that antipsychotics and mood stabilizers have some effects on the epigenetic status of brain cells and peripheral blood . Because of the absence of drug information in our sample set, we investigated the effects of antipsychotics on DNA methylation in the candidate regions using a nonhuman primate, the common marmoset, administered with risperidone.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that antipsychotics and mood stabilizers have some effects on the epigenetic status of brain cells and peripheral blood. [37][38][39][40][41][42] Because of the absence of drug information in our sample set, we investigated the effects of antipsychotics on DNA methylation in the candidate regions using a nonhuman primate, the common marmoset, administered with risperidone. Although we examined the evolutionarily conserved CpG sites in three candidate regions (FAM63B, ARHGAP26, and IR on chromosome 16), we did not observe any possible effects of risperidone on DNA methylation.…”

Section: Ir In Chromosome 16mentioning

confidence: 99%

DNA methylation analyses of the candidate genes identified by a methylome‐wide association study revealed common epigenetic alterations in schizophrenia and bipolar disorder

Sugawara

Murata

Ikegame

et al. 2018

Psychiatry Clin Neurosci

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Effects of quetiapine on DNA methylation in neuroblastoma cells

Cited by 26 publications

References 29 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

Epigenetic profiling of human brain differential DNA methylation networks in schizophrenia

DNA methylation analyses of the candidate genes identified by a methylome‐wide association study revealed common epigenetic alterations in schizophrenia and bipolar disorder

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