title: Effects of quetiapine on DNA methylation in neuroblastoma cells.
abstract: Epigenetic regulation may be involved in the pathophysiology of mental disorders, such as schizophrenia and bipolar disorder, and in the pharmacological action of drugs. Characterizing the epigenetic effects of drugs is an important step to optimal treatment. We performed comprehensive and gene-specific DNA methylation analyses of quetiapine using human neuroblastoma cells. Human neuroblastoma cells were cultured with quetiapine for 8 days, and DNA methylation analysis was performed using Infinium HumanMethylation27 BeadChip. A total of 1173 genes showed altered DNA methylation. Altered DNA methylation predominantly occurred as hypomethylation within the CpG island compared to DNA isolated from non-treated cells. Gene ontology analysis revealed that these genes were related to the cellular process of intracellular protein binding. There was no common effect of quetiapine with three mood stabilizers (lithium, valproate, and carbamazepine). However, common DNA methylation changes in eight genes, including ADRA1A, which encodes adrenoceptor alpha 1A, were found with quetiapine and lithium treatments. Finally, bisulfite-sequencing analysis revealed that quetiapine decreased the DNA methylation level of the promoter region of SLC6A4, where hypermethylation with bipolar disorder and hypomethylation with mood stabilizers have been reported.
authors.affiliation: Department of Psychiatry, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sugawara
authors.affiliation: Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Bundo
authors.affiliation: Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Asai
authors.affiliation: Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sunaga
authors.affiliation: Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Ueda
authors.affiliation: Department of Psychiatry, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ishigooka
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kasai
authors.affiliation: Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: kaziwamoto-tky@umin.ac.jp.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwamoto
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019175:DNA Methylation / Q000187:drug effects*; D003987:Dibenzothiazepines / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D000069348:Quetiapine Fumarate; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C547713:ADRA1A protein, human; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D018340:Receptors, Adrenergic, alpha-1; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D000069348:Quetiapine Fumarate
keywords: Bipolar disorder; DNA methylation; Mood stabilizer; Quetiapine; SLC6A4