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ID 115714
著者
Nakazawa, Takanobu Osaka University
Kikuchi, Masataka Osaka University
Ishikawa, Mitsuru Keio University
Yamamori, Hidenaga Osaka University
Nagayasu, Kazuki Osaka University
Matsumoto, Takuya Keio University|Ajinomoto
Fujimoto, Michiko Osaka University
Yasuda, Yuka Osaka University
Fujiwara, Mikiya Osaka University
Okada, Shota Osaka University
Matsumura, Kensuke Osaka University
Kasai, Atsushi Osaka University
Hayata-Takano, Atsuko Osaka University
Shintani, Norihito Osaka University
Takuma, Kazuhiro Osaka University
Akamatsu, Wado Keio University|Juntendo University
Okano, Hideyuki Keio University
Nakaya, Akihiro Osaka University
Hashimoto, Hitoshi Osaka University
Hashimoto, Ryota Osaka University
キーワード
iPS cell
Monozygotic twins
Treatment-resistant schizophrenia
Clozapine
Drug response
資料タイプ
学術雑誌論文
抄録
Schizophrenia is a chronic psychiatric disorder with complex genetic and environmental origins. While many antipsychotics have been demonstrated as effective in the treatment of schizophrenia, a substantial number of schizophrenia patients are partially or fully unresponsive to the treatment. Clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia; however, clozapine has rare but serious side-effects. Furthermore, there is inter-individual variability in the drug response to clozapine treatment. Therefore, the identification of the molecular mechanisms underlying the action of clozapine and drug response predictors is imperative. In the present study, we focused on a pair of monozygotic twin cases with treatment-resistant schizophrenia, in which one twin responded well to clozapine treatment and the other twin did not. Using induced pluripotent stem (iPS) cell-based technology, we generated neurons from iPS cells derived from these patients and subsequently performed RNA-sequencing to compare the transcriptome profiles of the mock or clozapine-treated neurons. Although, these iPS cells similarly differentiated into neurons, several genes encoding homophilic cell adhesion molecules, such as protocadherin genes, showed differential expression patterns between these two patients. These results, which contribute to the current understanding of the molecular mechanisms of clozapine action, establish a new strategy for the use of monozygotic twin studies in schizophrenia research.
掲載誌名
Schizophrenia Research
ISSN
09209964
cat書誌ID
AA10703465
AA11539775
出版者
Elsevier
181
開始ページ
75
終了ページ
82
発行日
2016-10-27
権利情報
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系