Differential gene expression profiles in neurons generated from lymphoblastoid B-cell line-derived iPS cells from monozygotic twin cases with treatment-resistant schizophrenia and discordant responses to clozapine

Takanobu Nakazawa, Masataka Kikuchi, Mitsuru Ishikawa, Hidenaga Yamamori, Kazuki Nagayasu, Takuya Matsumoto, Michiko Fujimoto, Yuka Yasuda, Mikiya Fujiwara, Shota Okada, Kensuke Matsumura, Atsushi Kasai, Atsuko Hayata-Takano, Norihito Shintani, Shusuke Numata, Kazuhiro Takuma, Wado Akamatsu, Hideyuki Okano, Akihiro Nakaya, Hitoshi HashimotoRyota Hashimoto

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalSchizophrenia Research
Volume181
DOIs
Publication statusPublished - 2017 Mar 1

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Keywords

  • Clozapine
  • Drug response
  • iPS cell
  • Monozygotic twins
  • Treatment-resistant schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Nakazawa, T., Kikuchi, M., Ishikawa, M., Yamamori, H., Nagayasu, K., Matsumoto, T., Fujimoto, M., Yasuda, Y., Fujiwara, M., Okada, S., Matsumura, K., Kasai, A., Hayata-Takano, A., Shintani, N., Numata, S., Takuma, K., Akamatsu, W., Okano, H., Nakaya, A., ... Hashimoto, R. (2017). Differential gene expression profiles in neurons generated from lymphoblastoid B-cell line-derived iPS cells from monozygotic twin cases with treatment-resistant schizophrenia and discordant responses to clozapine. Schizophrenia Research, 181, 75-82. https://doi.org/10.1016/j.schres.2016.10.012