TY - JOUR
T1 - DNA methylation of ANKK1 and response to aripiprazole in patients with acute schizophrenia
T2 - A preliminary study
AU - Miura, Itaru
AU - Kunii, Yasuto
AU - Hino, Mizuki
AU - Hoshino, Hiroshi
AU - Matsumoto, Junya
AU - Kanno-Nozaki, Keiko
AU - Horikoshi, Sho
AU - Kaneko, Haruka
AU - Bundo, Miki
AU - Iwamoto, Kazuya
AU - Yabe, Hirooki
N1 - Funding Information:
This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant Numbers 25116520 and 15K19739 ).
Funding Information:
Dr. Miura has received speaker's honoraria from Daiichi Sankyo, Dainippon Sumitomo, Janssen, Meiji Seika, Mochida, Otsuka, Tanabe Mitsubishi, and Yoshitomi. He had received grant support from Janssen , Hoshi General Hospital Foundation , and the Eli Lilly Fellowship for Clinical Psychopharmacology . Dr. Matsumoto has received speaker's honoraria from Janssen and MSD.
Publisher Copyright:
© 2018
PY - 2018/5
Y1 - 2018/5
N2 - Epigenetic modification including DNA methylation may affect pathophysiology and the response to antipsychotic drugs in patients with schizophrenia. The objective of the present study was to investigate the effect of the DNA methylation of ANKK1 (ankyrin repeat and kinase domain containing 1) on the response to aripiprazole and plasma levels of monoamine metabolites in antipsychotic-free acute schizophrenia patients. The subjects were 34 Japanese patients with schizophrenia who had been treated with aripiprazole for 6 weeks. Comprehensive DNA methylation of ANKK1 was determined using a next-generation sequencer. DNA methylation levels at CpG site 387 of ANKK1 were higher in responders to treatment with aripiprazole and correlated with the changes in Positive and Negative Syndrome Scale scores, although the associations did not remain significant after Bonferroni correction. In responders, methylation at all CpG sites was significantly correlated with plasma levels of homovanillic acid (r = 0.587, p = 0.035) and 3-methoxy-4hydroxyphenylglycol (r = 0.684, p = 0.010) at baseline. Despite our non-significant results after multiple correction, our preliminary findings suggest that methylation levels at CpG site 387 of ANKK1 may be associated with treatment response to aripiprazole. Furthermore, methylation of ANKK1 may affect dopaminergic neural transmission in the treatment of schizophrenia, and may influence treatment response. Caution is needed in interpreting these findings because of the small sample size, and further studies are needed to confirm and expand our preliminary results.
AB - Epigenetic modification including DNA methylation may affect pathophysiology and the response to antipsychotic drugs in patients with schizophrenia. The objective of the present study was to investigate the effect of the DNA methylation of ANKK1 (ankyrin repeat and kinase domain containing 1) on the response to aripiprazole and plasma levels of monoamine metabolites in antipsychotic-free acute schizophrenia patients. The subjects were 34 Japanese patients with schizophrenia who had been treated with aripiprazole for 6 weeks. Comprehensive DNA methylation of ANKK1 was determined using a next-generation sequencer. DNA methylation levels at CpG site 387 of ANKK1 were higher in responders to treatment with aripiprazole and correlated with the changes in Positive and Negative Syndrome Scale scores, although the associations did not remain significant after Bonferroni correction. In responders, methylation at all CpG sites was significantly correlated with plasma levels of homovanillic acid (r = 0.587, p = 0.035) and 3-methoxy-4hydroxyphenylglycol (r = 0.684, p = 0.010) at baseline. Despite our non-significant results after multiple correction, our preliminary findings suggest that methylation levels at CpG site 387 of ANKK1 may be associated with treatment response to aripiprazole. Furthermore, methylation of ANKK1 may affect dopaminergic neural transmission in the treatment of schizophrenia, and may influence treatment response. Caution is needed in interpreting these findings because of the small sample size, and further studies are needed to confirm and expand our preliminary results.
KW - ANKK1
KW - Aripiprazole
KW - DNA methylation
KW - Dopamine D2 receptor
KW - Schizophrenia
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U2 - 10.1016/j.jpsychires.2018.02.018
DO - 10.1016/j.jpsychires.2018.02.018
M3 - Article
C2 - 29499474
AN - SCOPUS:85042631698
SN - 0022-3956
VL - 100
SP - 84
EP - 87
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
ER -
