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ID 110039
タイトル別表記
強迫性障害におけるセロトニン再取り込み阻害薬治療および抗精神病薬付加療法への治療反応性はカルシウムシグナリングパスウェイと関連する
GWAS of Clinical Response in OCD
著者
梅原, 英裕 徳島大学大学院医科学教育部(医学専攻) 徳島大学 教育研究者総覧 KAKEN研究者をさがす
田嶋, 敦 Kanazawa University|Tokushima University KAKEN研究者をさがす
Nishi, Akira Tokushima University
キーワード
obsessive-compulsive disorder
clinical response
calcium signaling
genome-wide association study
資料タイプ
学位論文
抄録
Background
Selective serotonin reuptake inhibitors (SSRI) are established first-line pharmacological treatments for obsessive-compulsive disorder (OCD), while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics.

Methods
We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) to examine the combined effects of genetic variants on the clinical response in OCD.

Results
While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses.

Conclusions
Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients.
掲載誌名
PLOS ONE
ISSN
19326203
出版者
PLOS
11
6
開始ページ
e0157232
発行日
2016-06-09
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨:LID201704131006.pdf
論文本文:LID201704131007.pdf
本論文は, 著者Hidehiro Umeharaの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
Copyright: © 2016 Umehara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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
博士論文全文を含む
文科省報告番号
甲第3015号
学位記番号
甲医第1319号
学位授与年月日
2017-03-23
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系
特別修学支援室