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ID 110039
Title Alternative
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
Author
Tajima, Atsushi Kanazawa University|Tokushima University KAKEN Search Researchers
Nishi, Akira Tokushima University
Keywords
obsessive-compulsive disorder
clinical response
calcium signaling
genome-wide association study
Content Type
Thesis or Dissertation
Description
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.
Journal Title
PLOS ONE
ISSN
19326203
Publisher
PLOS
Volume
11
Issue
6
Start Page
e0157232
Published Date
2016-06-09
Remark
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。
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3015号
Diploma Number
甲医第1319号
Granted Date
2017-03-23
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences
Academic Support Office for Students with Special Needs