並列タイトル等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
一般注記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.
著作権情報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.
関連情報(DOI)10.1371/journal.pone.0157232
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース(IRDB)(機関リポジトリ)