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Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder

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 treat...

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Autores principales: Umehara, Hidehiro, Numata, Shusuke, Tajima, Atsushi, Nishi, Akira, Nakataki, Masahito, Imoto, Issei, Sumitani, Satsuki, Ohmori, Tetsuro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900663/
https://www.ncbi.nlm.nih.gov/pubmed/27281126
http://dx.doi.org/10.1371/journal.pone.0157232
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author Umehara, Hidehiro
Numata, Shusuke
Tajima, Atsushi
Nishi, Akira
Nakataki, Masahito
Imoto, Issei
Sumitani, Satsuki
Ohmori, Tetsuro
author_facet Umehara, Hidehiro
Numata, Shusuke
Tajima, Atsushi
Nishi, Akira
Nakataki, Masahito
Imoto, Issei
Sumitani, Satsuki
Ohmori, Tetsuro
author_sort Umehara, Hidehiro
collection PubMed
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.
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spelling pubmed-49006632016-06-24 Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder Umehara, Hidehiro Numata, Shusuke Tajima, Atsushi Nishi, Akira Nakataki, Masahito Imoto, Issei Sumitani, Satsuki Ohmori, Tetsuro PLoS One Research Article 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. Public Library of Science 2016-06-09 /pmc/articles/PMC4900663/ /pubmed/27281126 http://dx.doi.org/10.1371/journal.pone.0157232 Text en © 2016 Umehara et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Umehara, Hidehiro
Numata, Shusuke
Tajima, Atsushi
Nishi, Akira
Nakataki, Masahito
Imoto, Issei
Sumitani, Satsuki
Ohmori, Tetsuro
Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder
title Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder
title_full Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder
title_fullStr Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder
title_full_unstemmed Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder
title_short Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder
title_sort calcium signaling pathway is associated with the long-term clinical response to selective serotonin reuptake inhibitors (ssri) and ssri with antipsychotics in patients with obsessive-compulsive disorder
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900663/
https://www.ncbi.nlm.nih.gov/pubmed/27281126
http://dx.doi.org/10.1371/journal.pone.0157232
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