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Influence of eight ABCB1 polymorphisms on antidepressant response in a prospective cohort of treatment‐free Russian patients with moderate or severe depression: An explorative psychopharmacological study with naturalistic design

Background Many antidepressants are substrates of P‐glycoprotein, an efflux transporter in the blood‐brain‐barrier encoded by the ABCB1 gene. Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eig...

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Published in:Human psychopharmacology 2022-05, Vol.37 (3), p.e2826-n/a
Main Authors: Geers, Lisanne M., Ochi, Taichi, Vyalova, Natalya M., Losenkov, Innokentiy S., Paderina, Diana Z., Pozhidaev, Ivan V., Simutkin, German G., Bokhan, Nikolay A., Wilffert, Bob, Touw, Daniël J., Loonen, Anton J.M., Ivanova, Svetlana A.
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container_title Human psychopharmacology
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creator Geers, Lisanne M.
Ochi, Taichi
Vyalova, Natalya M.
Losenkov, Innokentiy S.
Paderina, Diana Z.
Pozhidaev, Ivan V.
Simutkin, German G.
Bokhan, Nikolay A.
Wilffert, Bob
Touw, Daniël J.
Loonen, Anton J.M.
Ivanova, Svetlana A.
description Background Many antidepressants are substrates of P‐glycoprotein, an efflux transporter in the blood‐brain‐barrier encoded by the ABCB1 gene. Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eight polymorphisms in the ABCB1 gene on antidepressant treatment response. Method 152 patients were included from psychiatric departments of the Mental Health Research Institute in Tomsk. The difference in Hamilton‐Depression‐Rating‐Scale (HAMD‐17)‐scores between baseline and week two, week two and four, and baseline and week four was used to estimate timing of improvement of depression. Associations between the ABCB1 gene‐polymorphisms and reduction in HAMD‐17 score were assessed using independent t‐test and multiple linear regression. Results Tricyclic antidepressants were associated with a higher reduction of HAMD‐17 score when compared to SSRIs. The SNP rs2235040 A‐allele had a significant positive influence on the ΔHAMD‐17(0→2W) score but a significant negative influence on the ΔHAMD‐17(2→4W) score. The rs4148739 G‐allele had a significant negative influence on the ΔHAMD‐17(0→2W) score but a significant positive influence on the ΔHAMD‐17(2→4W) score. The SNP rs2235015 T‐allele is significant negatively related to the ΔHAMD‐17(2→4W) score. Conclusion ABCB1 Genetic variations appear to affect speed but not magnitude of antidepressant drug response.
doi_str_mv 10.1002/hup.2826
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Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eight polymorphisms in the ABCB1 gene on antidepressant treatment response. Method 152 patients were included from psychiatric departments of the Mental Health Research Institute in Tomsk. The difference in Hamilton‐Depression‐Rating‐Scale (HAMD‐17)‐scores between baseline and week two, week two and four, and baseline and week four was used to estimate timing of improvement of depression. Associations between the ABCB1 gene‐polymorphisms and reduction in HAMD‐17 score were assessed using independent t‐test and multiple linear regression. Results Tricyclic antidepressants were associated with a higher reduction of HAMD‐17 score when compared to SSRIs. The SNP rs2235040 A‐allele had a significant positive influence on the ΔHAMD‐17(0→2W) score but a significant negative influence on the ΔHAMD‐17(2→4W) score. The rs4148739 G‐allele had a significant negative influence on the ΔHAMD‐17(0→2W) score but a significant positive influence on the ΔHAMD‐17(2→4W) score. The SNP rs2235015 T‐allele is significant negatively related to the ΔHAMD‐17(2→4W) score. Conclusion ABCB1 Genetic variations appear to affect speed but not magnitude of antidepressant drug response.</description><identifier>ISSN: 0885-6222</identifier><identifier>EISSN: 1099-1077</identifier><identifier>DOI: 10.1002/hup.2826</identifier><identifier>PMID: 34788473</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>ABCB1 gene ; Alleles ; Antidepressants ; Antidepressive Agents - therapeutic use ; ATP Binding Cassette Transporter, Subfamily B - genetics ; Blood-brain barrier ; Depression ; Depressive Disorder, Major - drug therapy ; Depressive Disorder, Major - genetics ; Genetic diversity ; Genotype ; Hamilton Depression Rating Scale ; Humans ; Mental depression ; Patients ; Polymorphism, Single Nucleotide - genetics ; Prospective Studies ; P‐glycoprotein ; Single-nucleotide polymorphism ; Tricyclic antidepressants</subject><ispartof>Human psychopharmacology, 2022-05, Vol.37 (3), p.e2826-n/a</ispartof><rights>2021 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley &amp; Sons Ltd.</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). 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Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eight polymorphisms in the ABCB1 gene on antidepressant treatment response. Method 152 patients were included from psychiatric departments of the Mental Health Research Institute in Tomsk. The difference in Hamilton‐Depression‐Rating‐Scale (HAMD‐17)‐scores between baseline and week two, week two and four, and baseline and week four was used to estimate timing of improvement of depression. Associations between the ABCB1 gene‐polymorphisms and reduction in HAMD‐17 score were assessed using independent t‐test and multiple linear regression. Results Tricyclic antidepressants were associated with a higher reduction of HAMD‐17 score when compared to SSRIs. The SNP rs2235040 A‐allele had a significant positive influence on the ΔHAMD‐17(0→2W) score but a significant negative influence on the ΔHAMD‐17(2→4W) score. The rs4148739 G‐allele had a significant negative influence on the ΔHAMD‐17(0→2W) score but a significant positive influence on the ΔHAMD‐17(2→4W) score. The SNP rs2235015 T‐allele is significant negatively related to the ΔHAMD‐17(2→4W) score. 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Ochi, Taichi ; Vyalova, Natalya M. ; Losenkov, Innokentiy S. ; Paderina, Diana Z. ; Pozhidaev, Ivan V. ; Simutkin, German G. ; Bokhan, Nikolay A. ; Wilffert, Bob ; Touw, Daniël J. ; Loonen, Anton J.M. ; Ivanova, Svetlana A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4386-696b2f6ced8e75812f3e716bc623b690a5a4c732e4862a323c19fd9ba62f242c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>ABCB1 gene</topic><topic>Alleles</topic><topic>Antidepressants</topic><topic>Antidepressive Agents - therapeutic use</topic><topic>ATP Binding Cassette Transporter, Subfamily B - genetics</topic><topic>Blood-brain barrier</topic><topic>Depression</topic><topic>Depressive Disorder, Major - drug therapy</topic><topic>Depressive Disorder, Major - genetics</topic><topic>Genetic diversity</topic><topic>Genotype</topic><topic>Hamilton Depression Rating Scale</topic><topic>Humans</topic><topic>Mental depression</topic><topic>Patients</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Prospective Studies</topic><topic>P‐glycoprotein</topic><topic>Single-nucleotide polymorphism</topic><topic>Tricyclic antidepressants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Geers, Lisanne M.</creatorcontrib><creatorcontrib>Ochi, Taichi</creatorcontrib><creatorcontrib>Vyalova, Natalya M.</creatorcontrib><creatorcontrib>Losenkov, Innokentiy S.</creatorcontrib><creatorcontrib>Paderina, Diana Z.</creatorcontrib><creatorcontrib>Pozhidaev, Ivan V.</creatorcontrib><creatorcontrib>Simutkin, German G.</creatorcontrib><creatorcontrib>Bokhan, Nikolay A.</creatorcontrib><creatorcontrib>Wilffert, Bob</creatorcontrib><creatorcontrib>Touw, Daniël J.</creatorcontrib><creatorcontrib>Loonen, Anton J.M.</creatorcontrib><creatorcontrib>Ivanova, Svetlana A.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health &amp; 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Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eight polymorphisms in the ABCB1 gene on antidepressant treatment response. Method 152 patients were included from psychiatric departments of the Mental Health Research Institute in Tomsk. The difference in Hamilton‐Depression‐Rating‐Scale (HAMD‐17)‐scores between baseline and week two, week two and four, and baseline and week four was used to estimate timing of improvement of depression. Associations between the ABCB1 gene‐polymorphisms and reduction in HAMD‐17 score were assessed using independent t‐test and multiple linear regression. Results Tricyclic antidepressants were associated with a higher reduction of HAMD‐17 score when compared to SSRIs. The SNP rs2235040 A‐allele had a significant positive influence on the ΔHAMD‐17(0→2W) score but a significant negative influence on the ΔHAMD‐17(2→4W) score. The rs4148739 G‐allele had a significant negative influence on the ΔHAMD‐17(0→2W) score but a significant positive influence on the ΔHAMD‐17(2→4W) score. The SNP rs2235015 T‐allele is significant negatively related to the ΔHAMD‐17(2→4W) score. Conclusion ABCB1 Genetic variations appear to affect speed but not magnitude of antidepressant drug response.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34788473</pmid><doi>10.1002/hup.2826</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-1052-855X</orcidid><orcidid>https://orcid.org/0000-0003-4942-6195</orcidid><orcidid>https://orcid.org/0000-0003-4285-690X</orcidid><orcidid>https://orcid.org/0000-0003-1238-7495</orcidid><orcidid>https://orcid.org/0000-0001-7458-2179</orcidid><orcidid>https://orcid.org/0000-0002-9813-3789</orcidid><orcidid>https://orcid.org/0000-0002-8759-5697</orcidid><orcidid>https://orcid.org/0000-0002-5546-7316</orcidid><orcidid>https://orcid.org/0000-0001-7078-323X</orcidid><orcidid>https://orcid.org/0000-0002-4856-2905</orcidid><orcidid>https://orcid.org/0000-0002-1429-4789</orcidid><orcidid>https://orcid.org/0000-0001-6464-6474</orcidid><oa>free_for_read</oa></addata></record>
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source Wiley-Blackwell Read & Publish Collection
subjects ABCB1 gene
Alleles
Antidepressants
Antidepressive Agents - therapeutic use
ATP Binding Cassette Transporter, Subfamily B - genetics
Blood-brain barrier
Depression
Depressive Disorder, Major - drug therapy
Depressive Disorder, Major - genetics
Genetic diversity
Genotype
Hamilton Depression Rating Scale
Humans
Mental depression
Patients
Polymorphism, Single Nucleotide - genetics
Prospective Studies
P‐glycoprotein
Single-nucleotide polymorphism
Tricyclic antidepressants
title Influence of eight ABCB1 polymorphisms on antidepressant response in a prospective cohort of treatment‐free Russian patients with moderate or severe depression: An explorative psychopharmacological study with naturalistic design
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