Epidemiological support for genetic variability at hypothalamic-pituitary-adrenal axis and serotonergic system as risk factors for major depression

Background Major depressive disorder (MDD) is a serious, and common psychiatric disorder worldwide. By the year 2020, MDD will be the second cause of disability in the world. The GranadΣp study is the first, to the best of our knowledge, epidemiological study of mental disorders carried out in Andal...

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Autores: Ching López, Ana, Cervilla, Jorge, Rivera, Margarita, Molina, Esther, McKenney, Kathryn, Ruiz-Perez, Isabel, Rodríguez-Barranco, Miguel, Gutiérrez, Blanca
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/62967
Acceso en línea:http://hdl.handle.net/11441/62967
https://doi.org/10.2147/NDT.S90369
Access Level:acceso abierto
Palabra clave:Genetic association analysis
Major depression
HPA axis
Serotonergic system
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spelling Epidemiological support for genetic variability at hypothalamic-pituitary-adrenal axis and serotonergic system as risk factors for major depressionChing López, AnaCervilla, JorgeRivera, MargaritaMolina, EstherMcKenney, KathrynRuiz-Perez, IsabelRodríguez-Barranco, MiguelGutiérrez, BlancaGenetic association analysisMajor depressionHPA axisSerotonergic systemBackground Major depressive disorder (MDD) is a serious, and common psychiatric disorder worldwide. By the year 2020, MDD will be the second cause of disability in the world. The GranadΣp study is the first, to the best of our knowledge, epidemiological study of mental disorders carried out in Andalusia (South Spain), being one of its main objectives to identify genetic and environmental risk factors for MDD and other major psychiatric disorders. In this study, we focused on the possible association of 91 candidate single nucleotide polymorphisms (SNPs) with MDD. Methods A total of 711 community-based individuals participated in the GranadΣp study. All individuals were extensively assessed for clinical, psychological, sociodemographic, life style, and other environmental variables. A biological sample was also collected for subsequent genetic analyses in 91 candidate SNPs for MDD. DSM-IV diagnosis of MDD was used as the outcome variable. Logistic regression analysis assuming an additive genetic model was performed to test the association between MDD and the genetic data. The experiment-wide significance threshold adjusted with the SNP spectral decomposition method provided a maximum P-value (8×10−3) required to identify an association. Haplotype analyses were also performed. Results One SNP (rs623580) located in the tryptophan hydroxylase 1 gene (TPH1; chromosome 11), one intergenic variant (rs9526236) upstream of the 5-hydroxytryptamine receptor 2A gene (HTR2A; chromosome 13), and five polymorphisms (rs17689966, rs173365, rs7209436, rs110402, and rs242924) located in the corticotropin-releasing hormone receptor 1 gene (CRHR1; chromosome 17), all showed suggestive trends for association with MDD (P<0.05). Within CRHR1 gene, the TATGA haplotype combination was found to increase significantly the risk for MDD with an odds ratio =1.68 (95% CI: 1.16–2.42, P=0.006). Conclusion Although limited, perhaps due to insufficient sample size power, our results seem to support the notion that the hypothalamic–pituitary–adrenal and serotonergic systems are likely to be involved in the genetic susceptibility for MDD. Future studies, including larger samples, should be addressed for further validation and replication of the present findings.Dove Medical PressEnfermería2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/11441/62967https://doi.org/10.2147/NDT.S90369reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésNeuropsychiatric Disease and Treatment, 11, 2743-2754.info:eu-repo/semantics/openAccessoai:idus.us.es:11441/629672026-06-17T12:51:07Z
dc.title.none.fl_str_mv Epidemiological support for genetic variability at hypothalamic-pituitary-adrenal axis and serotonergic system as risk factors for major depression
title Epidemiological support for genetic variability at hypothalamic-pituitary-adrenal axis and serotonergic system as risk factors for major depression
spellingShingle Epidemiological support for genetic variability at hypothalamic-pituitary-adrenal axis and serotonergic system as risk factors for major depression
Ching López, Ana
Genetic association analysis
Major depression
HPA axis
Serotonergic system
title_short Epidemiological support for genetic variability at hypothalamic-pituitary-adrenal axis and serotonergic system as risk factors for major depression
title_full Epidemiological support for genetic variability at hypothalamic-pituitary-adrenal axis and serotonergic system as risk factors for major depression
title_fullStr Epidemiological support for genetic variability at hypothalamic-pituitary-adrenal axis and serotonergic system as risk factors for major depression
title_full_unstemmed Epidemiological support for genetic variability at hypothalamic-pituitary-adrenal axis and serotonergic system as risk factors for major depression
title_sort Epidemiological support for genetic variability at hypothalamic-pituitary-adrenal axis and serotonergic system as risk factors for major depression
dc.creator.none.fl_str_mv Ching López, Ana
Cervilla, Jorge
Rivera, Margarita
Molina, Esther
McKenney, Kathryn
Ruiz-Perez, Isabel
Rodríguez-Barranco, Miguel
Gutiérrez, Blanca
author Ching López, Ana
author_facet Ching López, Ana
Cervilla, Jorge
Rivera, Margarita
Molina, Esther
McKenney, Kathryn
Ruiz-Perez, Isabel
Rodríguez-Barranco, Miguel
Gutiérrez, Blanca
author_role author
author2 Cervilla, Jorge
Rivera, Margarita
Molina, Esther
McKenney, Kathryn
Ruiz-Perez, Isabel
Rodríguez-Barranco, Miguel
Gutiérrez, Blanca
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Enfermería
dc.subject.none.fl_str_mv Genetic association analysis
Major depression
HPA axis
Serotonergic system
topic Genetic association analysis
Major depression
HPA axis
Serotonergic system
description Background Major depressive disorder (MDD) is a serious, and common psychiatric disorder worldwide. By the year 2020, MDD will be the second cause of disability in the world. The GranadΣp study is the first, to the best of our knowledge, epidemiological study of mental disorders carried out in Andalusia (South Spain), being one of its main objectives to identify genetic and environmental risk factors for MDD and other major psychiatric disorders. In this study, we focused on the possible association of 91 candidate single nucleotide polymorphisms (SNPs) with MDD. Methods A total of 711 community-based individuals participated in the GranadΣp study. All individuals were extensively assessed for clinical, psychological, sociodemographic, life style, and other environmental variables. A biological sample was also collected for subsequent genetic analyses in 91 candidate SNPs for MDD. DSM-IV diagnosis of MDD was used as the outcome variable. Logistic regression analysis assuming an additive genetic model was performed to test the association between MDD and the genetic data. The experiment-wide significance threshold adjusted with the SNP spectral decomposition method provided a maximum P-value (8×10−3) required to identify an association. Haplotype analyses were also performed. Results One SNP (rs623580) located in the tryptophan hydroxylase 1 gene (TPH1; chromosome 11), one intergenic variant (rs9526236) upstream of the 5-hydroxytryptamine receptor 2A gene (HTR2A; chromosome 13), and five polymorphisms (rs17689966, rs173365, rs7209436, rs110402, and rs242924) located in the corticotropin-releasing hormone receptor 1 gene (CRHR1; chromosome 17), all showed suggestive trends for association with MDD (P<0.05). Within CRHR1 gene, the TATGA haplotype combination was found to increase significantly the risk for MDD with an odds ratio =1.68 (95% CI: 1.16–2.42, P=0.006). Conclusion Although limited, perhaps due to insufficient sample size power, our results seem to support the notion that the hypothalamic–pituitary–adrenal and serotonergic systems are likely to be involved in the genetic susceptibility for MDD. Future studies, including larger samples, should be addressed for further validation and replication of the present findings.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11441/62967
https://doi.org/10.2147/NDT.S90369
url http://hdl.handle.net/11441/62967
https://doi.org/10.2147/NDT.S90369
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Neuropsychiatric Disease and Treatment, 11, 2743-2754.
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Dove Medical Press
publisher.none.fl_str_mv Dove Medical Press
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.198674

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