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Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study
BACKGROUND: Increased cortisol levels and genetic polymorphisms have been related to both major depressive disorder and antidepressant treatment outcome. The aim of this study is to evaluate the relationship between circadian salivary cortisol levels, cortisol suppression by dexamethasone and geneti...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149200/ https://www.ncbi.nlm.nih.gov/pubmed/25086452 http://dx.doi.org/10.1186/s12888-014-0220-0 |
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author | Ventura-Juncá, Raúl Symon, Adriana López, Pamela Fiedler, Jenny L Rojas, Graciela Heskia, Cristóbal Lara, Pamela Marín, Felipe Guajardo, Viviana Araya, A Verónica Sasso, Jaime Herrera, Luisa |
author_facet | Ventura-Juncá, Raúl Symon, Adriana López, Pamela Fiedler, Jenny L Rojas, Graciela Heskia, Cristóbal Lara, Pamela Marín, Felipe Guajardo, Viviana Araya, A Verónica Sasso, Jaime Herrera, Luisa |
author_sort | Ventura-Juncá, Raúl |
collection | PubMed |
description | BACKGROUND: Increased cortisol levels and genetic polymorphisms have been related to both major depressive disorder and antidepressant treatment outcome. The aim of this study is to evaluate the relationship between circadian salivary cortisol levels, cortisol suppression by dexamethasone and genetic polymorphisms in some HPA axis-related genes to the response to placebo and fluoxetine in depressed patients. METHODS: The diagnosis and severity of depression were performed using the Mini International Neuropsychiatric Interview (M.I.N.I.) and Hamilton depression scale (HAM-D(17)), respectively. Euthyroid patients were treated with placebo (one week) followed by fluoxetine (20 mg) (two months). Severity of depression was re-evaluated after placebo, three weeks and two months of fluoxetine treatments. Placebo response was defined as HAM-D(17) score reductions of at least 25% and to < 15. Early response and response were reductions of at least 50% after three weeks and two months, and remission with ≤ 7 after two months. Plasma TSH, free-T4, circadian salivary cortisol levels and cortisol suppression by dexamethasone were evaluated. Seven genetic polymorphisms located in the Corticotrophin-releasing-hormone-receptor-1 (rs242939, rs242941, rs1876828), Corticotrophin-releasing-hormone-receptor-2 (rs2270007), Glucocorticoid-receptor (rs41423247), FK506-binding-protein-5 (rs1360780), and Arginine-vasopressin (rs3729965) genes were determined. Association analyses between response to placebo/fluoxetine and polymorphism were performed by chi-square or Fisher exact test. Cortisol levels were compared by t-test, ANOVA and the general linear model for repeated measures. RESULTS: 208 depressed patients were recruited, 187 of whom were euthyroid. Placebo responders, fluoxetine responders and remitters exhibited significantly lower circadian cortisol levels than those who did not respond (p-values of 0.014, 0.008 and 0.021 respectively). Patients who abandoned treatment before the third week also exhibited a trend to low cortisol levels (p = 0.057). The polymorphisms rs242939 (CRHR1) and rs2270007 (CRHR2) were not in Hardy-Weinberg equilibrium. Only the rs242939 polymorphism (CRHR1) exhibited association with early response (three weeks) to fluoxetine (p-value = 0.043). No other association between outcomes and polymorphisms was observed. CONCLUSIONS: These results support the clinical relevance of low salivary cortisol levels as a predictor of antidepressant response, either to placebo or to fluoxetine. Only one polymorphism in the CRHR1 gene was associated with the early response. Other factors may be involved in antidepressant response, although further studies are needed to identify them. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12888-014-0220-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4149200 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-41492002014-08-30 Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study Ventura-Juncá, Raúl Symon, Adriana López, Pamela Fiedler, Jenny L Rojas, Graciela Heskia, Cristóbal Lara, Pamela Marín, Felipe Guajardo, Viviana Araya, A Verónica Sasso, Jaime Herrera, Luisa BMC Psychiatry Research Article BACKGROUND: Increased cortisol levels and genetic polymorphisms have been related to both major depressive disorder and antidepressant treatment outcome. The aim of this study is to evaluate the relationship between circadian salivary cortisol levels, cortisol suppression by dexamethasone and genetic polymorphisms in some HPA axis-related genes to the response to placebo and fluoxetine in depressed patients. METHODS: The diagnosis and severity of depression were performed using the Mini International Neuropsychiatric Interview (M.I.N.I.) and Hamilton depression scale (HAM-D(17)), respectively. Euthyroid patients were treated with placebo (one week) followed by fluoxetine (20 mg) (two months). Severity of depression was re-evaluated after placebo, three weeks and two months of fluoxetine treatments. Placebo response was defined as HAM-D(17) score reductions of at least 25% and to < 15. Early response and response were reductions of at least 50% after three weeks and two months, and remission with ≤ 7 after two months. Plasma TSH, free-T4, circadian salivary cortisol levels and cortisol suppression by dexamethasone were evaluated. Seven genetic polymorphisms located in the Corticotrophin-releasing-hormone-receptor-1 (rs242939, rs242941, rs1876828), Corticotrophin-releasing-hormone-receptor-2 (rs2270007), Glucocorticoid-receptor (rs41423247), FK506-binding-protein-5 (rs1360780), and Arginine-vasopressin (rs3729965) genes were determined. Association analyses between response to placebo/fluoxetine and polymorphism were performed by chi-square or Fisher exact test. Cortisol levels were compared by t-test, ANOVA and the general linear model for repeated measures. RESULTS: 208 depressed patients were recruited, 187 of whom were euthyroid. Placebo responders, fluoxetine responders and remitters exhibited significantly lower circadian cortisol levels than those who did not respond (p-values of 0.014, 0.008 and 0.021 respectively). Patients who abandoned treatment before the third week also exhibited a trend to low cortisol levels (p = 0.057). The polymorphisms rs242939 (CRHR1) and rs2270007 (CRHR2) were not in Hardy-Weinberg equilibrium. Only the rs242939 polymorphism (CRHR1) exhibited association with early response (three weeks) to fluoxetine (p-value = 0.043). No other association between outcomes and polymorphisms was observed. CONCLUSIONS: These results support the clinical relevance of low salivary cortisol levels as a predictor of antidepressant response, either to placebo or to fluoxetine. Only one polymorphism in the CRHR1 gene was associated with the early response. Other factors may be involved in antidepressant response, although further studies are needed to identify them. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12888-014-0220-0) contains supplementary material, which is available to authorized users. BioMed Central 2014-08-03 /pmc/articles/PMC4149200/ /pubmed/25086452 http://dx.doi.org/10.1186/s12888-014-0220-0 Text en © Ventura-Juncá et al., licensee BioMed Central Ltd. 2014 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 work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Ventura-Juncá, Raúl Symon, Adriana López, Pamela Fiedler, Jenny L Rojas, Graciela Heskia, Cristóbal Lara, Pamela Marín, Felipe Guajardo, Viviana Araya, A Verónica Sasso, Jaime Herrera, Luisa Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study |
title | Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study |
title_full | Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study |
title_fullStr | Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study |
title_full_unstemmed | Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study |
title_short | Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study |
title_sort | relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149200/ https://www.ncbi.nlm.nih.gov/pubmed/25086452 http://dx.doi.org/10.1186/s12888-014-0220-0 |
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