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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.

ABSTRACT: 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-D17), 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-D17 score reductions of at least 25% and to?

SUBMITTER: Ventura-Junca R

PROVIDER: S-EPMC4149200 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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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.

Ventura-Juncá Raúl R Symon Adriana A López Pamela P Fiedler Jenny L JL Rojas Graciela G Heskia Cristóbal C Lara Pamela P Marín Felipe F Guajardo Viviana V Araya A Verónica AV Sasso Jaime J Herrera Luisa L

BMC psychiatry 20140803

<h4>Background</h4>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.<h4>Methods</h4>The diagnosis and severity of depression were performed using the ...[more]

PMID: 25086452

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Project description:OBJECTIVES:To evaluate the short-term efficacy and safety of desvenlafaxine (25-50 mg/d) compared with placebo in children and adolescents with major depressive disorder (MDD). METHODS:Outpatient children (7-11 years) and adolescents (12-17 years) who met DSM-IV-TR criteria for MDD and had screening and baseline Children's Depression Rating Scale-Revised (CDRS-R) total scores >40 were randomly assigned to 8-week treatment with placebo, desvenlafaxine (25, 35, or 50 mg/d based on baseline weight), or fluoxetine (20 mg/d). The primary efficacy endpoint was change from baseline in CDRS-R total score at week 8, analyzed using a mixed-effects model for repeated measures. Secondary efficacy endpoints included week 8 Clinical Global Impressions-Severity, Clinical Global Impressions-Improvement (CGI-I), and response (CGI-I ≤ 2). Safety assessments included adverse events, physical and vital sign measurements, laboratory evaluations, electrocardiogram, and the Columbia-Suicide Severity Rating Scale. RESULTS:The safety population included 339 patients (children, n = 130; adolescents, n = 209). The primary endpoint, change from baseline in CDRS-R total score at week 8, did not statistically separate from placebo, for either desvenlafaxine (adjusted mean [standard error] change, -22.6 [1.17]) or fluoxetine (-24.8 [1.17]; placebo, -23.1 [1.18]). Week 8 CGI-I response rates were significantly greater for fluoxetine (78.2%; p = 0.017) than for placebo (62.6%); desvenlafaxine (68.7%) did not differ from placebo. Other secondary outcomes were consistent with those obtained with CDRS-R. Rates of treatment-emergent adverse events were comparable among treatment groups (desvenlafaxine, 60.0%; placebo, 70.5%; and fluoxetine, 64.3%). CONCLUSION:Desvenlafaxine did not demonstrate efficacy for treating MDD in children and adolescents in this trial. Because neither desvenlafaxine nor the reference medication, fluoxetine, demonstrated a statistically significant difference from placebo on the primary endpoint, this was considered a failed trial and no efficacy conclusions can be drawn. Desvenlafaxine 25-50 mg/d was generally safe and well tolerated in children and adolescents in this study.

Project description:BackgroundStudies testing the relationship between cortisol levels, depression, and antidepressant treatment response have yielded divergent results suggesting the possibility of moderators of a cortisol effect. Several studies indicate that age may moderate the relationship between cortisol and depression. In patients with Major Depressive Disorder (MDD), we studied the interactive effects of age and cortisol in association with MDD diagnostic status and mood and memory response to antidepressant treatment.MethodsSerum cortisol levels in 66 unmedicated patients with MDD and 75 matched healthy controls (HC) were measured at baseline and retrospectively analyzed. Logistic regression was used to determine an association of age, cortisol and their interaction with MDD diagnosis in the pooled sample of MDD and HC participants. Thirty-four of the MDD participants (age range: 19-65 years; median: 36) underwent treatment with a selective serotonin reuptake inhibitor (SSRl) for 8 weeks. Clinician and self-ratings of depression symptoms, as well as tests of verbal and visual delayed recall were obtained at baseline and post treatment. Moderation analyses determined the effect of age on the relationship between baseline cortisol and treatment outcome.ResultsCortisol, moderated by age, was associated with MDD diagnosis (p < .05), treatment-associated reduction of depression symptoms (p < .001) and improvement of delayed recall (p < .001). Modeling the Cortisol × Age interaction suggested that for participants below the median age of our sample, lower cortisol levels were associated with a lower rate of MDD diagnosis and higher antidepressant effects. On the contrary, in those above the median sample age, lower cortisol was associated with a higher rate of MDD and less improvement in depression symptoms and memory performance.ConclusionsOur results add to the body of literature suggesting that age might be an important factor in moderating the relationship between peripheral cortisol levels, depression, cognition, and prognosis. These results indicate that previous disparities in the literature linking peripheral cortisol levels with depression characteristics and treatment response may critically relate, at least in part, to the age of the participants studied.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Dataset Information

Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study.

Publications

Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study.

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