Glucocorticoids as Predictors of Treatment Response in Depression

Horstmann, Sonja; Binder, Elisabeth B.

doi:10.3109/10673229.2011.586550

Cited by 25 publications

(15 citation statements)

References 153 publications

(114 reference statements)

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“…Moreover, they also found associations of the same marker with the antidepressant response, faster response to antidepressant treatment, lower activity of the HPA axis during a depressive episode, and a higher recurrence of depressive episodes in their lifetime, with an over-representation of T/T homozygotes among the responders [93]. These results have been replicated in some studies [81], but not in others [94]. The causes of this discrepancy may reside in genetic differences in the ethnic populations tested, lifetime recurrence of depressive episodes, or differences in the phenotypes and drugs used.…”

Section: Genetic Differences Influence Responses To Antidepressantsmentioning

confidence: 85%

“…Although the most common antidepressants target the monoaminergic systems, they also decrease HPA axis hyperactivity, alleviating depressive symptoms (reviewed in [81]). The effects of antidepressants on monoamine levels are exerted rapidly, within few hours; however, the therapeutic response is only observed several weeks after the initiation of treatment.…”

Section: Genetic Differences Influence Responses To Antidepressantsmentioning

confidence: 99%

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Sex, Stress, and Mood Disorders: At the Intersection of Adrenal and Gonadal Hormones

et al. 2012

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The risk for neuropsychiatric illnesses has a strong sex bias, and for major depressive disorder (MDD), females show a more than 2-fold greater risk compared to males. Such mood disorders are commonly associated with a dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. Thus, sex differences in the incidence of MDD may be related with the levels of gonadal steroid hormone in adulthood or during early development as well as with the sex differences in HPA axis function. In rodents, organizational and activational effects of gonadal steroid hormones have been described for the regulation of HPA axis function and, if consistent with humans, this may underlie the increased risk of mood disorders in women. Other developmental factors, such as prenatal stress and prenatal overexposure to glucocorticoids can also impact behaviors and neuroendocrine responses to stress in adulthood and these effects are also reported to occur with sex differences. Similarly, in humans, the clinical benefits of antidepressants are associated with the normalization of the dysregulated HPA axis, and genetic polymorphisms have been found in some genes involved in controlling the stress response. This review examines some potential factors contributing to the sex difference in the risk of affective disorders with a focus on adrenal and gonadal hormones as potential modulators. Genetic and environmental factors that contribute to individual risk for affective disorders are also described. Ultimately, future treatment strategies for depression should consider all of these biological elements in their design.

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Section: Genetic Differences Influence Responses To Antidepressantsmentioning

confidence: 85%

Section: Genetic Differences Influence Responses To Antidepressantsmentioning

confidence: 99%

Sex, Stress, and Mood Disorders: At the Intersection of Adrenal and Gonadal Hormones

et al. 2012

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“…The most common antidepressants currently available, including fluoxetine (FLX), are targeted to the monoaminergic systems [5,6]. The effects of antidepressants on monoamines are observed within a few hours.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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BackgroundIncreased 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.MethodsThe 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 < 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.Results208 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.ConclusionsThese 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 materialThe online version of this article (doi:10.1186/s12888-014-0220-0) contains supplementary material, which is available to authorized users.

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“…The vast majority of these studies have been conducted in the context of antidepressant medications (Young et al, 2004; Horstmann and Binder, 2011), but several studies have also observed an association between pretreatment cortisol levels and posttreatment outcomes following a psychosocial intervention (Bockting et al, 2006; Jason et al, 2008; Yehuda et al, 2009; Otto et al, 2010; Bockting et al, 2012). In particular, some preliminary evidence suggests that hypercortisolism predicts poorer response to CBT (Thase et al, 1993; Thase et al, 1996; Thase and Friedman, 1999).…”

Section: Introductionmentioning

confidence: 99%

Pretreatment cortisol levels predict posttreatment outcomes among older adults with depression in cognitive behavioral therapy

Holland

Schatzberg

O’Hara

et al. 2013

Psychiatry Research

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Previous studies suggest that individuals with elevated levels of cortisol (the “stress hormone”) could be particularly resistant to treatment for depression. However, most of these studies have been conducted in the context of antidepressant medications, and no study has examined pretreatment cortisol levels as a predictor of treatment outcomes among older adults with depression in cognitive-behavioral therapy (CBT), despite the relevance of this population for such a research question. The current study includes 54 older adults with depression who provided salivary cortisol samples at baseline and completed measures of depression at pretreatment and posttreatment, following a 12-week course of CBT. Structural equation modeling results suggest that those with higher daily outputs of cortisol and flatter diurnal slopes were less likely to benefit from CBT—a finding which if replicated could have important implications for clinical practice and future research.

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Glucocorticoids as Predictors of Treatment Response in Depression

Abstract: The glucocorticoid system is potentially of great use in predicting antidepressant response. New combinations of biomarkers including these measures should be tested to develop clinically relevant predictors.

Cited by 25 publications

References 153 publications

Sex, Stress, and Mood Disorders: At the Intersection of Adrenal and Gonadal Hormones

Sex, Stress, and Mood Disorders: At the Intersection of Adrenal and Gonadal Hormones

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

Pretreatment cortisol levels predict posttreatment outcomes among older adults with depression in cognitive behavioral therapy

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