Autonomous Cortisol Secretion Influences Psychopathological Symptoms in Patients With Primary Aldosteronism.

Context: Primary aldosteronism (PA) is associated with impaired quality of life (QoL). Autonomous cortisol cosecretion (ACS) is a relevant phenotype of PA, which could contribute to depression and anxiety disorders. This has not been investigated so far.

Cost-Effectiveness of Screening for Primary Aldosteronism and Subtype Diagnosis in the Resistant Hypertensive Patients.

Background: Primary aldosteronism (PA) is a common and underdiagnosed disease with significant morbidity potentially cured by surgery. We aim to assess if the long-term cardiovascular benefits of identifying and treating surgically correctable PA outweigh the upfront increased costs in patients at the time patients are diagnosed with resistant hypertension (RH).

Methods And Results: A decision-analytic model compares aggregate costs and systolic blood pressure changes of 6 recommended or implemented diagnostic strategies for PA in a simulated population of at-risk RH patients.

Quality of life in patients with primary aldosteronism: gender differences in untreated and long-term treated patients and associations with treatment and aldosterone.

Psychopathological symptoms in patients with primary aldosteronism (PA) have been reported. In a cross-sectional design the self-reported physical and mental condition among patients with PA of the German Conn's Registry differently treated during the course of the disease were analysed. 27 patients were investigated before initiation of specific therapy (U), 56 patients were on chronic mineralocorticoid antagonist treatment (MRA) and 49 patients had undergone adrenalectomy (ADX).

Gender differences in anxiety and depressive symptoms in patients with primary hyperaldosteronism: a cross-sectional study.

Objective: The renin-angiotensin-aldosterone-system (RAAS) has gained increasing attention in the investigation of the pathogenesis of depression. Primary hyperaldosteronism (PA) is associated with a marked aldosterone excess. Prior studies on PA describe an increased prevalence of anxiety and sub-threshold depressive symptoms in these patients.

Changes in the sleep electroencephalogram (EEG) during male to female transgender therapy.

Steroids, including estrogens, participate in sleep regulation. For example estrogen replacement therapy improved sleep quality in postmenopausal women. Patients, who undergo a cross-gender hormone therapy, receive high doses of estrogens.

Outcome in delusional depression comparing trimipramine monotherapy with a combination of amitriptyline and haloperidol--a double-blind multicenter trial.

Background: Patients with delusional depression are difficult to treat. The atypical antidepressant trimipramine was effective in a previous 4-week open label pilot study in patients with this disorder. The major neurobiological effect of trimipramine is the inhibition of the hypothalamic-pituitary-adrenocortical (HPA) system.

Changes in the hypothalamic-pituitary-adrenal axis and leptin levels during antidepressant treatment.

Background: In depressed patients, overstimulation of the hypothalamo-pituitary-adrenocortical (HPA) system, probably caused by glucocorticoid receptor resistance, is the most consistent neurobiological finding. Glucocorticoids themselves are reported to increase leptin synthesis and secretion in humans.

Methods: We examined alterations in plasma levels of leptin as well as changes in the HPA system function using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test on admission and at discharge in 74 depressed inpatients.

High-affinity CRF1 receptor antagonist NBI-34041: preclinical and clinical data suggest safety and efficacy in attenuating elevated stress response.

There is an extensive evidence that corticotropin releasing factor (CRF) is hypersecreted in depression and anxiety, and blockade of CRF could have therapeutic benefit. We report preclinical data and the results of a clinical Phase I study with the novel nonpeptide CRF(1) antagonist NBI-34041/SB723620. Preclinical data conducted with different cell lines expressing human CRF receptors and in Wistar and Sprague-Dawley rats indicate that NBI-34041 is effective in reducing endocrine responses to pharmacological and behavioral challenge mediated by CRF(1) receptors.

Combined dexamethasone/corticotropin releasing hormone test predicts treatment response in major depression - a potential biomarker?

Background: Exaggerated corticotropin (ACTH) and cortisol response to the combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test, indicating impaired regulation of the hypothalamus-pituitary-adrenocortical (HPA) system, is frequently observed in depression. In the present study, we examined whether change in HPA system function during the first weeks of hospitalization predicts response to antidepressant treatment in major depression and thus constitutes a potential biomarker.

Methods: We conducted the DEX/CRH test in 50 inpatients suffering from severe major depression, once after study inclusion and a second time 2 to 3 weeks later while under continuous antidepressant treatment.

Increased nocturnal secretion of ACTH and cortisol in obsessive compulsive disorder.

Information on the function of the hypothalamic-pituitary-adrenal (HPA) axis, the main mammalian system of stress response, in obsessive compulsive disorder (OCD) is inconsistent. In this study, nine inpatients with a DSM-IV diagnosis of OCD without comorbid major depression (Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score >15; HAMD-21 total score 16) and nine healthy matched controls were included. Blood of patients (seven males; 31.

Successful antidepressant therapy restores the disturbed interplay between TNF-alpha system and HPA axis.

Background: In depressed patients, alterations in the hypothalamo-pituitary-adrenocortical (HPA) system are the most consistent neurobiological finding. HPA axis activity and cytokines are intrinsically intertwined: inflammatory cytokines stimulate adrenocorticotropic hormone (ACTH) and cortisol secretion, while, in turn, glucocorticoids suppress the synthesis of proinflammatory cytokines.

Methods: We examined alterations in plasma levels of tumor necrosis factor-alpha (TNF-alpha), levels of its soluble receptors p55 (sTNF-R p55) and p75 (sTNF-R p75) as well as changes in the HPA system function using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test on admission and at discharge in 70 depressed inpatients without inflammation.

The combined dexamethasone/CRH test as a potential surrogate marker in depression.

There is compelling evidence that impaired corticosteroid receptor function is the key mechanism in the pathogenesis of depression resulting in a dysfunctional stress hormone regulation, which can be most sensitively detected with the combined dexamethasone (dex)/corticotropin releasing hormone (CRH) test. Treatment with different kinds of antidepressants is associated with a reduction of the hormonal responses to the combined dex/CRH test suggesting normalization of impaired corticosteroid receptor signaling as the final common pathway of these drugs. Consequently, the combined dex/CRH test is suggested as a screening tool to decide whether new compounds designed as antidepressants provide sufficient efficacy to normalize corticoid receptor signaling in depressed patients.

Ghrelin plasma levels during psychopharmacological treatment.

The mechanisms underlying weight gain induced by psychopharmacological agents are poorly understood. Because the recently discovered enteric hormone, ghrelin, stimulates food intake, we hypothesized that increases in circulating ghrelin levels might mediate the weight gain caused by certain antidepressants and atypical antipsychotic drugs. Fifty-two patients receiving psychopharmacological treatments were included in the study: 16 patients received antidepressants that are not known to induce weight gain, and 13 patients received mirtazapine or trimipramine, which are antidepressants known to lead to weight gain; 6 patients received clozapine and olanzapine, which have the highest liability among the antipsychotics to cause weight gain, and 17 patients received other antipsychotics.

Treatment with a CRH-1-receptor antagonist (R121919) does not affect weight or plasma leptin concentration in patients with major depression.

Weight gain during treatment with psychotropic drugs is frequently observed and is assumed to be responsible for non-compliance and for an elevated risk to develop a number of somatic co-morbidities including cardiovascular disorders and type 2 diabetes. Absence of weight inducing effects is therefore a major objective for the development of new compounds. Recently, R121919, the first corticotropin releasing hormone receptor 1 (CRH1R) antagonist, was tested in major depression.

Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment.

The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples.

Treatment of depression with the CRH-1-receptor antagonist R121919: endocrine changes and side effects.

A dysregulation of the hypothalamus-pituitary-adrenocortical (HPA) system has been hypothesized to account for a myriad of cardinal symptoms of affective disorders. Specifically, increased CRH signalling via CRH type 1 receptors is thought to be an important factor in the pathogenesis of major depression and anxiety disorders. Consequently, a number of drugs have been developed in order to target the postulated increase in CRH/CRH 1 receptor signalling.