Background Hypothalamic-pituitary-adrenal (HPA) axis function, as variously measured by the responses to the combined dexamethasone/corticotrophin-releasing hormone (dex/CRH) test, the dexamethasone suppression test (DST) and basal cortisol levels, has been reported to be abnormal in bipolar disorder.

Aims To test the hypothesis that HPA axis dysfunction persists in patients in remission from bipolar disorder.

Method Salivary cortisol levels and the plasma cortisol response to the DST and dex/CRH test were examined in 53 patients with bipolar disorder, 27 of whom fulfilled stringent criteria for remission, and in 28 healthy controls. Serum dexamethasone levels were measured.

Results Patients with bipolar disorder demonstrated an enhanced cortisol response to the dex/CRH test compared with controls ( P =0.001). This response did not differ significantly between remitted and non-remitted patients. These findings were present after the potentially confounding effects of dexamethasone levels were accounted for.

Conclusions The dex/CRH test is abnormal in both remitted and non-remitted patients with bipolar disorder. This measure of HPA axis dysfunction is a potential trait marker in bipolar disorder and thus possibly indicative of the core pathophysiological process in this illness.

/pdf/hypothalamic-pituitary-adrenal-axis-function-in-patients-3k6dzgfamm.pdf

Hypothalamic-pituitary-adrenal axis function in patients with bipolar disorder

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. We summarize own data and findings from the literature suggesting that (1) the neuroendocrine response to the combined dex/CRH test is elevated during a major depressive episode, but (2) tends to normalize after successful treatment. (3) Favorable response to antidepressant treatment can be predicted by determining the dex suppresser status on admission. For optimal prediction of non-response to antidepressant treatment, however, the results of a second dex/CRH test are necessary. These findings, together with the fact that impaired corticosteroid receptor signaling is considered as key mechanism of the pathogenesis in depression, support the suitability of the combined dex/CHR test as a surrogate marker for treatment response in depression. In conclusion, the combined dex/CRH test is a promising candidate to serve as a screening tool for the antidepressive effects of new compounds in clinical drug trials. Furthermore, the test appears to be capable of predicting the individual likelihood to respond to a current antidepressant treatment. If a drug treatment fails to normalize the outcome of the combined dex/CRH test, a change of the treatment strategy is recommended. Further systematic research is required and already ongoing to confirm the suitability of the combined dex/CRH test as a surrogate marker in depression.

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

The allostatic load (AL) model represents an interdisciplinary approach to comprehensively conceptualize and quantify chronic stress in relation to pathologies throughout the life cycle. This article first reviews the AL model, followed by interactions among early adversity, genetics, environmental toxins, as well as distinctions among sex, gender, and sex hormones as integral antecedents of AL. We next explore perspectives on severe mental illness, dementia, and caregiving as unique human models of AL that merit future investigations in the field of developmental psychopathology. A complimenting transdisciplinary perspective is applied throughout, whereby we argue that the AL model goes beyond traditional stress-disease theories toward the advancement of person-centered research and practice that promote not only physical health but also mental health.

/pdf/a-transdisciplinary-perspective-of-chronic-stress-in-24az4rvjc6.pdf

A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development

Major depressive disorder (MDD) is a global problem for which current pharmacotherapies are not completely effective. Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has long been associated with MDD; however, the value of assessing cortisol as a biological benchmark of the pathophysiology or treatment of MDD is still debated. In this review, we critically evaluate the relationship between HPA axis dysfunction and cortisol level in relation to MDD subtype, stress, gender and treatment regime, as well as in rodent models. We find that an elevated cortisol response to stress is associated with acute and severe, but not mild or atypical, forms of MDD. Furthermore, the increased incidence of MDD in females is associated with greater cortisol response variability rather than higher baseline levels of cortisol. Despite almost all current MDD treatments influencing cortisol levels, we could find no convincing relationship between cortisol level and therapeutic response in either a clinical or preclinical setting. Thus, we argue that the absolute level of cortisol is unreliable for predicting the efficacy of antidepressant treatment. We propose that future preclinical models should reliably produce exaggerated HPA axis responses to acute or chronic stress a priori, which may, or may not, alter baseline cortisol levels, while also modelling the core symptoms of MDD that can be targeted for reversal. Combining genetic and environmental risk factors in such a model, together with the interrogation of the resultant molecular, cellular, and behavioral changes, promises a new mechanistic understanding of MDD and focused therapeutic strategies.

/pdf/cortisol-and-major-depressive-disorder-translating-findings-5floe4tw7j.pdf

Cortisol and Major Depressive Disorder-Translating Findings From Humans to Animal Models and Back.

Depression has been linked to increased cortisol concentrations using point measures taken from urine, blood, or saliva samples. However, with regard to hypercortisolism-induced consequences, long-term cumulative cortisol burden is of relevance. Our objective was to use hair analysis as a new method to assess cortisol exposure over 6 months in depressed patients and healthy controls. We examined 23 depressed patients (8 men and 15 women, mean age: 41.6 years ( ± standard deviation (SD), 13.1 years); mean duration of current depressive episode 9 months ( ± SD, 13 months)) and 64 healthy controls, matched for age and gender. Cortisol concentrations in two 3-cm hair segments from near to the scalp were analyzed, representing cortisol secretion during the 6 months prior to sampling. Compared with healthy individuals, depressed patients had higher hair cortisol concentrations in the first (mean ± SD: 26.7 ± 20.8 vs. 18.7 ± 11.5 pg/mg, p < 0.05) and second hair segment (mean ±  SD: 21.9 ± 23.7 vs. 13.4 ± 9.6 pg/mg, p < 0.05). In conclusion, hair cortisol analysis confirmed enhanced cortisol secretion in depressed patients over a prolonged time period. Because of the retrospective and cumulative nature of cortisol in hair, the assessment of hair cortisol concentration may help in addressing unanswered questions regarding hypothalamic-pituitary-adrenal axis overactivity and associated health consequences in psychiatric disorders.

Introducing a novel method to assess cumulative steroid concentrations: Increased hair cortisol concentrations over 6 months in medicated patients with depression

Lithium augmentation increases the ACTH and cortisol response in the combined DEX/CRH test in unipolar major depression.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Christopher Baethge

Author Tools

Chat about Author

Papers

Lithium augmentation increases the ACTH and cortisol response in the combined DEX/CRH test in unipolar major depression.