Trial reportPsychoneuroendocrinology2021
Glucocorticoid ultradian rhythmicity differentially regulates mood and resting state networks in the human brain: A randomised controlled clinical trial.
Trial report in Psychoneuroendocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Neuroscience meets behavior: A systematic literature review on magnetic resonance imaging of the brain combined with real-world digital phenotyping.Human brain mapping · 2024Pooled it
- Comparison of adrenalectomy with conservative treatment on mild autonomous cortisol secretion: a systematic review and meta-analysis.Frontiers in endocrinology · 2024Pooled it
- Effects of Cortisol Administration on Resting-State Functional Connectivity in Women with Depression.Psychiatry research. Neuroimaging · 2024Trial
- Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial.Journal of internal medicine · 2024Trial
- Influence of the HPA Axis on Anxiety-Related Processes: An RDoC Overview Considering Their Neural Correlates.Current psychiatry reports · 2025Review
- Coping with the multifaceted and multifunctional role of cortisol in the brain.Neuroscience applied · 2024Review
- How an appreciation of dynamics has altered our understanding of the HPA axis.Stress (Amsterdam, Netherlands) · 2024Article
- Brain structure in autoimmune Addison's disease.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- The role of the hypothalamic-pituitary-adrenal axis in depression across the female reproductive lifecycle: current knowledge and future directions.Frontiers in endocrinology · 2023Review
- Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation.Neurobiology of stress · 2023Article
- Depressive and anxiety disorders and antidepressant prescriptions among insured children and young adults with congenital adrenal hyperplasia in the United States.Frontiers in endocrinology · 2023Article
- Role of microRNAs and long non‑coding RNAs in glucocorticoid signaling (Review).International journal of molecular medicine · 2022Review
- Modelling Hydrocortisone Pharmacokinetics on a Subcutaneous Pulsatile Infusion Replacement Strategy in Patients with Adrenocortical Insufficiency.Pharmaceutics · 2021Article
- Efficacy of Treatments Targeting Hypothalamic-Pituitary-Adrenal Systems for Major Depressive Disorder: A Meta-Analysis.Frontiers in pharmacology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Adrenal glucocorticoid secretion into the systematic circulation is characterised by a complex rhythm, composed of the diurnal variation, formed by changes in pulse amplitude of an underlying ultradian rhythm of short duration hormonal pulses. To elucidate the potential neurobiological significance of glucocorticoid pulsatility in man, we have conducted a randomised, double-blind, placebo-controlled, three-way crossover clinical trial on 15 healthy volunteers, investigating the impact of different glucocorticoid rhythms on measures of mood and neural activity under resting conditions by recruiting functional neuroimaging, computerised behavioural tests and ecological momentary assessments. Endogenous glucocorticoid biosynthesis was pharmacologically suppressed, and plasma levels of corticosteroid restored by hydrocortisone replacement in three different regimes, either mimicking the normal ultradian and circadian profile of the hormone, or retaining the normal circadian but abolishing the ultradian rhythm of the hormone, or by our current best oral replacement regime which results in a suboptimal circadian and ultradian rhythm. Our results indicate that changes in the temporal mode of glucocorticoid replacement impact (i) the morning levels of self-perceived vigour, fatigue and concentration, (ii) the diurnal pattern of mood variation, (iii) the within-network functional connectivity of various large-scale resting state networks of the human brain, (iv) the functional connectivity of the default-mode, salience and executive control networks with glucocorticoid-sensitive nodes of the corticolimbic system, and (v) the functional relationship between mood variation and underlying neural networks. The findings indicate that the pattern of the ultradian glucocorticoid rhythm could affect cognitive psychophysiology under non-stressful conditions and opens new pathways for our understanding on the neuropsychological effects of cortisol pulsatility with relevance to the goal of optimising glucocorticoid replacement strategies.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.