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  1. Article ; Online: Temporal associations between salivary cortisol and emotions in clinically depressed individuals and matched controls: A dynamic time warp analysis.

    Koning, Anne-Sophie C A M / Booij, Sanne H / Meijer, Onno C / Riese, Harriëtte / Giltay, Erik J

    Psychoneuroendocrinology

    2023  Volume 158, Page(s) 106394

    Abstract: Depression can be understood as a complex dynamic system where depressive symptoms interact with one another. Cortisol is suggested to play a major role in the pathophysiology of depression, but knowledge on the temporal interplay between cortisol and ... ...

    Abstract Depression can be understood as a complex dynamic system where depressive symptoms interact with one another. Cortisol is suggested to play a major role in the pathophysiology of depression, but knowledge on the temporal interplay between cortisol and depressive symptoms is scarce. We aimed to analyze the temporal connectivity between salivary cortisol and momentary affective states in depressed individuals and controls. Thirty pair-matched depressed and non-depressed participants completed questionnaires on momentary positive (PA) and negative (NA) affect and collected saliva three times a day for 30 days. The association between cortisol and affect was analyzed by dynamic time warp (DTW) analyses. These analyses involved lag-1 backward to lag-1 forward undirected analyses and lag-0 and lag-1 forward directed analyses. Large inter- and intra-individual variability in the networks were found. At the group level, with undirected analysis PA and NA were connected in the networks in depressed individuals and in controls. Directed analyses indicated that increases in cortisol preceded specific NA items in controls, but tended to follow upon specific affect items increase in depressed individuals. To conclude, at group level, changes in cortisol levels in individuals diagnosed with a depression may be a result of changes in affect, rather than a cause.
    MeSH term(s) Humans ; Depression/psychology ; Hydrocortisone/analysis ; Emotions ; Surveys and Questionnaires ; Saliva/chemistry
    Chemical Substances Hydrocortisone (WI4X0X7BPJ)
    Language English
    Publishing date 2023-09-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 197636-9
    ISSN 1873-3360 ; 0306-4530
    ISSN (online) 1873-3360
    ISSN 0306-4530
    DOI 10.1016/j.psyneuen.2023.106394
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1235: Show issues Location:
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  2. Article: Mineralocorticoid receptor status in the human brain after dexamethasone treatment: a single case study.

    Koning, Anne-Sophie C A M / Habets, Philippe C / Bogaards, Marit / Kroon, Jan / van Santen, Hanneke M / de Bont, Judith M / Meijer, Onno C

    Endocrine connections

    2022  Volume 11, Issue 3

    Abstract: Background: Synthetic glucocorticoids like dexamethasone can cause severe neuropsychiatric effects. They preferentially bind to the glucocorticoid receptor (GR) over the mineralocorticoid receptor (MR). High dosages result in strong GR activation but ... ...

    Abstract Background: Synthetic glucocorticoids like dexamethasone can cause severe neuropsychiatric effects. They preferentially bind to the glucocorticoid receptor (GR) over the mineralocorticoid receptor (MR). High dosages result in strong GR activation but likely also result in lower MR activation based on GR-mediated negative feedback on cortisol levels. Therefore, reduced MR activity may contribute to dexamethasone-induced neuropsychiatric symptoms.
    Objective: In this single case study, we evaluate whether dexamethasone leads to reduced MR activation in the human brain. Brain tissue of an 8-year-old brain tumor patient was used, who suffered chronically from dexamethasone-induced neuropsychiatric symptoms and deceased only hours after a high dose of dexamethasone.
    Main outcome measures: The efficacy of dexamethasone to induce MR activity was determined in HEK293T cells using a reporter construct. Subcellular localization of GR and MR was assessed in paraffin-embedded hippocampal tissue from the patient and two controls. In hippocampal tissue from the patient and eight controls, mRNA of MR/GR target genes was measured.
    Results: In vitro, dexamethasone stimulated MR with low efficacy and low potency. Immunofluorescence showed the presence of both GR and MR in the hippocampal cell nuclei after dexamethasone exposure. The putative MR target gene JDP2 was consistently expressed at relatively low levels in the dexamethasone-treated brain samples. Gene expression showed substantial variation in MR/GR target gene expression in two different hippocampus tissue blocks from the same patient.
    Conclusions: Dexamethasone may induce MR nuclear translocation in the human brain. Conclusions on in vivo effects on gene expression in the brain await the availability of more tissue of dexamethasone-treated patients.
    Language English
    Publishing date 2022-03-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2668428-7
    ISSN 2049-3614
    ISSN 2049-3614
    DOI 10.1530/EC-21-0425
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Neuropsychiatric adverse effects of synthetic glucocorticoids: A systematic review and meta-analysis.

    Koning, Anne-Sophie C A M / van der Meulen, Merel / Schaap, Daphne / Satoer, Djaina D / Vinkers, Christiaan H / van Rossum, Elisabeth F C / van Furth, Wouter R / Pereira, Alberto M / Meijer, Onno C / Dekkers, Olaf M

    The Journal of clinical endocrinology and metabolism

    2023  

    Abstract: Background: Synthetic glucocorticoids are widely used among patients suffering from a wide range of diseases. Glucocorticoids are very efficacious, but can be accompanied by neuropsychiatric adverse effects. This systematic review and meta-analysis ... ...

    Abstract Background: Synthetic glucocorticoids are widely used among patients suffering from a wide range of diseases. Glucocorticoids are very efficacious, but can be accompanied by neuropsychiatric adverse effects. This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids.
    Methods: Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and non-users were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model.
    Results: We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95%CI 14%-33%), 11% for mania (95%CI 2%-46%), 8% for anxiety (95%CI 2%-25%), 16% for delirium (95%CI 6%-36%), and 52% for behavioural changes (95%CI 42%-61%). Questionnaire scores for depression (SMD of 0.80 (95%CI 0.35-1.26)), and mania (0.78 (95%CI 0.14-1.42)) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use.
    Conclusions: The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed.
    Language English
    Publishing date 2023-12-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3029-6
    ISSN 1945-7197 ; 0021-972X
    ISSN (online) 1945-7197
    ISSN 0021-972X
    DOI 10.1210/clinem/dgad701
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Glucocorticoid and Mineralocorticoid Receptors in the Brain: A Transcriptional Perspective.

    Koning, Anne-Sophie C A M / Buurstede, Jacobus C / van Weert, Lisa T C M / Meijer, Onno C

    Journal of the Endocrine Society

    2019  Volume 3, Issue 10, Page(s) 1917–1930

    Abstract: Adrenal glucocorticoid hormones are crucial for maintenance of homeostasis and adaptation to stress. They act via the mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs)-members of the family of nuclear receptors. MRs and GRs can mediate ...

    Abstract Adrenal glucocorticoid hormones are crucial for maintenance of homeostasis and adaptation to stress. They act via the mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs)-members of the family of nuclear receptors. MRs and GRs can mediate distinct, sometimes opposite, effects of glucocorticoids. Both receptor types can mediate nongenomic steroid effects, but they are best understood as ligand-activated transcription factors. MR and GR protein structure is similar; the receptors can form heterodimers on the DNA at glucocorticoid response elements (GREs), and they share a number of target genes. The transcriptional basis for opposite effects on cellular physiology remains largely unknown, in particular with respect to MR-selective gene transcription. In this review, we discuss proven and potential mechanisms of transcriptional specificity for MRs and GRs. These include unique GR binding to "negative GREs," direct binding to other transcription factors, and binding to specific DNA sequences in conjunction with other transcription factors, as is the case for MRs and NeuroD proteins in the brain. MR- and GR-specific effects may also depend on specific interactions with transcriptional coregulators, downstream mediators of transcriptional receptor activity. Current data suggest that the relative importance of these mechanisms depends on the tissue and physiological context. Insight into these processes may not only allow a better understanding of homeostatic regulation but also the development of drugs that target specific aspects of disease.
    Language English
    Publishing date 2019-07-24
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2472-1972
    ISSN (online) 2472-1972
    DOI 10.1210/js.2019-00158
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Transcriptional glucocorticoid effects in the brain: Finding the relevant target genes.

    Meijer, Onno C / Buurstede, Jacobus C / Viho, Eva M G / Amaya, Jorge Miguel / Koning, Anne-Sophie C A M / van der Meulen, Merel / van Weert, Lisa T C M / Paul, Susana N / Kroon, Jan / Koorneef, Lisa L

    Journal of neuroendocrinology

    2022  Volume 35, Issue 2, Page(s) e13213

    Abstract: Glucocorticoids are powerful modulators of brain function. They act via mineralocorticoid and glucocorticoid receptors (MR and GR). These are best understood as transcription factors. Although many glucocorticoid effects depend on the modulation of gene ... ...

    Abstract Glucocorticoids are powerful modulators of brain function. They act via mineralocorticoid and glucocorticoid receptors (MR and GR). These are best understood as transcription factors. Although many glucocorticoid effects depend on the modulation of gene transcription, it is a major challenge to link gene expression to function given the large-scale, apparently pleiotropic genomic responses. The extensive sets of MR and GR target genes are highly specific per cell type, and the brain contains many different (neuronal and non-neuronal) cell types. Next to the set "trait" of cellular context, the "state" of other active signaling pathways will affect MR and GR transcriptional activity. Here, we discuss receptor specificity and contextual factors that determine the transcriptional outcome of MR/GR signaling, experimental possibilities offered by single-cell transcriptomics approaches, and reflect on how to make sense of lists of target genes in relation to understanding the functional effects of steroid receptor activation.
    MeSH term(s) Glucocorticoids/metabolism ; Receptors, Mineralocorticoid/metabolism ; Receptors, Glucocorticoid/metabolism ; Brain/metabolism ; Receptors, Steroid/metabolism ; Signal Transduction ; Hippocampus/metabolism
    Chemical Substances Glucocorticoids ; Receptors, Mineralocorticoid ; Receptors, Glucocorticoid ; Receptors, Steroid
    Language English
    Publishing date 2022-11-25
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1007517-3
    ISSN 1365-2826 ; 0953-8194
    ISSN (online) 1365-2826
    ISSN 0953-8194
    DOI 10.1111/jne.13213
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2634: Show issues Location:
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  6. Article ; Online: The DEXA-CORT trial: study protocol of a randomised placebo-controlled trial of hydrocortisone in patients with brain tumour on the prevention of neuropsychiatric adverse effects caused by perioperative dexamethasone.

    Koning, Anne-Sophie C A M / Satoer, Djaina D / Vinkers, Christiaan H / Zamanipoor Najafabadi, Amir H / Biermasz, Nienke R / Nandoe Tewarie, Rishi D S / Moojen, Wouter A / van Rossum, Elisabeth F C / Dirven, Clemens M F / Pereira, Alberto M / van Furth, Wouter R / Meijer, Onno C

    BMJ open

    2021  Volume 11, Issue 12, Page(s) e054405

    Abstract: Introduction: The synthetic glucocorticoid dexamethasone can induce serious neuropsychiatric adverse effects. Dexamethasone activates the glucocorticoid receptor (GR) but, unlike endogenous cortisol, not the mineralocorticoid receptor (MR). Moreover, ... ...

    Abstract Introduction: The synthetic glucocorticoid dexamethasone can induce serious neuropsychiatric adverse effects. Dexamethasone activates the glucocorticoid receptor (GR) but, unlike endogenous cortisol, not the mineralocorticoid receptor (MR). Moreover, dexamethasone suppresses cortisol production, thereby eliminating its MR binding. Consequently, GR overactivation combined with MR underactivation may contribute to the neuropsychiatric adverse effects of dexamethasone. The DEXA-CORT trial aims to reactivate the MR using cortisol to reduce neuropsychiatric adverse effects of dexamethasone treatment.
    Methods and analysis: The DEXA-CORT study is a multicentre, randomised, double-blind, placebo-controlled trial in adult patients who undergo elective brain tumour resection treated perioperatively with high doses of dexamethasone to minimise cerebral oedema. 180 patients are randomised between treatment with either two times per day 10 mg hydrocortisone or placebo during dexamethasone treatment. The primary study outcome is the difference in proportion of patients scoring ≥3 points on at least one of the Brief Psychiatric Rating Scale (BPRS) questions 5 days postoperatively or earlier at discharge. Secondary outcomes are neuropsychiatric symptoms, quality of sleep, health-related quality of life and neurocognitive functioning at several time points postoperatively. Furthermore, neuropsychiatric history, serious adverse events, prescribed (psychiatric) medication and referrals or evaluations of psychiatrist/psychologist and laboratory measurements are assessed.
    Ethics and dissemination: The study protocol has been approved by the Medical Research Ethics Committee of the Leiden University Medical Center, and by the Dutch competent authority, and by the Institutional Review Boards of the participating sites. It is an investigator-initiated study with financial support by The Netherlands Organisation for Health Research and Development (ZonMw) and the Dutch Brain Foundation. Results of the study will be submitted for publication in a peer-reviewed journal.
    Trial registration number: NL6726 (Netherlands Trial Register); open for patient inclusion. EudraCT number 2017-003705-17.
    MeSH term(s) Adult ; Humans ; Hydrocortisone/therapeutic use ; Quality of Life ; Glucocorticoids ; Double-Blind Method ; Dexamethasone/adverse effects ; Brain Neoplasms ; Treatment Outcome ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic
    Chemical Substances Hydrocortisone (WI4X0X7BPJ) ; Glucocorticoids ; Dexamethasone (7S5I7G3JQL)
    Language English
    Publishing date 2021-12-30
    Publishing country England
    Document type Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2021-054405
    Database MEDical Literature Analysis and Retrieval System OnLINE

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