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Florian Holsboer - One of the best experts on this subject based on the ideXlab platform.
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Hypothalamic-Pituitary-Adrenocortical Dysfunction in Elderly, Male Marathon Runners: Feedback Sensitivity, Stress Response, and Effects on Verbal Memory.
Neuroendocrinology, 2016Co-Authors: Michael Deuschle, Florian Holsboer, Ulrike Gotthardt, Ulrich Schweiger, Michael Dettling, Isabella HeuserAbstract:Animal studies suggest that repeated episodes of elevated glucocorticoids lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) System at a suprapituitary level, and to impaired mnemonic
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Suppressive effect of mirtazapine on the HPA System in acutely depressed women seems to be transient and not related to antidepressant action
Psychoneuroendocrinology, 2008Co-Authors: Sonja Horstmann, T. Dose, Susanne Lucae, Stefan Kloiber, Andreas Menke, Johannes Hennings, Derek Spieler, Florian Holsboer, Marcus IsingAbstract:Summary Impaired regulation of the hypothalamus–pituitary–adrenocortical (HPA) System is a consistent finding among patients with depression, which can be most sensitively detected with the combined dexamethasone (dex)/corticotrophin releasing hormone (CRH) test. The majority of patients with acute depression shows an exaggerated plasma corticotrophin (ACTH) and cortisol response to this test that normalizes gradually during successful antidepressant therapy. In contrast, persistently high HPA-responses to this challenge are prognostically less favorable. It has been recently questioned, whether this observation applies also to treatment with the atypical antidepressant mirtazapine, as patients treated with this drug showed a distinct attenuation of the endocrine response to the dex/CRH test already after 1 week of treatment. In the present study, we investigated whether the attenuating effect of mirtazapine on the HPA System is an acute pharmacological reaction disappearing after physiological adaptation or whether this effect is related to the antidepressant action of the drug. We examined plasma ACTH and cortisol responses to the dex/CRH test in acutely depressed inpatients treated either with mirtazapine ( n = 55) or a monoamine reuptake inhibitor ( n = 105) according to doctor’s choice and compared the test results with healthy controls ( n = 40). Patients treated with monoamine reuptake inhibitors received either selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA) or the combined serotonin and noradrenalin reuptake inhibitor venlafaxine. We found increased plasma ACTH and cortisol responses to the dex/CRH test in depressed patients compared with healthy controls, but also significantly ( p = .017) attenuated plasma cortisol secretion in the mirtazapine group compared to the group of monoamine reuptake inhibitor treated patients. This effect was not significant in male patients. Furthermore this effect was independent of the psychopathological state, but depended on treatment duration. Patient treatment with mirtazapine for up to 7 days resulted in dex/CRH test outcome that was indistinguishable from controls. This effect, however waned as it was not observable in patients treated for a longer period. These results suggest that short-term administration of mirtazapine has immediate but only transient suppressive effects on the HPA System predominantly in women. Our results confirm that dex/CRH tests can be used as predictors of clinical course also under mirtazapine treatment.
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Blunted ACTH response to dexamethasone suppression-CRH stimulation in posttraumatic stress disorder.
Journal of Psychiatric Research, 2008Co-Authors: Andreas Strohle, Sieglinde Modell, Michael Scheel, Florian HolsboerAbstract:Abstract Previous studies have suggested that patients with posttraumatic stress disorder (PTSD) have an enhanced negative feedback sensitivity of the hypothalamic–pituitary–adrenal (HPA) System and a blunted ACTH response to corticotropin releasing hormone (CRH). The effects of two dexamethasone dosages (0.75 and 1.5 mg) on the ACTH and cortisol concentrations after CRH stimulation (100 μg) were studied in eight patients with PTSD and matched healthy control subjects. Compared to healthy subjects, patients with PTSD have a blunted ACTH response to CRH. Cortisol concentrations were only significantly influenced by dexamethasone dosage. Our results give further evidence for a central role of the pituitary in reflecting changes of the negative feedback sensitivity of the HPA System in patients with PTSD.
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persistent cognitive impairment in depression the role of psychopathology and altered hypothalamic pituitary adrenocortical HPA System regulation
Biological Psychiatry, 2007Co-Authors: Simone Reppermund, Susanne Lucae, Stefan Kloiber, Sonja Horstmann, Florian Holsboer, Josef Zihl, Marcus IsingAbstract:Background Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) System and cognitive impairment are consistent findings in depression. This study examines the associations between HPA System regulation, cognitive functioning, and psychopathology in depressed inpatients on admission and at discharge. Methods The HPA System dysregulation was evaluated with the dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test. Cognitive assessment included speed of information processing, divided and selective attention, as well as short-term and working memory. Psychopathology was evaluated with the Hamilton Rating Scale for Depression (HAMD). Data from 75 depressed inpatients are reported, 51 (68%) of them achieved remission. Results Despite a significant reduction of depressive symptoms between admission and discharge, a high rate of patients remained cognitively impaired. Selective attention improved significantly in remitters and nonremitters, while speed of information processing increased only in remitters. The cortisol response to the DEX/CRH test decreased significantly only in remitters, which was uncorrelated with cognitive performance. In nonremitters, severity of depression was significantly correlated with information processing time while improvement in short-term memory was negatively associated with the cortisol response at discharge. Conclusions Our data support the assumption that psychopathological symptoms and the HPA System dysregulation can be dissociated in their impact on cognitive functioning in depressed patients.
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Changes in the Hypothalamic-Pituitary-Adrenal Axis and Leptin Levels during Antidepressant Treatment
Neuropsychobiology, 2007Co-Authors: Hubertus Himmerich, Susanne Lucae, Stefan Kloiber, Marcus Ising, Elisabeth B. Binder, Heike E. Künzel, Petra Zimmermann, Florian HolsboerAbstract:Background: In depressed patients, overstimulation of the hypothalamo-pituitary-adrenocortical (HPA) System, probably caused by glucocorticoid receptor resistance, is the most consi
Isabella Heuser - One of the best experts on this subject based on the ideXlab platform.
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Hypothalamic-Pituitary-Adrenocortical Dysfunction in Elderly, Male Marathon Runners: Feedback Sensitivity, Stress Response, and Effects on Verbal Memory.
Neuroendocrinology, 2016Co-Authors: Michael Deuschle, Florian Holsboer, Ulrike Gotthardt, Ulrich Schweiger, Michael Dettling, Isabella HeuserAbstract:Animal studies suggest that repeated episodes of elevated glucocorticoids lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) System at a suprapituitary level, and to impaired mnemonic
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HPA System activity in alexithymia a cortisol awakening response study
Psychoneuroendocrinology, 2013Co-Authors: Elif Alkan Hartwig, Sabine Aust, Isabella HeuserAbstract:Summary Objectives: Alexithymia is a personality trait characterized by difficulties in identifying, describing and communicating one’s own emotions. It is also associated with several stress-related psychiatric disorders. The aim of the study was to examine the cortisol awakening response (CAR) as a measure of HPA-System function in a community based sample of psychologically and physically healthy adults with alexithymia. Methods: Fourty-one high alexithymic individuals and thirty-seven low alexithymic subjects, well-controlled regarding gender, age and sociodemographic status, provided three saliva cortisol samples each day for three consecutive days for the calculation of mean CAR. Participants filled out questionnaires on alexithymia (TAS-20, BVAQ) and interpersonal reactivity (IRI) prior to cortisol assessment. Results: The mean CAR of three sampling days was significantly lower in the alexithymic group in comparison to control participants. Additionally there was a negative correlation between CAR and perceived stress, which points to lower CAR in alexithymia accompanied by higher perceived stress in socio-emotional situations. CAR was negatively correlated with age in the alexithymic group, indicating to alterations in HPA System over longer time to stress exposure. Conclusion: Alexithymic individuals have a lower CAR. Hence the results of the present study indicate that certain aspects of personality modulate HPA-System functioning.
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Insulin-like growth factor-I (IGF-I) serum concentrations in depressed patients: relationship to saliva cortisol and changes during antidepressant treatment.
Pharmacopsychiatry, 2009Co-Authors: Bettina Weber-hamann, Isabella Heuser, Maria Gilles, Werner F. Blum, Kratzsch J, Michael DeuschleAbstract:INTRODUCTION: The present study was designed to test the hypothesis that total and free insulin-like growth factor-I (IGF-I) serum concentrations in depressed patients are related to hypothalamus-pituitary-adrenal (HPA) System activity and show a longitudinal decline in patients responding to treatment as well as to declining HPA System activity. METHODS: We measured total and free IGF-I as well as IGF-binding protein-3 in 77 depressed patients after wash-out of pre-medication and again after 28 or 35 days of treatment with paroxetine or amitriptyline. RESULTS: Total but not free IGF-I serum concentrations are related to saliva cortisol concentrations in drug-free depressed patients. In responders to both amitriptyline and paroxetine, total IGF-I serum concentrations declined during treatment. DISCUSSION: Our findings show IGF-I to be related to HPA System activity and to decline in responders to treatment while serum concentrations of the biologically active free IGF-I are neither related to HPA System activity nor do they change during the course of treatment. Our data do not support the hypothesis that free IGF-I may play a major role in physical disturbances in depressed patients.
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hippocampal volume reduction and HPA System activity in major depression
Journal of Psychiatric Research, 2007Co-Authors: Michael Colla, Michael Deuschle, Golo Kronenberg, Kornelia Meichel, T Hagen, Markus Bohrer, Isabella HeuserAbstract:Abstract Structural imaging studies investigating hippocampal volumes in patients suffering from major depression have yielded mixed results. Here, 24 unipolar depressed in-patients and 14 healthy controls carefully matched for age, gender, and years of education underwent quantitative magnetic resonance imaging (MRI). Saliva cortisol was measured at 0800 and 1600 h in patients during a one-week wash-out and the following 4 weeks. Hippocampal volumes were significantly reduced in the patient group even after adjusting for intracranial brain volume (ICV) and age. Across groups, age was significantly negatively correlated with uncorrected hippocampal volumes. In patients, severity of disease (baseline HAMD scores) and baseline cortisol levels were not related to hippocampal volumes. However, there was a negative association between duration of the index episode before hospitalization and hippocampal volumes. Additionally, hippocampal volumes were significantly negatively correlated with duration of illness. Finally, we observed a trend for higher hippocampal volumes in those patients who showed a subsequent decrease in cortisol levels under pharmacotherapy.
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The Hypothalamic-Pituitary-Adrenal System in Depression
Pharmacopsychiatry, 2007Co-Authors: Isabella HeuserAbstract:: Patients with depression frequently have symptom clusters which point strongly to involvement of the hypothalamic-pituitary-adrenal (HPA) System as a relay station between neurocircuitries in the brain and peripheral hormone and autonomic nervous function. It has been proposed that this increased, state-dependent hyperactivity of the HPA-System in depression is probably initiated and/or maintained by the combination of enhanced central production of CRH and desensitization of the binary, glucocorticoid receptor binding System in the hippocampus, which is the central regulator of HPA System activity. In a first series of studies a refined neuroendocrine test to probe the integrity of HPA System status--the combined dexamethasone suppression/CRH challenge (DEX/CRH) test--was developed and the differential effects of aging and depressed psychopathology on DEX/CRH test outcome were described. In a second set of studies, the chronological relationship between improvement of psychopathology in depressed patients treated with antidepressants and normalization of the disturbed HPA System function in these patients was further elucidated. Given the evidence from animal studies, we conclude that antidepressants induce an up-regulation of hippocampal glucocorticoid receptor mRNA concentration, thus amplifying the negative feedback effect of glucocorticoids. This then results in the normalization of DEX/CRH test results observed in the depressed patients in our study. We further conclude that dampening of HPA System hyperactivity in depression by means of antidepressants is a conditio sine qua non for successful improvement of psychopathology.
Marcus Ising - One of the best experts on this subject based on the ideXlab platform.
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The influence of psychosocial stress on HPA System regulation and cognitive performance in patients recovered from depression
European Journal of Psychotraumatology, 2012Co-Authors: Claudia Lange, Marcus Ising, Felix Bermpohl, Mazda AdliAbstract:Rationale/statement of the problem : Despite numerous studies on the influence of psychosocial stress on hypothalamic-pituitary-adrenal axis (HPA) System responsivity, heterogeneous results have been found with regard to depression in remission. In addition, knowledge concerning cognitive functioning in the remitted state is also narrow showing thus far inconsistent results. The present study investigated the effect of psychosocial stress on the cortisol response and cognitive performance in patients recovered from depression in comparison to healthy controls. Methods : Eighty patients who have recovered from depression for at least 6 months (average: 31 months) and 80 healthy matched controls were investigated on the effects of psychosocial stress (TSST) on the performance in an affective go/nogo task. Cortisol responses, behavioral inhibition, reaction time performance and emotional-cognitive functioning were analyzed. We hypothesized that stress vulnerability of cognitive performance is positively correlated to HPA System responsiveness (measured by salivary cortisol) in both healthy subjects and remitted patients but larger in remitted patients compared to healthy controls. Results : Thus far, preliminary analyses reveal no abnormal stress-associated HPA System response in patients recovered from depression in comparison to healthy controls. However, remitted patients showed impaired attentional set shifting in the go/nogo task. This impairment was positively correlated with the duration of illness. Conclusion : Our study is the first to investigate affective go/nogo task performance and effects of a stress challenge test in patients recovered from depression. Our data demonstrate that attentional set shifting deficits are not only present during acute episodes but also in remission. These deficits seem to be correlated with the duration of illness. Nonetheless, restored stress-associated HPA System function suggests recovery of the HPA System reactivity to psychosocial stress in patients remitted from depression. This in turn suggests that the observed cognitive impairment is not mediated by abnormal HPA responses.Cognitive impairment in the area of executive functioning may be considered a specific trait marker that persists after clinical and neuroendocrinological remission
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impact of citalopram on the HPA System a study of the combined dex crh test in 30 unipolar depressed patients
Journal of Psychiatric Research, 2012Co-Authors: Tom Bschor, Marcus Ising, Sebastian Erbe, Patricia Winkelmann, Dirk Ritter, Ute LewitzkaAbstract:Background: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) System is one of the best replicated pathophysiological findings in depression. However, studies on the influence of treatment on the HPA System have partly yielded inconsistent results. Objective: To assess the effects of citalopram monotherapy on the HPA System of mainly drug naive patients with major depression by means of the combined DEX/CRH test. Methods: The DEX/CRH test was conducted twice in 30 patients (25 drug naive for the index episode) with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed): directly before the start of a citalopram monotherapy (day 0) and four weeks thereafter (day 28). Results: Twenty-three patients responded (� 50% reduction in the HDRS21-score), and 17 of them also reached criteria of remission (HDRS � 7). Baseline (dexamethasone-suppressed) and CRH-stimulated ACTH concentrations significantly decreased from day 0 to day 28. CRH-stimulated cortisol concentrations also fell, although not significantly, but baseline cortisol concentrations exhibited a significant increase from day 0 to day 28. Conclusions: The blunting of the ACTH response in the DEX/CRH test under citalopram is in line with what has been observed in most studies with antidepressants. However, the partial rise in cortisol concentrations indicates an increase in the sensitivity of the adrenal cortex to ACTH. State-dependent alterations in the volume and the ACTH responsiveness of the adrenal gland have repeatedly been reported in depressed subjects, which indicates the possibility that SSRIs such as citalopram might exhibit a direct or indirect effect on the adrenal cortex.
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Lithium Monotherapy Increases ACTH and Cortisol Response in the Dex/CRH Test in Unipolar Depressed Subjects. A Study with 30 Treatment-Naive Patients
PLOS ONE, 2011Co-Authors: Tom Bschor, Marcus Ising, Sebastian Erbe, Patricia Winkelmann, Dirk Ritter, Ute LewitzkaAbstract:Background Distorted activity of the hypothalamic-pituitary-adrenocortical (HPA) System is one of the most robustly documented biological abnormalities in major depression. Lithium is central to the treatment of affective disorders, but little is known about its effects on the HPA System of depressed subjects. Objective To assess the effects of lithium monotherapy on the HPA System of patients with major depression by means of the combined DEX/CRH test. Method Thirty drug-naive outpatients with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed) were treated with lithium monotherapy for four weeks. The DEX/CRH test was conducted directly before intake of the first lithium tablet and four weeks thereafter. Weekly ratings with the HDRS21 were used to determine response (≥50% symptom reduction) and remission (HDRS ≤7). Results Lithium levels within the therapeutic range were achieved rapidly. Tolerability was good; no patient terminated the treatment prematurely. Response and remission rates were 50% and 33% respectively. Compared to the DEX/CRH test before the start of the treatment, a considerable and significant increase in all CRH-stimulated ACTH and cortisol parameters could be detected in the second DEX/CRH test. When analysed with particular regard to responders and non-responders, that significant increase was only present in the responders. Conclusions We were able to demonstrate that lithium leads to a significant activation of the HPA System. This is possibly connected to stimulation of hypothalamic arginine vasoporessin (AVP), to direct intracellular effects of lithium on pituitary cells and to an induction of gene expression. Trial Registration drks-nue.uniklinik-freiburg.de DRKS00003185
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Impact of citalopram on the HPA System. A study of the combined DEX/CRH test in 30 unipolar depressed patients
Journal of Psychiatric Research, 2011Co-Authors: Tom Bschor, Marcus Ising, Sebastian Erbe, Patricia Winkelmann, Dirk Ritter, Ute LewitzkaAbstract:Background: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) System is one of the best replicated pathophysiological findings in depression. However, studies on the influence of treatment on the HPA System have partly yielded inconsistent results. Objective: To assess the effects of citalopram monotherapy on the HPA System of mainly drug naive patients with major depression by means of the combined DEX/CRH test. Methods: The DEX/CRH test was conducted twice in 30 patients (25 drug naive for the index episode) with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed): directly before the start of a citalopram monotherapy (day 0) and four weeks thereafter (day 28). Results: Twenty-three patients responded (� 50% reduction in the HDRS21-score), and 17 of them also reached criteria of remission (HDRS � 7). Baseline (dexamethasone-suppressed) and CRH-stimulated ACTH concentrations significantly decreased from day 0 to day 28. CRH-stimulated cortisol concentrations also fell, although not significantly, but baseline cortisol concentrations exhibited a significant increase from day 0 to day 28. Conclusions: The blunting of the ACTH response in the DEX/CRH test under citalopram is in line with what has been observed in most studies with antidepressants. However, the partial rise in cortisol concentrations indicates an increase in the sensitivity of the adrenal cortex to ACTH. State-dependent alterations in the volume and the ACTH responsiveness of the adrenal gland have repeatedly been reported in depressed subjects, which indicates the possibility that SSRIs such as citalopram might exhibit a direct or indirect effect on the adrenal cortex.
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long term outcome after lithium augmentation in unipolar depression focus on HPA System activity
Neuropsychobiology, 2009Co-Authors: Mazda Adli, Marcus Ising, Tom Bschor, Ute Lewitzka, Michael Bauer, Claudia Lucka, Bruno Muelleroerlinghausen, Christopher BaethgeAbstract:Background: Lithium augmentation is a first-line strategy for depressed patients resistant to antidepressive therapy, but little is known about patients’ subsequent long-term course
Ute Lewitzka - One of the best experts on this subject based on the ideXlab platform.
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impact of citalopram on the HPA System a study of the combined dex crh test in 30 unipolar depressed patients
Journal of Psychiatric Research, 2012Co-Authors: Tom Bschor, Marcus Ising, Sebastian Erbe, Patricia Winkelmann, Dirk Ritter, Ute LewitzkaAbstract:Background: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) System is one of the best replicated pathophysiological findings in depression. However, studies on the influence of treatment on the HPA System have partly yielded inconsistent results. Objective: To assess the effects of citalopram monotherapy on the HPA System of mainly drug naive patients with major depression by means of the combined DEX/CRH test. Methods: The DEX/CRH test was conducted twice in 30 patients (25 drug naive for the index episode) with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed): directly before the start of a citalopram monotherapy (day 0) and four weeks thereafter (day 28). Results: Twenty-three patients responded (� 50% reduction in the HDRS21-score), and 17 of them also reached criteria of remission (HDRS � 7). Baseline (dexamethasone-suppressed) and CRH-stimulated ACTH concentrations significantly decreased from day 0 to day 28. CRH-stimulated cortisol concentrations also fell, although not significantly, but baseline cortisol concentrations exhibited a significant increase from day 0 to day 28. Conclusions: The blunting of the ACTH response in the DEX/CRH test under citalopram is in line with what has been observed in most studies with antidepressants. However, the partial rise in cortisol concentrations indicates an increase in the sensitivity of the adrenal cortex to ACTH. State-dependent alterations in the volume and the ACTH responsiveness of the adrenal gland have repeatedly been reported in depressed subjects, which indicates the possibility that SSRIs such as citalopram might exhibit a direct or indirect effect on the adrenal cortex.
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Lithium Monotherapy Increases ACTH and Cortisol Response in the Dex/CRH Test in Unipolar Depressed Subjects. A Study with 30 Treatment-Naive Patients
PLOS ONE, 2011Co-Authors: Tom Bschor, Marcus Ising, Sebastian Erbe, Patricia Winkelmann, Dirk Ritter, Ute LewitzkaAbstract:Background Distorted activity of the hypothalamic-pituitary-adrenocortical (HPA) System is one of the most robustly documented biological abnormalities in major depression. Lithium is central to the treatment of affective disorders, but little is known about its effects on the HPA System of depressed subjects. Objective To assess the effects of lithium monotherapy on the HPA System of patients with major depression by means of the combined DEX/CRH test. Method Thirty drug-naive outpatients with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed) were treated with lithium monotherapy for four weeks. The DEX/CRH test was conducted directly before intake of the first lithium tablet and four weeks thereafter. Weekly ratings with the HDRS21 were used to determine response (≥50% symptom reduction) and remission (HDRS ≤7). Results Lithium levels within the therapeutic range were achieved rapidly. Tolerability was good; no patient terminated the treatment prematurely. Response and remission rates were 50% and 33% respectively. Compared to the DEX/CRH test before the start of the treatment, a considerable and significant increase in all CRH-stimulated ACTH and cortisol parameters could be detected in the second DEX/CRH test. When analysed with particular regard to responders and non-responders, that significant increase was only present in the responders. Conclusions We were able to demonstrate that lithium leads to a significant activation of the HPA System. This is possibly connected to stimulation of hypothalamic arginine vasoporessin (AVP), to direct intracellular effects of lithium on pituitary cells and to an induction of gene expression. Trial Registration drks-nue.uniklinik-freiburg.de DRKS00003185
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Impact of citalopram on the HPA System. A study of the combined DEX/CRH test in 30 unipolar depressed patients
Journal of Psychiatric Research, 2011Co-Authors: Tom Bschor, Marcus Ising, Sebastian Erbe, Patricia Winkelmann, Dirk Ritter, Ute LewitzkaAbstract:Background: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) System is one of the best replicated pathophysiological findings in depression. However, studies on the influence of treatment on the HPA System have partly yielded inconsistent results. Objective: To assess the effects of citalopram monotherapy on the HPA System of mainly drug naive patients with major depression by means of the combined DEX/CRH test. Methods: The DEX/CRH test was conducted twice in 30 patients (25 drug naive for the index episode) with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed): directly before the start of a citalopram monotherapy (day 0) and four weeks thereafter (day 28). Results: Twenty-three patients responded (� 50% reduction in the HDRS21-score), and 17 of them also reached criteria of remission (HDRS � 7). Baseline (dexamethasone-suppressed) and CRH-stimulated ACTH concentrations significantly decreased from day 0 to day 28. CRH-stimulated cortisol concentrations also fell, although not significantly, but baseline cortisol concentrations exhibited a significant increase from day 0 to day 28. Conclusions: The blunting of the ACTH response in the DEX/CRH test under citalopram is in line with what has been observed in most studies with antidepressants. However, the partial rise in cortisol concentrations indicates an increase in the sensitivity of the adrenal cortex to ACTH. State-dependent alterations in the volume and the ACTH responsiveness of the adrenal gland have repeatedly been reported in depressed subjects, which indicates the possibility that SSRIs such as citalopram might exhibit a direct or indirect effect on the adrenal cortex.
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long term outcome after lithium augmentation in unipolar depression focus on HPA System activity
Neuropsychobiology, 2009Co-Authors: Mazda Adli, Marcus Ising, Tom Bschor, Ute Lewitzka, Michael Bauer, Claudia Lucka, Bruno Muelleroerlinghausen, Christopher BaethgeAbstract:Background: Lithium augmentation is a first-line strategy for depressed patients resistant to antidepressive therapy, but little is known about patients’ subsequent long-term course
Michael Deuschle - One of the best experts on this subject based on the ideXlab platform.
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Hypothalamic-Pituitary-Adrenocortical Dysfunction in Elderly, Male Marathon Runners: Feedback Sensitivity, Stress Response, and Effects on Verbal Memory.
Neuroendocrinology, 2016Co-Authors: Michael Deuschle, Florian Holsboer, Ulrike Gotthardt, Ulrich Schweiger, Michael Dettling, Isabella HeuserAbstract:Animal studies suggest that repeated episodes of elevated glucocorticoids lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) System at a suprapituitary level, and to impaired mnemonic
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Hypercortisolemic Depressed Women: Lean but Viscerally Obese?
Neuroendocrinology, 2015Co-Authors: Michael Deuschle, Maria GillesAbstract:Background: Activation of the hypothalamic-pituitary-adrenal (HPA) System in depressed patients has been related to visceral adiposity. In contrast, low HPA syste
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Restless legs syndrome: Evidence for nocturnal hypothalamic-pituitary-adrenal System activation†
Movement Disorders, 2010Co-Authors: Claudia Schilling, Michael Schredl, Philipp Strobl, Michael DeuschleAbstract:Epidemiological studies consistently point to a relationship between restless legs syndrome (RLS) and cardiovascular disease. The mechanism underlying this association is unclear. Activation of the hypothalamic-pituitary-adrenal (HPA) System has been shown to contribute to the metabolic syndrome and an enhanced cardiovascular risk. We investigated cortisol levels as an indicator of HPA System activity in RLS during the nighttime, when RLS symptoms are at their maximum. We assessed nocturnal urinary cortisol excretion in 73 patients with RLS and 34 healthy controls, controlling for age and gender. Urine sampling was paralleled by polysomnographic recordings. We found significantly enhanced nocturnal cortisol excretion in RLS, demonstrating nocturnal HPA System overactivity in RLS. HPA System overactivity is a possible mechanism contributing to the enhanced load of cardiovascular disease in RLS patients. Nocturnal cortisol release showed weak correlations with some polysomnographic parameters of disturbed sleep, making a potential contribution of RLS-induced sleep disruption to HPA System activation conceivable. © 2010 Movement Disorder Society
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Insulin-like growth factor-I (IGF-I) serum concentrations in depressed patients: relationship to saliva cortisol and changes during antidepressant treatment.
Pharmacopsychiatry, 2009Co-Authors: Bettina Weber-hamann, Isabella Heuser, Maria Gilles, Werner F. Blum, Kratzsch J, Michael DeuschleAbstract:INTRODUCTION: The present study was designed to test the hypothesis that total and free insulin-like growth factor-I (IGF-I) serum concentrations in depressed patients are related to hypothalamus-pituitary-adrenal (HPA) System activity and show a longitudinal decline in patients responding to treatment as well as to declining HPA System activity. METHODS: We measured total and free IGF-I as well as IGF-binding protein-3 in 77 depressed patients after wash-out of pre-medication and again after 28 or 35 days of treatment with paroxetine or amitriptyline. RESULTS: Total but not free IGF-I serum concentrations are related to saliva cortisol concentrations in drug-free depressed patients. In responders to both amitriptyline and paroxetine, total IGF-I serum concentrations declined during treatment. DISCUSSION: Our findings show IGF-I to be related to HPA System activity and to decline in responders to treatment while serum concentrations of the biologically active free IGF-I are neither related to HPA System activity nor do they change during the course of treatment. Our data do not support the hypothesis that free IGF-I may play a major role in physical disturbances in depressed patients.
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Effect of single-dose sertraline on the hypothalamus-pituitary-adrenal System, autonomic nervous System, and platelet function.
Journal of Clinical Psychopharmacology, 2007Co-Authors: Thorben Ahrens, Florian Lederbogen, P Frankhauser, Michael DeuschleAbstract:Objective: Pharmacological treatment with selective serotonin reuptake inhibitors (SSRIs) is thought to decrease coronary risk in patients with depressive disorder. Selective serotonin reuptake inhibitor intake may (1) attenuate the hypothalamus-pituitary-adrenal (HPA) System, (2) improve disturbances of the autonomous nervous System, and (3) dampen the aggregability of platelets. There is only limited information about the influence of acute treatment with SSRIs on these Systems, which is especially important for the initiation of therapy in high-risk cardiac patients. We compared the reaction of these Systems to physical stress with single-dose SSRI treatment (100 mg) with that of placebo treatment. Methods: Using a double-blind, crossover, placebo-controlled design, we assessed HPA System activity via serum cortisol and corticotropin as well as sympathetic nervous System by determining serum norepinephrine and epinephrine levels at baseline and as a response to stress. Analysis of heart rate variability (HRV) provided information on sympathetic/parasympathetic balance. Platelet activity was measured via flow-cytometric determination of platelet surface activation markers along with the serotonin (5-HT) uptake of platelets. Results: We studied 12 healthy young men under placebo and verum conditions. We found higher HPA System activity at baseline and after physical activity under sertraline when compared with placebo, no difference in sympathetic nervous System activity after physical exertion and only slightly heightened baseline epinephrine values after sertraline intake. No difference was seen between sertraline and placebo intake regarding platelet activity and 5-HT uptake, HRV, blood pressure, and HR. Conclusions: Initiating sertraline treatment increases HPA System activity and epinephrine concentrations. We found no clinically relevant effect of single-dose sertraline treatment on autonomous nervous function, platelet activity, or platelet 5-HT uptake. These findings may not be extrapolated to patients with affective or cardiac disorders or to other SSRIs.