Extent of cortisol suppression at baseline predicts improvement in HPA axis function during antidepressant treatment

2020 ◽  
Vol 114 ◽  
pp. 104590 ◽  
Author(s):  
Maike Scherf-Clavel ◽  
Catherina Wurst ◽  
Felix Nitschke ◽  
Saskia Stonawski ◽  
Carolin Burschka ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Antidepressant Treatment ◽  
Cortisol Suppression

scholarly journals Neuroendocrine Assessment of Dopaminergic Function during Antidepressant Treatment in Major Depressed Patients

2021 ◽  
Vol 11 (4) ◽  
pp. 425
Author(s):  
Fabrice Duval ◽  
Marie-Claude Mokrani ◽  
Alexis Erb ◽  
Felix Gonzalez Lopera ◽  
Vlad Danila ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Antidepressant Treatment ◽  
Cortisol Response ◽  
Mesolimbic Pathway ◽  
Suppression Test ◽  
Pre Treatment ◽  
Hpa Axis Activity ◽  
Drug Free ◽  
Hypothalamic Level ◽  
Dexamethasone Suppression

The effects of antidepressants on dopamine (DA) receptor sensitivity in the mesolimbic–hypothalamic system have yielded contradictory results. The postsynaptic DA receptor function was evaluated by the cortisol response to apomorphine (APO; 0.75 mg SC) in 16 drug-free DSM-5 major depressed inpatients and 18 healthy hospitalized control (HC) subjects. Cortisol response to the dexamethasone suppression test (DST) was also measured. After two and four weeks of antidepressant treatment (ADT), the DST and APO test were repeated in all patients. Cortisol response to APO (∆COR) was not influenced by the hypothalamic–pituitary–adrenal (HPA) axis activity, as assessed by the DST. Pre-treatment ∆COR values did not differ significantly between patients and HCs. During ADT, ∆COR values were lower than in HCs at week 2 and 4. After four weeks of treatment, among the eight patients who had blunted ∆COR values, seven were subsequent remitters, while among the eight patients who had normal ∆COR values, seven were non-remitters. Considering the limitations of our study, the results suggest that following chronic ADT, the desensitization of postsynaptic DA receptors connected with the regulation of the HPA axis at the hypothalamic level is associated with clinical remission. These results could reflect increased DA levels in the mesolimbic pathway.

scholarly journals Salivary Cortisol and Psychopathology in Adults Bereaved by the September 11, 2001 Terror Attacks

2009 ◽  
Vol 39 (3) ◽  
pp. 215-226 ◽  
Author(s):  
Cynthia R. Pfeffer ◽  
Margaret Altemus ◽  
Moonseong Heo ◽  
Hong Jiang
Keyword(s):  
Hpa Axis ◽  
Salivary Cortisol ◽  
Time Course ◽  
September 11 ◽  
Diagnostic Interview ◽  
Terror Attacks ◽  
Spouse Death ◽  
Basal Cortisol ◽  
Suppression Test ◽  
Cortisol Suppression

Objective: This prospective study aimed to describe the nature and time course of HPA axis dysregulation and psychopathology among terror-bereaved spouses. Method: Twenty-three spouses bereaved from September 11, 2001 terror attacks and 22 nonbereaved spouses were compared using a psychiatric diagnostic interview (SCID), 3 days of salivary cortisol collection, and a dexamethasone suppression test. Most subjects had repeated assessments at 6 month intervals during the 2 year study. Results: After September 11, 2001, bereaved compared to nonbereaved had significantly higher rates of posttraumatic stress disorder (PTSD; 68.1% versus 0%) and major depressive disorder (MDD; 45.5% versus 9.5%). Bereaved had significantly higher morning basal cortisol and less afternoon postdexamethasone cortisol suppression than nonbereaved. Among bereaved, those with PTSD without comorbid MDD had significantly greater afternoon postdexamethasone cortisol suppression than those without psychiatric disorders. Conclusions: Terror-related spouse death is a severe stressor associated with persistent HPA axis activation, PTSD, and MDD. However, bereaved spouses who developed PTSD and were not depressed had enhanced post-dexamethasone cortisol suppression, evidence of heightened glucocorticoid receptor sensitivity.

Effects of lithium on the HPA axis in patients with unipolar major depression

2011 ◽  
Vol 26 (S2) ◽  
pp. 612-612
Author(s):  
T. Bschor ◽  
D. Ritter ◽  
U. Lewitzka ◽  
M. Bauer ◽  
M. Uhr ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Antidepressant Treatment ◽  
Challenge Test ◽  
Tricyclic Antidepressant ◽  
List Type ◽  
Depressed Patients ◽  
Design And Methods ◽  
Hpa Axis Activity ◽  
Drug Free ◽  
Lithium Augmentation

Background(I)Profound alterations of the hypothalamic-pituitary-adrenocortical (HPA) axis regulation were repeatedly shown in depressed patients. The most sensitive challenge test of the HPA axis, the combined dexamethasone/CRH test (DEX/CRH test), shows an overstimulation of ACTH and cortisol in depressed patients. Under tricyclic antidepressant treatment, a normalization of the HPA axis overdrive was found to precede the clinical improvement.(II)Lithium is a well established drug for the treatment of affective disorders. Yet, its exact mode of action and its effects on the HPA axis are still unknown.Design and methodsThree 4-week studies with each 30 acutely depressed patients (unipolar, SCID I confirmed) were conducted. In study 1, patients refractory to a treatment trial with an antidepressant of at least four weeks were treated with lithium augmentation. In study 2 and 3, drug free patients were treated with lithium monotherapy or citalopram monotherapy respectively. Weekly HAM-D ratings were performed. In each study, the DEX/CRH test was conducted right before and four weeks after initiation of the pharmacotherapy.ResultsAll three pharmacological strategies showed good antidepressive efficacy. Both lithium monotherapy and lithium augmentation led to a (for most parameters significant) increase in the HPA axis activity. In contrast, citalopram monotherapy resulted in a decrease of the hormone response to the DEX/CRH test.

scholarly journals Social Instability is an Effective Chronic Stress Paradigm for both Male and Female Mice

2019 ◽  
Author(s):  
Christine N. Yohn ◽  
Sandra A. Ashamalla ◽  
Leshya Bokka ◽  
Mark M. Gergues ◽  
Alexander Garino ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Hpa Axis ◽  
Social Stress ◽  
Antidepressant Treatment ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Social Instability ◽  
Female Mice ◽  
Negative Valence ◽  
Males And Females

ABSTRACTDespite stress-associated disorders having a higher incidence rate in females, preclinical research mainly focuses on males. Chronic stress paradigms, such as chronic social defeat and chronic corticosterone administration, were mainly designed and validated in males and subsequent attempts to use these paradigms in females has demonstrated sex differences in the behavioral and HPA axis response to stress. Here, we developed a social stress paradigm, social instability stress (SIS), which exposes adult mice to unstable social hierarchies for 7 weeks. SIS effectively induces negative valence behaviors and hypothalamus-pituitary-adrenal (HPA) axis activation in both males and females. Importantly, while there were effects of estrous cycle on behavior, this variability did not impact the overall effects of SIS on behavior, suggesting estrous does not need to be tracked while utilizing SIS. Furthermore, the effects of SIS on negative valence behaviors were also reversed following chronic antidepressant treatment with fluoxetine (FLX) in both males and females. SIS also reduced adult hippocampal neurogenesis in female mice, while chronic FLX treatment increased adult hippocampal neurogenesis in both males and females. Overall, these data demonstrate that the SIS paradigm is an ethologically valid approach that effectively induces chronic stress in both adult male and adult female mice.

scholarly journals The effect of antidepressant treatment on the HPA axis, changes in depression score and serum levels of TNF-α in depressed infertile women

2020 ◽  
Vol 47 (1) ◽  
pp. 7-12
Author(s):  
SEDIGHEH KESHAVARZ ◽  
BAHAR MORSHED-BEHBAHANI ◽  
MOHAMMAD EBRAHIM PARSANEZHAD ◽  
AHMAD GHANIZADEH ◽  
MEHRAP SAYADI ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Antidepressant Treatment ◽  
Serum Levels ◽  
Depression Score ◽  
Infertile Women ◽  
Tnf Α

Molecular mechanisms of glucocorticoid receptor sensitivity and relevance to affective disorders

2003 ◽  
Vol 15 (6) ◽  
pp. 354-367 ◽  
Author(s):  
Mario F Juruena ◽  
Anthony J Cleare ◽  
Moisés E Bauer ◽  
Carmine M Pariante
Keyword(s):  
Glucocorticoid Receptor ◽  
Hpa Axis ◽  
Affective Disorders ◽  
Molecular Mechanisms ◽  
Antidepressant Treatment ◽  
Brain Regions ◽  
Suppression Test ◽  
Treatment Research ◽  
Second Messenger Pathways ◽  
The Impact

Changes in the hypothalamic–pituitary–adrenocortical (HPA) system are characteristic of depression, and in the majority of these patients these result in HPA axis hyperactivity. This is further supported by the reduced sensitivity to the inhibitory effects of the glucocorticoid, dexamethasone (DEX), on the production of adrenocorticotropic hormone (ACTH) and cortisol, during the DEX suppression test and the DEX-corticotropin-releasing hormone (DEX/CRH) test. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR), several studies have examined the number and/or function of GRs in depressed patients. These studies have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of CRH in various brain regions postulated to be involved in the causality of depression. This article summarizes the literature on GR in depression and on the impact of antidepressants on the GR in clinical and preclinical studies, and supports the concept that impaired GR signaling is a key mechanism in the pathogenesis of depression, in the absence of clear evidence of decreased GR expression. The data also indicate that antidepressants have direct effects on the GR, leading to enhanced GR function and increased GR expression. Hypotheses regarding the mechanism of these receptor changes involve non-steroid compounds that regulate GR function via second messenger pathways, such as cytokines and neurotransmitters. Moreover, we present recent evidence suggesting that membrane steroid transporters such as the multidrug resistance (MDR) p-glycoprotein, which regulate access of glucocorticoids to the brain, could be a fundamental target of antidepressant treatment. Research in this field will lead to new insights into the pathophysiology and treatment of affective disorders.

Protein Kinase A in Major Depression: The Link Between Hypothalamic-Pituitary-Adrenal Axis Hyperactivity and Neurogenesis

CNS Spectrums ◽  
2001 ◽  
Vol 6 (7) ◽  
pp. 565-572 ◽  
Author(s):  
Tarique Perera ◽  
Sarah H. Lisanby ◽  
Harold A. Sackeim
Keyword(s):  
Major Depression ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Hpa Axis ◽  
Antidepressant Treatment ◽  
Long Term Potentiation ◽  
Hippocampal Neurogenesis ◽  
Hypothalamic Pituitary Adrenal ◽  
Term Potentiation ◽  
Kinase A

AbstractThe latest and most generative biological theories of major depression center on two major hypotheses. The first focuses on the concept that hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis leads to many of the pathological changes in the brain that accompany major depression. The second posits that neurogenesis leads to the repair of depression-related injuries. These two hypotheses are complementary: the former alludes to the etiology or consequences of depression, while the latter suggests mechanisms of antidepressant action. Significant crosstalk occurs between these two systems at many levels. Protein kinase A (PKA) may play an important role in this crosstalk at the intracellular level of signaling cascades. PKA is involved in the formation of long-term potentiation and fear conditioning in response to stress. Chronic stress leads to the suppression of hippocampal activity, which may cause the hyperactivity of the HPA axis during melancholic depression. PKA is also involved in the stimulation of hippocampal neurogenesis after antidepressant treatment. In theory, neurogenesis may lead to the restoration of hippocampal function, and this may be the mechanism that leads to antidepressant-mediated normalization of HPA hyperactivity. Thus, PKA is active during processes that potentially lead to depression and other processes that lead to the resolution of the illness. These opposing processes may be mediated by separate PKA isozymes that activate two distinct pathways. This review highlights the dual role of this enzyme in two biological hypotheses pertaining to depression and its treatment.

scholarly journals Gender-Specific Association of Galanin Polymorphisms with HPA-Axis Dysregulation, Symptom Severity, and Antidepressant Treatment Response

2010 ◽  
Vol 35 (7) ◽  
pp. 1583-1592 ◽  
Author(s):  
Paul G Unschuld ◽  
Marcus Ising ◽  
Darina Roeske ◽  
Angelika Erhardt ◽  
Michael Specht ◽  
...  
Keyword(s):  
Treatment Response ◽  
Hpa Axis ◽  
Symptom Severity ◽  
Antidepressant Treatment ◽  
Hpa Axis Dysregulation ◽  
Specific Association ◽  
Gender Specific

Stress and the Serotonergic System, Observations from Pet Imaging

2017 ◽  
Vol 41 (S1) ◽  
pp. S19-S19
Author(s):  
M. Spies ◽  
R. Lanzenberger
Keyword(s):  
Hpa Axis ◽  
Acute Stress ◽  
Antidepressant Treatment ◽  
Brain Regions ◽  
The Other ◽  
Serotonergic System ◽  
Other Hand ◽  
Positron Emission ◽  
Hpa Axis Activity

IntroductionStress response and the neuroendocrinologic factors through which it is mediated are disturbed in anxiety and in affective disorders. While acute stress is thought to result in hypothalamus-pituitary-adrenal- (HPA) axis hyperactivity (Varghese 2001), chronic stress may result in decreased HPA-response (Booji 2013). Antidepressant treatment, on the other hand, is thought to realign HPA–axis activity (Schüle 2007).On the other hand, dysregulation within the serotonergic neurotransmitter system is understood as a central moderator in the pathophysiology of affective and anxiety disorders. Serotonergic transmission both regulates- and is regulated by- glucocortocoids. Cortisol results in an increase in serotonin synthesis and release while serotonergic transmission is thought to downregulate HPA-axis activity (Lanfumey, 2008). Positron emission tomography (PET) studies have demonstrated the link between the serotonergic system and the HPA-axis in humans in vivo. For example, a negative correlation between cortisol and 5HT1A receptor levels in various brain regions has been shown (Lanzenberger, 2010). SERT expression, on the other hand, was shown using PET to be positively related to HPA-axis reactivity (Frokjaer 2013).Methodsn.a.AimsAvailable literature on interactions between the HPA-axis and the serotonergic system will be discussed with a focus on data acquired via PET studies.Resultsn.a.ConclusionsThe interaction between the serotonergic system and the HPA-axis is likely bilateral and may be understood as a neurobiological link by which stress may foster the development of depression and anxiety.Disclosure of interestM. Spies has received travel grants from AOP Orphan Pharmaceuticals AG, Janssen-Cilag Pharma Gmbh, and Eli Lilly, workshop participation from Eli Lilly, and speaker honoraria from Janssen-Cilag Pharma Gmbh. R. Lanzenberger received travel grants and conference speaker honoraria from AstraZeneca, Lundbeck A/S, Roche Austria GmbH, Dr. Willmar Schwabe GmbH & Co. KG, AOP Orphan Pharmaceuticals, and Janssen-Cilag Pharma Gmbh.

scholarly journals Plasma Cortisol Levels and Physical Aggression in Depressed Patients

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
B. Mattioli ◽  
G. Camardese ◽  
G. Pizi ◽  
F. Adamo ◽  
P. Bria
Keyword(s):  
Major Depression ◽  
Hpa Axis ◽  
Physical Aggression ◽  
Plasma Cortisol ◽  
Antidepressant Treatment ◽  
Serotoninergic System ◽  
Depressed Patients ◽  
Serotonergic Activity ◽  
Aggression Questionnaire ◽  
Cortisol Levels

An analysis of the biological mechanisms underlying both aggression and major depression (MD) shows the implication of common features. There is a well known link between MD and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, the HPA axis dysfunction has been identified as a promising predictor of suicidal behaviours in mood disorders.The aim of the study was to examine the relationship between aggressive behaviour and plasma cortisol levels during a Major Depression Episode (MDE).83 patients (M/F = 43/40; mean age 47,70±14,52) with a Mood Disorder during a MDE have been recruited at the Day Clinic of Psychiatry of the Catholic University in Rome.A blood sample for the determination of plasma cortisol levels was collected before antidepressant treatment. Aggression Questionnaire (AQ) was used to evaluate aggression traits such as Verbal Aggression (VA), Physical Aggression (PA), Anger (A), Hostility (H) and total Aggression score (AQtot). No significant correlation between plasma cortisol levels and VA, A, H or AQtot was found. A positive correlation between PA scores and plasma cortisol levels was reported (r = 0.39; p = 0.007).Physical Aggression underline a risk for subsequent inner-directed violence, including suicidal thoughts and behaviours and it is also associated to a serotoninergic system dysfunction. An abnormal interaction between the HPA mechanisms and serotonergic systems has also been suggested in suicidal behaviours.Our results confirm the importance of further research with more sensitive markers to monitor HPA axis activity (e.g. Dexamethasone/CRH test), serotonergic activity and psychopathological features in depressed patients.

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