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

2004 ◽  
Vol 184 (6) ◽  
pp. 496-502 ◽  
Author(s):  
Stuart Watson ◽  
Peter Gallagher ◽  
James C. Ritchie ◽  
I. Nicol Ferrier ◽  
Allan H. Young
Keyword(s):  
Bipolar Disorder ◽  
Hpa Axis ◽  
Cortisol Response ◽  
Hypothalamic Pituitary Adrenal ◽  
The Core ◽  
Basal Cortisol ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Dexamethasone Suppression ◽  
Pituitary Adrenal Axis

BackgroundHypothalamic-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.AimsTo test the hypothesis that HPA axis dysfunction persists in patients in remission from bipolar disorder.MethodSalivary 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.ResultsPatients 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.ConclusionsThe dex/CRH test is abnormal in both remitted and non-remitted patients with bipolar disorder. Thismeasure of HP Aaxis dysfunction is a potential trait marker in bipolar disorder and thus possibly indicative of the core pathophysiological process in this illness.

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 Hypothalamic–pituitary–adrenal axis activity in adults who were prenatally exposed to the Dutch famine

2006 ◽  
Vol 155 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Susanne R de Rooij ◽  
Rebecca C Painter ◽  
David I W Phillips ◽  
Clive Osmond ◽  
Robert P J Michels ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Area Under The Curve ◽  
Later Life ◽  
Hypothalamic Pituitary Adrenal ◽  
Adult Age ◽  
Suppression Test ◽  
Design And Methods ◽  
Prenatal Famine ◽  
Hpa Axis Activity ◽  
Dexamethasone Suppression

Objective: The hypothalamic–pituitary–adrenal (HPA) axis has been proposed to be susceptible to fetal programming, the process by which an adverse fetal environment elicits permanent physiological and metabolic alterations predisposing to disease in later life. It is hypothesized that fetal exposure to poor circumstances alters the set point of the HPA axis, leading to increased HPA axis activity and subsequent increased cortisol concentrations. In this study, we tested the hypothesis that prenatal exposure to famine during different periods of gestation is associated with increased activity of the HPA axis. Design and methods: We assessed plasma cortisol concentrations after a dexamethasone suppression and an ACTH1–24-stimulation test in a group of 98 men and women randomly sampled from the Dutch famine birth cohort. Cohort members were born as term singletons around the 1944–1945 Dutch famine. Results: Cortisol profiles after dexamethasone suppression and ACTH1–24 stimulation were similar for participants exposed to famine during late, mid- or early gestation (P=0.78). Cortisol concentrations after dexamethasone suppression test did not differ between those exposed and those unexposed to famine in utero (mean difference −2% (95% confidence interval (CI) −27 to 23)). Neither peak cortisol concentration (20 nmol/l (95% CI −27 to 66)), cortisol increment (−5 nmol/l (95% CI −56 to 47)) or cortisol area under the curve post-ACTH1–24 injection (4% (95% CI −4 to 12)) differed between exposed and unexposed participants. Conclusions: Prenatal famine exposure does not seem to affect HPA axis activity at adult age, at least not at the adrenal level. This does not exclude altered HPA axis activity at the levels of the hippocampus and hypothalamus.

The dexamethasone suppression test and DSM-III-R diagnoses in suicide attempters

2003 ◽  
Vol 18 (7) ◽  
pp. 350-355 ◽  
Author(s):  
Åsa Westrin ◽  
Karin Frii ◽  
Lil Träskman-Bendz
Keyword(s):  
Personality Disorders ◽  
Stressful Events ◽  
Suicide Attempter ◽  
Axis Ii ◽  
Suppression Test ◽  
Axis I ◽  
Cortisol Levels ◽  
Low Cortisol ◽  
Hpa Axis Activity ◽  
Dexamethasone Suppression

AbstractPrevious research on hypothalamic-pituitary adrenal (HPA) axis-activity in suicide attempter research has shown conflicting outcomes. The design of the present study was to test the influence of personality disorders and concominant axis I diagnoses on the dexamethasone suppression diagnostic test by use of multiple regression analyses. The sample consisted of 184 patients with a recent suicide attempt and 42 healthy controls. As expected, the lowest pre- and postdexamethasone cortisol levels were found in patients with personality disorders axis II, cluster B as compared to the other patients. The results remained significant when analysed for covariance with DSM-III-R axis I diagnoses, age or sex. Whether these low cortisol levels are due to previous experience of extreme stressful events or long-lasting burden, or whether they may be a consequence of biogenetic or psychological predisposal of interest, remains to be elucidated. Axis I comorbidity needs to be further examined.

scholarly journals Decreased pituitary sensitivity to glucocorticoids in endurance-trained men

2001 ◽  
pp. 363-368 ◽  
Author(s):  
M Duclos ◽  
JB Corcuff ◽  
F Pehourcq ◽  
A Tabarin
Keyword(s):  
Hpa Axis ◽  
Low Dose ◽  
Urinary Free Cortisol ◽  
Test Results ◽  
O2 Uptake ◽  
Plasma Acth ◽  
Free Cortisol ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Dexamethasone Suppression

OBJECTIVE: Muscular exercise induces hypothalamo-pituitary-adrenal (HPA) axis activation and when regularly repeated, as in endurance training, leads to HPA axis adaptation. To assess whether non-professional endurance-trained (ET) men with a substantial training load and no clinical or biological features of HPA axis overactivity can present subtle alterations of HPA axis sensitivity to glucocorticoid negative feedback, nine ET men were subjected to HPA axis testing using the dexamethasone-corticotrophin-releasing hormone (CRH) test. DESIGN: Nine endurance-trained men and eight healthy age-matched sedentary men were studied. Morning plasma cortisol and 24 h urinary free cortisol (UFC) were determined and a low dose dexamethasone suppression test (LDDST) was performed followed by CRH stimulation (dexamethasone-CRH test). RESULTS: After a day without physical exercise, at 0800 h, plasma ACTH and cortisol concentrations, and the 24 h UFC and UFC/urinary creatinine (UC) ratio were similar in ET and sedentary men. By contrast, clear differences between the groups were seen in cortisol and ACTH responses to the dexamethasone-CRH test. In eight ET subjects, after LDDST, basal ACTH and cortisol levels were similar to those of sedentary men, whereas one ET subject displayed a poor suppression of cortisol level (131 nmol/l). After injection of CRH, however, three of nine ET men's cortisol levels were not suppressed by dexamethasone but instead displayed significant CRH-induced increase (peak cortisol: 88, 125 and 362 nmol/l). No sedentary subject exhibited any increase in cortisol levels. CONCLUSION: Three of nine ET men with a mean maximum rate of O2 uptake (VO2, max) of 61 ml/kg per min, running 50-70 km per week, were resistant to glucocorticoid suppression during the combined dexamethasone-CRH test.

scholarly journals Disrupting Hypothalamic Glucocorticoid Receptors Causes HPA Axis Hyperactivity and Excess Adiposity

2013 ◽  
Vol 27 (10) ◽  
pp. 1655-1665 ◽  
Author(s):  
Gloria Laryea ◽  
Günther Schütz ◽  
Louis J. Muglia
Keyword(s):  
Hpa Axis ◽  
Glucocorticoid Receptors ◽  
Plasma Acth ◽  
Exon 2 ◽  
Stunted Growth ◽  
Excess Adiposity ◽  
Corticosterone Secretion ◽  
Basal Plasma ◽  
Hpa Axis Activity ◽  
Dexamethasone Suppression

The glucocorticoid receptor (GR) regulates hypothalamic-pituitary-adrenal (HPA) axis activity during the stress response. The paraventricular nucleus (PVN) is a major site of negative feedback to coordinate the degree of the HPA axis activity with the magnitude of the exposed stressor. To define the function of endogenous PVN GR, we used Cre-loxP technology to disrupt different GR exons in Sim1-expressing neurons of the hypothalamus. GR exon 2-deleted mice (Sim1Cre-GRe2Δ) demonstrated 43% loss of PVN GR compared with an 87% GR loss in exon 3-deleted mice (Sim1Cre-GRe3Δ). Sim1Cre-GRe3Δ mice display stunted growth at birth but develop obesity in adulthood and display impaired stress-induced glucose release. We observed elevated basal and stress-induced corticosterone levels in Sim1Cre-GRe3Δ mice, compared with control and Sim1Cre-GRe2Δ mice, and impaired dexamethasone suppression, indicating an inability to negatively regulate corticosterone secretion. Sim1Cre-GRe3Δ mice also showed increased CRH mRNA in the PVN, increased basal plasma ACTH levels, and reduced locomotor behavior. We observed no differences in Sim1Cre-GRe2Δ mice compared with control mice in any measure. Our behavioral data suggest that GR deletion in Sim1-expressing neurons has no effect on anxiety or despair-like behavior under basal conditions. We conclude that loss of PVN GR results in severe HPA axis hyperactivity and Cushing's syndrome-like phenotype but does not affect anxiety and despair-like behaviors.

Childhood traumata, Dexamethasone Suppression Test and psychiatric symptoms: a trans-diagnostic approach

2010 ◽  
Vol 40 (12) ◽  
pp. 2037-2048 ◽  
Author(s):  
C. Faravelli ◽  
S. Gorini Amedei ◽  
F. Rotella ◽  
L. Faravelli ◽  
A. Palla ◽  
...  
Keyword(s):  
Life Events ◽  
Hpa Axis ◽  
Salivary Cortisol ◽  
Psychiatric Symptoms ◽  
Dexamethasone Suppression Test ◽  
Diagnostic Approach ◽  
Stressful Event ◽  
Suppression Test ◽  
Hpa Response ◽  
Dexamethasone Suppression

BackgroundChildhood traumatic events and functional abnormalities of the hypothalamus–pituitary–adrenal (HPA) axis have been widely reported in psychiatric patients, although neither is specific for any diagnosis. Among the limited number of studies that have evaluated these topics, none has adopted a trans-diagnostic approach. The aim of the present research is to explore the relationship between childhood stressors, HPA axis function and psychiatric symptoms, independent of the diagnosis.MethodA total of 93 moderate to severely ill psychiatric out-patients of Florence and Pisa University Psychiatric Units and 33 healthy control subjects were recruited. The assessment consisted of salivary cortisol pre- and post-low dose (0.5 mg) Dexamethasone, early and recent life events, 121 psychiatric symptoms independent of diagnosis, SCID, BPRS.ResultsIn total, 33.5% of patients were Dexamethasone Suppression Test (DST) non-suppressors, compared with 6.1% of controls (p=0.001). Among patients, non-suppression was associated with particular symptoms (i.e. depressive and psychotic), but not to any specific diagnosis. Early stressful life events were significantly associated with higher salivary cortisol levels, with DST non-suppression and with approximately the same subset of symptoms. A recent stressful event seemed to be associated to the HPA response only in those subjects who were exposed to early traumata.ConclusionsOur report suggests a relationship between life stress, HPA axis and psychopathology. A cluster of specific psychiatric symptoms seems to be stress related. Moreover, it seems that an abnormal HPA response is possibly triggered by an excessive pressure in vulnerable individuals.

scholarly journals Characterizing the postnatal hypothalamic–pituitary–adrenal axis response of in utero heat stressed pigs at 10 and 15 weeks of age

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jacob M. Maskal ◽  
Luiz F. Brito ◽  
Alan W. Duttlinger ◽  
Kouassi R. Kpodo ◽  
Betty R. McConn ◽  
...  
Keyword(s):  
In Utero ◽  
Dexamethasone Suppression Test ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
Cortisol Response ◽  
Hypothalamic Pituitary Adrenal ◽  
Releasing Hormone ◽  
Adrenal Axis ◽  
Suppression Test ◽  
Dexamethasone Suppression ◽  
Pituitary Adrenal Axis

AbstractIn utero heat stress alters postnatal physiological and behavioral stress responses in pigs. However, the mechanisms underlying these alterations have not been determined. The study objective was to characterize the postnatal hypothalamic–pituitary–adrenal axis response of in utero heat-stressed pigs. Pigs were subjected to a dexamethasone suppression test followed by a corticotrophin releasing hormone challenge at 10 and 15 weeks of age. Following the challenge, hypothalamic, pituitary, and adrenal tissues were collected from all pigs for mRNA abundance analyses. At 10 weeks of age, in utero heat-stressed pigs had a reduced (P < 0.05) cortisol response to the corticotrophin releasing hormone challenge versus controls. Additionally, the cortisol response tended to be greater overall (P < 0.10) in 15 versus 10-week-old pigs in response to the dexamethasone suppression test. The cortisol response tended to be reduced overall (P < 0.10) in 15 versus 10-week-old pigs in response to the corticotrophin releasing hormone challenge. Hypothalamic corticotropin releasing hormone mRNA abundance tended to be greater (P < 0.10) in in utero heat-stressed versus control pigs at 15-weeks of age. In summary, in utero heat stress altered some aspects of the hypothalamic–pituitary–adrenal axis related to corticotropin releasing hormone signaling, and age influenced this response.

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