The relationships between the availability ofL-tryptophan to the brain, the spontaneous HPA-axis activity, and the HPA-axis responses to dexamethasone in depressed patients

SYNOPSISIn order to investigate the relationship between the immune apparatus and the hypothalamic–pituitary–adrenal (HPA)-axis activity in depressed patients, we measured in vitro lymphocyte responses to the mitogens Phytohaemagglutinin (PHA), Pokeweed (PWM) and Concanavalin A (Con A) and 8 a.m. baseline cortisol values in plasma, free cortisol excretion in 24 h urine (UFC), basal and post-dexamethasone βendorphin values. Major depressed patients with melancholia/psychotic features exhibited a significantly lower mitogen-induced blast transformation as compared to minor and simple major depressed patients. The lymphocyte responses to the three mitogens were significantly inversely related to baseline cortisol values and postdexamethasone β-endorphin values. The proliferative capacity of lymphocytes to stimulation with PHA and PWM was significantly and positively related to UFC excretion. Up to 45% of the variance in the immune responses to the mitogens was explained by the baseline cortisol, post-dexamethasone β-endorphin and UFC values.

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

European Psychiatry ◽

10.1016/s0924-9338(11)72319-7 ◽

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.

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Higher HPA axis activity in healthy participants compared to depressed patients after MR blockade: Evidence for attenuated MR function in depression

Psychoneuroendocrinology ◽

10.1016/j.psyneuen.2015.07.537 ◽

2015 ◽

Vol 61 ◽

pp. 54 ◽

Cited By ~ 1

Author(s):

Kim Hinkelmann ◽

Julian Hellmann-Regen ◽

Katja Wingenfeld ◽

Linn Kuehl ◽

Marie Mews ◽

...

Keyword(s):

Hpa Axis ◽

Depressed Patients ◽

Hpa Axis Activity ◽

Healthy Participants

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TheKampoMedicine Yokukansan Decreases MicroRNA-18 Expression and Recovers Glucocorticoid Receptors Protein Expression in the Hypothalamus of Stressed Mice

BioMed Research International ◽

10.1155/2015/797280 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Shoko Shimizu ◽

Takashi Tanaka ◽

Takashi Takeda ◽

Masaya Tohyama ◽

Shingo Miyata

Keyword(s):

Hpa Axis ◽

Stress Responses ◽

Glucocorticoid Receptors ◽

Psychological Symptoms ◽

Plasma Corticosterone ◽

Mrna Levels ◽

Stress Exposure ◽

Protein Levels ◽

Hpa Axis Activity ◽

The Brain

It is well known that glucocorticoid receptor (GR) signaling regulates the hypothalamic-pituitary-adrenal (HPA) axis, and GR expression level is associated with HPA axis activity. Recent studies revealed that microRNA- (miR-) 18 and/or 124a are candidate negative regulators of GR in the brain. TheKampomedicine Yokukansan (YKS) can affect psychological symptoms such as depression and anxiety that are associated with stress responses. In this study, we evaluated the effect of YKS on miR-18 and 124a and GR levels in mice exposed to stress. We found that YKS pretreatment normalized elevated plasma corticosterone levels in stress-exposed mice. In addition, GR mRNA levels were downregulated in the brain following stress exposure. While miR-124a expression levels were not altered in the hypothalamus of stress-exposed mice, miR-18 levels decreased in the hypothalamus of YKS-pretreated mice after stress exposure. Finally, GR protein levels in the paraventricular nucleus (PVN) of the hypothalamus after stress exposure recovered in YKS-pretreated mice. Collectively, these data suggest that YKS normalizes GR protein levels by regulating miR-18 expression in the hypothalamus, thus normalizing HPA axis activity following stress exposure.

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Leptin’s hunger-suppressing effects are mediated by the hypothalamic–pituitary–adrenocortical axis in rodents

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1901795116 ◽

2019 ◽

Vol 116 (27) ◽

pp. 13670-13679 ◽

Cited By ~ 17

Author(s):

Rachel J. Perry ◽

Jon M. Resch ◽

Amelia M. Douglass ◽

Joseph C. Madara ◽

Aviva Rabin-Court ◽

...

Keyword(s):

Central Nervous System ◽

Hpa Axis ◽

Homeostatic Regulation ◽

Adaptive Responses ◽

Cns Neurons ◽

The Central Nervous System ◽

Hpa Axis Activity ◽

The Brain ◽

Stimulation Of

Leptin informs the brain about sufficiency of fuel stores. When insufficient, leptin levels fall, triggering compensatory increases in appetite. Falling leptin is first sensed by hypothalamic neurons, which then initiate adaptive responses. With regard to hunger, it is thought that leptin-sensing neurons work entirely via circuits within the central nervous system (CNS). Very unexpectedly, however, we now show this is not the case. Instead, stimulation of hunger requires an intervening endocrine step, namely activation of the hypothalamic–pituitary–adrenocortical (HPA) axis. Increased corticosterone then activates AgRP neurons to fully increase hunger. Importantly, this is true for 2 forms of low leptin-induced hunger, fasting and poorly controlled type 1 diabetes. Hypoglycemia, which also stimulates hunger by activating CNS neurons, albeit independently of leptin, similarly recruits and requires this pathway by which HPA axis activity stimulates AgRP neurons. Thus, HPA axis regulation of AgRP neurons is a previously underappreciated step in homeostatic regulation of hunger.

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Sleep deprivation and hypothalamic-pituitary-adrenal (HPA) axis activity in depressed patients

Journal of Psychiatric Research ◽

10.1016/s0022-3956(01)00027-9 ◽

2001 ◽

Vol 35 (4) ◽

pp. 239-247 ◽

Cited By ~ 11

Author(s):

Cornelius Schüle ◽

Thomas Baghai ◽

Peter Zwanzger ◽

Christo Minov ◽

Frank Padberg ◽

...

Keyword(s):

Sleep Deprivation ◽

Hpa Axis ◽

Hypothalamic Pituitary Adrenal ◽

Depressed Patients ◽

Hpa Axis Activity

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Plasma soluble interleukin-2-receptor in depression: relationships to plasma neopterin and serum IL-2 concentrations and HPA-axis activity

European Psychiatry ◽

10.1016/0924-9338(96)80345-2 ◽

1995 ◽

Vol 10 (8) ◽

pp. 397-403 ◽

Cited By ~ 12

Author(s):

M Maes ◽

E Bosmans ◽

S Scharpé ◽

P D'Hondt ◽

R Desnyder

Keyword(s):

Hpa Axis ◽

Interleukin 2 ◽

Severity Of Illness ◽

Normal Serum ◽

Cell Mediated Immunity ◽

Interleukin 2 Receptor ◽

Depressed Patients ◽

Measurable Serum ◽

Soluble Interleukin 2 Receptor ◽

Hpa Axis Activity

SummaryThe present study examined the plasma concentration of the soluble interleukin-2-receptor (sIL-2R) in depressed subjects in relation to hypothalamic pituitary adrenal (HPA) axis function and plasma neopterin and serum IL-2 concentrations. Plasma sIL-2R concentration was significantly higher in depressed patients (n = 47) than in controls (n = 19). There were no significant correlations between plasma sIL-2R and severity of illness. In the depressed subjects, there was a highly significant relationship between plasma sIL-2R and neopterin concentrations. Depressed patients with pathologically increased plasma neopterin levels had significantly higher plasma sIL-2R values than those with normal serum neopterin. There were no significant relationships between plasma sIL-2R and indices of HPA-axis function in depression. There was no significant effect of dexamethasone administration on sIL-2R levels. Significantly more depressed subjects had measurable serum IL-2 levels than normal controls. Our data support the notion that a moderate activation of cell-mediated immunity may play a role in the pathophysiology of depression.

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