Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthetic ovine corticotropin releasing factor (o-CRF) was administered as an intravenous bolus (100 micrograms) to eight patients suffering from a major depressive disorder, endogenous subtype. All patients showed inadequately suppressed cortisol levels after 1 mg dexamethasone. After clinical remission and normalized dexamethasone responses, these patients were reinvestigated with o-CRF stimulation. The mean adrenocorticotropic hormone (ACTH) release from the pituitary corticotroph cells was indiscriminate at both test sessions. Cortisol and corticosterone output after o-CRF tended to be higher during depression than after recovery. The o-CRF-induced increments observed with corticosterone were more marked in comparison with cortisol. Within the limitations of the current protocol, our preliminary data lend support to the view that an increased pituitary ACTH reserve or adrenocortical steroid reserve is not likely to be responsible for the defective pituitary-adrenal regulation in some dexamethasone-resistant depressives.
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PMID:ACTH, cortisol, and corticosterone output after ovine corticotropin-releasing factor challenge during depression and after recovery. 298 88

To further explore hypothalamic pituitary adrenal regulation in patients with affective illness, we administered 1 microgram/kg of synthetic ovine corticotropin releasing factor at 2000h to 26 drug-free patients with this disorder and to 15 healthy controls. Compared to controls, depressed patients (N = 12) showed a significant elevation in baseline cortisol and significant reductions in the net ACTH and cortisol responses to corticotropin releasing factor. These findings were normal in manic (N = 6) and improved (N = 8) subjects. An additional finding was that baseline cortisol and net ACTH and cortisol responses to CRF were negatively correlated in the entire group of patients and controls as well as in the patients alone. These data indicate that the reduced ACTH and cortisol responses to CRF in depression reflect normal functioning of the pituitary corticotroph cell (i.e., that the negative feedback effect of cortisol on ACTH secretion in depression is physiologically intact, effectively serving as a brake on the ACTH response to exogenous CRF. Thus, the hypercortisolism of depression may be due to a hypothalamic defect, possibly involving hypersecretion of endogenous CRF. This possibility may be of particular interest in light of clinical observations that depression can often be precipitated by stress and by data in experimental animals that CRF may influence several processes known to be altered in the overall symptom complex of depression.
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PMID:Abnormal ACTH and cortisol responses to ovine corticotropin releasing factor in patients with primary affective disorder. 301 Mar 82

Delayed-type hypersensitivity (DTH) was depressed in mice that had been treated with monosodium glutamate (MSG) in their suckling period. Analysis of the DTH depression by use of the macrophage migration inhibition assay showed dysfunction of DTH effector T cells. The neuronal loss of nuclei in the hypothalamus, which elaborates the corticotropin-releasing factor and the hypersecretion of adrenocorticotrophic hormone, was observed in the MSG-treated mice. Therefore, DTH response may be modulated by the neuroendocrine system.
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PMID:Depression of delayed-type hypersensitivity in mice with hypothalamic lesion induced by monosodium glutamate: involvement of neuroendocrine system in immunomodulation. 301 79

The central biochemical pathology of anorexia and the natural aging of the brain is similar. Biochemical models for drug withdrawal and depression may also assist in understanding geriatric anorexia. Norepinephrine, corticotropin releasing factor and beta-endorphin may key neurotransmitters in all of these conditions.
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PMID:Drug abuse and depression: possible models for geriatric anorexia. 326 10

Corticotropin-releasing hormone (CRH) has been considered a major coordinator of the overall physical and behavioral response to stress. Moreover, prolonged hypersecretion of CRH has been implicated in the pathogenesis of disorders characterized by anxiety and/or depression. Drugs acting through the gamma-aminobutyric acid/benzodiazepine (GABA/BZD) receptor system have anxiolytic and/or antidepressant properties whereas benzodiazepine inverse agonists cause anxiety and stimulate the pituitary-adrenal axis in vivo. To examine the involvement of the GABA/BZD system in the regulation of hypothalamic CRH secretion, we studied the effects of various agonists and antagonists of GABAA and GABAB receptors using a sensitive rat hypothalamic organ culture with radioimmunoassayable CRH (IR-rCRH) as endpoint. The GABAA and GABAB receptor agonist GABA inhibited serotonin (5-HT)-induced IR-rCRH secretion from 10(-9) to 10(-6) M, but failed to do so at 10(-5) M. The GABAA receptor agonist muscimol was a weak inhibitor of 5-HT-induced IR-rCRH secretion, being effective only at the concentration of 10(-6) M. In contrast, the specific GABAB receptor agonist baclofen was able to inhibit 5-HT-induced IR-rCRH secretion from 10(-7) to 10(-5) M. The rank of potency was thus, GABA much greater than baclofen greater than muscimol. Bicuculline, a GABAA receptor antagonist, partially reversed the inhibitory effects of GABA. Diazepam, a classic benzodiazepine which interacts with the benzodiazepine-site of the GABAA receptor complex, inhibited 5-HT-induced IR-rCRH secretion from 3.3 X 10(-9) to 10(-5) M, an effect that could be reversed by the BZD inactive ligand Ro15-1788.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction between GABAergic neurotransmission and rat hypothalamic corticotropin-releasing hormone secretion in vitro. 326 1

The induction of hypothyroidism in young rats by feeding thiouracil to their mothers during pregnancy has been shown to depress hypothalamic content of bioactive and immunoactive corticotropin-releasing factor (CRF). The present study was done to determine whether genetically hypothyroid young mice (hyt/hyt) born to euthyroid mothers (+/hyt) exhibited a similar depression in hypothalamic CRF immunoreactivity. Young euthyroid and hypothyroid littermate mice were examined by radioimmunoassay for hypothalamic CRF content at 15, 20, 25, or 30 days of age. Mean CRF content was depressed insignificantly (to about 80% of normal) by hypothyroidism, at 15-25 days of age. However, after weaning by the mother, 30-day-old hypothyroid pups demonstrated significantly depressed hypothalamic CRF levels (71%). It is suggested that maternal factors may be assisting in the maintenance of hypothalamic CRF until after weaning. Furthermore, genetic hypothyroidism does not appear to have nearly as marked an influence as thiouracil feeding on hypothalamic CRF levels.
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PMID:Hypothalamic CRF immunoreactivity in genetically hypothyroid (hyt/hyt) mice. 349 6

To further investigate the hypothesis that hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with depression may be mediated by hypersecretion of corticotropin-releasing factor (CRF), the authors measured CRF-like immunoreactivity in CSF samples from 138 neurological control, 54 depressed, and 27 nondepressed (23 schizophrenic and four manic) subjects. The CSF CRF concentration was markedly higher (almost twofold) in depressed patients than in control subjects and nondepressed psychiatric patients. The concentration of CSF CRF was slightly but significantly higher in schizophrenic patients than in control subjects. These findings provide further support for the hypothesis that CRF hypersecretion occurs in major depression.
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PMID:CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia. 349 2

One hundred micrograms of ovine-corticotropin releasing factor (o-CRF) was administered intravenously to eight unmedicated patients with severe endogenous depression. Responses of immunoreactive (ir)-ACTH and the adrenal glucocorticosteroids corticosterone (B), 11-deoxycortisol (S), cortisol (F) and cortisone (E) were measured and compared with those following synthetic corticotropin stimulation and dexamethasone suppression. A comparative evaluation of the three pituitary--adrenal function tests suggests that hypersecretion of ir-ACTH and adrenal corticosteroids (B, S, F, and E) in depression reflects a central dysfunction rather than an altered responsiveness of the pituitary or adrenal glands. The data illustrate that the o-CRF paradigm is a valuable instrument to further support the hypothesis that a limbic--hypothalamic overdrive is the basic mechanism underlying exaggerated adrenocortical output in the endogenous subgroup of depressed patients.
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PMID:ACTH and multisteroid responses to corticotropin-releasing factor in depressive illness: relationship to multisteroid responses after ACTH stimulation and dexamethasone suppression. 608 43

The mechanism of the circadian hormonal secretions is still obscure. The cyclic activity of the hypothalamus-ACTH-adrenal (H-A-A) axis is perhaps the most studied. ACTH derives with other peptides from a common precursor, proopiomelanocortin. ACTH secretion is under inhibitory and stimulatory influences. The inhibitory influence is mediated by the negative feed-back of adrenal corticosteroids and by the short loop feed-back of ACTH on its own secretion. The stimulatory influence is exerted by the hypothalamic corticotropin releasing factor (CRF), recently isolated in the ovine hypothalamus. CRF is regulated by various neurotransmitttttorial activities. Serotonin and acetylcholine play a stimulatory role, while dopamine and norepinephrine, in particular, seem to exert an inhibitory tonic control. The increased ACTH secretion in stress-response seems to be mediated by a reduction of this tone. However, the neurotransmitorial modifications involved in the rhythmic secretion of the H-A-A axis are still obscure. So chrononeuroendocrine study of the H-A-A axis in various psychoneuroendocrine diseases is of great interest in clearing up the neurotransmitorial mechanisms of this rhythm. Primary depression represents an interesting model being characterized by monoaminergic neurotransmitorial alterations. We have observed in this pathology an increase of the H-A-A axis activity and an alteration of the circadian cortisol profile characterized by an increase both in numeric and quantitative secretory bursts.
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PMID:Chrononeuroendocrine perspectives of ACTH and related peptides. 613 88

Neuroendocrine abnormalities present in depressive illness and use of the dexamethasone suppression test (DST) in diagnosing depression are reviewed. The coexistence of neuroendocrine disturbances and depressive illness may be explained by a central nervous system neurochemical abnormality. Norepinephrine appears to inhibit hypothalamic corticotropin-releasing factor, thus decreasing ACTH secretion by the pituitary and, in turn, cortisol secretion by the adrenal glands. Thus, a deficiency in brain norepinephrine may lead to both depressive symptoms and increased adrenal cortisol production. Episodes of cortisol secretion are longer and more frequent in depressed patients, and the circadian rhythm of cortisol release is altered. Dexamethasone does not suppress plasma cortisol levels in depressed patients as compared with normal subjects. Abnormal DST results were obtained in 40-70% of inpatients and 20-50% of outpatients diagnosed as having unipolar primary depression or major depressive illness. The incidence of abnormal DST results in most nondepressed psychiatric patients is comparable with that in normal subjects. DST results do not distinguish between unipolar and bipolar depression but may differentiate primary from secondary depression. Depressed patients with abnormal DSTs responded positively to drug treatment. DST nonsuppressors responded more favorably to norepinephrine-reuptake blockers, while DST suppressors preferentially improved with serotonin-reuptake blockers. Normalization of DST response has been associated with clinical improvement. Certain drugs, a number of psychiatric conditions, and several major physical illnesses may alter DST response. The DST is a commonly used and practical tool in evaluating depressive illness; however, its diagnostic value in depressed outpatients and elderly depressed patients is not clear.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dexamethasone suppression test in diagnosis of depressive illness. 614 96


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