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)

Evidence is reviewed in favour of a close relationship between the pineal hormone, melatonin and ACTH--cortisol in man. Subgroups of patients with Cushing's disease as well as with major depressive disorder have low levels of nocturnal serum melatonin. Depressed patients with an abnormal dexamethasone suppression test (DST) have lower melatonin levels than do patients with a normal DST. Low melatonin levels may be a genetic trait marker for vulnerability to depression. The mechanism may be related to increased corticotropin-releasing factor (CRF), secondary to hypofunction of a pineal factor which physiologically inhibits CRF.
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PMID:The relationship between the pineal gland and the pituitary--adrenal axis in health, endocrine and psychiatric conditions. 630

Corticotropin-releasing factor (CRF) is a newly sequenced neuropeptide thought to be a principal stimulus to pituitary corticotropin (ACTH) secretion. Evidence obtained from laboratory animals and primates is reviewed which indicates that CRF not only stimulates the pituitary-adrenal axis but also influences several aspects of CNS function which may be of relevance to psychiatric illness. Clinically, experience in administering ovine CRF to more than 150 individuals shows that CRF can be helpful in resolving differential diagnostic dilemmas in patients with various disorders of the hypothalamic-pituitary-adrenal axis and in furthering an understanding of the pathophysiology of conditions such as Cushing's disease and depression.
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PMID:Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. 632 97

Depression of thyroid status with thiouracil has been shown to delay the response of the hypothalamus-pituitary-adrenal axis to stress in young rats. In vivo and in vitro bioassay studies have indicated that the hypothalamus is the main site of axis alteration in 15 day old animals. The present study has found a significantly depressed hypothalamic content of immunoassayable corticotropin-releasing factor (CRF) in thiouracil treated young rats.
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PMID:Depressed hypothalamic CRF immunoreactivity in 15 day old thiouracil-treated rats. 633 81

The present survey highlights the rationale for the use of state-dependent biological markers as predictors of clinical course in depression. Cortisol plasma levels after dexamethasone provide such a tool to monitor clinical progress. Since dexamethasone-resistant cortisol gradually returns to normalcy before a complete clinical remission is seen this measure has a possible predictive potential. Moreover, reversion to abnormal dexamethasone responses is prognostically infaust. Though the dexamethasone test has some merits, technical factors (e.g. exclusion criteria, dexamethasone-kinetics) which invalidate test results deserve careful consideration in future studies. Cortisol hypersecretion is considered as a physiological readout of a central disinhibition. This hypothesis is tested applying corticotropin-releasing factor and corticotropin in normal and abnormal DST responders. The data support the validity of the concept which assumes an intact but overactive pituitary-adrenal axis in a depressed subpopulation. A thesis is submitted which places the variety of biological disturbances in depression between two extreme viewpoints. One view considers all biological disturbances as sequelae to one particular dysfunction, e.g. disinhibition of corticosteroid secretion. The opposite view considers the myriad of biological disturbances as a sign of general loss of order, i.e. increased entropy, the precipitating mechanism of which is unknown.
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PMID:Prediction of clinical course by dexamethasone suppression test (DST) response in depressed patients - physiological and clinical construct validity of the DST. 666 28

Dextroamphetamine sulfate administered intravenously in the morning to 11 unmedicated depressed patients suppressed previously elevated plasma cortisol levels to normal in 90 minutes, a fall of 33% from baseline. Ten other depressed patients, without amphetamine, maintained high cortisol levels during the same time period. In each of five normal young men, amphetamine identically administered stimulated a rise in cortisol between 15 and 30 minutes after infusion, an acute response absent in ten of the 11 depressed patients; by 90 minutes after amphetamine administration, plasma cortisol had fallen to normal and identical levels in both groups. Since noradrenalin normally inhibits hypothalamic corticotropin releasing factor (and adrenocorticotropic hormone) secretion, a noradrenergic deficit may account for cortisol hypersecretion in depression; amphetamine may transiently "correct" this deficit in depressed patients, thereby reducing their cortisol secretion.
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PMID:Dextroamphetamine and cortisol in depression. Morning plasma cortisol levels suppressed. 719 Mar 80

Abnormal adrenocortical regulation has been reported in patients with endogenous depression, including excessive cortisol production with loss of circadian periodicity and decreased suppression by dexamethasone. The inhibitory effect of the neurotransmitter norepinephrine (NE) on the hypothalamic-pituitary adrenal (HPA) axis through the regulation of corticotropin-releasing factor has been suggested by animal in vitro studies. In this study of six normal human subjects we have examined the relationship of basal cortisol activity and its sensitivity to dexamethasone suppression, measured by 24-hr urinary free cortisol, with basal noradrenergic activity, diurnal variation, and response to postural stimulation, measured by plasma NE. Base-line cortisol and the degree of dexamethasone suppression were significantly inversely correlated with all base-line measures of NE response to stimulation. NE response to stimulation on the morning after dexamethasone was also inversely correlated with the degree of cortisol suppression. The increase in the morning NE response to stimulation after dexamethasone was inversely correlated with both base-line and suppressed cortisol levels. There is significant diurnal variation in stimulated NE activity after dexamethasone. There results are consistent with an inhibitory role for NE in the regulation of HPA system and a reciprocal effect for cortisol on noradrenergic activity. The implication of this relationship for the understanding of adrenocortical regulation in depression is discussed.
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PMID:Adrenocortical function and plasma norepinephrine in normal human subjects. 727 80

A test with dexamethasone was performed in 52 patients with endogenous depression, 35 chronic alcoholics, and 85 healthy individuals. In the patients with the depression the test was pathological (inhibition in 19%), and in chronic alcoholics abnormal but to a lesser degree (44%). In the healthy subjects the inhibition was 64%. In periods of remissions the test was normal in all the persons examined. A treatment with tryptophan, DOPA and phenazepam increased the degree of the inhibition. On the basis of these findings, as well as proceeding from literary data it was supposed that the disturbance of the inhibition of corticosteroid secretion by dexamethasone was due to a deficit of serotonin and norepinephrine in the brain, since serotonin directly stimulates the secretion of the corticotropin-releasing factor, but at the same time intensifies the inhibitory action of glucocorticoids on its secretion. These results, as well as the literary data of the existence of a genetic connection between endogenous depression and chronic alcoholism in a number of cases give one grounds to assume that in patients with endogenous depression and in a part of chronic alcoholics the predisposition to the disease is associated with some common, hereditarily-determined defects of the metabolism of biogenic amines in the brain.
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PMID:[Various factors common to the pathogenesis of endogenous depression and chronic alcoholism]. 732 94

Anxiety is a key symptom of the cocaine withdrawal syndrome in human addicts, and it is considered to be one of the major factors in precipitating relapse to chronic cocaine abuse. Corticotropin-releasing factor (CRF) plays an important role in the pathophysiology of anxiety and depression, and it may also be involved in the acute behavioral and neuroendocrine actions of cocaine. The role of endogenous CRF in cocaine withdrawal-induced anxiety was investigated in the present study. Animals were subjected to chronic cocaine (20 mg/kg, intraperitoneally, once a day for 14 days) administration. Rats tested 30 min after the last cocaine injection did not show withdrawal anxiety on the elevated plus maze or any alterations in brain CRF levels. Withdrawal (48 h) from chronic cocaine administration produced an intense anxiety-like behavior characterized by decreased open arm exploration. Immunoreactive CRF (CRF-LI) levels were selectively altered in the hypothalamus, in the amygdala and in the basal forebrain structures at the time of the behavioral anxiety, reflecting an increased activity of brain CRF systems. Daily intracerebroventricular (i.c.v.) pretreatment with an immunoserum raised against CRF completely prevented the development of anxiety induced by cocaine withdrawal. These data suggest that extrahypothalamic-limbic CRF hypersecretion may be involved in the development of anxiety related to cocaine withdrawal and that the CRF system may be a useful target for new pharmacotherapies for cocaine withdrawal and relapse.
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PMID:Brain corticotropin-releasing factor mediates 'anxiety-like' behavior induced by cocaine withdrawal in rats. 779 57

Hypersecretion of corticotropin-releasing factor (CRF), has been hypothesized to occur in depression. Because CRF may serve as a neurotransmitter in the locus coeruleus (LC), it was proposed that CRF hypersecretion in the LC is responsible for some characteristics of depression, and that antidepressants act by interfering with CRF neurotransmission in the LC. To test this hypothesis, the acute and chronic effects of four antidepressants and cocaine were characterized on LC spontaneous and sensory-evoked discharge, LC activation by a stressor that requires CRF release, and LC activation by exogenously administered CRF. None of the antidepressants or cocaine altered LC activation by intracerebroventricularly administered CRF (3.0 microgram) after chronic administration. However, chronic administration of desmethylimipramine and mianserin inhibited LC activation by a hypotensive stress that requires endogenous CRF release, suggesting that they decrease CRF release in the LC. Chronic administration of sertraline and phenelzine altered LC responses to repeated sciatic nerve stimulation in a manner opposite to the effect produced by CRF, suggesting that these drugs may functionally antagonize CRF actions in the LC. Cocaine did not appear to interfere with CRF actions in the LC. In conclusion, chronic administration of antidepressants may have the potential to interfere with CRF neurotransmission in the LC.
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PMID:Corticotropin-releasing factor neurotransmission in locus coeruleus: a possible site of antidepressant action. 785 15

Patients with Alzheimer's disease (AD) and major depression have been shown to have overlapping clinical symptoms and biological markers, including decreased concentrations of cerebrospinal fluid (CSF) somatostatin-like immunoreactivity (SLI), which may be related to alterations in the hypothalamic-pituitary-adrenal axis activity. As in prior studies, we found that CSF SLI was significantly decreased in a group of AD patients (N = 49) and a group of elderly patients with major depression (N = 18), as compared with 13 age-matched controls (F[2, 77] = 12.9, p < .001). In the present study, CSF SLI and CSF corticotropin-releasing factor correlated significantly within the group of AD patients (r = 0.49, p < .0004) and almost attained significance in the depressed patients (r = 0.47, p < .07). CSF SLI correlated significantly with urinary free cortisol within each patient group (r = -0.51, p < .03). Clinical measures of dementia severity and depression did not consistently correlate with CSF SLI in either patient group.
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PMID:CSF somatostatin in Alzheimer's disease and major depression: relationship to hypothalamic-pituitary-adrenal axis and clinical measures. 790 67


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