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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stress precipitates depression and alters its natural history. Major depression and the stress response share similar phenomena, mediators and circuitries. Thus, many of the features of major depression potentially reflect dysregulations of the stress response. The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction). Because depression is a heterogeneous illness, we studied two diagnostic subtypes, melancholic and atypical depression. In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning. They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes. Patients with atypical depression present with a syndrome that seems the antithesis of melancholia. They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning. In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency in atypical depression, and our data show us that these are of central origin. Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately. In the present paper, we shall first review the mediators and circuitries of the stress system to lay the groundwork for placing in context physiologic and structural alterations in depression that may occur as part of stress system dysfunction.
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PMID:Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. 1192 Jan 53

The symptomatology characterizing fibromyalgia comprises three systems: the musculoskeletal system with widespread muscular pain, neuroendocrine disorders, and psychological distress including anxiety and depression. Fibromyalgia is predominantly found in middle aged women. Though the most prominent symptom of fibromyalgia is pain in defined regions of the locomotor system, the numerous other somatoform and psychological disorders suppose a common primary disturbance which is considered to originate within higher levels of the central nervous system. Studies of the entire endocrine profile of fibromyalgia patients support the hypothesis that an elevated activity of corticotropin releasing hormone (CRH) neurons determines not only many symptoms of fibromyalgia but may also cause alterations observed in the hormonal axes. Hypothalamic CRH neurons thus may play a key role not only in resetting the various endocrine loops but possibly also nociceptive and psychological mechanisms as well
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PMID:Pathogenic mechanisms of fibromyalgia. 1203 41

Obesity and starvation have opposing affects on normal physiology and are associated with adaptive changes in hormone secretion. The effects of obesity and starvation on thyroid hormone, GH, and cortisol secretion are summarized in Table 1. Although hypothyroidism is associated with some weight gain, surveys of obese individuals show that less than 10% are hypothyroid. Discrepancies have been reported in some studies, but in untreated obesity, total and free T4, total and free T3, TSH levels, and the TSH response to TRH are normal. Some reports suggest an increase in total T3 and decrease in rT3 induced by overfeeding. Treatment of obesity with hypocaloric diets causes changes in thyroid function that resemble sick euthyroid syndrome. Changes consist of a decrease in total T4 and total and free T3 with a corresponding increase in rT3. untreated obesity is also associated with low GH levels; however, levels of IGF-1 are normal. GH-binding protein levels are increased and the GH response to GHRH is decreased. These changes are reversed by drastic weight reduction. Cortisol levels are abnormal in people with abdominal obesity who exhibit an increase in urinary free cortisol but exhibit normal or decreased serum cortisol and normal ACTH levels. These changes are explained by an increase in cortisol clearance. There is also an increased response to CRH. Treatment of obesity with very low calorie diets causes a decrease in serum cortisol explained by a decrease in cortisol-binding proteins. The increase in cortisol secretion seen in patients with abdominal obesity may contribute to the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, and hypertension). States of chronic starvation such as seen in anorexia nervosa are also associated with changes in thyroid hormone, GH, and cortisol secretion. There is a decrease in total and free T4 and T3, and an increase in rT3 similar to findings in sick euthyroid syndrome. The TSH response to TRH is diminished and, in severe cases, thyroid-binding protein levels are decreased. In regards to GH, there is an increase in GH secretion with a decrease in IGF-1 levels. GH responses to GHRH are increased. The [table: see text] changes in cortisol secretion in patients with anorexia nervosa resemble depression. They present with increased urinary free cortisol and serum cortisol levels but without changes in ACTH levels. In contrast to the findings observed in obesity, the ACTH response to CRH is suppressed, suggesting an increased secretion of CRH. The endocrine changes observed in obesity and starvation may complicate the diagnosis of primary endocrine diseases. The increase in cortisol secretion in obesity needs to be distinguished from Cushing's syndrome, the decrease in thyroid hormone levels in anorexia nervosa needs to be distinguished from secondary hypothyroidism, and the increase in cortisol secretion observed in anorexia nervosa requires a differential diagnosis with primary depressive disorder.
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PMID:Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol secretion. 1205 88

Neuroendocrine studies strongly suggest that the hypothalamic-pituitary-adrenocortical (HPA) system plays a crucial role in the development and course of depression. The interaction between the disease process and HPA system function in long-term course, however, is unclear. Since improvement of HPA system deterioration has been demonstrated to be associated with treatment response, the question has arisen whether the course of therapy response as reflected by, for example, early improvement or response (after 1 or 2 weeks of therapy) is also based on HPA system dysfunction and whether the course of HPA regulation during treatment is only a state marker or has additional predictive implications for long-term outcome. In order to elucidate these questions a long-term study was carried out to investigate whether HPA system disturbance is associated (1) with the course of treatment response, predominantly early treatment response, during acute depression and (2) with the long-term course of depression, i.e. number of episodes. Twenty patients with affective disorders who participated in earlier controlled antidepressant treatment studies over 6 weeks were enrolled in an exploratory follow-up study. Using the combined DEX/CRH test it was demonstrated that (1) early improvement, early treatment response and beneficial treatment outcome after 6 weeks were associated with a lower HPA system activity and that (2) in long-term course of depression the HPA system deterioration increases in parallel with the number of previous episodes. These findings suggest that HPA system alterations are closely related to treatment response and long-term outcome of depression.
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PMID:The combined DEX-CRH test in treatment course and long-term outcome of major depression. 1212 96

The Dex/CRH test is one of the most reliable neuroendocrine function tests for hypothalamic-pituitary-adrenocortical (HPA) system dysregulation in depression. Persistent overdrive of HPA system activity after successful antidepressant treatment predicts an enhanced risk for relapse of a depressive episode. As the renin-angiotensin system has been shown to play a role in HPA system activity, we investigated the impact of the angiotensin converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism, which determines ACE plasma concentrations, on HPA system dysregulation. We performed repeated combined Dex/CRH tests in 115 patients suffering from major depression. Dex/CRH test results were related to the I/D polymorphism within the ACE gene, which was assessed by PCR. Genotype frequencies were comparable to those in the general population (I/I 16.8%, I/D 59.3%, D/D 23.9%). D/D genotypes showed a higher cortisol stimulation during the first Dex/CRH test after admission than homozygous I-allele carriers (repeated measurement ANOVA: P=0.034). Cortisol area under the curve values were highest in those with the D/D genotype (mean+/-SEM [nmol/l*75 min]: 12700+/-2220), intermediate in those with the I/D genotype (9570+/-1000), and lowest in those with the I/I genotype (5160+/-1000; ANOVA: P=0.04). After successful antidepressive treatment and attenuation of HPA system overdrive these differences were no more detectable. The HPA axis stimulating properties of higher ACE and consecutively higher AT-II and/or lower substance P concentrations may be crucial factors for the HPA system hyperactivity during major depressive episodes.
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PMID:Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene. 1214 30

Lithium augmentation is a well established strategy for treatment-resistant depression. The exact mode of its action is unknown, but an enhancement of serotonergic transmission is hypothesized. The authors investigated changes in the hypothalamic-pituitary-adrenocortical (HPA) system during lithium augmentation and their correlation to clinical response by means of the combined dexamethasone/CRH test (DEX/CRH test). Thirty patients with unipolar major depressive episodes (DSM IV) who had not responded to an adequate trial with an antidepressant were assessed on the day before lithium augmentation (baseline) with the DEX/CRH test (pretreatment with 1.5 mg dexamethasone p.o. at 11 P.M. and CRH stimulation at 3 P.M. on the next day). Twenty-four patients were re-assessed after response was determined or, in cases of non-response, four weeks after initiation of lithium augmentation. Response to lithium augmentation was measured by weekly ratings on the Hamilton Depression Rating Scale (HDRS 17-item version). Response was defined as a DeltaHDRS of > or =50% and an endpoint score of < 10. Patients had a significantly higher ACTH and cortisol response to CRH stimulation during lithium augmentation compared with the values at baseline. There was no difference in ACTH and cortisol reaction between responders and non-responders to lithium augmentation. This increase is in contrast to the known normalization of HPA-axis overdrive after treatment with a tricyclic antidepressant like amitriptyline. Because the effect was independent of response status we suggest that this increase reflects an effect of lithium that is independent from the psychopathological state or its change. This effect might be explained by the serotonergic effects of lithium.
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PMID:Lithium augmentation increases the ACTH and cortisol response in the combined DEX/CRH test in unipolar major depression. 1222 4

Benzodiazepines (BDZ) are one of the most prescribed classes of drugs because of their marked anxiolytic, anticonvulsant, muscle relaxant and hypnotic effects. The pharmacological actions of BDZ depend on the activation of 2 specific receptors. The central BDZ receptor, present in several areas of the central nervous system (CNS), is a component of the GABA-A receptor, the activation of which increases GABAergic neurotransmission and is followed by remarkable neuroendocrine effects. The peripheral benzodiazepine receptors (PBR), structurally and functionally different from the GABA-A receptor, have been shown in peripheral tissues but also in the CNS, in both neurones and glial cells, and in the pituitary gland. BDZ receptors bind to a family of natural peptides called endozepines, firstly isolated from neurons and glial cells in the brain and then in several peripheral tissues as well. Endozepines modulate several central and peripheral biological activities, including some neuroendocrine functions and synthetic BDZ are likely to mimic them, at least partially. BZD, especially alprazolam (AL), possess a clear inhibitory influence on the activity of the HPA axis in both animals and humans. This effect seems to be mediated at the hypothalamic and/or suprahypothalamic level via suppression of CRH. The strong negative influence of AL on hypothalamicpituitary-adrenal (HPA) axis agrees with its peculiar efficacy in the treatment of panic disorders and depression. BZD have also been shown to increase GH secretion via mechanisms mediated at the hypothalamic or supra-hypothalamic level, though a pituitary action cannot be ruled out. Besides the impact on HPA and somatotrope function, BDZ also significantly affect the secretion of other pituitary hormones, such as gonadotropins and PRL, probably acting through GABAergic mediation in the hypothalamus and/or in the pituitary gland. In all, BDZ are likely to represent a useful tool to investigate GABAergic activity and clarify its role in the neuroendocrine control of anterior pituitary function; their usefulness probably overrides what had been supposed before.
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PMID:Benzodiazepines and anterior pituitary function. 1224 Sep 8

The diagnosis of Cushing's syndrome rests on the demonstration of clinical features and biochemical abnormalities that reflect hypercortisolism. If a patient presents with typical clinical features such as weight gain with truncal obesity and supraclavicular fat deposition, wide purple striae, and proximal muscle weakness, the diagnosis is clear-cut and is nearly always substantiated by a 24-hour urine free cortisol excretion value more than four times the normal level. However, many patients present with signs and symptoms that are common in the general population, such as hypertension, generalized weight gain, reproductive abnormalities, and depression. Many of these patients have normal cortisol excretion and do not have Cushing's syndrome. Others have mild hypercortisolism caused by psychiatric disorders, obligate exercise, morbid obesity, sleep apnea, or uncontrolled diabetes mellitus. These patients may be confused with those with the true Cushing's syndrome, and thus are considered to have a "pseudo-Cushing" state. Additional observation over time, and testing with midnight cortisol measurements, the 2-day-2-mg dexamethasone suppression test, or the dexamethasone suppression-CRH stimulation test may be useful to identify true Cushing's syndrome in these patients.
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PMID:Diagnostic tests for Cushing's syndrome. 1238 46

The intention of this review is to summarize the current knowledge on the bidirectional interaction between sleep EEG and the secretion of corticotropin (ACTH) and cortisol. The administration of various hypothalamic-pituitary- adrenocortical (HPA) hormones and their antagonists exerts specific sleep-EEG changes in several species including humans. It is well documented that corticotropin releasing hormone (CRH) impairs sleep and enhances vigilance. In addition, it may promote REM sleep. Changes in the growth hormone-releasing hormone (GHRH):CRH ratio in favour of CRH appear to contribute to shallow sleep, elevated cortisol levels and blunted GH in depression and ageing. On the other hand, in women GHRH appears to exert CRH-like effects on sleep. Acute cortisol administration increases slow-wave sleep (SWS) and GH, probably due to feedback inhibition of CRH, and inhibits REM sleep. With the mixed glucocorticoid and progesterone receptor antagonist mifepriston sleep is disrupted. Subchronic administration of the glucocorticoid agonist methylprednisolone desinhibited REM sleep. A synergism of elevated CRH and cortisol activity may contribute to REM disinhibition during depression. Also ACTH and vasopressin modulate sleep specifically but their physiological role remains unclear. For example acute icv vasopressin enhances wakefulness in rats, whereas its long-term administration increases SWS in the elderly. In various studies the interaction of sleep EEG and HPA hormones has been investigated at the baseline, after manipulation of sleep-wake behaviour and after environmental changes. Most studies agree that the circadian pattern of cortisol is relatively independent from sleep and environmental influences. Some data suggest a major effect of light on cortisol secretion. Sleeping is widely associated with blunting and awakenings are linked with increases of HPA hormones.
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PMID:Sleep and the hypothalamo-pituitary-adrenocortical system. 1253 Nov 48

It has been suggested that hypothalamic-pituitary-adrenal (HPA) system dysregulation plays an important role in the pathophysiology of depression and that normalization of HPA axis hyperactivity precedes successful treatment with antidepressants. We report the case of a 61-year-old patient suffering from a major depressive episode who underwent the combined dexamethasone suppression/CRH stimulation test (DEX/CRH test) before and again after one week of mirtazapine treatment. While the patient showed a marked decrease of cortisol and ACTH secretion during the DEX/CRH test within one week, a pronounced and ongoing deterioration of depressive symptoms with suicidal thoughts occurred that was resistant to antidepressant medication and had to be treated with electroconvulsive therapy. Apparently, mirtazapine rapidly attenuates HPA axis hyperactivity in depressed patients via direct pharmacoendocrinological effects. However, this amelioration of HPA system dysregulation is not necessarily accompanied by clinical improvement.
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PMID:Attenuation of HPA axis hyperactivity and simultaneous clinical deterioration in a depressed patient treated with mirtazapine. 1258 93


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