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

In 40 patients with Alzheimer's disease (AD) 56 patients with senile dementia of Alzheimer type (SDAT) and 45 patients with vascular dementia (VAD) degree of dementia was rated into mild, moderate and severe according to DSM-III-R and on the GBS scale. Basal cortisol levels were determined and a dexamethasone test (DST) performed. Basal cortisol levels were high in all the dementia groups. Forty percent of AD patients, 54% of SDAT patients and 49% of VAD patients were non suppressors. Significant correlations between post DST cortisol levels and rated variables were seen mainly in the VAD group. The pathological DST could hardly be explained by presence of depression. In dementia, especially those with white matter disturbances, disconnections between cortical areas (hippocampus) and hypothalamus can be assumed explaining a reduced inhibitory tone on hypothalamus. When characterizing VAD patients with pathological DST these patients were significantly more intellectually impaired, showed higher degree of anxiety, restlessness and fear-panic than VAD patients with normal DST. Some behaviourial disturbances in dementia disorders may be a consequence of HPA over activity rather than a consequence of the dementia process itself.
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PMID:Hypothalamic dysfunction in dementia. 788 1

This paper describes the construction of a computer model that simulates the hypothalamic-pituitary-adrenal axis (HPA axis) regulation of cortisol production. It is presented to illustrate the process of physiological modeling using standard "off the shelf" technologies. The model simulates components of the HPA axis involved in the continuous secretion and elimination of cortisol, adrenocorticotropin (ACTH), and corticotropin releasing hormone (CRH). The physiological relations of these component pieces were modeled based on the current knowledge of their functioning. Rate constants, half lives, and receptor affinities were assigned values derived from the experimental literature. At its current level of development the model is able to accurately simulate the timing, magnitude and decay of the ACTH and cortisol concentration peaks resulting from the ovine-CRH stimulation test in normal and hypercortisolemic patients. The model will be used to predict the effects of lesions in different components of the HPA axis on the time course of cortisol and ACTH levels. We plan to use the model to explore the experimental conditions required to distinguish mechanisms underlying various disorders of the HPA axis, particularly depression. Efforts are currently underway to validate the model for a large variety of normal and pathological perturbations of the HPA axis.
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PMID:A computer simulation of the hypothalamic-pituitary-adrenal axis. 794 52

1. Delta TSH, REM latency, 4 pm and 11 pm post-dexamethasone cortisol values were determined after a wash-out period in a group of 74 non-selected depressed patients who were diagnosed (according to RDC with the SADS) as follows: 46 definite and 10 probable MD, 4 minor and 14 intermittent depression. 2. These biological variables, as well as gender, age and basal TSH were introduced in a principal component analysis. The four first PC scores explaining up to 77% of the data set were further calculated for each patients and used in a cluster analysis. A three clusters solution was retained. 3. DST escape and increased TSH response to TRH each identified subgroups of depressed patients. Conversely, blunted TSH response or REM latency were inefficient to classify patients. 4. Thus, HPA hyperactivity characterized CL-I patients (n = 29). These were more severely depressed, displayed more endogenous features and were reported as being more anxious. 5. Increased TSH response to TRH identified CL-III, exclusively composed of female patients (n = 10) that displayed more apparent sadness and tended to be older. 6. In CL-II, the usual sex-ratio for depressive illness was reversed and patients (n = 35) exhibited the least HPA axis disturbances and the same rate of blunted TSH response than in CL-I. They were also less severely depressed, displayed less endogenous characteristics and were rated as more mood reactive. 7. These results suggest heterogeneity in biological disturbances in depression and further stress the importance for controlling age, gender and severity of illness in studies investigating biological markers in depression.
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PMID:Biological markers as classifiers for depression: a multivariate study. 797 60

A corticotropin-releasing hormone (CRH) stimulation test with four cumulative doses of human CRH (0.01, 0.06, 0.2 and 1 microgram/kg body weight) and infusion of a low dose of [Arg8]-vasopressin (0.004 U/kg body weight/30 min) was performed in five depressed patients and six healthy subjects. Plasma samples for the measurement of cortisol, ACTH and beta-endorphin were taken at regular intervals and considered as measures of pituitary-adrenal function. A dose-response relationship between CRH and the hormones measured was found in patients and controls. Depressed patients already responded to the lowest dose of CRH with respect to cortisol release, whereas ACTH and beta-endorphin responded to the second and third doses, respectively. In control subjects the cortisol and ACTH response started after the third dose of CRH, whereas beta-endorphin responded significantly to the highest dose only. When both groups were compared, differences in response were found to the higher doses of CRH with respect to cortisol, ACTH and, less markedly, beta-endorphin and to the lowest dose of CRH with respect to cortisol. Although numbers are small, the data show 'blunting' of the ACTH response to the higher doses of CRH in patients with an enhanced cortisol response of the adrenals to lower and higher doses of CRH. There was no significant difference in response when CRH was used with vasopressin as compared to treatment with CRH alone. Thus, in this design vasopressin did not contribute significantly to CRH activity. The data suggest that pituitary cell sensitivity might be changed in depression as part of HPA dysfunction.
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PMID:Stimulation of the pituitary-adrenal system with graded doses of CRH and low dose vasopressin infusion in depressed patients and healthy subjects: a pilot study. 811 Dec 27

In contrast to the effects of GHRH in young normal human subjects, in which repetitive i.v. administration of GHRH prompts an increase in the amount of slow wave sleep (SWS) and in GH secretion and blunting of cortisol release, both in young and in old patients with depression there is no effect on SWS and cortisol release after GHRH, while GH secretion is stimulated. We assume that HPA activity and SWS are inert to the influence of GHRH during acute depression because of a slight CRH overactivity, whereas GHRH exerts effects on GH secretion.
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PMID:[Action of growth hormone releasing hormone (GHRH) on sleep EEG and nocturnal secretion of growth hormone, cortisol and ACTH in patients with major depression]. 858 84

Hypercortisolism in depression seems to preferentially reflect activation of hypothalamic CRH secretion. Although it has been postulated that this hypercortisolism is an epiphenomenon of the pain and stress of major depression, our data showing preferential participation of AVP in the hypercortisolism of chronic inflammatory disease suggest specificity for the pathophysiology of hypercortisolism in depression. Our findings that imipramine causes a down-regulation of the HPA axis in experimental animals and healthy controls support an intrinsic role for CRH in the pathophysiology of melancholia and in the mechanism of action of psychotropic agents. Our data suggest that hypercortisolism is not the only form of HPA dysregulation in major depression. In a series of studies, commencing in patients with Cushing's disease, and extending to hyperimmune fatigue states such as chronic fatigue syndrome and examples of atypical depression such as seasonal affective disorder, we have advanced data suggesting hypofunction of hypothalamic CRH neurons. These data raise the question that the hyperphagia, hypersomnia, and fatigue associated with syndromes of atypical depression could reflect a central deficiency of a potent arousal-producing anorexogenic neuropeptide. In the light of data presented elsewhere in this symposium regarding the role of a hypofunctioning hypothalamic CRH neuron in susceptibility to inflammatory disease, these data also raise the question of a common pathophysiological mechanism in syndromes associated both with inflammatory manifestations and atypical depressive symptoms. This concept of hypofunctioning of hypothalamic CRH neurons in these disorders also raises the question of novel forms of neuropharmacological intervention in both inflammatory diseases and atypical depressive syndromes.
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PMID:Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs. 859 44

Adrenal sensitivity was assessed in 16 non-depressed patients with NINCDS/ADRDA Alzheimer's disease (AD) and 18 control subjects by measuring cortisol response to low dose (0.05 microgram/kg i.v.) exogenous adrenocorticotrophic hormone (ACTH). Controlling for sex and medication, both peak cortisol level (peak-baseline) and area under cortisol response curve (AUC above baseline) were significantly greater in AD subjects. This shows that HPA axis hyperactivity, as demonstrated by enhanced adrenal sensitivity to ACTH, occurs in AD. Similar findings have been reported to occur in depression. Among AD subjects, AUC cortisol response correlated with current age (r = 0.70, P = 0.001) and age at onset of dementia (r = 0.73, P = 0.001) and an inverse correlation was seen between cortisol AUC and cognitive test (CAMCOG) score (r = -0.51, P = 0.044). Our findings suggest that HPA axis hyperactivity in AD is associated with advancing age and cognitive dysfunction. Such changes may be cause, or consequence, of neuronal loss.
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PMID:Enhanced adrenal sensitivity to adrenocorticotrophic hormone (ACTH) is evidence of HPA axis hyperactivity in Alzheimer's disease. 864 65

This study investigates cortisol and ACTH (corticotropin) responses to an infusion of human CRH (corticotropin-releasing hormone) in prepubertal children with major depressive disorder (MDD). Following a period of 24 hours of adaptation to the laboratory environment with an intravenous catheter in place, 34 children with MDD and 22 healthy controls received 1 microgram/kg of human CRH at 5:00 PM. Blood samples for cortisol and ACTH were measured at baseline and post-CRH. Overall, there were no significant differences between the MDD and the normal controls in baseline or post CRH stimulation values of either cortisol or ACTH. Melancholic (n = 4) patients had significantly higher baseline cortisol levels than nonmelancholic (n = 24) patients. Compared with the outpatients and the nonmelancholics, the inpatients (n = 10) and the melancholics showed significantly lower total ACTH secretion (effect size: 0.9 and 1.4, respectively) after CRH infusion. These results are consistent with a broad literature suggesting that the HPA axis abnormalities occur less frequently in early-onset depression than reported in adult studies. The pattern of results in the subgroups of inpatients and in melancholic children, however, raise questions about possible continuities with adult studies.
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PMID:Corticotropin-releasing hormone challenge in prepubertal major depression. 864 73

Adrenocorticotropic hormone (ACTH) and cortisol secretion have been shown to be abnormal in approximately half of depressed patients. Information from pituitary and adrenal studies suggests that the locus of this dysregulation is at or above the level of the hypothalamus; however, direct evidence from provocative studies of the hypothalamic corticotropin releasing hormone (CRH) neuron does not exist. The current study was designed to stimulate hypothalamic CRH release using the opiate antagonist naloxone in patients with depression and elevated urinary-free cortisols as well as healthy and psychiatric controls. All subjects received naloxone and placebo on separate days in a double-blinded, randomized fashion at a dose determined previously to reliably induce significant increases in ACTH and cortisol secretion. No significant differences were noted among groups. We conclude that although naloxone is an effective central stimulant of the hypothalamic CRH neuron, stimulation of the hypothalamic CRH neuron with naloxone does not provide evidence of dysregulation of the HPA axis in depression.
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PMID:Naloxone-induced pituitary-adrenal activation does not differ in patients with depression, obsessive compulsive disorder, and healthy controls. 884 Mar 57

The stress system is controlled by brain nuclei at the hypothalamus and brainstem. These nuclei interact with each other and control the HPA axis and sympathetic nervous systems, respectively. Major inputs to the stress system arise from the cerebral cortex and subcortical systems, the sensory organs and nerves, and the endocrine and immune systems. The major peripheral effectors of the stress system are glucocorticoids and the catecholamines. Pathological hypoactivity of the stress system has been associated with atypical depression, the chronic fatigue/fibromyalgia syndromes and autoimmune inflammatory disease; hyperactivity with melancholic depression and anxiety disorders. The stress system responds in a quantitatively and qualitatively specific fashion to different stressors. A major role of the HPA axis is to restrain the immune system and prevent tissue damage. Reciprocal interactions between the HPA axis and immune system constitutes a new endocrine feedback loop that has given rise to the field of neuroendocrine immunology. Gonadal axis hormones directly, and indirectly via the HPA axis, alter the tone of the immune system and the quality and quantity of the inflammatory responses. Effects of the HPA axis on the gonadal axis are consistent with conservation and redirection of valuable resources towards homeostasis during times of stress. These complex interactions between the HPA axis, immune and the gonadal systems may prove to be fundamental in the genesis and perpetuation of autoimmune disease.
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PMID:The three-way interactions between the hypothalamic-pituitary-adrenal and gonadal axes and the immune system. 891 46


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