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)

1. Growth hormone (GH) secretion during sleep was studied in ten male patients with major depression according to DSM III and eight normal controls. 2. Samples were collected through a continuous blood withdrawal pump while sleep was recorded in the laboratory. 3. The results showed a marked decrease in the GH secretion mainly during the first three hours of sleep in depressed patients as compared to normal controls. DST and TRH tests were also administered to the same patients but no correlation was observed between a positive test and a blunted GH secretion, suggesting that the various neuroendocrinological disturbances do not coexist in all depressed patients. 4. This disturbance in GH secretion during sleep, along with reduced slow wave sleep (SWS), gives support to the theory that GHRH is the common stimulus of SWS and GH release and that the ratio of GHRH and its counterpart CRH plays a major role in the pathophysiology of disturbed endocrine activity during sleep in depression.
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PMID:Growth hormone secretion during sleep in male depressed patients. 961 44

The role of arginine vasopressin (AVPNP) in the control of adrenocorticotropic hormone (ACTH) secretion is explored, and in particular, its involvement in various stress response paradigms which may be of relevance in our understanding of the pathophysiology of depression. VP is released from two sites in the hypothalamus; the parvicellular division of the paraventricular nucleus (PVN), where corticotropin releasing hormone (CRH) is also formed, and from the magnocellular neurons of the supraoptic nucleus (SON) and the PVN. The intricate interaction with CRH, the other main ACTH secretagogue, and with glucocorticoids, the inhibitory feedback component of hypothalamic-pituitary-adrenal-axis (HPA) activity, is outlined. That VP plays an important role in the stress response is now beyond doubt. Examination of the impact of psychological stressors on the differential expression of VP and CRH at a hypothalamic and pituitary level has been facilitated by advances in molecular biological techniques. Of importance has been the cloning of the V1b receptor gene, the receptor at which AVP is active in the anterior pituitary. Chronic stress paradigms, associated with HPA hyperresponsiveness, and ACTH release following a novel superimposed stress, have been found with relative consistency to show a shift in the CRH:AVP ratio. This may relate to differing feedback sensitivity of AVP to glucocorticoid feedback restraint and the greater responsivity of AVP over CRH to chronic stimulatory stress input. Evidence for functionally distinct pools of ACTH releasing corticotropes, and the finding that AVP levels more closely correlate with ACTH levels than do CRH levels, suggest a more dynamic role for AVP in activity of the stress axis, and a primarily permissive function for CRH. The renewed interest in the role of VP in HPA axis activity may have important implications for furthering our understanding of psychiatric conditions such as depression, where significant dysregulation of this axis is seen. Elevated baseline cortisol, dexamethasone non-suppression and blunted CRH/ACTH release have been consistently documented. The possible contribution of VP to this hyperactivity, despite its known synergy with CRH, has been largely neglected. In animal models there is clear evidence that chronic psychological stressors increase the ratio of AVP to CRH production. Psychosocial stressors are intrinsically linked with depressive illness. The finding of elevated levels of AVP in postmortem studies of depressives and the lowering of CSF AVP levels by antidepressants, raises the question of the precise role of AVP in the overactivity of the HPA in depression, a finding that is currently attributed to overdrive of its HPA regulatory companion, CRH.
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PMID:Vasopressin and the regulation of hypothalamic-pituitary-adrenal axis function: implications for the pathophysiology of depression. 962 97

Chronic fatigue syndrome (CFS) is characterized by profound fatigue and an array of diffuse somatic symptoms. Our group has established that impaired activation of the hypothalamic-pituitary-adrenal (HPA) axis is an essential neuroendocrine feature of this condition. The relevance of this finding to the pathophysiology of CFS is supported by the observation that the onset and course of this illness is excerbated by physical and emotional stressors. It is also notable that this HPA dysregulation differs from that seen in melancholic depression, but shares features with other clinical syndromes (e.g., fibromyalgia). How the HPA axis dysfunction develops is unclear, though recent work suggests disturbances in serotonergic neurotransmission and alterations in the activity of AVP, an important co-secretagogue that, along with CRH, influences HPA axis function. In order to provide a more refined view of the nature of the HPA dusturbance in patients with CFS, we have studied the detailed, pulsatile characteristics of the HPA axis in a group of patients meeting the 1994 CDC case criteria for CFS. Results of that work are consistent with the view that patients with CFS have a reduction of HPA axis activity due, in part, to impaired central nervous system drive. These observations provide an important clue to the development of more effective treatment to this disabling condition.
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PMID:Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. 962 95

The neurobiological alterations commonly found in affective disorders (e.g., alterations in the nocturnal sleep profile, dysfunction of the hypothalamic-pituitary-adrenocortical system) gradually recover with improvement of the depressive syndrome. Their persistence during full clinical remission, however, is associated with an increased risk for relapse and, thus may represent trait markers for affective disorders. In order to test this hypothesis, we designed a prospective study in which healthy first-degree relatives (high-risk probands; HRPs; n = 54) of patients with an affective disorder are investigated by means of polysomnography, the combined dexamethasone and corticotropine-releasing hormone (DEX-CRH) test and a variety of psychometric scales. In the present part of the study (index assessment), these HRPs, as a group, showed depression-like alterations in both the sleep pattern and the DEX-CRH-test outcome; furthermore, their psychometric profile was characterized by elevated scores on the scales assessing "rigidity" and "autonomic lability". On a single-case level, 35% of the HRPs were identified as conspicuous (depression-like) in at least two of the three areas investigated. A decision of whether or not this "conspicuousness" indeed represents a trait marker for affective disorders can be reached when the follow-up part of the study has identified those HRPs with their respective premorbide status who have developed an affective disorder in the meantime.
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PMID:[The Munich Vulnerability Study of Affective Disorders. Overview of the results at index study]. 971 75

The effect of amitriptyline upon hypothalamic-pituitary-adrenal [HPA]-system-regulating neuropeptides (corticotropin-releasing hormone [CRH], vasopressin, somatostatin) was studied in a group of depressed elderly patients and controls. A first lumbar puncture was performed in 37 depressed in-patients. This was followed by a 6-week medication phase with amitriptyline. Upon its completion a second cerebrospinal fluid (CSF) sample was obtained in 18 of these 37 patients. In 25 healthy controls a first lumbar puncture was done eleven of these individuals agreed to take 75 mg/d amitriptyline for 6 weeks and to participate in the follow-up CSF study. Within the group of depressed patients amitriptyline led to a significant decrease of CSF CRH in treatment responders only (F1, 16 = 5.2; P < 0.02). Also, in normal controls CSF CRH concentration tended to decrease with amitriptyline treatment (t-test; P < 0.09). No effects of amitriptyline upon vasopressin or somatostatin were observed. In normal controls (r = 0.4; P < 0.02) and in patients (r = 0.4; P < 0.03) age correlated positively with baseline CSF somatostatin. A trend for CSF CRH to increase with aging was found only in controls (r = 0.3; P < 0.09); patients did not show a significant association here. Finally, CSF neuropeptide concentration at baseline did not differ between the group of depressed patients and healthy controls. Our study corroborates the evolving concept that antidepressants effect various components of the HPA system with the net result of a reduction in its activity. In addition, we found CSF CRH and CSF somatostatin concentrations to be better reflections of age than of depression and, finally, that during aging and during depression the HPA system changes in similar directions.
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PMID:Cerebrospinal fluid concentrations of corticotropin-releasing hormone, vasopressin, and somatostatin in depressed patients and healthy controls: response to amitriptyline treatment. 978 81

The cardinal clinical manifestations of major depression with melancholic features include sustained anxiety and dread for the future as well as evidence of physiological hyperarousal (e.g., sustained hyperactivity of the two principal effectors of the stress response, the corticotropin-releasing-hormone, or CRH, system, and the locus ceruleus-norepinephrine, or LC-NE, system). Sustained stress system activation in melancholic depression is thought to confer both behavioral arousal as well as the hypercortisolism, sympathetic nervous system activation, and inhibition of programs for growth and reproduction that consistently occur in this disorder. Data also suggest that activation of the CRH and LC systems in melancholia are involved in the long-term medical consequences of depression such as premature coronary artery disease and osteoporosis, the two-three-fold preponderance of females in the incidence of major depression, and the mechanism of action of antidepressant drugs. In addition, recent data reveal important bidirectional interactions between stress-system hormonal factors in depression and neural substrates implicated in many discrete behavioral alterations in depression (e.g., the medial prefrontal cortex, important in shifting affect based on internal and external cues, the mesolimbic dopaminergic reward system, and the amygdala fear system). We have also advanced data indicating that the hypersomnia, hyperphagia, lethargy, fatigue, and relative apathy of the syndrome of atypical depression are associated with concomitant hypofunctioning of the CRH and LC-NE systems. These data indicate the need for an entirely different therapeutic strategy than that used in melancholia for the treatment of atypical depression, and they suggest that this subtype of major depression will be associated with its own unique repertoire of long-term medical consequences.
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PMID:The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences. 989 54

After elucidating the components and theory of neuroticism (N) as well as of psychosomatic complaints and their relationships to personality dimensions and to psychosomatic diseases, comparisons are performed between patients suffering from fibromyalgia syndrome (FMS) or related pain diseases with healthy subjects scoring high on personality dimensions related to neuroticism. FMS and pain patients score high on depression, anxiety, and experience of stress although questionnaire scores on depression are higher in subjects not exhibiting somatic features of the disease. High subjective pain sensitivity and low thresholds for pain perception are also common features in high N subjects and FMS patients. On the endocrinological level cortisol responses to challenge tests with CRH as well as prolactin responses to TRH are higher in FMS patients than in high N healthy subjects indicating an endocrinological difference. A common feature, however, is the lack of adaptability in the two groups, since neurotics are in particular characterized by a low capacity to shift their behavior from one state to the other (waking-sleeping, working-relaxing), to re-adapt to baseline levels after endocrinological or physiological stress responses, or to adjust to conditions of shift work. This is reflected by chronobiological disturbances in FMS patients and could also explain their maintainance of pain perception, because they are incapable of correcting conditioned pain-producing muscle tension.
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PMID:The fibromyalgia syndrome as a manifestation of neuroticism? 1002 96

In order to receive a further understanding of stress-regulation in depressed suicide attempters, peptides that are supposed to be related to the stress system (the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system) were studied in plasma. When compared with healthy controls, cortisol was high (p<0.001) and corticotropin releasing hormone (CRH) and neuropeptide Y (NPY) appeared to be low (p<0.001) in patients who had recently attempted suicide. Patients who had repeatedly attempted suicide had the lowest NPY. A correlation between NPY and cortisol (p<0.05) was found in suicidal patients with depression NOS, whereas beta-endorphins correlated with cortisol (p<0.01) in suicidal patients with major depressive disorder. A postdexamethasone decrease of NPY was noted in the controls but not in the patients. These results suggest stress system alterations in suicidal patients with mood disorders.
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PMID:Alterations of corticotropin releasing hormone (CRH) and neuropeptide Y (NPY) plasma levels in mood disorder patients with a recent suicide attempt. 1020 89

Neuroendocrine studies strongly suggest that dysregulation of the hypothalamic pituitary-adrenocortical (HPA) system plays a causal role in the development and course of depression. Whereas the initial mechanism resulting in HPA hyperdrive remains to be elucidated, evidence has emerged that corticosteroid receptor function is impaired in many patients with depression and in many healthy individuals at increased genetic risk for an depressive disorder. Assuming such impaired receptor function, then central secretion of CRH would be enhanced in many brain areas, which would account for a variety of depressive symptoms. As shown in rats and also in transgenic mice with impaired glucocorticoid receptor function, antidepressants enhance the signaling through corticosteroid receptors. This mechanism of action can be amplified through blocking central mechanisms that drive the HPA system. Animal experiments using antisense oligodeoxynucleotides directed against the mRNA of both CRH receptor subtypes identified the CRH1 receptor as the mediator of the anxiogenic effects of CRH. Studies in mouse mutants in which this receptor subtype had been deleted extended these findings as the animals were less anxious than wild-type mice when experimentally stressed. Thus, patients with clinical conditions that are causally related to HPA hyperactivity may profit from treatment with a CRH1 receptor antagonist.
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PMID:The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety. 1036 86

Major depression is associated with significant disturbance in hypothalamic-pituitary-adrenal axis functioning, including blunted release of ACTH in response to CRH infusion. Eight melancholic depressives and eight matched healthy comparison subjects underwent, in random order, the following challenges: placebo, CRH, CRH + DDAVP. Blood for ACTH and cortisol estimation was drawn at -15, 0, 15, 30, 45, 60, 90, and 120 min. A blunted release of ACTH, in response to CRH challenge, was observed in depression (P < 0.01), whereas maximal cortisol responses in both groups were similar, despite elevated baseline levels in depression (P < 0.05). The combined CRH/DDAVP infusion produced similar ACTH and cortisol release in both groups. These results suggest that melancholic depression is associated with enhanced pituitary vasopressinergic responsivity.
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PMID:Desmopressin normalizes the blunted adrenocorticotropin response to corticotropin-releasing hormone in melancholic depression: evidence of enhanced vasopressinergic responsivity. 1037 38


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