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

Chronic macrophage activation with subsequent failure of activated macrophages to properly control T-lymphocyte secretion of interleukin-2 and interleukin-2 receptors is proposed as the basic biological mechanism of schizophrenia. Fundamental to this theory are the clinical observations on interleukin-2 provoking the active phase symptoms of schizophrenia in psychiatrically normal human volunteers and macrophage cytokines producing the prodromal and residual phase symptoms. This theory provides a completely new and unified mechanisms for the antipsychotic action of typical and atypical neuroleptics, bromocriptine, naloxone and DMSO. Furthermore, this hypothesis reveals why the dopamine theory of schizophrenia was a false lead. The effects of prolactin, estrogens and androgens are consistent with the model. Age of onset, male/female incidence, course of the disease from prodromal to active to residual phase, the protection afforded by rheumatoid arthritis and the close relationship between depression and schizophrenia can be explained by this theory. The gastrointestinal tract is suggested as the preferred site to investigate for the cause of the immune activation in schizophrenia.
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PMID:A comprehensive macrophage-T-lymphocyte theory of schizophrenia. 136 59

In this study we have examined the direct glucoregulation of prolactin secretion from normal anterior pituitary cells in vitro and have found that changes in medium glucose concentration regulate the amount of prolactin released. Nature and/or degree of this response to glucose was influenced by some effect, long-lived in vitro, which was correlatable to serum insulin levels. When the cells were derived from animals with mean low-normal serum insulin levels, there was a stimulation of prolactin secretion by hypoglycemia, the response was rapid, transient, dose-dependent, and could be duplicated by 2-deoxyglucose. When the cells were derived from animals with a higher mean serum insulin level, the prolactin secretion from the cells was slowly, adversely affected by hypoglycemia. Conversely, elevated glucose caused a depression in prolactin secretion in the first group and a stimulation of prolactin secretion in the second. We conclude (1) that modulation of glucose levels in vitro regulates prolactin release from pituitary mammotrophs and (2) that this glucose regulation of prolactin release is in turn coregulated with or regulated by insulin.
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PMID:In vitro glucoregulation of prolactin secretion. 136 92

The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), human chorionic gonadotropin (hCG), estradiol, progesterone, androstenedione, testosterone (total and free) and dehydroepiandrosterone sulphate (DHEAS) were investigated prior to surgery in 24 postmenopausal women with benign and 28 postmenopausal women with malignant epithelial ovarian tumors. The serum concentrations of hormones were compared with those of 28 healthy, postmenopausal, age-matched controls. Significantly lower serum FSH levels were demonstrated in women with malignant tumors. No significant differences were found between the groups regarding the serum LH levels. The hCG levels were low in all groups. Regarding progesterone and estradiol levels, low postmenopausal steroid levels were found in all groups examined and no significant differences were demonstrated within the groups. No significant correlations between the levels of estradiol and FSH or progesterone and LH were demonstrated. To exclude a central depression of gonadotropin release mediated by the dopaminergic system we examined the thyroid stimulating hormone (TSH) and prolactin. No differences were found between the groups regarding TSH and prolactin levels. A possible relationship between other hormones/factors produced by the tumor and exerting a negative feedback, either centrally or directly, on the gonadotropin release remains to be investigated. A change in biological activity in the gonadotropins might explain the present findings.
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PMID:The pituitary-gonadal axis in women with benign or malignant ovarian tumors. 138 13

Serotonergic mechanisms have been implicated in the pathophysiology of depression and in the neuropharmacology of antidepressant treatment. One measure of central serotonergic function is the prolactin (PRL) response to IV L-tryptophan (L-TRP). We used the L-TRP test to assess the role of serotonin in the mechanism of action of lithium augmentation in refractory major depression. Twenty-six patients with antidepressant-refractory major depression each received three L-TRP tests (after 2 weeks of placebo, after 4 weeks of active primary antidepressant, and after 1 week of lithium augmentation). Primary antidepressant treatment did not increase the PRL response, but lithium augmentation resulted in a statistically significant increase in PRL response as compared to both placebo pretreatment (P less than 0.04) and antidepressant treatment alone (P less than 0.025). This study supports a role for serotonergic mechanisms in the action of lithium augmentation.
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PMID:Serotonergic function during lithium augmentation of refractory depression. 141 Jan 50

The neuroendocrine response to L-5-hydroxytryptophan was compared in 37 prepubertal children who met the Research Diagnostic Criteria for major depressive disorder with that in 23 normal children with no lifetime history of any psychiatric disorder and very low rates of depression in both first- and second-degree relatives. Intravenous L-5-hydroxytryptophan (0.8 mg/kg) was given over a 1-hour interval after preloading with oral carbidopa, an inhibitor of peripheral but not central L-5-hydroxytryptophan metabolism. L-5-Hydroxytryptophan, a precursor of serotonin, increases serotonin turnover in the central nervous system when given after carbidopa. Seven (19%) of the 37 children with major depressive disorder and two (9%) of the 23 normal children had nausea or vomiting and therefore did not complete the full infusion. They were subsequently excluded from data analysis. After this stimulation, prolactin, cortisol, and growth hormone secretion were compared between diagnostic groups. The depressed children secreted significantly less cortisol (effect size, 0.70) and significantly more prolactin (effect size, 0.83). There was a sex-by-diagnosis interaction in prolactin response to L-5-hydroxytryptophan and, on examination, the prolactin hypersecretion was seen in depressed girls but not in depressed boys compared with same-sex controls. There was no significant stimulation of growth hormone in either group. These findings are consistent with dysregulation of central serotonergic systems in childhood major depression.
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PMID:Neuroendocrine response to L-5-hydroxytryptophan challenge in prepubertal major depression. Depressed vs normal children. 144 21

In order to test the effects of various biological treatments on serotonergic function in depression, twenty-one patients with a diagnosis of major depression underwent neuroendocrine challenge tests before and after treatment with either ECT, fluoxetine or amitriptyline. The serotonin (5-HT) releasing agent d-fenfluramine was used as a challenge drug and cortisol (CORT) and prolactin (PRL) plasma levels were monitored over a 5-h period. Overall PRL responses were significantly enhanced following pharmacotherapy irrespective of therapeutic outcome. Effective treatment in each case lowered baseline CORT levels but CORT response to d-fenfluramine remained blunted. Hypercortisolaemia may be involved in the impaired pretreatment PRL response as a strong inverse relationship was established, for the combined studies, between basal CORT plasma concentrations and PRL responses.
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PMID:D-fenfluramine-induced prolactin and cortisol release in major depression: response to treatment. 146 Jan 63

Neuroendocrine dysfunctions, in part similar to those found in depression, are present in chronic alcoholism. The aim of this investigation was to evaluate the effects of chronic alcohol intake on cortisol secretion in basal conditions, after dexamethasone (DXT) suppression or corticotropin (ACTH) stimulation in 10 alcoholic men, during active drinking and after two weeks of alcohol withdrawal. The 24-hour, day- and night-time urinary cortisol and melatonin levels, and the effects of thyrotropin releasing hormone (TRH) on thyrotropin (TSH) and prolactin (PRL) secretions were studied in the same subjects. The data were correlated to the scores obtained by the Hamilton Rating Scale for depression and compared to those found in healthy subjects. Increased cortisol levels and the lack of DXT suppression of cortisol secretion are considered to be alcohol-dependent inasmuch as they disappear in most patients after alcohol withdrawal. The cortisol response to ACTH 1-24 infusion measured before and after alcohol withdrawal was similar in the patients we studied; moreover no significant difference was found between patients and controls. The increment of urine free cortisol levels in active alcoholics was not statistically significant. Urine cortisol levels became similar to those of the control subjects after alcohol withdrawal. The increased diurnal values of urine melatonin and the inversion of the physiological ratio between nocturnal and diurnal levels observed during alcohol intake became normal upon alcohol withdrawal. The TSH and PRL responses after the administration of 50 or 200 micrograms TRH were higher in alcoholics than in controls, while a blunted response is known to occur in depression.
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PMID:[The neuroendocrine aspects of chronic alcoholism: the effect of alcohol intake and its withdrawal]. 146 29

1. Studies of the biochemical mechanism of action of antidepressant drugs show that virtually all drugs, regardless of acute biochemical effects, result in the down regulation of CNS beta-1 adrenergic, serotonin-2 (5HT2), and perhaps 5HT1A receptors in rats in a time course which parallels the onset of antidepressant action in patients with major depressive disorder. 2. Recently, neuroendocrine techniques have been described which allow the study of 5HT receptor subtypes in man. These include fenfluramine-induced changes in ACTH, cortisol and prolactin secretion (perhaps for 5HT2 receptors) and ipsapirone-induced changes in ACTH and cortisol (for 5HT1A receptors). 3. Depressed subjects treated with antidepressants down regulate these markers of both 5HT2 and 5HT1A receptors in a time course consistent with their recovery from depression. 4. Studies in progress are attempting to demonstrate links between these receptor changes and clinical antidepressant responses.
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PMID:Neuroendocrine markers of serotonin responsivity in depression. 149 23

Medium hyperosmolarity between 300 (normal medium osmolarity) and 600 mOsm inhibited in a concentration-correlated fashion (r greater than 0.97, p less than 0.001) the rise in intracellular Ca2+ concentration ([Ca2+]i) and prolactin (PRL) secretion induced in GH4C1 cells by depolarizing 30 mM K+. [Ca2+]i concentration and PRL secretion were tightly related between 300 and 600 mOsm (r = 0.976, p less than 0.001); 50% inhibition of both occurred at 450 mOsm. Medium hyperosmolarity slowed the rate of Ca2+ influx. At 600 mOsm the rise in both [Ca2+]i and PRL secretion was abolished but PRL secretion induced by 1 microM phorbol 12-myristate 13-acetate was not significantly reduced. Our data suggest that inhibition of Ca2+ influx may be the primary mechanism by which extracellular hyperosmolarity inhibits PRL secretion induced by high medium K+ in GH4C1 cells. Depression of the Ca2+ intracellular transduction system may play a pathophysiological role in vivo in conditions such as dehydration and hypertonic coma.
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PMID:Medium hyperosmolarity inhibits prolactin secretion induced by depolarizing K+ in GH4C1 cells by blocking Ca2+ influx. 155 72

The success of serotonergic reuptake inhibitors in the treatment of obsessive-compulsive disorder (OCD) has suggested that serotonergic neurotransmission may play a role in the pathogenisis of this disorder. Prolactin responses to a 60-mg oral dose of fenfluramine in 26 medication-free patients with a DSM-III-R diagnosis of OCD were compared with those of 20 controls subjects. Fenfluramine produced a significant elevation of prolactin levels in both OCD patients and controls. Prolactin responses were significantly blunted in OCD patients compared with responses in control subjects. Female subjects in both groups showed greater prolactin responses to fenfluramine than did their male counterparts. There was a significant interaction between sex and the presence of OCD such that female patients had lower prolactin responses than their controls, while the difference between male patients and controls was not significant. Prolactin responses were not correlated with age, weight, drug level, depression, anxiety, or degree of OCD symptoms. The results are consistent with a relative reduction in serotonergic efficacy in the setting of OCD.
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PMID:Fenfluramine stimulation of prolactin in obsessive-compulsive disorder. 160 84


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