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

A patient suffering from endogenous depression was treated with mianserin and developed agranulocytosis. After recovering from this, and with the depression in remission, the patient was given L-tryptophan. When this medication was removed from the market, due to the newly described eosinophilia-myalgia syndrome, a change was made to oxitriptan, which then caused a serious asymptomatic eosinophilia. No similar cases have yet been reported. Following withdrawal of oxitriptan, the eosinophilia disappeared. Evidence for any other cause of the condition was not found. Causes and physiopathology of drug-induced agranulocytosis and eosinophilia and the circumstances of such complications following use of mianserin and oxitriptan are discussed.
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PMID:[Mianserin agranulocytosis followed by oxitriptan eosinophilia]. 160 92

In this study, we have measured the following biological variables in 78 depressed inpatients: adrenocorticotrophic hormone (ACTH) responses to corticotropin releasing factor (CRH: 100 micrograms intravenously), postdexamethasone cortisol and ACTH values, and circulating concentrations of L-tryptophan (L-TRP). Patients were categorized according to the DMS-III as (1) minor depression, (2) simple major depression, and (3) major depression with melancholia/psychotic features. By means of various pattern recognition methods, we determined whether these diagnostic groups constitute discrete biological classes or form relevant stages (i.e., continuous categories) in a continuum of progressing biological dysfunction. We established that unipolar depression constitutes one biological continuum characterized by a progression of lower CRH-induced ACTH responses, lower L-TRP levels, and higher postdexamethasone cortisol and ACTH values along the diagnostic spectrum. However, the biological differences in these markers between melancholia and minor depression are quantitatively prominent to the extent that they become qualitative. These findings support the biological heterogeneity hypothesis of melancholia. Simple major depression is a heterogeneous class with regard to the biological markers employed.
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PMID:Biological heterogeneity of melancholia: results of pattern recognition methods. 165 16

The addition of lithium to the tricyclic antidepressant medication of 23 patients with major depression resulted in an increase in the prolactin response to intravenous L-tryptophan after both four days and four weeks of treatment. The extent of this increase did not distinguish the ten patients who were classified as clinical responders (greater than 50% reduction in score on the HRSD). Among the responders there was a modestly significant correlation between the decrease in score on the HRSD and the enhancement of tryptophan-induced prolactin release. Some responders, however, showed very little change in this endocrine response over the four weeks of lithium treatment. Lithium may increase brain 5-HT function in tricyclic-resistant depression but there is only limited support for the hypothesis that changes in brain 5-HT function are involved in the antidepressant effect of this treatment combination.
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PMID:Lithium in tricyclic-resistant depression. Correlation of increased brain 5-HT function with clinical outcome. 165 18

Several developments in serotonin neuropharmacology have implications for psychiatric disorders and have already begun to impact their treatment. Selective inhibitors of serotonin uptake, which enhance serotonergic function by preventing the removal of serotonin from the synaptic cleft via the membrane transporter, have been introduced for the treatment of depression and may be effective in other disorders. Precursor loading can increase serotonin concentrations in the synaptic cleft, and tryptophan--which has been available in health food stores and drug stores--had become increasingly used for self-medication of depression, insomnia, and premenstrual syndrome. Conversion to serotonin is not the major metabolic pathway for tryptophan, and large increases in other tryptophan metabolites (such as quinolinic acid, a substance that is excitotoxic at high concentrations) accompany small increases in extracellular serotonin. The recent epidemic of the eosinophilia-myalgia syndrome associated with tryptophan now appears due to a trace contaminant in the product from a single manufacturer. A major advance in serotonin pharmacology has been the elucidation of serotonin receptor heterogeneity. At least seven receptor subtypes (5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2, 5-HT3, 5-HT4) have been identified in brain. Direct-acting agonists and antagonists can have selective affinity for specific receptor subtypes. Selective activation of 5-HT1A receptors seems to cause anxiolytic and possibly antidepressive effects. Selective antagonists of 5-HT2 or 5-HT3 receptors may be useful in treating anxiety and schizophrenia. Drugs that enhance serotonergic function suppress aggression in animals, but the specific receptor subtypes involved are not known. The advances being made in serotonin pharmacology will help define the role of this brain neurotransmitter in psychiatric and other disorders and can be expected to lead to further therapeutic advances.
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PMID:Role of serotonin in therapy of depression and related disorders. 167 51

An association between the ingestion tryptophan and a syndrome characterized by scleroderma-like skin abnormalities, fasciitis, and eosinophilia has recently been recognized in the United States. We report the clinical and histopathological findings in nine patients and the results of biochemical analyses of tryptophan metabolism in seven patients with this syndrome. Edema of the extremities, frequently accompanied by pruritus, paresthesia, and myalgia, developed in the nine patients (six women and three men; age range, 30 to 66 years) 1 to 18 months after the start of therapy with tryptophan (1.5 to 3.0 g daily) for insomnia, depression, or obesity. Five patients were taking drugs (benzodiazepines) known to inhibit hypothalamic-pituitary-adrenal function, and one had adrenal insufficiency. All had blood eosinophilia in the acute phase of their illness (mean eosinophil count [+/- SD], 3.62 +/- 2.87 X 10(9) cells per liter). All had histopathological changes in the dermis and subcutaneous tissue typical of scleroderma, and seven patients had eosinophils. The fascia was inflamed and fibrotic, and adjacent skeletal muscle often showed perifascicular inflammation. Tryptophan was discontinued in all patients, and eight received prednisone. The cutaneous symptoms improved, but only two patients had complete resolution of their illness. The patients had plasma levels of tryptophan before and after an oral dose of tryptophan that were similar to those in normal subjects. Plasma levels of L-kynurenine and quinolinic acid, which are metabolites of tryptophan, were significantly higher in four patients with active disease than in three patients studied after eosinophilia had resolved or in five normal subjects (P less than 0.001)--findings consistent with the activation of the enzyme indoleamine-2,3-dioxygenase. This illness resembles eosinophilic fasciitis and probably represents one aspect of the recently reported eosinophilia-myalgia syndrome. The development of the syndrome may result from a confluence of several factors, including the ingestion of tryptophan, exposure to agents that activate indoleamine-2,3-dioxygenase, and possibly, impaired function of the hypothalamic-pituitary-adrenal axis.
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PMID:Scleroderma, fasciitis, and eosinophilia associated with the ingestion of tryptophan. 231 25

The studies reported here represent a continuing search for mechanisms which may play a role in neurological disturbances resulting from brain injury. In particular, they are part of an effort to elucidate the involvement of both the serotonergic and noradrenergic neurotransmitter systems in the wide-spread decrease in cortical glucose utilization, interpreted as reflecting a functional depression, associated with a focal cortical lesion in the rat. Quinolinic acid, an endogenous metabolite of L-tryptophan, a neurotoxin and an N-methyl-D-aspartate (NMDA) receptor agonist was found to accumulate in cortical areas of a traumatized rat hemisphere in parallel with a previously demonstrated increase of 5-hydroxyindoleacetic acid. Ketanserin (20 mg/kg/day), a 5-HT2 receptor blocker ameliorated the depression of glucose utilization in traumatized brain while MK-801 (3 mg/kg, before and after lesion), an NMDA receptor blocker, had no effect. Alpha 1-adrenergic receptors, quantitated in vivo with [125I]-HEAT (iodo-2-[beta-(4-hydroxyphenyl)-ethyl-aminomethyl]tetralone), were found to be elevated in cortical areas of the lesioned hemisphere, but not in other structures.
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PMID:Neurochemical approaches to the amelioration of brain injury. 169 29

Streptozocin-induced diabetic (STZ-D) mice have reduced brain concentrations of tryptophan, a precursor substance for 5-hydroxytryptamine, and show lengthened immobility in Porsolt's swim test, a putative animal model of depression. This study investigated whether tryptophan affects behavior in Porsolt's swim test in STZ-administered male National Institutes of Health Swiss mice. In addition, the effect of tryptophan on behavior in the resident-intruder test of aggression was studied. Tryptophan is effective in the treatment of mild depression and may reduce aggressive behavior. Diabetes was induced with injection of 200 mg/kg body wt i.p. STZ. Two weeks after STZ treatment, the mice received 0, 50, and 100 mg/kg i.p. tryptophan 60 min before the swim test. The STZ-administered mice exhibited lengthened immobility in the swim test, and tryptophan caused a dose-related shortening in their immobility times. The control and STZ mice, which were isolated for 1 wk before the resident-intruder test, did not show any difference in the time spent in social investigation or aggressive or defensive behaviors. However, 100 mg/kg i.p. tryptophan 60 min before the test reduced the social interaction and aggressive behavior of the STZ-D mice but increased these behaviors in controls. Results indicate that tryptophan shortens the increased immobility time and reduces social and aggressive behavior in STZ-D mice. Therefore, the reported reductions in the brain-tryptophan concentrations in STZ-D mice may participate in regulating their behavior.
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PMID:Effects of tryptophan on depression and aggression in STZ-D mice. 175

Some children with coeliac disease show behavioural disorders such as depression and other signs which have been correlated with reduced central monoamine metabolism. We have therefore investigated the brain availability of the monoamine precursors tryptophan and tyrosine in 15 untreated children with coeliac disease and 12 treated children with coeliac disease as well as in 12 control children. Significantly decreased plasma concentrations of tryptophan were found in untreated children (mean (SD) 13 (4) mumols/l, p less than 0.001) compared with treated children (31 (13) mumols/l), and in both groups of coeliac children when compared with control children (81 (22) mumols/l). A significantly lower ratio of plasma tryptophan to large neutral amino acids (tyrosine, valine, isoleucine, leucine, and phenylalanine) was also observed, which could indicate impaired brain availability of tryptophan in coeliac children and was more pronounced in untreated children. The impaired availability of tryptophan could produce decreased central serotonin synthesis and in turn behaviour disorders in children with coeliac disease.
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PMID:Plasma precursor amino acids of central nervous system monoamines in children with coeliac disease. 177 52

Feeding a 13% CP diet based on corn and soybean meal and supplemented with methionine to laying hens results in reduced egg weight in comparison with hens fed a corn and soybean meal methionine-supplemented diet containing 16% CP. An experiment was conducted to determine whether the egg weight reduction could be eliminated by supplementing the low-protein diet with additional lysine, methionine, and tryptophan or by adding glycine and glutamic acid to increase the amino nitrogen to a level equivalent to 16% CP. The influence of the dietary treatments on the weight of the major egg components was also determined. In a second experiment, the influence of time of day of feeding the 13 or 16% CP diets on egg weight and egg components was determined. Adding additional amino nitrogen in the form of glycine and glutamic acid or increasing the levels of lysine, methionine, or tryptophan individually or in combination failed to prevent the depression in egg weight of hens fed the lower protein diet. Measurement of egg components demonstrated that the reduction in egg weight was primarily associated with a reduction in albumen content of the egg. Feeding a high-protein diet from 1400 to 0800 h and a low-protein diet from 0800 to 1400 h resulted in egg weight equivalent to that from hens continuously fed the high-protein diet. The lower weight of the albumen in eggs from hens fed a 13% CP diet may be due to a lower availability of amino acids for protein synthesis during the 3- to 4-h period when the ovum is in the magnum.
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PMID:Influence of protein concentration, amino acid supplementation, and daily time to access to high- or low-protein diets on egg weight and components in laying hens. 178 67

In four studies, all carried out more than 20 years ago, the combination of tryptophan plus a monoamine oxidase inhibitor was significantly better than tryptophan plus placebo in the treatment of depression. However, there is no evidence that tryptophan has any clinically significant effect on other treatments such as tricyclic antidepressants and ECT. Side effects of the combination of tryptophan and a monoamine oxidase inhibitors have limited the use of this combination. The risk of the serotonin syndrome is small, but it can occur. However, rapid cessation of tryptophan seems to avoid any long lasting adverse effects of the serotonin syndrome. In situations where enhancement of the therapeutic effect of monamine oxidase inhibitors outweighs the risk of adverse effects, the combination of tryptophan and a monoamine oxidase inhibitor is clinically useful. As the studies to date have looked at regular depressed patients, what is needed now is studies of this combination in therapy resistant depression.
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PMID:Use of tryptophan in combination with other antidepressant treatments: a review. 179 98


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