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

The relationship between the ratio in plasma of tryptophan to competing amino acids, which indicates brain serotonin synthesis, and the clinical response in depressed patients to treatments that act by enhancing brain serotoninergic function has been studied. There was a significantly positive correlation between the pretreatment plasma tryptophan ratio and the final depression score in patients treated with L-tryptophan or amitriptyline, and a trend towards a positive correlation in patients treated with lithium plus L-tryptophan or clomipramine. Patients with a low plasma tryptophan ratio generally showed greater clinical improvement than patients with a high ratio. When the plasma tryptophan ratio and the ratio in plasma of tyrosine to competing amino acids were considered together there was also a significant relationship between clinical and biochemical findings in patients treated with imipramine. These studies strongly indicate that brain serotoninergic function can be disturbed in depressed patients and, thus, lend support to the serotonin deficiency hypothesis in depression. Evidence has furthermore been presented which suggests that, rather than a low brain serotonin level per se, the hypofunction may be associated with disturbances in adaptive and regulatory mechanisms, e.g. postsynaptic serotonin receptors.
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PMID:Tryptophan to competing amino acids ratio in depressive disorder: relation to efficacy of antidepressive treatments. 241 37

Concentrations of several large neutral amino acids (LNAA) were earlier shown to be low, especially in brain, in rats fed a low protein diet containing a mixture of LNAA analogues. The purpose of this study was to learn if individual analogues would induce similar effects. Four hours after first feeding one meal containing norleucine, norvaline, alpha-aminophenylacetic acid, or alpha-aminooctanoic acid, concentrations of branched-chain amino acids were low in plasma, brain, liver and muscle; tyrosine and phenylalanine were more effectively reduced in brain than in other tissues. Lysine and arginine concentrations were low in brains of rats fed the basic amino acid analogue, homoarginine; concentrations of large and small neutral amino acids were unchanged. Dopamine was not low in brains having low tyrosine levels; serotonin was low in rats receiving alpha-aminooctanoate, the only analogue associated with a significant depression in brain tryptophan. The results suggest that the analogues have differing abilities to alter concentrations of tissue components. Decreases, especially in brain amino acid concentrations, may result from selective competition by analogues of a given transport class with natural amino acids transported from blood into brain by the same system.
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PMID:Tissue amino acids in rats fed norleucine, norvaline, homoarginine or other amino acid analogues. 242 57

The potential role of autoreceptors in regulating the activity of serotonin-containing nucleus raphe dorsalis (RD), raphe medianus (RM) and raphe pallidus (RPA) neurons was examined by recording the activity of these neurons under a variety of conditions both in vivo and in vitro. Raphe neurons recorded in vivo displayed the characteristic slow, rhythmic discharge pattern previously described for rat and cat raphe cells. The activity of these neurons was suppressed in a dose-dependent manner by tryptophan, LSD and chlorimipramine administered intravenously. There were no significant changes in the spontaneous discharge rate of raphe neurons over time when recorded in vitro, even though tissue serotonin and its metabolite, 5-hydroxyindoleacetic acid, decreased dramatically. RPA neurons fired significantly faster than either RD or RM neurons both in vivo and in vitro. Prior depletion of brain serotonin by p-chlorophenylalanine administration resulted in no significant change in raphe unit activity recorded in vitro. Elevation of brain serotonin by monoamine oxidase inhibition produced a total inhibition of raphe unit activity in vitro. Similarly, increasing the concentration of serotonin in the tissue slice by adding serotonin directly to the incubation medium resulted in a profound, though transitory, depression of unit activity. This depressant effect of serotonin was rapidly reversible upon drug wash-out. Serotonin receptor blockers, methiothepin, cypoheptadine, and methysergide, produced no significant change in unit activity. The serotonin reuptake blocker, fluoxetine, produced a total inhibition of raphe unit activity in all three nuclei in vitro. These data suggest that excess serotonin suppresses the activity of raphe neurons, apparently by an action on autoreceptors, but that a deficiency, or normal concentration, of serotonin does not influence the spontaneous activity of these cells. The data also show that RD and RM are much more sensitive to the depressant effects of serotonin than the caudal RPA neurons. More generally, these studies provide a data base for examining the electrophysiological and pharmacological characteristics of serotonergic neurons in the three major serotonin-containing nuclei in mouse brain. The mouse has proven to be a much easier species than the rat to use in these types of studies, based on the finding that mouse brain slices are more viable in vitro than are rat brain slices.
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PMID:A comparison of the electrophysiological and pharmacological properties of serotonin-containing neurons in the nucleus raphe dorsalis, raphe medianus and raphe pallidus recorded from mouse brain slices in vitro: role of autoreceptors. 243 25

It was shown previously that focal cortical freezing lesions in rats cause widespread depression of local cerebral glucose utilization (LCGU) in cortical areas of the lesioned hemisphere. This was interpreted as reflecting functional depression. The underlying mechanisms were postulated to involve alterations of biogenic amine systems. Accordingly, levels of serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5-HIAA), and its precursor tryptophan were determined by an HPLC method with electrochemical detection in frontoparietal cortical areas of both hemispheres at 4 h and 1, 3, 6, 8, and 10 days after a unilateral cortical freezing lesion. The 5-HT content was significantly lower than normal in the lesioned hemisphere only at 24 h, whereas the 5-HIAA level peaked at 24 h but was significantly elevated above normal values between 4 h and 6 days after lesioning. No changes were noted in 5-HT and 5-HIAA contents in the hemisphere contralateral to the lesion. These results indicate that cortical 5-HT metabolism is increased throughout the lesioned hemisphere of a focally injured brain. The increase in tryptophan content of the lesioned brain appeared to have a time course more closely related to previously demonstrated changes in cortical LCGU than to the increase in 5-HIAA content.
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PMID:Effects of injury on the indoleamines in cerebral cortex. 243 85

Following a finding that single doses (approximating to average intakes and to potential 'over-use') of aspartame administered orally to mice caused significant increases in norepinephrine and dopamine concentrations in various brain regions, the effect of repeated exposure to aspartame was studied. Male CD-1 mice were given a daily oral dose of 0, 13, 133 or 650 mg/kg for 30 days and 1 day after the last dose the animals were decapitated and their brain regions were quickly isolated. Analyses of the different regions for catecholamine and indoleamine neurotransmitters and their major metabolites indicated that the increases in adrenergic chemicals observed shortly after a single exposure were not apparent after repeated dosing. In contrast, concentrations of serotonin and its metabolite, 5-hydroxyindoleacetic acid, were decreased in several regions. An increased supply of phenylalanine may be responsible for a decrease in tryptophan uptake by the brain tissue or for a depression in tryptophan conversion to serotonin.
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PMID:Effects of repeated doses of aspartame on serotonin and its metabolite in various regions of the mouse brain. 244 82

The role of serotonin in the anorexic response of rats to an amino acid-imbalanced diet was investigated. After chronic depletion of serotonin with parachlorophenylalanine (PCPA, 300 mg/kg) or 5,7-dihydroxytryptamine (DHT, 200 micrograms/rat, intracisternally), initial intake of a mild isoleucine-imbalanced diet was reduced by 60% vs. a 17% reduction after saline injection. After acute treatment with the agonist, quipazine (quip, 5 mg/kg ip) or the precursor, tryptophan (TRP, 1% added to the diet), imbalanced diet intake was also exacerbated. PCPA and DHT may have caused receptor supersensitivity, such that the food intake depression after serotonin depletion was similar to that seen with the quip and TRP treatments. Injection of the autoreceptor agonist, 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT, 500 micrograms/kg sc), to reduce transmission in the serotonergic systems resulted in an attenuation of the usual food intake depression of the amino acid-imbalanced diet (only a 7%, nonsignificant reduction). Also measurements made in the absence of pharmacological treatment showed that the ratio 5-hydroxyindole acetic acid-to-serotonin, a putative index of serotonin turnover, was increased 155% in the raphe nuclei and 140% in the hippocampus 3.5 h after ingestion of the mild isoleucine-imbalanced diet. Therefore increased serotonergic activity in some brain areas may be associated with the initial depression of food intake in rats fed an imbalanced amino acid diet.
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PMID:Serotonin and feeding responses of rats to amino acid imbalance: initial phase. 244 14

The addition of lithium to the tricyclic antidepressant medication of 11 depressed patients resulted in an increase in the prolactin response to L-tryptophan after both 4 days and 4 weeks of lithium treatment. There was also a significant fall in Hamilton Depression scores. The results suggest that lithium and tricyclic antidepressants may act synergistically to enhance certain aspects of brain 5-HT function in depressed patients.
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PMID:Lithium increases 5-HT-mediated neuroendocrine responses in tricyclic resistant depression. 250 59

The biological treatment of depression includes administration of psychoactive drugs (cyclic antidepressants, MAO-inhibitors, neuroleptics and lithium), use of certain substances which in small amounts are normally present in food such as, L-tryptophan (L-TP) and L-5-hydroxytryptophan (L-5HTP), electroconvulsive therapy (ECT) and various manipulations of the sleep-wake rhythms. This paper reviews the literature on the efficacy of these treatments in patients resistant to earlier adequate treatment(s) with cyclic antidepressants. Subsequently the following strategy for the biological treatment of (non-psychotic) major depression is suggested: (1) administration of a cyclic antidepressant; (2) if after a period of 4 to 6 weeks a patient has not responded to an adequate dose, another cyclic antidepressant should be tried, adding lithium if the patient still does not respond; (3) MAO-inhibitors and (4) ECT. In psychotic depression the suggestions for the first, third and fourth steps are the same. In the second step, the cyclic antidepressant should be combined with a neuroleptic.
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PMID:Treatment of resistant depression. Review on the efficacy of various biological treatments, specifically in major depression resistant to cyclic antidepressants. 257 35

We have compared levels of albumin and serum amino acids in a group of 87 recent admissions to a nursing home, average age 83 years, with a group of healthy moderately old subjects, average age 69 years. We found that the nursing home group was characterized by decreased levels of albumin, by increased total levels of the measured amino acids, and by increased levels of the nonessential amino acids. In contrast, there were no significant group differences in the essential amino acids. Among the nursing home patients, there was a negative correlation between essential amino acids and disability, consistent with nutritional deficits in the more disabled patients, and a positive correlation between essential amino acids and subjective complaints of pain, suggesting that pain is associated with breakdown or mobilization of endogenous protein stores. Though the nursing home patients had decreased serum levels of tryptophan, there was no association between serum tryptophan or other variables that could be related to the availability of tryptophan for transport into brain, with ratings of either depression or pain. Glutamine levels were significantly increased in the nursing home residents, and among these patients they were positively correlated with measures of cognitive impairment.
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PMID:Amino acid levels in elderly nursing home residents. 263 18

The evidence indicating a specific abnormality of brain 5-HT function in depressed patients is reviewed. Biochemical studies have indicated that low plasma levels of tryptophan are unlikely to be the primary 'cause' of depression or of abnormal brain 5-HT function in depression. However, there may be a reduction of 5-HT synthesis or function in the brains of depressed patients and the uptake of 5-HT into platelets from depressed patients is consistently reduced. Neuroendocrine studies have suggested that various groups of depressed patients may exhibit different types of abnormal 5-HT-mediated responses. It is important to distinguish between the acute and chronic pharmacological effects of antidepressant treatment, which may account for the latency seen between onset of therapy and full clinical effect. Clinical studies have provided further evidence that 5-HT is implicated in the causation and treatment of depression, as both 5-HT precursors and selective inhibitors of 5-HT uptake are effective in the treatment of depression. Furthermore, inhibition of 5-HT synthesis can block the effect of antidepressant compounds. It is concluded that 5-HT function is decreased during depression, and that this carries important implications for the pharmacology of antidepressant drugs.
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PMID:Serotonin function in affective disorders. 268 91


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