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)

Cluster analyses were carried out on a sample of 100 depressed females. The study was based on the 14 items relevant to depressive phenomenology of the Structured Clinical Interview for DSM-III-R (SCID). Our findings support the existence of two classes, i.e., a vital (melancholic) vs. a nonvital cluster. The vital cluster is characterized by the following symptoms: a distinct quality of depressed mood, nonreactivity, early morning awakening, anorexia-weight loss, and cognitive and psychomotor disturbances. Patients belonging to the vital cluster exhibit disorders in the hypothalamic-pituitary-adrenal and thyroid axes and a markedly decreased availability of L-tryptophan to the brain. The vital depressives score significantly higher on the Hamilton Rating Scale for Depression as compared to those suffering from nonvital depression. The cluster-analytically derived class of vital depression and the DSM-III subtype of melancholia tend to be quite similar. Our findings support the isolation and the descriptive validity of a vital (melancholic) depressive syndrome.
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PMID:Clinical subtypes of unipolar depression: Part I. A validation of the vital and nonvital clusters. 226 62

The purpose of this study was to examine whether biological variables, such as erythrocyte membrane transports and plasma levels of monoamine precursor amino acids (tyrosine, tryptophan and phenylalanine), exhibit a particular pattern relatively to DSM-III depressive subgroups (dysthymic disorders, major recurrent depression and biopolar depression), when they are treated synthetically by a stepwise discriminant analysis. We conducted two tests in 97 subjects (64 depressed patients vs. 33 controls): the first before any antidepressant treatment, and the second after pharmacotherapy and clinical improvement. Our results clearly indicate a satisfying homogeneity for the controls and bipolar depressed patients as opposed to dysthymic disorders and major recurrent depression in both tests. The most informative biological variables are the erythrocyte membrane transports before treatment, tryptophan parameters after clinical improvement. Evidence is provided that multivariate analysis constitutes an interesting approach in biological psychiatry.
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PMID:A multivariate analysis of red blood cell membrane transports and plasma levels of L-tyrosine and L-tryptophan in depressed patients before treatment and after clinical improvement. 228 Aug 25

Eosinophilia-myalgia syndrome (EMS) is a newly recognized illness characterized by intense eosinophilia, debilitating myalgia, and absence of any condition that could account for the eosinophilia or myalgia. The disorder has previously been associated with ingestion of capsules containing the amino acid L-tryptophan. In 1989, the Wisconsin Division of Health began surveillance for EMS. Each of 25 persons reported with the illness and meeting a standardized case definition were using L-tryptophan when their symptoms began, between June 1989 and January 1990. The median age of the patients was 43 years (range 26-82 years); 92% were female, and 96% were white. The majority of patients reported were using L-tryptophan for insomnia (36%), premenstrual syndrome (28%), or depression (20%). Common signs and symptoms in these cases included cough or dyspnea (60%), arthralgia (44%), edema of the extremities (44%), fever (36%), and rash (32%). Other epidemiologic investigations to date suggest that EMS may be associated with a product contaminant.
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PMID:Eosinophilia-myalgia syndrome in Wisconsin. 229 89

To investigate whether depression is a consequence of disturbed function in 5HT systems, neuroendocrine responses to infusions of the 5HT precursor L-tryptophan (LTP) were studied in patients and controls. After an overnight fast and 60 min bed rest, a solution of LTP (10 g/l) was infused intravenously to a dose of 100 mg/kg over 30 min. Circulating growth hormone (GH), prolactin (PRL), cortisol and tryptophan concentrations were followed from 60 min pre-infusion to 60 min post-infusion. GH responses were attenuated in 23 major depressives (DSM-III) compared with 22 controls and were almost absent in endogenous depressives (New-castle criteria). PRL responses were normal in depressives who had lost more than 3 kg body weight but attenuated in those who had not. GH and PRL responses did not correlate with each other. Reduced basal tryptophan concentrations and more rapid tryptophan clearance were observed in the depressives, but there were no correlations with GH or PRL responses. However, basal cortisol concentrations, which were raised in depressives with chronic psychosocial difficulties, were strongly and inversely predictive of PRL responses in depressives and controls. Blunted GH and PRL responses to LTP appear to be distinct abnormalities in depression which may relate to two processes; (1), an endogenous mechanism indicated by reduced GH responses, and (2), an impairment in 5HT systems, indicated by blunted PRL responses and perhaps caused by raised circulating cortisol or reduced tryptophan concentrations.
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PMID:A neuroendocrine study of 5HT function in depression: evidence for biological mechanisms of endogenous and psychosocial causation. 234 77

Twenty-four acutely ill schizophrenic patients (DSM-III-R), 18-42 years old, were treated for 6 weeks with sulpiride. Sulpiride was administered in three different daily dosages (400, 800 or 1200 mg) according to a double dummy blind randomized administration schedule. The psychopathology of the patients was rated by the Comprehensive Psychopathological Rating Scale (CPRS) and the Nurse's Observation Scale for Inpatient Evaluation (NOSIE). The monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA), 4-hydroxy-3-methoxy-phenylglycol (HMPG) and the amino acids tyrosine, tryptophan, glutamate and glutamine were measured in serum before and once a week during sulpiride treatment. There were no significant correlations between the CPRS or the NOSIE morbidity scores and the biochemical measures before drug treatment. HVA levels were not correlated to rating scores during treatment, but after 6 weeks HVA had decreased significantly in the patients with a good response but not in the patients with a poor response. A negative relationship between 5-HIAA levels and depressive and negative symptoms was found. Non-responders according to the subscale for depression had low 5-HIAA levels throughout the treatment. An increase of tryptophan was correlated to improvement in the early part of treatment. High levels of glutamate or glutamine were found in non-responders before treatment. During treatment an increase of the glutamate level was correlated to improvement. Low levels of glutamine were related to improvement according to global and NOSIE (total) rating scores. Peripheral biochemical measures may be a valuable tool in the study of pathophysiological mechanisms and treatment effects in patients with schizophrenia.
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PMID:Relationships between clinical effects and monoamine metabolites and amino acids in sulpiride-treated schizophrenic patients. 236 52

The behavioral and neurochemical effects of four intraventricular infusions of octopamine (3,200 micrograms), tryptophan (800 micrograms), and octopamine plus tryptophan delivered over 6 hours was studied in rats after performing a portacaval anastomosis or a sham operation. After each infusion, each animal was rated for neurologic depression with a 17 point test battery. Although overt coma was not induced, octopamine infusions severely depressed neurologic function. Concentrations of norepinephrine, dopamine, and serotonin in the brain were significantly decreased after the infusion of octopamine. Levels of norepinephrine in the brain were significantly correlated with neurologic status and greater depletion of norepinephrine was associated with greater neurologic depression. These studies demonstrate that infusing large amounts of the trace amine octopamine depresses behavior in the rat and this depression is most closely associated with depletion of stores of norepinephrine in the brain.
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PMID:Behavioral depression after intraventricular infusion of octopamine in rats. 241 12

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


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