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)

In psychiatric illness like depression, difference is essential between noradrenergic and serotoninergic sources. Therefore the measurement of urinary excretion of MHPG (3-methoxy-4-hydroxy-phenylethylene-glycol) is interesting, because MHPG seems to be the best reflect of central noradrenergic activity. Analytical assay of MHPG includes an enzymatic hydrolysis and an extraction by ethyl acetate. Separation is conducted by HPLC with fluorometric detection for MHPG and VMA, and electrochemical detection for 5-HIAA, which measurement is simultaneous. Quality control is evaluated (detection limit, linearity, precision, reproducibility, hydrolysis and extraction efficiency). Control values of 15 healthy subjects are 18.9 +/- 8.0 mumol/24 h of total MHPG, 1.5 +/- 1.0 of free MHPG, 8.5 +/- 2.0 of sulfate, and 10.7 +/- 4.4 of glucuronide MHPG (m +/- 2 sigma). In our study on depression, the best biological witness seems to be the sulfate-MHPG: in 16 depressed patients without treatment, its rate is very lowered (1.2 +/- 1.2 mumol/24 h). Total and glucuronide MHPG decrease weaker than sulfate (respectively -51% and -65%), while free MHPG increases (+ 193%) versus controls. Urinary VMA and 5-HIAA, peripheric catabolites of respectively adrenalin and serotonin are not significantly altered. There is no correlation neither between urinary sulfate-MHPG and scale evaluation before treatment, nor between urinary sulfate-MHPG and clinic improvement after antidepressive treatment. At last, the association clomipramine + mianserine shows a clinic improvement faster than clomipramine only, although no significative difference appears in biological markers.
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PMID:[Determination of 3-methoxy-4-hydroxyphenyethylene-glycol and its urinary conjugates. Value in the diagnosis and therapeutic follow-up of depression]. 245 2

The neurochemical and receptor theories relate depression to deficient neurotransmission at critical sites in the brain. While this concept has generated a number of theories of depression over the years, the research findings do not fully support any single theory in its entirety. Several issues thus remain controversial or inconclusive. For instance, the monoamine deficit theory is supported by low urinary MHPG in some forms of bipolar, but not unipolar depression. Cerebrospinal fluid MHPG and 5-HIAA studies are inconclusive. Amine metabolite research is also limited in scope because the information derived pertains to pre-synaptic and synaptic events and ignores post-synaptic events. Receptor research, which includes study of both pre-and post-synaptic sites, suggests supersensitivity of Beta-adrenergic receptors in depression. But this research is criticized because it is mostly animal based. Also, the findings of low melatonin in depression contradict the supersensitivity-hypothesis. Abnormally low post-synaptic alpha-2 adrenoceptors is indicated by findings of an attenuated GH response to clonidine. But abnormality of pre-synaptic alpha-2 adrenoceptor functions has not been demonstrated conclusively. Recent findings in depression suggest a dysregulation in the dynamic and interactive relationship between neurotransmitters and receptors. Accordingly, a comprehensive view of the abnormalities of the various neurotransmitter systems in depression requires studies which investigate pre- and post-synaptic events simultaneously, preferably during illness and remission.
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PMID:Neurochemical and receptor theories of depression. 256 46

Clinical and biochemical effects of two selective 5-HT uptake inhibitors, zimeldine and alaproclate, were studied in 24 hospitalized patients with endogenous depression. According to a randomized parallel group design 14 patients were treated with zimeldine and 10 with alaproclate. The dosage of both zimeldine and alaproclate was 200 mg daily. For the evaluation of the clinical effect, Montgomery & Asberg Depression Rating Scale (MADRS) was used. Seven of 14 patients treated with zimeldine and seven of 10 treated with alaproclate improved. 5-HT uptake inhibition in patients' platelets and concentration of amine metabolites (5-HIAA, HVA, HMPG) in CSF were studied before and during treatment. After 3 weeks of treatment with zimeldine 5-HIAA and HMPG in CSF decreased significantly while HVA in CSF increased significantly. Zimeldine produced a significant 5-HT uptake inhibition in platelets. During treatment with alaproclate no significant change in amine metabolites concentration in CSF was found and there were no mean changes on 5-HT uptake inhibition in platelets.
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PMID:Alaproclate a novel antidepressant? A biochemical and clinical comparison with zimeldine. 258 Apr 22

In post-partum depressive illness ("post-partum blue") we measured urinary MHPG, VMA, 5-HIAA and free and total Trp. VMA and especially MHPG reflect the brain noradrenaline metabolism. Trp is the precursor of 5-HT synthesis and 5-HIAA is the main urinary catabolite of 5-HT. The clinical evaluation consisted in self-evaluation scales: Pitt scale 1, 3 and 5 days after delivery, CESD scale of NIMH (depression) and BONIS scale (anxiety) at 6th day. Moreover a psychiatrist measured depression intensity on the MADRS scale and DSM III data. First results seem to indicate a decrease of free MHPG and VMA, an increase of 5-HIAA and no alteration of free and total Trp. These modifications could involve adrenergic and serotoninergic alterations in brain.
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PMID:[Changes in urinary levels of MHPG, VMA and 5-HIAA and plasma tryptophan in post-partum blues. Initial results]. 258 64

A previous report by our group and results published by other research groups have indicated a dichotomy in MHPG levels in depressed patients. This study attempted to characterize phenomena associated with this dichotomy in plasma MHPG levels. First, we have noted, at least in female patients, that homogeneity of MHPG levels, as tested by fitting with a normal curve, can be ruled out. In contrast, in the total population, a dichotomy was less evident in this study; the 2 subgroups, high and low levels of MHPG, partially overlap, and this results in a gaussian distribution. However, based on the hypothesis of a bimodal distribution, as shown by others and not excluded here, it was possible to find some factors associated with heterogeneity. Thus, polarity of depression, sex and age of the patients, age of disease onset and depression score affect MHPG levels. On the other hand, other elements suspected to modify MHPG values, such as the different lengths of the washout period (minimum 10 days), or some medication (chloralhydrate or levomepromazine) required during the washout period, did not show any effect. The aim of this study was to better characterize this peripheral index for its possible use in clinical application.
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PMID:The heterogeneity of 3-methoxy-4-hydroxyphenylglycol levels among depressed patients. 259 50

1. The paper presents a naturalistic study of 3-Methoxy-4-hydroxyphenylglycol and treatment response in panic disorder. 2. Twenty-eight patients unmedicated for at least one month were entered in a study of MHPG in panic disorder, and given the option of continuing or not continuing treatment. 3. At baseline and on average follow-up 6.8 months later, patients continuing in treatment had significantly lower MHPG than those who did not. 4. At baseline, the two groups of patients did not differ significantly as to number of panic attacks, Zung anxiety scale, and Beck and Hamilton Depression scales. 5. Treated patients did better on all clinical measures at follow-up. 6. Low MHPG may be related to persistence in seeking treatment for panic disorder, and perhaps to treatment response.
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PMID:Low MHPG and continuing treatment in panic disorder. 278 Oct 42

Twelve patients suffering from mental anorexia were examined on clinical and biological grounds, based on the hypothesis of the functional depression of the noradrenergic track. The initial values of MHPG and of catecholamines were below normal. The quantitative results for depression and retardation were lessened significantly under beta-stimulant treatment. Only glucuro-conjugate MHPG excretion increased significantly, but the MHPG values were much lower than normal at the end of the treatment. The correlations between biochemical and behavioural parameters were worth noticing as far as the retardation scale was concerned. The present study shows the advantage of the dexamethasone suppression test and of the response of TSH under TRH.
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PMID:[Disorders of noradrenergic pathways in anorexia nervosa. Results]. 285 80

We examined red blood cell (RBC) and plasma lithium concentrations and RBC/plasma lithium ratios in 14 manic patients during lithium treatment as part of the National Institute of Mental Health's Collaborative Program on the Psychobiology of Depression, Biological Studies. All of the lithium measures increased during treatment, especially RBC lithium. There were positive correlations between the RBC lithium concentration and the RBC/plasma lithium ratio and their maximal values in a single-dose pharmacokinetic experiment before treatment. After 5 and 16 days of treatment, patients with good subsequent outcome had higher RBC/plasma lithium ratios than did patients with poor outcome. Early in treatment, there was a negative correlation between lithium concentrations and severity of mania. During treatment, there was a negative correlation between RBC lithium and urinary MHPG excretion. There was a positive correlation between RBC or plasma lithium during the first few days of treatment and subsequent reduction in norepinephrine excretion during treatment. At 3 weeks, there were negative correlations between reductions in catecholamine measures and lithium concentrations. These data suggest that there are changes in the sensitivity of behavior and catecholamine function to lithium during treatment. RBC concentrations of lithium appear to be a potentially useful indicator of its behavioral and neurochemical effects.
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PMID:Lithium distribution in mania: plasma and red blood cell lithium, clinical state, and monoamine metabolites during lithium treatment. 288 35

Pretreatment plasma ratios of tryptophan (Trp) and tyrosine (Tyr) to other large neutral amino acids were determined in 27 depressed patients who completed a double-blind trial of citalopram, a selective serotonin uptake inhibitor, against maprotiline, a selective noradrenaline uptake inhibitor. The Trp ratio and the Tyr ratio were decreased in the total patient sample as compared with healthy controls. Plasma Tyr ratio was normal in the endogenous, but significantly decreased in the non-endogenous depressives. There was no significant relationship between the plasma Trp ratio and the probenecid-induced accumulation of 5-HIAA in the CSF, or between the plasma Tyr ratio and HVA level in CSF, whereas the CSF level of MHPG correlated significantly with the plasma Tyr ratio. There was a significantly positive correlation between the Trp ratio, the Tyr ratio, their sum and the final Hamilton depression score in 14 patients treated with citalopram; on the whole, this association was evident also in the endogenous and non-endogenous subgroups. In 13 patients on maprotiline there was a significantly positive correlation between the plasma Tyr ratio and the percent reduction of Hamilton depression score; this association was poor in the endogenous, whereas a trend towards a correlation remained in the non-endogenous subgroup. The results suggest that the plasma Trp and Tyr ratios may be determinants of clinical improvement in depressed patients to treatment with citalopram and maprotiline. However, further studies are needed on larger patient samples to allow a firm conclusion.
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PMID:Plasma tryptophan and tyrosine ratios to competing amino acids in relation to antidepressant response to citalopram and maprotiline. A preliminary study. 308 Jul 81

A new selective MAO-A-inhibitor (noclobemide) was used in a double-blind comparative study of 23 patients with severe unipolar or bipolar depressive disorder. Two different doses of medication were given for 4 weeks. Effectiveness was measured by improvements in the Hamilton Rating Scale for Depression, a self-rating scale and clinical global impression. Platelet MAO-activity and urinary MHPG-excretion was also determined. Moclobemide proved to be a well-tolerated and effective antidepressant, with both groups showing improvement. Platelet MAO-activity was not markedly influenced by moclobemide, possibly because it selectively inhibits MAO-A. Urinary MHPG did not change significantly with treatment.
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PMID:A clinical study of the selective MAO-A-inhibitor moclobemide (Ro 11-1163): a comparison of 2 different dosages with particular reference to platelet MAO-activity and urinary MHPG-excretion. 329 20


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