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)

This review of the literature concerning the biochemical factors of resistance to antidepressants is essentially based on the anomalies of neurotransmitters and the enzymes which regulate them. In the case of 5HIAA, because of the bimodal distribution in depressed patients, it appears to be generally accepted that when a low level of this catabolite is found in the cerebrospinal fluid, this may represent a factor of resistance to noradrenergic antidepressants, or even to all antidepressants. In contrast, a high level of this catabolite represents a factor of poor response to serotoninergic antidepressants. Low levels of urinary MHPG predict a poor response to serotoninergic antidepressants, while high levels are observed in cases of depression resistant to noradrenergic antidepressants. MAO activity, evaluated after two weeks' treatment with MAOI, is considered to be a biochemical factor of resistance when it is inhibited by less than 80%. High levels of COMT (related to the degree of anxiety and agitation) reflect a poor response to noradrenergic antidepressants. Finally, a number of strategies designed to control resistant depression (reserpine, lithium carbonate, ...) could, in certain cases, suggest the existence of a functional defect in the serotoninergic systems.
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PMID:[Biochemical factors of resistance to antidepressants]. 354 87

Disturbed noradrenaline (NA) metabolism is thought to play a causal role in certain types of endogenic depression. This study was based on data from 88 patients with depression. The metabolism of NA was investigated by measuring urinary MHPG and plasma DOPEG concentrations and platelet nonoamine oxidase activity to determine if there were any differences in subgroups of depression defined by the DSM3. There was no difference in plasma DOPEG concentrations or of MAO activity in the different subgroups of depression, especially between episodes of major and non-major depression. On the other hand, depressed patients with an episode of major depression had significantly higher urinary MHPG concentrations than those with non-major depression.
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PMID:[Cerebral noradrenaline metabolism and classification of depression]. 356 12

Rhesus monkeys were studied for changes in noradrenergic functioning before and after chronic oral administration (28 days) of the tricyclic antidepressant desipramine (DMI). Decreases in cerebrospinal fluid concentration of the norepinephrine metabolite MHPG were evident following the first dose (5.0 mg/kg) of DMI, but not after chronic administration of the drug. The alpha 2-adrenoceptor agonist clonidine reduced plasma norepinephrine prior to DMI treatment, but not after 28 days of treatment with DMI. These adaptive changes in noradrenergic function were evident in spite of very low plasma levels of DMI due to rapid metabolism of the drug in the rhesus monkey. The development of changes compatible with alpha 2-adrenoceptor subsensitivity in the presence of plasma levels of the drug that are well below those considered therapeutic in the treatment of depression suggests that such a receptor change may be dissociated from the drug's antidepressant effect.
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PMID:Acute and chronic effects of desipramine administration to rhesus monkeys. 359 17

The Dexamethasone Suppression Test (DST) was performed in 64 depressed inpatients, in 48 schizophrenics, and in 20 normal controls. Thirty-four percent of depressive inpatients were found to escape from dexamethasone suppression significantly higher than either schizophrenics (13%) or normal subjects (5%). Among subgroups, bipolar and unipolar endogenous depression patients had much higher abnormal rates for the DST (59% and 48%, respectively) than nonendogenous cases (8%). DST results were also found to be positively correlated with patients' Hamilton scores. These findings suggested that DST could be helpful in diagnosis, discrimination of subtypes, and in assessment of severity of symptoms. In 32 of the 64 depressed inpatients, urinary MHPG X SO4 excretion was determined and compared with 21 normal controls. Bipolar patients (n = 7) had less MHPG X SO4 excretion than unipolar endogenous patients (n = 16). Excretion was positively correlated with cortisol level at 17 hr after dexamethasone administration in 32 depressive inpatients, especially in the unipolar subgroup. A trend toward negative correlation, though not statistically significant, was found in bipolar depression between cortisol levels at 17 hr after dexamethasone administration and urinary MHPG X SO4 excretion. This may indicate that some differences in norepinephrine (NE) metabolism may exist between unipolar and bipolar depression, leading to differing correlations between deviation of central NE function and hypothalamus-pituitary-adrenal (HPA) axis in different subgroups of depression.
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PMID:Dexamethasone suppression test and urinary MHPG X SO4 determination in depressive disorders. 360 15

The urinary excretion of 3-methoxy, 4-hydroxyphenyl-glycol, (3-MHPG) was measured in 20 unipolar depressed patients before treatment with imipramine and electroconvulsive therapy (ECT) to investigate the relationship between pretreatment urinary excretion of 3-MHPG and clinical response. There was no difference in 3-MHPG excretion for depressed patients and controls. There was no significant difference between the mean percentage reduction of Hamilton Depression Rating Scale Scores in "low" and "high" excretors of 3-MHPG in the imipramine and ECT group of patients after four weeks of treatment.
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PMID:3-MHPG as a non-predictor of antidepressant response to imipramine and electroconvulsive therapy. 378 51

A number of arguments support the hypothesis that changes in urinary levels of MHPG sulfate and MHPG glucuronide respectively reflect central and peripheral norepinephrine metabolism (NE) in man. In this line, the daily excretion of both conjugates was determined in 36 depressed women comparatively to 23 healthy women in order to assess the extent and the central or peripheral location of their possible NE dysfunction. About 80% of the patients suffering from depression (6 endogenous, 19 neurotic, 11 reactive depressions) exhibited a central NE defect, as evidenced by low MHPG sulfate, and many of them had probably also diminished sympathetic activity, as suggested by low MHPG glucuronide. Clinical symptoms possibly related to the psychic state (mood alteration) or associated to sympathetic changes (anxiety, motor activity) respectively altered sulfate or glucuronide excretion. Sulfate (S) and glucuronide (G) MHPG excretions were significantly correlated in healthy subjects (r = 0.53, p = 0.01), thus supporting the concept of the functional link between central NE activity and sympathetic function. Such a correlation was not found in depressive patients. However the lack of significant changes in the mean ratio S/G in the patient sub-groups suggests that as in normal subjects, central and peripheral NE activity are linked in depressed patients, but other factors may also modify sympathetic function. Taken together our data show that the separate assay of sulfate and glucuronide MHPG provides a better picture of NE dysfunction in depression than total MHPG measurement.
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PMID:Sulfate and glucuronide conjugates of 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine of depressed patients: central and peripheral influences. 406 98

Beside neurochemical imbalances, there are numerous disruptions of circadian rhythms in endogenous depression. Recent studies have actually shown instability in rhythmicity and phase advance of many circadian rhythms in depression (central temperature, cortisol, urinary MHPG...). We have observed the longitudinal evolution of circadian rhythms (core temperature, plasma cortisol) of depressed patients who were treated by a two weeks phase-advance process, then with antidepressant drugs. Our results show that clinical improvement during phase-advance process is much faster than under tricyclics, with the same Hamilton scale level after two weeks of treatment. From a biological point of view, we show an ultradian instability, a phase advance (2 to 4 hours) and modifications of averages and amplitudes of circadian rhythms. These abnormalities tend to disappear during phase-advance process and antidepressant therapy. Phase response curves to the phase shift in depressed patients could be explained by a bad sensitivity of these subjects to external synchronisers linked to an internal dyschronism. These disturbances lead us to link desynchronisation and endogenous depression.
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PMID:[Circadian rhythms of the central temperature and blood cortisol in endogenous depression]. 408 5

We investigated the relationship between urinary excretion of MHPG and the clinical response of 17 depressed patients to nortriptyline hydrochloride. Plasma concentrations of nortriptyline were monitored to assure optimal doses. Patients were classified as having "low" or "normal-high" excretion of MHPG based on one to five 24-hour urine specimens. Hamilton Depression Rating Scale scores were not reduced significantly more among the nine low excreters as compared with the eight normal-high excreters. However, when a true bimodal distribution of MHPG excretion was created by comparing only the six lowest excreters with the six highest excreters, the low group improved significantly more than the high group. This differential response to nortriptyline somewhat supports the notion that MHPG excretion may predict response to specific tricyclics. Collecting urine for MHPG determination in depressed patients is not easy; the variability of excretion within patients is considerable, and the range of MHPG excretion closely parallels that in normal persons. The clinical utility of this procedure is still to be determined.
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PMID:Subtypes of depression based on excretion of MHPG and response to nortriptyline. 615 27

Fifteen depressed patients were treated with increasing doses of bromocriptine in an open study. Twelve were treated for 5 weeks (final dose 20-60 mg daily) and nine of these recovered almost completely. As expected from a dopamine agonist, bromocriptine decreased the level of homovanillic acid (HVA) in cerebrospinal fluid (CSF) by 15% (P less than 0.05) and 23% (P less than 0.01) after 2 and 5 weeks of treatment, respectively. After 2 but not after 5 weeks of treatment there was also a small but significant decrease (13%; P less than 0.001) of the noradrenaline metabolite HMPG in CSF. Although there was no mean effect on 5-HIAA in CSF, there was a significant relationship between the HVA and 5-HIAA levels (as % of pretreatment level) both after 2 and 5 weeks of treatment (r = 0.96 and r = 0.62, respectively). This may indicate that the drug has an effect on the serotonin system secondary to the dopamine receptor stimulation. The amelioration of depression was not related to HVA, but did correlate to HMPG in CSF (r = 0.65; P less than 0.05) both metabolites measured before treatment. These results indicate that bromocriptine may have antidepressant effects possibly mediated through the noradrenergic system rather than the dopaminergic system.
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PMID:Bromocriptine treatment of depressive disorders. Clinical and biochemical effects. 617 6

The biochemical features of depressions able to guide the prescription of antidepressants are seen through a review of the literature. The papers were mainly focused on the peripheral catabolites of brain monoamines. Depressions characterized by low levels of 5 HIAA in the C.S.F. would predict a better efficacy of the antidepressants acting on the re-uptake of serotonin. The dosage of urinary MHPG seems to be a valuable index for the choice of the drug. Subjects with low levels response better to IMI, DE-IMI and NT, and those with normal levels to AMI. COMT activity and platelet MAO activity are may be a valuable index for the predictivity of the therapeutic results. Finally, the dexamethasone suppression test can be useful in order to guide the length of the treatment.
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PMID:[Therapeutic implications of the biochemical features about depressive illness (author's transl)]. 617 68


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