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Biomedical subjects

C Benkelfat

Publications and source records attributed to C Benkelfat.

89 records · Page 5Linked to original sources

Lack of correlation between plasma DOPEG and urinary MOPEG levels in depressed patients.

Twenty-four-hour urinary excretion of 3-methoxy,4-hydroxyphenylethyleneglycol (MOPEG) and levels of free and conjugated plasma 3,4-dihydroxyphenylethyleneglycol (DOPEG) were measured in 56 depressed patients to find a possible correlation between these two peripheral indices of cerebral noradrenergic activity. Plasma DOPEG was measured at 9:00 AM on the same day that urine was collected for the measurement of MOPEG. All depressed patients were diagnosed as having affective disorders according to DSM-III. No correlation was found between plasma free or conjugated DOPEG levels and urinary MOPEG output. This lack of correlation was found in the total sample of depressed patients (56), in 45 patients diagnosed as having major depressive episodes, and in 24 depressed patients diagnosed as major depressive with melancholia. The authors discuss the significance of this lack of correlation between two peripheral indices of central noradrenergic metabolism.

Adult↗

Plasma 3,4-dihydroxyphenylethyleneglycol and therapeutic response to maprotiline and indalpine in major depression.

Plasma levels of free and conjugated 3,4-dihydroxyphenylethyleneglycol (DOPEG), the main deaminated metabolite of norepinephrine, were assayed in 48 depressed patients before initiating a treatment with either maprotiline, an inhibitor of norepinephrine reuptake, or indalpine, a specific inhibitor of serotonin reuptake. The two groups of depressed patients were comparable. The therapeutic effect was evaluated by using the Hamilton Rating Scale for Depression. No difference in pretreatment plasma free and conjugated DOPEG levels was found between the responders and the nonresponders to maprotiline or indalpine. Neither was there any difference in the pretreatment levels of plasma free DOPEG between the two groups of responders and the two groups of nonresponders to either drug. Finally, there was no difference in the therapeutic response to maprotiline or to indalpine between the patients with high and low plasma DOPEG levels before treatment. These results indicate that there is no relationship between the initial plasma levels of DOPEG in depressed patients and their therapeutic response to a norepinephrine or a serotonin reuptake blocker.

Adult↗

Plasma 3,4-dihydroxyphenylethyleneglycol levels in depressed patients with and without abnormal dexamethasone suppression.

Escape from dexamethasone-induced suppression of plasma cortisol is an abnormality found in about half of patients with major depression. It has been hypothesized that this hyperactivity of the hypothalamo-pituitary-adrenal axis might be related to a central noradrenergic hypofunction. The present study was designed to test this hypothesis by measuring plasma 3,4-dihydroxyphenylethyleneglycol (DOPEG) levels (free and conjugated forms), an index of central noradrenergic activity, and by simultaneously carrying out a dexamethasone suppression test. Forty-five patients with a diagnosis of major depression (according to the DSM-III) were investigated. Plasma DOPEG levels (measured at 8 a.m.) were found to be similar in dexamethasone suppressor and nonsuppressor depressed patients. These results do not support the hypothesis that central noradrenergic hypoactivity underlies nonsuppression of dexamethasone in major depression.

Adult↗

Use of interactive computer technology in open clinical trials. Study with trazodone in depressed patients.

This study reports the efficacy and safety of trazodone as an antidepressant drug in a national telematic multicenter outpatient open clinical trial. In less than 3 months, 1,700 patients completed a 1-month treatment and among them, 65% were considered as responders. The side effect profile of the drug included sedation, gastrointestinal discomfort and moderate hypotension. One case of trazodone-induced priapism is presented and briefly discussed.

Adolescent↗

[Good and bad therapeutic combinations in the treatment of resistant depressions].

The definition of resistant depression is imprecise and variable according to the different authors. In most cases, the definition concerns depressed patients who have received well managed treatment with optimal doses of a thymoanaleptic over a sufficiently long period of time. The distinction of manic-depressive psychoses (MDP) with a rapid cycle also raises the problem of resistance to the prophylactic effect of mood regulators in MDP. The inefficacy of treatment in at least 20% of cases of depression has led a number of authors to propose original drug combinations with the aim of potentiating the action of previous treatments. Most of the studies published report isolated cases in which the therapeutic approach is often empirical and rarely explained. The most frequently reported combination is that of 2 drugs, generally including one antidepressant. Such combinations can induce pharmacodynamic or pharmacokinetic interactions resulting in either a potentiation or a reduction of the effects of one of the 2 drugs or to the induction of toxicity. These last two possibilities illustrate what the authors describe as "bad combinations". Various drug combinations are reviewed and critically analysed. The most interesting and best documented combinations involve the addition of lithium, MAOI and thyroid hormones to tricyclic treatment in non-responding patients. Other combinations with tricyclics have been reported less frequently: ECT, neuroleptics, reserpine, carbamazepine, 5 HTP, tryptophan, amphetamines, oestrogens, sleep deprivations.(ABSTRACT TRUNCATED AT 250 WORDS)

Antidepressive Agents↗

[Cerebral noradrenaline metabolism and classification of depression].

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.

Blood Platelets↗

[Telematic multicenter study of Pragmarel 100 mg (trazodone)].

Trazodone is a molecule which is already well known throughout the world for its antidepressant properties and its good global safety. We have conducted a large national study in outpatients. By means of a computerized communication network (233 psychiatrists equipped with Minitel), almost 2,000 depressed patients have been followed over a four week period of treatment with Pragmarel 100 mg, in less than three months. Computerized DSM III diagnostic criteria were used to define two sub-groups of patients. The results confirm the therapeutic indications of trazodone in various forms of depression, major affective disorders (689 cases) and other affective disorders (1,257 cases). 82% good and very good results were obtained in the overall population of patients, with a decrease by more than 50% in the initial score on the MADRS scale in 65% of cases. The low incidence of side effects and the excellent acceptability of treatment also confirm the date reported in the literature.

Adult↗

[Study of the metabolism of cerebral noradrenaline in depressed patients by the assay of plasma dihydroxyphenylethylene glycol].

Dihydroxy-phenyl-ethylene-glycol (DOPEG or DHPG), a deaminated catabolite of noradrenaline formed after presynaptic re-uptake, is a good marker of metabolic activity in noradrenergic pathways. Plasma levels of free, conjugated and total DOPEG were measured by a radioenzymatic method in 45 patients with major depression selected according to the DSM 3 criteria and in 45 matched controls. A significant decrease in man DOPEG levels was observed in all depressive patients. A dexamethasone suppression test performed in these patients showed no difference in DOPEG levels between responders and non-responders, thus failing to support the hypothesis that subjects with low noradrenergic drive escape suppression. There was no correlation between plasma DOPEG levels and urinary excretion of methoxy-hydroxy-phenylglycol (MOPEG), another marker of noradrenaline metabolic activity. Thirty-one patients were treated with a specific monoaminergic antidepressant: maprotiline or indalpine; contrary to urinary MOPEG levels, plasma DOPEG levels had no predictive value concerning the response to this category of antidepressants. The various possible reasons for the fall in DOPEG observed in depressive patients are discussed.

Adult↗

Electroencephalographic cartography. II. By means of statistical group studies-activation by visual attention.

10 male volunteers, right-handers, mean age 30.4 years, were recorded in four successive sequences: under 'eyes closed' conditions, right and then left hemisphere, followed by an 'eyes open' situation with visual attention fixed on a cartoon, right and then left hemisphere recordings. Each EEG recording was made simultaneously over 16 EEG channels for each hemisphere, according to a protocol previously described as well as Fourier analysis and EEG mapping on a minicomputer (HP 5451 C, HP 1000). Each EEG recording was stored on a cartography data base, and 90 maps could be drawn from 10 spectral parameters applied to the raw EEG and 5 frequency bands. Permutation paired Fisher tests were applied to three main EEG parameters: mean centroid frequencies, RMS amplitudes in microvolts and relative (%) amplitudes. Activation of EEG in the 'eyes open' situation during visual fixation was found compared to the 'eyes closed' situation: decreasing dominant EEG frequency and low delta and theta mean frequencies, no change in a mean alpha frequency; increasing fast mean beta frequencies, together with a major decrease in theta, alpha, beta 1 amplitudes, and a concomitant increase in raw EEG, delta and beta 2 amplitudes. Finally, the percent alpha amplitude was decreased when other percent amplitudes were increased in delta, theta, beta 1 and beta 2 frequency bands. A symmetry between hemispheres was observed in the 'eyes closed' situation. Averaged EEG maps between subjects illustrate these findings, especially relative (%) alpha amplitude maps and also maps of coefficients of resonance of the alpha rhythm.

Adult↗

[3H]Imipramine binding and [3H]5HT uptake in human blood platelets: changes after one week chlorimipramine treatment.

In platelets of normal volunteers taking chlorimipramine (50 mg/day) for one week, the saturable uptake of [3H]5HT was fully inhibited at day 8, but returned to control values at day 15. The Bmax of [3H]imipramine binding was decreased by 65% at day 8 and remained significantly below control values at day 15. If the present findings can be extrapolated to other antidepressants, the reported decreases in [3H]imipramine binding in depression may partly reflect residual treatment effects. It cannot be excluded that, in depression, the platelet [3H]imipramine receptor already is down-regulated maximally which would preclude a further down-regulation due to antidepressant drug therapy.

Adult↗

[Decrease in transcortin binding activity in depression].

In a preliminary study, Cortico-Binding Globuline (CBG) has been determined in 10 depressed major inpatients (DSM3) and compared with healthy volunteers. A clear cut fall of binding activity of transcortin is reported in depressed patients associated with an increase of total and free plasmatic cortisol.

Adult↗

[Study of noradrenaline metabolism in depressed patients by the determination of plasma dihydroxyphenylethylene glycol].

The plasmatic levels of free, sulfoconjugated and total dihydroxyphenylethyleneglycol (DOPEG), the main deaminated metabolite of noradrenaline, have been measured in thirty DSM3 major depressive inpatients and in thirty healthy controls matched for sex and age. DOPEG levels have been measured by a radioenzymatic assay. Almost fifty per cent of depressed inpatients were D.S.T. non suppressors, thirteen patients were unipolar and thirteen bipolar. Plasmatic DOPEG levels were significantly lower in depressed patients as compared to healthy controls despite a wide interindividual range of DOPEG values. However, the ratio of free over conjugated DOPEG was not statistically different in the two groups. DOPEG levels were slightly higher in the female population of healthy volunteers but not in the depressed patients. In the healthy volunteers, but not in depressed patients, there was a trend for free DOPEG to increase and for conjugated DOPEG to decrease with age. There was no statistical correlation between the DOPEG levels and Hamilton Depression Scores. Also plasmatic DOPEG values were not different in uni or bipolar patients and in DST suppressor or DST non suppressor inpatients. The significance of the decrease of plasmatic DOPEG levels in depressed patients is discussed: this diminution may reflect a deficiency in noradrenaline metabolism in CNS or else may be attributed to other factors e.g. alteration in circadian rhythms, differences in motor activity, in level of anxiety, in sleep and feeding behaviors; cotreatment with benzodiazepine and opiate compounds; monoamine oxidase activity.

Adult↗

DRD3 and DAT1 genes in schizophrenia: an association study.

OBJECTIVE: To investigate the role of the dopamine receptor 3 (DRD3) and transporter 1 (DAT1) genes in schizophrenia or in modulating its phenotype. METHODS: a Ser9Gly polymorphism in codon 9 of the DRD3 and a VNTR polymorphism in the DAT1genes were examined in two groups of schizophrenic patients, one of excellent neuroleptic responders (N=42) and one of nonresponders (N=64). A group of healthy volunteers screened for major psychiatric disorders was also included (N=89). In addition, age at onset of psychotic symptoms, attention performance and family loading for schizophrenia spectrum disorders were compared between patients with different genotypes in the DRD3 and DAT1 genes. RESULTS: No significant differences in the allelic distribution of the DRD3 and DAT1 polymorphisms were detected between schizophrenic patients and controls. A trend toward an excess of DRD3 genotype Gly/Gly was observed in neuroleptic nonresponder schizophrenic patients compared to controls (chi(2)=3. 30, df=1, p=0.07). No significant differences in age at onset of psychotic symptoms, attention task performance or family loading for schizophrenia spectrum disorders were observed between groups with different DRD3 and DAT1 genotypes. CONCLUSION: These results do not support the role of either of these genes in increasing susceptibility to schizophrenia or in modulating its phenotype in the studied population.

Adult↗

[Biochemical effects of electroconvulsotherapy].

ECT and ECS biochemical, pharmacological and electrophysiological effects on Norepinephrine, Dopamine, Serotonin, Acetylcholine, GABA and Opiates are reviewed. ECS and ECT seem to potentiate behavioral responses to Serotoninergic and Dopaminergic agonists, and up-regulate post-synaptic 5-HT2 receptors. However, the mechanism of the antidepressant effect remains unknown and probably involves several interacting neurotransmitters.

Animals↗

[Cognitive therapies of depression].

Among brief psychotherapies of depression, cognitive therapy, a theoretical model which was proposed by A.T. Beck as early as the sixties, holds that depression comes from a distorted view of the environment: depressed patients view themselves, the world and the future negatively (cognitive triad). This conception is based upon cognitions, preconscious schemes and faulty information processing, that cognitive therapy corrects, using in a pragmatic way cognitive and behavioral techniques requiring an active collaboration of the patient. Cognitive therapy is indicated, alone or combined with anti-depressants, in neurotic depressions (DSM-II) and in most of major depressions (DSM-III) treated on an outpatient basis. Comparative outcome studies prove the effectiveness of cognitive therapy.

Behavior Therapy↗