[Phenomenology in dysthymic disorders].
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Chronic Disease↗
Biomedical subjects
J M Azorin
Publications and source records attributed to J M Azorin.
[The atypical neuroleptic concept].
Atypical neuroleptics can be defined as dopamine (DA) receptor blockers which differ from typical neuroleptics in that they have a markedly lower or absent propensity for the induction of parkinsonian side effects of tardive dyskinesias. Some of them, but not all, are also more effective in treating schizophrenic patients, i.e. those with negative symptoms or who resist to classical treatments. There may be four classes of potential atypical neuroleptics: 1) Antipsychotics such as sulpiride and remoxipride that block a subgroup of D2 receptors; 2) D1 antagonists that may prove to be a valuable new type of antipsychotic drug; 3) Partial D2 agonists and 4) Antipsychotics such as clozapine and risperidone which block DA as well as other receptors and which appear to have the most pronounced antipsychotic effect. The differences between typical and atypical neuroleptics may first relate to regional specificity in site of actions. Animal studies suggest that atypical neuroleptics may act preferentially on mesolimbic and mesocortical as opposed to striatal DA systems. Most studies which have attempted to define the biological mechanisms which subserve the differences between atypical and typical neuroleptic drugs have focused on receptor binding profile of these drugs. Relatively higher affinity for the serotonin (5HT2) receptor than for the D2 receptor may be important to the action of clozapine-like compounds. However, many other systems might be involved and it seems likely that the atypical neuroleptic profile could be achieved in more than one way.(ABSTRACT TRUNCATED AT 250 WORDS)
Antipsychotic Agents↗
[A 15 years' follow-up of use of lithium at the Department of Psychiatry of Marseille University. Data concerning the follow-up of 205 patients].
The authors report descriptive data from a follow-up study of 205 patients taking lithium therapy and treated at the Department of Psychiatry (Marseille, France), during a 15 years period (1972-1987). Methods of investigation consisted in a detailed examination of their hospital and clinic case notes and in medical interviews of psychiatrists in charge of patients. 25 features have been selected in order to precise clinical and biological characteristics of patients: Diagnosis (INSERM, ICD9), family history of psychiatric disorders, illness course, salt used, serum and erythrocytes lithium levels, dose maintenance, additional medications, psychological and physical side effects, compliance with medication and clinical response.
Adult↗
Beta-adrenoceptor density of intact mononuclear leukocytes in subgroups of depressive disorders.
Binding parameters of (-)-iodopindolol to beta 2-adrenoceptors were determined on intact mononuclear cells in 41 untreated patients with different DSM-III subtypes of depression. Both maximal beta-receptor density (Bmax) and dissociation constant (Kd) were not significantly different between control and all depressed subjects. However, Bmax was significantly decreased in unipolar patients as compared to controls (p less than 0.001) whereas no significant difference was found in bipolar or dysthymic patients. In unipolar patients, a very strong association was found between Bmax values and the severity of the depression as assessed by the Hamilton Depression Rating Scale score (r = -0.75; p less than 0.005). This correlation was also highly significant in the entire depressed population (r = -0.58; p less than 0.0009). These results suggest that the lower number of beta-adrenoceptors in intact leukocyte cells of depressed patients is related to the depression severity.
Adrenergic beta-Antagonists↗
Early decrease in density of mononuclear leukocyte beta-adrenoceptors in depressed patients following amineptine treatment: possible relation to clinical efficiency.
1. The effect of chronic amineptine treatment (200mg/day) on beta-adrenoceptor density of intact mononuclear leukocytes (MNL) was examined in unmedicated major unipolar depressed patients. 2. Pretreatment parameters of (-)-[125I]-iodopindolol specific binding did not differ significantly from age- and sex-matched healthy controls as the patients were only moderately depressed. 3. All patients showed a highly significant clinical improvement as assessed by the AMDP-depression scale after one week of amineptine (D7), while 2 patients relapsed after one month of treatment (D28) and were considered to be non-responders. 4. The maximal density of beta-adrenoceptors (Bmax) was significantly decreased at D7 (by 33%) compared to pretreatment level (D0) in the treatment responders and remained lower at D28, although the difference was no longer significant. No alteration in beta-receptor affinity (Kd) was detected during the treatment. 5. These results indicate that treatment with amineptine, an antidepressant drug known to selectively inhibit the dopamine uptake system, can rapidly affect MNL beta-adrenoceptors. 6. Moreover, the present findings show that the reduction in MNL beta-adrenoceptor density, which is associated with a stable clinical improvement, may provide a predictive index for successful antidepressant treatment.
Adult↗
L-tyrosine and L-tryptophan membrane transport in erythrocytes and antidepressant drug choice.
In the treatment of depression, when antidepressant drug choice is made according to alterations of erythrocyte membrane transport of L-tyrosine and L-tryptophan in the individual patient, the clinical results are superior to those obtained when drugs are prescribed according to the physician's judgment. This is demonstrated by comparing three experimental groups: I, 100 patients treated in relation to their L-tyrosine and L-tryptophan transport; II, 30 patients treated according to the clinician's experience; III, 38 subjects treated against the L-tyrosine and L-tryptophan transport indications. In these groups, the frequency of patients improved by more than 70% is 77%, 47%, and 16%, respectively.
Adult↗
Des-enkephalin-gamma-endorphin in the treatment of schizophrenia.
Ninety-three patients with an exacerbation of chronic schizophrenia were included in a 4 week trial comparing placebo with 1, 3 and 10 mg des-enkephalin-gamma-endorphin (DE gamma E; beta-lipotrophin 66-77; Org 5878) per day (i.m.). Maintenance antipsychotic and other medications were continued unchanged. Treatment effects were assessed by means of the Comprehensive Psychopathological Rating Scale--subscale schizophrenia (CPRS-S), Brief Psychiatric Rating Scale (BPRS) and Global Assessment Scale (GAS) rating scales at weekly intervals. Safety data, i.e. laboratory investigations, vital signs and ECG recordings, were assessed before and during the trial. Side-effects were evaluated by means of a Record of Symptoms Emerging. Sixty-eight patients completed the trial, the reason for drop-out mainly being inadequate treatment effects and refusal of medication administration. One patient violated the protocol. After 4 weeks of treatment the mean CPRS-S score of the group receiving 10 mg DE gamma E daily had decreased statistically significantly more than the corresponding score of the placebo group (p less than 0.01). The same trend was apparent with BPRS (p = 0.08) and GAS (p greater than 0.1) scores. Therefore, the study should be considered inconclusive. No clinically relevant side-effects attributable to DE gamma E were observed.
Adult↗
Plasma 3-methoxy-4-hydroxyphenylglycol in manic patients: relationships with clinical variables.
Plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were found to be significantly higher in manic patients than in age- and sex-matched normal controls (n = 22). In 18 manic patients plasma MHPG correlated with manic symptoms but not with anxiety, depression, motor behaviour, acute psychosis, schizophrenia and severity of illness. A positive correlation between MHPG and grandiosity items on rating scales suggests a link with cognitive contents and therefore a relationship with central factors.
Adolescent↗
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.
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.
Adult↗
Plasma levels of 3-methoxy-4-hydroxyphenylglycol in depressed patients compared with normal controls.
Plasma levels of total 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in a group of 104 hospitalized depressed patients and a group of 104 age- and sex-matched normal controls. Plasma MHPG levels were found to be normally distributed in both groups and significantly lower in depressives than in controls. However, this difference could be related to an increase in plasma MHPG levels with age found in controls (r = 0.601, d.f. = 102, p less than 0.01) but not in depressives (r = 0.013, d.f. = 102, NS). Men had significantly higher levels than women in both groups. There was no significant difference in plasma MHPG levels among any DSM-III-R diagnostic subgroups of depressives or between patients who were suppressors on the dexamethasone suppression test and those who were nonsuppressors. Significant correlations were found between AMDP Depression Rating Scale item and total scores and levels of plasma MHPG. Age, sex and clinical symptoms appeared to be main sources of variance in studying depressed patients and comparing them with normal controls.
Adult↗
[Different aspects of the cognitive activities of patients with schizophrenia. IV. Imbalance between assertions and negations].
Not being able to equilibrate affirmations and negations, the schizophrenic patient accedes only exceptionally to the majoring equilibrations of the second and third levels. In the logico-mathematic field, he does not approach the constructive synthetizing generalisations of reasoning. Lacking reflective abstraction, he cannot balance his logico-mathematic reasoning and differentiate what is structurally possible from what is materially possible, thus explaining his inaccessibility to perceive logic necessities, contrasting with the certainties of his delirium. In the logico-experimental domain, he reaches only rarely clause reasoning generalisation, and relapses regularly to the level of inappropriate generalisations of the extended inductive type. It is useless to try to find the "primum movens" of his difficulties, either in his imbalance assimilation/accommodation, or in his impossibility to see his contradictions, or even in his incapacity to equilibrate affirmations and negations. The majoring equilibrations, of which he is unable, are the functional expression of structures which do not follow the linear causality of Laplace's determinism but the circular causality characteristic of teleonomic processes. After a month of neuroleptic treatment, the decompensated schizophrenic's balance between assimilation and accommodation is partially restored.
Adult↗
Platelet [3H]-imipramine binding according to DSM-III subtypes of depression.
The question of the previously reported changes in the density of high-affinity binding sites for [3H]-imipramine (IMI) in platelets from depressed patients was reexamined among the different diagnostic subtypes of depression according to the DSM-III classification and taking into account the possible influence of the low-affinity binding site. Using a least-square computer-assisted analysis, a precise determination of the [3H]-IMI binding parameters exclusively in relationship to the high-affinity site was performed in 46 untreated depressed patients and compared to 35 healthy controls. The results revealed a clear and highly significant 22% decrease in the maximal density (Bmax) of [3H]-IMI binding in all of the depressed patients compared to controls with no change in affinity values. Considering the diagnostic subgroups, we found that all the bipolar patients, the depressed as well as the euthymic or manic ones, had very low Bmax values and that some of them also exhibited an unusual low-affinity binding. Mean Bmax of the unipolar and dysthymic patients significantly decreased when compared to controls, although the Bmax values showed a large variability. Only dysthymic patients presented Bmax values which were significantly associated to symptom severity as assessed by the Hamilton Depression Rating Scale scores. Our results confirm the lower density of platelet [3H]-IMI binding in affective disorders, particularly in bipolar patients, and also suggest that this biological parameter is a trait marker in bipolar depression and a state marker in dysthmic disorder.
Adolescent↗
Plasma 3,4-dihydroxyphenylethyleneglycol and 3-methoxy-4-hydroxyphenylethyleneglycol as indicators of central noradrenergic activity. A comparative study on control subjects and depressed patients.
Animal studies have suggested interspecies differences in brain norepinephrine (NE) metabolism, especially with regard to the relative proportions of 3,4-dihydroxyphenylethyleneglycol (DOPEG) compared to 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG). In order to question the value of both glycol metabolites as peripheral indices of central noradrenergic activity, a comparative study of plasma DOPEG and MOPEG (measured by HPLC) related to depression, sex, age and diagnostic categories (DSM-III) was carried out on depressed and control subjects. In addition, two groups of 8 patients were randomly submitted to a desipramine 150 mg/day, or a metapramine 450 mg/day antidepressant treatment influencing the formation of DOPEG and MOPEG in a different way. The study did not demonstrate any difference between DOPEG and MOPEG for most of the experimental factors. We found also a significant positive correlation between plasma levels of DOPEG and MOPEG. Our results support the idea that each of these two biological indices can be used in the assessment of central noradrenergic activity.
Adult↗
Determination of 3,4-dihydroxyphenylglycol (DHPG) by HPLC with coulometric detection, and correlation with 3-methoxy-4-hydroxyphenylglycol (MHPG) in human plasma.
A method for determining plasma 3,4-dihydroxyphenylethyleneglycol (DHPG), a central noradrenaline (NA) metabolite, is described. The method used HPLC with dual coulometric detection set in screen mode of operation. The isolation of DHPG and related catecholamines (noradrenaline, dopamine and dihydroxybenzylamine) was performed on acid washed alumina extracted with 0.2 M HCIO4 containing EDTA (0.2%), and reduced glutathione as stabilizer. A reversed phase column with an eluting system containing 0.025 M citric acid-sodium hydrogen phosphate buffer in the ratio 3:2 (v:v) and 5% methanol was used. The experimental results of plasma DHPG levels compared favourably with the results from the literature, and a positively significant correlation with plasma MHPG was found. This method could be used as an alternative in central NA assessment.
Catecholamines↗
Kindling models and antikindling effects of mood normalizers.
In animal experiments, kindling designates the appearances of increasing EEG and behavioral responses when an initially ineffective stimulus on certain cerebral areas is repeated (Goddard et al., 1969). Its development occurs in association with increasing duration and spread over the major part of the brain of electric afterdischarges. This process may lead to critical changes in behavior. Kindling can be caused by electric stimulation or pharmacological inducement. The nature of the behavioral response varies with that of the stimuli, so different types of kindling have been described, constituting animal models notably for epileptogenesis. Their psychiatric interest stems from evidence of an inhibiting effect of certain substances, such as carbamazepine or phenytoin, which are effective in the treatment of both epilepsy and mental disorders, but this effect is also found for lithium (Post et al., 1982, 1984). Applied to the development of periodic psychoses, kindling models would account for certain unexplained clinical data and precisely explain the mechanisms and the specific action of various mood normalizers.
Animals↗
[Various aspects of cognitive activities of schizophrenics. III. Maladjustment assimilation/accommodation and generalization of reasoning].
Paranoid schizophrenics are unable to balance affirmation and negation. Using the terms of Jean Piaget, they therefore only partially achieve the "équilibrations majorantes" of level II and never those of level III. In their thinking, they have access to the "généralisations inductives" (often excessive ones), but rarely to the "généralisations constructives complétives". They do not have access to the "généralisations synthétisantes" or to the feeling that logic is necessary. They oscillate between the positivist need to measure or verify and absolute beliefs issued from magical thinking.
Adult↗
[Practical management of the agitated patient].
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Aged↗
[Current concept of pseudodementia].
The concept of pseudodementia was coined in the late XIXth century to refer to a syndrome mimicking dementia, but without underlying neurological lesions. Depressive disorders represent the main etiological factor and may present under two different forms, either "depressive cognitive disorders", or the more severe feature of "Wernicke's pseudodementia". The main issue remains diagnosing pseudodementia form organic dementia, especially from cortical degenerations of the Alzheimer type. Thus, the recognition of this clinical syndrome represents an alternative to the diagnosis of dementia which may lead to earlier and more effective psychiatric treatment. Recently, diagnostic criteria have been proposed to facilitate this distinction. Such criteria include clinical history, neuropsychological features, biological findings (dexamethasone suppression test and plasma MHPG) and electroencephalographic sleep studies. Finally, from a theoretical point of neurological conception of depression as well as for current hypotheses on the relationship of this last one with dementia.
Dementia↗