R. Tissot

Pick’s Disease

Study of 32 cases of Pick’s lobar atrophy offers evidence that one must distinguish some particular histopathological forms, characterized by the presence or absence of argyrophilic inclusions and/or

Guidelines for the dosage of neuroleptics. I: Chlorpromazine equivalents of orally administered neuroleptics.

Chlorpromazine (CPZ) equivalents are often used as a relative measure of the antipsychotic potency of neuroleptics. We review the CPZ equivalents of 33 neuroleptics and illustrate why imprecisions or discrepancies will be difficult to eliminate from these values. We nevertheless underline that CPZ equivalents can be clinically useful, since they facilitate the choice of doses of different neuroleptics that should induce comparable antipsychotic effects.

Some Aspects of Language in Various Forms of Senile Dementia (Comparisons with Language in Childhood)

A comparison of child language with deteriorated language in senile dementia shows the two to be very dissimilar. The principal language symptoms in dementia are impoverished vocabulary, word groping, repetitiveness, disorders of syntax, semantics, and phonology resembling the paraphasic phenomena in aphasia due to sudden focal lesions. It is proposed that the language disorganization is due to a combination of breakdowns in various functions and processes. The authors reject the notion that aphasias due to localized lesions are simply disturbances in performance (in Chomskys sense) while the language disturbances in the demented are a simple consequence of underlying thought disorders.

Evolution of blood magnesium, sodium and potassium in depressed patients followed for three months.

No consensus has been obtained about blood electrolyte status, especially about magnesium, in affective disorders. This is mainly due to the lack of information about the distribution of the patients in clinical subgroups, sex, type of treatment and about the severity of their illnesses. Most of these studies concerned treated patients. We confirmed in this study that drug-free depressed patients have higher erythrocyte and plasma magnesium than controls, as shown in previous reports. Significant differences are observed in as shown in previous reports. Significant differences are observed in patients for sex and between clinical subgroups. Low plasma potassium levels are described in both male and female depressed patients. The erythrocyte magnesium level tends to normalize in parallel with clinical improvement, depending on sex and clinical subgroup, and seems then to be related to the intensity of the depression. Plasma magnesium in male and female patients, except for female unipolars, remains higher than controls in all conditions and might be related to the diagnosis of affective disorders.

Guidelines for the dosage of neuroleptics. II: Changing from daily oral to long acting injectable neuroleptics.

When changing from daily oral to long acting injectable neuroleptic therapy, it is essential to choose a dose that will maintain clinical efficacy without increased adverse reactions. Information on pharmacokinetics is needed to achieve this. The authors present guidelines based on this information and observe that previous recommendations sometimes differ substantially from these guidelines. Whether these guidelines will improve the results of long term treatment of psychotic patients remains to be determined.

Platelet membrane alpha2-adrenergic receptors in depression

The platelet membrane was used as a model system to examine alpha 2-adrenergic receptors in 30 depressed patients and 30 healthy control subjects. The number of binding sites and their affinity for 3H-UK 14304 (5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline), a potent, highly selective alpha 2-adrenergic receptor agonist, was measured. Plasma magnesium and free 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were assayed in the same sample. A decreased agonist-receptor affinity was found in depressed patients, whereas receptor density was not significantly altered compared with that in control subjects. In bipolar depressed and dysthymic patients, there was a tendency toward a higher density of alpha 2-adrenergic receptors. This trend was not apparent in unipolar, recurrent depressed subjects. Moreover, a positive correlation between Bmax and Kd values was observed in patients but not in control subjects--a finding that suggests that a compensatory phenomenon occurs in depression. After the patients were treated with antidepressant drugs, an increased affinity (decrease in Kd) was observed, together with a decrease in binding sites. Plasma magnesium concentrations were higher in drug-free depressed patients than in control subjects. In addition, magnesium concentrations were negatively correlated with the density of alpha 2-adrenergic receptor binding sites in depressed patients, both before and during treatment. Lastly, a trend toward a negative correlation between plasma MHPG concentration and the number of binding sites was also observed. These results suggest a complex multifactorial regulation of alpha 2-adrenergic receptors, which are probably hyposensitive in depressive syndromes.

Adrenaline-Induced Platelet Aggregation in Depressed Patients and Control Subjects

We measured alpha 2-adrenoceptor-mediated platelet primary aggregation in depressed patients and healthy subjects. Both initial velocity and maximum amplitudes of platelet response to increasing concentrations of adrenaline were decreased in drug-free depressed patients as compared with controls. The EC50 of both initial slope and maximum amplitude were also increased in drug-free depressed patients. The results suggested a lowered platelet alpha 2-adrenoceptor function. Demographic factors (age and sex) and the time between blood collection and start of aggregation monitoring did not influence the results. This report is consistent with postsynaptic receptor desensitization in depressed patients. The precise molecular mechanism for this impairment remains to be elucidated.

La barrière capillaire enzymatique pour la DOPA au niveau de quelques noyaux du tronc cérébral du rat

An enzymatic barrier for Dopa exists at the level of the cerebral capillaries which changes Dopa into Dopamine by means of endothelial decarboxylase. It is abolished by a decarboxylase inhibitor. Its intensity is weaker in structures containing Dopamine (Striatum, Locus Niger). Neurones of the Raphé containing serotonin can be charged with catecholamines. There are close contacts between neurones and capillaries.

Differential effects of acute and chronic administration of haloperidol on substance P and enkephalins in diverse rat brain areas.

Rats received 10 mg/kg/day of haloperidol during up to 9.5 weeks. Substance P, Leu- and Met-enkephalins, were studied in brain using immunohistochemical methods. Haloperidol modified the peptides immunoreactivity in most brain areas. The time necessary to observe the effects of haloperidol on the peptides varied individually, depending on the peptide and the brain area. Moreover, inversions of these effects were often observed, generally occurring between in 5th and 7th day of drug administration. Substance P was increased after haloperidol in the hypophysis, a finding hereto not described. This descriptive study identified none of these three peptides as a single and specific target for dopaminergic receptor blockade. Methodological issues in evaluating the effects of neuroleptics on brain peptides are discussed.

Early decrease in density of mononuclear leukocyte β-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.