Clozapine and negative symptoms. An open study.

1. Clozapine, the first atypical antipsychotic, has demonstrated an efficacy in the treatment of resistant schizophrenia. But one of the major challenge in the treatment of schizophrenia remains the lack of efficacy of antipsychotics on negative symptoms of schizophrenia. 2. The authors studied the efficacy of clozapine in an open study in a population of 51 patients, who met the DSM IV criteria for schizophrenia. Using the positive and negative symptom scale (P.A.N.S.S.), and the Extra Pyramidal Symptoms Rating Scale (E.S.R.S.), we try to identify the specificity of the action of clozapine on the different symptomatic dimensions of schizophrenia. 3. The efficacy of clozapine was clinically significant on the negative symptomatology but was delayed compared to the efficacy on the other dimensions of symptomatology evaluated using the PANSS. 4. Nine patients, were considered as deficit patients; in this sample clozapine also demonstrated a significant efficacy on negative symptoms. The efficacy of clozapine did not seem to be a consequence of the better neurological tolerance of this antipsychotic evaluated with ESRS.

[Clinical expressions of depression]. / Expressions cliniques de la dépression.

The main clinical manifestations of depression can be described as a decrease of the psychic tone resulting in a disturbance of mood prone to sadness and a psychomotor retardation with slowness and feeling of fatigue. Anxiety is usually associated to these core symptoms as well as somatic signs. Suicidal risk is always present and is increased during melancolic states. A great clinical polymorphism makes the diagnosis difficult in some cases. If the spontaneous course of depression is usually favorable within a year, antidepressant treatments are necessary to shorten the duration of the illness and to avoid chronicisation and relapse.

A multicentre double-blind comparison of hydroxyzine, buspirone and placebo in patients with generalized anxiety disorder.

The efficacy of hydroxyzine and buspirone, controlled by placebo, was investigated in a double-blind, parallel group, multicentre study conducted in France and the UK. A total of 244 patients with generalised anxiety disorder in primary care was allocated randomly to treatments with hydroxyzine (12.5 mg morning and mid-day, 25 mg evening), buspirone (5 mg morning and mid-day, 10 mg evening) or placebo (three capsules/day) for 4 weeks, preceded by a 1-week single-blind placebo run-in and followed by 1-week single-blind placebo administration. Rating scales were applied on days -7,0,7,14, 12,28 and 35. Seventy percent of the patients were female, the average age was 41 +/- 11 years, and the mean Hamilton Anxiety Score at day 0 was 26.5 +/- 4.2. Only 31 of the 244 patients dropped out, but equally in the three groups. Intention-to-treat LOCF analyses on the primary variable showed a significant difference only between hydroxyzine and placebo with respect to improvement on the Hamilton Anxiety Scale (10.75 versus 7.23 points, respectively). Secondary variables such as CGI and self-ratings (HAD scale) showed both hydroxyzine and buspirone to be more efficacious than placebo. Thus, hydroxyzine is a useful treatment for GAD.

[Psychometric properties of PANSS (Positive and Negative Syndrome Scale) in the French version in a sample of schizophrenic patients]. / Etude des propriétés psychométriques de la PANSS dans sa version française dans une population de patients schizophrènes.

Our study focuses on psychometrics properties of the french version of the Positive and Negative Syndrom Scale (PANSS). 85 schizophrenic subjects, in accordance with DSM III-R criteria were included in this study. Our results allow us to discuss the construct validity and the reliability of this scale. The traditional 3 dimensions of the PANSS (positive, negative and general psychopathology) are discuss. We show that expect positive scale and general psychopathology scale average several symptomatic dimensions. We propose a 5 dimensions solution (negative, hostility, positive, disorganization, anxiety), which represent 54% of the total inertie. The internal consistency of this solution is presented.

[Frontal lobe cognition disorders in 42 schizophrenic patients compared with 19 normal probands]. / Etude des perturbations cognitives frontales chez 42 patients schizophrènes comparés à 19 témoins.

In schizophrenia, the hypothesis of frontal dysfunctions is sustained by various clinical, neuroradiological and neuropsychological observations. We have studied the degree of frontal cognitive impairment in 42 schizophrenic patients according to the DSM IV as compared to 19 normal subjects. Furthermore, the performances of the different tests were connected with the age, the duration of the disease, the severity of the illness (measured by the PANSS scale) and the incidence of the treatments. The neuropsychological tests used in this study were the D48, the Wisconsin card sorting test, the Stroop color and word test, the word fluency and a target detection test. The results obtained from this study agree with the occurrence of frontal cognitive impairments in schizophrenia. Such impairments are increased with the age and the duration of the disease.

[Cycloid psychoses]. / Psychoses cycloïdes.

Cycloid psychoses constitute an original classification originally proposed by Leonhard and comprising clinical pictures intermediate between schizophrenic psychoses and bipolar disorders. The exact situation of these disorders in psychiatric classifications has been the subject of debate, and their existence is still questioned. Only schizo-affective psychoses have been accepted as autonomous. Treatment of cycloid psychoses most often consists of neuroleptics but also mood regulators, particularly those having anti-epileptic effects Lastly, prognosis of these disorders usually is not as poor as that of schizophrenia and is marked by a cycloid course, with symptom-free periods between episodes.

[Drug addiction and AIDS]. / Toxicomanie et SIDA.

Drug abusers are one of the main groups exposed to the HIV contamination: they account for 23.3% of the cumulative cases of contamination in France. If sharing injection equipment is the major risk factor, we must consider the use of some specific drugs, personality factors, socioeconomic status and sexual behaviors to be significant risk factors. Nowadays, programmes aimed at reducing the transmission of HIV among drug injectors are raising. Information, education, HIV testing, free access to sterile injecting equipment, methadone maintenance programmes and prevention of risky sexual behaviors are the main tools of this policy.

[The depressed patient: remission or recovery?]. / Le déprimé: rémission ou guérison?

Since Kraepelin's works, depressive disorders have been considered as transient pathological episodes which are easily cured with antidepressive medications. Among these disorders, only manic-depressive illness, due to its periodic course, and neurotic depression, prone to recurrences and chronicity, do not fit with this model. In fact, many recent studies, conducted for the most part on large samples of depressive patients followed during a long period of time (many years), lead to other perspectives. it seems that, for most of the patients if not for all of them, recurrence and chronicity should be the rule. Comorbid personality disorders are of some importance for the course of depressive disorders but cannot explain why so many depressive patients experience recurrences of the disease. Some new hypothesis are investigated and one of them, proposed by R. Post and colleagues, postulate that stressors, like some life events, can induce transcription factors (mainly the proto-oncogene c-fos) which then affect neurotransmitters and, by consequence, the responsibility of the limbic system. Thus, these neurobiological changes could lead to further occurrences of depressive illness in patients who had experienced one depressive episode. All these data highlight the critical importance of early therapeutic intervention in the illness and of sustained maintenance treatment in order to avoid recurrences or chronicity.

[Descriptive approach to latent forms of schizophrenia]. / Approche descriptive des formes frontières des schizophrénies.

The computerized medical file, used in routine work in an Adult Psychiatry University-Hospital Unit enabled us to select 113 cases among 1,000 consecutive hospitalizations, the diagnosis of which could possibly lead to schizophrenia. These cases which we named "paraschizophrenic states" are linked to DSM III-R criteria of borderline (27 cases), schizoid (40 cases) or schizotypical (15 cases) personalities, schizophreniform trouble and unspecified psychotic trouble (17 cases), brief reactional psychosis (14 cases). We selected 196 cases of schizophrenia in the same cohort of hospitalized patients. As it is now usually admitted, we marked out two subgroups in this second group: the positive schizophrenia which gather together the paranoid and undifferentiated patterns and the negative schizophrenia which correspond to disorganized, catatonic and residual models, according to DSM III-R criterion. We compared the "paraschizophrenic states'" group and its five subgroups (we indeed joined schizophreniform trouble and unspecified psychotic trouble under the name of "other psychotic trouble" by reason of their relative nosographic lacks of precision and of their too small sizes) with the schizophrenia's group and its two subgroups. Each group is matched for sex (1.51 men for 1 woman in the first group and 1.45 men for 1 woman in the second group). We evaluated statistics for markers usually studied in schizophrenia in each subgroup. These markers are of three classes: biographical: age during the study, age of troubles' onset, season of birth; socioeconomic: socioeconomic level of family and patient's student status; psychiatric: family (history affective trouble, psychotic trouble, alcoholism), treatment response and short- and middle-term prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

[The health of foreign populations in France]. / La santé des populations d'origine étrangère en France.

In France, 8% of the population are foreign. They come from the lowest socio-economic level. In distinguishing the new arrivals from those who have lived in France for several years, the migrant related health patterns are applied. Health problems of foreigners in France can be examined in a number of different ways: --Foreign workers are found in unskilled work and in jobs where they are constantly subjected to hazards of the workplace, occupational health risks and accidents. --The quality of maternal and child health care among foreign women is lower than among the French. --Foreign children are hospitalized more often and for longer than French children. The types of illness are not specific. The truancy rate is more significant than the national mean. --Restrictions on the opportunities for enjoying certain social rights, administrative and financial obstacles encountered as well as difficulties in communication all make it harder to meet the needs of this section of the population.

[Erythrocyte membrane transport of tyrosine and tryptophan and plasma level of MHPG in depressive disorders]. / Transports membranaires érythrocytaires de la tyrosine et du tryptophane et taux plasmatique de MHPG dans les dépressions.

Both plasma MHPG level and red blood cell membrane transports (TM) of L-tyrosine (L-TYR) and L-tryptophan (L-TRY) were evaluated in 29 depressed patients and compared to 16 control subjects. On the basis of MHPG plasmatic levels, we were able to define two subgroups in the depressed population showing a biological homogeneity: in the first one, both MHPG level and TYR TM decreased, while in the second one neither of these indices were disturbed. These biological features were not related to the nosographic subgroups. Bipolar depressed subjects showed a decrease in both MHPG and TYR TM; unipolar depressed subjects exhibited a decrease in both MHPG and TYR TM associated to an increase in TRY TM, whereas no change was found in dysthymic disorders. The time course of MHPG and MT were desynchronized if followed during the antidepressant treatment. At day 7, MHPG level increased significantly, while clinical improvement showed a normalisation of MHPG and TYR TM.

[Plasma levels of metapramine and its 3 major metabolites in patients with depression. Results and preliminary interpretations]. / Concentrations plasmatiques de la métapramine et de ses trois principaux métabolites chez des patients déprimés. Résultats et interprétations préliminaires.

Metapramine (Timaxel) and his three major metabolites (19148 RP, 23669 RP, 19749 RP) have been determined in the plasma of 18 depressed inpatients treated by the antidepressant drug (12 women and 6 men; 7 are smokers and 11 non-smokers). In a steady state, interindividual variability is very important, especially for 23669 RP. No significant correlation exists between normalized doses (mg.kg-1) and normalized plasma concentrations (ng.ml-1/dose mg.kg-1) of metapramine or anyone of its metabolites. The plasma metabolic ratios reveal also important intraindividual and interindividual variability. Two populations of patients seem to exist: extensive metabolizers and relatively poor metabolizers, without apparent clinical consequence because 23669 RP shows an antidepressant activity. Women seem, with equal normalized doses, to exhibit higher plasma levels of unchanged metapramine than men, due to a lower protein-binding rather than to a more active metabolism. In patients who received a poly-medication smoking seems not to induce desmethylation of metapramine. The plasma metabolic ratios, compared by the analysis of variance and the Wilcoxon distribution-free test, are significatively influenced by sex and not by tobacco-smoking.

[Visual potentials evoked by a pattern reversal checkerboard in 50 depressed patients]. / Etude des potentiels évoqués visuels par damiers alternants chez 50 patients déprimés.

The pertinency of the visual evoked potentials (VEP) was studied as an index of depression in a group of 50 depressed patients (according to DSM III criteria). The VEP recordings were realized before an antidepressive treatment (D0) and 4 weeks after the beginning of the treatment (D28). Identical recordings were realized with 15 healthy and voluntary reference subjects. Stimulations were reversal checkerboard. The analysis of the results indicate at D0 a reduction of P1 and N1 latencies in the depressed people compared to the reference subjects, and an increase of the P1-N1 amplitude. These differences disappear at D28 (after the antidepressive treatment), as we don't notice any significative difference between D0 and D28 with the reference subjects. The interpretation of these results leads to the hypothesis of a neurophysiological modification of the attentional processes during the depression state. The antidepressive treatment seems merely to produce a normalization of the evoked responses in the depressed patients.

[Multidisciplinary approach to depression. Preliminary results]. / Approche multidisciplinaire de la dépression. Résultats préliminaires.

In the present study, clinical interview, Visual Evoked Potentials, psychological tests, TRH test, plasmatic MHPG dosage were investigated in 30 depressed patients with major depressive disorders. All the explorations were realised before and after 28 days of an antidepressant treatment. Thanks to analysis we found out the value of psychological tests. The study of evoked potentials brings to light the existence of electrophysiological variables, subordinate to the clinical state. On the contrary, "TRH Test" does not give us any useful indication, and plasmatic MOPEG dosage, although it confirms the existence of two groups of depressed patients, does not suggest any relationship with evolutive types.