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Biomedical subjects

J P Olie

Publications and source records attributed to J P Olie.

At least 19 recordsLinked to original sources

Neurological and morphological anomalies and the genetic liability to schizophrenia: a composite phenotype.

BACKGROUND: Neurological soft signs (NSS) and minor physical anomalies (MPA) are frequent in patients with schizophrenia and their biological relatives. We examined whether the NSS and MPA are related to the genetic loading in schizophrenia. METHODS: Patients with schizophrenia (DSM-IV) (n=61), nonpsychotic parents of these patients (n=76) and healthy comparison subjects (n=44) took part in the study. Parents were further classified as "presumed carriers" of the genetic loading (n=26) if they had a second relative with schizophrenia in their ascendants and/or collaterals (first or second degree) or as "presumed noncarriers" (n=50). NSS and MPA were compared in these groups. RESULTS: A multivariate analysis indicated that total NSS and MPA scores, adjusted for age and gender, were significantly related to group status. Univariate tests showed higher scores in motor coordination and integration subscores (p=0.005 and 0.008, respectively) in presumed carriers than in presumed noncarriers. In addition, a discriminant function analysis based on total NSS and MPA scores correctly classified 71% of nonpsychotic parents in presumed carriers or presumed noncarriers. CONCLUSIONS: Neurological impairments and slight morphological anomalies seem to be associated with the genetic risk for schizophrenia, even when the disease itself is absent. Their presence might be a valuable composite intermediate phenotype for genetic studies.

Adult↗

Evolution of plasma homovanillic acid (HVA) levels during treatment in schizo-affective disorder.

1. Plasma Homovanillic Acid (p HVA) levels were measured by HPLC (high performance liquid chromatography) in 5 schizo-affective depressed patients receiving a standardized treatment. (lithium, chlorpromazine and clomipramine) during 4 weeks. 2. Four patients were pretreated, without a washout period. 3. No significant difference was observed between patients and normal controls at baseline. Under treatment, pHVA levels increased (p<0.02) with clinical improvement (MADRS and PANSS scores). 4. Although effects of medications prior to the study period were not controlled, these findings suggest that depressed schizo-affective patients may have normal pHVA levels that increase with clinical improvement, unlike schizophrenic patients whose increased pHVA concentrations decline with neuroleptic treatment.

Adolescent↗

Brain derived neurotrophic factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia.

Schizophrenia is a heterogeneous disease involving genetic and environmental factors. The frequency of structural brain abnormalities or physical anomalies supports a neurodevelopmental etiology, especially in early onset schizophrenia. Brain-Derived-Neurotrophic-Factor (BDNF) is involved in the neurodevelopment of dopaminergic (DA)-related systems and interacts with the meso-limbic DA systems, involved in the therapeutic response to antipsychotic drugs and substance abuse. In addition, BDNF promotes and maintains dopamine D3 receptor (DRD3) expression. In a French Caucasian population, we found no statistical difference in allele or genotype distribution of the BDNF gene dinucleotide repeat polymorphism (166-174 bp) between the whole group of schizophrenic patients and controls. By contrast, an excess of the 172-176 bp alleles was found in patients with late onset, in neuroleptic-responding patients and in non-substance-abusing patients. BDNF gene variants thus appear to be associated with developmental features of schizophrenia. In addition, this association with good treatment responding was independent from the association found with the DRD3 Ball gene polymorphism in the same population. These results suggest an independent contribution of each gene to a treatment-sensitive form of schizophrenia.

Adult↗

[New antipsychotic agents].

Since the discovery of the neuroleptics in 1952, french psychiatrists have proposed a classification of neuroleptics taking into account the pharmalogical and therapeutic differences between these drugs. They distinguished three different clinical effects of neuroleptics: sedative effects, effects on the positive symptoms of schizophrenia and effects on the negative symptoms. However these agents have many side effects including the extrapyramidal syndrome (EPS), akathisia, dystonia and parkinsonism. These side effects occur in up to 75% of patients receiving typical neuroleptics and are the main cause of non-compliance. Since the eighties, clozapine was introduced for use in refractory patients because it has a better efficacy (than haloperidol) specifically on negative symptoms, a better tolerance and fewer effects. After clozapine, several new antipsychotic agents are now available, such as risperidone, olanzapine, sertindole, quietapine, ziprasidone ... Their therapeutical effects are probably linked with a dual antagonist effect on 5HT2 and D2 receptors. The present article reviews the evolution of the use of these new agents, their real efficacy, their adverse effects and their expanding indications. Future research will more clearly establish appropriate treatment guidelines for their use. These new antipsychotics should add a positive modification in schizophrenia care and in some mood disorders. The approach consisting on individualizing dimensions and clusters analysis might be useful to test the efficiency of each antipsychotic on a syndromic dimension.

Amisulpride↗

Maintenance ECT in intractable manic-depressive disorders.

Twenty-two patients suffering from intractable recurrent unipolar or bipolar mood disorders were enrolled in a maintenance-ECT protocol (ECT-M) for more than 18 months, with a treatment at approximately monthly intervals. Eleven have continued treatment for > 2 years. Whereas 44% of the year had been spent in the hospital with at least three episodes a year prior to ECT-M, only 7% of the year was spent in the hospital during ECT-M with only one relapse every 16 months requiring admission (p < 0.001). Forty-five percent of the patients were in full remission and 27% in partial remission according to DSM-III-R criteria. ECT-M responsiveness of rapid-cyclers and delusional depressed patients usually drug refractory has been very encouraging with full or partial remission for 100% of rapid-cyclers and 80% of delusional depressed patients.

Adult↗

[Treatment of heroin addicts by substitution with methadone. Importance, limits and experience in France].

The authors present a review of literature and their personal experience concerning the practice of methadone substitutive therapy for heroin addicts in France. In their experience, the use of methadone, within the frame of a controlled administration and in the perspective of a specific pharmaco-therapeutic profile, is a valuable therapeutical option. Otherwise, methadone could only induce a new and further pharmacological dependence. The use of methadone has often been the subject of controversies overlooking the clinical reality of drug addiction. Therefore, a controlled use of methadone remains a valuable therapeutic tool if its indications are strictly delimited.

France↗

Urinary 3-methoxy, 4-hydroxyphenylethylene glycol and therapeutic response to maprotiline and indalpine in major depression.

The potential value of pretreatment urinary 3-methoxy, 4-hydroxyphenylethyleneglycol (MHPG) levels to predict the therapeutic response to antidepressants was studied by measuring urinary MHPG output in 42 depressed inpatients treated with a selective inhibitor of serotonin (Indalpine) or noradrenaline (Maprotiline) reuptake. Among the 42 depressed inpatients there were 33 cases of major depressive episode. Patients were treated for at least 3 weeks, firstly with intravenous infusions of maprotiline or indalpine which have been administered at random. No difference in pretreatment urinary MHPG levels was found between the responders to indalpine (1.08 +/- 0.48 micrograms/24 h/mg of creatinine) and the responders to maprotiline (1.15 +/- 0.62 micrograms/24 h/mg of creatinine). However, there was a difference in the pretreatment levels of urinary MHPG between the non-responders to indalpine (0.56 +/- 0.28 microgram/24 h/mg of creatinine) and the non-responders to maprotiline (1.37 +/- 0.68 micrograms/24 h/mg of creatinine). No correlation between this biochemical parameter and HDRS score was found. These results indicate that, in this study, there is no obvious relationship between the pretreatment urinary MHPG levels in depressed patients and their therapeutic response to specific inhibitors of noradrenaline or serotonin reuptake. However, there was a positive trend towards a lower pretreatment MHPG level to be associated with lack of response to indalpine.

Adult↗

[3H-Imipramine binding to human platelets. A peripheral index in depressive syndromes (author's transl)].

3H-imipramine shows specific, high-affinity binding to human platelet sites. The characteristics of these specific binding sites are very similar to those previously described in the rat brain. The inhibitory effects of 11 tricyclic antidepressants on 3H-imipramine binding to human platelets were investigated. There was a significant correlation between the inhibition observed and the average therapeutic doses of antidepressants, which suggests that the binding sites may be involved in the mode of action of these drugs. The number of binding sites (Bmax) for 3H-imipramine was compared in 39 controls and in 37 hospital patients with untreated severe depressive syndrome and was found to be significantly smaller in depressed patients, without any modification of the affinity constant Kd. The significance of these findings and their changes under treatment are discussed.

Adult↗

[The value of the measurement of intra-erythrocytic lithium in the bio-clinical surveillance of lithium therapy (author's transl)].

THe correlation between red cell lithium concentration and signs of neurotoxicity have been reported in the literature by a great majority of authors. A deficiency in the lithium-sodium counter-transport mechanism may be responsible. Measurement of blood lithium levels only is not always sufficient to identify in the laboratory patients showing signs of intolerance. The three cases reported here indicate the limitations of the measurement of plasma lithium levels and the perfect correlation between neurological signs and erythrocyte levels. In vitro studies of transmembrane ion exchanges should make it possible to undertake an investigation before starting treatment in order to identify the risks of cellular toxicity.

Adult↗

[Survey on the announcement of schizophrenia diagnosis in France].

Medical information for the general public, patients and their families is a current Public Health priority. What information can be given to a patient suffering from schizophrenia, whose understanding and judgement capacities are supposedly affected by this mental disease? In the United States, 70% of psychiatrists inform patients of schizophrenia and diagnosis of schizophreniform disorder, while in Japan less than 30% do this. The lack of information given to the general public on the disease may contribute to reinforcing the difficulty in announcing the diagnosis. Indeed, the beliefs and attitudes of the patient, his/her family, the general population and health carers concerning the disease do not match up. However, the first two years seem to be a main issue for the subsequent evolution of the disease. No specific data on the attitude of French clinicians with respect to the announcement of the diagnosis is available. In the current legal context and in view of the advances in treatment, we have carried out a survey among French psychiatrists. It is an auto-questionnaire, transversal epidemiological, descriptive and analytical. The questionnaire was sent to a population of 12,958 psychiatrists. It comprised 48 questions: 7 referred to the socio-demographic and professional characteristics of the subjects, 22 to the attitude with respect to the announcement of the diagnosis to the patients, and the last 18 concerned the attitude with respect to the announcement of the diagnosis to the families. 1,691 questionnaires were returned by free post and analysed. The socio-demographic characteristics of the sample are close to those of French psychiatrists as a whole. The number of patients suffering from schizophrenia in the active files of the psychiatrists is 24% (+/- 21.4) on the entire sample. Approximately a third (37.8%) of psychiatrists deem it necessary to announce the schizophrenia diagnosis and approximately two thirds (69.5%) declare that they sometimes announce it. Among the patients suffering from schizophrenia in the active files of the psychiatrists who responded, approximately a third (34%) were informed of their diagnosis. The main reasons for not announcing the diagnosis are firstly the "reticence to give a diagnosis label" and secondly "the functional incapacity of the patient to understand the concept". The alternative diagnosis term most commonly used is "psychosis" (46.5%). However, 48.1% of practitioners state that the announcement of a specific diagnosis allows a better therapeutic combination. Depending on the proportion of patients suffering from schizophrenia in their active file presented in two categories (< 10% and > 10%), psychiatrists significantly most frequently announce the specific diagnosis (17.3% vs 25.3%, p < 10(-3). A statistically significant proportion of younger psychiatrists (44.4 vs 46.3, p < 10(-3) with fewer years of practice (14.1 vs 15.8), more often believe that it is necessary to announce the diagnosis. The rate of response (13.5%) for this type of survey seems high, which could indicate a high interest among psychiatrists with respect to this question. Our data showed the existence of a correlation between age, number of years in practice, type of practice and the proportion of patients suffering from schizophrenia in the active file on the one hand and the attitude of the psychiatrists with respect to the announcement of the diagnosis on the other hand. It is possible that the multi-disciplinary team work of public practice psychiatrists and the fact that they are more often confronted with schizophrenic disease facilitate the announcement of this diagnosis. In the survey population, the inability to give a diagnosis may be related to the questions of the practitioners about the capacity of the subjects to understand, the lack of precision of this diagnosis, the fear of disheartening the patients and the absence of curative treatment. The risk of suicide does not seem to be one

Adult↗