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Biomedical subjects

E Zarifian

Publications and source records attributed to E Zarifian.

At least 19 recordsLinked to original sources
PubMed1999

Relationships between trait and state anxiety and the central benzodiazepine receptor: a PET study.

The central benzodiazepine receptor (cBZr) has long been implicated in anxiety disorders on the basis of: (i) the well-known anxiolytic and anxiogenic properties of cBZr agonists and inverse agonists, respectively; (ii) a possibly reduced sensitivity to benzodiazepines in anxious subjects; and (iii) a putative endogenous ligand. Thus, two main hypothesis have been advanced, namely changes in the concentration or properties of the latter, and changes in the GABAA complex conformation, which contains the cBZr. Neither postmortem studies nor appropriate animal models are available to investigate these ideas. We have used positron emission tomography (PET) to measure both the density and affinity of the cBZr in multiple brain regions in unmedicated patients and age- and sex-matched healthy volunteers, and have looked for differences between groups as well as correlations between cBZr parameters and state and trait anxiety scores. We studied 10 unmedicated patients (sex ratio 1 : 1; mean age: 39 years), prospectively recruited using DSM III-R criteria, and 10 age- and gender-matched healthy unmedicated volunteers. Thanks to a PET procedure using two successive administrations of 11C-flumazenil (at high and low specific radioactivity) and previously validated by us, we estimated the Bmax, Kd and bound : free (B/F) ratios in 11 neocortical areas and in the cerebellum. Before and after the PET session, anxiety scores from Spielberger's and Covi's scales were obtained. There was no statistically significant difference in Bmax, Kd or B/F-values between the two groups for any region. Across the two groups, there were only a few marginally significant anxiety-score-PET correlations, suggesting chance findings. This is the first fully quantitative study to report on the relationships between cBZr parameters and anxiety. Using two independent approaches (i.e. group comparison and across-group correlations), we found no evidence for a link between anxiety trait or state and the cBZr in neocortex or cerebellum in this sample. These findings, if confirmed by studies on larger samples, have implications for the pharmacotherapy of anxiety disorders, and will need to be considered when designing new neurobiological models of anxiety.

Adolescent↗
PubMed1998

No association between dopamine D1, D2, and D3 receptor genes and manic-depressive illness.

BACKGROUND: The dopaminergic receptor genes are candidate genes for manic-depressive illness (MDI). To test this putative involvement we used a case-control study on samples from the native population of the northwest part of France. METHODS: Fifty patients for D1 and D2, 61 patients for D3, and 86-223 controls were tested. RESULTS: No significant association was found between allelic frequencies or genotype counts and MDI, even when the data were pooled with those from published studies. CONCLUSIONS: Single mutations of either of the studied receptor genes are not major determinants of MDI.

Adult↗
PubMed1998

Risk factors associated with suicide attempt in young French people.

Demographic data, personal and familial characteristics, as well as DSM-III-R-based psychiatric diagnoses were collected in 369 adolescents and young adults aged between 15 and 29 years, referred to an Emergency Department for psychological problems. In total, 60% of them were suicide attempters. Separations before the age of 12 years and depression in the family emerged as the main features distinguishing the suicidal group from the psychiatric control group. Fifty per cent of suicide attempters were repeaters. Fostering during childhood, suicide attempts and depression in the family were found to be risk factors for repeated self-attempts. These results support the view that significant levels of dysfunction, together with increased psychiatric morbidity, especially suicidal behaviour, characterize the families of young self-attempters.

Adjustment Disorders↗
PubMed1998

[Prescription of psychotropic drugs; use, misuse and abuse].

The prescription of psychotropic drugs in France rises questions dealing with public health and medical ethics. Mental disorders are too often turned into target-symptoms for psychotropic drugs minimizing the importance of individual psychism which requires specific help. Prescribed either excessively or insufficiently psychotropic drugs are used mainly in general practice according to questionable criteria. The importance of a good initial training in pharmacology and therapeutics is stressed. A post graduate medical training totally independent is the only warranty of a prescription adapted to patients' needs.

Drug Prescriptions↗
PubMed1997

[Psychological profile of suicide using firearms to the face. Review of the literature. Our experiences at the university hospital center at Caen].

We studied the psychological feature of subjects who attempted suicide with firearms. This retrospective study included 36 cases of "facial suicide" treated at the Caen University Hospital since 1981 and data in the literature. An analysis of the different parameters showed in several cases, that this population is different from the others, particularly hospitalized drug overdose suicide patients. Two notions were particularly remarkable in these patients: history of patients psychiatric disorders were very rare and recurrent suicide attempts.

Adolescent↗
PubMed1996

Central benzodiazepine receptor occupancy by zolpidem in the human brain as assessed by positron emission tomography.

The central benzodiazepine receptor occupancy by zolpidem in man is unknown. The present study used positron emission tomography (PET) and [11C]flumazenil to assess in five healthy volunteers, central benzodiazepine receptor occupancy in brain regions with high receptor densities 1 h following an acute oral administration of twice the usual hypnotic dose of zolpidem (20 mg). Receptor occupancy was measured in five discrete structures (middle frontal gyrus, middle temporal gyrus, posterior occipital cortex, lateral parietal cortex, and cerebellar cortex) and in a large neocortical area as the fractional change in the [11C]flumazenil bound/free ratio for the interval 15-40 min post-administration of the radiotracer. The free-radioligand concentration was estimated from the pons, a reference structure virtually devoid of central benzodiazepine receptor. With individual pons values, mean occupancy was about 21% but with spurious inter-subject variability. With pons values averaged across the five subjects and separately for control and treated condition, the occupancy was (mean +/- S.D.) 27 +/- 11% for the whole neocortex, and ranged from 26 to 29% in the five discrete structures (P < 0.01). By showing hypnotic effect at moderate occupancies, this study directly provides evidence for the full-agonist properties of zolpidem in human.

Adult↗
PubMed1996

A comprehensive investigation of plasma and brain regional pharmacokinetics of imipramine and its metabolites during and after chronic administration in the rat.

The relationship between the serum imipramine concentration and its antidepressant effects remain undefined despite > 30 years of clinical investigation. No study to date has assessed the kinetic relationships between the concentrations of imipramine and its metabolites in plasma and in various brain structures. In this study, we examine the pharmacokinetics of imipramine (IMI) and its desmethylated and hydroxylated metabolites in rats given IMI chronically (20 mg/kg, intraperitoneally twice a day for 14 days). The concentrations in serum, cerebrospinal fluid, and six brain structures were measured by high-performance liquid chromatography at 13 different times from 0.5 to 120 h after the end of treatment. The concentrations of IMI, desipramine (DMI), and didesmethylimipramine (DDMI) in brain tissue were much higher than in the serum; concentrations were maximal at 1-2 h in the serum and the brain, which is indicative of the rapid metabolism of IMI with immediate and massive entry of the metabolites into the brain. The elimination halflives of desmethylated compounds increased with the degree of desmethylation, and DDMI was still present in brain tissue 96 h after the end of treatment. These results suggest that DDMI should be taken into account in clinical investigations of the effects of serum concentrations of IMI. The hydroxylated metabolites 2-OH imipramine (2-OH IMI) and 2-OH desipramine (2-OH DMI) were detected in serum, but not in cerebral tissue. The 10-OH metabolites were detected in both serum and brain, but the antidepressant action of these metabolites have not been clearly established. Finally, there were significant differences in the distributions of IMI and several of its metabolites in brain structures. Such differences may have clinical relevance if they also occur in humans.

Animals↗
PubMed1996

[Epidemiological study of patients and suicidal patients admitted to a psychiatric emergency department of a general hospital].

The present study involves a review of all patients who visited the Emergency Psychiatric Service during the period from December, 6, 1993 to June, 5, 1994. A questionnaire was proposed to 1073 subjects (57.2% females; 42.8% males; mean age = 36.6). Demographic data, familial and personal characteristics, previous contacts with professional health services, and diagnosis (DSM III R criteria) were collected. 52% of them were self-attempters, younger than the general population and more frequently females (61.5%). The parasuicides were more frequent in their families and in their personal past history. The previous contacts with health services (hospitalizations, consultations) were more frequent among patients who were admitted for psychological and/or psychiatric problems. 54% of self-attempters were repeating suicidal patients. There were more depressive disorders, parasuicides and drug/alcohol abuse in their families. A logistic regression analysis (stepwise) revealed the role of these factors in the repetition of parasuicides. This study supports the significance of a better knowledge of the potential significant factors for parasuicide. Preventive measures are necessary.

Adult↗
PubMed1995

Topographic EEG activations during timbre and pitch discrimination tasks using musical sounds.

Successive auditory stimulation sequences were presented binaurally to 18 young normal volunteers. Five conditions were investigated: two reference tasks, assumed to involve passive listening to couples of musical sounds, and three discrimination tasks, one dealing with pitch, and two with timbre (either with or without the attack). A symmetrical montage of 16 EEG channels was recorded for each subject across the different conditions. Two quantitative parameters of EEG activity were compared among the different sequences within five distinct frequency bands. As compared to a rest (no stimulation) condition, both passive listening conditions led to changes in primary auditory cortex areas. Both discrimination tasks for pitch and timbre led to right hemisphere EEG changes, organized in two poles: an anterior one and a posterior one. After discussing the electrophysiological aspects of this work, these results are interpreted in terms of a network including the right temporal neocortex and the right frontal lobe to maintain the acoustical information in an auditory working memory necessary to carry out the discrimination task.

Adolescent↗
PubMed1992

[Recent progresses in the biology of schizophrenia].

Investigations designed to improve our understanding of the physiopathology of schizophrenia are progressing along various, but no necessarily exclusive, lines. The most important aspects of the recently established biological data and their potential value are discussed and compared to classical hypotheses and results.

Humans↗
PubMed1992

Central benzodiazepine receptors in human brain: estimation of regional Bmax and KD values with positron emission tomography.

Studies of central benzodiazepine receptors in the human brain in vivo are now possible using positron emission tomography (PET) and [11C]flumazenil. With the aim of measuring Bmax and Kd in brain regions, we used a two-injection [11C]flumazenil (at high and low specific radioactivity, respectively) pseudo-equilibrium paradigm to evaluate, in seven unmedicated healthy volunteers, the relative merits of three 'reference' structures (pons, hemispheric white matter and corpus callosum) in which the free radioligand concentration in brain tissue was estimated 15-40 min after i.v. injection of the radioligand. By means of high-resolution PET, the Bmax and Kd were calculated for each subject in 18 gray matter structures, based on a two-point Scatchard plot. We found that the use of the corpus callosum as reference often resulted in spurious Bmax and Kd values. The pons was the best reference structure because it provided satisfactory Bmax values (closest to in vitro data) and most consistent Kd values, and was the region easiest to sample on PET images. The pattern of regional Bmax was consistent with that expected from in vitro studies, with values highest in the cerebral cortex, intermediate in the cerebellum, and lowest in the striatum and the thalamus. The Kd values were uniform among regions and were consistent with earlier in vitro and in vivo data. This work documents the feasibility of estimating Bmax and Kd of central benzodiazepine receptors in multiple brain regions for clinical research.

Adult↗
PubMed1991

[Benzodiazepines in the treatment of anxiety].

During the last ten years, the treatment of anxiety disorders has changed considerably. Cognitive-behavioural therapies and new chemotherapies have been added to benzodiazepine therapy and psychotherapy which for a long time had been the only treatment of these frequent and invalidating disorders. Recent reports of possible drawbacks in prolonged benzodiazepine therapy provide another reason to reconsider the indications of these drugs now that other drugs are available. Benzodiazepines remain the treatment of choice for recent anxiety states requiring some degree of sedation and rapid relief, but their long-term administration should be reserved to patients who did not respond to other treatments. The authors propose several guidelines for a better prescription of these anxiolytic agents and for more rational indications taking into account the advantages of other available treatments.

Anxiety↗
PubMed1990

EEG cartography before and after visual stimulation: a group study with descriptive non-parametric analysis of EEG data.

Ten right-handed students were submitted to a protocol of cognitive visual stimulations based on six successive sequences: EC1, EO, B1, B2, B3, EC2. Following a first "eyes closed" (EC1) multiple EEG recording (16 EEG leads, plus polygraphy), and an "eyes-open" recording (EO) with central visual fixation, 60 computer-controlled slides were presented successively for each of three successive recordings (B1, B2, B3) before the last "eyes-closed" recording (EC2). In B1, the subjects were asked to look at the meaningful black and white drawings presented without comment. In B2, a second set of similar pictures was presented, with the advice to try to remember later on the visually projected slides. In B3, a memory recognition task was introduced with 20 slides coming from the B1 set, 20 from the B2 set, completed by 20 new slides. Each slide was presented for 10.24s. followed by a beep audio-signal indicating that the subjects should press electronic mouse knobs alternatively in B1, B2, and for indicating their answers in B3. After artifact rejection, EEG spectral analysis was followed by parametrization and group studies applying Fisher non-parametric paired exact probability tests. Nine comparisons were computed: EC1-EC2, EC1-EO, EC2-EO, EO-B1, EO-B2, EO-B3, B1-B2, B1-B3, B2-B3. A statistical strategy of descriptive inter-individual non-parametric. Fisher tests was undertaken, together with computation and mapping of averaged spectral parameter differences (mean amplitudes and frequencies, mean amplitudes %, resonance coefficients) for raw EEG, delta, theta, alpha, alpha 1, alpha 2, beta 1 and beta 2 frequency bands and probability maps.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Anxiety disorders in a French general psychiatric outpatient sample. Comparison between DSM-III and DSM-IIIR criteria.

In a general psychiatric outpatient sample (n = 1271) gathered through a cross-national French survey, anxiety and somatoform syndromes were assessed according to DSM-III and DMS-III-revised criteria. Lifetime and one-month prevalence rates in this population are provided and the high level of comorbidity between the anxiety syndromes is noted. The patient symptom profiles for panic syndrome, simple attacks, agoraphobia and generalized anxiety are displayed. The conspicuous consequences of the modifications brought in by the Revision-anticipatory anxiety in panic syndrome, and restricted period criteria for generalized anxiety- are discussed, with the conclusion that more field study assessment is required before further revision.

Anxiety Disorders↗
PubMed1989

Substantial rise in sparteine metabolic ratio during haloperidol treatment.

A sparteine test was carried out in 14 patients suffering from acute schizophrenic psychoses before and 1-2 times during oral haloperidol treatment in doses of 10-40 mg day-1. In patients classified as extensive metabolisers (sparteine MR less than 20 before treatment), haloperidol treatment resulted in a rise in sparteine MR that correlated with the serum-haloperidol concentration both within and between patients. At the highest serum haloperidol concentrations (60-80 nM) an increase in sparteine MR by a factor 15-50 was seen, but no patients were transformed into phenotypically poor metabolisers. The steady state concentration of haloperidol on the initial standard dose of 10 mg day-1 was the same in one patient classified as a sparteine poor metaboliser (MR = 112) as in eleven patients classified as extensive metabolisers (MR:0.22-1.47).

Adult↗
PubMed1989

Buspirone and diazepam: comparison of subjective, psychomotor and biological effects.

The effects of oral buspirone (BUS, 10 mg) and diazepam (DZP, 10 mg) were studied in 12 healthy women volunteers using subjective ratings, objective tests of psychomotor and cognitive functions and urinary dosage of catecholamine output. Drugs were randomly administered to the same subjects, in a crossover, double-blind study, each drug administration being separated by at least 1 week. BUS subjective effects were less severe than those of DZP and not accompanied by feelings of sleepiness that characterized DZP sedative effects. Furthermore, BUS did not impair psychomotor functioning while DZP induced both an impairment of central sensory processing and, to a lesser extent, an impairment in delayed memory.

Arousal↗
PubMed1989

Aberrant T cell-mediated immunity in untreated schizophrenic patients: deficient interleukin-2 production.

The authors examined the immune status at the cellular and humoral levels of 16 untreated schizophrenic patients. No abnormality in the distribution of T cell subsets (CD4+, CD8+) was detected. The proliferative response to the T cell mitogen phytohemagglutinin was normal. No increase in the number of T cells showing activation markers, such as human leukocyte antigens and interleukin-2 receptors, was noted. Conversely, function studies revealed a clear deficiency in interleukin-2 production by purified T cells. This lower production was probably intrinsic to the patients' T cells, since interleukin-2 production showed normal sensitivity to prostaglandin E2-mediated down-regulation by autologous monocytes.

Adolescent↗