The present case corresponds to a 1-month-old male patient with a diagnosis of non-compacted cardiomyopathy associated with congenital heart defects. Noncompacted cardiomyopathy is newly included by the AHA as its own since the second half of the last decade. The diagnosis is mainly echocardiographic. Symptoms in children under one year may start with heart failure. The evolution is variable and tends to improve in some cases. Finally, in later decades, heart failure, thromboembolic events, malignant arrhythmias and sudden death become more pronounced. The management is in medicines for heart failure, to avoid malignant arrhythmias and thromboembolic events.

To characterize patients treated with olanzapine pamoate in French centers and investigate the conditions of use of olanzapine pamoate in real-life treatment situation.Data came from French sites participating in an international post-authorization safety study. In this observational study, patients diagnosed with schizophrenia were receiving commercially available olanzapine pamoate, in accordance with their physician's usual standard of care. Data were collected during routine visits within the standard course of patient care.One hundred and thirty eight patients (male, 73.9%; mean age, 39.4 years; mean duration of disease, 12.7 years) received olanzapine pamoate and were included in the study by 32 investigative psychiatrists distributed across 20 different sites (psychiatric hospitals). During the period of analysis, a total of 2975 injections of olanzapine pamoate was administered to the patients. The mean duration of olanzapine pamoate exposure was 475 days (1.3 years). During follow-up, 13.8% of all patients had at least one psychiatric hospitalization, 15.9% had at least one same-day psychiatric hospitalization (information documented for 116 patients), and 44.2% received at least one concomitant drug. Three cases of post-injection delirium/sedation syndrome were reported during the analysis period. Treatment emergent adverse events (incidence, 20.3%) were in line with the known profile of olanzapine.Patients were administered olanzapine pamoate and monitored in compliance with label recommendations. The safety profile assessment of olanzapine pamoate in actual conditions was consistent with that described in clinical studies.

Ces dernières années, la découverte de l’effet antidépresseur rapide et puissant de la kétamine, antagoniste non compétitif des récepteurs NMDA au glutamate chez des patients présentant une dépression résistante a conduit à repenser en partie la physiopathologie de la dépression. De nombreuses études, chez l’homme et chez l’animal, se sont intéressées aux mécanismes d’action sous-tendant cet effet, dégageant un certain nombre de pistes explicatives. Cet article fait la revue des différentes hypothèses concernant le mode d’action et les voies de signalisation associées à l’effet antidépresseur rapide de la kétamine. Ces hypothèses permettent d’enrichir la compréhension de la physiopathologie de la dépression, autour du rôle du système glutamatergique, et de guider l’innovation thérapeutique.

BACKGROUND:Depressive disorders have a major impact on public health. They are prevalent and disabling, with high economic burden for society. Antidepressants have a delayed action and at least one third of patients do not achieve adequate response. The recent discovery of ketamine's unique antidepressant properties, with rapid onset of response and high rate of responders opens new perspectives for treatment-resistant depression (TRD). METHOD:The aim of this article is to summarize preclinical trials and clinical trials demonstrating ketamine antidepressant properties and to review the different modalities of use. RESULTS:Most clinical studies used ketamine with a single subanesthetic intravenous administration in patients with treatment-resistant depression, demonstrating a rapid but transient antidepressant response with high response rates. To prevent relapse and maintain the initial benefits, few studies have shown the interest of serial infusions of ketamine, while others combined ketamine and electroconvulsive therapy using the former as an anesthetic. So far, relay treatments with glutamatergic agents such as riluzole are disappointing. Although most studies were conducted in patients with TRD in recurrent depression or bipolar disorder, efficacy in acutely suicidal patients is promising. CONCLUSION:Our review highlights the increasing interest in the use of ketamine in the treatment of treatment-resistant depression. Although a widespread use of ketamine as an antidepressant in routine clinical settings seems limited by psychotomimetic effects and the lack of strategy to maintain initial benefits, ketamine or related drugs might be used to target specific conditions, such as bipolar depression or high suicide risk.

La prise en charge médicamenteuse de la dépression se heurte aux limites des traitements antidépresseurs conventionnels que sont leur délai d’action et le pourcentage non négligeable de patients résistants aux stratégies thérapeutiques proposées. La prise en charge de ces dépressions résistantes est un enjeu de santé publique majeur. Depuis quelques années, la découverte d’un effet antidépresseur rapide et puissant de la kétamine, antagoniste non compétitif du récepteur NMDA au glutamate, a conduit à un nombre grandissant d’études sur cette nouvelle voie thérapeutique originale et prometteuse. Cette revue de la littérature a pour but de faire la synthèse des différents essais cliniques ayant mis en évidence cette propriété de la kétamine ainsi que des potentielles indications thérapeutiques et modalités d’utilisations.

Background. - In recent years, discovery of ketamine's fast and powerful antidepressant effects for treatment-resistant depression (TRD) has led to rethinking of the pathophysiology of depression. Numerous studies in humans and animals have focused on mechanisms of action underlying this effect, producing a number of explanatory pathways.Method. - The aim of this article is to summarize the various hypotheses underlying rapid antidepressant action of ketamine and therefore to better understand the mechanisms underlying depression and antidepressant action.Results. - Ketamine unique antidepressant properties have led to many studies on its neurobiological grounds. Intracellular signaling pathways such as mTOR, GSK3 or eEF2 seem to play a key role and are associated with an increased synaptic plasticity. Other hypotheses are discussed such as ketamine effects on neuro-inflammation, the role of anterior cingulate cortex in brain changes induced by ketamine, and the potential benefits of analgesic properties of ketamine in depressive disorders.Conclusion. - Our review highlights the potential role of the glutamatergic system in the pathophysiology and treatment of mood disorders. Understanding which pathways underlie the fast antidepressant effect of ketamine paves the way for the development of new antidepressants. (C) L'Encephale, Paris, 2013.

Maintenance electroconvulsive therapy (M-ECT) is a treatment indicated for the treatment and prevention of recurrent depression in patients who either do not respond or do not tolerate psychotropic medication. We evaluated, retrospectively, clinical response to a 6-month minimum course of M-ECT in 25 patients with a diagnosis of bipolar disorder or schizoaffective disorder according to DSM IV-TR criterion. Our study demonstrated a significant improvement of Global Assessment of functioning (GAF) scores after a six month minimum course of M-ECT (34.8 ± 12.6 vs 65.6 ± 10.8; P<0.05) as well as Brief Psychiatric Rating Scale scores (BPRS): 79.3 ± 12.4 vs 43.4 ± 10.2; P<0.05). We observed a slight increase of Mini Mental State Examination (MMSE) scores after M-ECT; nonetheless, it was not statistically significant (24.2 ± 2.4 vs 26.2 ± 2.4; P=0.2). Regarding the mean duration of hospitalizations, we showed a statistically significant decrease in the median number of days of hospitalization (72 [59-93.50] days before M-ECT vs 43 [25-76] days since the first M-ECT; P=0.017). Maintenance ECT allowed a significant improvement in psychiatric symptoms and global functioning of the patients included in this study, as well as a decrease in the number of days of hospitalization. However, our pattern is limited because of its small size; so, further prospective studies in this field, including larger population is highly recommended.

Introduction and objective. -The frequency of agranulocytosis induced by psychoactive drugs is estimated the first year of around 0.8% under clozapine, against 0.13% under chlorpromazine (King and Wager, 1998 [3]). It is associated with a mortality rate of 5 to 10%, and requires heavy treatment, usually in an intensive care unit. The objective of this paper is to present a practical therapeutic answer (clozapine rechallenge with filgrastim) through a case report following a neutropenia episode preventing clozapine use.Case and methods. -B.N. aged 35, native of Martinique, shows a resistant schizophrenia disorder "ultra sensitive" to clozapine. Without any treatment, after 4 years in stable clinical state under clozapine, B.N. suffered three neutropenia episodes when absorbing clozapine (2008, 2010 and 2011). First, a literature survey was conducted along with a consultation of the head of pharmacovigilance regional center and the hematology referee. Then, a 4th clozapine treatment was decided under cover of filgrastim (G-CSF), the role of which is to limit the risk of a new neutropenia.After stopping all psychoactive drugs, except morphine, the subject benefited from a first, 0.3 mg filgrastim injection, the day before re-introducing 25 mg clozapine. Before treatment: Leucocytes = 4.8 G/L while absolute neutrophils count = 2.4 G/L. Filgrastim injections were carried out at a rate of two 0.3 mg injections per week. Clozapine was increased to reach 25 mg every 3 days and electroconvulsivotherapy continued fortnightly while supervision was double: on the first hand, daily and clinical search for an increase in body temperature and signs of treatment intolerance, and on the other hand biological surveillance with NFS three times a week besides weekly clozapinemia. The well-informed consent of the patient was obtained.Results. -Signs of improvement were noticed as early as the 8th day and after 8 weeks of treatment and 31 sessions of ECT, the patient was stabilized under clozapine at 300 mg per day. The evolution is clearly favorable, as PANNS evolved from 158 to 90. Neutropenia episodes were not observed with a lowest measured rate of 1.9 G/L neutrophils. The filgrastim dosage was then reduced to 0.3 mg per week from the 7th week onwards, along with the pursuit of a weekly NFS supervision throughout the treatment. Tolerance is satisfying, with an improvement in lipid check, glycaemia, blood pressure and QT intervals during ECG.Discussion and conclusion. -The B.N. case isn't an isolated one as several articles refer to filgrastim use, combined with clozapine. This confirms the role of hematopoietic cytokines (mainly G-CSF) in neutropenia episodes induced by clozapine. Filgrastim dosage appears to be an important point with regards to the risk of a new neutropenia episode. Let's mention also that it is not a harmless treatment, it could hide the occurrence of neutropenia, besides it's expensive and invasive. Clinical and biological supervision is essential as the probability of an enhanced malignant hemopathy is low but nonetheless present. We also noticed a "biased notoriety of the clozapine", with the association with other hematotoxic molecules, the existence of a circadian rhythm of neutrophils or G-CSF, along with transitional or ethnical neutropenia. These points should be discussed thoroughly before exclusively accusing clozapine; this in turn would have consequences regarding the possibility of treatment resumption. Finally, association with lithium is also an option; several cases have already been reported. (C) L'Encephale, Paris, 2013.

Summary A multicentre study was designed to treat patients presenting with a major depressive episode, single or recurrent, or dysthymic disorder with tianeptine for 1 year. 22% of these patients had a concurrent diagnosis of alcoholism. This intermediate analysis presents results obtained with the first 122 depressed alcoholic patients included, of which 63 were treated for 1 year. The results allow the evaluation of the long term efficacy and tolerability of tianeptine. The antidepressant activity of tianeptine was confirmed by an almost 50% reduction of initial Montgomery-Asberg depression rating scale scores after 1 month of treatment. Total scores and subscores of the Hamilton anxiety rating scale and Hopkins symptom checklist self-ratings improved concomitantly. Single item and factor scores of the checklist for assessment of somatic symptoms indicated improvement in complaints present at the beginning of the study and an absence of notable adverse effects, particularly of the anticholinergic type. Three patients took massive doses of tianeptine; despite the association with alcohol, these patients did not show marked adverse effects. These results indicate the potential of tianeptine as an antidepressant in alcoholic patients after withdrawal of alcohol, its long term efficacy, and its good tolerability in patients who are particularly susceptible to the adverse effects of psychotropic drugs. The drug does not provoke orthostatic hypotension or weight change.

Conversion disorder refers to the occurrence of neurological-like symptoms or deficits that are neither intentionally produced nor simulated. While it cannot be explained by an organic disease, it is often related to psychological events.Case report. - We report the case of a 33-year-old patient with a fluctuating hysterical tetraplegia, which had started three years earlier. After the failure or the exhaustion of several biological (psychotropic medication, transcranial magnetic stimulation) and psychotherapeutic strategies, treatment with electroconvulsive therapy (ECT) was conducted. A total of thirty-five ECT sessions were performed. Whereas the patient's clinical state was initially characterized by a complete quadriplegia and an uncontrollable muscular hypertonia, we noted that the ECT sessions were associated with a slow, though remarkable, progress. At first, the sessions were followed by moments of altered consciousness during which the patient would be relaxed and could make simple movements. Secondarily, not only was our patient able to consciously move his four limbs, but he was also able to walk. However, those improvements remained partial and fluctuating, sometimes allowing the symptom to return temporarily secondary to frustrations or annoyances. Finally, our patient relapsed. Nevertheless, his clinical state presently remains better than that in which we first knew him.Discussion. - The treatment of conversion disorders has been the subject of few studies and predominantly remains symptomatic. Its main goals are: to lessen secondary gains impact by adopting a neutral behaviour towards the symptom and by encouraging physical rehabilitation; to lower the symptom by allowing the patient to understand the normal functioning of the diseased organ, and; to help the patient to deal with stressful situations. There is no evidence that hypnosis is superior to medical and other psychotherapeutic approaches. Pharmacological treatments may be helpful in the case of anxiety, impulsivity or depression, albeit delivered with caution. According to some case reports, transcranial magnetic stimulation has also been associated with clinical remission. Although the use of ECT in motor conversion disorders constitutes an uncommon procedure, and even if no clinical trial has evaluated its impact on such a pathological condition, several case reports suggest that electroconvulsive therapy can be efficient in the treatment of motor conversion disorders. This efficacy may rely on several hypotheses. ECT could induce neural modifications, and participate in the suppression of an active inhibition, which is responsible for hysterical symptoms. Indeed, conversion cerebral disorder correlates can be explored with the help of functional neuro-imaging techniques, which could therefore also identify ECT neural effects. ECT adverse effects on memory could lead to a new relationship with the symptom, and modulate the psychological conflict which has participated in its emergence. Narcoanalysis, ECT sessions could have an impact on consciousness by means of some dissolution and reorganization phenomenon. It could therefore participate in the ending of an emotional block, the psychic integration of traumatic events and the recovery of a voluntary motor control. Finally, ECT could be efficient thanks to its antidepressant properties, especially its ability to stimulate triaminergic, and particularly dopaminergic transmission. This case report reminds us how difficult it can be to deal with severe conversion disorders, and to navigate between two reefs, which are abstention, and therapeutic escalation. (C) L'Encephale, Paris, 2011.

INTRODUCTION:The use of illicit drugs by students and the possible psychological repercussions in this population of young adults is an important public health issue. While some data in the literature suggest a relationship between cannabis and the occurrence of mental health disorders, and in particular psychotic illnesses, epidemiologic surveys have shown that cannabis is the most consumed illicit drug in France. AIM OF THE STUDY:To carry out a quantitative and qualitative epidemiological investigation of substance use within a student population seen during their mandatory preventive health visit at the University medical facility. METHOD:Students were asked to take part in an investigation of their substance consumption and their individual experiences with cannabis in particular. Personality autoquestionnaires were performed and the psychotomimetic effects of cannabis were investigated with substance use within a student population seen during their mandatory preventive health visit at the University medical facility. RESULTS:A total of 3,807 students took part in the survey with a response rate of approximately 50%. Preliminary results relating to a subsample of this study are presented here (n = 880, mean age 20 years, 65% women). 44% of the students consumed cannabis at least once in their life. The prevalence of regular consumption in students (at least once a week) was of 18%, 11% had periods of daily or close to daily consumptions, and 13% used cannabis in the last month. For each of the drugs cocaine, ecstasy (MDMA), and mushrooms (psilocybin) the prevalence of experimentation (at least once) was 5% for cocaine, 4% for ecstasy and mushrooms, and for LSD the rate was 1,5%. Other evaluated substances had a prevalence of consumption lower than 1%. For the first cannabis consumptions, a majority of students state to felt "pleasant" effects: relaxation (71%) and euphoria (53%). 13% state to have felt effects of anxiety or sadness. 25% admit having had difficulties of expression, 24% memory deficits, 35% trouble with coordination or balance and 39% difficulties of concentration. Approximately 16% had impressions of depersonalization and derealization. Lastly, some experienced "psychotic-like" effects such as visual (10%) and auditory (6%) hallucinations, as well as referential ideas (16%), mistrust or feelings of persecution (11%). 26% of the student sample had felt at least one of these last four "psychotic-like" effects. DISCUSSION:The results are consistent with the idea that the impact of cannabis consumption is highly variable among different consumers. Implications for prevention strategies are discussed such as educational interventions based on recognition and motivation for change.

La question de la consommation de substances addictives en population étudiante et des éventuels retentissements psychiques dans cette population d’adultes jeunes est une question importante en termes de santé publique. Différentes données épidémiologiques attestent que le cannabis est la principale substance illicite consommée. De plus, certaines données tendent à montrer qu’il existe une relation entre consommation de cannabis et survenue de troubles psychiques ultérieurs notamment de nature psychotique. Ces enjeux ont amené une collaboration entre deux partenaires : le Service Inter-Universitaire de Médecine Préventive et de Promotion de la Santé de Paris (SIUMPPS) et le Laboratoire de Physiopathologie de Maladies Psychiatriques (Inserm U894) afin de réaliser une enquête épidémiologique sur la consommation de substances illicites en population étudiante. Des résultats préliminaires portant sur un sous-échantillon de cette étude sont présentés. Les perspectives en termes de démarche de prévention et de prise en charge qui pourraient se dégager tant des données issues de la littérature que des premiers résultats sont discutées.

Introduction: Visual orientation and attention are impaired in schizophrenia. Engagement and disengagement of attention and the ability to prompt responses to a stimulus in patients before and after six weeks of risperidone were compared to controls.Methods: Ten unmedicated (nine naive) schizophrenic patients, and eleven controls performed 1) A visual orienting task, the Cued Target Detection task (CTD), with the detection of a visual stimulus in valid, invalid, no cue and double cue trials, two conditions for fixation offset for a modulation of visual fixation: Gap: 200 ms before target; No Gap: simultaneous with target, 2) Choice Reaction Time (CRT 0.5 and 2 s delays). Results: At baseline, patients showed longer RT than controls in CRT, but not in CTD, with in CTD, no facilitation of RT with the gap procedure. The alertness index was almost null in CTD-Gap and comparable to controls in CTD-No Gap. Efficiency to detect attended stimuli (CTD-No Gap) and warning effect (CRT 0.5 s) were negatively correlated to disorganization. After treatment, readiness to act in CRT had decreased. In CTD-No Gap, change in PANSS disorganization was correlated to an increased validity index, change in negative sub-score was correlated to decreased attention cost.Conclusion: Untreated patients displayed a deficit of Gap effect and a slowing in sustained attention. Disorganization interfered with warning and visual detection. After treatment, its improvement and negative symptoms improvement were associated with better visual detection. These alterations in visual orienting provide new evidence for an oculomotor dysregulation of attentional engagement in schizophrenia. (C) 2009 Elsevier Inc. All rights reserved.

« Dépression » et « âge avancé » sont souvent associés chez nos contemporains. « Dépression » est alors entendu dans le sens de « désespoir existentiel » et non celui de « maladie dépressive » : sont amalgamés l’éprouvé du tragique de l’existence et une condition pathologique. Des tableaux dépressifs dont le caractère pathologique ne fait aucun doute sont fréquents chez la personne âgée mais les frontières entre normal et pathologique deviennent plus imprécises en deçà d’un certain seuil symptomatique, en présence d’évolutions chroniques et dans les situations de comorbidités. L’outil nosographique, malgré ses limites, s’avère précieux. Les études épidémiologiques incluant les comorbidités de l’épisode dépressif avec des troubles cognitifs et/ou des affections somatiques permettent de meilleures estimations des taux de prévalence des symptômes et des troubles dépressifs au sein des populations âgées. La formule, « la dépression est la dépression à tout âge », recèle une part de vérité à condition de prendre en compte les multiples facteurs qui modifient l’expression symptomatique de la dépression avec l’avance en âge. Le facteur le plus documenté est la comorbidité de la dépression avec des affections somatiques, présente chez la majorité des plus de 80 ans. D’autres facteurs, psychologiques ou socioculturels, sont également à l’œuvre mais leur influence a été moins étudiée. La baisse des performances cognitives observée au cours des troubles dépressifs n’est pas l’apanage des personnes âgées mais elle est indéniablement plus marquée dans cette population. Poser un diagnostic précoce de maladie d’Alzheimer ou, au contraire, éliminer ce diagnostic chez un patient déprimé rapportant un affaiblissement cognitif constitue une étape essentielle de la prise en charge. Avec le bilan neuropsychologique et l’imagerie cérébrale, nécessaires au diagnostic, s’impose aussi la nécessité d’une évaluation pluridisciplinaire, neuropsychogériatrique. La prise en charge d’un état dépressif gériatrique emprunte à différentes approches de soins incluant les soins somatiques, les médicaments psychotropes, les techniques de stimulation cérébrale et la psychothérapie mais aussi l’accompagnement médicosocial. La coordination des soins incombe au médecin généraliste, au cœur du dispositif. Mais cette mission théorique peut s’avérer impossible pour la gestion des cas complexes. De ce constat est née la réflexion sur des modalités d’adaptation du modèle anglo-saxon des « soins en collaboration » dans notre pays : la coordination des différentes interventions thérapeutiques par un gestionnaire du soin offrirait une efficacité supérieure à celle des modalités habituelles de soins.

Des anomalies du développement sont identifiées comme facteurs de risque de devenir schizophrénique ultérieur : petit poids de naissance, malformations congénitales, retards des acquisitions motrices ou sociales. Les déficits cognitifs et les signes neurologiques mineurs font partie des indices du spectre schizophrénique. Les études de neuro-imagerie ont signalé diverses anomalies structurelles présentes dès l’éclosion de la pathologie schizophrénique. Ces changements structuraux pourraient témoigner d’une accentuation du processus neurodéveloppemental normal. Par ailleurs, les gènes de susceptibilité de la schizophrénie sont impliqués à différentes étapes du neurodéveloppement : les associations les mieux établies sont des variantes dysfonctionnelles des gènes DISC-1 et Neuregulin-1, le rôle d’autres gènes du neurodéveloppement (dysbindin, BDNF, reelin…) étant moins certain. Enfin, le constat d’anomalies structurales chromosomiques chez 15 % des patients atteints de schizophrénie (versus 5 % en population contrôle), plus fréquentes encore dans les formes de schizophrénie à début précoce (32 % des cas) oriente vers l’hypothèse d’un trouble neurodéveloppemental. Une telle compréhension dynamique du trouble schizophrénique est en cohérence avec la connaissance des phénomènes de plasticité cérébrale tout au long de la vie. Cela n’exclut pas la recherche d’indicateurs de mécanismes de neurodégénérescence. L’enjeu est désormais une meilleure caractérisation du phénotype vulnérable afin de savoir le dépister avant l’éclosion de la maladie.