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Objectives: Schizophrenia spectrum disorders are associated with incapacitating social impairments, mostly due to Theory of Mind (ToM) deficits. Theory of mind difficulties often precede the beginning of schizophrenia spectrum disorders and contribute highly to the social withdrawal of patients. They also predict bad outcome for individuals suffering from this condition. The use of samples of individuals presenting subclinical forms of schizophrenia spectrum disorders constitute an opportunity to study theory of mind capacities. Notably, the study of theory of mind deficits in schizotypy allows a better understanding of predictive markers of schizophrenia spectrum disorders. They also contribute to the identification of primary processes involved in social difficulties associated with these disorders., Methods: We searched PubMed, Science Direct and Google Scholar databases for peer-reviewed articles studying the association between theory of mind performance and schizotypal traits up to the 1 April 2020. The following syntax was used: schizotypy AND ("theory of mind" OR "social cognition" OR "irony" OR "false belief" OR "social inference" OR "hinting task"). We also checked the references from these articles for additional papers. Only English and French written articles were considered., Results: Twenty-three articles were included in the review. The majority of these studies (n=20) used behavioral measures of theory of mind (i.e. percentages of correct responses on a theory of mind task). Only a few (n=3) recent studies used brain imaging to study theory of mind in psychometric schizotypy. In those 23 studies, 18 report theory of mind difficulties in individuals with high schizotypal traits. Ten out of these 19 studies report an association between positive schizotypy and theory of mind deficits/hypomentalizing. The positive dimension was the most associated with theory of mind difficulties. The negative dimension was associated with theory of mind deficits in six studies out of 19 (33 %). The association between disorganization and theory of mind deficits was weak, mostly because of a lack of studies measuring this dimension (only one study out of 13 measured this particular trait). The association between hypermentalizing and schizotypy was poorly characterized, due to high heterogeneity in how this feature was conceptualized and measured. In summary, some authors consider good performance on a theory of mind task as a sign of hypermentalizing, while other authors consider that this feature relates to the production of erroneous interpretations of mental states. We advocate in favor of the second definition, and more studies using this framework should be conducted. Interestingly, the three studies using fMRI showed no significant behavioral differences between high and low schizotypal groups on theory of mind performance, while the patterns of brain activation differed. This shows that in individuals with schizotypy, theory of mind anomalies are not always captured just by behavioral performance. Brain imagery should be included in more studies to better understand theory of mind in schizotypy. In general, high heterogeneity in ways of assessing schizotypy, and in the tasks used to evaluate theory of mind, were found. Notably, some tasks require shallower theory of mind processing than others. It is a priority to design theory of mind tasks that allow for manipulating the difficulty of the items within one task, as well as the level of help that can be given, in order to allow for a better assessment of the impact of theory of mind difficulties and the ways to compensate for them., Conclusions: The studies included in this review confirm the association between psychometric schizotypy and theory of mind. But the high heterogeneity in methods used in these studies, and notably the diversity in ways of assessing schizotypal traits and theory of mind, hinder a precise description of such an association. Additional studies are required. In particular, fMRI studies using tasks allowing for a precise description of altered and preserved theory of mind processes could be of great use in characterizing theory of mind difficulties associated with schizotypy., (Copyright © 2021 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Predictive prospective studies of schizophrenia date back to the late 1950s. At the turn of the Millennium, an Australian research group initiated programs of early detection of schizophrenia and early therapeutic intervention. The theoretical foundations of early schizophrenia detection usually remain unaddressed. In this paper, we focus on the issue of prediction of future schizophrenia in the general population on the basis of a symptomatic picture. Several notions used in this research program such as disease, symptom, and clinical staging derive from a medical model, which in our view is not entirely adequate for grasping the nature of schizophrenia. Schizophrenia is a spectrum of disorders with a shared core Gestalt comprising dis-order of selfhood and intersubjectivity. This core Gestalt has manifold manifestations, often predominantly in the existential or experiential domain. It is not feasible to apply medical concepts to this symptomatically poorly demarcated spectrum for which we do not know robust biological validators. Moreover, there is increasing evidence that the current DSM and ICD criteria of schizophrenia distort the original concept of schizophrenia and are formulated on a very high severity level. This often results in incorrect diagnoses of young help-seeking patients. In sum, it seems more appropriate to detect psychosis among already help-seeking patients than to implement detection programs in the general population. We discuss a reorientation of psychiatry towards more refined psychopathological knowledge and assessment that are needed in order to optimize the treatment of young help-seeking patients., (© 2018 L’Encéphale, Paris.)

Objectives: Video games and virtual reality have recently become used by clinicians for training or information media or as therapeutic tools. The purpose is to review the use of these technologies for therapy destined for schizophrenia patients., Methods: We conducted a review in October 2016 using Pubmed, Scopus and PsychInfo using the following Medical Subject Headings (MESH): "video games", "virtual reality" and "therapy, computer-assisted/methods", each associated with "schizophrenia". Papers were included in the review if: (a) they were published in an English, Spanish or French-language peer-reviewed journal, (b) the study enrolled patients with schizophrenia or schizo-affective disorder, (c) the patients used a therapeutic video game or therapeutic virtual reality device., Results: Eighteen publications were included. The devices studied are mainly therapeutic software developed specifically for therapeutic care. They can be classified according to their therapeutic objectives. These targets corresponded to objectives of psychosocial rehabilitation: improvement of residual symptomatology, cognitive remediation, remediation of cognition and social skills, improvement of everyday life activities, support for occupational integration. Very different devices were proposed. Some researchers analysed programs developed specifically for patients with schizophrenia, while others were interested in the impact of commercial games. Most of the studies were recent, preliminary and European. The impact of these devices was globally positive, particularly concerning cognitive functions., Conclusions: Computer-assisted therapy, video games and virtual reality cannot replace usual care but could be used as adjunctive therapy. However, recommending their use seems premature because of the recent and preliminary character of most studies. Moreover, a link is still lacking between this field of research in psychiatry and other fields of research, particularly game studies. Finally, it might be interesting to analyse more precisely the neuropsychological impact of existing commercial games which could potentially be useful for psychosocial rehabilitation., (Copyright © 2018 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The progressive shifts in the legal and social contexts, along with major changes in information seeking habits with the development of the Internet, have placed patients' information at the core of medical practice. This has to be applied to the psychiatric fields as well, and to questions about how schizophrenic patients are being told their diagnosis nowadays in France., Methods: This paper is a national and international literature review about schizophrenia diagnosis disclosure practices, from 1972 to 2014, using French and English languages and various psychology and medical databases. The used key words were "diagnosis", "disclosure", "communication", "breaking bad news", "information", "schizophrenia" and "psychosis"., Results: Proportions of diagnosis announcement: our results show that the proportion of psychiatrists delivering schizophrenia diagnosis to their patients varies between countries. Although we must acknowledge that the questionnaires and samples are diverse, we have found that psychiatrists are in general less prone to deliver diagnosis information in France (from 13,5% to 39% given the studies), Germany (28%), Italy (30%), and Japan (30%), than in Anglo-Saxon countries. Thus, 70% of the psychiatrists in North America and 56% in Australia claim that they disclose their diagnosis to schizophrenic patients. In the United-Kingdom, a study targeting psychotic patients themselves has shown that 47% of them had been told their diagnosis by their doctor. Even in the countries where the proportion of diagnosis disclosure is the highest, there remains a substantial difference with other mental illnesses such as affective or anxiety disorders, which are almost always labeled as such in the information communicated to the patient (90% in North America). Diagnostic information about schizophrenia continues therefore to appear problematic for health professionals, which can seem a paradox given the recent social and legal evolutions, the therapeutic progress, the proved benefits of disclosure on compliance and therapeutic alliance, and the fact that numerous studies have shown that a majority of patients already know their diagnosis having discovered it on the Internet or by reading their treatments' notice. Reasons alleged for not disclosing diagnosis: the reasons alleged by psychiatrists for not disclosing diagnosis are various, including fear of aggravating the stigma and the emotional state of the patient, fear of giving a wrong diagnosis, fear of suicidal behavior, risk of misunderstanding, low level of patient's insight, absence of therapeutic advantage, or absence of request from the patient. Evolution of the French position about diagnosis disclosure: The publication of the relatively large study of Baylé et al. in 1999, as well as the patients' rights evolutions, has led to a debate among psychiatrists about the reasons alleged in France for not disclosing diagnosis. Among other explanations, it appeared that the theoretical reference of the psychiatrist plays a role, a psychoanalytic practice leading to increased reluctance in breaking the bad news. Thus, the psychiatrist's view of the disease, in terms of etiology and prognosis, is important as the diagnosis could become accusing if the psychiatrist believes the family environment played a role, or harmful if he has a pessimistic conception of prognosis. The question of stigma: among other reasons alleged by psychiatrists for not announcing the diagnosis, the fear of causing an increased stigma is frequently reported by professionals. In France, stigma about schizophrenia is high, not only among the general population but also among health practitioners. Even if the context has evolved during the past 30 years and the therapeutic efficiency has improved, French representations of schizophrenia remain often tinted with catastrophism and should be modified. Benefits of diagnosis disclosure: however, the benefits of disclosing diagnosis have been constantly proved in France as in other environments. Several studies have shown that patients knowing their diagnosis were likely to develop a better compliance and a stronger therapeutic alliance with their doctor. No aggravation of symptoms, suicidal risk or anxiety has been linked to the diagnosis disclosure. On the contrary, the relief of being able to put some words on symptoms, better recognize them and anticipate them, and be part of a group of patients sharing the same symptomatology has been described by patients. Furthermore, disclosing a schizophrenia diagnosis can be essential to the psychotherapeutic project, in the sense that it places the patient into an active role towards the disease and the care plan. Last but not least, the relatives can benefit from the disclosure as well and build a partnership with health professionals about medical care. Existing recommendations: in the French context, apart from individual recommendations produced by a few authors in the literature, there are no official specific recommendations about how to disclose a difficult diagnosis in the psychiatric field; only recommendations concerning severe chronic somatic disease are available. The complexity of the schizophrenia diagnosis disclosure has led some researchers - especially in North America and Australia - to adapt and use in the context of schizophrenia protocols, recommendations and even communication skills training programs that have been developed in oncology or in the field of severe chronic somatic disease., Discussion: For the situation to evolve in France, tools able to measure patients' consent - including consent to hear the bad news - ability could be used. The question of how much information and what kind of information the patients really wish should therefore be explored in deep. Also, we have seen that schizophrenia representations should be modified in the general public understanding as well as in the professional environment. Families should be more included in the reflection about diagnosis announcement, as psycho-education programs have shown their efficiency and usefulness for both patients and relatives. Finally, in order to overcome some of the difficulties related to breaking the bad news about a schizophrenia diagnosis, developing the existing Anglo-Saxon models and recommendations in France, where only very few protocols exist, could allow a positive evolution in clinical practice and help to set a therapeutic and partnering approach of diagnosis disclosure. However, in order to better understand the situation in France regarding schizophrenia diagnosis disclosure, the present state of clinical practice still remains to be analyzed precisely, as the last study on a relatively large sample was made only in 1999. Thus, the obvious limits of our study lie in the fact that most available surveys in France are not recent enough to have taken into account legal and social evolutions. Also, the studies that we used for this paper use different methodologies, in the majority focus solely on health professionals, and they are not representative enough in terms of size or sample to inform about the present state of the practice., Conclusion: As a conclusion, having stressed the lack of recent data about schizophrenia diagnosis disclosure in France, we suggest a new study using validated tools on a representative sample and taking into account both perceptions of psychiatrist and patient. As has been the case for other severe pathologies, we also suggest that a consensus conference take place on the subject of schizophrenia diagnostic information in order to elaborate guidelines to support this difficult disclosure., (Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Getting and keeping a job are not only one of the criteria of recovery from schizophrenia, but are also one of its main means. Indeed, recovery is partly defined by the ability to work. Despite the lack of data in France about employment of people with schizophrenia, it is widely acknowledged that the employment rate of people with schizophrenia remains quite low, and frequently it is only an employment in sheltered workshops, not on the regular work market. International research data show that it is possible to improve significantly this employment rate, with an appropriate support, that is precisely defined by the current researches, and that is quickly spreading in most developed countries. The aim of this paper is to present, on the basis of a broad current literature review, the key predictive factors of the return to work for people with schizophrenia, and the strategies to optimize vocational services. It will appear that there are several ways to improve practices and interventions in France to support work integration. To begin with individual factors of work integration, dependant on each person, the clinical state and the cognitive skills (in a broad sense, including social cognition and metacognition) are to be taken into account, and optimized by means of the association of a finely tuned pharmacological treatment and psychosocial interventions such as cognitive remediation adjusted to the person's specific needs. The other main kind of factors is environmental factors, particularly the kind of vocational support, which turns out to have a major impact not only on job acquisition, but importantly also on job tenure. The most effective vocational services are based on the "Place and train" model, and even more precisely on the Individual Placement and Support (IPS) model, that allows to the majority of people with a severe mental illness (more than 50%) to obtain a competitive employment after 6 to 18 months of individualized support. This approach is now widely recommended as "an evidence-based practice" of rehabilitation. It is important to promote in France the development of this kind of practice, already implemented as an experiment by few militant and involved associations. This development remains in France slow and delayed (compared to the practices in the other European countries) because of the lack of public funding. It implies an evolution of the social and medico-social practices, taking into account current research data, and assessing the outcomes of their practices in order to improve them. The employment specialist (sometimes called also the "job coach") turns out to play a key role, emphasized by current research, implying, among many other tasks, to coordinate the net of people supporting the work integration, including the clinical team, the employer and the colleagues of the workplace., (Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Context: Informed consent to research remains a complex issue, while sometimes staying difficult to obtain, even in the general population. This problem may be maximized with patients suffering from schizophrenia., Objective: This paper summarizes available data in the literature about informed consent for research involving patients suffering from schizophrenia., Method: Medline and Google Scholar searches were conducted using the following MESH terms: schizophrenia, informed consent and research., Results: Studies using dedicated standardized scales (e.g. MacCAT-CR) revealed a decrease in the capacity to consent of patients with schizophrenia when compared with healthy individuals. Keeping in mind that schizophrenia is an heterogeneous disorder, patients with the lowest insight as well as those with the most severe cognitive symptoms appeared more impaired in their capacity to consent. Such a poor capacity to understand and consent to trials was shown linked with alterations in decision-making. For these specific patients, interventions may be set up to increase their capacity to consent. Various strategies were proposed: enhanced consent forms, extended discussion, test/feedback method or multimedia interventions. Among them, interventions relying on communication and the growing field of information technologies (e.g. web-based tools) seem promising. Finally, associations grouping families and patients (like the French Association UNAFAM) may facilitate the involvement of patients in research programs with safer conditions., Conclusion: Patients suffering from schizophrenia appear able to consent to research programs when suitable interventions are proposed. Further studies are now needed to optimize and individualize such interventions., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

From a historical perspective, this article describes the use of antipsychotic long-acting injections (LAI) in the treatment of schizophrenia, a disorder that was defined in the final years of the 19th century. An efficient treatment for schizophrenia was discovered only in 1952 with the introduction of chlorpromazine, a phenothiazine derivative. Fairly soon, antipsychotics became available as LAI. The first compounds were fluphenazine enanthate (1966) and decanoate (1968) whose development is attributed to G.R. Daniel, a medical director at Squibb & Sons. Other first-generation antipsychotics long-acting injections (FGA-LAIs) were introduced in a rapid succession in the 1960s and 1970s. FGA-LAIs made a key contribution to the development of community psychiatry. As neuroleptics emptied psychiatric hospitals, it was important to ensure that patients could be taken care of in outpatient facilities. FGA-LAIs prevented covert non-compliance. Compliance was further reinforced by the social and psychological support of patients. The introduction of second-generation antipsychotics (SGA) led to a loss of interest in FGA-LAIs. This is evidenced by a drop in the number of papers published on this topic. The interest in LAI was revived with the introduction of the first SGA-LAI in 2003. Four different preparations have been approved in the decade between 2003 and 2013. SGA-LAIs differ from FGA-LAIs in the technology that is used to produce the depot effect, and also in the treatment objectives. The rationale for using SGA-LAIs is not only to prevent relapses due to treatment interruption, but also to achieve more constant plasma levels in order to reduce side effects due to excessive plasma levels and loss of efficacy due to insufficient plasma levels. Also, treatment objectives are no longer limited to controlling acute symptoms. Treatment objectives now include the alleviation of negative symptoms and cognitive deficits that are key prognostic factors., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

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 0.3mg filgrastim injection, the day before re-introducing 25mg 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 0.3mg injections per week. Clozapine was increased to reach 25mg 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 0.3mg 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., (Copyright © 2013 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: Evidence of variations in schizophrenia incidence rates has been found in genetically homogenous populations, depending on changes within time or space of certain environmental characteristics. The consideration of the impact of environmental risk factors in etiopathogenic studies has put the environment in the forefront of research regarding psychotic illnesses. Various environmental factors such as urbanicity, migration, cannabis, childhood traumas, infectious agents, obstetrical complications and psychosocial factors have been associated with the risk of developing schizophrenia. These risk factors can be biological, physical, psychological as well as social and may operate at different times in an individual's life (fetal period, childhood, adolescence and early adulthood). Whilst some of these factors act on an individual level, others act on a populational level, modulating the individual risk. These factors can have a direct action on the development of schizophrenia, or on the other hand act as markers for directly implicated factors that have not yet been identified., Literature Findings: This article summarizes the current knowledge on this subject. An extensive literature search was conducted via the search engine Pubmed. Eight risk factors were selected and developed in the following paper: urbanicity (or living in an urban area), cannabis, migration (and ethnic density), obstetrical complications, seasonality of birth, infectious agents (and inflammatory responses), socio-demographic factors and childhood traumas. For each of these factors, we provide information on the importance of the risk, the vulnerability period, hypotheses made on the possible mechanisms behind the factors and the level of proof the current research offers (good, medium, or insufficient) according to the amount, type, quality and concordance of the studies at hand. Some factors, such as cannabis, are "unique" in their influence on the development of schizophrenia since it labels only one risk factor. Others, such as obstetrical complications, are grouped (or "composed") in that they include various sub-factors that can influence the development of schizophrenia., Discussion: The data reviewed clearly demonstrates that environmental factors have an influence on the risk of developing schizophrenia. For certain factors - cannabis, migration, urbanicity, obstetrical complications, seasonality - there is enough evidence to establish an association with the risk of schizophrenia. This association, however, remains weak (especially for seasonality). With the exception of cannabis, no direct link can yet be established. Concerning the three remaining factors - childhood traumas, infectious agents, socio-demographic factors - the available proof is insufficient. One main limitation concerning all environmental factors is the generalization of results due to the fact that the studies were conducted on geographically limited populations. The current state of knowledge does not allow us to determine the mechanisms by which these factors may act., Conclusion: Further research is needed to fill the gaps in our understanding of the subject. In response to this need, a collaborative European project (European Study of Gene-Environment Interactions [EU GEI]) was set-up. This study proposes the analysis of those environmental factors that influence the incidence of schizophrenia in various European countries, in both rural and urban settings, migrant and native populations, as well as their interaction with genetic factors., (Copyright © 2011 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Assertive Community Treatment (ACT) is known to have a positive impact on the number and length of inpatient stays. Yet, research is needed in order to help understand how ACT programs may ease off families' burden, e.g. in terms of economic expenditures. Indeed, many families with siblings suffering from chronic mental illness, who disengaged from psychiatric services, report needs related to ACT. This paper aims to describe the impact of a new ACT program in Geneva on patients and their families' burden., Methods: Out of 91 patients consecutively treated by the ACT program for at least 3 months, 55 consented to participate in the research. Twenty-one allowed us to contact their families (out of 37 who had relatives in the area). Data were gathered on patients and families before and after a 6-month-follow-up., Results: For the patients, after adjustment for the time spent during follow-up, most of the studied variables evolved favorably, particularly for their symptoms. At baseline, most of the family members felt overburdened by the financial cost (59.1%) related to their relatives with severe mental disorder and experienced inconvenience at having to give them assistance in daily life (68.2%) and to supervise them in daily activities (54.5%). Several variables evolved favorably during follow-up. Notably the best changes were observed for the inconvenience relating to assistance in daily life and relatives' emotional distress. Families of patients with delusional disorder featured less or no improvement during the ACT follow-up. The best correlate of improvement in familial burdens was improvement in patient's positives symptoms. Among those patients, being a female and suffering from a schizo-affective disorder was known to have had a higher impact on the number of interventions provided by families., Discussion: ACT should be recommended for patients who feature a poor outcome when treated in other settings. In addition, our results suggest that their families can also improve considerably, particularly those confronted with patients with persistent and enduring disturbing behaviors related to positive symptoms which do not, however, warrant hospitalization. Clinicians should pay particular attention to patients suffering from delusional disorder and their families, as this disorder does not appear to be associated with improvement in family burdens. These data do not allow definitely disentangling whether the improvement of families' burden is directly related to ACT interventions with them, to the implementation of support by other structures (such as peer support groups) or to an indirect effect related to patients' improvement. To our knowledge no similar study on the effect of ACT on family burden exists. Hence, such research needs to be replicated in other areas with different clinical and cultural backgrounds., (Copyright © 2011 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

The robust and specific associations between cognitive abilities and the functional prognosis of patients suffering from schizophrenia lead to a major concern for cognitive impairment in this disorder. Among the strategies considered to correct or enhance cognition in schizophrenia, drugs hold a pivotal place. Evidently, antipsychotic drugs, which are inextricable from patients' management, have generated considerable scrutiny in this topic. This paper first aims to outline the current views on the impact of antipsychotic drugs in schizophrenia. The distinction between conventional and atypical drugs is reminded in order to more precisely review existing data comparing the impact of these two types of molecules on cognitive impairment. More specifically, an elementary framework is proposed to facilitate the recognition of methodological flaws and offer a critical examination of previous findings. It emerges subsequently that differences between atypical and conventional drugs appear far less contrasted than initially suggested. Also, atypical antipsychotics compose a disparate pharmacological class and much clarification could be obtained by differentiating the individual effects of these molecules rather than considering them as a group. Finally, the relevance of these cognitive measures is also considered. In particular, we address alternative measures closer to real life situations as well as the growing interest in the broad field of social cognition. A last part of this article deals with strategies relying on adjunctive therapies. The fairly modest results obtained with these approaches is evoked and briefly reviewed., (Copyright © 2011 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Tragic and high profile killings by people with mental illness have been used to suggest that the community care model for mental health services has failed. It is also generally thought that schizophrenia predisposes subjects to homicidal behaviour., Objective: The aim of the present paper was to estimate the rate of mental disorder in people convicted of homicide and to examine the relationship between definitions. We investigated the links between homicide and major mental disorders., Methods: This paper reviews studies on the epidemiology of homicide committed by mentally disordered people, taken from recent international academic literature. The studies included were identified as part of a wider systematic review of the epidemiology of offending combined with mental disorder. The main databases searched were Medline. A comprehensive search was made for studies published since 1990., Results: There is an association of homicide with mental disorder, most particularly with certain manifestations of schizophrenia, antisocial personality disorder and drug or alcohol abuse. However, it is not clear why some patients behave violently and others do not. Studies of people convicted of homicide have used different definitions of mental disorder. According to the definition of Hodgins, only 15% of murderers have a major mental disorder (schizophrenia, paranoia, melancholia). Mental disorder increases the risk of homicidal violence by two-fold in men and six-fold in women. Schizophrenia increases the risk of violence by six to 10-fold in men and eight to 10-fold in women. Schizophrenia without alcoholism increased the odds ratio more than seven-fold; schizophrenia with coexisting alcoholism more than 17-fold in men. We wish to emphasize that all patients with schizophrenia should not be considered to be violent, although there are minor subgroups of schizophrenic patients in whom the risk of violence may be remarkably high. According to studies, we estimated that this increase in risk could be associated with a paranoid form of schizophrenia and coexisting substance abuse. The prevalence of schizophrenia in the homicide offenders is around 6%. Despite this, the prevalence of personality disorder or of alcohol abuse/dependence is higher: 10% to 38% respectively. The disorders with the most substantially higher odds ratios were alcohol abuse/dependence and antisocial personality disorder. Antisocial personality disorder increases the risk over 10-fold in men and over 50-fold in women. Affective disorders, anxiety disorders, dysthymia and mental retardation do not elevate the risk. Hence, according to the DMS-IV, 30 to 70% of murderers have a mental disorder of grade I or a personality disorder of grade II. However, many studies have suffered from methodological weaknesses notably since obtaining comprehensive study groups of homicide offenders has been difficult., Conclusions: There is an association of homicide with mental disorder, particularly with certain manifestations of schizophrenia, antisocial personality disorder and drug or alcohol abuse. Most perpetrators with a history of mental disorder were not acutely ill or under mental healthcare at the time of the offence. Homicidal behaviour in a country with a relatively low crime rate appears to be statistically associated with some specific mental disorders, classified according to the DSM-IV-TR classifications.

Introduction: Anhedonia is defined as a diminished capacity to experience pleasant emotion and is commonly included among the negative symptoms of schizophrenia. However, if patients report experiencing a lower level of pleasure than controls, they report experiencing as much pleasure as controls with online measurements of emotion., Objective: The Temporal Experience of Pleasure Scale (TEPS) measures pleasure experienced in the moment and in anticipation of future activities. The TEPS is an 18-item self-report measurement of anticipatory (10 items) and consummatory (eight items) pleasure. The goal of this paper is to assess the psychometric characteristics of the French translation of this scale., Methods: A control sample was composed of 60 women and 22 men, with a mean age of 38.1 years (S.D.: 10.8). Thirty-six were without qualification and 46 with qualified professional diploma. A sample of 21 patients meeting DSM IV-TR criteria for schizophrenia was recruited among the community psychiatry service of the department of psychiatry in Lausanne. They were five women and 16 men; mean age was of 34.1 years (S.D.: 7.5). Ten obtained a professional qualification and 11 were without qualification. None worked in competitive employment. Their mean dose of chlorpromazine equivalent was 431 mg (S.D.: 259). All patients were on atypical antipsychotics. The control sample fulfilled the TEPS and the Physical Anhedonia Scale (PAS). The patient sample fulfilled the TEPS and was independently rated on the Calgary Depression Scale and the Scale for Assessment of Negative Symptoms. For comparison with controls, patients were matched on age, sex and professional qualification. This required the supplementary recruitment of two control subjects., Results: Results with the control sample indicate that the TEPS presents an acceptable internal validity with Crombach alphas of 0.84 for the total scale, 0.74 for the anticipatory pleasure scale and 0.79 for the consummatory pleasure scale. The confirmatory factor analysis indicated that the model is well adapted to our data (chi(2)/dl=1.333; df=134; p<0.0006; root mean square residual, RMSEA=0.064). External validity measured with the PAS showed R=-0.27 (p<0.05) for the consummatory scale and R=-0.26 for the total score. Comparisons between patients and matched controls indicated that patients were significantly lower than control on anticipatory pleasure (t=2.7, df(40), 2-tailed p=0.01; cohen's d=0.83) and on total score of the TEPS (t=2.8, df (40), 2-tailed p=0.01; cohen's d=0.87). The two samples did not differ on consummatory pleasure. The anticipatory pleasure factor and the total TEPS showed significant negative correlation with the SANS anhedonia, respectively R=-0.78 (p<0.01) for the anticipatory factor and R=-0.61 (p<0.01) for the total TEPS. There was also a negative correlation between the anticipatory factor and the SANS avolition of R=-0.50 (p<0.05). These correlations were maintained, with partial correlations controlling for depression and chlorpromazine equivalents., Conclusion: The results of this validation show that the French version of the TEPS has psychometric characteristics similar to the original version. These results highlight the discrepancy between results of direct or indirect report of experienced pleasure in patients with schizophrenia. Patients may have difficulties in anticipating the pleasure of future enjoyable activities, but not in experiencing pleasure once in an enjoyable activity. Medication and depression do not seems to modify our results, but this should be better controlled in a longitudinal study. The anticipatory versus consummatory pleasure distinction appears to be useful for the development of new psychosocial interventions, tailored to improve desire in patients suffering from schizophrenia. Major limitations of the study are the small size of patient sample and the under representation of men in the control sample.

Background: Cognitive impairments are a core feature in schizophrenia. They impact several cognitive abilities but most importantly attention, memory and executive functions, consequently leading to great difficulties in everyday life. Most schizophrenia patients need assurance and require assistance and help from care workers, family members and friends. Family members taking care of a patient have additional daily work burden, and suffer psychological anguish and anxiety. Therefore, improving cognitive functions in schizophrenia patients is essential for the well-being of patients and their relatives. Reducing these deficits may decrease the economic burden to the health care system through lower numbers of hospital admissions and shorter hospitalisation periods, for example. Cognitive rehabilitation was developed to address the limited benefits of conventional treatments on cognitive deficits through the use of assistive technology as a means of enhancing memory and executive skills in schizophrenia patients., Objective: To provide clinicians with comprehensive knowledge on cognitive trainings, programs of remediation, and cognitive assistive technologies., Method: Literature review. A search in the electronic databases (PubMed, EMBASE, Index Medicus) for recent articles in the last 10 years related to cognitive remediation published in any language using the words: cognitive and remediation or rehabilitation and schizophrenia, and a search for chapters in psychiatry and rehabilitation textbooks., Results: We found 392 articles and 112 review paper mainly in English. First, we identified cognitive remediation programs that were beneficial to schizophrenia patients. Programs available in French (IPT, RECOS, and RehaCom) and others (CET, NET, CRT, NEAR, APT and CAT) were identified. In addition, since memory and executive function impairments could be present in people without schizophrenia, we reviewed inventories of cognitive assistive technologies proven to enhance cognitive skills in other populations. Finally, we present a review of recent studies testing innovative devices developed to assist schizophrenia patients., Discussion: First, we found several cognitive programs proven to be effective with schizophrenia patients, but only three were validated in French. It could be useful to adapt other programs for French-speaking populations. Unfortunately, we found that very few of the existing cognitive assistive technologies are proposed to be used with schizophrenia patients. In fact, most of the available cognitive orthoses were tested primarily in people with neurological injuries (for example, various memory impairments caused by traumas), and in elderly illnesses (like Alzheimer disease). Devices for patients with mental deficits (e.g., mental retardation) were developed later, and only very recently explored for use in schizophrenia. As a result of an international collaboration between France and Canada, currently a tool called MOBUS is being tested. This technology aims at improving the autonomy of schizophrenia patients, by helping them plan and remember their daily activities. Furthermore, it encourages patient-caregiver communication, and permits monitoring patients' subjective reports of their symptoms. The use of cognitive assistive technologies is not meant to isolate patients by replacing the human element of relatives and caregivers by a machine. On the contrary, they offer a sense of security and they improve interpersonal relationships by permitting enhanced autonomy and greater self-confidence. Finally, a literature review of cognitive remediation in schizophrenia emphasizes the importance of a structured application of the technique in order for it to succeed. First, it is crucial to detect the impairments that will be targeted in each patient presenting a specific pattern of impairments. For this purpose, validated and customised neuropsychological tests are required. Then, cognitive remediation programs must be customised to each patient's needs in order to motivate the patient to participate. Finally, long-term effects must be assessed in order to verify whether reinforcement is needed. Following these steps, most of the studies show an improvement in the well-being of patients with schizophrenia. These recommendations are also suitable for the cognitive remediation programs, as for treatments with cognitive assistive devices. An important hurdle facing the advance of cognitive assistive technology programs is that different research groups work individually without a coordinated effort to improve and validate the existing programs., Conclusion: Schizophrenia treatments must take into account not only patients' symptoms, but also the associated cognitive deficits which constitute an important factor in their social problems. It has been shown that several cognitive remediation programs are efficient in schizophrenia. New technologies complement the benefits of such programs, and support pharmacological treatments and psychotherapies.

Background: An increasing interest in the study of cognition in Schizophrenia has developed within the last few years although cognitive problems have been described in this disorder since the beginning of the 20th century. Presently, various data tend to assert that cognitive disorders are the core disturbance in schizophrenia and that their severity is predictive of the course of the disease. Indeed, studies have shown that the disturbances measured in cognitive tests are neither the consequences of positive or negative symptoms, nor related to motivation or global intellectual deficit, nor to anti-psychotic medication. It is also presently known that the severity of cognitive symptoms is a better indicator of social and functional outcome than the severity of the negative or positive symptoms. The patients who have the most severe cognitive deficits during the first episode of the disease are most likely to present a chronic and severe form later on. The aspects of cognition that are specifically impaired in schizophrenia are verbal memory, working memory, motor function, attention, executive functions, and verbal fluency. Cognitive disturbances are thus very important in several fields of research in schizophrenia such as: understanding the psychopathology, epidemiology (indicators of vulnerability), genetics (endophenotypes), neuro-imaging (including functional neuro-imaging), and psychopharmacology (they can be used as a parameter of evaluation in therapeutic trials with new molecules, or cognitive psychotherapy). LIMITS OF COGNITION ASSESSMENTS: However, there are some methodological limits to these cognitive evaluations. First, schizophrenia is a heterogeneous disease and there are no specificities of the different subgroups in terms of cognition. Secondly, the time chosen to evaluate the abilities of the patient is also a limiting factor. But most of all, the batteries of tests used in different studies are not standardized. BRIEF ASSESSMENT OF COGNITION IN SCHIZOPHRENIA: It is therefore of great interest to create an available and easily used battery of validated tests. This would enable one to measure the different cognitive deficits and to repeat the tests, and assess evolution through longitudinal follow up of the patients. The BACS is a new instrument developed by Keefe et al. in the Department of Psychiatry and Behavioural Sciences at the University of Duke Medical Centre. It evaluates the cognitive dimensions specifically altered in schizophrenia and correlated with the evolution of the disease. This test is simple to use, requiring only paper, pencils and a stopwatch. It can be administered by different carers. The duration of the test session is approximately 35min. This battery of tests was validated on a sample of 150 patients compared with a sample of 50 controls, matched for age, parent education and ethnic groups. This aim of this study is to create a French adaptation of the BACS (translation and back translation approved by the Department of Psychiatry and Behavioural Sciences at the University of Duke Medical Centre) and then to test its easiness of administration and its sensitivity, performing correlation analysis between the French Version of the BACS (version A) and a standard battery. Its adaptation and validation in French would at first be useful for the French-speaking areas and then would add some new data for the pertinence of using the BACS., Methods: 35 French stabilized schizophrenic patients were recruited from the inpatient and outpatient facilities at the Clermont-de-L'Oise Mental Health Hospital (Picardie area, France) in Dr Boitard's Psychiatric Department (FJ 5.) Patients were required to meet DSM-IV criteria for schizophrenia or schizoaffective illness. The patients were tested on two separate days by two independent clinicians with less than two weeks between the two assessments. During the first test session, subjects received the French A version of the BACS and during the second session, they were administered the standard battery of cognitive tests including: the Rey Auditory-Verbal learning test, the Wechsler Adult Intelligence Scale, third edition, subtests (Digit inverse sequencing, Digit Symbol-Coding), the Trail-Making A, Verbal Fluency (Controlled Oral Word Association Test, Category Instances), and the Wisconsin Card Sort Test (128 card version). The factor structure of the French BACS A Version was determined by performing a principal components analysis with oblique rotation. The relationship between the French BACS sub-scores and the standard battery sub-scores was determined by calculating Pearson's correlations among the sub-scores, with a level of significance of alpha<0.05., Results: All the 35 patients completed the standard battery and each subtest of the French BACS A Version without interruption and with good understanding of the instructions. The average duration of the BACS test sessions was 36.51min (S.D.=12.14.) compared to the standard battery in which the sessions lasted more than one hour with more difficulty during the Wisconsin tests. The factor analysis conducted on the data collected from patients suggests that there is a single dimension, a factor of general cognitive performance, which accounted for the greatest amount of variance. The BACS thus permits an assessment of overall cognitive function as a global score, more than some individual specific cognitive domains. The sub-scores from the French BACS A Version were strongly correlated with the standard battery corresponding sub-scores. We observed significant correlations for all the subtests evaluating: verbal memory (Pearson=0.83; p<0.001; IC [0.69; 0.91]), working memory (Pearson=0.67; p<0.001; IC[0.43; 0.80]), verbal fluency (semantic: Pearson=0.64; p<0.001; IC[0.40; 0.80]), alphabetical (Pearson=0.87; p<0.001;IC[0.77; 0.93]), attention and speed of information processing (Pearson=0.69; p<0.001; IC[0.47; 0.83]), executive function (Pearson=0.64; p<0.001; IC[0.39; 0.80]). We almost found a significant correlation for motor speed (Pearson=-0. 32; p=0.06; IC [-0.59; -0.014])., Conclusion: The French adaptation of the BACS scale is easier to use in schizophrenic patients with French as mother tongue, with a completion rate equal to 1, and also with less than 35min to complete and check. We obtained significant correlations for all domains except motor speed, which is almost significant. The BACS is as sensitive to cognitive impairment in patients with schizophrenia as a standard battery of tests that required over 2h to complete. Moreover, these results demonstrate that the BACS, the global score of which may be the most powerful indicator of functional outcome, can also be a good neuropsychological instrument for assessing global cognition in patients with schizophrenia.

Background: Electroconvulsive therapy, a standard treatment in mood disorders, is sometimes also indicated in psychotic disorders, especially in the treatment of refractory schizophrenia. In this instance, maintenance electroconvulsive therapy (M-ECT) can also become a long-term treatment. This paper presents the effects of M-ECT in the treatment of refractory schizophrenia using a retrospective analysis. Previous works showed that electroconvulsive therapy is effective on catatonia, anxiety with somatisation, lack of compliance, opposition, delusions especially with hallucinations and persecution, anorexia, agitation, carelessness, aggressive behaviour and moral pain. It is ineffective on bewilderment, somatic complaints and negative symptoms., Aim of the Study: A retrospective analysis of a clinical cohort of patients treated with M-ECT was carried out to determine the specific indications of M-ECT, its effectiveness on clinical symptoms, quality of life, relapse rates and use of medication. Nineteen patients with DSM-IV diagnosis of paranoid schizophrenia (n=5), schizophrenia with neurotic symptoms (n=3), disorganized schizophrenia (n=1), hebephrenia (n=3) and schizoaffective disorder (n=8), treated in the department of the University Hospital of Sainte-Anne in Paris, received M-ECT between 1991 and 2005. Seven patients are still under this treatment. Their mean age at the beginning of treatment was 47.5 years with a mean duration of the illness of 24 years. The indication of M-ECT was the increase of acute episodes, an increase of symptoms intensity, the inefficiency or intolerance to pharmacological treatments or an early relapse after ECT discontinuation. All patients had previously been successfully treated by ECT during an acute episode. Each patient received an average of 47 bilateral M-ECT under general anaesthesia at one to five weeks' intervals for a mean period of 43 months. All of them were also treated by antipsychotics; in addition, 30% received mood stabilizers and 10% antidepressants. The dosage of antidepressants and mood stabilizers was reduced during M-ECT treatment, especially in patients with schizoaffective disorder, probably in relation with the effectiveness of ECT on mood symptoms., Results: During M-ECT, the mean duration of yearly hospitalizations was decreased by 80% and the mean duration of each hospitalization by 40% with a better ability to take part in activities, sometimes even to return home or go back to work. There was also a positive effect on quality of life considering the severity of symptoms and the long psychiatric history of these patients. The possibility to go from a full time hospitalization to a day-care facility or to live in a halfway house can be considered as a huge progress. M-ECT was efficient on mood symptoms, delusions, anorexia, suicidal impetus, anxiety symptoms and increased cooperation and treatment compliance. Efficacy on obsessive compulsive symptoms was less obvious. There was no effect on dissociation and negative symptoms. Relapses essentially occurred after a stressful life event, a too long interval between the M-ECT sessions or, in 50% of the cases, without any obvious etiology. It required a revision of the M-ECT program and, most of the time, an hospitalization for full ECT treatment., Discussion: There is no consensus on the rate and number of M-ECT as it varies from patient to patient and depends upon the extent of the clinical response and side effects. The discontinuation of M-ECT will depend on the clinical symptoms, compliance and tolerance to ECT. As it is the case with ECT treatment for an acute episode, available evidence suggests that treatment with antipsychotics should continue during the maintenance ECT course., Conclusion: Maintenance electroconvulsive therapy combined with medication may be an efficient alternative to pharmacological treatment alone in refractory schizophrenia. Alternative therapeutical strategies are crucial in this domain, due to the important public health problem it raises. There are few randomised prospective controlled clinical trials regarding this treatment and further clinical investigations are necessary, notably to define standardized criteria for M-ECT programs.

Introduction: While many neurocognitive models of schizophrenia coexist, a lot of attention has been centered on C.D. Frith's model over the past few years, especially in regard to its parsimony., Background: The aim of this paper is to examine its validity. The model relies on the assumption that there are two main components: self-monitoring and monitoring. The first permits one to keep consciousness of personal goals and intentions with metarepresentations. Losing consciousness of personal goals would be the source of schizophrenics' avolition and losing consciousness of personal intentions would generate reference ideas. The second component refers to the so-called "theory of mind", which is the monitoring of others' mental content (knowledge and intentions). Disturbing monitoring would cause schizophrenics persecution disillusions, third order persecutions or speech content disorders., Literature Findings: After reviewing the empirical and theoretical bases of Frith's model, strengths and weaknesses are highlighted, in particular by contrasting Hardy-Baylé's and Abu-Akel's theoretical proposals. For explaining the monitoring impairments of schizophrenics, Hardy-Baylé's model emphasizes the executive functioning defect, while Abu-Akel's model proposes a "hyper theory of mind" where too many hypotheses would lead to misattributions. In addition, several criticisms of Frith's model are examined, particularly those voiced by phenomenologists who underline its reductionism presupposition and argue that the underlying cognitive conception of the "theory of mind" neglects the fundamental intersubjectivity issue. In addition, Gallagher points out that monitoring is a tautological concept and that intention is not like thinking inherent to behaviour., Conclusion: Frith's model validity is finally discussed at large in the light of these criticisms and competing models, and it is concluded that the self-monitoring part of the model needs to be redefined and that the measurement of the "theory of mind" has to be standardized.

This paper is a review of the principal, currently proposed, biological models of schizophrenia. The convergence of recent neurobiological studies indicates that schizophrenia may be a neurodevelopmental and progressive disorder with multiple biochemical abnormalities involving dopamine, serotonin, glutamate and gamma-aminobutyric acidergic systems. In post-mortem tissue, structural abnormalities and alterations in synaptic connectivity have been observed in the intracortical circuitry of the prefrontal dorsal cortex. These morphological modifications could be sequelae of earlier environmental insults and genetic processes. There are probably multiple susceptibility genes, each of small effect, which act in conjunction with environmental factors: obstetric abnormalities, intra-uterine infection and abnormal nutrition. Candidate identified genes could influence neurodevelopment, synaptic plasticity and neurotransmission. If schizophrenia is clearly related to an abnormality of early brain development, the clinical expression of the illness itself is delayed typically for about two decades after birth. A similar delayed onset is also observed in the secondary psychosis associated with metachromatic leukodystrophy, a genetic disease affecting myelin. Schizophrenia is a term reserved for idiopathic cases of chronic psychosis. Strictly speaking, schizophrenia is a syndrome. There are no established laboratory tests, neuro-imaging studies, electrophysiological paradigms or neuropsychological testing batteries that can explicitly confirm this behavioural disorder to the exclusion of symptomatology: what physicians diagnose as schizophrenia today may prove to be a cluster of different illnesses, with similar and overlapping symptoms. The diagnosis criteria of the various DSM reflect the American psychiatrists' concern for establishing a consensus classification preserving a wider definition of schizophrenia or more precisely of the schizophrenic disorder. One can presume that research work established from too numerous and insufficiently specific variables doesn't permit the definition of one or several aetiologies. We hope that one day all schizophrenia will be correlated to one precise causal factor permitting the optimal targeting of interesting therapeutic approaches. The multiplicity of concepts and models reflects our questioning.

The high prevalence and chronic evolution of schizophrenia are responsible for a major social cost. The adverse consequences of such psychiatric disorders for relatives have been studied since the early 1950s, when psychiatric institutions began discharging patients into the community. According to Treudley (1946) "burden on the family" refers to the consequences for those in close contact with a severely disturbed psychiatric patient. Grad and Sainsbury (1963) and Hoenig and Hamilton (1966) developed the first burden scales for caregivers of severely mentally ill patients, and a number of authors further developed instruments trying to distinguish between "objective" and "subjective" burden. Objective burden concerns the patient's symptoms, behaviour and socio-demographic characteristics, but also the changes in household routine, family or social relations, work, leisure time, physical health.... Subjective burden is the mental health and subjective distress among family members. While the first authors referred to those problems which are deemed to be related to, or caused by the patient, Platt et al. (1983) tried to distinguish between the occurrence of a problem, its alleged aetiology, and the perceived distress, when developing the SBAS questionnaire. These authors also proposed separate evaluations of behavioral disturbance and social performance by relatives, and a report of extra-disease stressors in family life. The SBAS is actually the most complete, but also complex instrument for evaluating burden in caregivers. Since 1967 Pasamanick and others proposed questionnaires for burden evaluation in relatives of schizophrenic patients. Relatives may be included in specific psychoeducational programs, but few of these programs have been evaluated in terms of caregiver burden. The theoretical approach in schizophrenia was not different from that one adopted in mentally ill population. Some instruments were validated first in a mentally ill group and then adapated for schizophrenic population. This paper describes the available data about intruments measuring caregiver burden in relatives of schizophrenic patients. Measures are summarized according to purpose, content and psychometric properties. Sixteen instruments have been collected from the litterature (1955-2001), and 2 instruments developed for relatives of mentally ill have also been taken into account. A group of 5 instruments focuses on the measurement of behavioural disturbance in persons with schizophrenia as perceived by their family members. Eleven scales include behavioural disturbance in a more complete decription of objective burden. Thirteen questionnaires also report the subjective distress in caregivers. One instrument has been developed in french language. Few of these instruments have been developed from a verbatim and really describe the caregiver's point of view. Most of them rely on experts point of view or on previously published studies. The content and domains explored by these instruments are variable. The psychometric properties are poorly documented for a number of them and no information is published about responsiveness. Some validated instruments are the Perceived Family Burden Scale (PFBS) the Involvement Evaluation Questionnaire (IEQ) and the Experience of Caregiving Inventory (ECI). In past studies, researchers more or less agreed about the dimensions that comprise the family burden. There was less agreement with regard to the definition of objective and subjective burden, and quite no agreement about the theoretical approach to the concept of burden. The evaluation of behavioural disturbance should now be excluded from the objective burden dimension. It is a specific domain, both objective and subjective, which can be described as a stressor in the stress-appraisal-coping model. A good approach of this domain can be found in the PFBS. It comprises 24 items and the principal components analysis produces 2 factors ("active" and "passive"), explaining 35% of the variance, with good consitency and acceptable test-retest reliability. The evaluation is both objective (presence or absence) and subjective (induced distress). The Behavior Disturbance Scale (BDS) may also be taken into account, although it is less validated. This scale derives from the SBAS, modified as a self-questionnaire, with both objective and subjective evaluations of all items. The concept of burden was recently modified in a new theoretical approach by Schene, when developing the IEQ. According to this author, the burden scale is supposed to exclude stressors (patient's behaviors), as well as outcome variables (distress or psychological impairment in caregiver). The "caregiving consequences" section comprises 36 items, which focus on the subjective aspects of the caregiver's experience. Principal component factor analysis generates 4 factors which explain 45% of the variance: tension, supervision, worrying, urging. The overall caregiving score substantially explains the connection between patient, caregiver, relationship variables and the caregiver's distress. This scale is a valid and simple instrument for caregiving eveluation The ECI also introduces a new approach of caregiving and rejects the notion of burden. The 66 item version is composed of 10 factors (8 "negative" and 2 "positive") with good internal consistency. The introduction of two positive factors (rewarding personal experiences, good aspects of the relationship with the patient) might be the basis of a useful outcome measure for intervention aimed at promoting caregiver well-being. Nevertheless, the authors fail to develop an overall score that includes these factors, and focus on the negative dimensions as predictors of morbidity and well-being. None of the variables included in the regression model explain a significant percent of the variance of the ECI positive score. None of these instruments was employed for evaluating programs or treatments, even psychoeducational programs for caregivers. This may be partly due to the lack of data about sensitivity to change. No instrument is now available for evaluating therapeutics from the caregiver's point of view. Developing such an instrument is necessary, in view of the increasing role of families in care for schizophrenic patients. These data and the review of the literature leeds us to propose the development of a self-administered questionnaire for evaluating subjective health-related quality of life in caregivers of schizophrenic patients. The instrument should be developed from the caregiver's point of view and be derived from qualitative interviews with relatives of patients suffering from schizophrenia. It's responsiveness should be documented before inclusion in clinical trials or evaluation of psychoeducational programs. We are now working with the National Union of Friends and Families of Patients to validate an instrument in french language.

Cognitive deficits in schizophrenia have been observed with neuropsychological tests of executive function, traditionally considered sensitive to frontal lobe damage. These impairments affect planning abilities, as well as the aptitude to initiate and regulate a goal-directed behaviour. On the other hand, negative symptoms of schizophrenia are widely suspected to reflect a frontal lobe dysfunction. Based on a review of a hundred papers, the present article analyses the anatomical and neuropsychological evidence of disturbed frontal lobe functioning in patients with negative schizophrenic symptoms. The phenomenological similarity of some schizophrenic symptoms to the clinical features of patients with prefrontal injury inspired the hypothesis of damaged frontal lobe in the former disorder. The morphological findings of neuroimaging studies brought inconsistent conclusions, with some researchers noting no differences between patients and control subjects while others observing reduced prefrontal volumes in schizophrenia. The functional neuroimaging demonstrated a reduced frontal blood flow relative to the general cerebral perfusion in patients with schizophrenia. Even though the overall neuroimaging literature provides reliable evidence of frontal impairment in schizophrenia, the average magnitude of the difference between patients and healthy controls is insufficient to defend the hypothesis of frontal lobe dysfunction, as far as brain volume, resting metabolism or blood flow are concerned. The only measure, which clearly distinguishes between the patients' and controls' distributions, is the functional neuroimaging of the frontal lobe while subjects are performing an experimentally controlled task. Schizophrenic patients fail to activate their frontal cortex when the task requires it. Analysing executive abilities in relation to symptom expression leads to recognising the fact that frontal dysfunction is a characteristic of only a sub-syndrome of schizophrenia. The factor analysis of the clinical features consistently reveals three syndromes in schizophrenia, termed disorganisation, positive and negative syndromes. The substantial body of evidence that patients exhibit more than one syndrome indicates these are dimensions within a single illness rather than discrete diseases. Liddle labelled the negative syndrome as "psychomotor poverty" and associated it with malfunction of the neuronal projections from dorsal prefrontal cortex to thalamus via striatum, connections involved in the initiation of mental activity. His hypothesis was supported by the work of other, independent research groups. The patients with negative symptoms, in contrast with the nonnegative symptom group, tend to demonstrate reduced neuronal activation of the frontal cortex during executive task realisation. The nonnegative patients are indistinguishable from the healthy control subjects in this region. Neuropsychological studies reveal that severity of psychomotor poverty is associated with slowing of mental processing and deficits in tasks that require planning abilities. These frontal functions are identified with the selection, the initiation and monitoring of a wide variety of behavioural processes. It was hypothesised that executive dysfunction will appear through different patterns across symptom subtypes, but few studies sought to validate this assumption. Finally, researchers make little effort to develop theoretical conceptualisations of the aetiology of negative schizophrenic symptoms, despite the growing body of evidence on its resemblance to the dorsolateral frontal lobe syndrome. Frith proposes that defects in the initiation of spontaneous action underlie these clinical phenomena, but his definition is not specific enough to be confronted to existing literature, neither has been empirically tested. Disturbed executive functioning has detrimental impact on the quality of daily living in patients with schizophrenia. Indirect observation of the latter accounts for defective long-term adaptation, which has been correlated to severity of negative symptoms and, although not consistently, to executive deficit as assessed by neuropsychological testing. Unfortunately, this area of research lacks ecologically valid studies. Measuring executive dysfunction as it occurs in the natural setting of the patient and validating dissocialbility of frontal deficits with respect to the schizophrenic symptomatology could lead to greater individualization of treatment plans and therefore to more efficient therapy outcome.

Deinstitutionalization and decentralization in psychiatry have by now been the first items of the agenda for more than 30 years. A theory of social psychiatry with social rehabilitation and reintegration was the underlying basis for the activities which should make the change from mainly inpatients to community-based outpatients treatment possible. By means of the National Danish Psychiatric Case Register this paper shows how the process mostly has concentrated on the deinstitutionalization (or reinstitutionalization?) of the old long-stay psychiatric patients. A new but smaller group of long-stay patients has appeared in the statistics. The average age of this group is 40 years compared to the old long-stay patients' average age of 60 years. It is also shown that the readmission rate during the first year after the discharge following the hospitalization during which the schizophrenia diagnosis was given for the first time ever is almost unchanged (with a small increase) for both males and females. So, in Denmark it is on average between 45% and 50% for females and males respectively. A break down on these data on counties shows that the situation varies broadly from a little over 30% for the best (mainly rural counties) to a maximum of 54%. It seems as if social psychiatry in the Nordic countries mainly concentrate on social care and only to a less degree on network, employment and other basic rehabilitation and reintegrative social work. A basis for a successful social integrative work must be a treatment initiated as early as possible with an antipsychotic treatment and maximum of compliance.

"Cognitive inhibition" is a concept that has found a firm place in the interpretation of performance by normal subjects on tasks involving adherence to a plan and suppression of incorrect responses to distractors. The presence of "negative priming" is the classical indicator of cognitive inhibition. Negative priming occurs when, in a sequence of stimuli each of which is composed of a target and a distractor, the distractor of the first stimulus becomes the target of the second stimulus: reaction time to the second stimulus is slowed because of the inhibition applied to the distractor of the first stimulus. The concept has been extended to the interpretation of pathological behavior and symptoms. Pathological subjects have been found to show deficient negative priming. Thus, negative ideation in depression as well as intrusive paranoid associations in schizophrenia have been related to a deficit in the capacity to inhibit inappropriate representations. In this paper, we briefly review some of the experimental evidence from normal subjects that has contributed to the acceptance of cognitive inhibition as a key process in the control of normal cognition, as well as more recent evidence that has led to a revision of the concept. Negative priming in normal subjects has been found to be dependent upon characteristics of the experimental situation as perceived by the subject. In particular, priming is observed when the subject anticipates difficulty in determining the response and proceeds with caution. Thus, inhibition is not an automatic "brake" applied to irrelevant material, but rather the product of strategic considerations within the experimental situation. This revision of the cognitive inhibition hypothesis leads to a re-interpretation of the apparently deficient cognitive inhibition seen in depressed or schizophrenic subjects. According to this more recent interpretation, deficient cognitive inhibition in pathological subjects can be seen as a less adaptive strategic adjustment to the task. The pathology seems to touch higher-level executive functions rather than a deficient inhibitory "brake". In depressed subjects, abnormal performance in selective attention tasks could be related to the underlying pathology in two ways: some depressed subjects show a marked lack of energy and a psychomotor slowing: these subjects do not exhibit normal negative priming, probably because of a reduction of cognitive resources. Other depressed subjects show abnormal performance as reflected by negative priming greater than normal: this result could be related to an exaggerated tendency to verify a correct response. Schizophrenic subjects show a lack of negative priming that seems most plausibly to be related to an ineffectual integration of the experimental instructions concerning both speed and accuracy in the response. This re-interpretation of the cognitive deficiency in pathological patients provides a better fit with recent experimental results from normal subjects, and with cognitive deficits measured in pathological subjects.

This study reports a clinical experience among twenty schizophrenic patients treated by clozapine during two years and eight months within a range extending from three months to seven years. These twenty patients had previously shown long-term resistance to usual neuroleptics but three out of them met the diagnosis of mental retardation or childhood disintegrative disorder (F.84.3-ICD 10). These patients were put under clozapine for their violent behavior. The methodology was retrospective, descriptive with intra-individual comparison, each patient being his own reference before and after treatment. Diagnosis met CD 10 criteria and were assessed without using standard examination. This study aimed at assessing once more clozapine efficacy and tolerance upon a long time follow up. Single therapy has been the rule and dosages have been progressively increased reaching a mean daily dosage of 350 mg per day. The efficacy, assessed by the way of BPRS, GAF (DSM III-R) and simplified form of CGIS, has been verified in approximately 30% of the patients, mainly concerning positive symptoms. Clozapine was also able to alleviate severe behavior troubles brought about by delusional states, without this latter being markedly softened when it was a long term one. Clozapine tolerance has shown it to be satisfactory, however we noticed the occurrence of a leucopenia with neutropenia after seventeen weeks of treatment, followed, some days later, by a Quincke oedema, which forced to interrupt the treatment. White blood cells came back in a normal range fifteen days later. The other side effects (transitory hypersialorrhea, tachycardia, without clinical and ECG perturbations) have been usually well tolerated and have never caused treatment interruption. No extrapyramidal side effect have been noticed among our twenty patients. The end of this paper consists in the presentation of four clinical cases: one about the efficacy of clozapine upon violent antisocial behaviour in a schizotypital disorder; one delusional chronic schizophrenic patient whose violence has been controlled despite of the delusion; one paranoid schizophrenic patient who has been able to maintain a satisfactory professional and family adaptation; and finally a childhood disintegrative disorder (F.84.3-ICD 10) in whom occurred the only leucopenia side effect of our study. These four clinical cases have seemed particularly meaningful regarding our clinical experience of clozapine which has been lasting for almost seven years now.

On the occasion of the Clozapine symposium we have had cause to reflect on the social life-histories of schizophrenic patients. After an analysis of a cohort of 40 patients aged over 65 years, whose medical records had been kept up since the start of their disease, we have set up a methodology which enables us to study the social life-histories of these patients. Our aim is ultimately to compare the course of the disease with the treatments received by these patients and the therapeutic structures they have been offered. For this purpose, we shall study three criteria of social exposure: 1) Autonomy, 2) Integration into the family, 3) Integration through work. The aim of the present paper is to record our initial analytical findings in these three years.

This didactic paper reviews the different receptors families, the principal characteristics of the dopaminergic and serotoninergic receptors and their role in the aetiology and pathophysiology of schizophrenia. The current knowledge on interactions between serotoninergic and dopaminergic systems is also summarized. The theoretical and potential interests of these interactions in alleviating neuroleptic-induced extrapyramidal symptoms and improving negative signs in schizophrenia are also examined.

Various pharmacologic agents have been reported to be effective in treating negative symptoms of schizophrenia. European schools of psychiatry and especially the French one assumed the opinion that part of negative symptoms of schizophrenia do respond to neuroleptics. In light of effects of reserpine and some phenothiazines on negative schizophrenia, various pharmacologic agents have been studied focusing on these properties. Various papers devoted to this question concluded that some drugs, particularly neuroleptics, can be considered as disinhibitors: phenothiazines (thiotixene, trifluoperazine, fluphenazine, pipotiazine), butyrophenones (trifluperidol, risperidone), diphenylbutylpiperidines (pimozide) and benzamides (sulpiride, amisulpiride). Major part of controlled studies concluded to the better efficacy of low doses of such drugs on negative symptoms, while high doses are almost inefficient. Some studies concluded in the activity of clozapine on negative symptoms of schizophrenic patients. To answer the question whether negative symptoms of schizophrenia are improved concomitantly or independently of improvement in positive symptoms or of decrease in extrapyramidal side effects and/or depressive symptoms, the authors prospectively followed up for 30 months, 13 DSM-IV resistant schizophrenics. Symptoms were assessed by means of 18 item Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale and Extrapyramidal Symptom Rating Scale (ESRS). Improvement in negative symptoms was significantly correlated to improvement in positive ones and to scores in ESRS. Many open studies concerning anti-depressants and other drugs have been published; however controlled studies are necessary to confirm these data.

The place of electroconvulsive therapy (ECT) in the treatment of affective disorders is presently important and even inequaled in some depressive illness forms. But ECT is still controversial and its indications in the treatment of schizophrenia remain debated. In order to evaluate the place of this "vielle thérapeutique du futur" (39) in the treatment of schizophrenia, we reviewed the literature of the two last decades and tried to answer these questions. 1) Is ECT effectiveness in treatment of schizophrenic symptoms proved? 2) What is the effectiveness of ECT compared with other efficacious treatment? 3) Does the ECT + neuroleptic combination provide some advantage? and in which cases? The literature provides many studies in the topic. However, a considerable proportion of these studies make no use of modern methodological criteria. We only consider papers which: --give a clear diagnostic definition in patients groups and control groups, --use a standardized method of treatment, --use quantitative tools to evaluate results, --randomize treatment and use, when possible, double blind design. 1) Curative effects of ECT in schizophrenic symptoms: Brandon et al. (14) compare two groups of schizophrenic patients diagnosed according to PSE for schizophrenia and receiving equivalent doses of neuroleptics. The first group receives ECT when the other one receives simulate ECT. The former improved significantly better than the later. The difference persists but is no longer significant from the forth week of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

This paper concerns the tomodensitometric (TDM) study, with the same clinical and radiological criteria, of 78 schizophrenic patients (age: less than 60 years) from psychiatric hospitals in Madrid and from Sainte-Anne hospital (Paris). The length of evolution and the severity of disturbances seemed to be the most important causal elements of cerebral atrophy. Some TDM peculiarities appeared correlated with some clinical forms (paranoid or hebephrenic). The review of previous works illustrates the importance of some etiological conditions for the production of cerebral atrophy: age, length of evolution and, more particularly, the severity of the disease. The confrontation of the anatomo-pathological and pneumoencephalographic studies with the TDM results suggests that, if the TDM is a good indicator of ventricular dilatation, appreciation of the widening of the cerebral sulci remains difficult.

This paper summarizes the presentations made during the Lucca symposium (1-3 October, 1977) on long-acting neuroleptics. The authors tried to present advantages and inconveniences of this therapeutic compared to the "classical" neuroleptic therapeutics: - in patients with an acute symptomatology; - in stabilized patients. The main advantage is that one can be ensured that the drug has been or not been taken.