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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.)

Introduction: Prognosis of schizophrenia has not significantly improved despite extensive research. There is often a relatively long delay between onset of symptoms and treatment initiation. Lately, duration of untreated psychosis (DUP), the time between the onset of psychosis and initiation of treatment, has been one of the most studied variables in patients presenting for a first psychotic episode in order to evaluate the impact of early intervention on the prognosis of schizophrenia. In the literature, a variety of criteria have been used to define both transition to psychosis and initiation of treatment. Furthermore, the dating of both of these variables is usually retrospective, further complicating the measurement of DUP., Methods: We conducted a comprehensive review about DUP using Pubmed and Google Scholar databases up to January 2015 using the following keywords "schizophrenia", "duration of untreated psychosis", "duration of untreated illness" and "early intervention". Papers were included if they were published in French or English., Results: The mean DUP was found to be 2 years but it can vary according to multiple factors such as denial of illness by the patient and family, withdrawal and isolation from friends and relatives, diagnostic errors, paranoid views of the mental health treatment systems, or negative symptoms. Long DUP may also be a correlate of poor premorbid functioning or of an insidiously unfolding psychosis. Considerable discrepancies exist in the way that DUP is estimated in different studies. Although the clinical interview remains the most common way of measuring DUP, so far there is no evidence for favoring one method over another. Regardless of measurement method, a longer DUP is found to be associated with poorer outcome in schizophrenia in both the short and long-term across a number of domains: symptoms severity, remission rates, the risk of relapse, global functioning and quality of life. Its role in functional outcome appears to be mediated largely by negative symptoms, for which there is still no effective treatment. A recent meta-analysis has shown that shorter DUP is associated with less severe negative symptoms at short and long-term follow-up, especially when DUP is shorter than 9 months. The mechanism of the relationship between DUP and outcome is still undefined. A hypothesis is that the shorter the DUP, the more likely the intervention is being applied during the period in which neurobiological deficit processes in schizophrenia are most active., Discussion: A study of the duration of untreated illness (DUI), which is defined as the DUP and the prodromal phase, seems necessary because results of studies evaluating the effect of early detection and intervention in individuals with clinical high risk for psychosis are promising. A number of interventions such as omega 3 fatty acids and integrated psychosocial interventions seem to delay transition in the at-risk population. However, replication studies are lacking, and a great proportion of at high-risk individuals will spontaneously remit or develop diseases other than chronic psychosis, making us question the advantages and disadvantages of a treatment. Taking into consideration the high prevalence of comorbidities in individuals referred for clinical high-risk state and their effect on the individual's functioning, future interventions in the field need to address not only the preventative efficacy on psychosis transition but also their effectiveness in improving the functioning of this population and their effect on the outcome of schizophrenia when transition to psychosis has occurred., Conclusion: Despite the huge advances in the field of schizophrenia, many questions remain unanswered and huge efforts are still necessary to understand the pathophysiology of this illness in order to improve its outcome., (Copyright © 2016 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.)

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.

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.

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.

"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.

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 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.

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.