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Objectives: Although mortality by suicide in schizophrenia seems to have decreased in some countries over the last 30 years, it remains much higher than in the general population. Studies have shown this risk to impact around 5% of patients, corresponding to a risk almost 2.5 times higher than in the general population. Family psychoeducation in schizophrenia has been demonstrated to lead to symptom reductions and to an improvement of the quality of life, two factors that should contribute to decreasing the suicidal risk. Therefore, if families attend an efficient psychoeducation program, we can expect a decrease in the patient suicidal risk. Attending a family psychoeducation program at the beginning of the disease would also be associated with a stronger preventive effect on suicidal mortality. The objective of this study is to describe the suicide attempt rate of patients who suffer from schizophrenia before and one year after one of their relatives participated to the family psychoeducation program Profamille., Method: We performed a retrospective study on 1209 people who attended the Profamille (V3.2 version) Family Psychoeducation Program. This program has 2 modules: an initial training module of 14 weekly or fortnightly sessions, and a consolidation module of 4 sessions over 2 years. Sessions last 4 hours and follow a precise and structured course. Data were collected from 40 different centers in France, Belgium and Switzerland and were based on participants assessed at the beginning and one year after the first module. Self-assessment from the relatives participating in the program provided the measure of patients' suicide attempts. An assessment at T0 explored the attempts over the 12 months before the beginning of the program while the assessment at T1 analyzed those during the 12 months following the end of the Program. The Chi 2 test was used to compare the suicide attempt rates for each period, using a significance threshold of 0.05. Since the risk of suicide is greater in the first years of the illness, rates of attempts are also calculated according to the age of disorder. The analysis was carried out with the statistical software R., Results: The number of participants reporting that their relative had attempted suicide in the previous 12 months decreased from 41 to 21. The annual attempts rate was evaluated at 6.4 % before the Profamille program and decreased to 2.4 % a year after the end of the program (P=0.0003). The reduction of the attempt rate was observed even for patients with schizophrenia for more than 10 years., Conclusion: This study shows the positive impact of Profamille on reducing the rate of suicide attempts in patients with schizophrenia. It has been shown that the risk is highest at the beginning of the disorder. Therefore, based on our results, it would seem appropriate to propose the Profamille program at an early stage., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objectives: The present article is a synthesis of the first 10 years of follow-up of the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ) cohort., Methods: More than 700 community-dwelling stabilized subjects have been recruited and evaluated to date. The mean age was 32 years with 75 % males, the mean illness duration was 11 years, the mean age at illness onset was 21 years, the mean duration of untreated psychosis was 1.5 years and 55 % were current daily tobacco smokers., Results: The major findings of the FACE-SZ cohort may be summarized as follows: the metabolic syndrome is twice more frequent in schizophrenia as compared to the general population and is not correctly assessed and treated; cognitive disturbances have been found in benzodiazepine consumers and in patients with chronic low-grade peripheral inflammation; major depressive disorder (MDD) is a common current comorbid condition in about 20% of the subjects at the evaluation. MDD is associated with impaired quality of life and with increased nicotine dependency in SZ daily tobacco smokers. Improving depression and negative symptoms may be the most effective strategies to improve quality of life in schizophrenia; the duration of untreated psychosis is much longer in cannabis smokers and in subjects with an age at illness onset<19 years. Adherence to treatment is diminished in subjects who report a subjective negative feeling after treatment intake independent of objective side effects (extrapyramidal syndrome and weight gain). Akathisia has been found in 18% of the subjects and has been associated with antipsychotic polytherapy., Conclusions: In the light of these results, some recommendations for clinical care may be suggested. The early detection of schizophrenia should be specifically increased in adolescents and/or cannabis smokers. All patients should be administered a comprehensive neuropsychological evaluation at the beginning of the illness and after stabilization under treatment. Improving metabolic parameters and lifestyle (diet and physical activity) should be reinforced. The benefit/risk ratio of benzodiazepine and antipsychotic polytherapy should be regularly reevaluated and withdrawn as soon as possible. If MDD remains underdiagnosed and undertreated, improving depression may strongly improve the quality of life of SZ subjects. In the end, Cognitive Remediation Therapy and anti-inflammatory strategies should be more frequently included in therapeutic strategies., (Copyright © 2018. Published by Elsevier Masson SAS.)

Major depression represents among the most frequent psychiatric disorders in the general population with an estimated lifetime prevalence of 16-17%. It is characterized by high levels of comorbidities with other psychiatric conditions or somatic diseases as well as a recurrent or chronic course in 50 to 80% of the cases leading to negative repercussions on the daily functioning, with an impaired quality of life, and to severe direct/indirect costs. Large cohort studies have supported that failure of a first-line antidepressant treatment is observed in more than 60% of patients. In this case, several treatment strategies have been proposed by classical evidence-based guidelines from internationally recognized scientific societies, referring primarily on: I) the switch to another antidepressant of the same or different class; II) the combination with another antidepressant of complementary pharmacological profile; III) the addition of a wide range of pharmacological agents intending to potentiate the therapeutic effects of the ongoing antidepressant medication; IV) the association with appropriate psychological therapies; and, V) the use of non-invasive brain stimulation techniques. However, although based on the most recently available data and rigorous methodology, standard guidelines have the significant disadvantage of not covering a large variety of clinical conditions, while currently observed in everyday clinical practice. From these considerations, formalized recommendations by a large panel of French experts in the management of depressed patients have been developed under the shared sponsorship of the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) and the Fondation FondaMental. These French recommendations are presented in this special issue in order to provide relevant information about the treatment choices to make, depending particularly on the clinical response to previous treatment lines or the complexity of clinical situations (clinical features, specific populations, psychiatric comorbidities, etc.). Thus, the present approach will be especially helpful for the clinicians enabling to substantially facilitate and guide their clinical decision when confronted to difficult-to-treat forms of major depression in the daily clinical practice. This will be expected to significantly improve the poor prognosis of the treatment-resistant depression thereby lowering the clinical, functional and costly impact owing directly to the disease., (© 2017 L’Encéphale, Paris.)

Introduction: The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22. 22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%). The inheritance of the syndrome (10%) is autosomal dominant. Most people with 22q11.2DS are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. A small percentage of affected individuals have shorter deletions in the same region (contiguous gene deletion syndrome). The general features of 22q11.2DS vary widely (more than 180 phenotypic presentations) and the syndrome is under diagnosed. Characteristic symptoms may include congenital heart disease, defects in the palate, neuromuscular problems, velo-pharyngeal insufficiency, hypoparathyroidism, craniofacial features and problems with the immune system T-cell mediated response (caused by hypoplasia of the thymus)., Cognitive Phenotype: The neurocognitive phenotype of the 22q11.2DS is complex. Cognitive deficits are seen in the majority (80-100%) of individuals with 22q11DS with impairments in sustained attention, executive function, memory and visual-spatial perception. Borderline intellectual function (IQ: 70-75) is most common, mild intellectual disability (IQ: 55-75) is slightly less frequent and a small percentage of children fall into the low average intelligence range. Most children with 22q11.2DS achieve higher scores in verbal tasks than in non-verbal tasks, although this pattern of dysfunction being not universal. Brain MRI studies have shown volumetric changes in multiple cortical and subcortical regions in individuals with 22q11DS that could be related to both cognition and psychoses., Psychiatric Phenotype: General psychiatric features included anxiety disorders, attention deficit disorder and poor social skills (40-50%). An elevated risk of bipolar disorder and major depression occurs in adolescence and young adulthood. A strong and specific relationship exists between the presence of the 22q11.2 microdeletion and schizophrenia (30-40%). This risk is not associated with any other neurogenetic syndrome. Social cognition is impaired in 22q11.2 DS and this observation is correlated with psychotic features. So, long-term medical care is increasingly being directed towards the treatment and recognition of these symptoms., Treatment: Required pharmacological treatment strategies have to be adapted to the syndrome. Moreover, cognitive remediation is a promising tool for treating neuro- and social cognitive deficits in 22q11.2DS. However, these new therapeutic strategies have to be developed to improve quality of life., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Impulsive traits are key characteristics in a lot of psychiatric disorders and are part of the "normal" behaviour spectrum. Although impulsivity is a controversial concept, some questionnaires have focused on its "dysfunctional" aspect. The Barratt Impulsive Scale (BIS-10) is the scale the most used to explore impulsiveness, but it does not explore antisocial or nonconform behaviour. The Chapman Impulsive and Nonconformity Scale (INCS) is a questionnaire of 51 items that measures the impulsivity and nonconformism. The INCS reflects "failure to internalize societal norms, lack of empathy for the pain of others, and an unrestrained yielding to impulse and self-gratification" and was originally designed to assess psychosis proneness. It has been validated in the USA, but has not yet been validated in France. Interestingly, although it was not predictive of psychosis, high scorers on INCS exceeded controls on depression, and on rates of substance abuse. Furthermore, participants scoring high on hypomanic personality scale and INCS were found to have an especially heightened risk for bipolar disorders., Objective: To translate and determine reliability and validity of the French version of the Chapman Impulsive and Nonconformity Scale in young adults by comparison with the BIS., Method: Chapman Impulsive and Nonconformity Scale has been back-translated into French, and filled out by 237 students (males: 104; females: 133; mean age: 20.4 [range 19-25]). BIS-10 was used for convergent validity. Each participant completed the two scales. Reliability and validity of the French form of INCS were assessed with the internal consistency (coefficient alpha of Cronbach and the split half reliability) and the convergent validity., Results: In the French version of the INCS, the 51 items have high internal reliability (Cronbach's alpha=0.81 and split half reliability=0.80). Concerning the BIS, internal reliability is good (Cronbach's alpha=0.72 and split half reliability=0.66). Moreover, Pearson's r of the INCS/BIS is statistically significant (0.65) and underlines the concomitant validity of the INCS with the BIS., Conclusion: The psychometric properties of the French version of the INCS are very similar to those of the English version. Hence, the INCS could provide a way to explore the two related dimensions: impulsivity and nonconformism.

Introduction: In 1985, Barker et al. showed that it was possible to stimulate both nerves and brain using external magnetic stimulation without significant pain. During the past 10 years, therapeutic effects of repeated Transcranial Magnetic Stimulation (rTMS) have been widely studied in psychiatry and its efficacy has been demonstrated in the treatment of major depressive disorders, particularly as an alternative to electroconvulsivotherapy (ECT). Facing the large range of studies, we found necessary to propose an up-to-date review in French of the methodological and therapeutic variations among them., Method: Based on an exhaustive consultation of Medline data and the Avery-George-Holtzheimer Database of rTMS Depression-Studies, supplemented by a manual research, only works evaluating the therapeutic efficacy of rTMS on depressive symptoms were retained, excluding all studies exclusively investigating the stimulation parameters or the tolerance as well as case reports., Results: Out the 66 available reports we retained 30 studies. After a description of the main results of these 30 studies, several elements of the 66 will be discussed. Open studies demonstrated that short courses rTMS (5 to 10 sessions) produced a decrease in the mean Hamilton Depression Ratting Scale (HDRS) scores, although significant remission of depression in individuals was rare. Most authors had used high frequency rTMS applied to the left Dorso Lateral Prefrontal Cortex (left DLPFC). However, low frequency rTMS applied to the right DLPFC was also followed by significant reduction of HDRS scores. Parallel arm, double blind versus placebo studies are designed to clarify the therapeutic efficacy of rTMS therapy but conclude in contradicting results. Literature data globally confirms a greater efficacy of rTMS compared to placebo (37% responders in the active group vs 20% in the sham). This efficacy could in fact be even greater because the sham procedure is disputable in most studies. Indeed, positioning rTMS coil at 45 or 90 from the scalp may not represent an accurate sham procedure and the use of real sham coil is to be recommended. Only one study has suggested that associating rTMS and ECT could decrease the number of general anesthesia required. Therapeutic efficacy has been shown by either inhibiting the right DLPFC or by stimulating the left DLPFC, although some patients exhibit paradoxical responses. High frequency rTMS (>5 Hz) increases cortical excitability and metabolism, while low-frequency rTMS stimulation ( 1 Hz) has the opposite effect. Other parameters are: relevant: intensity (from 80 to 110% of motor threshold), total number of stimulations (from 120 to 2 000) and total number of rTMS sessions (from 5 to 20). As suggested in most recent studies, higher-intensity pulses, higher number of stimulation or longer treatment courses may be more effective. Greater responsiveness to rTMS may be predicted by several patients' factors, including the absence of psychosis, younger age and previous response to rTMS therapy., Discussion: Conclusions on these factors and others, such as the importance of anatomically accurate coil placement and the distance from the coil to the brain, await further investigation. Despite heterogeneity of these reports according to methodology and treatment parameters, the antidepressive properties of rTMS now appear obvious, opening interesting prospects, in particular in the treatment of pharmacoresistant major depressive patients and, we hope, administered as adjuvant therapy in non-resistant depression., Conclusion: Thus, many questions remain unanswered concerning the optimal stimulation parameters, privileged indications and maintenance sessions. This justifies the development of structured evaluation trials on larger samples.

Introduction: Despite recent developments, the impact of pharmacotherapy on social autonomy and interpersonal problem solving skills in patients with schizophrenia remains limited, with consequences in terms of socio-professional functioning. Indeed, independently of the positive, negative and/or disorganization symptoms, functional deficits in patients with schizophrenia rely mainly on various cognitive impairments., Objectives: To determine the impact of a new Cognitive Remediation Strategy on interpersonal problem solving skills, social autonomy and symptoms in patients with schizophrenia., Methods: Thirty patients with schizophrenia were enrolled in a program consisting of 14 training sessions of 4 cognitive functions (attention/concentration, topological memory, logical reasoning, executive functions) using the REHACOM software. Measurements of attention (Continuous Performance Test, CPT), memory (Rivermead Behavioural Memory Test, RBMT) and executive functions (Wisconsin Card Sorting Test, WCST) as well as interpersonal problem solving skills (Assessment of Interpersonal Problem-Solving Skills, AIPSS) and social autonomy (Social Autonomy Scale, EAS) and finally schizophrenia symptoms (Positive And Negative Syndrom Scale, PANSS) were undertaken at the beginning and the end of the 14 remediation meetings., Results: Cognitive functions, interpersonal problems solving skills, social autonomy and symptoms were significantly improved by the Cognitive Remediation Strategy., Conclusion: Our results confirm the therapeutic impact of a Cognitive Remediation Strategy among 30 schizophrenic patients stabilised on clinical, therapeutic and functional levels. The question of the long-term maintenance of such improvements still requires further investigation.

Drugs of the Benzodiazepine family are among the most frequently prescribed in France. Since anxiety disorders, for which these substances are mostly indicated, affect 10% of pregnant women, it is very likely that such a treatment could expose many foetuses to BZD during the first three Months of pregnancy. We know that the teratologic effect is not necessarily based on dose rate, but that it is associated with fetal drug exposure during the first 12 weeks of gestation, when organ formation occurs. Most epidemiologists concur that the baseline incidence of congenital damage is 2-2,5% in Europe. The results from a large number of stu-dies on associations between the use of BZDs in pregnancy and congenital malformations are conflicting. An in-depth analysis of existing literature shows results that are hardly comparable, if not contradictory, due to extreme differences in methodological approaches. In a recent meta-analysis case-control studies and cohort studies were analyzed separately. Among the case-control studies significant associations were found between BZD exposure and both, major malformations and oral clefts, whereas the cohort studies showed no association between BZD and any kind of malformation. The purpose of our study is to search for a specific teratogenic effect of this class of drugs, using data collected (1976-1997) by the French Central-East (FCE) registry of congenital malformations, member of the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS) located in Lyon, France. This registry monitor malformations among 100,000 births per Year. We analyzed 13,703 cases where information is available on whether or not the mother took a drug during her first trimester of pregnancy. Among them, 3,603 (28%) actually took a drug, and 262 (6.8%) took some sort of benzodiazepine (BDZ). BZD were divided into 9 categories, 8 being the most frequently present, plus one broad category of "others". Malformations were divided into ten categories: congenital anomalies of heart, cleft lip and/or cleft palate, neural tube defects, other anomalies of central nervous system, hypospadias, urinary malformations, anal atresia, other digestive anomalies, limb reduction defects, and genetic anomalies, including chromosome aberrations and monogenic conditions. Other malformations were grouped in an eleventh category. The interesting aspect of this study is that it takes into account the BZD metabolism. It is worth noting that the hepatic catabolism of benzodiazepine is a very complex one, because it leads to derived molecules which are sometimes active and/or present in the common metabolic route of major commercial drugs. Our hypothesis is that if one BZD is associated specifically to a certain type of congenital defect, we may find this BZD to be overrepresented, as compared with other BZDs, in newborns exhibiting some type of congenital defect. The analysis was run according to a case-control approach. Odd ratios (OR) and their 95% confidence intervals were calculated by logistic regression with adjustment for maternal age and parity. When one category of defects was considered, infants having the corresponding malformation were considered as cases, while infants with other malformations were considered as controls. In a similar way infants having being exposed to a given drug were considered as exposed, while infants exposed to any other drug were considered as unexposed. The analysis then was run in 4 steps. Step 1: full sample. With 13,703 cases. We observed no increased risk for any specific malformation type associated with use of BZD. Step 2: further defining drug exposure as a specific BZD, and all others unexposed, a significant association was seen between lorazepam and anal atresia. OR=6.2 (95% CI2.4-15.7, p=0.01). Step 3: this finding was upheld and no other emerged when exposure was defined as the drug or any of its active metabolites. This step was performed because hepatic catabolism of BDZs leads to derived molecules that are sometimes active and/or present in the common metabolic route of major marketed BZDs. Step 4: similarly, the lorazepam/anal atresia finding was upheld when the analysis was restricted to the 262 malformed infants exposed to BZDs in utero. Six cases of anal atresia were found among all newborns exposed to BZD in utero, and five of them were exposed to lorazepam, representing a hypothesis to be tested in further. We are not aware of other reports of this association, and it should be regarded as preliminary until confirmed in other data sets.

Although some neuropsychological deficits and a high rate of schizotypal personality disorders have been found in the first-degree relatives of patients with schizophrenia, few studies have looked for a link between those two types of potential marker of vulnerability to this disease. The aims of this study were: 1) to confirm some executive/attentional deficits in a group of first-degree relatives including not only siblings but also parents; 2) to evaluate the schizotypal traits using the French version of 4 self-reporting scales proposed by Chapman and his colleagues; 3) to look for a dependence or independence between the neuropsychological performance and the scores on the scales of schizotypy. Twenty four patients with schizophrenia, 48 of their first-degree relatives and 31 controls were included in the study. Both attentional tests (a Digit Symbol Substitution Test and a Degraded Stimulus-Continuous Performance Test) confirmed a worse performance in the patient and in the first-degree relative groups than in the control group. On the opposite side, the executive performance assessed by the Wisconsin Sorting Card Test, was poorer in the patient group only. Scores of the first-degree relative group on the social anhedonia, physical anhedonia and perceptual aberrations scales were at an intermediate level between those of the patient and control groups; moreover, only scores on the social anhedonia scale tended to be significantly higher in the first-degree relative group than in the control group. Among the first-degree relative group, the only significant correlation found was between the number of perseverative errors on the WCST and the scores on the physical anhedonia scale.

Several lines of evidence suggest that the glutamatergic N-methyl-D-aspartate (NMDA) receptor is involved in schizophrenia pathophysiology. Post-mortem studies have revealed a lower density of glutamatergic receptors in patients with schizophrenia. Other studies of cerebrospinal fluid reported lower levels of glutamate in patients with schizophrenia in healthy comparison subjects. The most compelling evidence is provided by the psychomimetic effects of the NMDA antagonists phencyclidine and ketamine. Recently, much interest has been given to the study related to the role of NMDA receptor in pathophysiology of schizophrenia by administration of sub-anesthetic doses of ketamine. A phencyclidine hydrochloride derivate, ketamine, is a dissociative anesthetic and a non competitive antagonist of the NMDA receptor. In healthy subjects, ketamine produces: 1) positive symptoms of psychosis, such as illusions, thought disorder and delusions; 2) negative symptoms similar to those associated with schizophrenia including blunted emotional responses, emotional detachment, and psychomotor retardation; 3) cognitive impairments, in particular impairments on tests of frontal cortical function including increased distractibility, reduced verbal fluency and poorer performance on the Wisconsin Card Sorting Test. During smooth pursuit eye tracking, ketamine induces nystagmus as well as abnormalities which are among the characteristics of schizophrenia. In patients with schizophrenia, the administration of ketamine produces an activation of their psychotic symptoms, which have striking similarities to symptoms of their usual psychotic episodes. Ketamine effects on memory and other cognitive functions in schizophrenic patients are controversial. The psychomimetic effects of ketamine are transitional, reversible and influenced by time, dose and administration conditions. Susceptibility to the psychotomimetic effects of ketamine is minimal or absent in children and becomes maximal in early adulthood. The similarity between ketamine effects and endogenous psychoses created interest in the capacity of antipsychotic medications to block ketamine effects. Haloperidol failed to block this ketamine-induced psychomimetic effects in healthy subjects and in schizophrenic patients. However, clozapine, the prototype of atypical antipsychotic agents significantly reduced the ketamine-induced increase in positive symptoms in schizophrenic patients. Recently, lamotrigine significantly decreased ketamine-induced positive and negative symptoms in healthy subjects. Brain regions responsible for NMDA-mediated psychosis have not been established. Using positron emission tomography and [18F] fluorodeoxyglucose, the sub-anesthetic ketamine administration produces bilateral increases in metabolic activity in the prefrontal cortex. In a [15O] H2O positron emission tomography study, ketamine selectively increases cerebral blood flow in the anterior cingulate cortex and reduces cerebral blood flow in the hippocampus and primary visual cortex. The mechanism of neuropsychiatric effects of sub-anesthetic ketamine is not clear. A dysfunction in glutamate-dopaminergic interactions has been suggested as a mechanism for these effects of ketamine. Ketamine has been reported to primarily block NMDA receptor complex giving support to a glutamate deficiency hypothesis in schizophrenia. In addition, ketamine caused increases in cortical and striatal synaptic dopamine concentrations. The effects of NMDA receptor antagonist administration are argued to support a neurobiological hypothesis of schizophrenia, which includes pathophysiology within several neurotransmitter systems, manifested in behavioral pathology. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia.

Most of existing self-report measures of schizotypal personality assess only few of the nine traits of Schizotypal Personality Disorder (SPD) according to DSM III-R or DSM IV. The Raine's Schizotypal Personality Questionnaire (SPQ) is one of the most widely used questionnaire for SPD diagnosis. This well adapted tool for screening SPD in large samples from general population allows simple and quick evaluations by the mean of 74 items and nine sub-scales exploring DSM IV criteria of the trouble. With the original sample of American students, Raine found SPQ to have high internal reliability (0.91) and reported cutoffs for the top and the bottom ten percents of SPQ scores at respectively 41/74 and 12/74. We reported here the validation study of the French version of the SPQ in a sample of 232 students (males: n = 107; females: n = 125; mean age: 21.17 +/- 1.47; mean educational level: 13.36 +/- 1.06). The French version has high internal reliability (SPQ total: Cronbach's alpha = 0.91; SPQ nine subscales: Cronbach's alpha = 0.57 to 0.76). The ten percent high and low cutoff scores on the distribution of SPQ scores are respectively 40/74 and 7/74 for the total sample. However, gender differences are observed: 38/74 and 9/74 for females; 42/74 and 6/74 for males. A Principal Component Analysis (PCA) confirms the high internal reliability. Moreover, PCA evidences a three-factor model of schizotypy reflecting "positive or cognitive-perceptual", "negative or social-interpersonal", and "disorganization" latent factors. These results replicate previous works on the topic with the same instrument.

Several lines of evidence seem to indicate that some neurocognitive measures could be phenotypic markers of predisposition to schizophrenia. The aim of this study was to investigate 21 patients with schizophrenia, 51 of their first-degree relatives and 46 nonpsychiatric controls, with a series of tests known to be sensitive to prefrontal cortical damage--the Trail Making Test, part B (TMT B), the Wisconsin Card Sorting Test (WCST) and a verbal fluency test (VFT)- and/or sensitive to temporo-hippocampic dysfunctions: verbal and visual memory and verbal learning tests from the Wechsler Memory Scale-Revised (Wechsler, 1987). Since parents and siblings share on average 50% of their genes with the schizophrenic proband, firstly we predicted that the first-degree relatives' performance would be at an intermediate level between patients and control subjects and secondly, we expected that a higher proportion of relatives than of control subjects would be impaired. The patients demonstrated deviant patterns of neuropsychological performance on the three tests sensitive to frontal dysfunctions and on most of the memory and learning tests. In the relative group, performance on the TMT B, VFT, immediate verbal recall and verbal learning was at an intermediate level between both other groups and significantly impaired compared to control subjects. However, the relative group did not differ from the control group on the WCST, immediate visual recall, and delayed verbal and visual recalls. Furthermore, compared to the control group, the percentages of patients and relatives who scored one standard deviation below the mean control group were significantly higher for the VFT and immediate verbal recall scores. Among all the tests studied, the verbal fluency and the immediate verbal recall appeared to be valuable phenotypic markers of schizophrenia since: (i) their mean scores were poorer in the patient and in the relative groups, (ii) the percentages of patients and relatives with poor performance were higher than the percentage of controls, (iii) these deficits were not due to poorer general intellectual abilities in the relative group, (iv) these deficits did not correlate with anxiety or depression scores.

Chapman and colleagues have developed symptom-oriented scales based on Meehl's manual of schizotypy, such as the Social Anhedonia (SA) and Physical Anhedonia (PhA) Scales, the Magical Ideation Scale (MIS), and the Perceptual Aberration Scale (PAS). Whereas Chapman's scales of psychosis proneness are the most internationally used instruments for the assessment of schizotypy, some of them, such as MIS and PAS, were still not available in French. We reported here the validation study of the MIS and the PAS French versions that we had published previously. This study was conducted in a sample of 233 students (males: n = 108; females: n = 125; mean age: 21.17 +/- 1.47; mean educational level: 13.36 +/- 1.06). The French versions of the MIS and the PAS have high internal reliability (MIS: Cronbach's alpha = 0.85; PAS: Cronbach's alpha = 0.88). French norms are given for each of these scales. They are respectively 19/30 for the MIS and 17/35 for the PAS high cutoff scores without any difference when gender was considered. These results are very closed to those found by Chapman and colleagues for University of Wisconsin undergraduate students.

Since several investigations have shown attentional deficits both in patients with schizophrenia and in subjects at high risk for schizophrenia, these deficits could be valuable vulnerability markers for schizophrenia. The aim of this study was to investigate wether non psychotic relatives of schizophrenic probands have deficits in sustained attention as measured by the Continuous Performance Test, Identical Pairs (CPT-IP) version. The study subjects were 25 schizophrenic probands, 50 of their first-degree relatives and 46 normal controls. For each subject, attention was assessed during 6 experimental conditions (2 standard, 2 slow, 2 easy conditions) of visual stimuli (digit-numbers and shapes). In each of the six conditions, the value of the sensitive index d' in the first-degree relative group was at an intermediate level between the patient and control groups. Moreover, in the standard shape condition, the d' value was significantly lower in the schizophrenic and in the relative groups than in the control group. This deficit was all the more interesting since it was not explained by a deficit in general intellectual abilities or by psychopathology such as anxiety or depression. Furthermore, the schizophrenic patients made more random errors in the standard and in the slow number conditions than both other groups. All groups improved their performance when the stimulus duration increased and when the processing load decreased. As a conclusion, this investigation seems: 1) to confirm the existence of an attentional deficit in the first-degree relatives of patients with schizophrenia; 2) to demonstrate the interest of the CPT-IP to detect this deficit. It must be emphasized that in order to detect the deficit, one only needs to explore the standard shape condition and that under such circumstances, the CPT-IP test has the advantage of being less time consuming than tests used in previous studies.

Meehl used the term "schizotype" to refer to individuals who possess an underlying vulnerability for schizophrenia. Because of the extremely varying degrees of the schizotype's clinical expression, he recommended assessing schizotypic signs through objective measures rather than clinical judgement. In this way, Chapman et al. have developed symptom-oriented scales based on Meehl's manual, such as the Social Anhedonia (SA) and Physical Anhedonia (PhA) Scales, the Magical Ideation Scale (MIS), the Perceptual Aberration Scale (PAS) and the Impulsive Nonconformity Scale (IN). Whereas Chapman's scales of psychosis proneness are the most internationally used instruments for the assessment of schizotypy, some of them, such as MIS and PAS, were still not available in French. Therefore, the first aim of this report was to offer French translations of the Magical Ideation and the Perceptual Aberration Scales; the agreement of the original authors were obtained for both translated versions and their back translations. The second aim of our study was to establish French norms for each of these scales. The preliminary norms presented here [MIS: 19/30 (for females) and 20/30 (for males); PAS: 18/35 (for both genders)] were obtained by administering both scales to a sample of 134 French students. They are very close to those found by Chapman et al. for University of Wisconsin undergraduate students. We will confirm them with a larger sample of French students.

Most of existing self-report measures of schizotypal personality assess only few of the nine traits of schizotypal personality disorder according to DSM III-R or DSM IV. Adrian Raine has developed a self-report scale named "Schizotypal Personality Questionnaire, [SPQ]" to evaluate all these traits. The questionnaire was found to have high sampling validity, high internal reliability [0.91] and test-retest reliability [0.82]. However, the SPQ was still not available in French. Therefore, the first purpose of this report was to offer a French translation of this tool with the agreement of A. Raine for both translated version and its back translation. The second purpose of our study was to establish French norms. The preliminary norms presented here were obtained by administering the SPQ to a sample of 134 French students of both gender (mean age: 20.11 +/- 1.53 years; mean educational level: 13.39 +/- 1.04 years). On that sample, the minimal score was 2/74 and the maximal one 54/74 (mean of the sample: 23.60 +/- 12.09). With the original English study, based on a sample of American students, the cut-offs for the top and the bottom ten percents of SPQ scores were respectively of 41/74 and 12/74. Very close preliminary cut-offs were observed in our own study i.e. respectively 40/74 and 9/74. We will confirm them in a larger sample.

The existence of a genetic background is well admitted in schizophrenia, but some individuals at genetic risk for that disease could never manifest it at a clinical level. However, several vulnerability models could help us to identify such individuals. According to them, when similar perturbations at a given task are observed both in clinically stable patients with schizophrenia and their nonschizophrenic first degree relatives, this task could be qualify as an indicator of the vulnerability to schizophrenia. In literature, that seems the case for auditory ERP late components in oddball paradigms. Our study was undertaken to replicate literature data. For that purpose, amplitude and latencies of auditory N100, P200, N200 and P300 wave-forms were assessed among 21 clinically, stable schizophrenics, 21 of their biological full siblings and 21 unrelated control subjects matched with the two others groups for several socio-demographic factors. Comparison were performed by non parametric analyses (Kruskal-Wallis one way ANOVA, and post-hoc Mann-Whitney). Compared to controls, delayed latencies and/or reduced amplitudes were observed for several ERP components--mainly with P300--in the sibling group. ERP values from this group did not statistically differ from those of the group with schizophrenia. In conclusion, results from the sibling group suggest that ERP impairments in auditory oddball paradigms may actually represent indicators of the genetic vulnerability to schizophrenia.

The existence of a genetic background is now a well admitted notion in schizophrenia, but some individuals at genetic risk for that disease could never manifest it at a clinical level. However, several vulnerability models could help us to identify such individuals. According to them, when similar perturbations at a given test are observed both in clinically stable schizophrenics and their nonschizophrenic first degree relatives, this test could be qualify as an indicator of the vulnerability to schizophrenia. In literature, that seems the case for several neuropsychological tasks, exploring attentional abilities (degraded version of the Continuous Performance Task [DS-CPT], and Span Of Apprehension task [SOA]) and executive functions (Wisconsin Card Sorting Test [WCST]). Our study was undertaken to replicate literature data and to further explore the relationship between these three neuropsychological markers. For that purpose, performances at DS-CPT, SOA and WCST were assessed among 18 clinically stable schizophrenics, 18 of their biological full siblings and 15 unrelated control subjects matched with the two others groups for several socio-demographic factors. Comparisons were performed by non parametric analysis (Kruskal-Wallis one way ANOVA, and Mann-Whitney). Compared to controls, the siblings group performances were significantly impaired on the three tasks, while they did not statistically differ from the schizophrenic ones. No relationship was observed between the markers, except for the "d'" index at DS-CPT and the number of successfully performed categories at the WCST. Results from the sibling group suggested that the observed impaired neuropsychological performances may actually represent indicators of the genetic vulnerability to schizophrenia. Moreover, the generally admitted relationship between WCST poor performances and an impairment of the prefrontal cortex, lead us to hypothesize some role of this brain area in schizophrenia vulnerability.

Unlabelled: The P3 component of the event-related potential (E.R.P.) is an endogenous positive wave with a latency of approximately 300 msec, which is typically elicited by rare target stimuli in a detection task. The P3 has been applied to the study of cognitive impairments. One of the most consistently replicated biologic observation in schizophrenia is the P3 amplitude reduction. More recently, a prolonged P 3 latency has been observed by some authors. Nevertheless, when the heterogeneity of the schizophrenic syndrome is taken into consideration, results reported in the literature do not show much agreement. In the present study, we attempted to explore the P 3 component in a group of schizophrenic patients with a precisely defined clinical symptomatology., Methods: Subjects. The study included 19 inpatients and 19 healthy control subjects age and sex-matched. Patients were medication-free for at least 15 days prior recording. According to the DSM III-R diagnosis criteria, 10 patients were classified as "paranoid subtype" and 9 as "disorganized subtype". Furthermore, on the day of the neurophysiological examination, the patients were interviewed using the Scale of the Assessment of Positive Symptoms (S.A. P.S.) and the Scale of the Assessment of Negative Symptoms (S.A.N.S.). The median age (SD) of the patients was 35.3 +/- 8 years, with a median duration of illness 12.5 +/- 7.2 years, a median duration of hospitalization 4.2 +/- 4.3 years and a median IQ 82.8 +/- 13.7. E.R.P. Recording. Subjects performed a two-tone auditory discrimination task: they were instructed to count silently infrequent high-pitched tones of 2000 Hz randomly presented within a serie of low-pitched tones of 1000 Hz. E.R.P. were recorded from 16 scalp electrodes (international 10-20 system) referred to nose. The P 3 was defined as the most positive wave between 250 and 500 msec after the stimulus onset. The amplitude was measured referred to the prestimulus baseline; the latency was measured at the point of maximum amplitude. Statistical analysis. The data were submited to a statistical analysis (ANOVA, Student's t-test, Fisher PLSD and Scheffe F-test, Spearman's correlation and linear regression analysis)., Results: 1) The schizophrenic group (N = 19) showed both a significantly prolonged latency and a reduced amplitude, compared to the control group (p < 0.01). 2) In the paranoid subgroup (N = 10), P 3 response was later and smaller than in the control group (p < 0.05). The P 3 latency and amplitude were not significantly different between the two groups of disorganized schizophrenics and controls. 3) A significant correlation between the global score of the S.A.P.S. and the P 3 amplitude was found (r = -0.67). There was no significant correlation between the P 3 parameters and a) the global score of the S.A.N.S. and b) the different items of each evaluation scale. 4) The P 3 amplitude showed a trend toward a negative correlation with the duration of hospitalization. 5) The duration of hospitalization was more important and the global score of the S.A.P.S. was higher in the paranoid than in the disorganized subgroup. There were no significant differences concerning the global score of the S.A. N.S., age, duration of illness, duration of hospitalization, IQ and performances in the detection task between the two subgroups of patients., Discussion: We confirmed the P 3 parameters modifications in schizophrenic patients. The P 3 reduced amplitude and prolonged latency only in the paranoid subgroup, while the disorganized subgroup had both values comparable to those of the controls, is the main finding in our study. Kütcher or Louza studies tend to the same results. Furthermore, we showed that task performances or clinical measures such as age, duration of illness, duration of hospitalization or IQ did not account as biases of P 3 parameters. These results could be a further indication that different subtypes of schizophrenia may have different biological substrates.

Computerized tomography (CT-scan) studies in schizophrenia revealed that some patients have neuromorphological abnormalities. The structural changes consist mainly in lateral and third ventricle enlargement, and in cortical atrophy. The present study evaluates these three changes in 42 schizophrenics aged 18 to 50, compared to 24 healthy controls. Diagnosis were established from information gathered by personal interview with the SADS-LA. Clinical sub-types were evaluated according to the DSM III-R criteria. Moreover, detailed symptoms were rated according to the Positive And Negative Syndrome Scale (PANSS). CT scans were recorded in floppy disks and blindly analyzed. Schizophrenics shown significant higher mean size of lateral and third ventricles, and higher mean anterior cortical atrophy than healthy subjects. Significant differences were also found between subtypes, with more marked abnormalities in the disorganized group. The relationship between brain abnormalities and clinical symptoms recorded with the PANSS, were analysed using Pearson correlates. Positive correlations concerned mainly negative symptoms like blunted affect, emotional withdrawal, difficulties in abstract thinking, passive apathetic social withdrawal and lack of spontaneity of conversation. Positive correlations are also observed with some symptoms classified with the PANSS in the General Psychopathology scale such as mannerism and disorientation. Negative correlation concerned most of PANSS positive symptoms.

Unlabelled: Births of schizophrenics tend to occur more often than expected during the first months of the year. This phenomenon has been repeatedly demonstrated in large samples of patients, but data from France are not yet available. METHOD. Medical records of 2,215 inpatients born in France, have been studied with DSM III-R. Admissions were unduplicated. Inpatient population is described table I. The 230 schizophrenic patients were also classified into three groups according with family history for psychotic diseases (Positive, Negative and Unknown). The year was divided in quarters, but also in two climatic half-years (Cold and Warm). Two different populations were used as controls: first, the live births data in France collected by the INSEE; and second, the 1726 non psychotic inpatients hospitalised in the same unit as the psychotics, during the same period. RESULTS. The season of birth effect can be demonstrated from our sample. When the whole schizophrenic group is compared to the INSEE data, a significant excess of births is found for the winter quarter (p less than .04) and for the cold half-year (p less than .01). In the DSM III-R disorganized patients the seasonal variation becomes significant at a level of p less than .001. The other subtypes of schizophrenia do not show significant seasonal variations (table II). The pattern of birth of the other DSM III-R diagnoses, does not significantly differ from INSEE control data (table III). Schizophrenic patients without psychiatrically ill relatives show a slight, non significant excess of births in winter which become significant for the cold half-year (p less than .03). Subjects with possible family history do not show any trend suggesting a seasonal effect (table IV). DISCUSSION. Few reports include an entire inpatient population as we have done. Such data in our study offers an element of useful comparison with the schizophrenics. Clinic data: Most of seasonal studies have used ICD-8, ICD-9 or Tsuang and Winokur criteria, to compare only paranoid and non paranoid subjects, and some of them found a very small excess of paranoid births in winter. The discrepancies between these studies and ours, can reflect both variability among environmental factors and variability in the diagnostic criteria., Control Data: Most of the subjects were born between 1920 and 1960. All live births in France for the same years could be used as controls, but unfortunately INSEE data were not available by months or quarters before 1949. But since in western and southern European general population, the season of birth appears to be relatively uniform and stable over time, it seemed possible to use the posterior INSEE data to compare with our anterior inpatients data. Familial data: We found a birth excess in the cold season, only for schizophrenics without any family history. This finding is consistent with various other reports. CONCLUSION. In conclusion, our findings are consistent with the suggestion that the season of birth is important in the aetiology of the disorganized subgroup of schizophrenic aetiology of the disorganized subgroups of schizophrenic patients. Moreover, the excess of winter births is only observed in the "negative family history" group.