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Individuals with schizophrenia generally show difficulties in interpersonal communication. Linguistic analyses shed new light on speech atypicalities in schizophrenia. However, very little is known about conversational interaction management by these individuals. Moreover, the relationship between linguistic features, psychopathology, and patients' subjectivity has received limited attention to date. We used a novel methodology to explore dyadic conversations involving 58 participants (29 individuals with schizophrenia and 29 control persons) and medical doctors. High-quality stereo recordings were obtained and used to quantify turn-taking patterns. We investigated psychopathological dimensions and subjective experiences using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Examination of Anomalous Self Experience scale (EASE), the Autism Rating Scale (ARS) and the Abnormal Bodily Phenomena questionnaire (ABPq). Different turn-taking patterns of both patients and interviewers characterised conversations involving individuals with schizophrenia. We observed higher levels of overlap and mutual silence in dialogues with the patients compared to dialogues with control persons. Mutual silence was associated with negative symptom severity; no dialogical feature was correlated with anomalous subjective experiences. Our findings suggest that individuals with schizophrenia display peculiar turn-taking behaviour, thereby enhancing our understanding of interactional coordination in schizophrenia., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Neural information processing is subject to noise and this leads to variability in neural firing and behavior. Schizophrenia has been associated with both more variable motor control and impaired cortical inhibition, which is crucial for excitatory/inhibitory balance in neural commands., Hypothesis: In this study, we hypothesized that impaired intracortical inhibition in motor cortex would contribute to task-related motor noise in schizophrenia., Methods: We measured variability of force and of electromyographic (EMG) activity in upper limb and hand muscles during a visuomotor grip force-tracking paradigm in patients with schizophrenia (N = 25), in unaffected siblings (N = 17) and in healthy control participants (N = 25). Task-dependent primary motor cortex (M1) excitability and inhibition were assessed using transcranial magnetic stimulation (TMS)., Results: During force maintenance patients with schizophrenia showed increased variability in force and EMG, despite similar mean force and EMG magnitudes. Compared to healthy controls, patients with schizophrenia also showed increased M1 excitability and reduced cortical inhibition during grip-force tracking. EMG variability and force variability correlated negatively to cortical inhibition in patients with schizophrenia. EMG variability also correlated positively to negative symptoms. Siblings had similar variability and cortical inhibition compared to controls. Increased EMG and force variability indicate enhanced motor noise in schizophrenia, which relates to reduced motor cortex inhibition., Conclusion: The findings suggest that excessive motor noise in schizophrenia may arise from an imbalance of M1 excitation/inhibition of GABAergic origin. Thus, higher motor noise may provide a useful marker of impaired cortical inhibition in schizophrenia., Competing Interests: Declaration of competing interest The authors declare that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The Pattern study was conducted to provide longitudinal observational data for individual patients with persistent symptoms of schizophrenia. Pattern is an international, multicenter, non-interventional, prospective cohort study of schizophrenia outpatients who were not considered to be in recovery. In the longitudinal phase reported herein, patients were assessed over 1 year using different clinical rating scales. Patient management followed routine local clinical practice. Primary outcome was disease state, defined by the Positive and Negative Syndrome Scale (PANSS), Negative Symptom Factor Score (NSFS), Positive Symptom Factor Score (PSFS), and Personal and Social Performance (PSP) Scale. In total, 1344 protocol-compliant patients (70.9% male) were included. Patients showed a high stability in disease state between consecutive study visits. Persistent negative persistent symptoms and symptomatic remission were the most prevalent and stable disease states. Patients in relapse generally transitioned to negative persistent symptoms or to symptomatic remission. PANSS, PSP, and quality of life ratings remained relatively stable. Relapses occurred in 10% of patients; probability of relapse was associated with younger age, extra-pyramidal symptoms, and more antipsychotic medications. Despite treatment, schizophrenia symptoms tend to remain stable over time, without overall improvement. One of the greatest challenges in schizophrenia is attainment of full symptom remission., (Copyright © 2018. Published by Elsevier B.V.)

Purpose: The objective of this study was to analyze the clinical factors associated with changes in HRQoL in outpatients with schizophrenia using both generic and condition-specific HRQoL scales., Methods: Adult outpatients with schizophrenia at least 18 years of age who did not have an acute psychotic exacerbation in the 3 months prior to baseline were recruited. PANSS dimensions were calculated based on Lindenmayer et al.'s five factors. HRQoL data were assessed by patients using the Schizophrenia Quality of Life Scale (SQLS), the Short Form-36 (SF-36), and the EuroQol-5 Dimension (EQ-5D) questionnaires., Results: Out of the 1345 patients included at baseline, 1196 (89%) were evaluated at 12 months. Regression models showed that the factor most consistently associated with HRQoL at endpoint was change in the PANSS negative symptoms score. A decrease in the PANSS negative symptoms score from baseline to 1 year was associated with a decrease in HRQoL during the same period. There were also significant associations of the change in PANSS excitatory factor with all the HRQoL scales except the SF-36 PCS. Female gender was associated with a decrease in all HRQoL ratings. There was also a relationship between years since onset and HRQoL. The longer the time since illness onset, the larger the decrease in HRQoL., Conclusions: This study has found that, in outpatients with schizophrenia, changes in negative and excitement symptoms may have a greater an association with HRQoL than changes in positive, cognitive and depressive symptoms.

Theory of Mind (ToM) is compromised in schizophrenia, and responsible for social disability. We aim to study the correlation between ToM deficits and Executive Functions (EF), using the Faux Pas Test (FPT) for ToM evaluation, Behavioral Assessment of the Dysexecutive Syndrome (BADS) and Wisconsin Card Sorting Test (WCST) for EF assessment. Two groups of patients with schizophrenia were included: 22 young (18-35 years-old) and 18 middle-aged (>50 years-old) Patients, compared to age-matched Controls. We found worst FPT performances in both groups of patients, but with a more generalized pattern of dysfunction in the middle-aged patient group. This group had worse EF scores than both controls and younger patients. The association of EF with FPT items was uneven. In young patients only empathy (Q6) remained significant after controlling for EF and level of education, while in middle-aged patients faux pas explanation (Q4), false belief (Q5) and total scores remained significant. In young patients only affective TOM was impaired. No correlation was found with clinical symptoms, nor age at onset of the disease. We conclude that ToM deficit arises early during the course of the illness (already present in young patients), increases in middle-aged patients, and relates only partially with EF., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Schizophrenic (SCZ) and autism (ASD) spectrum disorders share several features including social cognition impairments. In SCZ, the link between symptomatic dimensions and social cognition deficits remains unclear. The Movie for the Assessment of Social Cognition (MASC) test, available in several languages including English, investigates mental state attribution capabilities in complex interpersonal situations. After its translation into French, we used MASC to direct compare social cognition in 36 young participants with SCZ to 19 with ASD and 20 healthy controls (HC) matched for gender, age (18-25y.o.) and level of education. The MASC discriminated each group from the others, patients with SCZ exhibiting difficulties compared to ASD (MASC total score 28.1 (4) and 24.2 (6.6), respectively; p<.001). In the whole sample, MASC scores were inversely correlated with autistic traits, evaluated by autism quotient, and with disorganization symptoms. Finally, in SCZ, over-mentalizing difficulties were correlated with age at disease onset. Our results demonstrate the validity of the French version of the MASC and bring direct evidence supporting the hypothesis of a phenotypic continuum between autism and schizophrenia., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Several clinical and radiological markers of early neurodevelopmental deviations have been independently associated with cognitive impairment in patients with schizophrenia. The aim of our study was to test the cumulative and/or interactive effects of these early neurodevelopmental factors on cognitive control (CC) deficit, a core feature of schizophrenia., Methods: We recruited patients with first-episode schizophrenia-spectrum disorders, who underwent structural MRI. We evaluated CC efficiency using the Trail Making Test (TMT). Several markers of early brain development were measured: neurological soft signs (NSS), handedness, sulcal pattern of the anterior cingulate cortex (ACC) and ventricle enlargement., Results: We included 41 patients with schizophrenia in our analysis, which revealed a main effect of ACC morphology ( p = 0.041) as well as interactions between NSS and ACC morphology ( p = 0.005), between NSS and handedness ( p = 0.044) and between ACC morphology and cerebrospinal fluid (CSF) volume ( p = 0.005) on CC measured using the TMT-B score - the TMT-A score., Limitations: No 3- or 4-way interactions were detected between the 4 neurodevelopmental factors. The sample size was clearly adapted to detect main effects and 2-way interactions, but may have limited the statistical power to investigate higher-order interactions. The effects of treatment and illness duration were limited as the study design involved only patients with first-episode psychosis., Conclusion: To our knowledge, our study provides the first evidence of cumulative and interactive effects of different neurodevelopmental markers on CC efficiency in patients with schizophrenia. Such findings, in line with the neurodevelopmental model of schizophrenia, support the notion that CC impairments in patients with schizophrenia may be the final common pathway of several early neurodevelopmental mechanisms.

Objective: We examined Theory of Mind (ToM) abilities in adolescents with early-onset schizophrenia (EOS) and their correlation with clinical findings and Executive Functions (EF)., Methods: The ToM abilities of 12 adolescents with EOS were compared with those of healthy participants matched in age and educational level. The Moving Shapes Paradigm was used to explore ToM abilities in three modalities: random movement, goal-directed movement and ToM - scored on the dimensions of intentionality, appropriateness and length of each answer. EF was tested using Davidson's Battery and the clinical psychopathology with the Positive and Negative Syndrome Scale (PANSS)., Results: Adolescents with EOS were significantly more impaired than controls in the three dimensions evaluated for the goal-directed and ToM modalities. Regarding the random movement modality, the only difference was in appropriateness (p<0.01). No correlation with age or level of education was evident for ToM skills. Total PANSS score was negatively correlated with appropriateness score for the goal-directed (p=0.02) and ToM modalities (p=0.01). No correlation existed between performance in the ToM Animated Tasks and positive, negative or disorganisation PANSS subscores. No correlations were found among the three scores in the Moving Shapes Paradigm and any measures of the accuracy of the three tasks assessing EF., Conclusion: Our results confirm previous findings of ToM deficits in adult individuals with schizophrenia and attest the severity of these deficits in patients with EOS.

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.)

Background: The high societal burden of schizophrenia is largely caused by the persistence of symptoms and accompanying functional impairment. To date, no studies have specifically assessed the course of persistent symptoms or the individual contributions of positive and negative symptoms to patient functioning. The cross-sectional analysis of the Pattern study provides an international perspective of the burden of schizophrenia., Methods: Clinically stable outpatients from 140 study centers across eight countries (Argentina, Brazil, Canada, France, Germany, Italy, Spain and the United Kingdom) were assessed using clinical rating scales: Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia (CGI-SCH) Scale and the Personal and Social Performance (PSP) Scale. Additional measures included patient-reported outcomes, patient socio-demographic variables, living situation, employment and resource use., Results: Overall, 1379 patients were assessed and analyzed and had similar sociodemographic characteristics across countries, with 61.6% having persistent positive and/or negative symptoms. Positive and negative symptoms had been persistent for a mean of 9.6 and 8.9 years (SD: 8.8 and 9.6), respectively. Approximately 86% of patients had a functional disability classified as greater than mild. Patients with a higher PANSS Negative Symptom Factor Score were more likely to have a poorer level of functioning., Conclusions: This analysis examines individual contributions of persistent positive and negative symptoms on patient functioning in different countries. A high prevalence of patients with persistent symptoms and functional impairment was a consistent finding across countries. Longitudinal observations are necessary to assess how to improve persistent symptoms of schizophrenia and overall patient functioning., (Copyright © 2015 Elsevier B.V. All rights reserved.)

This article aims to present the validation study of the French version of the Comprehensive Assessment of at risk mental states (CAARMS), an interview that seeks to determine whether young adults criteria for at-risk (AR) mental states, or psychosis. We assessed 40 young subjects, 15 were considered as "prodromal" (Prd) and 10 as experiencing a first episode of psychosis (PEP) by our expert clinician at the center - centre d'évaluation des jeunes adultes et adolescents, University Hospital Centre, Paris - and 15 were healthy controls matched for age and sex. When assessed with the CAARMS, 73 % (n=11) of the prodromal subjects reached the criteria for AR mental state, four subjects did not reach the criteria for AR, nor psychosis (P) and 100 % of the PEP reached the criteria for P. The three groups were significantly different on CAARMS total score (P<0.001) and subscores ; Prd subjects had intermediate scores between PEP (P<0.001) and controls (P<0.001) scores, PEP showing the highest scores. Post-hoc analysis showed that Prd significantly differed from Controls on each subscale (P<0.001) and that Prd differed from PEP on the "positive symptoms" subscale (P<0.001), as well as on "behavioural change" (P=0.021), owing to difference on the item "impaired role function". We used the brief psychiatric rating scale 24 items with anchor (BPRS24-EA) in addition to with the CAARMS, the AR group showed intermediate scores between controls and P subjects. Total scores of both scales were correlated (r=0.408 ; P=0.043) and the BPRS24-EA "positive symptoms" score was correlated with CAARMS' scores on the "Positive symptoms" subscale (r=0.456, P=0.022), "emotional disturbance" (r=0.506, P=0.01), and "behavioural change" (r=0.666 P=0.001). We found no correlation between BPRS negative and depression subscales and any of the CAARMS' subscales. When looking at its reliability, reliability coefficients (Cronbach's alpha) showed excellent reliability for "positive symptoms", "emotional disturbance", "behavioural change" and "general psychopathology" (respectively r=0.82, 0.75, 0.78, 0.84, 0.83) and moderate reliability for "cognitive change", "negative symptoms" and "motor/physical change" (respectively r=0.39, 0.59, 0.43). Overall, analysis of the results of construct validity, concurrent validity and reliability of the CAARMS indicates that the French version is valid and reliable. It is now available to develop and implement early detection programs in French speaking countries., (Copyright © 2014. Published by Elsevier Masson SAS.)

Background: Schizophrenia is a frequent and disabling disease associated with heterogeneous psychiatric phenotypes. It emerges during childhood, adolescence or young adulthood and has dramatic consequences for the affected individuals, causing considerable familial and social burden, as well as increasing health expenses. Although some progress has been made in the understanding of their physiopathology, many questions remain unsolved, and the disease is still poorly understood. The prevailing hypothesis regarding psychotic disorders proposes that a combination of genetic and/or environmental factors, during critical periods of brain development increases the risk for these illnesses. Epigenetic regulations, such as DNA methylation, can mediate gene x environment interactions at the level of the genome and may provide a potential substrate to explain the variability in symptom severity and family heritability. Initially, epigenetics was used to design mitotic and meiotic changes in gene transcription that could not be attributed to genetic mutations. It referred later to changes in the epigenome not transmitted through the germline. Thus, epigenetics refers to a wide range of molecular mechanisms including DNA methylation of cytosine residues in CpG dinucleotides and post-translational histone modifications. These mechanisms alter the way the transcriptional factors bind the DNA, modulating its expression. Prenatal and postnatal environmental factors may affect these epigenetics factors, having responsability in long-term DNA transcription, and influencing the development of psychiatric disorders., Object: The object of this review is to present the state of knowledge in epigenetics of schizophrenia, outlining the most recent findings in the matter., Methods: We did so using Pubmed, researching words such as 'epigenetics', 'epigenetic', 'schizophrenia', 'psychosis', 'psychiatric'. This review summarizes evidences mostly for two epigenetic mechanisms: DNA methylation and post-translational histone modifications., Results: First, in terms of epidemiology and transmission, the theoretical model of epigenetics applies to schizophrenia. Then, most environmental factors that have proved a link with this disease, may generate epigenetic mechanisms. Next, mutations have been found in regions implied in epigenetic mechanism among populations with schizophrenia. Some epigenetic alterations in DNA regions have been previously linked with neurodevelopmental abnormalities. In psychosis, some authors have found methylation differences in COMT gene, in reelin gene and in some genes implicated in dopaminergic, serotoninergic, GABAergic and glutamatergic pathways. Histone modifications have been described, in particular the H3L4 histone methylation. Finally, we tried to underline the difficulties in epigenetic research, notably in psychiatry, and the limits in this matter., Conclusion: The epigenetic field may explain a lot of questions around the physiopathology of the complex psychiatric disease that is schizophrenia. It may be a substratum to the prevailing hypothesis of gene x environment interaction. The research in the matter is definitely expanding. It justifies easily the need to improve the effort in the domain to overpass some limits inherent to the matter., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Cognitive deficits are of fundamental importance to the clinical picture of schizophrenia and are on the verge to be included as diagnostic criteria in the DSM-V. While focusing on information processing deficits, no emphasis has been put on whether patients' deficits can be accounted for by maladaptive information acquisition strategy deployment., Methods: We tested 24 stabilized patients with schizophrenia and 25 matched controls in a visuo-spatial analogy task with graded difficulty. Eye movement recordings served to identify information acquisition strategies., Results: Patients compared to healthy controls showed slower reaction times in the easiest condition and higher error rates in the more difficult conditions. Eye movement recordings illustrated that overall mean fixation duration increased with increasing task difficulty in healthy controls only. Further, patients deployed a more efficient strategy ("constructive matching") less often than healthy controls in the easier conditions., Conclusions: These results suggest that information acquisition strategies mediate visuo-spatial cognitive performance in schizophrenia. Patients adopt a less efficient strategy independently of task difficulty indicated by a characteristic behavioural pattern. Our results point to a powerful tool of improving patients' performance in cognitively demanding tasks by training them in more flexible cognitive (e.g., information acquisition) strategy deployment.

Three common missense variants of the Disrupted in Schizophrenia 1 (DISC1) gene, rs3738401 (Q264R), rs6675281 (L607F) and rs821616 (S704C), have been variably associated with the risk of schizophrenia. In a case-control study, we examine whether these gene variants are associated with schizophrenia and ultra-resistant schizophrenia (URS) in a population of French Caucasian patients. The URS phenotype is characterized according to stringent criteria as patients who experience no clinical, social and/or occupational remission in spite of treatment with clozapine and at least two periods of treatment with distinct conventional or atypical antipsychotic drugs. We find a significant association between DISC1 missense variants and URS. The association with rs3738401 remains significant after appropriate correction for multiple testing. These results suggest that the DISC1 rs3738401 missense variant is statistically linked with ultra-resistance to antipsychotic treatment.

There is now compelling evidence that cannabis consumption might precipitate psychosis onset. The objective of the present study was to assess the role of individual sensitivity to the psychotogenic effect of cannabis in male patients with schizophrenia. The lifetime diagnosis, disease and substance-use history were determined using a standardized interview in 190 patients with schizophrenia. Of patients with lifetime cannabis use (n=121), 44 were characterized as Cannabis-sensitive (CS) patients if the onset of psychotic symptoms occurred within 1 month following the initiation of cannabis consumption, or following a marked rise of cannabis consumption, or marked aggravation of psychotic symptoms each time the subject used cannabis. Age at onset of psychosis was not different in patients with lifetime cannabis use compared to non-users. By contrast, the first psychotic episode occurred 2.6 yr earlier in CS compared to Non-cannabis-sensitive (NCS) patients (p=0.006). Moreover, a specific excess of family history of psychotic disorder was found in CS patients, but not of any other psychiatric disorder, as well as an earlier age at exposure to cannabis (16.7+/-2.5 yr, p=0.03). Sensitivity to psychotogenic effects of cannabis in schizophrenia patients could be related to both genetic vulnerability to schizophrenia and the influence of cannabis on brain maturation and could modulate the influence of cannabis on the onset of schizophrenia.

Psychotic symptoms in schizophrenia patients encompass the difficulty to distinguish between the respective points of view of self and others. The capacity to adopt and switch between different perspectives is, however, fundamental for ego- and allocentric spatial referencing. We tested whether schizophrenia patients are able to adopt and maintain a non-egocentric point of view in a complex visual environment. Twenty-four chronic schizophrenic outpatients (11 females) and 25 controls matched for age, gender, years of education and handedness were recruited from a population-based sample. In a virtual environment, participants had to make a decision as to which of two trash cans was closest to themselves (viewer-centered, egocentric), to a ball (object-centered, unstable allocentric), or to a palace (landmark-centered, stable allocentric). Main outcome measures were reaction time, error rate, learning rate and local task switch cost. While egocentric reaction time was preserved, patients showed an increased reaction time in both allocentric referencing conditions (stable and unstable) and an overall increased error rate. Switch cost was diminished in patients when changing from the egocentric to the landmark-centered condition and elevated when changing from the landmark-centered to the egocentric condition. The results imply that schizophrenia patients' adoption of an egocentric perspective is preserved. However, adopting an allocentric point of view and switching between egocentric and landmark-centered perspectives are impaired. Perturbations in non-egocentric referencing and transferring efficiently between different referential systems might contribute to altered personal and social world comprehension in schizophrenia., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Visual orienting tasks reveal an impaired disengagement of attention in schizophrenia. We explored visual orientation in 20 schizophrenia patients (SZ), 20 full siblings (FS), and 20 controls (C) using a cued target detection (gap vs. no gap) and a choice reaction time task. SZ but not FS had longer reaction time with comparable reactions to warning. In contrast to C, SZ and FS did not display a significant gap effect. The disengagement deficit in schizophrenia patients and their siblings provides arguments for altered early attention mechanisms (in schizophrenic patients and their nonpsychotic relatives).

The objectives were to determine the neurological soft signs (NSS) scores in unaffected siblings of patients with schizophrenia compared with healthy controls and to examine their relationships with schizotypal dimensions. Participants comprised 31 unaffected siblings of patients with schizophrenia and 60 healthy controls matched according to age, gender and school level who were assessed by the Schizotypal Personality Questionnaire (SPQ) and the Krebs et al. NSS Scale. Higher NSS total scores and sub-scores were found in the unaffected siblings compared with the controls. The SPQ total score was significantly higher in unaffected siblings compared with control subjects. The NSS total score was positively correlated with the SPQ total score and the SPQ disorganization sub-score in unaffected siblings of patients with schizophrenia. Additionally, in unaffected siblings, motor coordination and integration abnormalities were positively correlated with the SPQ total score and the cognitive-perceptual sub-score. Motor integration abnormalities were also correlated with the SPQ disorganization sub-score. These results reveal that NSS, especially motor signs, are associated with some schizotypal dimensions in siblings of patients with schizophrenia, suggesting the value of using both assessments to study high risk populations.

Investigations of memory impairment in schizophrenia have frequently revealed a strategic processing deficit at encoding. The authors studied an early encoding process, refreshing (in this case, thinking of a stimulus that has just-previously been presented), and its impact on recognition memory in schizophrenia. Following simultaneous presentation of three words or a single word in the top, middle, or bottom position of the screen, 25 patients with schizophrenia and 25 control participants saw and read a new word (read condition), or a word presented on the previous screen (repeat condition), or saw a dot indicating that they should think of and say the last word to have appeared in that position (refresh condition). Later, on a surprise test, participants were asked to recognize words seen previously and give a Remember, Know, or Guess response according to whether they recognized each on the basis of conscious recollection, familiarity, or guessing. The cognitive operation of refreshing was impaired in schizophrenia: patients were slower on 1-word trials and less accurate on 3-word trials to refresh a word, and their Remember responses did not benefit from refreshing., (Copyright 2009 APA, all rights reserved.)

Objective: Neurological Soft Signs (NSS) and impairments in oculomotor saccadic paradigms are both frequent in patients with schizophrenia but their correlation has never been explored., Methods: 78 patients with DSM-IV schizophrenia (including 43 non-treated) and 41 matched healthy controls were tested for NSS, and on three saccadic tasks: prosaccades, predictive saccades and memory-guided saccades) using infrared oculometry. We analyzed correlations between NSS scores and latencies in all three tasks, rate of errors in memory-guided saccades, and rate of anticipated predictive saccades., Results: No correlations were found in healthy controls. In the patient group, the NSS total and motor coordination scores were positively correlated with three saccadic variables: the latency of prosaccades (r=0.36, p<0.01 and r=0.36, p<0.01 respectively), of memory-guided saccades (r=0.35, p<0.01 and r=0.32, p<0.05 respectively) and, negative correlations were found, with the rate of anticipated predictive saccades (r=-0.33, p<0.01; r=-0.35, p<0.01 respectively). NSS total, motor coordination and sensory integration scores were correlated to the latency of non-anticipated predictive saccades (r=0.34, p<0.01; r=0.24, p<0.05 and r=0.40, p<0.001 respectively). The NSS total, motor integration and sensory integration scores were correlated with the rate of errors in memory-guided saccades (r=0.38, p<0.01; r=0.37, p<0.01 and r=0.34, p<0.01 respectively)., Conclusions: These results support a common pathological mechanism with partial overlapping neural substrates between NSS and saccades in schizophrenia.

Background: Ocular-motor inhibition errors and saccadic hypometria occur at elevated rates in biological relatives of schizophrenic patients. The memory-guided saccade (MS) paradigm requires a subject to inhibit reflexive saccades (RSs) and to programme a delayed saccade towards a remembered target., Method: MS, RS, and central fixation (CF) tasks were administered to 16 patients who met the criteria for DSM-IV schizophrenia, 19 of their psychiatrically healthy siblings, and 18 controls., Results: Patients and siblings showed elevated MS error rates reflecting a failure to inhibit RSs to a visible target, as required by the task. In contrast to controls, prior errors did not improve MS accuracy in patients and siblings., Conclusions: The specific characteristics of the elevated MS error rate help to clarify the nature of the disinhibition impairment found in schizophrenics and their healthy siblings. Failure to inhibit premature saccades and to improve the accuracy of subsequent volitional saccades implicates a deficit in spatial working-memory integration, mental representation and/or motor learning processes in schizophrenia.

Among the second generation antipsychotics, aripiprazole presents a new pharmacological profile, basically differentiated by a partial agonist effect on the D2 and D3 dopaminergic receptors. Five short-term efficacy studies, conducted on 1648 patients presenting with schizophrenia or acute relapse of schizoaffective disorders, demonstrated the greater efficacy of aripiprazole than the placebo and comparable efficacy to that of haloperidol and risperidone. The short-term tolerance profile was characterised by a lesser incidence of the extrapyramidal side effects and drowsiness than with haloperidol. Two thousand six hundred and eighty five patients were followed-up over a period of 26 to 52 weeks in five clinical trials versus a placebo and haloperidol, olanzapine, quetiapine and risperiodone: demonstrated efficacy in maintaining the response to treatment and on the delay before relapse was comparable to the other antipsychotics. The classical side effects of antipsychotics decreased in the long-term. Versus olanzapine, a glucid and lipid profile, clearly in favour of aripiprazole, was completed by a lesser incidence of hyperprolactinaemia. Aripiprazole is effective on all the dimensions of schizophrenia: the positive and negative and depressive and anxious symptomatology. It appears to be of interest, notably on the cognitive dimension, which should motivate more in-depth exploration of its place in the treatment in the early stages of schizophrenia. Its therapeutic schedule and the methods of initiation are an essential criterion to the success of treatment, notably during the substitution of other antipsychotics. The clinical and pharmacological originality of aripiprazole would justify the terminology of a "third generation antipsychotic".

The role of personality in nicotine use has been little studied in patients with schizophrenia. The objectives of the present study were to compare impulsivity, sensation seeking and anhedonia in a group of schizophrenic patients with and without current cigarette smoking. One hundred patients with schizophrenia or schizoaffective disorder (DSM-III-R criteria) were assessed with the Positive and Negative Syndrome Scale, the Fagerström Scale, the Barratt Impulsivity Scale, the Zuckerman Seeking Sensation Scale, and the Chapman Physical Anhedonia Scale. Among these patients, 67% were current smokers. The mean scores for sensation seeking were higher in the group of smokers than in the group of nonsmokers. The differences were found exclusively with the "disinhibition" subscale. No significant difference was found for impulsivity and physical anhedonia mean scores. The scores on the Sensation Seeking Scale were especially low in nonsmokers. Cigarette smoking could influence disinhibition and possibly help to normalize inhibition in schizophrenic patients.

It has been shown that schizophrenic patients treated with conventional neuroleptics display a general slowness in latency in simple reaction-time tasks and a disengagement deficit in visual-orienting tasks. Yet, the influence of atypical neuroleptics on attention is still controversial. The purpose of our study was to investigate the effect of atypical neuroleptics in tasks requiring alertness, selective attention or visual orienting. Thirteen stabilized schizophrenic patients receiving atypical neuroleptics were compared to 13 healthy controls matched for age, gender, and study level, in a choice reaction time (CRT) task and a visual-orienting task cued target detection (CTD) task. The results showed that patients and controls obtained comparable reaction times (RTs) in the CRT task. In the CTD task, both groups had comparable RTs but the presence of invalid cues caused a greater attentional cost in both visual fields for patients compared to controls, indicating a symmetrical disengagement deficit. To conclude, patients treated with atypical neuroleptics had a phasic alertness ability similar to controls. By contrast, an impairment of disengagement was present in those patients. Thus, atypical neuroleptics could have a positive influence on certain but not all attentional domains.

Since reports have underscored that panic attacks (PA) may be an identifiable state occurring in schizophrenia, we studied the symptomatology of PA in a group of schizophrenic patients. Of 40 patients (21 males and 19 females) attending a clinic for maintenance therapy of schizophrenia, 19 (36.8%) had a lifetime history of PA. Seven among those 19 patients (36.8%) had or had had spontaneous panic attacks, not related to phobic fears or delusional fears, and for the 12 remaining patients, the PA were related to paranoid ideas. Moreover, the paranoid subtype of schizophrenia tends to be more often associated with a history of panic attack than other subtypes of schizophrenia (52.6% vs 23.8%; chi2 = 3.5, P =.06). It seems that there are at least two types of PA in schizophrenic patients. The first one could be independent from the psychotic feature, with no psychopathological link. The second kind of PA could be directly related to a schizophrenic disorder, and found in patients with the paranoid subtype.

Objective: The authors compared impulsivity, sensation seeking, and anhedonia in a group of schizophrenic patients with and without lifetime substance abuse or dependence., Method: Patients (N=100) with schizophrenia or schizoaffective disorder (per DSM-III-R criteria) were assessed with the Composite International Diagnostic Interview's section on psychoactive substance use disorder, the Positive and Negative Syndrome Scale, the Barratt Impulsivity Scale, the Zuckerman Seeking Sensation Scale, and the Chapman Physical Anhedonia Scale., Results: The mean scores for impulsivity and sensation seeking were higher in the group with substance abuse (N=41) than in the group without substance abuse (N=59). No significant difference between groups was found regarding physical anhedonia., Conclusions: As in the general population, high levels of impulsivity and sensation seeking are associated with substance abuse in patients with schizophrenia.

Eye movement anomalies are more frequent in schizophrenic patients than in healthy subjects. This study deals with visually guided saccadic eye movements in seventeen schizophrenic patients [ten untreated (neuroleptic-naive or free), seven treated patients] and their correlations between symptoms presented by patients and oculomotor performances. There was no significant difference between the patients and the control group in visually guided saccades tasks. However, negative correlations between oculomotor performance and positive or disorganisation symptomatology were found. Thus, although no major oculomotor dysfunction in response to external stimulus was seen in schizophrenic patients, some symptoms were linked to oculomotor performance impairment. Thus psychiatric symptoms might share some common cerebral circuits which those involved in oculomotor tasks.

The deficit forms of schizophrenia have given rise to important research and controversy for the last 15 years. It is now recognized that some negative symptoms in schizophrenia are part of a pure and primary deficit syndrome which could be related to decreased dopaminergic function and which is not well improved by standard antipsychotic drugs. Amisulpride is a substituted benzamide neuroleptic with an original pharmacologic profile. Prescription of high doses (600-1 200 mg/day) yields to an usual antipsychotic activity on positive symptoms, through the blockage of post-synaptic dopamine receptors. At low doses, amisulpride preferentially blocks presynaptic dopamine autoreceptors, with a poor affinity for striatal sites. Three recent double-blind placebo controlled studies have suggested an efficacy of low doses (50-300 mg/day) of amisulpride in deficit forms of schizophrenia. The first study was carried out in young never-treated schizophrenic patients, and showed a significant improvement of negative symptoms with a 6-week amisulpride treatment. In the second study, subjects with a long-course deficit schizophrenia were included after a 6-week wash-out period. Reduction of scores of negative symptoms (Andreasen's scale) was about twice as important in the amisulpride group compared to the placebo group, whereas positive symptoms, modest at inclusion, remained unchanged. Finally, the efficacy of amisulpride was shown in another double-blind long-term study over 6 months in patients with predominantly negative symptoms. The overall safety profile of amisulpride in these studies was good, in particular with a low incidence of extrapyramidal symptoms. Thus, amisulpride at low doses appeared to be a well tolerated treatment for various deficit forms of schizophrenia, with a short-term and long-term efficacy.

The neurological effects of neuroleptic drugs are well known from the very beginning of their history and are even part of the initial definition of this therapeutic class. However, these effects are not necessary for an antipsychotic efficacy as demonstrated by the fully effective "atypical" neuroleptics, which induce minimal neurological side-effects. The neurobiological mechanisms underlying this "atypicity" are not well elucidated but could involve a preferential action on mesocorticolimbic dopaminergic system. This preferential action on mesocorticolimbic dopaminergic system. This specificity of action seem especially interesting in the case of patients suffering of severe tardive dyskinesia. Hence, the absence of rebond of preexistent dyskinesia when stopping a long term treatment with clozapine suggest that the pursuit of neuroleptic with this substance in dyskinetic patients would not worsen the long term prognosis of their dyskinesia. Available data on other atypical neuroleptics are insufficient to conclude if this benefit action on tardive dyskinesia is specific of clozapine or shared with other new neuroleptics.