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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.)

International studies measuring wellbeing/multidimensional mental health before/ during the COVID-19 pandemic, including representative samples for >2 years, identifying risk groups and coping strategies are lacking. COH-FIT is an online, international, anonymous survey measuring changes in well-being (WHO-5) and a composite psychopathology P-score, and their associations with COVID-19 deaths/restrictions, 12 a-priori defined risk individual/cumulative factors, and coping strategies during COVID-19 pandemic (26/04/2020-26/06/2022) in 30 languages (representative, weighted non-representative, adults). T-test, χ 2 , penalized cubic splines, linear regression, correlation analyses were conducted. Analyzing 121,066/142,364 initiated surveys, WHO-5/P-score worsened intra-pandemic by 11.1±21.1/13.2±17.9 points (effect size d=0.50/0.60) (comparable results in representative/weighted non-probability samples). Persons with WHO-5 scores indicative of depression screening (<50, 13% to 32%) and major depression (<29, 3% to 12%) significantly increased. WHO-5 worsened from those with mental disorders, female sex, COVID-19-related loss, low-income country location, physical disorders, healthcare worker occupations, large city location, COVID-19 infection, unemployment, first-generation immigration, to age=18-29 with a cumulative effect. Similar findings emerged for P-score. Changes were significantly but minimally related to COVID-19 deaths, returning to near-pre-pandemic values after >2 years. The most subjectively effective coping strategies were exercise and walking, internet use, social contacts. Identified risk groups, coping strategies and outcome trajectories can inform global public health strategies., Competing Interests: Declaration of competing interest Conflict of interest statements of all authors are detailed in eTable 8., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology "P-score"., Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed., Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex., Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health., Competing Interests: Conflict of interest Conflict of interest statements of all authors are detailed in Supplementary Table 7., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed., Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others., Results: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of ≥1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged ≥65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive., Limitations: . Cross-sectional survey, preponderance of non-representative participants., Conclusions: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics., (Copyright © 2021. Published by Elsevier B.V.)

Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial., Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www.coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via non-probability/snowball and representative sampling and assessed via self-rating and parental rating. Non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co-primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life., Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COH-FIT project, with representative samples from eleven countries., Limitations: Cross-sectional and anonymous design., Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on children's, adolescents' and families', mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Primary prevention has the potential to modify the course of depression, but the consistency and magnitude of this effect are currently undetermined., Methods: PRISMA and RIGHT compliant (PROSPERO:CRD42020179659) systematic meta-review, PubMed/Web of Science, up to June 2020. Meta-analyses of controlled interventions for the primary prevention of depressive symptoms [effect measures: standardized mean difference (SMD)] or depressive disorders [effect measure: relative risk (RR)] were carried out. Results were stratified by: (i) age range; (ii) target population (general and/or at-risk); (iii) intervention type. Quality (assessed with AMSTAR/AMSTAR-PLUS content) and credibility (graded as high/moderate/low) were assessed. USPSTF grading system was used for recommendations., Results: Forty-six meta-analyses (k=928 individual studies, n=286,429 individuals, mean age=22.4 years, 81.1% female) were included. Effect sizes were: SMD=0.08-0.53; for depressive symptoms; RR=0.90-0.28 for depressive disorders. Sensitivity analyses including only RCTs did not impact the findings. AMSTAR median=9 (IQR=8-9); AMSTAR-PLUS content median=4.25 (IQR=4-5). Credibility of the evidence was insufficient/low in 43 (93.5%) meta-analyses, moderate in two (4.3%), and high in one (2.2%): reduction of depressive symptoms using psychosocial interventions for young adults only, and a combination of psychological and educational interventions in primary care had moderate credibility; preventive administration of selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in individuals with a stroke had high credibility., Limitations: Intervention heterogeneity and lack of long-term efficacy evaluation., Conclusions: Primary preventive interventions for depression might be effective. Among them, clinicians may offer SSRIs post-stroke to prevent depressive disorders, and psychosocial interventions for children/adolescents/young adults with risk factors or during the prenatal/perinatal period., (Copyright © 2021. Published by Elsevier B.V.)

Treatment-Resistant Schizophrenia (TRS) and Non-Treatment-Resistant Schizophrenia (NTRS) may represent different subtypes of schizophrenia. However, few studies have investigated their PANSS symptom dimensions by Exploratory (EFA) or Confirmatory (CFA). Data from the present study are derived from 1429 patients of the Pattern study. TRS was defined by the use of clozapine in the previous year whereas NTRS by the use of non-clozapine antipsychotics ("by proxy"). Factors were chosen based on the Kaiser criterion and considered valid when loadings were greater than or equal to 0.5. The fit to the data was evaluated by CFA in comparison with well-established PANSS models, using fit indexes. The EFA yielded similar five-factor model in both groups: Negative, Positive, Anxiety/Depression, Cognitive and Excited. CFA showed a satisfactory, but not perfect, fit to the data, as compared with the previous PANSS factor analytic models. Despite the limitations regarding the 'by proxy' definition of TRS, the results of the present study show that there are no differences in the factorial structure of PANSS in patients with TRS and NTRS., (Copyright © 2019. Published by Elsevier B.V.)

Olanzapine long-acting injections (OLAIs) are often prescribed to patients with severe schizophrenia who are typically excluded from randomized clinical trials. To date, no mirror-image study has examined the impact of OLAIs on healthcare resource utilizations in these patients. We conducted a retrospective, one-year mirror-image study of OLAIs on 40 patients with severe schizophrenic disorder. Illness severity was defined by failure to respond to two sequential antipsychotics. Outcomes included: (i) healthcare resource utilizations via hospitalization admissions, bed days, outpatient visits, and inpatient service costs computations (ii) clinical efficacy through changes in the Brief Psychiatric Rating Scale (BPRS) and in the Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and (iii) adverse effects. After one year, OLAIs were associated with significant decreases of 65.7%, 86.2% and 86.2% in hospitalization admissions, bed days, and inpatient service costs respectively. A significant mean change of -0.47 and -0.63 was determined the BPRS and the CGI-SCH scores, respectively. There were no significant differences in the number of outpatient visits and adverse effects, except for post-injection sedation/delirium syndrome whose incidence was 0.30% per injection. This mirror-image study provides the first evidence that prescribing OLAIs reduces in a cost-effective manner average bed days and hospital admissions in patients with severe schizophrenia., (Copyright © 2018. Published by Elsevier B.V.)

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.)

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.)

Alterations in eye tracking and motor impairments as well as Neurological Soft Signs (NSS) are frequently reported in patients with schizophrenia as well as in their relatives, and are proposed as endophenotype of the disease. This study investigated smooth pursuit eye movement and fixation task with distractors with a gap condition, two markers of inhibitory control mechanism, in 49 patients with schizophrenia, 24 ultra-high risk subjects, 41 full biological clinical siblings of patients and 48 controls. NSS were assessed as a marker of abnormal neurodevelopment. The results revealed more intrusive saccades respectively in smooth pursuit eye movement and in fixation task with distractors with a gap condition in patients, respect to controls and full siblings. Ultra high-risk participants with high NSS committed intrusive saccades compared to controls. Patients with schizophrenia with high NSS also displayed more of these abnormalities, compared to patients with schizophrenia with low NSS and controls. These findings highlight a global inhibitory control defect, and suggested that ultra-high risk subjects and patients with schizophrenia could share oculomotor abnormalities, especially when they express a high neurodevelopmental deviance. These oculomotor alterations might suggest that cerebral structures such as prefrontal and cerebellum could be involved in the expression of this vulnerability., (Copyright © 2017. Published by Elsevier B.V.)

Anomalous activations of the prefrontal cortex (PFC) and posterior cerebral areas have been reported in previous studies of working memory in schizophrenia. Several interpretations have been reported: e.g., neural inefficiency, the use of different strategies and differences in the functional organization of the cerebral cortex. To better understand these abnormal activations, we investigated the cerebral bases of a working memory component process, namely refreshing (i.e., thinking briefly of a just-activated representation). Fifteen patients with schizophrenia and 15 control subjects participated in this functional magnetic resonance imaging (fMRI) study. Participants were told that whenever they saw a word on the screen, they had to read it silently to themselves (read and repeat conditions), and when they saw a dot, they had to think of the just-previous word (refresh condition). The refresh condition (in comparison with the read condition) was associated with significantly increased activation in the left inferior frontal gyrus and significantly decreased connectivity within the prefrontal cortex and between the prefrontal and parietal cortices in patients with schizophrenia in comparison with control subjects. These results suggest that prefrontal dysfunctions in schizophrenia might be related to a defective ability to initiate (rather than to execute) specific cognitive processes., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Many motor and cognitive alterations in schizophrenia suggest the involvement of the cerebellum. Neurological soft signs (NSS) are frequent in patients with schizophrenia and reductions in cerebellar volume have been associated with high NSS scores. In this study, we tested saccadic adaptation, a well-characterised oculomotor paradigm involving the cerebellum, in schizophrenic patients with high NSS scores. We used a backward reactive saccade adaptation task, in which the target moves intrasaccadically toward initial fixation, causing the saccade to complete with an endpoint error. A group of 12 schizophrenic patients (SZ; DSM IV) with high NSS scores was compared to a group of 13 matched healthy controls (HC). SZ patients showed lower saccade adaptation than HC. Nevertheless, the time course of adaptation was similar for both groups. This study indicates cerebellar dysfunction in patients with schizophrenia and high NSS scores. Part of the deficit seen in schizophrenia may have a cerebellar origin., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Numerous reports have emphasized the value of neurological soft signs (NSS) as endophenotypic markers in schizophrenia. NSS also appear as useful prognostic predictors for functional outcome, response and tolerance to antipsychotics. Although several standardized scales have been proposed and offer fair inter-rater reliability, they still rely on the experience and accuracy of the investigators. This study was designed to assess NSS objectively. We evaluated 27 patients who met the Diagnostic and Statistical Manual, fourth edition (DSM-IV) criteria for schizophrenia and 15 healthy controls using a standardized examination encompassing a 23-item NSS scale as well as an assessment of parkinsonism and dyskinesia. Movements were then recorded using inertia sensors while the patients were performing a selection of motor items from the aforementioned scale (balance tasks, rapid alternative movements, rigidity). To our knowledge, this study is the first to provide an objective assessment of specific NSS in schizophrenia using inertial sensors. The results objectively demonstrate impairments in patients with schizophrenia when balance relies on proprioceptive information, with specific differences in groups of patients based on their NSS scores. Inertia sensors are promising, inexpensive and 'easy-to-use' tools that could improve the assessment of motor and sensory impairments in patients with schizophrenia in daily clinical practice, especially when the dysfunction is subtle., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

Background: Suicide behavior is very frequent in Bipolar Disorder (BD) and they are both closely associated with impulsivity. Furthermore they are, impulsivity, BD and suicide behavior, associated with serotonergic function, at least partially, under genetic determinism and somewhat associated with the serotonin transporter gene polymorphism, the 5-HTTLPR. We aimed to assess different impulsivity components in BD sub-grouped by suicidal attempt and healthy controls. We hypothesized that the non-planning/cognitive impulsivity, could be more closely associated with suicidal behavior. We further associated 5-HTTLPR genotypes with neuropsychological results to test the hypothesis that this polymorphism is associated with cognitive impulsivity., Method: We assessed 95 euthymic bipolar patients sub-grouped by suicidal attempt history in comparison with 94 healthy controls. All subjects underwent a laboratory assessment of impulsivity (Continuous Performance Test and Iowa Gambling Test). Furthermore the genotyping of 5-HTTLPR was performed in all subjects., Results: We found that bipolar patients are more impulsive than healthy controls in all impulsivity dimensions we studied. Furthermore bipolar patients with a suicide attempt history have a greater cognitive impulsivity when compared to both bipolar patients without such a history as well when compared to healthy controls. No association was found between 5-HTTLPR genotypes and neuropsychological measures of impulsive behavior., Limitations: The sample studied can be considered small and a potentially confounding variable - medication status - was not controlled., Conclusion: A lifetime suicide attempt seems associated with cognitive impulsivity independently of the socio-demographic and clinical variables studied as well with 5-HTTLPR genotype. Further studies in larger samples are necessary., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Bipolar disorder (BD) is a complex disorder where genetic factors play a major role in its etiology. Probably, no other axis I diagnosis has a co-morbidity prevalence as high as BD. Since BDNF is involved in different ways in various psychiatric disorders we hypothesized that its genetic polymorphisms could be associated with the co-morbidity phenomenon in BD., Methods: We studied 320 subjects (160 BD patients and 160 healthy controls). Genotyping was performed using made-to-order TaqMan genotyping assays (rs4923463, rs6265, rs2049045, and rs7103411). Statistical analyses were performed using UNPHASED version 3.0.12 and Haploview 4.1., Results: No genotypic, allelic or haplotype differences were found between bipolar patients and healthy controls. Concerning exclusively the rs4923463 (G/G) there was a significant association with alcoholism (p=0.009), smoking (p=0.006) and violent suicide attempt (p=0.03). We further found that the G-G haplotype (rs4923463-rs2049045) (adjusted p=0.029) and the G-T haplotype (rs4923463-rs7103411) (adjusted p=0.029) were significantly more frequent in the group with alcoholism co-morbidity when compared with the group without this co-morbidity., Limitations: Sample size and retrospective assessment of suicide behavior and psychiatric comorbidities., Conclusions: The results obtained in our study indicate that BDNF variants may confer susceptibility to additional psychiatric diagnosis in BD., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: The 39-item TEMPS-A self-rated questionnaire assesses affective temperaments. We examined the factorial structure of its French version in a large sample of young adults and examined the relation to schizotypy, depression and anxiety., Method: University students were enrolled during their mandatory preventive health visit in the University medical facility (n = 3807, 19.9 ± 2.5 y.o.). They answered to the 39-TEMPS-A questionnaire, the Schizotypal Personality Questionnaire (SPQ) and the Hospital Anxiety Depression Scale (HADS). We performed an exploratory Factorial Component Analysis (FCA) with varimax rotation of the 39-TEMPS-A in half of the sample, randomly selected, followed by a Confirmatory Factor Analysis (CFA) in the remaining subsample. TEMPS-A dimensions were correlated to HADS and SPQ sub-scores., Results: A five-factor structure was found by PCA and confirmed by the confirmatory analysis. The scale showed a good internal consistency (whole scale Cronbach's α: 0.83 and from 0.78 to 0.59 for Cyclothymic, Depressive, Irritable, Hyperthymic, Anxious subscales). Depressive and Anxious TEMPS-A subscales were moderately correlated to HADS Depression and Anxiety subscales (Spearman ρ = 0.37 to 0.33). Cyclothymic and Depressive TEMPS-A subscales were respectively correlated to SPQ Paranoid (ρ = 0.53) and Negative dimensions (ρ = 0.52)., Limitation: Representativity of the sample (higher education, response rate)., Conclusion: We confirmed the five factor structure of the 39-item TEMPS-A in a large non-clinical population of young adults and found consistent correlations with anxiety - depression state markers and schizotypal traits., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In addition to classical delusional, negative, and cognitive deficit, schizophrenia has consistently been associated with impairments in saccadic eye movements, e.g., an increased error rate in the antisaccade task. We hypothesized that a deficit in inhibitory control is a core defect in untreated patients with schizophrenia leading to impairment in different oculomotor paradigms. Ten drug-free or drug-naïve patients with schizophrenia were matched in age and gender to 11 healthy controls with no psychoactive substance use or abuse. They were explored using reflexive saccades with unpredictable targets with or without the gap procedure, predictive saccades and a fixation/distracter paradigm. Patients with schizophrenia displayed shorter latency in reflexive and predictive saccades. In the GAP condition, patients made more anticipatory saccades, fewer regular saccades, and had a shorter latency of express saccades than controls. In addition, patients had an increased error rate in the fixation/distracters task. Altogether, these results provide new evidence of reduced prefrontal inhibitory regulation of subcortical and brainstem systems involved in the control of saccades., (Copyright © 2009 Elsevier Ltd. All rights reserved.)

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.

The TEMPS developed from classical temperament concepts at the Universities of Tennessee (Memphis) and California (San Diego) in collaboration with clinical scientists in Pisa and Paris. It presently exists in 20 languages and full validation of its 110-item version has been accomplished in American English, Italian, French, German, Hungarian, Japanese, Turkish, Lebanese Arabic and Argentinean Spanish. For many studies, a shorter version is easier to use. Accordingly, the 39-item validated English version has just been rendered into French, to facilitate clinical use and research in Francophone countries.

Despite a delayed emergence of the symptoms, schizophrenia is thought to be a late consequence of early disturbances during development. Several reports have found decreased levels of reelin in the cortex and the hippocampus of postmortem brains of schizophrenic patients. In the rat, intraperitoneal injection of the anti-mitotic agent methylazoxymethanol (MAM) during intra-uterine development (embryonic day 17) induces cytoarchitectural abnormalities in the hippocampus and the cortex and behavioural changes reminiscent of positive, negative and cognitive symptoms of schizophrenia. We aimed to examine whether a transient prenatal disturbance of neurogenesis induces postnatal changes in the expression of reelin in the hippocampus. Cellular modifications were explored using hippocampal organotypic slice cultures, which allow for conservation of the in vivo cytoarchitecture. MAM effect on hippocampal neurogenesis was confirmed by birthdating experiments. After 3 weeks in vitro, reelin was expressed by calretinin-negative cells. The number of reelin-positive neurons was increased whereas the total neuron number was decreased in the stratum oriens in the E17 MAM-exposed animals as compared to the control group. Not only an increase in the number of cells expressing reelin was observed, but there was also a slight increase in reelin mRNA levels in hippocampal pyramidal cells of MAM-exposed animals. In contrast, there was no significant change in the dentate gyrus. These results show that transient prenatal disturbance of neurogenesis induces long-term modifications in specific areas of the hippocampus and in particular in the number of neurons expressing reelin. They also confirm the value of organotypic slices to study postnatal maturation in the hippocampus.

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.

Epidemiological data and family studies in schizophrenia show that genetic factors contribute to the vulnerability to this disorder. The homeogene Engrailed 2 (EN2) is specifically involved in patterning the region that gives rise to the cerebellum and controls the plasticity of midbrain dopaminergic neurons. We carried out an association study for a CA repeat polymorphism located in the 3' region of the homeogene EN2. The subjects consisted of 165 patients with schizophrenia and 97 controls matched for age and ethnicity from a French Caucasian population. We found no significant association of schizophrenia with this bi-nucleotide repeat polymorphism of the EN2 gene.

Background: To explore clinical features of symptoms and comorbidity according to the age of onset of patients suffering from obsessive-compulsive disorder (OCD)., Methods: The survey involved collecting data from both patient members of an OCD association, and a sample of 175 OCD patients seen in OCD specialty practice. All the patients (n=617) responded to a questionnaire on family and personal psychiatric OCD history, phenomenological features of OCD and comorbidity. They were classified according to OCD age at onset [group early age of onset (EO): under 15, group late age of onset (LO): older than 15]., Results: A higher percentage of patients from Group LO complained of OCD triggering by factors such as professional difficulties and childbirth (P<0.05); also they more often had (P=0.05) a sudden onset of symptoms. On the other hand, clinical features, such as superstition and magic thoughts, parasite obsessions and repeating, counting, hoarding, tapping/rubbing and collecting compulsions were significantly more frequent (P<0.05) in EO; likewise, history of tics was more frequent in this group. The existence of comorbid depression (at least one episode) did not show any significant difference between groups. However, depression preceding OCD was more frequent in LO. There was no significant difference in treatment response according to age of onset OCD., Conclusions: The results showed a clear association of EO with obsessions of superstition and parasites, repetitive compulsions and motor and vocal tics, whereas a sudden onset, triggering factors and a more frequent depression preceding OCD characterized LO.

The frequency of minor physical anomalies (MPAs) in patients with schizophrenia suggests an early disturbance in the development of the neuroectoderm. To improve the phenotypic delimitation of this disorder, we used a comprehensive scale of MPAs (41 items) in patients with schizophrenia and their first-degree relatives. This scale, adapted from a revised version of the Waldrop Scale (Ismail et al. Minor physical anomalies in schizophrenic patients and their siblings, American Journal of Psychiatry 155, 1998a, 1695-1702), introduced new items assessing facial and limbs asymmetry. The interrater reliability between two examiners was good: intraclass correlation coefficient: 0.68 (0.42-0.92). Patients with schizophrenia (n=40; mean=5.8, S.D.=4) and their non-psychotic parents (n=45; mean=4.7, S.D.=2.8) had significantly more MPAs than healthy comparison subjects (n=42; mean=2.2, S.D.=1.2). A logistical regression model showed the ability of several items to predict group status, including facial asymmetry, cleft palate, hair whorls and abnormal palmar crease. The high prevalence of facial asymmetry in patients with schizophrenia and their first-degree relatives provides new insights into the underlying dysembryogenic processes. This revised scale thus appears to be a useful complementary tool in pathophysiological studies aiming at the identification of developmental factors in schizophrenia.

The aim of this study is to circumscribe the cognitive deficits according to schizophrenic syndromes in a population of sub-acute untreated patients. We have studied the cross-sectional correlation between cognitive deficits and schizophrenic symptoms, in a group of 24 untreated patients (including 17 neuroleptic-naive patients) with recent onset of the disease. A task of alertness, a working memory (WM) test (including two levels of difficulty) and an abbreviated version of the Wisconsin Card Sorting Test (WCST) were selected. WM deficits and poor performance on the WCST were highly correlated with disorganized symptoms, modestly with the positive syndrome and not with the negative syndrome. Thus, disorganized symptoms, more than any other, appear to be related to the impairment of executive function and WM in recent onset unmedicated patients with schizophrenia.

Lifetime substance abuse comorbidity is frequent in schizophrenic patients, but the clinical correlates remain unclear. We have explored the chronological relations between substance abuse and course of schizophrenia, and compared several clinical characteristics and personality dimensions in 50 schizophrenic patients with or without lifetime substance abuse or dependence. Abuse occurred mainly after the first prodromal symptoms and just before the first psychotic episode. Substance-abusing patients were not different from non-substance-abusing patients on the Chapman Physical Anhedonia Scale, PANSS total score, negative subscore or depression item, CGI, treatment response and demographic variables. In contrast, substance-abusing patients had higher scores on the Barratt Impulsivity Scale (total, cognitive and non-planning scores) and had attempted suicide more often. In patients with schizophrenia, as in the general population, substance abuse or dependence appears associated with higher impulsivity and suicidality. High impulsivity could facilitate substance abuse as a maladaptive behavior in response to prodromal symptoms, precipitating the onset of a characterized psychosis.

In two areas of the rat striatum, the in vitro N-methyl-D-aspartate (NMDA, 50 microM)-evoked release of [3H]dopamine was studied in the presence of bicuculline (5 and 50 microM), an antagonist of GABAA receptors. The responses observed with the higher concentration (50 microM) is compatible with an antagonistic activity of bicuculline on NMDA receptor, as recently reported by Wright and Nowak.