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International audience; Caffeine is the most consumed psychoactive substance worldwide. Previous studies suggested higher caffeine consumption in subjects with schizophrenia spectrum disorders (SSD) as well as associations with symptoms, medication and medication side-effects. In a large and well-characterized sample of SSD subjects we explored the association between caffeine consumption and clinical (psychosis related, severity, general health) as well as pharmacological (antipsychotic treatment, sedation potential) variables. Eight hundred four subjects with data on their caffeine (coffee and tea) consumption successively recruited were included in this study. After controlling for potential confounders (demographic variables, smoking) only the negative dimension of psychosis was associated with the amount of caffeine ingested. Less severe negative symptoms were associated with higher caffeine consumption. The effect size of this association was small (partial correlation coefficient = −0.12) but significant.

International audience; Background: Aggressiveness is a stigma frequently associated with schizophrenia. The role of insight as a risk factor of aggressiveness remains contradictory; mainly because single measures of these states mask their complexity and heterogeneity.Methods: This study was conducted on 666 patients aged 15 and above with a DSM-IV-TR diagnosis of schizophrenia spectrum disorder, drawn from the French national network of schizophrenia expert center database. Collected data comprised socio-demographics and standardized psychiatric assessments. Aggressiveness was evaluated using the Buss-Perry Aggression Questionnaire and insight using the Scale to assess Unawareness of Mental Disorder (SUMD) and Birchwood Insight Scale (BIS).Results: Hostility was the aggressiveness dimension the most strongly associated with SUMD insight dimensions. Patients aware of their illness were nearly twice as likely to show hostility than those seriously unaware (OR = 1.95, 95% CI.: 1.08-3.5), but not when further adjusting for depression. Similarly, those aware of the consequences of their illness and of their symptoms were more hostile. Patients moderately aware of illness consequences had a higher risk of both anger and physical aggressiveness than those unaware (OR = 2.63, 95% CI.: 1.42-4.86, OR = 2.47, 95% CI.: 1.33-4.60, respectively), even when adjusting for depression for anger.Conclusion: Our study confirms that a multi-dimensional approach to insight and aggressiveness is essential to understand the types of links between these clinical states. Insight may trigger the expression of an underlying hostile tendency, maybe via depression and self-stigmatisation. This should be taken into account in therapeutic approaches to improve insight.

Youth subcultures mostly arise within mainstream cultures that determine the norms of the way of living in communities. The antagonistic way of thinking and manners of youth subcultures emerge together with unique dialects, dressing styles and behavioural patterns. The youth subcultures aim to shatter the predetermined and inherited notions, that are patriarchal, restrictor and discriminator, in the public sphere therefore they are mostly found violent, rebellious and peevish. This study aims to show how youth subcultures emerge from mainstream cultures in societies as reactions to dominant notions of communities and the ways to control them through the excerpts from Anthony Burgess’s A Clockwork Orange (1962). The work will be examined briefly throughout this study to show that with argots and styles, the members of the subcultures, which may mostly be derived from violent actions, become dissidents in the controlling governments. The government’s aim is to penalise dissidents with forced punishments through its institutions, such as prisons or/and asylums. However, any forceful action that is against free will, even if it is innately good, is bad, and dissidents become the victims of the government because the governmental punishments do not pave the way to betterment, on the contrary, its forced solutions against anomalous agents—any agent that performs unorthodoxly—in the communities exacerbate the predicament further.

Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics.

International audience; The aim of our study was to compare the performance of three different instruments measuring clinical and cognitive dimensions of insight. Data on 182 outpatients with schizophrenia and one-year follow-up assessments was drawn from the FACE-SZ cohort. Awareness of clinical state (« clinical insight ») was measured using both a clinician-rated measure (the Scale to assess Unawareness of Mental Disorder (SUMD)), and a self-report measure (the Birchwood Insight Scale (BIS). Cognitive insight was measured using a self-report measure (the Beck Cognitive Insight Scale (BCIS)). For each scale, change in insight was examined at the follow-up. Correlations between SUMD and BIS subscales measuring same dimensions were significant. BIS-BCIS correlations were weak for all combinations except between BIS illness dimension and BCIS composite score. At the follow-up, BIS and SUMD awareness of treatment need improved whereas illness and symptom awareness increased only on the SUMD. Conversely, cognitive insight composite scores decreased. Despite relatively good overall agreement between the two clinical insight instruments, considerable variability for similar insight dimensions measured by different instruments was found. Agreement between cognitive and clinical insight is moderate. Our study strengthens the argument that insight is harder to operationalize than other symptoms and may explain why it is so seldom explicitly targeted in schizophrenia treatment.

International audience; 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.; Objectifs Le présent article propose de faire un retour sur les 10 ans d’expérience du réseau national des 10 centres experts schizophrénie Français, à travers une revue des principales publications scientifiques qui en sont issues. Méthodes À ce jour, les données de plus de 700 patients ont pu être analysées. Globalement, cette population est composée de trois quarts d’hommes, est âgée en moyenne de 32 ans, la durée moyenne de maladie est d’environ 11 ans, l’âge moyen de début de maladie est de 21 ans, la durée de psychose non traitée est d’environ un an et demi. 55 % des sujets sont consommateurs de tabac au moment de l’évaluation. Enfin, un focus sera fait sur les projets de recherche multicentriques collaboratifs déployés au sein de ce réseau. Résultats Les principales données obtenues peuvent être résumées comme suit : le syndrome métabolique reste deux fois plus fréquent dans la schizophrénie qu’en population générale et n’est pas correctement pris en charge ; des troubles cognitifs spécifiques ont été identifiés chez les patients consommateurs de benzodiazépines et chez les patients présentant une inflammation périphérique. Des spécificités liées au sexe ont également été observées ; la dépression comorbide reste très fréquente, elle est associée à une diminution de la qualité de vie et à une augmentation de la dépendance nicotinique chez les fumeurs. Prendre en charge la dépression et les symptômes négatifs pourraient fortement améliorer la qualité de vie des patients ; le délai à l’instauration du traitement est plus long pour les schizophrénies se déclenchant avant 19 ans et chez les consommateurs de cannabis. L’adhésion au traitement est diminuée chez les patients rapportant un ressenti subjectif négatif du traitement, indépendamment de la prise de poids ou d’un syndrome extrapyramidal. Enfin, l’akathisie est très fréquente et fortement associée à la polythérapie antipsychotique. Conclusions Ces résultats conduisent à formuler plusieurs recommandations. Le dépistage du trouble et le traitement devraient être renforcés chez les adolescents et les consommateurs de cannabis. Tous les patients devraient bénéficier d’une évaluation neuropsychologique au début de leur trouble, après stabilisation sous traitement, puis de façon plus espacée au cours de leur suivi. La prise en charge des paramètres métaboliques, de l’alimentation et de l’activité physique devrait être renforcée. La balance bénéfice/risque de la prescription de benzodiazépines doit être réévaluée régulièrement au regard de son impact notamment sur la cognition. La monothérapie antipsychotique est recommandée autant que possible pour limiter les effets indésirables. La dépression reste sous-diagnostiquée et doit faire l’objet d’une évaluation systématique et d’un traitement spécifique. La remédiation cognitive doit également être plus largement proposée chez les patients présentant des troubles cognitifs.

Introduction This study aimed was to investigate the relationship between different types of childhood trauma and the level of insight (i.e., awareness of having a psychiatric disorder) in subjects suffering from schizophrenia, as well as the putative role of clinical mediators. Methods 294 community-dwelling subjects with stable schizophrenia were included into FACE-SZ, a multicentre cross-sectional study. All patients were assessed by specialized multidisciplinary teams. The level of insight was assessed by the Scale to assess Unawareness of Mental Disorder (SUMD), and childhood trauma by the Childhood Trauma Questionnaire (CTQ). Path analyses from the five CTQ subscales (physical abuse and neglect, emotional abuse and neglect, and sexual abuse) and the SUMD, with current symptomatology (i.e., positive, negative, global psychopathology and depression) as mediator, was performed. Results Physical neglect (β = 0.14) and abuse (β = 0.13) were significantly associated with poor insight. Negative symptoms were a clinical mediator of the relationship between physical neglect and poor insight. Moreover, positive (β = 0.21) and negative (β = 0.30) symptoms were associated with poor insight, whereas depression (β = −0.14) was associated with higher levels of insight. Discussion For the first time, this study shows a significant relationship between childhood trauma, specifically physical neglect and abuse, and poor insight. The level of insight was linked to different clinical dimensions. Among subjects with schizophrenia, these results provide support for a role of childhood trauma in poorer management outcomes, and the need to provide treatment, including psycho-education that better targets the consequences of childhood trauma.

Objectives Reducing the duration of untreated psychosis (DUP) may improve the prognosis of schizophrenia. This study investigated the prevalence, and associated risk factors, of long DUP in a large, non-selected sample of community-dwelling schizophrenia patients (SZ). Method 478 community-dwelling stable SZ participants (122 women and 356 men; mean age 32.37 ± 9.86 years) were recruited between 2010 and 2016. The mean retrospective DUP was evaluated from both patient and family reports, as well as hospital/psychiatrists records. Long DUP was defined as > 2 years. Results The mean DUP was 1.5 years. 80 participants (16.7%) had a DUP > 2 years. In multivariate analyses, after adjustment for sex, education level, history of childhood trauma and history of maternal schizophrenia or bipolar disorder, long DUP was associated with a younger age of illness onset (19.3 ± 6.67 years vs. 22.0 ± 6.51 years, adjusted odd ratio aOR = 0.91, 95%CI [0.86; 0.97], p = 0.003) and cannabis use disorder (20.0% vs. 10.3%, aOR = 2.41, 95%CI [1.14–5.09], p = 0.02). Conclusion A high proportion of SZ patients still have a long DUP. The present results suggest that illness onset before age 19 years and cannabis use are associated with long DUP in schizophrenia patients. Early psychosis detection programs should prioritize the targeting of these populations.

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.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.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 onset19 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.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.

International audience; The functional outcome in schizophrenia spectrum disorders is affected by multiple factors such as cognitive performance and clinical symptoms. Psychiatric disability may be another important determinant of functional outcome. The purpose of this study was to test whether schizophrenia symptoms and psychiatric disability mediated the association between cognition and functioning. Between April 2013 and July 2017, we included 108 community-dwelling adults with stable schizophrenia spectrum disorder in a multicenter study. Psychiatric disability was assessed with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale by relatives of patients. ECPDS focused on the broad array of motivational, neurocognitive, sociocognitive, and metacognitive impairments that result in activity restrictions. We used a battery of tests to assess seven cognition domains (processing speed, attention/vigilance, working, verbal and visual memory, reasoning and problem solving, and executive functioning) and cross-sectional structural equation modeling (SEM) for the mediation analyses. We estimated the one-year temporal stability of ECPDS scores in 45 participants. The model provided showed good fit and explained 43.9% of the variance in functioning. The effect of neurocognition on functioning was fully mediated by symptoms (proportion mediated: 36.5%) and psychiatric disability (proportion mediated: 31.3%). The ECPDS score had acceptable one-year temporal stability. The ECPDS scale has satisfactory psychometric properties, and shows significant convergence with neurocognition and functioning, suggesting a role for this tool in the routine evaluation of cognitive remediation needs. Our model validates psychiatric disability as a crucial step from cognitive impairment to restricted participation in life situations.

Low-grade inflammation has repeatedly been associated with schizophrenia (SZ) and in particular with cognitive impairment. Female gender, overweight and tobacco smoking have been suggested as risk factors to increase inflammation while preclinical inconsistent findings have been found regarding the association with psychotropic drugs. The aim of this study was to explore if psychotropic drugs were associated with inflammation in SZ and to determine which psychotropic drug was associated with inflammation in stable SZ subjects while considering clinical confounding factors. Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment, including recording of current treatment. High-sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. The zero-inflated Poisson regression model estimated the relationship between low-grade inflammation and psychotropic drug. Four hundred and five stabilized, community-dwelling SZ subjects (mean age = 32.6 years, 74% male gender) have been included. In total, 148 participants (36.5%) were found with undetectable blood hs-CRP level. The probability of having an undetectable CRP was associated with a lower body mass index (p 0.0001) and no cyamemazine add-on antipsychotic therapy (p = 0.001). The other 257 participants (63.5%) were found to have low-grade inflammation (hs-CRP 0 mg/L). Low-grade inflammation was significantly associated with female gender (p = 0.004), higher body mass index (p 0.0001), current tobacco smoking (p 0.0001), clomipramine (p = 0.04), quetiapine (p 0.0001) and hypnotic (p = 0.0006) consumption while decreased hs-CRP blood levels was associated with aripiprazole (p = 0.004) and valproate/valpromide (p = 0.03) consumption. The present study suggests that some psychotropic drugs (quetiapine, cyamemazine, clomipramine) may be associated with increased peripheral low-grade inflammation in SZ patients while others (aripiprazole, valproate) may be associated with decreased peripheral low-grade inflammation. These results should be replicated in SZ and non-SZ populations and the biological underpinnings should be further explored.

Supplemental material, Supplemental_Material for Screening for cognitive deficits with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia scale by Paul Roux, Mathieu Urbach, Sandrine Fonteneau, Fabrice Berna, Lore Brunel, Delphine Capdevielle, Isabelle Chereau, Julien Dubreucq, Catherine Faget-Agius, Guillaume Fond, Sylvain Leignier, Claire-Cécile Perier, Raphaëlle Richieri, Priscille Schneider, Franck Schürhoff, Anne Marie Tronche, Hanan Yazbek, Anna Zinetti-Bertschy, the FondaMental Advanced Centers of Expertise in Schizophrenia (FACE-SCZ) Collaborators, Christine Passerieux, Eric Brunet-Gouet, M Andrianarisoa, B Aouizerate, N Bazin, F Berna, O Blanc, L Brunel, E Bulzacka, D Capdevielle, I Chereau-Boudet, G Chesnoy-Servanin, JM Danion, T D’Amato, A Deloge, C Delorme, H Denizot, JM Dorey, C Dubertret, J Dubreucq, C Faget, C Fluttaz, G Fond, S Fonteneau, F Gabayet, E Giraud-Baro, D Lacelle, C Lançon, H Laouamri, M Leboyer, T Le Gloahec, Y Le Strat, PM Llorca, J Mallet, E Metairie, D Misdrahi, I Offerlin-Meyer, C Passerieux, P Peri, S Pires, C Portalier, L Ramet, R Rey, C Roman, A Schandrin, F Schürhoff, A Tessier, AM Tronche, M Urbach, F Vaillant, A Vehier, P Vidailhet, E Vilà, H Yazbek and A Zinetti-Bertschy in Clinical Rehabilitation

Objective Latent Toxoplasma infection has been associated with widespread brain immune activation, increased blood brain barrier permeability, neural disruption, increased dopamine release in dopaminergic neurons, with NMDA activation and with schizophrenia (SZ) onset risk. Toxoplasma has been suggested to be a source of chronic low-grade inflammation and this inflammation has been associated with cognitive impairment in SZ. The objective of the present study were (i) to determine if latent Toxoplasma infection was associated with specific clinical features in stabilized SZ subjects, with cognitive impairment and with increased low-grade peripheral inflammation and (ii) to determine if Treatments with Anti-Toxoplasmic Activity (TATA) were associated with improved outcomes in subjects with latent Toxoplasma infection. Methods A comprehensive 2 daylong clinical and neuropsychological battery was administered in 250 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Solid phase-enzyme microplate immunoassay methods were used to measure IgG class of antibodies to T. gondii in blood sample. Latent Toxoplasma infection was defined by T . gondii IgG ratio ≥0.8, equivalent to ≥10 international units. Chronic peripheral inflammation was defined by highly sensitive C reactive protein blood level ≥ 3 mg/L. Results Latent Toxoplasma infection has been found in 184 (73.6%) of this national multicentric sample. In the multivariate analyses, latent Toxoplasma infection has been significantly associated with higher PANSS negative (aOR = 1.1 [1.1–1.1], p = 0.04) and excitement subscores (aOR = 1.3 [1.1–1.6], p = 0.01), with two specific symptoms (i.e., reference delusion (aOR = 3.6 [1.2–10.6] p = 0.01) and alogia (aOR = 16.7 [2.0–134.7], p = 0.008)) and with chronic low-grade peripheral inflammation (27.2% vs. 7.6%, aOR = 3.8 [1.4–10.3], p = 0.004). Extrapyramidal symptoms remained significantly associated with latent Toxoplasma infection. On the opposite, no significant association of latent Toxoplasma infection with age, gender, age at SZ onset, suicide behavior or cognitive deficits has been found in these models (all p > 0.05). TATA were associated with lower depressive symptoms (aOR = 0.8[0.7–0.9], p = 0.01), and with lower rates of chronic peripheral inflammation (20.9% vs. 48.6%, aOR = 3.5 [1.5–7.9], p = 0.003) but not with higher cognitive scores (p > 0.05). Conclusion The present findings suggest that Toxoplasma is almost 3 times more frequent in SZ population compared to general population in France. The potential cerebral underpinnings of the association of latent Toxoplasma infection and the above-mentioned outcomes have been discussed. Future studies should confirm that TATA may be effective to reduce Toxoplasma-associated depressive symptoms and low-grade peripheral inflammation.

Background Tobacco use is common in patients with schizophrenia (SZ) but little is known on the role of tobacco in the physiopathology or on the course of the disease. Only few studies embrace an extensive examination of clinical and therapeutic characteristics in stabilized patients. The objective of the present study was to determine the prevalence of tobacco smoking in stabilized SZ outpatients and the clinical and treatment characteristics associated with daily tobacco use in a large community-dwelling sample of patients. Methods Three-hundred-and-sixty-one patients were included in the network of the FondaMental Expert Centers for Schizophrenia. Current tobacco status was self-declared. Results 53.7% were smokers. Mean age at tobacco onset was 17.2 years old. In multivariate analyses, after adjustment for confounding factors, positive symptoms and mean daily antipsychotic dose were associated with a higher frequency of tobacco use (OR = 1.06 95%IC[1.02–1.12], for positive symptoms, OR = 1.1, 95%IC[1.02–1.18] for daily antipsychotic dose). Education level, negative symptoms, anticholinergic agents, clozapine or aripiprazole administration were independently associated with a lower frequency of tobacco use (respectively OR = 0.87, 95%IC [0.79, 0.95], OR = 0.95, 95%IC[0.91–0.98], OR = 0.41, 95%IC[0.22–0.76], OR = 0.56, 95%IC = [0.32, 0.99] and OR = 0.49, 95%IC [0.26–0.91]). Conclusion The prevalence of current tobacco smoking in a French community-dwelling SZ patients is higher that observed in the general population. Patients with tobacco use present clinical and therapeutic specificities that may involve interaction between cholinergic-nicotinic and dopaminergic systems. The present study suggests that some therapeutics may improve daily smoking behavior in smokers. These results should be confirmed in longitudinal studies.

International audience; OBJECTIVES:Depression and negative symptoms have been associated with impaired Quality of life (QoL) in schizophrenia (SZ). However, childhood trauma may influence both QoL and depression in SZ patients, with consequences for the management of impaired QoL in SZ patients. The aim of the present study was to determine if childhood trauma was associated with impaired QoL in schizophrenia.METHOD:A sample of 544 community-dwelling stabilized SZ patients enrolled in FACE-SZ cohort were utilized in this study (74.1% males, mean aged 32.3years, mean illness duration 10.6years). QoL was self-reported with the S-QoL18 questionnaire. Childhood trauma was self-reported with the Childhood Trauma Questionnaire. Depression was measured by the Calgary Depression Rating Scale for Schizophrenia. Psychotic severity was measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Other clinical factors, treatments, comorbidities, functioning and sociodemographical variables were also recorded, with validated scales.RESULTS:Overall, 151 participants (27.8%) had a current major depressive episode and 406 (82.5%) reported at least one episode of historical childhood trauma. In multivariate analyses, lower QoL total score was associated with a history of childhood trauma (β=-0.21, p

Objectives Sex differences can yield important clues regarding illness pathophysiology and its treatment. Schizophrenia (SZ) has a lower incidence rate, and a better prognosis, in women versus men. The present study investigated the cognitive profiles of both sexes in a large multi-centre sample of community-dwelling SZ patients. Method 544 community-dwelling stable SZ subjects (141 women and 403 men; mean age 34.5 ± 12.1 and 31.6 ± 8.7 years, respectively) were tested with a comprehensive battery of neuropsychological tests. Results Although community-dwelling SZ men had more risk factors for impaired cognition (including first-generation antipsychotics administration and comorbid addictive disorders), women had lower scores on a wide range of cognitive functions, including current and premorbid intellectual functioning, working memory, semantic memory, non-verbal abstract thinking and aspects of visual exploration. However, women scored higher in tests of processing speed and verbal learning, as well as having a lower verbal learning bias. No sex difference were evident for visuospatial learning abilities, cued verbal recall, sustained attention and tests of executive functions, including cognitive flexibility, verbal abstract thinking, verbal fluency and planning abilities. Conclusion Sex differences are evident in the cognitive profiles of SZ patients. The impact on daily functioning and prognosis, as well as longitudinal trajectory, should be further investigated in the FACE-SZ follow-up study. Sex differences in cognition have implications for precision-medicine determined therapeutic strategies. Limits Given the restricted age range of the sample, future research will have to determine cognitive profiles across gender in late onset SZ.

Aytar, Mammadov and Pehlivan have introduced the concepts of statistical limit inferior and limit superior for sequences of fuzzy numbers. In this paper, we define lamda-statistical limit inferior and limit superior for sequences of fuzzy numbers. Also we will discuss the relations among ¸ lambda-statistical limit inferior and limit superior for sequences of fuzzy numbers

La notion d’une transmission inter et transgenerationnelle d’une vulnerabilite voire de troubles psychiatriques connait un interet grandissant depuis les travaux presentes dans les deux conferences precedentes (celle du Professeur Mansuy portant sur des modeles animaux de transmission transgenerationnelle et celle du Professeur Rutten en epigenetique humaine). Ces travaux apportent en effet des donnees scientifiques et experimentales permettant de concevoir un support biologique a cette transmission transgenerationnelle. Pour autant, il n’y a pas que nos genes que nous heritons de nos ancetres. En effet, nous « heritons » aussi de tout un ensemble de contenus psychiques : valeurs, regles, croyances, schemas de pensees qui peuvent eux-memes constituer une vulnerabilite au developpement de troubles psychiques. Ces contenus sont pour partie conscients et pour partie adoptes de facon inconsciente, dans l’ignorance des circonstances qui ont pu les generer, une voire plusieurs generations auparavant. Il existe ainsi de nombreux modeles, certains analytiques (e.g. theorie analytique des cryptes et fantomes familiaux), d’autres systemiques (e.g. loyautes invisibles de Boszormenyi-Nagy) qui ont tente de modeliser les modalites de la transmission de la vie psychique a travers les generations. Apres une breve presentation de ces modeles, nous tenterons d’examiner a partir de quelques exemples cliniques comment ces modeles peuvent ou non s’integrer ou non avec les donnees biologiques mentionnees dans les deux conferences precedentes. Dans un second temps, nous examinerons certains courants de psychotherapies qui proposent un traitement symbolique des facteurs transgenerationnels supposes en jeu dans la problematique d’un patient. Ces psychotherapies, dans lesquelles on peut regrouper la psychogenealogie ou encore les Familienaufstellungen developpees en Allemagne dans les annees 1990 (methode proche des sculptures familiales de Virginia Satir mais qui s’etendent au-dela de la famille actuelle du patient), ont donne lieu a une litterature assez vaste mais detachee d’une demarche evaluative, a quelques rares exceptions (Weinhold et al. 2013). Nous examinerons les fondements theoriques de ces courants, leur place eventuelle comme approche de soins en milieu institutionnel mais aussi certaines derives dont ces approches peuvent faire l’objet.

Les nombreuses etudes sur l’etiologie des troubles mentaux ont revele qu’une combinaison de facteurs genetiques et environnementaux est responsable de ces troubles. Les recherches les plus recentes ont ainsi mis en lumiere des facteurs epigenetiques dans les mecanismes conduisant a l’expression de ces troubles mais aussi a leur transmission aux generations suivantes. Ces recherches soulevent a la fois beaucoup d’espoirs et d’interrogations. Ce symposium reunissant trois specialistes de la question chez l’homme et l’animal tentera d’y repondre. Le Pr. Rutten presentera ses travaux et d’autres donnees recentes illustrant une possible contribution transgenerationnelle aux troubles psychiques chez l’homme. Il precisera comment cette hypothese a emerge dans la continuite des recherches sur les facteurs genetiques et environnementaux des troubles psychiques chez l’homme et dans la suite des premiers travaux montrant le role de facteurs transgenerationnels chez l’animal. Pour autant, si ces recherches peuvent paraitre prometteuses, leur methodologie reste complexe et expose ainsi a de nombreux pieges. L’auteur s’arretera plus particulierement sur ces points. Le Pr. Mansuy poursuivra en decrivant les principaux facteurs epigenetiques dans le cerveau et montrera comment ils contribuent aux comportements et aux fonctions cognitives chez l’adulte. L’accent sera mis sur les mecanismes epigenetiques lies aux traumatismes precoces et sur leur etude chez un modele de souris de laboratoire. Les dernieres recherches sur ces mecanismes et leur induction chez des individus directement exposes et leurs descendants seront decrites. Les donnees actuelles impliquant les cellules germinales dans la transmission transgenerationelle epigenetique, et la possibilite de corriger des alterations epigenetiques induites par les traumatismes seront egalement presentees. Le Pr. Berna conclura par un regard critique porte sur les courants de psychotherapies qui ont tente de theoriser les modalites par lesquelles des elements de la vie psychique se transmettent a travers les generations (par ex, theorie analytique des cryptes et des fantomes familiaux, theorie systemique des loyautes invisibles). L’expose se penchera plus particulierement sur trois questions que soulevent ces theories : s’articule-t-elle ou non avec les donnees actuelles de l’epigenetique? Quelles derives d’interpretation ces theories peuvent-elles contenir? Existe-t-il des donnees empiriques qui valident leur demarche?

International audience; The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio=2.04, p=.025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications.

Objective Abdominal obesity was suggested to be a better predictor than Metabolic Syndrome (MetS) for cardiovascular mortality, however this is has not been extensively studied in schizophrenia. Hyperuricemia (HU) was also suggested to be both an independent risk factor for greater somatic comorbidity and a global metabolic stress marker in patients with schizophrenia. The aim of this study was to estimate the prevalence of MetS, abdominal obesity and HU, to examine the association between metabolic parameters with HU in a cohort of French patients with schizophrenia or schizo-affective disorder (SZ), and to estimate the prevalence rates of treatment of cardio-vascular risk factors. Method 240 SZ patients (age = 31.4 years, male gender 74.3%) were systematically included. Metabolic syndrome was defined according to the International Diabetes Federation and HU if serum uric acid level was above 360 μmol/L. Results MetS, abdominal obesity and HU were found respectively in 24.2%, 21.3% and 19.6% of patients. In terms of risk factors, multiple logistic regression showed that after taking into account the potential confounders, the risk for HU was higher in males (OR = 5.9, IC95 [1.7–21.4]) and in subjects with high waist circumference (OR = 3.1, IC95 [1.1–8.3]) or hypertriglyceridemia (OR = 4.9, IC95 [1.9–13]). No association with hypertension, low HDL cholesterol or high fasting glucose was observed. Only 10% of patients with hypertension received a specific treatment, 18% for high fasting glucose and 8% for dyslipidemia. Conclusions The prevalence of MetS, abdominal obesity and hyperuricemia is elevated in French patients with schizophrenia, all of which are considerably under-diagnosed and undertreated. HU is strongly associated with abdominal obesity but not with psychiatric symptomatology.

In this paper we consider an interaction between a monoclonal tumor and the macrophages, which show a prey-predator structure. This model is analyzed with fuzzy initial values, where the concept of generalized differentiability is used. The graphical solutions for the problem show us interesting results comparing it with the differential equation model.

Disorders of self in schizophrenia have been considered as the core feature of the illness since its early clinical description. However, until recently, the understanding of these disorders referred mostly to philosophical considerations. The aim of this work is to examine how the various aspects of autobiographical memory deficits may be considered as possible cognitive mechanisms accounting for self-disorders in patients.We performed a theoretical review of the literature on autobiographical memory studies in schizophrenia. Our approach of cognitive psychopathology was grounded in the model of the Self-Memory System put forward by Conway (2005), which posits reciprocal relationships between autobiographical memory and the self. This model stresses the distinction between the working-self and the autobiographical memory knowledge base. The latter contains all autobiographical information stored in our life and is organized according to the specificity of this information. The role of the working-self is to maintain the coherence of the self and to control the access to autobiographical memories and corresponding memory details. The working-self supports an experiential or phenomenological dimension of the self, especially when a highly detailed autobiographical memory is retrieved, and a past event is re-experienced by the rememberer. The working-self also entails a conceptual part, the conceptual self, which contains self-knowledge and self-images.Our review showed that autobiographical memories of patients with schizophrenia are less specific and contain fewer phenomenological details than those of healthy participants. Patients also have difficulty assessing the subjective temporal distance of past events, and their ability to re-experience unique past personal events is affected as shown by a reduced conscious recollection and a smaller frequency of Field visual perspective during recall of autobiographical memories. This global alteration of all phenomenological characteristics of autobiographical memories strongly suggests an alteration of the phenomenological dimension of the self in schizophrenia. Since some of these alterations are also found in patients when they plan for future personal events, the ability to mentally travel in time is reduced in patients and reflects an impaired sense of self across time. The literature also shows that self-images are more passive, less coherent and less stable in time in patients compared to healthy participants. These results point to an alteration of the conceptual dimension of the self in schizophrenia. This may be partly explained by a weaker connection between the self and autobiographical memory and by other alterations of autobiographical memories closely linked to the self. In fact, the reminiscence bump is disorganized in patients and comprises poorly detailed memories. Memories grounding self-images are less organized and weakly connected to self-images. Finally, patients have an impaired ability to give a meaning to or to draw lessons from self-defining memories of their life.Based on these results, we discuss current and future therapeutic interventions including both cognitive remediation methods and cognitive psychotherapy applied to autobiographical memory. These methods appear relevant to help patients improve both the sense of self associatied with their autobiographical memory retrieval and the coherence and stability of the self.

Bu çalışmanın amacı; günümüzün en yaygın çağdaş anlatım biçimlerinden biri olan enstalasyonu oluştururken, tarihi mekanların tasarım oluşturmaya katkısını ön plana çıkarmak, bu amaçtan yola çıkarak Silahtar Mustafa Paşa Kervansarayı' nın enstalasyon çalışmalarındaki etkisini yapılan uygulamalarla anlatmaktır.Birinci bölümde; enstalasyonun tanımına değinerek Marcel Duchamp'ın başlattığı sanatta hazır nesne kullanımının günümüze gelene kadar kat ettiği yol, tarihsel gelişim sürecine bağlı kalarak anlatılmış, farklı disiplinlerde verilen yerli ve yabancı sanatçı örnekleriyle günümüzde yapılan enstalasyonlar ve seramik enstalasyonlardan bahsedilmiştir. Enstalasyonla kurduğu bağdan dolayı ayrı düşünülemeyen mekan kavramı açıklanmış, enstalasyon düzenleme alanı olarak kullanılan mekanlar ve kullanan sanatçılardan bahsedilmiş, ülkemizde yerli ve yabancı birçok sanatçının sergileme alanı olarak kullandığı tarihi mekanlar ve yapıtlarından örnekler verilmiştir.İkinci bölümde; yapıtların oluşumunda esin kaynağı olan Silahtar Mustafa Paşa Kervansarayının bulunduğu Malatya şehrinin coğrafi konumu, Kervansarayın mimari özellikleri, planı ve Kervansarayı yaptıran Silahtar Mustafa Paşa hakkında bilgiler verilmiştir. Tarihi yapının mimari özelliklerinin ve formlarının, tasarımların oluşmasına katkısından örneklerle bahsedilmiştir. Mekândaki yaşanmışlıktan ve insanlar arası iletişimden yola çıkılarak düşünsel boyutta şekillenen konuların, formlara dönüşümü anlatılmıştır.Üçüncü ve son bölümde ise; tarihi kervansaray mekânından yola çıkarak ve esinlenerek yapılan seramik enstalasyon uygulamaları, farklı düzenlemeler oluşturularak, bu düzenlemelerin oluşumuna kaynaklık eden mekansal etkenlerin anlatımlarıyla birlikte ele alınmıştır. The objective of this study is to determine the contribution of historical places, which also have created installation art that is one of the most common and contemporary way of expression, to the designs, and by the way to examine the influence of Silahtar Mustafa Paşa Caravanserai on the installation art works through the applications.In the first section, the definition of installation, the evolution of readymade objects used in the installation art that was firstly introduced by Marcel Duchamp, and installation samples from both native and foreign artists from different disciplines, and the present and ceramic installations are presented. The concept ?site? having a close relationship with the installation art, so cannot be separated, is explained; the sites used as installation area and those artists performing this art in those sites are mentioned, and the historical sites and constructions used by many native and foreign artists as exhibition site are exemplified.The geographical location of Malatya Province where Silahtar Mustafa Paşa Caravanserai, which has been the source of inspiration for the similar constructions, is located, the architectural characteristics of that caravanserai, its plan, and information about Silahtar Mustafa Paşa who had that caravanserai constructed are given in the second section. The contribution of architectural characteristics and forms of the historical constructions to the designs is explained through the examples, and the transformation of abstract issues to the forms is discussed considering the slice of life and communication between people.In the third section, the ceramic installation art performances inspired by that historical caravanserai and arranged distinctly, and the narration of spacial factors affecting these arrangements are presented. 100

Psychotic symptoms are not readily recognized in multiple sclerosis, especially at the beginning of the disease.We report the cases of four patients who developed psychotic symptoms that led to the diagnosis of multiple sclerosis. We describe the psychiatric and neurological features, MRI findings, clinical outcome and treatment.Two patients developed persecutory delusions, one presented a manic episode and the fourth melancholia with catatonia. Mean age was 39 years (range 20-49 years). Two patients had a personal history, but none a familial history of psychiatric disease. Examination of the cerebrospinal fluid revealed an oligoclonal pattern in all patients. All patients fulfilled Barkhof's MRI criteria. Three have had brain MRI with injection during psychotic symptoms. In these three cases, a frontal lesion appeared. The patient with catatonia also had a new lesion in the cerebellum and in the brainstem. All patients needed a "psychiatric" treatment, including antipsychotics. The psychiatric event lasted three months for two patients and the two others experienced relapse.Acute psychiatric symptom may reveal multiple sclerosis at the beginning of the disease. Frontal lobe localization is suggested. We propose that a psychotic event may correspond to a multiple sclerosis event.

Aytar has introduced the concepts of statistical limit and cluster points of a sequence of fuzzy numbers based on the definitions given in Fridy's study for sequences of real numbers. In this paper, we define A-statistical limit and A-statistical cluster points of sequences of fuzzy numbers and discuss the relations among the sets of ordinary limit points, A-statistical limit points and A-statistical cluster points of sequences of fuzzy numbers. (C) 2007 Elsevier Inc. All rights reserved.

Yirminci yüzyılın önemli akımlarından biri olan yapısalcılığın ve bu akımla bağlantılı yapısalcılık sonrası düşüncesinin Georg Wilhelm Friedrich Hegelle ilgisinin incelendiği bu çalışmada, yapısalcılıktaki açık ve örtük Hegel etkilerini yakalamak, bu etkilerin yapısalcılık sonrasında nasıl bir biçim aldığını saptamak hedeflenmektedir. Çalışmanın temel savı, Hegel'in -özellikle yapısalcılık sonrası düşünürleri tarafından sık sık eleştirilen bir filozof olsa da- birtakım kabulleriyle yapısalcılık - yapısalcılık sonrası çizgisinin oluşumunda etkili olduğudur. Çalışmanın ilk bölümü Hegel düşüncesinin yirminci yüzyılı etkileyen yönlerinin özetlenmesine ayrılmıştır; bu bölümde Hegel'in sistemi ana hatlarıyla özetlenmekte, filozofun yapısalcılık ile yapısalcılık sonrasında benimsenen görüşleri belirlenmeye çalışılmaktadır, ikinci bölümde Ferdinand de Saussure, Claude Levi- Strauss ve Roland Barthes üzerinde durulmakta, Saussure'ün ortaya attığı yapısal dilbilimin eski filoloji geleneğiyle ve Hegel düşüncesiyle bağlantısı, buna koşut olarak da Levi-Strauss'un yapısal budunbilimi ile Barthes'ın yapısalcılık yaklaşımı üzerindeki Hegel etkisi incelenmektedir. Üçüncü bölüm yapısalcılık sonrası düşünürlerine ayrılmıştır; bu bölümde, -yapısalcılıktan yapısalcılık sonrasına geçişi açıklamak üzere- yapısal yöntemin ardından yapısalcılık sonrası düşüncesini benimsemiş olan Barthes'ın görüşleri irdelenmekte, Gilles Deleuze, Michel Foucault ve Jacques Derrida'nın Hegel düşüncesiyle bağlantısı sorgulanmaya çalışılmaktadır. Çalışmanın son bölümünde ise, yapısalcılık - yapısalcılık sonrası çizgisinde saptanan Hegel etkisinin sonuçlarına değinilmekte, birtakım tipik sonuçlan ortaya koymak için siyasetbilimci Thierry Hentch'in çalışması Hayali Doğu incelenmekte, yapısalcılık sonrası düşüncesinin yerleşik hale getirdiği Hegelci klişeler bu kitap aracılığıyla serimlenmeye çalışılmaktadır. Both structuralism and post-structuralism, which are considered as the most influential approaches of twentieth century thought, do posses connections with the philosophy of Georg Wilhelm Hegel. The aim of this study is to identify the effects of Hegelian philosophy on structuralism and post-structuralism. Our main argument is that certain aspects of Hegelian thought have an important and determining influence on the formation of the structuralist and post-structuralist approaches, even though Hegel's philosophy subjected to the severe criticism of post-structuralist thinkers. The first chapter of this study is devoted to a brief account of Hegel's philosophy and some themes of his philosophy which are adopted by the structuralist and post-structuralist way of thinking. The main subject of the second chapter is structuralism: in this chapter Saussurean linguistics and its connections with Hegel and with the philological tradition of the nineteenth century is analyzed; subsequently the Hegelian aspects of the structuralist ethnology of Levi-Strauss and the structuralist criticism of Barthes are exposed. The third chapter deals with post-structuralist philosophy: the post-structuralist views of Barthes are introduced in order to explain the transition from structuralism to post-structuralism, and the philosophical approaches of Grilles Deleuze, Michel Foucault and Jacques Derrida are analyzed in respect to the role of Hegelian themes in these approaches. The fourth and last chapter is an attempt to evaluate the structuralist and post-structuralist approaches to Hegel himself. 148

Felsefe alanında modernizm-postmodernizm tartışma sına bakıldığında, bu tartışmanın, hep, birtakım `kriz` tanılarına dayanılarak yapıldığı görülür. Modernizm- postmodernizm tartışmasının önemli isimlerinden biri olan Jean Francois Lyotard da, bu tartışmaya `anlatılar krizi` adını verdiği bir kriz tanısını ortaya koyarak katılır. Lyotard' ın `anlatılar krizi` olarak adlandırdığı kriz dikkate alındığında, düşünürün gerçeklikle ilgili bir soruna dikkat çektiği, `anlatılar krizini ortaya koyarken, `gerçekliğe` ilişkin bir kaygı taşıdığı görülmektedir. Öte yandan, postmodernizme ilişkin yaygın bir kanının, bir `postmodernist` olduğu düşünülen Lyotard 'la ilgisinde sınanması da, düşünürün `gerçeklik` görüşüne bakmayı gerektirmektedir. Postmodernist olduğu varsayılan düşünürlerin, her şeyi söylemenin -ve yapmanın- aynı derecede meşru ve serbest olduğu bir dünya tasarladıkları, pluralizmi destekledikleri kanısı, yaygın bir kanıdır; ancak, Lyotard 'm görüşleri, özellikle de `gerçeklik` görüşü dikkate alındığında, bu kanının Lyotard için doğru olmadığı ortaya çıkar. Bu çalışmanın amacı, Lyotard 'm `gerçeklik` anlayışını, bu iki hareket noktasının kılavuzluğunda incelemektir. Bu inceleme, dört bölümde gerçekleştirilmiştir: İlk bölümde, Lyotard 'm `anlatılar krizi`ne ilişkin görüşleri, düşünürün `modern` ve `postmodern` söyleme, `bilgi`ye, `bilim`e ve `postmodern durum` saptamasına ilişkin görüşleriyle birlikte serimlenmektedir. İkinci bölümde, düşünürün ilk bölümde ortaya konulan görüşlerine de kaynaklık eden temel bir problemi, `gerçeklikteki birşeyin sunulması`na ilişkin görüşleri incelenmektedir. Üçüncü bölümde, Lyotard' in hedefi ve `felsefi politika` dediği şeye ilişkin görüşleri ele alınmaktadır. Dördüncü ve son bölümde de, Lyotard' m ilk üç bölümde ortaya konulan görüşlerinin ve Lyotard hakkındaki görüşlerin eleştirilmesine, özellikle de Lyotard 'm niçin bir post modernist sayılamayacağının ortaya konulmasına çalışıl maktadır. When the discussion of modernism and postmodernism in philosophy is taken into consideration and when it is asked what the core of this discussion might be, it is observed that most of the thinkers participating in this discussion diagnose a `crisis`; actually, the common feature of this discussion is the diagnosis of a `crisis`. Jean-François Lyotard, who is of great impor tance for this discussion, also diagnoses a `crisis`, namely the `crisis of narratives`. Thus Lyotard tries to draw attention to a problem regarding `reality`. The determination of Lyotard' s position within this recent discussion requires the examination of his diagnosis concerning the `crisis of narratives`, and of his concep tion of `reality` as the basic theme of his diagnosis. Besides, there is the prevalent opinion of the thinkers considered as, or supposed to be postmodernists that `they project a world in which everything is permit ted and legally said - and done`, and they would `support pluralism`. Still, Lyotard' s conception of `reality` shows that he would never accept such a projection. As regards Lyotard, this prevalent opinion is not true, since his conception of `reality` makes this impossible. Therefore this opinion must be tested in connection with Lyotard; and to do this, his conception of `reality` has to be scrutinized as the basic theme of his philosophy. The aim of this study is to scrutinize Lyotard' s conception of `reality`, starting from the two above-men tioned points. This study consists of four chapters: In the first chapter, Lyotard' s views concerning the `crisis of narra tives` are presented as well as his views concerning thetives` are presented as well as his views concerning the `modern` and `postmodern` discourses, and those connected with `knowledge`, `science` and the `postmodern condi tion`. The second chapter is devoted to the problem of presentation, which is the fundamental problem of his diagnosis, and of his views exposed in the first chapter. In the third chapter we deal with Lyotard's `aim` and his conception of `philosophical politics`. The fourth and last chapter is an attempt to evaluate Lyotard's own views, as well as some other people's views on Lyotard. 158

06.03.2018 tarihli ve 30352 sayılı Resmi Gazetede yayımlanan “Yükseköğretim Kanunu İle Bazı Kanun Ve Kanun Hükmünde Kararnamelerde Değişiklik Yapılması Hakkında Kanun” ile 18.06.2018 tarihli “Lisansüstü Tezlerin Elektronik Ortamda Toplanması, Düzenlenmesi ve Erişime Açılmasına İlişkin Yönerge” gereğince tam metin erişime açılmıştır. Bu çalışmada Hannah Arendt tarafından geliştirilen kötülüğün sıradanlaşması fikrinin analiz edilmesi amaçlanmıştır.Çalışmanın birinci bölümünde, Arendt'in politik düşüncesi üzerinde durulmuş, bu bağlamda onun hareket noktası olan totalitarizmin eleştirisi üzerinden ve temel kavramları çerçevesinde politika anlayışı açıklanmaya çalışılmıştır. İkinci bölümde ise, totalitarizmin pratikteki karşılığı olan Nazi Almanyası dönemi incelenmiş, Arendt'in bu döneme ait eleştirilerine yer verilmiş, kötülüğün sıradanlaşması fikri, Arendt'in bu fikri geliştirmesinin nedeni olan Eichmann davası ve ilk kez bu dava sonrasında tartıştığı kavramlar ele alınmıştır.Filozofun tüm eserleri incelenerek onun temel kavramları çıkarılmış ve çalışmamız bu kavramlar eşliğinde oluşturulmuştur.Çalışmamızın sonucunda Arendt'te kötülüğün sıradanlaşması değerlendirmesinin düşünme yoksunluğu ve yargı yetisinin kaybını tanımlamak için geliştirildiği tespit edilmiştir. The aim of this study is to analyze Hannah Arendt?s conception of the banality of evil.The first chapter of the study is devoted to an overview of Arendt?s political thought in order to provide an introduction necessary for a proper approach to the conception of the banality of evil. In this introductory chapter we present the conceptual order of the political philosophy of Arendt starting with her criticism of totalitarianism. In the second chapter of the study the period of Nazism in Germany is scrutinized with the help of Arendt?s political analysis. The focus of her analysis is the conception of the banality of evil which was developed by the philosopher during the trial of Eichmann.In the conclusion chapter of the study, the focus is the analysis of the conception of the banality of evil in respect to its causes ? e.g. the deprivation of the power of reasoning and the loss of judging ability.All the works of Arendt have been analyzed in order to determine the main structure of the study and then the philosopher?s basic concepts and their interrelations have been elaborated within the framework of the predetermined structure.

Background: Sub-optimal response in schizophrenia is frequent, warranting augmentation strategies over treatment-as-usual (TAU)., Methods: We assessed nutraceuticals/phytoceutical augmentation strategies via network meta-analysis. Randomized controlled trials in schizophrenia/schizoaffective disorder were identified via the following databases: PubMed, MEDLINE, EMBASE, Scopus, PsycINFO, CENTRAL, and ClinicalTrials.gov. Change (Standardized Mean Difference=SMD) in total symptomatology and acceptability (Risk Ratio=RR) were co-primary outcomes. Secondary outcomes were positive, negative, cognitive, and depressive symptom changes, general psychopathology, tolerability, and response rates. We conducted subset analyses by disease phase and sensitivity analyses by risk of bias and assessed global/local inconsistency, publication bias, risk of bias, and confidence in the evidence., Results: The systematic review included 49 records documenting 50 studies (n=2,384) documenting 22 interventions. Citicoline (SMD=-1.05,95%CI=-1.85; -.24), L-lysine (SMD=-1.04,95%CI=-1.84;-.25), N-acetylcysteine (SMD=-.87,95%CI=-1.27;-.47) and sarcosine (SMD=-.5,95%CI=-.87-.13) outperformed placebo for total symptomatology. High heterogeneity (tau 2 =.10, I 2 =55.9%) and global inconsistency (Q=40.79, df=18, p=.002) emerged without publication bias (Egger's test, p=.42). Sarcosine improved negative symptoms (SMD=-.65, 95%CI=-1.10; -.19). N-acetylcysteine improved negative symptoms (SMD=-.90, 95%CI=-1.42; -.39)/general psychopathology (SMD=-.76, 95%CI=-1.39; -.13). No compound improved total symptomatology within acute phase studies (k=7, n=422). Sarcosine (SMD=-1.26,95%CI=-1.91; -.60), citicoline (SMD=-1.05,95%CI=-1.65;-.44), and N-acetylcysteine (SMD=-.55,95%CI=-.92,-.19) outperformed placebo augmentation in clinically stable participants. Sensitivity analyses removing high-risk-of-bias studies confirmed overall findings in all phases and clinically stable samples. In contrast, the acute phase analysis restricted to low risk-of-bias studies showed a superior effect vs. placebo for N-acetylcysteine (SMD=-1.10,95%CI=-1.75,-.45), L-lysine (SMD=-1.05,95%CI=-1.55,-.19), omega-3 fatty acids (SMD=-.83,95%CI=-1.31,-.34) and withania somnifera (SMD=-.71,95%CI=-1.21,-.22). Citicoline (SMD=-1.05,95%CI=-1.86,-.23), L-lysine (SMD=-1.04,95%CI=-1.84,-.24), N-acetylcysteine (SMD=-.89,95%CI=-1.35,-.43) and sarcosine (SMD=-.61,95%CI=-1.02,-.21) outperformed placebo augmentation of TAU ("any phase"). Drop-out due to any cause or adverse events did not differ between nutraceutical/phytoceutical vs. placebo+TAU., Conclusions: Sarcosine, citicoline, and N-acetylcysteine are promising augmentation interventions in stable patients with schizophrenia, yet the quality of evidence is low to very low. Further high-quality trials in acute phases/specific outcomes/difficult-to-treat schizophrenia are warranted., Competing Interests: Conflict of interest MF received honoraria for his speaker activity from the American Society of Clinical Psychopharmacology (ASCP) and served as a consultant for Angelini, Otsuka, Lundbeck, Sanofi-Aventis, and Boehringer Ingelheim. WM has previously received funding from the Cancer Council Queensland and university grants/fellowships from La Trobe University, Deakin University, University of Queensland, and Bond University. WM has received funding and/or has attended events funded by Cobram Estate Pty. Ltd and Bega Dairy and Drinks Pty Ltd. WM has received travel funding from the Nutrition Society of Australia. WM has received consultancy funding from Nutrition Research Australia and ParachuteBH. WM has received speakers honoraria from The Cancer Council Queensland and the Princess Alexandra Research Foundation. MS has received honoraria/has been a consultant for AbbVie, Angelini, Lundbeck, and Otsuka. VBM received honoraria from Angelini, unrelated to the present work. CUC has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Adock Ingram, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer-Ingelheim, Bristol-Meyers Squibb, Car dio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Delpor, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Jamjoom Pharma, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Sage, Seqirus, SK Life Science, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Tabuk, Takeda, Teva, Tolmar, Vertex, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Kuleon Biosciences, LB Pharma, Mindpax, and Quantic. All other authors declare no conflicts of interest relevant to this work.