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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.

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.

Resume Les patients atteints du trouble de la personnalite borderline sont souvent diagnostiques a tort comme ayant un trouble bipolaire et inversement. En effet, un certain nombre de caracteristiques communes aux deux troubles pourraient expliquer ce probleme : l’instabilite affective ainsi que l’impulsivite representent des facteurs de confusion et contribuent au risque de mauvais diagnostic. Cependant, ces caracteristiques se manifestent de manieres differentes selon la pathologie. Les dimensions emotionnelles et impulsives de 40 patients (21 patients presentant un trouble bipolaire et 19 patients presentant un trouble de la personnalite borderline) ont ete comparees a l’aide des echelles ALS, AIM et UPPS. Les patients borderline obtiennent des scores significativement plus eleves que les patients bipolaires aux echelles ALS et AIM. En ce qui concerne l’UPPS, les patients borderline presentent des scores significativement plus eleves que les patients bipolaires aux dimensions « manque de premeditation » et « manque de perseverance » ; en revanche, les patients bipolaires ont obtenu des scores significativement plus eleves que les patients borderline a la dimension « urgence negative ». Cette etude montre que l’on peut differencier le trouble bipolaire du trouble de la personnalite borderline grâce aux dimensions affectives ainsi qu’aux differentes dimensions de l’impulsivite.

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.

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.

Resume Le trouble bipolaire et le trouble de la personnalite borderline presentent une incidence sur la vie des patients tant sur la symptomatologie que sur la qualite de vie. Ces deux troubles semblent avoir des similitudes cliniques ne facilitant pas le diagnostic. En effet, les dimensions affectives, tant d’un point de vue de la labilite que de l’intensite ainsi qu’au niveau de l’impulsivite, rendent difficile la distinction clinique entre ces deux pathologies. Au travers de cette revue de la litterature, nous tenterons de mettre en avant les differences, au niveau de l’affectivite et de l’impulsivite, entre le trouble bipolaire et le trouble de la personnalite borderline afin de tenter d’apporter une finesse clinique entre ces deux pathologies dans le but, a plus long terme, d’affiner la prise en charge therapeutique.

Early onset of heroin use is a severity marker of heroin use disorder. We studied the interaction between early onset and rapid transition to heroin dependence recorded with retrospective interviews in 213 patients with severe heroin dependence and history of methadone maintenance treatment. General linear models were used to identify independent factors associated with early onset, factors associated with rapid transition to dependence, and a multivariate model was used to study the interaction of those two dimensions. Lifetime history of anxiety disorders and age at onset of cannabis use are shared common risk factors and are associated with the interaction.

Studies have shown that patients with borderline personality disorder are often misdiagnosed to have bipolar disorder and conversely. Indeed, a number of characteristics common to both disorders could explain this problem: emotional instability as well as impulsivity represent confounding factors and contribute to the risk of misdiagnosis. However, it appears that these characteristics manifest themselves in different ways according to the pathology. The aim of the study is to show differences between affective lability, emotional intensity and impulsivity dimensions. The clinical aim is to refine bipolar disorder and borderline personality disorder diagnosis, to improve psychological care for these patients in the long-term.We compared the emotional and impulsive dimensions in two groups of patients: a group of 21 patients with bipolar disorder and a group of 19 patients with borderline personality disorder. Tools: ALS, a self-report questionnaire to evaluate affective lability, AIM, a self-report questionnaire to see affective intensity, and UPPS, a self-report questionnaire to measure impulsivity according to several dimensions.The results indicate that borderline patients scored significantly higher than bipolar patients at the ALS and AIM scales. Regarding the UPPS, borderline patients scored significantly higher than bipolar patients for the dimensions "lack of premeditation" and "lack of perseverance"; however, bipolar patients had significantly higher scores than borderline patients for the dimension "negative emergency".This study shows that bipolar disorder and borderline personality can be differentiated thanks to emotional dimensions as well as different dimensions of impulsivity: borderline patients appear to have an affective lability and intensity more important than bipolar patients; it also appears that impulsivity manifests itself differently according to the disorder.

Introduction Cocaine users often experience transient psychotic symptoms following cocaine use (Smith et al. 2009). The severity of such psychotic symptoms is influenced by cocaine dose (Vorspan et al. 2011). Several authors observed a higher prevalence of childhood trauma in cocaine addicts than control subjects (Enoch et al. 2010). Objective Describe cocaine induced psychosis and evaluate if it is associated with childhood trauma. Aim Define the population of cocaine users who experiment cocaine induced psychotic symptoms. Method We did a transversal retrospective study. 100 outpatient cocaine users were evaluated with Scale for the Assessment of Positive Symptoms of Crack Induced Psychosis (SAPS-CIP) and Childhood Trauma Questionnaire (CTQ). Informations were obtained about lifetime cocaine use (age of onset, DSM IV dependence criteria, route of administration, daily dose, days of use per month). Results We did not observe any link between SAPS-CIP and CTQ or CTQ and cocaine consumption. About cocaine consumption, more often patients took cocaine during the worst period, higher is the SAPS-CIP score. If patients are (or were) dependent to cocaine, they have higher scores on SAPS-CIP. Moreover, if patients took cocaine intravenously, they have higher scores on SAPS-CIP than if they took it by snorting, or smoking. Conclusion In the conditions of our study, childhood trauma isn’t a mediator for cocaine induced psychosis. About psychotic symptoms, they seem to be more severe among daily cocaine dependents who take it intravenously.