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In C4 plants, the pyruvate (Pyr), phosphate dikinase regulatory protein (PDRP) regulates the activity of the C4 pathway enzyme Pyr, phosphate dikinase (PPDK) in a light-/dark-dependent manner. The importance of this regulatory action to C4 pathway function and overall C4 photosynthesis is unknown. To resolve this question, we assessed in vivo PPDK phospho-regulation and whole leaf photophysiology in a CRISPR–Cas9 PDRP knockout (KO) mutant of the NADP-ME C4 grass green millet (Setaria viridis). PDRP enzyme activity was undetectable in leaf extracts from PDRP KO lines. Likewise, PPDK phosphorylated at the PDRP-regulatory Thr residue was immunologically undetectable in leaf extracts. PPDK enzyme activity in rapid leaf extracts was constitutively high in the PDRP KO lines, irrespective of light or dark pretreatment of leaves. Gas exchange analysis of net CO2 assimilation revealed PDRP KO leaves had markedly slower light induction kinetics when leaves transition from dark to high-light or low-light to high-light. In the initial 30 min of the light induction phase, KO leaves had an ∼15% lower net CO2 assimilation rate versus the wild-type (WT). Despite the impaired slower induction kinetics, we found growth and vigor of the KO lines to be visibly indistinguishable from the WT when grown in normal air and under standard growth chamber conditions. However, the PDRP KO plants grown under a fluctuating light regime exhibited a gradual multi-day decline in Fv/Fm, indicative of progressive photosystem II damage due to the absence of PDRP. Collectively, our results demonstrate that one of PDRP’s functions in C4 photosynthesis is to ensure optimal photosynthetic light induction kinetics during dynamic changes in incident light.

Background Obsessive-compulsive disorder (OCD) has long been considered as an anxiety disorder, disgust is the dominant emotion in contamination-based OCD. However, disgust seems resistant to exposure with response prevention partly due to the fact that disgust is acquired through evaluative conditioning. Aims The present research investigates a counter-conditioning intervention in treating disgust-related emotional responses in two groups of individuals with high (High contamination concerns, HCC, n = 24) and low (Low contamination concerns LCC, n = 23) contamination concerns. Methods The two groups completed a differential associative learning task in which neutral images were followed by disgusting images (conditioned stimulus; CS+), or not (CS-). Following this acquisition phase, there was a counter-conditioning procedure in which CS+ was followed by a very pleasant unconditional stimulus while CS- remained unreinforced. Results Following counter-conditioning, both groups reported significant reduction in their expectancy of US occurrence and reported less disgust with CS+. For both expectancy and disgust, reduction was lower in the HCC group than in the LCC group. Disgust sensitivity was highly correlated with both acquisition and maintenance of the response acquired, while US expectation was predicted by anxiety. Conclusion Counter-conditioning procedure reduces both expectations and conditioned disgust.

Background If obsessive-compulsive disorder (OCD) has long been considered as an anxiety disorder, disgust is the dominant emotion in contamination-based OCD. However, disgust seems resistant to exposure with response prevention partly due to the fact that disgust is acquired through evaluative conditioning. The present research investigates a counter-conditioning intervention in treating disgust-related emotional responses in two groups of individuals with high (HDCC, n = 25) and low (LDCC, n = 23) contamination concerns. Methods The two groups completed a differential associative learning task in which neutral images were followed by disgusting images (conditioned stimulus; CS+), or not (CS-). Following this acquisition phase, there was a counterconditioning procedure in which CS + was followed by a very pleasant US, while CS- remained unreinforced. Results Following counterconditioning, both groups reported significant reduction in their expectancy of US occurrence and reported less disgust with CS+. For both expectancy and valence, reduction was lower in the HDCC group than in the LDCC group. Disgust sensitivity was highly correlated with both acquisition and maintenance of the response acquired, while US expectation was predicted by anxiety. Conclusion Desensitization to disgust handled by counter-conditioning procedure reduces both expectations and conditioned valence.

International audience; Most individuals with schizophrenia will be confronted with some form of stigma. In recent years, clinicians and family members have increasingly contested the term "schizophrenia". Many of them discuss changing this name, as a means to fight stigma. Up until now, surprisingly, most research has been conducted using self-reports and behavioral research is lacking. The aim of our study was to assess through an experimental design if the term "schizophrenia" itself modifies social behaviours. Forty participants were asked to engage in a synchronization task with a dot displayed on a screen and moved by another person. Non-clinicians participants had to synchronize their movements as accurately as possible with either a "schizophrenia" patient, a patient with "neuro-emotional integration disorder" or a "healthy" subject, kept out of sight. Each condition was counterbalanced between participants. In fact, the movements of the dot were pre-recorded (five trajectories) and were therefore identical for all three conditions. Measuring the error between the displayed and performed trajectories, participants exhibited more errors when they thought they were interacting with a patient in comparison to the "healthy" subject. Post-hoc analysis revealed an even higher difference between "schizophrenia" and "healthy" conditions. Altogether, our results show a significant behavioral impact of the term "schizophrenia" with possibly negative consequences on social interactions. The effect of changing the name reduces this impact but remains unclear.

Resume Contexte Alors que le medecin generaliste (MG) est en premiere ligne pour la prise en charge des troubles psychiatriques courants, seule la moitie de ces troubles est connue du MG. L’objectif etait de comparer leur reperage par les MG avant et apres l’introduction du dispositif du medecin traitant. Methodes Deux enquetes ont ete conduites aupres de 46 MG et 1151 patients (25 patients/MG) en 2003, et 38 MG et 1133 patients (30/MG) en 2013, dans la region de Montpellier. Les patients, recrutes en salle d’attente, ont rempli des auto-questionnaires, dont le Patient Health Questionnaire, appliquant les criteres diagnostiques du DSM-IV. Resultats Au total, 51 % (en 2003) et 52,6 % (en 2013) des patients presentant un trouble psychiatrique courant d’apres le PHQ ont ete detectes par le MG. En 2003, le MG voyait 15,5 % des patients pour la premiere fois, compare a 9,8 % en 2013 (p = 0,006). Le pourcentage de patients consultant plus d’un MG different sur les six derniers mois a egalement diminue, que ce soit pour des raisons pratiques (18,4 % en 2003 et 12,1 % en 2013) ou d’insatisfaction (9,8 % en 2003 et 4,2 % en 2013) (p Conclusion Compare a d’autres etudes, le niveau de detection des troubles psychiatriques est relativement eleve aux deux periodes. Toutefois, il n’a pas augmente apres l’introduction du dispositif du medecin traitant, bien qu’on note une plus grande fidelisation des patients a un MG dans le cadre de ce dispositif.

International audience; OBJECTIVE:Frequent Attenders (FAs) have high rates of both common mental disorders (CMD) and physical disorders, partly justifying this service use behaviour. This study examines both case and non-case concordance between CMDs as estimated by a self-report screening questionnaire and as rated by the general practitioner (GP), in FAs compared to Other Attenders (OAs).METHODS:2275 patients of an overlapping sample of 55 GPs from 2 surveys performed 10 years apart, completed in the waiting room the Patient Health Questionnaire (PHQ) and Client Service Receipt Inventory on 6-month service use. For each patient, the GP rated mental health on a 0-4 scale, with a clear indication that scores of 2 and above referred to caseness. PHQ-CMDs included major and other depressive, anxiety, panic, and somatoform disorders, identified using the original PHQ DSM-IV criteria-based algorithms. FA was defined as the top 10% of attenders in age, sex and survey-year stratified subgroups.RESULTS:FAs had higher rates of PHQ-CMDs (42% versus 23% for OAs, p

International audience; Alors que le médecin généraliste (MG) est en première ligne pour la prise en charge des troubles psychiatriques courants, seule la moitié de ces troubles est connue du MG. L’objectif était de comparer leur repérage par les MG avant et après l’introduction du dispositif du médecin traitant.Deux enquêtes ont été conduites auprès de 46 MG et 1151 patients (25 patients/MG) en 2003, et 38 MG et 1133 patients (30/MG) en 2013, dans la région de Montpellier. Les patients, recrutés en salle d’attente, ont rempli des auto-questionnaires, dont le Patient Health Questionnaire, appliquant les critères diagnostiques du DSM-IV.Au total, 51 % (en 2003) et 52,6 % (en 2013) des patients présentant un trouble psychiatrique courant d’après le PHQ ont été détectés par le MG. En 2003, le MG voyait 15,5 % des patients pour la première fois, comparé à 9,8 % en 2013 (p = 0,006). Le pourcentage de patients consultant plus d’un MG différent sur les six derniers mois a également diminué, que ce soit pour des raisons pratiques (18,4 % en 2003 et 12,1 % en 2013) ou d’insatisfaction (9,8 % en 2003 et 4,2 % en 2013) (p < 0,0001). L’orientation des patients chez un médecin spécialiste a augmenté de 9,7 % à 14,7 % entre les deux périodes (p = 0,014).Comparé à d’autres études, le niveau de détection des troubles psychiatriques est relativement élevé aux deux périodes. Toutefois, il n’a pas augmenté après l’introduction du dispositif du médecin traitant, bien qu’on note une plus grande fidélisation des patients à un MG dans le cadre de ce dispositif.

International audience; Self-face recognition is crucial for sense of identity and for maintaining a coherent sense of self. Most of our daily life experiences with the image of our own face happen when we look at ourselves in the mirror. However, to date, mirror self-perception in schizophrenia has received little attention despite evidence that face recognition deficits and self abnormalities have been described in schizophrenia. Thus, this study aims to investigate mirror self-face perception in schizophrenia patients and its correlation with clinical symptoms. Twenty-four schizophrenia patients and twenty-five healthy controls were explicitly requested to describe their image in detail during 2min whilst looking at themselves in a mirror. Then, they were asked to report whether they experienced any self-face recognition difficulties. Results showed that schizophrenia patients reported more feelings of strangeness towards their face compared to healthy controls (U=209.5, p=0.048, r=0.28), but no statistically significant differences were found regarding misidentification (p=0.111) and failures in recognition (p=0.081). Symptoms such as hallucinations, somatic concerns and depression were also associated with self-face perception abnormalities (all p-values>0.05). Feelings of strangeness toward one's own face in schizophrenia might be part of a familiar face perception deficit or a more global self-disturbance, which is characterized by a loss of self-other boundaries and has been associated with abnormal body experiences and first rank symptoms. Regarding this last hypothesis, multisensorial integration might have an impact on the way patients perceive themselves since it has an important role in mirror self-perception.

Apathy is a multidimensional symptom composed of cognitive, behavioral, and emotional facets including impaired motivation and reduced goal-directed behavior. Apathy belongs to schizophrenia's negative symptomatology which has received increased attention over the last years including a growing interest in the assessment and the consequences of apathy. Nevertheless, the pathological mechanisms are still insufficiently explored as well as the multidimensional aspect of this symptom. The aim of this article is to provide a review of the main measures used to explore apathy in schizophrenia as well as the cognitive and neural correlates of apathy while taking into account the multidimensionality of this symptom. Studies have shown important correlations between apathy, executive functions and specific brain regions such as the anterior cingulate cortex, orbitofrontal cortex and the ventral and dorsal striatum. Nevertheless, most studies have neglected the multidimensional aspect of apathy, which is assessed as a single-dimension concept. These and other limitations are discussed as well as the main strengths of the current evidence on apathy in schizophrenia.

Background Recent studies suggest that parents' awareness of their offspring's schizophrenia could influence their offspring's insight. Low patient insight is linked to impairment of specific cognitive abilities, and biological parents of schizophrenia patients have impaired capacities in these same domains. However, little is known about what specific socio-demographic, affective or cognitive factors may influence biological parents' awareness of their offspring's disease. Method Data were drawn from 41 patient–parent dyads. Insight was assessed with a modified version of Amador's Scale to assess Unawareness of Mental Disorders, exploring dimensions of parents' awareness and attribution of their offspring's illness and symptoms. Results Higher educational levels, better working memory and executive functioning of parents were associated with better attribution of their offspring's symptoms to schizophrenia. Conclusions Parents' insight into their offspring's schizophrenia is associated with cognitive abilities. This must be taken into account when developing family interventions.

Background Clinical insight in schizophrenia patients is partly associated with familial environment but has been poorly studied to date. We aimed to explore (1) the relationship between parents' cognitive insight and their offspring's; (2) the relationship between parents' cognitive insight and their clinical insight into the disease of their offspring; and (3) the clinical and cognitive determinants of cognitive insight in parents. Methods Cognitive insight was assessed in 37 patient–biological parent pairs/dyads with the Beck Cognitive Insight Scale (BCIS). Other measures included the Scale to assess Unawareness of Mental Disorder and cognitive assessments. Results We found no significant association between parents' cognitive insight and their offspring's. Conversely, a positive association between parents' cognitive insight and parents' insight into their offspring's symptoms was found. Better awareness of their offspring's specific symptoms was associated with lower levels of overconfidence in one's beliefs and with BCIS total score. BCIS Self-Certainty and BCIS total score were associated with better executive functioning and verbal comprehension. Conclusions Better insight into their offspring's symptoms is associated with cognitive insight in biological parents of schizophrenia patients. Our results support the integration of cognitive intervention targeting parents' cognitive flexibility in family psychoeducational programs and provide an important first step towards developing a more refined understanding of the factors involved in insight into symptoms of illness in parents of schizophrenia patients.

Ketamine’s efficacy in depressive disorders has been established in several controlled trials. The aim of the present study was to determine whether or not ketamine administration significantly improves depressive symptomatology in depression and more specifically in major depressive disorder (MDD), bipolar depression, resistant depression (non-ECT studies), and as an anesthetic agent in electroconvulsive therapy (ECT) for resistant depression (ECT studies). Secondary outcomes were the duration of ketamine’s effect, the efficacy on suicidal ideations, the existence of a dose effect, and the safety/tolerance of the treatment. Studies were included if they met the following criteria (without any language or date restriction): design: randomized controlled trials, intervention: ketamine administration, participants: diagnosis of depression, and evaluation of severity based on a validated scale. We calculated standardized mean differences (SMDs) with 95 % confidence intervals (CIs) for each study. We used fixed and random effects models. Heterogeneity was assessed using the I2 statistic. We included nine non-ECT studies in our quantitative analysis (192 patients with major depressive disorder and 34 patients with bipolar depression). Overall, depression scores were significantly decreased in the ketamine groups compared to those in the control groups (SMD = −0.99; 95 % CI −1.23, −0.75; p

The relationship between clinically effective antipsychotic drugs in obsessive-compulsive disorders (OCD) and binding affinities to cloned dopamine and serotonin receptor subtypes was analyzed in an effort to clarify the contribution of individual receptor subtypes to medication response.Meta-analysis was used to update previous meta-analyses of effectiveness data of add-on antipsychotic drugs to selective serotonin reuptake inhibitors (SSRIs) in OCD. Twelve previously analyzed randomized controlled trials (RCTs) and one new RCT were included. We performed a metaregression using a mixed-effect model to examine the association between antipsychotic's effectiveness and receptor affinity.A total of 5 treatment arms obtained from 13 RCTs (431 patients) were included in our study. The results of our metaregression showed a significant association between D2 and D3 dopamine receptor affinities and effectiveness in OCD (respectively, slope = -0.36, p = 0.01; and slope = -0.50, p = 0.01) whereas other dopamine receptors and serotonin receptors were not significantly associated.These observations suggest that increasing D2 and D3 dopamine receptor binding affinities enhances antipsychotics' effectiveness in obsessive-compulsive disorders.

The present study examined the internal and external validity of the French version of the 12-item Disgust Propensity and Sensitivity Scale-Revised (DPSS-12) in a nonclinical sample from the general population. Two hundred and eighty-two participants completed the DPSSf-12 questionnaire as well as the Anxiety Sensitivity Index (ASI), Anxiety Trait (STAI B), Obsessional Belief Questionnaire 44 items (OBQ 44), Obsessive Compulsive Inventory-Revised (OCI-R) and Positive and Negative Affect Schedule (PANAS). Confirmatory Factor Analysis supported a 2-factor structure after two sensitivity items were removed. The 10-item scale showed good internal consistency, construct validity and test-retest reliability. These adequate psychometric properties make the DPSSf-10 appropriate for use by researchers and practitioners.

Resume De nouveaux defis se presentent a la medecine et en particulier a la psychiatrie. Le role du psychiatre pourrait se transformer a l’avenir en une gestion d’equipes de sante mentale (medecins generalistes, infirmiers, psychologues, educateurs specialises…). Interviennent ici les concepts de charisme et de leadership. Le charisme est « une qualite qui permet a son possesseur d’exercer un ascendant, une autorite sur un groupe ». Le leadership designe, « la fonction, la position de chef, et par extension, une position dominante ». Objectif de l’article Proposer quelques pistes de reflexion sur le charisme et le leadership, les moyens de les developper dans trois situations de la pratique psychiatrique au quotidien : la communication duale (entre soignants ou avec le patient), la communication orale lors d’un colloque et la gestion d’une equipe de sante mentale. Methode Les bases Medline et Web of science ont ete explorees selon les criteres PRISMA sans limite de date de publication. Le paradigme de recherche etait ([psychiatrist OR physician] AND mental health AND [leadership OR charisma]). Resultats Trente-quatre articles ont ete inclus dans l’analyse qualitative. Le chef doit d’abord s’interroger sur sa vision de l’avenir, pour la transmettre avec passion a son equipe de sante mentale. Le leadership ne depend pas de la position hierarchique et des responsabilites administratives. Le clinicien travaillera sur les moyens de developper son charisme, par ses interactions avec ses pairs et son equipe, par l’attention apportee a son apparence et a son lieu de travail, par le renforcement positif. Il apprendra a gerer et harmoniser les differents types de personnalites au sein de son equipe en prenant particulierement garde aux attitudes passive-agressives. Il comptera parmi ses qualites la ponctualite, la politesse, le sourire, l’auto-derision, la regulation de ses propres emotions. Discussion et conclusion Le charisme semble etre une dimension indispensable du chef qui va pouvoir mettre en place efficacement son leadership et la gestion de son equipe. Bien au-dela de la psychiatrie, ces reflexions nous semblent utiles a l’ensemble de la medecine.

Resume Soixante-quinze pour cent des patients presentant une phobie du sang-injection-accident (PSIA) presentent des pertes de connaissance lors de l’exposition aux stimuli phobogenes. Cette specificite aurait des implications medicales importantes (pathologies somatiques non diagnostiquees et non traitees) responsables d’un cout individuel et social. Ses mecanismes psychophysiologiques sont peu connus et les donnees de la litterature concernant les therapeutiques n’ont pas fait l’objet d’une revue a notre connaissance. Synthese des mecanismes psychophysiologiques a l’œuvre dans la PSIA : la specificite psychophysiologique de la PSIA est la survenue d’une syncope vasovagale biphasique. La vision du stimulus phobogene est suivie de l’apparition d’une emotion de peur et de l’activation du systeme sympathique. L’emotion de degout serait secondairement associee a la stimulation du systeme parasympathique qui serait responsable de la perte de connaissance. Une dysfonction circulatoire predisposante au malaise vasovagal serait presente chez ces patients, meme en l’absence de stimulus phobogene. Plusieurs etudes suggerent que les individus presentant une PSIA ont un plus haut niveau de sensibilite au degout. Efficacite des differentes therapeutiques evaluees dans la PSIA : les techniques de psychotherapie comportementale telles que l’exposition seule, la relaxation durant l’exposition, la tension durant l’exposition, et la tension seule, ont demontre leur efficacite, sans difference significative entre les techniques. L’exposition repetee prealable au degout ne permettrait pas d’optimiser l’efficacite de l’exposition. Nous avons montre les specificites psychophysiologiques de la PSIA. Leur comprehension est necessaire pour developper des techniques specifiques visant a ameliorer le pronostic de ce trouble.

INTRODUCTION: Toxoplasma gondii is the most common protozoan parasite in developed nations. Up to 43% of the French population may be infected, depending on eating habits and exposure to cats, and almost one third of the world human's population may be infected. Two types of infection have been described: a congenital form and an acquired form. Although the medical profession treats these latent cases as asymptomatic and clinically unimportant, results of animal studies and recent studies of personality profiles, behavior, and psychomotor performance have led to reconsider this assumption. PRECLINICAL DATA: Among rats: parasite cysts are more abundant in amygdalar structures than those found in other regions of the brain. Infection does not influence locomotion, anxiety, hippocampal-dependent learning, fear conditioning (or its extinction) and neophobia in rats. Rats' natural predator is the cat, which is also T. gondii's reservoir. Naturally, rats have an aversion to cat urine, but the parasite suppresses this aversion in rats, thus influencing the infection cycle. Tachyzoites may invade different types of nervous cells, such as neurons, astrocytes and microglial cells in the brain, and Purkinje cells in cerebellum. Intracellular tachyzoites manipulate several signs for transduction mechanisms involved in apoptosis, antimicrobial effectors functions, and immune cell maturation. Dopamine levels are 14% higher in mice with chronic infections. These neurochemical changes may be factors contributing to mental and motor abnormalities that accompany or follow toxoplasmosis in rodents and possibly in humans. Moreover, the antipsychotic haloperidol and the mood stabilizer valproic acid most effectively inhibit Toxoplasma growth in vitro with synergistic activity. CLINICAL DATA: The effects of the parasite are not due to the manipulation in an evolutionary sense but merely due to neuropathological or neuroimmunological effects of the parasite's presence. Toxoplasmosis and schizophrenia: epidemiological studies point to a role for toxoplasmosis in schizophrenia's etiology, probably during pregnancy and early life, this association being congruent with studies in animal models indicating that animal exposures of the developing brain to infectious agents or immune modulating agents can be associated with behavioral changes that do not appear until the animal reaches full maturity. Psychiatric patients have increased rates of toxoplasmic antibodies, the differences between cases and controls being greatest in individuals who are assayed near the time of the onset of their symptoms. The increase of dopamine in the brain of infected subjects can represent the missing link between toxoplasmosis and schizophrenia. Toxoplasmosis and Obsessive Compulsive Disorder (OCD): the seropositivity rate for anti-T. gondii IgG antibodies among OCD patients is found to be significantly higher than the rate in healthy volunteers. Infection of basal ganglia may be implicated in the pathogenesis of OCD among Toxoplasma seropositive subjects. Toxoplasmosis and personality: infected men appear to be more dogmatic, less confident, more jealous, more cautious, less impulsive and more orderly than others. Conversely, infected women seem warmest, more conscientious, more insecure, more sanctimonious and more persistent than others. It is possible that differences in the level of testosterone may be responsible for the observed behavioral differences between Toxoplasma-infected and Toxoplasma-free subjects. CONCLUSION: In the future two major avenues for research seem essential. On one hand, prospective studies and research efforts must still be carried out to understand the mechanisms by which the parasite induces these psychiatric disorders. On the other hand, it has not yet been demonstrated that patients with positive toxoplasmic serology may better respond to haloperidol's or valproic acid's antiparasitic activity. These results may appear as a major issue in the drug's prescribing choices and explain variability in response to the treatment of patients with schizophrenia that is not explained by the genetic polymorphism.

This systematic review summarizes and critically appraises the literature on the effect of erythropoietin (EPO) in schizophrenia patients and the pathophysiological mechanisms that may explain the potential of its use in this disease. EPO is mainly known for its regulatory activity in the synthesis of erythrocytes and is frequently used in treatment of chronic anemia. This cytokine, however, has many other properties, some of which may improve the symptoms of psychiatric illness. The review follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement guidelines. Three databases (Medline, Web of Science, and Cochrane) were searched combining the search terms 'erythropoietin AND (psychotic disorders OR schizophrenia)'. Seventy-eight studies were included in qualitative synthesis, a meta-analytic approach being prohibited. The findings suggest that several EPO cerebral potential properties may be relevant for schizophrenia treatment, such as neurotransmission regulation, neuroprotection, modulation of inflammation, effects on blood-brain barrier permeability, effects on oxidative stress and neurogenesis. Several potentially detrimental side-effects of EPO therapy, such as increased risk of thrombosis, cancer, increased metabolic rate and mean arterial blood pressure leading to cerebral ischemia could severely limit or halt the use of EPO. Overall, because the available data are inconclusive, further efforts in this field are warranted.

International audience; Pharmacological cognitive enhancement refers to improvement in cognitive functions after drug use in healthy individuals. This popular topic attracts attention both from the general public and the scientific community. The objective was to explore innovative mechanisms of psychostimulant's action, whose potential effectiveness was assessed in randomized placebo-controlled trials (RCTs). A systematic review was carried out, using the words "attention", "memory", "learning", "executive functions", and "vigilance/wakefulness" combined to "cognitive enhancer" or "smart drug". Methylphenidate, amphetamines, modafinil, nicotine, acetylcholine esterase inhibitors and antidepressants were extensively studied in previous meta-analyses and were not included in the present work. Drugs were classified according to their primary mode of action, namely catecholaminergic drugs (tolcapone, pramipexole, guanfacine), cholinergic drugs (anticholinergics), glutamatergic drugs (ampakines), histaminergic drugs, and non-specified (glucocorticoids). Overall, 50 RCTs were included in the present review. In conclusion, a number of new active drugs were found to improve some cognitive functions, in particular verbal episodic memory. However the number of RCTs was limited, and most of the studies found negative results. Future studies should assess both effectiveness and tolerance of repeated doses administration, and individual variability in dose response (including baseline characteristics and potential genetic polymorphisms). One explanation for the limited number of recent RCTs with new psychostimulants seems to be the ethical debate surrounding pharmaceutical cognitive enhancement in healthy subjects.

International audience; The gut microbiota is increasingly considered as a symbiotic partner in the maintenance of good health. Metagenomic approaches could help to discover how the complex gut microbial ecosystem participates in the control of the host's brain development and function, and could be relevant for future therapeutic developments, such as probiotics, prebiotics and nutritional approaches for psychiatric disorders. Previous reviews focused on the effects of microbiota on the central nervous system in in vitro and animal studies. The aim of the present review is to synthetize the current data on the association between microbiota dysbiosis and onset and/or maintenance of major psychiatric disorders, and to explore potential therapeutic opportunities targeting microbiota dysbiosis in psychiatric patients.; Le microbiote intestinal est considéré de plus en plus comme un partenaire symbiotique contribuant au bon état de santé général de l’organisme. Les approches métagénomiques, en pleine expansion, permettent de mieux en mieux appréhender la complexité de l’écosystème intestinal et de son impact sur le développement et le fonctionnement du système nerveux central de son hôte. Elles pourraient permettre à l’avenir le développement de thérapeutiques spécifiques ciblant le microbiote intestinal, comme les probiotiques, les prébiotiques et les approches nutritionnelles chez les patients souffrant de troubles mentaux. Ces traitements existent déjà dans le traitement de certaines pathologies intestinales, mais l’efficacité, le type de souches, la quantité et la durée administrée restent à déterminer chez l’humain, alors que les résultats animaux sont très prometteurs dans les modèles de troubles anxieux et de stress chronique. Le but de la présente revue est de synthétiser les données actuelles, d’une part, sur l’association entre la dysbiose du microbiote intestinal et le déclenchement ou l’entretien de troubles psychiatriques, et d’autre part, d’explorer les thérapeutiques potentielles qui pourraient être proposées aux patients souffrant de troubles psychiatriques associés à une dysbiose intestinale.

International audience; Poor insight is found in up to 80% of schizophrenia patients and has been associated with multiple factors of which cognitive functioning, social and environmental factors. Few studies have explored associations between patient insight and that of their biological parents', and the influence of parental factors. Insight was assessed in 41 patients and their biological parents with Amador's Scale for the assessment of Unawareness of Mental Disorder (SUMD). Parents' knowledge about schizophrenia and critical attitudes were assessed with validated self-report questionnaires. Both groups underwent cognitive assessments for working memory and executive functioning. Insight in patients and their parents was not associated for any of the SUMD dimensions but a significant correlation was found between patient and parent awareness of treatment effect for patient-parent dyads with frequent daily contact. Low parental critical attitude was associated with higher patient awareness of symptoms and a high parental memory task score with high patient insight. Our study is the first to suggest a possible influence of parental factors such as critical attitudes and cognitive performance on patient insight.

International audience

International audience; It is unclear whether adult smokers with childhood attention-deficit/hyperactivity disorder history (CH) have more severe smoking behavior than non-CH smokers, while it is clearly suggested that CH adolescents have more severe smoking behavior than CH adolescents. The aim of the present comprehensive meta-analysis is to determine whether CH smokers have more severe smoking behavior characteristics than those without and the effect of age on the association between CH and smoking behavior. We included all case-control studies and first round data collection of observational studies addressing the difference in smoking behavior characteristics of CH smokers versus non-CH smokers, with validated scales or structured interviews, without any language or date restriction. Nine studies (including 365 smokers with CH and 1,708 smokers without) were included. Compared to non-CH smokers, CH smokers smoked significantly more cigarettes [standardized mean differences (SMD) = 0.15, 95 % CI 0.01-0.28, p = 0.04] and began to regularly smoke earlier (SMD = -0.28, 95 % CI -0.49; -0.07, p = 0.01) but were not significantly more nicotine dependent (SMD = 0.23, 95 % CI -0.04 to 0.48, p = 0.08). After removing the single adolescent study, the significant association between CH and number of daily smoked cigarettes disappeared, and subgroups analyses confirmed that the significant association between CH and number of daily smoked cigarettes disappeared as age increased. Our meta-analysis illustrates a clinically important link between CH and tobacco smoking in adolescence but not later in life. Further high-quality studies are needed to confirm this finding, as only two studies included participants with a mean age below 20 years.

International audience; Recent studies have shown a strong link between Toxoplasma gondii infection and psychiatric disorders, especially schizophrenia and bipolar disorders (odd ratio ≈2.7 for each disorder). Antipsychotic drugs and mood stabilizers may have anti-toxoplasmic activity that potentially may be associated with better effectiveness in these disorders, but previous results have been few in number and conflicting. We therefore sought to determine which daily prescribed antipsychotics and mood stabilizer have the best anti-toxoplasmic activity during the development phase of the parasite. In the present study, we examined the effects of commonly used antipsychotic drugs (amisulpride, cyamemazine, fluphenazine, haloperidol, levomepromazine, loxapine, olanzapine, risperidone and tiapride) and one mood-stabilizing agent (valproate) on toxoplasmic activity. We replicated that fluphenazine has a high anti-toxoplasmic activity, but it does not seem to be a phenothiazine-specific class effect: indeed, we found that another first-generation antipsychotic, zuclopenthixol, has a high anti-toxoplasmic activity. Valproate, tiapride and amisulpride have no anti-toxoplasmic activity on parasite growth, and the other antipsychotic drugs showed low or intermediate anti-toxoplasmic activity. As it is not possible to know the intracellular concentrations of antipsychotics in the brain, further clinical studies are warranted to determine whether these in vitro findings have potential implications in treatment of toxo-positive patients with schizophrenia. These findings may be potentially relevant for the choice of the first-line antipsychotic drug or mood stabilizer in previously infected patients.

International audience

International audience; Nanomedicine is defined as the area using nanotechnology's concepts for the benefit of human beings' health and well being. In this article, we aimed to provide an overview of areas where nanotechnology is applied and how they could be extended to care for psychiatric illnesses. The main applications of nanotechnology in psychiatry are (i) pharmacology. There are two main difficulties in neuropharmacology: drugs have to pass the blood-brain barrier and then to be internalized by targeted cells. Nanoparticles could increase drugs bioavailability and pharmacokinetics, especially improving safety and efficacy of psychotropic drugs. Liposomes, nanosomes, nanoparticle polymers, nanobubbles are some examples of this targeted drug delivery. Nanotechnologies could also add new pharmacological properties, like nanoshells and dendrimers (ii) living analysis. Nanotechnology provides technical assistance to in vivo imaging or metabolome analysis (iii) central nervous system modeling. Research teams have succeeded to modelize inorganic synapses and mimick synaptic behavior, a step essential for further creation of artificial neural systems. Some nanoparticle assemblies present the same small worlds and free-scale networks architecture as cortical neural networks. Nanotechnologies and quantum physics could be used to create models of artificial intelligence and mental illnesses. We are not about to see a concrete application of nanomedicine in daily psychiatric practice. Even if nanotechnologies are promising, their safety is still inconsistent and this must be kept in mind. However, it seems essential that psychiatrists do not forsake this area of research the perspectives of which could be decisive in the field of mental illness.

Abnormal decision-making has been described as a key-concept to understand some behavioral disturbances in schizophrenia. However, whether schizophrenia patients display impairments in profitable decision-making on experimental designs is still controversial (1) to assess performance on decision-making paradigms under ambiguity and under risk conditions in a large sample of schizophrenia patients and (2) to study the impact of clinical variables on decision-making performance in schizophrenia. The Iowa gambling task (IGT) and the game of dice task (GDT) were administered to assess, respectively, decision-making under ambiguity and under risk in 63 schizophrenia patients and 67 healthy controls. In addition, clinical variables (e.g., schizophrenic symptoms, self-reported depression, and impulsivity) were evaluated using appropriate questionnaires the same day. Pharmacological treatments were reported. Schizophrenia patients had impaired performances on both IGT and GDT tasks. No correlation between the decision-making tasks performance and clinical variables was found. Lower gains on the GDT were associated with executive dysfunctioning in schizophrenia. These findings give evidence that schizophrenia patients display impairments in both decision-making under ambiguity and under risk.

article i nfo Article history: The processes underlying the ability to make decisions about recommended treatments remain poorly understood in schizophrenia. The aim of this study was to explore the relationships between capacity to consent to medication and cognitive biases in 60 schizophrenia patients. Main measures included the MacArthur Competence Assessment tool forTreatment (MacCAT-T) and the Beck Cognitive Insight Scale(BCIS). After Bonferroni's correction for multiple correlations, the Self-Reflectiveness dimension of the BCIS was significantly associated with the dimension "Reason- ing" of the MacCAT-T. Cognitive therapy, by enhancing patients' Self-Reflectiveness and considering alternative explanations, could lead to better capacity to consent to treatment in schizophrenia.

International audience; Clinicians have found that fasting was frequently accompanied by an increased level of vigilance and a mood improvement, a subjective feeling of wellbeing, and sometimes of euphoria. Therapeutic fasting, following an established protocol, is safe and well tolerated. We aim in this article to explore the biological mechanisms activated during fasting that could have an effect on brain function with particular focus on mood (we do not discuss here the mechanisms regulating eating behavior) and to provide a comprehensive review on the potential positive impact of therapeutic fasting on mood. We explored Medline, Web of Science and PsycInfo according to the PRISMA criteria (Preferred Reporting Items for Systematic reviews and Meta-Analysis). The initial research paradigm was: [(fasting OR caloric restriction) AND (mental health OR depressive disorders OR mood OR anxiety)]. Many neurobiological mechanisms have been proposed to explain fasting effects on mood, such as changes in neurotransmitters, quality of sleep, synthesis of neurotrophic factors. Many clinical observations relate an early (between day 2 and day 7) effect of fasting on depressive symptoms with an improvement in mood, alertness and a sense of tranquility reported by patients. The persistence of mood improvement over time remains to be determined.

This systematic review summarizes and critically appraises the literature on the effect of erythropoietin (EPO) in schizophrenia patients and the pathophysiological mechanisms that may explain the potential of its use in this disease. EPO is mainly known for its regulatory activity in the synthesis of erythrocytes and is frequently used in treatment of chronic anemia. This cytokine, however, has many other properties, some of which may improve the symptoms of psychiatric illness. The review follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement guidelines. Three databases (Medline, Web of Science, and Cochrane) were searched combining the search terms 'erythropoietin AND (psychotic disorders OR schizophrenia)'. Seventy-eight studies were included in qualitative synthesis, a meta-analytic approach being prohibited. The findings suggest that several EPO cerebral potential properties may be relevant for schizophrenia treatment, such as neurotransmission regulation, neuroprotection, modulation of inflammation, effects on blood-brain barrier permeability, effects on oxidative stress and neurogenesis. Several potentially detrimental side-effects of EPO therapy, such as increased risk of thrombosis, cancer, increased metabolic rate and mean arterial blood pressure leading to cerebral ischemia could severely limit or halt the use of EPO. Overall, because the available data are inconclusive, further efforts in this field are warranted.

Introduction: Important data was recently published on the potential genotoxic or carcinogenic effects of antipsychotics, as well as on their cytotoxic properties on cancer cells, that must be considered by psychiatrists in the benefit/risk ratio of their prescriptions. Aim of the study: To answer whether or not antipsychotics, as a class or only some specific molecules, may influence cancer risk among treated patients. Methods eligibility criteria: All studies (in vitro, animal studies and human studies) concerning effects of antipsychotic drugs on cancer development were included. The search paradigm [neoplasms AND (antipsychotic agents OR neuroleptic OR phenothiazine)] was applied to Medline (1966–present) and Web of Science (1975–present). Results: Ninety-three studies were included in the qualitative synthesis. Results can be summarized as follows: (1) patients with schizophrenia may be less likely to develop cancer than the general population, (2) antipsychotics as a class cannot be considered at the moment as at risk for cancer, even if some antipsychotics have shown carcinogenic properties among rodents, (3) phenothiazines seem to have antiproliferative properties that may be useful in multidrug augmentation strategies in various cancer treatments, but their bad tolerance may decrease usage amongst non-psychotic patients, and (4) clozapine appears to have a separate status given that this molecule shows antiproliferative effects implied in agranulocytosis as well as a potential increased risk for leukemia. Conclusion: Benefit/risk ratio regarding cancer risk is in favor of treating patients with schizophrenia with antipsychotic drugs. The practicing clinician should be reassuring on the subject of cancer risk due to antipsychotic drugs.

We report the case of a 35-year-old patient suffering from schizo-affective disorder since the age of 19 years, treated by a combination of first-generation antipsychotics, zuclopenthixol (100 mg/day) and lithium (1200 mg/day) (serum lithium=0.85 mEq/l). This patient had no associated personality disorder (particularly no antisocial disorder) and no substance abuse disorder. Within the 48 h following the gradual introduction of quetiapine (up to 600 mg/day), the patient presented severe agitation without an environmental explanation, contrasting with the absence of a history of aggressiveness or personality disorder. The diagnoses of manic shift and akathisia were dismissed. The withdrawal and the gradual reintroduction of quetiapine 2 weeks later, which led to another severe agitation, enabled us to attribute the agitation specifically to quetiapine.