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Objective: To investigate the interest in the attitudes toward antipsychotic medication in exploring medication non-adherence., Methods: Schizophrenic patients (N=120) completed the Beliefs about Medicines Questionnaire and measures of medication adherence, and clinical outcomes. Comparison between four attitudinal groups and logistic regressions were performed., Results: High level of adherence varied significantly between attitudinal groups (Accepting, 70%; Indifferent, 63%; Ambivalent, 50%; Sceptical, 14%; p<0.001). Poor insight and psychic side effects were the most significant predictors of negative beliefs., Conclusion: The attitudinal groups approach could facilitate the identification of patients with non-adherence and determine individual targets of interventions to improve negative beliefs., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: This study assesses the psychometric properties of Ward's seven-subtest short form (SF) for WAIS-IV in a sample of adults with schizophrenia (SZ) and schizoaffective disorder., Method: Seventy patients diagnosed with schizophrenia or schizoaffective disorder were administered the full version of the WAIS-IV. Four different versions of the Ward's SF were then calculated. The subtests used were: Similarities, Digit Span, Arithmetic, Information, Coding, Picture Completion, and Block Design (BD version) or Matrix Reasoning (MR version). Prorated and regression-based formulae were assessed for each version., Results: The actual and estimated factorial indexes reflected the typical pattern observed in schizophrenia. The four SFs correlated significantly with their full-version counterparts, but the Perceptual Reasoning Index (PRI) correlated below the acceptance threshold for all four versions. The regression-derived estimates showed larger differences compared to the full form. The four forms revealed comparable but generally low clinical category agreement rates for factor indexes. All SFs showed an acceptable reliability, but they were not correlated with clinical outcomes., Conclusions: The WAIS-IV SF offers a good estimate of WAIS-IV intelligence quotient, which is consistent with previous results. Although the overall scores are comparable between the four versions, the prorated forms provided a better estimation of almost all indexes. MR can be used as an alternative for BD without substantially changing the psychometric properties of the SF. However, we recommend a cautious use of these abbreviated forms when it is necessary to estimate the factor index scores, especially PRI, and Processing Speed Index., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of the present study was (i) to assess the prevalence of Violent Behavior in Schizophrenia (VBS) in a sample of community-dwelling outpatients in three middle-income countries of Latin America and (ii) to determine the clinical and socio-demographical risk factors associated with VBS and aggression level., Methods: The study included 253 stabilized outpatients with schizophrenia and their principal caregivers from 3 public ambulatory psychiatric care centers in Bolivia (N=83), Chile (N=85), and Peru (N=85). VBS was defined according to the Overt Aggression Scale (OAS) score and the aggression level was measured by the aggression subscore of the Agitated Behavior Scale of Corrigan. We collected socio-demographic information and clinical data. Multiple linear and logistic regressions were performed to determine which variables were associated with VBS and aggression level., Results: The prevalence of VBS differed statistically between the three countries (p<0.001) with 3.5% in Chile, 14.6% in Peru and 55.4% in Bolivia. After adjustment for confounding factors, VBS was associated with a younger age, a more severe psychotic symptomatology, a lower family income and unemployment. After adjustment for confounding factors, aggression level was associated with a more severe psychotic symptomatology, a lower family income, a younger age at illness onset and higher number of hospitalizations in the last 3years., Conclusion: These results may guide future health policies to specifically provide social support and rehabilitation care to VBS patients in middle-income countries, including psychoeducation and a more integrated work between the treating medical team and the social workers., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: It is unknown whether a cytokine signature may help the identification of subgroup of patient who would respond to personalized treatment. As interleukin-1 beta (Il-1β) seems to play a major role in mood disorder, a systematic review and meta-analysis of its potential role in major depressive disorder (MDD) was carried out., Methods: A systematic search was performed to identify appropriate MDD vs. control studies pertaining to Il-1β. Methodological quality and possible moderators were also assessed., Results: A total of 1922 studies were identified, and 53 articles were selected. Results showed an association between increased blood IL-1β and MDD in high-quality studies only. No association with age was found. No IL-1β gene-related polymorphisms has been associated with MDD. No effect of antidepressant on IL-1β level has been found, although the antidepressants investigated were various. Qualitative analyses indicate that MDD coupled to a history of childhood trauma may be a subgroup for IL-1β -targeted therapies. No difference in studies utilizing a stimulation method has been identified to date., Conclusions: The present work has confirmed IL-1β as a biological marker of interest for innovative MDD treatments. However, further studies are needed to clarify the patients with MDD who may benefit from these therapies., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Competing Interests: D. Misdrahi, G. Fond et P.-M. Llorca déclarent n’avoir aucun lien d’intérêts.

Objective: Medication nonadherence is one of the most important, and potentially modifiable, prognostic factors in the outcome of patients with schizophrenia. The aim of this article is to propose a new classification of adherence profiles according to the Medication Adherence Rating Scale (MARS) in a large community-dwelling sample of French patients with schizophrenia to provide a new tool to help clinicians in daily practice., Methods: 319 community-dwelling patients from a national network of 10 Schizophrenia Expert Centers were interviewed between January 2009 and January 2014. Assessments were conducted with a dedicated electronic medical record including the Structured Clinical Interview for DSM-IV Disorders. A cluster analysis was performed to explore clinical variables associated with poor adherence., Results: Two distinct groups of patients were identified relative to their main adherence style. Items about medications' subjective negative effects constituted the greatest discriminating factor between the 2 clusters. Patients with poor adherence (n = 117) were significantly younger (adjusted OR [aOR] = 1.036; 95% CI, 1.004-1.069) and had higher levels of current depression (aOR = 0.894; 95% CI, 0.829-0.964) and lower insight (aOR = 0.820; 95% CI, 0.693-0.970)., Conclusions: The MARS provides a useful tool for clinicians and can also aid in the evaluation of adherence styles and their determinants in patients with schizophrenia. The element providing the greatest discriminative power between the 2 clusters was a subjective negative attitude toward medication. The findings also suggest that depression is more frequent in schizophrenia patients with poor adherence and that improving insight into illness might be suggested as a first-line intervention to improve adherence in this population., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Background: New determinants of quality of life in schizophrenia need to be identified. As sensory gating deficit is core impairment in schizophrenia, the present study hypothesized that sensory gating deficit is a determinant of impaired quality of life in schizophrenia. This study therefore investigated the relationship between sensory gating deficit and quality of life in patients with schizophrenia after adjusting for key confounding factors., Subjects and Methods: Sensory gating was assessed with the auditory event-related potential method by measuring P50 amplitude changes in a double-click conditioning-testing procedure, perceptual impairments related to sensory gating deficit was assessed with the SGI questionnaire and quality of life was assessed with the SQoL 18 questionnaire in 39 patients with schizophrenia., Results: Patients with sensory gating deficit (n=14) had a lower subjective quality of life on the psychological well-being dimension evaluated with SQoL 18 questionnaire (p=0.008) compared to those without it (n=25). This result remained significant (B=-0.45, Wald=4.84, p=0.02) after taking into account 7 potential confounding factors (gender, age, level of education, duration of disorder, positive symptoms, depressive symptoms and anxiety symptoms). Poorer psychological well-being was related to a higher score on the SGI (rho=-0.40, p=0.01), in particular on the Distractibility dimension (rho=-0.47, p=0.001)., Conclusions: These findings suggest that sensory gating deficit may be a determinant of impaired quality of life in schizophrenia. Further studies are needed to address the causal relationship between sensory gating deficit, perceptual impairments, attentional deficit and impaired quality of life in schizophrenia in order to act more efficiently on the quality of life of patients with this disorder.

Competing Interests: D. Misdrahi, G. Fond et P.-M. Llorca déclarent n’avoir aucun lien d’intérêts.

Objectives: Inflammation, measured by abnormal blood C-reactive protein (CRP) level, has been described in schizophrenia (SZ), being inconsistently related to impaired cognitive functions. The aim of the present study is to investigate cognitive impairment associated with abnormal CRP levels in a large multi-centric sample of community-dwelling SZ patients, using a comprehensive neuropsychological battery., Method: Three hundred sixty-nine community-dwelling stable SZ subjects (76.2% men, mean age 32.7 y) were included and tested with a comprehensive battery of neuropsychological tests. Abnormal CRP level was defined as >3mg/L., Results: Multiple factor analysis revealed that abnormal CRP levels, found in 104 patients (28.2%), were associated with impaired General Intellectual Ability and Abstract Reasoning (aOR = 0.56, 95% CI 0.35-0.90, P = .014), independently of age, sex, education level, psychotic symptomatology, treatments, and addiction comorbidities. Abnormal CRP levels were also associated with the decline of all components of working memory (respectively effect size [ES] = 0.25, P = .033; ES = 0.27, P = .04; ES = 0.33, P = .006; and ES = 0.38, P = .004) and a wide range of other impaired cognitive functions, including memory (ES = 0.26, P = .026), learning abilities (ES = 0.28, P = .035), semantic memory (ES = 0.26, P = .026), mental flexibility (ES = 0.26, P = .044), visual attention (ES = 0.23, P = .004) and speed of processing (ES = 0.23, P = .043)., Conclusion: Our results suggest that abnormal CRP level is associated with cognitive impairment in SZ. Evaluating the effectiveness of neuroprotective anti-inflammatory strategies is needed in order to prevent cognitive impairment in SZ., (© The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The Medication Adherence Rating Scale (MARS) is one of the most widely used measurements of adherence in schizophrenia (SZ), but there is no available data regarding its psychometric properties in homeless SZ patients (HSZ). The aim of this study was therefore to assess the psychometric properties of the MARS in a large multicenter sample of HSZ subjects. This multi-centre prospective study was conducted in the following 4 French cities: Lille, Marseille, Paris and Toulouse. Three hundred and fifty-three patients were included. The 3-factor structure of the MARS was confirmed using confirmatory factor analysis: RMSEA = 0.045, CFI = 0.98, TLI = 0.97 and WRMR = 0.76. The unidimensionality of each factor was supported by the satisfactory INFIT statistics. Item internal consistencies were all higher than 0.20 and the Kuder-Richardson were higher than to 0.6, except for factor 2, which was closed to 0.5. Significant associations with symptoms, functioning and quality of life showed satisfactory external validity. The acceptability was satisfactory with missing data lower than 5% for each dimension. The MARS is a short self-administered instrument with acceptable psychometric properties in homeless SZ patients that yields interesting information about medication adherence.

Background: Childhood trauma (CT) and cannabis use are both environmental and modifier risk factors for schizophrenia. However, little is known about how they interact in schizophrenia. We examined the main effect of each of these two environmental factors on the clinical expression of the disease using a large set of variables, and we tested whether and how cannabis and CT interact to influence the course and the presentation of the illness., Methods: A sample of 366 patients who met the DSM-IV-TR criteria for schizophrenia was recruited through the FACE-SCZ (Fondamental Advanced Centre of Expertise - Schizophrenia) network. Patients completed a large standardized clinical evaluation including Structured Clinical Interview for DSM Disorders-I (SCID-I), Positive and Negative Symptoms Scale (PANSS), Columbia-Suicide Severity Rating Scale (C-SSRS), Global Assessment of Functioning (GAF), Short-Quality of Life-18 (S-QoL-18), and Medication Adherence Rating Scale (MARS). We assessed CT with the Childhood Trauma Questionnaire and cannabis status with SCID-I., Results: CT significantly predicted the number of hospitalizations, GAF, and S-QoL-18 scores, as well as the PANSS total, positive, excitement, and emotional distress scores. Cannabis use disorders significantly predicted age of onset, and MARS. There was no significant interaction between CT and cannabis use disorders. However, we found evidence of a correlation between these two risk factors., Conclusions: CT and cannabis both have differential deleterious effects on clinical and functional outcomes in patients with schizophrenia. Our results highlight the need to systematically assess the presence of these risk factors and adopt suitable therapeutic interventions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

For 25years work has been underway in France for the implementation of an alternative to public financing of health care. In the absence of progress, some regional health agencies are engaged in work related to the reallocation of public finances between psychiatric institutions. We propose a reflection with suggestion on the method proposed by the Provence Alpes Côte d'Azur Regional Health Agency. Without questioning the need for a reallocation of resources between psychiatric institutions, the method proposed here needs to evolve further to be applied in a legitimate and appropriate manner. There is a kind of urgency for a reallocation of resources between psychiatric institutions in France, but it implies a collective thinking and especially the definition of evaluation procedures for the selected models. These conditions are necessary to guarantee the quality of French psychiatry and equity in access to psychiatric care., (Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Objective: The objectives are to determine the rate of potentially inappropriate psychotropic (PIP) prescription at discharge in the elderly psychiatric inpatients and to determine whether PIP is associated with lowered functioning outcomes., Methods: Sociodemographic, clinical, and treatment data for all inpatients aged ≥ 65 years consecutively hospitalized during 1 year in 13 psychiatry departments was analyzed. PIP+/PIP- groups were defined according to the French-updated Beers criteria. Daily functioning was evaluated by the daily living (ADL) scale. Logistic regression analysis was used to estimate odds ratios for the association between PIP administration at discharge and respectively functioning and potential confounding factors., Results: Data was obtained for 327 patients. Overall, 124 (37.9 %) patients were males, and the mean age was 73.9 years (SD = 5.6); 163 (49.8 %) patients were diagnosed with affective disorders and 89 (27.2 %) with schizophrenia/schizotypal/delusional disorders. Overall, 249 (76.1 %) had one or more PIP medications, mainly anxiolytics (69.9 %) and hypnotics (17.2 %). In a multivariate analysis, PIP prescription at discharge has been associated with patient lowered personal care functioning, independently of age, gender, and psychiatric or somatic diagnoses (OR = 0.88 (0.79-0.97, p = 0.01)., Conclusion: In the current increasingly fragmented health care systems, special attention must be given to PIP prescription in older population suffering from psychiatric disorders. Using the Beers criteria, the present study demonstrates the high prevalence of PIP prescription, which concerns a large panel of drugs but mostly anxiolytics and hypnotics independently of psychiatric or somatic diagnoses and sociodemographic characteristics. Our study has demonstrated for the first time an association between PIP prescription and lowered patient functioning. Further longitudinal studies should confirm a potential causal relation.

The aim of this study was to estimate the prevalence of psychostimulant use in the French medical community and their motives. A population-based cross-sectional study using a self-administered online survey was done. A total of 1718 French students and physicians (mean age, 26.84±7.19 years, 37.1% men) were included. Self-reported lifetime use, motives, socio-demographic and academic features for over the counter (OTC), medically prescribed (MPP), and illicit (IP) psychostimulant users were reported. Lifetime prevalence of psychostimulant use was 33% (29.7% for OTC, 6.7% for MPP, and 5.2% for IP). OTC consumption mainly aimed at increasing academic performance and wakefulness during competitive exams preparation. OTC consumption started early and was predictive of later MPP use. Corticoids were the most frequently consumed MPP (4.5%) before methylphenidate and modafinil. Motives for MPP consumption were increased academic performance, concentration, memory, and wakefulness. Psychostimulant use is common among French medical community. Our results suggest that restrictions on methylphenidate and modafinil prescriptions are effective at limiting their use. However, these restrictions may explain the observed rates of corticoids consumption, which raise a new public health problem, given that corticoids may have severe side effects.

Objective: This study aimed to analyse the relationships among psychotic symptoms, depression, neurocognition and functioning as determinants of quality of life (QoL) in patients with schizophrenia., Methods: In this cross-sectional study, we evaluated QoL with the Schizophrenia Quality of Life 18-item scale (S-QoL 18), neurocognition with multiple tests exploring memory, attention and executive functions, the severity of psychotic symptoms with the Positive and Negative Syndrome Scale (PANSS), depression with the Calgary Depression Scale for Schizophrenia (CDSS) and functioning using the Functional Remission Of General Schizophrenia (FROGS) scale. We used Structural Equation Modelling (SEM) to describe the relationships among the severity of psychotic symptoms, depression, neurocognition, functioning and QoL., Results: Two hundred and seventy-one outpatients with schizophrenia participated in our study. SEM showed good fit with χ(2)/df=1.97, root mean square error of approximation=0.06, comparative fit index=0.93 and standardized root mean square residuals=0.05. This model revealed that depression was the most important feature associated with QoL, mainly for the self-esteem, autonomy and resilience dimensions (direct path coefficient=-0.46). The direct path between functioning and QoL was also significant (path coefficient=0.26). The severity of psychotic symptoms and neurocognitive impairment were weakly and indirectly associated with QoL via functioning (path coefficients=-0.18 and 0.04, respectively)., Conclusions: This study contributes to a better understanding of the determinants of QoL in schizophrenia. Our findings should be considered in developing effective strategies for improving QoL among this population., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The objective was to examine changes in temporal trends in suicide mortality in 26 Western countries by retrospective trend analysis of the WHO mortality database on causes of deaths. From 1990 to 2010, there was a median reduction in suicide mortality of 22.7%, ranging from a 46% reduction in Estonia to a 26.2% increase in Romania. Suicide mortality decreased by ≥ 20% in 15 countries, and the reduction tended to be greater in countries with higher mortality in 1990. In most of the central European countries mortality strongly declined. The median changes in the age groups were -25.3% (range -62.9% to 72.6%) in people aged 15-24 years, -36.9% (-60.5% to 32.4%) in 25-34 years, -3.6% (-57.1% to 92%) in 35-54 years, -12.2% (-37% to 65,7%) in 55-74 years and -16.1% (-54.5% to 166.7%) in ≥ 75 years. Suicide prevention programs in youths and in the elderly seem to be effective (at least in females for the elderly) and efforts should be pursued in this way. However, suicide mortality of the people aged 35-54 years has increased in half of the studied countries between 1990 and 2010. Public policies should further orientate their efforts toward this population.

It remains unclear whether children and adolescents in the child welfare system (CWS) exhibit a higher prevalence of mental disorders compared with the general population. The objective of this study was to perform a systematic review and meta-analysis to assess the prevalence of mental disorders in the CWS.A ll of the epidemiological surveys assessing the prevalence of mental disorders in children and adolescents in the CWS were included. The pooled prevalence was estimated with random effect models. Potential sources of heterogeneity were explored using meta-regression analyses.E ight studies provided prevalence estimates that were obtained from 3104 children and adolescents. Nearly 1 child or adolescent of every 2 (49%; 95% confidence interval (CI) 43-54) was identified as meeting criteria for a current mental disorder. The most common mental disorder was disruptive disorder (27%; 95% CI 20-34), including conduct disorder (20%; 95% CI 13-27) and oppositional defiant disorder (12%; 95% CI 10-14). The prevalence of attention-deficit/hyperactivity disorder was estimated to be 11% (95% CI 6-15). The prevalence estimates of anxiety and depressive disorders were 18% (95% CI 12-24) and 11% (95% CI 7-15). Posttraumatic stress disorder had the lowest prevalence (4%; 95% CI 2-6). High prevalences of mental disorders in the CWS were reported, which highlights the need for the provision of qualified service. The substantial heterogeneity of our findings is indicative of the need for accurate epidemiological data to effectively guide public policy., Competing Interests: The authors have no conflicts of interest to disclose.

Introduction: The primary objective of this study was to determine if second-generation antipsychotic (SGA) administration was associated with lower aggressiveness scores compared to first-generation (FGA) in schizophrenia (SZ). The secondary objective was to determine if antidepressants, mood stabilizers, and benzodiazepines administration were respectively associated with lower aggressiveness scores compared to patients who were not administered these medications., Methods: Three hundred thirty-one patients with schizophrenia (N = 255) or schizoaffective disorder (N = 76) (mean age = 32.5 years, 75.5 % male gender) were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with the structured clinical interview for DSM-IV Axis I disorders and validated scales for psychotic symptomatology, insight, and compliance. Aggressiveness was measured by the Buss-Perry Aggression Questionnaire (BPAQ) score. Ongoing psychotropic treatment was recorded., Results: Patients who received SGA had lower BPAQ scores than patients who did not (p = 0.01). More specifically, these patients had lower physical and verbal aggression scores. On the contrary, patients who received benzodiazepines had higher BPAQ scores than patients who did not (p = 0.04). No significant difference was found between BPAQ scores of patients respectively being administered mood stabilizers (including valproate), antidepressant, and the patients who were not. These results were found independently of socio-demographical variables, psychotic symptomatology, insight, compliance into treatment, daily-administered antipsychotic dose, the way of antipsychotic administration (oral vs long acting), current alcohol disorder, and daily cannabis consumption., Conclusion: The results of the present study are in favor of the choice of SGA in SZ patients with aggressiveness, but these results need further investigation in longitudinal studies. Given the potent side effects of benzodiazepines (especially dependency and cognitive impairment) and the results of the present study, their long-term prescription is not recommended in patients with schizophrenia and aggressive behavior.

Objectives: The relation between C-Reactive Protein (CRP), depression and antidepressant consumption has been well explored in major depressive disorders but not in schizophrenia, which has a high rate of depression comorbidity. The objectives of this study were: (i) to determine the prevalence of abnormal CRP levels, depression and antidepressant consumption in a multicenter community-dwelling sample of subjects with schizophrenia (ii) to determine the association between abnormal CRP levels, depression and antidepressant consumption in schizophrenia., Method: 219 stable patients with schizophrenia (mean age=31.6 years, 75.3% male gender) were systematically included in the multicentre network of FondaMental Expert Center for schizophrenia (FACE-SZ) and assessed with a dedicated electronic medical record including the Structured Clinical Interview for DSM-IV Axis I Disorders and Calgary Depression Scale for depression. High sensitivity CRP (hs-CRP) was measured with an assay using nephelometry (Dade Behring). Abnormal CRP level was defined by levels >3mg/L. Current medication was recorded., Results: Overall, 63 subjects (28.8%) were found to have abnormal CRP levels, 43 (20.1%) received a diagnosis of comorbid current depression, and 51 (31.9%) had ongoing antidepressant treatment. In univariate analysis, abnormal CRP levels were found to be significantly associated with body mass index (BMI) (p<0.0001), hypertriglyceridemia (p=0.0015), high waist circumference (p<0.0001), metabolic syndrome (p=0.0011), abdominal obesity (p<0.0001) and with antidepressant consumption (p=0.01), while depression, psychotic symptomatology, age of onset, illness duration, sociodemographic characteristics, current tobacco or cannabis status, hypertension or high fasting glucose were not (all p>0.05). In a multivariate model, abnormal CRP was associated with antidepressant consumption independently of other confounding variables (adjusted Odds Ratio=2.8, 95% confidence interval 1.22-6.62). Metabolic syndrome was also independently associated with abnormal CRP (adjusted Odds Ratio=2.6, 95% confidence interval 1.01-6.71)., Conclusion: Abnormal CRP levels in schizophrenia were found to be associated with antidepressant consumption, but not with depression. The potential mechanisms were discussed. Antidepressant consumption should be systematically recorded in future studies exploring inflammation in schizophrenia. Future clinical trials of interventions directed at lowering the level of CRP and other inflammatory markers are discussed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The aim of this study was to assess the efficacy and tolerability/acceptability of 6 anesthetic agents in ECT for depressive disorders. We systematically reviewed 14 double-blind randomized controlled trials (610 participants). Efficacy was measured by the mean scores on validated depression scales at 6 ECT (or the nearest score if not available), number of responders at the end of treatment and seizure duration. The acceptability was measured by the proportion of patients who dropped out of the allocated treatment, and the tolerability by the number of serious adverse events and post-treatment cognition assessment. After excluding the trials responsible for heterogeneity, depression scores of patients who were administered methohexital were found to be significantly more improved than those who received propofol (p = 0.001). On the contrary, those who were administered propofol had lower depression scores than those with thiopental at the end of treatment (p = 0.002). Compared to propofol, methohexital was found to be significantly associated with higher seizure duration (p = 0.018). No difference was found for the acceptability profile (all p > 0.05). In summary, ketamine and methohexital may be preferred to propofol or thiopental in regard of effectiveness in depression scores and increased seizure duration. Further studies are warranted to compare ketamine and methohexital.

While forecasts predict an increase in the prevalence of mental health disorders in the worldwide general population, the response rate to classical psychiatric treatment remains unsatisfactory. Resistance to psychotropic drugs can be due to clinical, pharmacological, pharmacokinetic, and pharmacodynamic factors. Among these factors, recent animal findings suggest that microbiota may have an underestimated influence on its host's behavior and on drug metabolism that may explain ineffectiveness or increased side effects of psychiatric medications such as weight gain. The following issues were identified in the present review: (i) microbiota dysbiosis and putative consequences on central nervous system functioning; (ii) chronic microbiota dysbiosis-associated illnesses in humans; (iii) microbiota-oriented treatments and their potential therapeutic applications in psychiatry., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Public health policies aim to prevent suicide in the general population. Assessing their effectiveness is required to further guide public health policies. The present article focuses on the French paradox. The French health care system was classified as the best in the world according the World Health Organization (WHO). However, suicide rates in France remain high compared to other European countries. The aim of the present article was to analyze (i) the evolution of suicide Age-Standardized Death (ASDRs) in France during the last three decades and the associations with socio-economic parameters and (ii) to understand which populations may specifically benefit from further targeted suicide prevention policies., Methods: The database of the World Health Organization (WHO), freely available, was explored in April 2015. ASDRs were calculated each year by ratio between the number of deaths by suicide and the total population (per 100,000 inhabitants). Number of deaths by gender and age were also analyzed., Results: Overall, ASDR suicide has decreased since 1987 in France (-32.8% between 1987 and 2010). However, France kept the same rank (10/26) when compared to other European countries between 1987 and 2010. The relative burden of suicide in all-causes mortality increased during the same period (+28.2%) while the total number of deaths by suicide increased only slightly (+3.9%). More specifically, the number of deaths by suicide increased substantially in [35-54] years old (+40%) and 75+ years old (+27%) males, and in [35-54] (+41%) years old females. Between 2000 and 2010, suicide rates significantly decreased when yearly mean income increased, and when general and psychiatric care beds decreased., Conclusion: Although ASDR suicide has decreased in France since 1987, this decline is quite modest when considering its universal access to care, the prevention of depression and suicide public policies. Suicide prevention public policies should focus on evaluation and improvement of prevention and care in the [35-54] years old population, and in the males aged 75+., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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=31.4years, 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 360μmol/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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Patients with psychiatric disorders display high levels of hypovitaminosis D (<50nmol/L). It remains unclear whether it is associated with specific diagnoses. To further explore vitamin D status in psychiatric inpatients, 82 individuals with mood disorders or schizophrenia/schizoaffective disorders were included. Hypovitaminosis D was significantly lower in patients with mood disorders than patients with schizophrenia (standardized β coefficient=0.385, p=0.007). Further studies are warranted to determine specific causes of hypovitaminosis D and the interest of supplementation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Schizophrenia is probably the most severe psychiatric disorder with much suffering for the patients and huge costs for the society. Efforts to provide optimal care by general practitioners and psychiatrists are undermined by the complexity of the disorder and difficulties in applying clinical practice guidelines and new research findings to the spectrum of cases seen in day-to-day practice. An innovative model of assessment aimed at improving global care of people with schizophrenia provided by the French national network of schizophrenia expert centres is being described. Each centre has established strong links to local health services and provides support to clinicians in delivering personalized care plans. A common set of assessment tools has been adopted by the ten centres spread over the whole French territory. A web application, e-schizo(©) has been created to record data in a common computerized medical file. This network offers systematic, comprehensive, longitudinal, and multi-dimensional assessments of cases including a medical workup and an exhaustive neuropsychological evaluation. This strategy offers an effective way to transfer knowledge and share expertise. This network is a great opportunity to improve the global patient care and is conceived as being an infrastructure for research from observational cohort to translational research., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: To perform a meta-analysis on studies reporting prevalence of Toxoplasma gondii (T. gondii) infection in any psychiatric disorder compared with healthy controls. Our secondary objective was to analyze factors possibly moderating heterogeneity., Method: A systematic search was performed to identify studies into T. gondii infection for all major psychiatric disorders versus healthy controls. Methodological quality, publication bias, and possible moderators were assessed., Results: A total of 2866 citations were retrieved and 50 studies finally included. Significant odds ratios (ORs) with IgG antibodies were found in schizophrenia (OR 1.81, P < 0.00001), bipolar disorder (OR 1.52, P = 0.02), obsessive-compulsive disorder (OR 3.4, P < 0.001), and addiction (OR 1.91, P < 0.00001), but not for major depression (OR 1.21, P = 0.28). Exploration of the association between T. gondii and schizophrenia yielded a significant effect of seropositivity before onset and serointensity, but not IgM antibodies or gender. The amplitude of the OR was influenced by region and general seroprevalence. Moderators together accounted for 56% of the observed variance in study effects. After controlling for publication bias, the adjusted OR (1.43) in schizophrenia remained significant., Conclusion: These findings suggest that T. gondii infection is associated with several psychiatric disorders and that in schizophrenia reactivation of latent T. gondii infection may occur., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Two studies have shown that increasing the consultation of the word "suicide" in the Google search engine was associated with a subsequent increase in the prevalence of suicide attempts. The main goal of this article was to explore the trends generated by a key-word search associated with suicide, depression and bipolarity in an attempt to identify general trends (disorders epidemics in the population/"real events" vs newsworthy advertisement/"media event"). Based on previous studies, the frequency of the search words "how to suicide" and "commit suicide" were analyzed for suicide, as well as "depression" (for depressive disorders) and "bipolar disorder". Together, these analyses suggest that the search for the words "how to suicide" or "commit suicide" on the Google search engine may be a good indicator for suicide prevention policies. However, the tool is not developed enough to date to be used as a real time dynamic indicator of suicide epidemics. The frequency of the search for the word "suicide" was associated with those for "depression" but not for "bipolar disorder", but searches for psychiatric conditions seem to be influenced by media events more than by real events in the general population., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The choice of an efficient psychotropic treatment for patients with schizophrenia is a key issue to improve prognosis and quality of life and to decrease the related burden and costs. As for other complex disorders, response to drugs in schizophrenia is highly heterogeneous and the underlying molecular mechanisms of this diversity are still poorly understood. In a carefully followed-up cohort of schizophrenic patients prospectively treated with risperidone or olanzapine, we used a specially designed single-nucleotide polymorphism (SNP) array to perform a large-scale genomic analysis and identify genetic variants associated with response to psychotropic drugs. We found significant associations between response to treatment defined by the reduction in psychotic symptomatology 42 days after the beginning of treatment and SNPs located in the chromosome 6, which houses the human leukocyte antigen (HLA). After imputation of the conventional HLA class I and class II alleles, as well as the amino-acid variants, we observed a striking association between a better response to treatment and a double amino-acid variant at positions 62 and 66 of the peptide-binding groove of the HLA-A molecule. These results support the current notion that schizophrenia may have immune-inflammatory underpinnings and may contribute to pave the way for personalized treatments in schizophrenia.

The motivational interview aims to help patients to resolve their ambivalence regarding problematic behaviors and to guide them into change. It differs from other therapeutic approaches mainly through the attitude of the therapist. In motivational interviewing, the therapist defends the statu quo. By reactance, the patient defends the change and enhance her/his motivation. This article provides a summary of the other concepts of motivational interviewing and its applications in the psychiatric daily practice., (Copyright © 2015. Published by Elsevier Masson SAS.)

Successful treatment of first-episode psychosis is one of the major factors that impacts long-term prognosis. Currently, there are no satisfactory biological markers (biomarkers) to predict which patients with a first-episode psychosis will respond to which treatment. In addition, a non-negligible rate of patients does not respond to any treatment or may develop side effects that affect adherence to the treatments as well as negatively impact physical health. Thus, there clearly is a pressing need for defining biomarkers that may be helpful to predict response to treatment and sensitivity to side effects in first-episode psychosis. The present systematic review provides (1) trials that assessed biological markers associated with antipsychotic response or side effects in first-episode psychosis and (2) potential biomarkers associated with biological disturbances that may guide the choice of conventional treatments or the prescription of innovative treatments. Trials including first-episode psychoses are few in number. Most of the available data focused on pharmacogenetics markers with so far only preliminary results. To date, these studies yielded-beside markers for metabolism of antipsychotics-no or only a few biomarkers for response or side effects, none of which have been implemented in daily clinical practice. Other biomarkers exploring immunoinflammatory, oxidative, and hormonal disturbances emerged as biomarkers of first-episode psychoses in the last decades, and some of them have been associated with treatment response. In addition to pharmacogenetics, further efforts should focus on the association of emergent biomarkers with conventional treatments or with innovative therapies efficacy, where some preliminary data suggest promising results., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The association between Toxoplasma gondii seropositivity and respectively Bipolar Disorder (BD) and Schizophrenia/Schizoaffective disorder (SZ) is one of the most studied link between one pathogen and psychiatric disorders. The aim of the present study was thus to retrospectively determine if the administration of an antipsychotic and/or a mood stabilizer having known in vitro Anti-Toxoplasmic Activity (TATA+) was associated with a better clinical outcome in a population of 152 BD or 114 SZ patients and seropositive for T. gondii infection compared to patients receiving a treatment without anti-toxoplasmic activity (TATA-)., Methods: This multicenter study was conducted in an academic public hospital during a 3-years period between 2009 and 2011. All consecutive inpatients and outpatients with SZ or BD diagnosis with a stable treatment for more than 4 weeks were recruited. socio-demographic and clinical characteristics measured with validated scales as well as a serological status for toxoplasmic infection were included. Treatments were classified according to their in vitro antitoxoplasmic activity. A multivariate model was used to determine the clinical characteristics that were significantly different between patients receiving a treatment with no antitoxoplasmic activity compared to others., Results: BD patients with positive serum antibodies against T. gondii presented more lifetime depressive episodes (p = 0.048) after adjustment for age, sex and sociodemographic characteristics when treated by drug having no anti-toxo activity, compared to patients having received drugs with anti-toxo activity. A significant difference was not found in BD toxonegative patients and in SZ toxopositive or toxonegative patients., Conclusions: It seems to be of importance to consider prescribing a drug with a clear anti-toxoplasmic activity (TATA+) for BD patients seropositive to T. gondii, in particular valproate that was found as the mood stabilizer with the highest antitoxoplasmic activity. Prospective randomized controlled trials are warranted to confirm this preliminary data., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: ADHD involves impairing core symptoms of inattention and hyperactivity/impulsivity in children (childhood ADHD = CH) that may persist in adulthood (adult ADHD = AD). Conflicting findings have been found regarding AD prevalences among adult smokers, and it is unclear whether AD is associated with a more severe smoking behavior in adulthood., Objective: The aim of this article is (a) to determine CH and AD prevalences in a nonselected sample of adult smokers, (b) to describe the characteristics of smokers with ADHD symptoms versus those without, and (c) to determine whether CH and/or AD symptoms are risk factors for more severe smoking in adulthood., Method: Three hundred and seventy-three participants aged 18 years and over were prospectively recruited in a smoking-cessation unit. Participants were classified as "no ADHD symptoms," "CH symptoms," or "AD symptoms" according to their baseline score on the Wender Utah Rating Scale (WURS) alone (for CH symptoms) and WURS combined to the Adult Self Report Scale (ASRS) for AD symptoms. Other clinical variables were reported at first consultation., Results: (a) CH symptoms were reported in 15.3% (57/373) of the total sample, 42.1% (24/57) of whom also had persistent ADHD symptoms in adulthood (prevalence of AD was 24/373 = 6.4%). (b) In comparison with participants without ADHD symptoms, smokers with ADHD symptoms consume significantly more tobacco, but ADHD symptoms were no longer significantly associated with the daily number of smoked cigarettes after adjustment for sociodemographic variables. No significant association was found between the two groups and age at the first cigarette, age at onset daily smoking, and nicotine dependence. (c) Participants were categorized into three groups: Group 1 without ADHD symptoms lifetime (NH; n = 316), Group 2 with childhood history of ADHD symptoms (CH; n = 33), and Group 3 with Adult ADHD symptoms (AD; n = 24). The association with tobacco consumption (>20 cigarettes/day) was significant for CH only (p = .02). After adjustment for gender, age, professional status, and educational level, this association was not longer significant., Conclusion: Childhood and adult ADHD symptoms are both highly prevalent among nonselected smokers but our study failed to show more severe smoking characteristics among these participants after adjustment with sociodemographic variables., (© 2013 SAGE Publications.)

While French authorities point to the need for rational prescribing, especially concerning psychotropic drugs, few data on the prescription of second-generation antidepressants (SGA) are synthesized for clinicians' use. Our objective is to carry out a comparative analysis of effectiveness and tolerability / acceptability of SGA. Considering the benefit/risk ratio and the cost (generic), the first-line treatment for a major depressive episode may be currently sertraline (50 mg / d). It may however have more digestive side effects than other SSRIs (due to the serotonin action), which calls for caution while increasing doses. Fluoxetine seems relevant in treatment of negative symptoms of schizophrenia (20mg / d) and in bulimia (60mg / d). Fluvoxamine seems relevant in the case of sexual side effects with a previous SSRI, in treatment of anxiety disorders (it's affinity for sigma receptors may confer a specific action) and in psychotic depression. Mirtazapine may be a treatment of interest when a fast remission of depressive symptoms (especially insomnia) is warranted but its tolerance profile makes it difficult to use.

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., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Introduction: Acceptance and commitment therapy (ACT) is a third generation of cognitive-behavioral therapies. The point is to help patients to improve their psychological flexibility in order to accept unavoidable private events. Thus, they have the opportunity to invest energy in committed actions rather than struggle against their psychological events., Objectives of the Study: (i) To present the ACT basic concepts and (ii) to propose a systematic review of the literature about effectiveness of this kind of psychotherapy., Method: (i) The core concepts of ACT come from Monestès (2011), Schoendorff (2011), and Harris (2012); (ii) we conducted a systematic review of the literature using the PRISMA's criteria. The research paradigm was « acceptance and commitment therapy AND randomized controlled trial ». The bases of the MEDLINE, Cochrane and Web of science have been checked., Results: Overall, 61 articles have been found, of which, after reading the abstracts, 40 corresponded to the subject of our study. (I) Psychological flexibility is established through six core ACT processes (cognitive defusion, acceptance, being present, values, committed action, self as context), while the therapist emphasizes on experiential approach. (II) Emerging research shows that ACT is efficacious in the psychological treatment of a wide range of psychiatric problems, including psychosis, depression, obsessive-compulsive disorder, trichotillomania, generalized anxiety disorder, post-traumatic stress disorder, borderline personality disorder, eating disorders. ACT has also shown a utility in other areas of medicine: the management chronic pain, drug-dependence, smoking cessation, the management of epilepsy, diabetic self-management, the management of work stress, the management of tinnitus, and the management of multiple sclerosis. Meta-analysis of controlled outcome studies reported an average effect size (Cohen's d) of 0.66 at post-treatment (n=704) and 0.65 (n=580) at follow-up (on average 19.2 weeks later). In studies involving comparison between ACT and active well-specified treatments, the effect size was 0.48 at post (n=456) and 0.62 at follow-up (n=404). In comparisons with waist list, treatment as usual, or placebo treatment, the effect sizes were 0.99 at post (n=248) and 0.71 at follow-up (n=176). Furthermore, ACT studies pointed out learning specific skills, such as decreasing experiential avoidance, increasing cognitive defusion, acceptance and contact with the present moment. Finally, all ACT studies showed an improved quality of life., Discussion: The loss of psychological flexibility is the origin of the pain caused by psychiatric disorders and chronic diseases. This is why other studies are needed to investigate ACT's full potential., (Copyright © 2013 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Irritable bowel syndrome (IBS) has been associated with high prevalence of psychological disorders. However, it remains unclear whether IBS and each of its subtypes (predominant diarrhea IBS-D, constipation IBS-C, mixed IBS-M) are associated with higher anxiety and depressive symptoms levels. This study aimed to determine the associations of IBS and each of its subtypes with anxiety and/or depression. We conducted a systematic review and meta-analysis using five electronic databases (PubMed, PsychINFO, BIOSIS, Science Direct, and Cochrane CENTRAL). We selected case-control studies comparing anxiety and depression levels of patients with IBS to healthy controls, using standardized rating scales. Outcomes were measured as random pooled standardized mean differences (SMD). Ten studies were included in our analysis (885 patients and 1,384 healthy controls). Patients with IBS had significant higher anxiety and depression levels than controls (respectively, SMD = 0.76, 95 % CI 0.47; 0.69, p < 0.01, I2 = 81.7 % and SMD = 0.80, 95 % CI 0.42; 1.19, p < 0.01, I2 = 90.7 %). This significant difference was confirmed for patients with IBS-C and -D subtypes for anxiety, and only in IBS-D patients for depression. However, other IBS subtypes had a statistical trend to be associated with both anxiety and depressive symptomatology, which suggests a lack of power due to the small number of studies included. Patients with IBS had significantly higher levels of anxiety and depression than healthy controls. Anxiety and depression symptomatology should be systematically checked and treated in IBS patients, as psychological factors are important moderators of symptom severity, symptom persistence, decisions to seek treatment, and response to treatment.

Objective: We undertook a meta-analysis of published Randomized Controlled Trials (RCT) with semi-active control and sham-NF groups to determine whether Electroencephalogram-neurofeedback (EEG-NF) significantly improves the overall symptoms, inattention and hyperactivity/impulsivity dimensions for probably unblinded assessment (parent assessment) and probably blinded assessment (teacher assessment) in children with Attention Deficit Hyperactivity Disorder (ADHD)., Data Sources: A systematic review identified independent studies that were eligible for inclusion in a random effects meta-analysis., Data Extraction: Effect sizes for ADHD symptoms were expressed as standardized mean differences (SMD) with 95% confidence intervals., Results: Five identified studies met eligibility criteria, 263 patients with ADHD were included, 146 patients were trained with EEG-NF. On parent assessment (probably unblinded assessment), the overall ADHD score (SMD = -0.49 [-0.74, -0.24]), the inattention score (SMD = -0.46 [-0.76, -0.15]) and the hyperactivity/impulsivity score (SMD = -0.34 [-0.59, -0.09]) were significantly improved in patients receiving EEG-NF compared to controls. On teacher assessment (probably blinded assessment), only the inattention score was significantly improved in patients receiving EEG-NF compared to controls (SMD = -0.30 [-0.58, -0.03])., Conclusions: This meta-analysis of EEG-NF in children with ADHD highlights improvement in the inattention dimension of ADHD symptoms. Future investigations should pay greater attention to adequately blinded studies and EEG-NF protocols that carefully control the implementation and embedding of training.

Introduction: 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., Methods: 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., Results: 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 < 0.01). Ketamine's efficacy was confirmed in MDD (resistant to previous pharmacological treatments or not) (SMD = -0.91; 95 % CI -1.19,-0.64; p < 0.01), in bipolar depression (SMD = -1.34; 95 % CI -1.94, -0.75), and in drug-free patients as well as patients under medication. Four ECT trials (118 patients) were included in our quantitative analysis. One hundred and three patients were diagnosed with major depressive disorder and 15 with bipolar depression. Overall, depression scores were significantly improved in the 58 patients receiving ketamine in ECT anesthesia induction compared to the 60 patients (SMD = -0.56; 95 % CI -1.10, -0.02; p = 0.04; I2 = 52.4 %). The duration of ketamine's effects was assessed in only two non-ECT studies and seemed to persist for 2-3 days; this result needs to be confirmed. Three of four studies found significant decrease of suicidal thoughts and one found no difference between groups, but suicidal ideations were only studied by the suicide item of the depressive scales. It was not possible to determine a dose effect; 0.5 mg/kg was used in the majority of the studies. Some cardiovascular events were described (mostly transient blood pressure elevation that may require treatment), and ketamine's use should remain cautious in patients with a cardiovascular history., Conclusion: The present meta-analysis confirms ketamine's efficacy in depressive disorders in non-ECT studies, as well as in ECT studies. The results of this first meta-analysis are encouraging, and further studies are warranted to detail efficacy in bipolar disorders and other specific depressed populations. Middle- and long-term efficacy and safety have yet to be explored. Extrapolation should be cautious: Patients included had no history of psychotic episodes and no history of alcohol or substance use disorders, which is not representative of all the depressed patients that may benefit from this therapy.

Rationale and Objective: 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., Methods: 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., Results: 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., Conclusions: These observations suggest that increasing D2 and D3 dopamine receptor binding affinities enhances antipsychotics' effectiveness in obsessive-compulsive disorders.

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., Competing Interests: Conflicts of Interest: None declared

Background: Pharmaceutical neuroenhancer consumption in college students is a rather unknown phenomenon in Europe and particularly in France, where surprisingly only one study was conducted in 1988., Aim: Our objective is to assess prevalence and motivations for licit (use inside medical indication) and illicit pharmaceutical neuroenhancer consumption (tablet form) in a non-selected French sample of Medicine and Pharmacology students., Subjects and Methods: A validated questionnaire was send to French sample of Medicine and Pharmacology students using email. The questionnaire investigate motives for use of pharmaceutical licit (vitamin C and caffeine tablets) and illicit (methylphenidate, amphetamines, modafinil, piracetam)., Results: Among 206 undergraduate students, 139 students (67.4%) declared to have consumed at least one cognitive enhancer in the past 12 months. Twelve students (8.6% of cognitive enhancers users and 5.8% of our total sample) used illicit pharmaceutical neuroenhancer. The motivations were first to improve their academic performances, second to improve their wakefulness/ vigilance, and third to improve their attention/concentration., Conclusions: Neuroenhancement is a widespread means of using pharmaceutical drugs in French as well as in US college campuses. Despites some limitations, these preliminary results highlight the need to boost the interest of professionals for the neuroenhancement issue in French and European students.