The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe.

BACKGROUND: We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe. METHODS: We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use. RESULTS: The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53). CONCLUSIONS: The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Incidence and predictors of metabolic syndrome onset in individuals with bipolar disorders: A longitudinal study from the FACE-BD cohort.

INTRODUCTION: Metabolic syndrome (MetS) is a cluster of components including abdominal obesity, hyperglycemia, hypertension, and dyslipidemia. MetS is highly prevalent in individuals with bipolar disorders (BD) with an estimated global rate of 32.6%. Longitudinal data on incident MetS in BD are scarce and based on small sample size. The objectives of this study were to estimate the incidence of MetS in a large longitudinal cohort of 1521 individuals with BD and to identify clinical and biological predictors of incident MetS. METHODS: Participants were recruited from the FondaMental Advanced Center of Expertise for Bipolar Disorder (FACE-BD) cohort and followed-up for 3 years. MetS was defined according to the International Diabetes Federation criteria. Individuals without MetS at baseline but with MetS during follow-up were considered as having incident MetS. A logistic regression model was performed to estimate the adjusted odds ratio and its corresponding 95% confidence interval (CI) for an association between each factor and incident MetS during follow-up. We applied inverse probability-of-censoring weighting method to minimize selection bias due to loss during follow-up. RESULTS: Among individuals without MetS at baseline (n = 1521), 19.3% developed MetS during follow-up. Multivariable analyses showed that incident MetS during follow-up was significantly associated with male sex (OR = 2.2, 95% CI = 1.7-3.0, p < 0.0001), older age (OR = 2.14, 95% CI = 1.40-3.25, p = 0.0004), presence of a mood recurrence during follow-up (OR = 1.91, 95% CI = 1.22-3.00, p = 0.0049), prolonged exposure to second-generation antipsychotics (OR = 1.56, 95% CI = 0.99, 2.45, p = 0.0534), smoking status at baseline (OR = 1.30, 95% CI = 1.00-1.68), lifetime alcohol use disorders (OR = 1.33, 95% CI = 0.98-1.79), and baseline sleep disturbances (OR = 1.04, 95% CI = 1.00-1.08), independently of the associations observed for baseline MetS components. CONCLUSION: We observed a high incidence of MetS during a 3 years follow-up (19.3%) in individuals with BD. Identification of predictive factors should help the development of early interventions to prevent or treat early MetS.

Functioning and neurocognition in very early and early-life onset bipolar disorders: the moderating role of bipolar disorder type.

Defining homogeneous subgroups of bipolar disorder (BD) is a major goal in personalized psychiatry and research. According to the neurodevelopmental theory, age at onset may be a key variable. As potential trait markers of neurodevelopment, cognitive and functional impairment should be greater in the early form of the disease, particularly type 1 BD (BD I). The age at onset was assessed in a multicenter, observational sample of 4190 outpatients with BD. We used a battery of neuropsychological tests to assess six domains of cognition. Functioning was measured using the Functioning Assessment Short Test (FAST). We studied the potential moderation of the type of BD on the associations between the age at onset and cognitive and functioning in a subsample of 2072 euthymic participants, controlling for potential clinical and socio-demographic covariates. Multivariable analyses showed cognition to not be impaired in individuals with early (21-30 years) and very early-life (before 14 years) onset of BD. Functioning was equivalent between individuals with early and midlife-onset of BD II and NOS but better for individuals with early onset of BD I. In contrast, functioning was not worse in individuals with very early-onset BD I but worse in those with very early-onset BD II and NOS. Early-life onset BDs were not characterized by poorer cognition and functioning. Our results do not support the neurodevelopmental view that a worse cognitive prognosis characterizes early-life onset BD. This study suggests that functional remediation may be prioritized for individuals with midlife-onset BD I and very early life onset BD 2 and NOS.

The impact of parent history of severe mental illness on schizophrenia outcomes: results from the real-world FACE-SZ cohort.

Parent history of severe mental illness (PHSMI) may have long-term consequences in adult offspring due to genetic and early environmental factors in preliminary studies. To compare the outcomes associated in subjects with PHSMI to those in patients without PHSMI. The participants with schizophrenia and schizoaffective disorders were recruited in the ongoing FACE-SZ cohort at a national level (10 expert centers) and evaluated with a 1-day-long standardized battery of clinician-rated scales and patient-reported outcomes. PHSMI was defined as history of schizophrenia or bipolar disorders in at least one parent and was included as explanatory variable in multivariate models. Of the 724 included patients, 78 (10.7%) subjects were classified in the PHSMI group. In multivariate analyses, PHSMI patients had a better insight into schizophrenia and the need for treatment and reported more often childhood trauma history compared to patients without PHSMI. More specifically, those with paternal history of SMI reported more severe outcomes (increased childhood physical and emotional abuses, comorbid major depression and psychiatric hospitalizations). PHSMI is associated with increased risk of childhood trauma, major depressive disorder and psychiatric hospitalization and better insight in individuals with schizophrenia. Specific public health prevention programs for parents with SMI should be developed to help protect children from pejorative psychiatric outcomes. PHSMI may also explain in part the association between better insight and increased depression in schizophrenia.

[Evaluation of the effectiveness of a cognitive remediation program in anorexia nervosa using new neuropsychological tools: A case study]. / Évaluer un programme de remédiation cognitive dans l'anorexie : nouveaux outils.

The management of anorexia nervosa (AN) remains complex with insufficient success rates. Based on clinical and empirical observations implicating neuropsychological difficulties in AN, cognitive remediation (CR) therapy appears to show positive effects. Nevertheless, these results remain subject to debate as some studies do not show this improvement, or in the case of positive improvements, a smaller effect size on cognitive performance. A possible explanation could lie in the cognitive tests used to assess CR. The aim of this study is to propose a new protocol for the evaluation of cognitive remediation for patients suffering from ED through the presentation of a case study.

Early-life factors associated with increased risk of disability pension in the national real-world schizophrenia FACE-SZ cohort study.

Among severe psychiatric disorders, schizophrenia has one of the highest impacts on professional and personal functioning with important indirect costs including disability pension allowance for the patients with the more severe forms of schizophrenia. To explore early-life factors associated with disability pension in schizophrenia. 916 patients were consecutively recruited at a national level in 10 expert centers and received a comprehensive standardized evaluation. Their disability pension status and early-life variables were reported from medical records and validated scales. Eight factors were explored: age, male sex, parental history of severe mental illness, childhood trauma exposure, education level, childhood ADHD, early age at schizophrenia onset and duration of untreated psychosis. 739 (80.7%) participants received a disability pension. In the multivariate model, early age at schizophrenia onset and low education level were associated with disability pension independently of age and sex while no significant association was found for parent history of severe mental illness, childhood trauma, childhood ADHD or duration of untreated psychosis. Low education level and early age at schizophrenia onset seem the best predictors of increased risk of disability pension in schizophrenia.

[French Expert advice on the management of valproate in childbearing and pregnant women with bipolar disorder]. / Avis d'experts français sur la prise en charge des femmes en âge de procréer et enceintes souffrant d'un trouble bipolaire traitées par valproate.

INTRODUCTION: The perinatal period is associated with high risk of relapses in women with untreated bipolar disorder (BD) and can have significant consequences on foetal and child development. Valproate is an effective mood stabilizer in BD but it is also the anticonvulsant associated to the highest risks of neurodevelopmental disorders and congenital malformations. The National Agency for the Safety of Medicines and Health Products (ANSM) changed the conditions of use and prescription of valproate in France in 2015. Its prescription is now contraindicated (i.e., not to be prescribed) in women able to have children unless alternative treatments are ineffective or not tolerated. Moreover, valproate could only be prescribed if the protocol of a specific pregnancy prevention program is followed. METHODS: A panel of experts from the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) provided consensus-based recommendations for switching and discontinuation of valproate in women with BD. The development of these recommendations consisted of an adaptation to French clinical practice based on a European expert opinion published in 2019. The experts discussed five real-world clinical situations in light of the scientific evidence and their clinical experience (a. Stable BD patient with valproate monotherapy who is planning pregnancy, b. Stable BD patient with valproate polytherapy who is planning pregnancy, c. Unstable BD patient with frequent relapses and valproate polytherapy who is planning pregnancy, d. Stable BD patient treated with valproate and unexpected pregnancy, e. Unstable BD patient treated with valproate and unexpected pregnancy) and developed, through several rounds of exchange drafts, a French version of clinical recommendations. RESULTS: First of all, some factors need to be considered for establishing personalized practical recommendations for a safe and effective switching or discontinuation of valproate in any clinical situations: planned pregnancy or unplanned pregnancy or current pregnancy, the existence or not of a pregnancy risk minimization program and a complete treatment history. Other factors that should be considered are the predominant polarity, the severity, the stability, the comorbidities associated with BD, the beliefs toward treatments, the family situation and the preference of the patient. The modalities for switching or discontinuation of valproate in women with BD were related to the clinical situation. First-line therapeutic alternatives such as lithium, lamotrigine, quetiapine, olanzapine or aripiprazole were preferred for patients suffering from a clinically stable BD considering pregnancy or pregnant. In patients suffering from clinically unstable BD, to reach stability was considered first. A shared decision-making should be systematically implemented and the patient must be fully informed of the risks related to an in-utero exposure to valproate, and the risks of the discontinuation/switch that is considered. CONCLUSION: Although the adaptation to French practice of the recommendations from the European expert opinion highlighted some differences in the criteria taken into consideration to guide the therapeutic decision, this expert advice will guide the clinician for switching and discontinuation of valproate in BD women able to have children or pregnant.

Épidémiologie descriptive du risque suicidaire dans le système médical français de médecine générale.

OBJECTIVE: Suicide prevention certainly includes a better knowledge of suicide risk in primary care. A number of international publications have shown interest in assessing this risk, but mostly through specific consultant populations: young patients, old patients, anhedonic, depressive, etc. Our study analyses suicide risk prevalence in patients consulting in general medicine for any somatic or psychiatric reason, their pathology or their age. METHOD: This cross-sectional study was conducted with adult patients (827 subjects included) who were consulting a French generalist doctor panel randomly selected. They filled a validated self-questionnaire (aRSD) assessing their suicide risk in the 15 preceding days and providing professional and personal data. RESULTS: The totally operable 757 files (483 female; 274 male) show that close to a quarter of consultants (24.3%) presents with a positive suicide risk in the 15 days preceding their consultation and 6.3%, reveal a severe risk (aRSD ≥ 7) with ideas and impulses to commit the act. When the reason to consult is psychiatric, 64.6% of these consultants have aRSD positive. One time out of two, the risk is even severe. CONCLUSIONS: This data shows how important the suicide risk prevalence is in general medicine. It confirms the main role played by primary care patricians in acting to prevent suicide risk. This data also shows the contribution represented by a self-questionnaire that would rapidly assess the suicide intent while screening, it.

[Hepatitis C in a psychiatric setting: A forgotten reservoir?] / Hépatite C en milieu psychiatrique : un réservoir oublié ?

Hepatitis C is a transmissible hepatic and extra-hepatic disease caused by the hepatitis C virus (HCV). HCV develops into a chronic infection among approximately 70% of the contaminated subjects. Chronic HCV infection is estimated to affect between 0.5% and 1 % of the general population in France, which causes an important burden of disease, in particular due to the occurrence of cirrhosis and liver cancer. New antiviral drugs now allow to cure more than 95% of patients in just a few weeks of treatment with very limited safety issues. This therapeutic revolution has led the World Health Organization and many national governments to aim for an elimination of HCV, which has been defined as a 90%-reduction of the incidence rate, and a 65%-reduction in the number of HCV-related deaths on the basis of the 2015 figures. In this respect, the French Ministry of Health has recently decided to extend the ability to prescribe the new antiviral drugs to any physician. However, the elimination campaign of HCV will also need to correctly identify, screen, and treat the main target populations. If people who inject drugs (PWIDs) certainly constitute the most important population concerned by the challenge of HCV elimination, more hidden reservoirs in which HCV transmission can insidiously evolve should be identified and specifically targeted as well. Inpatient psychiatric populations might constitute one of these hidden reservoirs. International data suggest that chronic HCV infection affects approximately 5% of psychiatric inpatients in Europe. This very high prevalence estimate can in part be due to the very frequent psychiatric disorders found among the current or former PWIDs. However, a part of the seropositive patients does not report a history of drug use, and other factors could contribute to the increased risk of contamination in this population including atypical routes of transmission related to institutional promiscuity. Exploring the general profile and risk-behaviors of the psychiatric inpatients found infected by the HCV is thus warranted for future studies. Screening and treating HCV in the specific population of psychiatric patients is part of the general public health objective of eliminating HCV at a national level. Moreover, it also directly fits into the individualized psychiatric care. Many recent data suggest that HCV also has a neural tropism, in particular within glial cells, such as astrocytes or oligodendrocytes. As such, HCV foments inflammatory processes in the brain and contributes to cognitive impairments and psychiatric symptoms such as anxiety or depression. At the individual level, treating HCV infection can improve the psychiatric state and increase patients' outcomes in terms of well-being and quality of life. For all these reasons, the field of psychiatry needs local and national actions for informing and training professionals about HCV screening and treating modalities. Patient and family associations also need to be involved in this general effort of micro-elimination. A key role should be assigned to the general practitioners embedded within inpatient psychiatric units. They are the best fitted professionals to screen, treat, and empower patients, to inform and train other caregivers of the psychiatric field, and to act as a relay with hepatology teams if required. Hospital pharmacists are other important stakeholders. In a national context in which the funding of psychiatric care, including medications, is based on predefined funding envelops, innovative initiatives will have to be set up by local or national health authorities, in partnership with pharmacists, to allow for the treatment of psychiatric inpatients. In conclusion, the world of psychiatry is a possible hidden reservoir of HCV and, as such, a part of the challenge for eliminating the virus. Patients, families, and caregivers will have to be correctly sensitized and trained to play their role in the process. Specific investigations will be required to better understand why such an increased prevalence of HCV is observed in this population. Specific adaptations of the cascade of care within psychiatric settings, including access to treatment, will need to be designed, implemented, and evaluated for reaching micro-elimination of HCV in psychiatry.

Psychotropics and COVID-19: An analysis of safety and prophylaxis.

The use of psychotropics during the COVID-19 pandemic has raised two questions, in order of importance: first, what changes should be made to pharmacological treatments prescribed to mental health patients? Secondly, are there any positive side effects of these substances against SARS-CoV-2? Our aim was to analyze usage safety of psychotropics during COVID-19; therefore, herein, we have studied: (i) the risk of symptomatic complications of COVID-19 associated with the use of these drugs, notably central nervous system activity depression, QTc interval enlargement and infectious and thromboembolic complications; (ii) the risk of mistaking the iatrogenic impact of psychotropics with COVID-19 symptoms, causing diagnostic error. Moreover, we provided a summary of the different information available today for these risks, categorized by mental health disorder, for the following: schizophrenia, bipolar disorder, anxiety disorder, ADHD, sleep disorders and suicidal risk. The matter of psychoactive substance use during the pandemic is also analyzed in this paper, and guideline websites and publications for psychotropic treatments in the context of COVID-19 are referenced during the text, so that changes on those guidelines and eventual interaction between psychotropics and COVID-19 treatment medication can be reported and studied. Finally, we also provide a literature review of the latest known antiviral properties of psychotropics against SARS-CoV-2 as complementary information.

[Challenges for psychotropics in the context of the SARS-Cov-2 pandemic]. / Enjeux de l'utilisation des psychotropes dans le cadre de la pandémie au SARS-Cov-2.

French recommendations have been proposed for psychotropics use and possible adaptations during the SARS-CoV-2 epidemic. Between uncertainties linked to the lack of data and speculations about possible benefits of psychotropics against the coronavirus, we propose here elements allowing to base the pharmacotherapeutic decisions potentially useful in Covid+ patients with psychiatric disorders.

Ensuring mental health care during the SARS-CoV-2 epidemic in France: A narrative review.

OBJECTIVE: The lack of resources and coordination to face the coronavirus epidemic raises concerns for the health of patients with mental disorders in a country where we still have memories of the dramatic experience of famine in psychiatric hospitals during the Second World War. This article aims to propose guidance to ensure mental health care during the SARS-CoV epidemic in France. METHODS: The authors performed a narrative review identifying relevant results in the scientific and medical literature and in local initiatives in France. RESULTS: We identified four types of major vulnerabilities among patients with mental disorders during this pandemic: (1) medical comorbidities that are more frequently found among patients with mental disorders (cardiovascular and pulmonary pathologies, diabetes, obesity, etc.) which are risk factors for severe covid-19 infection; (2) age (the elderly form the population most vulnerable to the coronavirus); (3) cognitive and behavioural disorders, which can hamper compliance with confinement and hygiene measures and finally and (4) psychosocial vulnerability as a result of stigmatization and/or socio-economic difficulties. Furthermore, the mental health healthcare system is more vulnerable than other healthcare systems. Current government plans are poorly suited to psychiatric establishments in a context of major shortages of organizational, material and human resources. In addition, a certain number of structural aspects make the psychiatric institution particularly vulnerable: many beds have been closed, wards have high densities of patients, mental health community facilities are closed, and medical teams are understaffed and poorly trained to face infectious diseases. There are also major issues when referring patients with acute mental disorders to intensive care units. To maintain the continuity of psychiatric care in this pandemic situation, several directions can be considered, in particular with the creation of "COVID+ units". These units are under the dual supervision of a psychiatrist and an internist/infectious disease specialist; all new entrants are placed in quarantine for 14 days; the nursing staff receives specific training, daily medical check-ups and close psychological support. Family visits are prohibited and replaced by videoconference. At the end of hospitalization, in particular for the population of patients in compulsory ambulatory care situations, specific case-management are organized with the possibility of home visits, in order to support patients when they get back home and to help them cope with the experience of confinement, which is liable to induce recurrences of mental disorders. The total or partial closure of community mental health facilities is particularly disturbing for patients, but a regular follow-up is possible with telemedicine and should include the monitoring of suicide risk and psycho-education strategies; developing support platforms could also be very helpful in this context. Private practice psychiatrists also have a crucial role of information towards their patients on confinement and barrier measures, and also on measures to prevent the psychological risks inherent in confinement: maintenance of regular sleep r, physical exercise, social interactions, stress management and coping strategies, prevention of addictions, etc. They should also be trained to prevent, detect and treat early warning symptoms of post-traumatic stress disorder, because their prevalence was high in the regions of China most affected by the pandemic. DISCUSSION: French mental healthcare is now facing a great and urgent need for reorganization and must also prepare in the coming days and weeks to face an epidemic of emotional disorders due to the confinement of the general population.

[Informations on psychotropics and their adaptations for patients suffering from mental disorders in France during the SARS-CoV-2 epidemic]. / Informations relatives aux psychotropes et à leurs adaptations éventuelles pour les patients souffrant de troubles psychiques en France pendant l'épidémie à SARS-CoV-2.

The 2019-20 coronavirus pandemic (SARS-CoV-2; severe acute respiratory syndrome coronavirus 2) has dramatic consequences on populations in terms of morbidity and mortality and in social terms, the general confinement of almost half of the world's population being a situation unprecedented in history, which is difficult today to measure the impact at the individual and collective levels. More specifically, it affects people with various risk factors, which are more frequent in patients suffering from psychiatric disorders. Psychiatrists need to know: (i) how to identify, the risks associated with the prescription of psychotropic drugs and which can prove to be counterproductive in their association with COVID-19 (coronavirus disease 2019), (ii) how to assess in terms of benefit/risk ratio, the implication of any hasty and brutal modification on psychotropic drugs that can induce confusion for a differential diagnosis with the evolution of COVID-19. We carried out a review of the literature aimed at assessing the specific benefit/risk ratio of psychotropic treatments in patients suffering from COVID-19. Clinically, symptoms suggestive of COVID-19 (fever, cough, dyspnea, digestive signs) can be caused by various psychotropic drugs and require vigilance to avoid false negatives and false positives. In infected patients, psychotropic drugs should be used with caution, especially in the elderly, considering the pulmonary risk. Lithium and Clozapine, which are the reference drugs in bipolar disorder and resistant schizophrenia, warrant specific attention. For these two treatments the possibility of a reduction in the dosage - in case of minimal infectious signs and in a situation, which does not allow rapid control - should ideally be considered taking into account the clinical response (even biological; plasma concentrations) observed in the face of previous dose reductions. Tobacco is well identified for its effects as an inducer of CYP1A2 enzyme. In a COVID+ patient, the consequences of an abrupt cessation of smoking, particularly related with the appearance of respiratory symptoms (cough, dyspnea), must therefore be anticipated for patients receiving psychotropics metabolized by CYP1A2. Plasma concentrations of these drugs are expected to decrease and can be related to an increase risk of relapse. The symptomatic treatments used in COVID-19 have frequent interactions with the most used psychotropics. If there is no curative treatment for infection to SARS-CoV-2, the interactions of the various molecules currently tested with several classes of psychotropic drugs (antidepressants, antipsychotics) are important to consider because of the risk of changes in cardiac conduction. Specific knowledge on COVID-19 remains poor today, but we must recommend rigor in this context in the use of psychotropic drugs, to avoid adding, in patients suffering from psychiatric disorders, potentially vulnerable in the epidemic context, an iatrogenic risk or loss of efficiency.

[Ensuring mental health care during the SARS-CoV-2 epidemic in France: A narrative review]. / Assurer les soins aux patients souffrant de troubles psychiques en France pendant l'épidémie à SARS-CoV-2.

OBJECTIVE: The lack of ressources and coordination to face the epidemic of coronavirus raises concerns for the health of patients with mental disorders in a country where we keep in memory the dramatic experience of famine in psychiatric hospitals during the Second World War. This article aims at proposing guidance to ensure mental health care during the SARS-CoV epidemy in France. METHODS: Authors performed a narrative review identifying relevant results in the scientific and medical literature and local initiatives in France. RESULTS: We identified four types of major vulnerabilities in patients suffering from mental disorders during this pandemic: (1) medical comorbidities that are more frequently found in patients suffering from mental disorders (cardiovascular and pulmonary pathologies, diabetes, obesity, etc.) which represent risk factors for severe infections with Covid-19; (2) age (the elderly constituting the population most vulnerable to coronavirus); (3) cognitive and behavioral troubles which can hamper compliance with confinement and hygiene measures and finally and (4) psychosocial vulnerability due to stigmatization and/or socio-economic difficulties. Furthermore, the mental health healthcare system is more vulnerable than other healthcare systems. Current government plans are poorly adapted to psychiatric establishments in a context of major shortage of organizational, material and human resources. In addition, a certain number of structural aspects make the psychiatric institution particularly vulnerable: many beds are closed, wards have a high density of patients, mental health community facilities are closed, medical teams are understaffed and poorly trained to face infectious diseases. We could also face major issues in referring patients with acute mental disorders to intensive care units. To maintain continuity of psychiatric care in this pandemic situation, several directions can be considered, in particular with the creation of Covid+ units. These units are under the dual supervision of a psychiatrist and of an internist/infectious disease specialist; all new entrants should be placed in quarantine for 14 days; the nurse staff should benefit from specific training, from daily medical check-ups and from close psychological support. Family visits would be prohibited and replaced by videoconference. At the end of hospitalization, in particular for the population of patients in compulsory ambulatory care situations, specific case-management should be organized with the possibility of home visits, in order to support them when they get back home and to help them to cope with the experience of confinement, which is at risk to induce recurrences of mental disorders. The total or partial closure of mental health community facilities is particularly disturbing for patients but a regular follow-up is possible with telemedicine and should include the monitoring of the suicide risk and psychoeducation strategies; developing support platforms could also be very helpful in this context. Private psychiatrists have also a crucial role of information with their patients on confinement and barrier measures, but also on measures to prevent the psychological risks inherent to confinement: maintenance of sleep regularity, physical exercise, social interactions, stress management and coping strategies, prevention of addictions, etc. They should also be trained to prevent, detect and treat early warning symptoms of post-traumatic stress disorder, because their prevalence was high in the regions of China most affected by the pandemic. DISCUSSION: French mental healthcare is now in a great and urgent need for reorganization and must also prepare in the coming days and weeks to face an epidemic of emotional disorders due to the containment of the general population.

[Psychopharmacotherapeutic guidelines : a challenge during health crisis]. / Recommandations psychopharmacothérapeutiques : un défi en temps de crise sanitaire.

The construction of pharmacological guidelines is a complex endeavor, and this is all the truer amidst a health crisis such as the current SARS-CoV-2 pandemic. In psychiatric settings, guidelines have to consider the handling of other drugs (i.e., psychotropic medications), that have been suggested as potentially prophylactic for COVID-19. These dialectics are discussed here, and the methodological foundations used for the elaboration of guidelines are put forward.

Réaliser des recommandations pharmacothérapeutiques est une démarche complexe, plus encore dans une période de crise sanitaire, comme celle que nous traversons avec la pandémie liée au SARS-CoV-2. En psychiatrie, les préconisations formulées se doivent de rappeler la légitime prudence à adopter dans le maniement des psychotropes, dans un contexte qui, par ailleurs, présente certaines de ces médications comme potentiellement prophylactiques de la COVID-19. Ces enjeux contradictoires sont débattus, les concepts méthodologiques de l'élaboration des recommandations sont rappelés.

Towards an improved access to psychiatric rehabilitation: availability and effectiveness at 1-year follow-up of psychoeducation, cognitive remediation therapy, cognitive behaviour therapy and social skills training in the FondaMental Advanced Centers of Expertise-Schizophrenia (FACE-SZ) national cohort.

Psychosocial Interventions (PIs) have shown positive effects on clinical and functional outcomes of schizophrenia (SZ) in randomized controlled trials. However their effectiveness and accessibility remain unclear to date in "real world" schizophrenia. The objectives of the present study were (i) to assess the proportion of SZ outpatients who benefited from PIs between 2010 and 2015 in France after an Expert Center Intervention in a national multicentric non-selected community-dwelling sample; (ii) to assess PIs' effectiveness at 1-year follow-up. 183 SZ outpatients were recruited from FondaMental Advanced Centers of Expertise for Schizophrenia cohort. Baseline and 1-year evaluations included sociodemographic data, current treatments, illness characteristics and standardized scales for clinical severity, adherence to treatment, quality of life, a large cognitive battery, and daily functioning assessment. Only 7 (3.8%) received a PI before the evaluation, and 64 (35%) have received at least one PI during the 1-year follow-up. Having had at least one PI during the follow-up has been associated in multivariate analyses with significantly higher improvement in positive and negative symptoms (respectively p =0.031; p = 0.011), mental flexibility (TMT B, p = 0.029; C-VF, p = 0.02) and global functioning (p =0.042). CBT and SST were associated with higher cognitive improvements, while CRT was associated with clinical improvement. These results have not been demonstrated before and suggest that the effect of each PI is larger than its initial target. The present study has confirmed the PIs' effectiveness in a large sample of community-dwelling SZ outpatients at 1 year follow-up. Efforts to improve access to PI should be reinforced in public health policies.

Tobacco smoking is associated with antipsychotic medication, physical aggressiveness, and alcohol use disorder in schizophrenia: results from the FACE-SZ national cohort.

Tobacco smoking is common in schizophrenia and is one of the main causes of premature mortality in this disorder. Little is known about clinical correlates and treatments associated with tobacco smoking in patients with schizophrenia. Still, a better characterization of these patients is necessary, in a personalized care approach. Aggressiveness and childhood trauma have been associated with tobacco smoking in general population, but this association has never been explored in schizophrenia. Our study examines the clinical and therapeutic characteristics of tobacco smoking in schizophrenia. 474 stabilized patients (mean age = 32.2; 75.7% male gender; smokers n = 207, 54.6%) were consecutively included in the network of the FondaMental Expert centers for Schizophrenia and assessed with valid scales. Current tobacco status was self-declared. Aggressiveness was self-reported with Buss-Perry Aggressiveness Questionnaire and Childhood Trauma with Childhood Trauma Questionnaire. Ongoing treatment was reported. In univariate analysis, tobacco smoking was associated with lower education level (p < 0.01), positive syndrome (p < 0.01), higher physical aggressiveness (p < 0.001), alcohol dependence (p < 0.001), and First Generation Antipsychotics (FGAs) use (p = 0.018). In a multivariate model, tobacco smoking remained associated with physical aggressiveness (p < 0.05), current alcohol dependence (p < 0.01) and FGA use (p < 0.05). No association was observed with childhood trauma history, mood disorder, suicidal behavior, psychotic symptom, global functioning or medication adherence. Patients with tobacco use present clinical and therapeutic specificities, questioning the neurobiological links between tobacco and schizophrenia. They could represent a specific phenotype, with specific clinical and therapeutic specificities that may involve interactions between cholinergic-nicotinic system and dopaminergic system. Further longitudinal studies are needed to confirm the potential efficacy of second generation antipsychotics (SGAs) on tobacco use in schizophrenia and to develop effective strategies for tobacco cessation in this population.

Chronic low-grade peripheral inflammation is associated with ultra resistant schizophrenia. Results from the FACE-SZ cohort.

A high rate of patients with schizophrenia (SZ) does not sufficiently respond to antipsychotic medication, which is associated with relapses and poor outcomes. Chronic peripheral inflammation has been repeatedly associated with schizophrenia risk and particularly to poor responders to treatment as usual with cognitive impairment in SZ subjects. The objective of present study was to confirm if ultra resistance to treatment in schizophrenia (UTRS) was associated to chronic peripheral inflammation in a non-selected sample of community-dwelling outpatients with schizophrenia. Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment, including recording of current treatment. Current psychotic symptomatology was evaluated by the Positive and Negative Syndrome scale for Schizophrenia (PANSS). UTRS was defined by current clozapine treatment + PANSS total score ≥ 70. Functioning was evaluated by the Global Assessment of Functioning scale. High sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. 609 stabilized community-dwelling SZ subjects (mean age = 32.5 years, 73.6% male gender) have been included. 60 (9.9%) patients were classified in the UTRS group. In multivariate analyses, UTRS has been associated independently with chronic peripheral inflammation (OR = 2.6 [1.2-5.7], p = 0.01), illness duration (0R = 1.1 [1.0-1.2], p = 0.02) and impaired functioning (OR = 0.9 [0.9-0.9], p = 0.0002) after adjustment for age, sex, current daily tobacco smoking, metabolic syndrome and antidepressant consumption. Peripheral low-grade inflammation is associated with UTRS. Future studies should explore if anti-inflammatory strategies are effective in UTRS with chronic low-grade peripheral inflammation.

Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental.

BACKGROUND: Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. METHOD: Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. RESULTS: The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. CONCLUSION: The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Clinical guidelines for the management of depression with specific comorbid psychiatric conditions French recommendations from experts (the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental).

BACKGROUND: Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. METHOD: The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. RESULTS: The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. CONCLUSION: These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.