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.

ADHD and addictive behavior in crack-cocaine users.

BACKGROUND: Crack consumption is a major public health issue in Martinique with a poor prognosis. A preliminary study has found a high prevalence of history of childhood ADHD (C-ADHD) in crack users. OBJECTIVE: To determine the prevalence of C-ADHD and adult ADHD (A-ADHD) in crack users and their potential associations with substance use behavior. METHODS: All consecutive patients consulting in the public academic hospital covering 376,000 inhabitants were included in the present study and received a comprehensive battery measuring addictive behavior, psychiatric and somatic comorbidities. C-ADHD groups and A-ADHD groups were defined with the Wender-Utah Rating Scale-25 and the Brown ADD Rating Scale, respectively. Impulsivity was evaluated with the Barratt Impulsiveness Scale (BIS-11). FINDINGS: In total, 111 participants were evaluated. Among them, 50 (45%) were classified in the C-ADHD group and 20 (18%) in the A-ADHD group. Compared to the patients without ADHD, those with ADHD were found to have higher impulsivity (C-ADHD: BIS total score 67.90 (10.1) vs. 63.28 (10.5), P=0.021, BIS attentional score 17.5 (3.6) vs. 15.3 (3.4), P=0.002, A-ADHD: BIS total score 75.1 (11.3) vs. 63.4 (9.2), P<0.001, BIS motor impulsivity 26.9 (5.3) vs. 22.6 (4.3), P<0.001, BIS attentional score 19.3 (3.3) vs. 15.6 (3.5), P<0.001, BIS planification 28.9 (5.7) vs. 25.10 (4.7), P=0.003). Fifty percent of A-ADHD patients were found with high impulsivity vs. 15% of patients without A-ADHD (P<0.001). However, ADHD was not associated with more severe addictive behavior or history of legal consequences. INTERPRETATION: ADHD prevalence is high in cocaine-crack users and associated with increased impulsivity. However, neither ADHD nor impulsivity explains addictive behaviors or legal consequences.

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.

Anxiety and depression in young physicians: Prevalence and associated factors. The MESSIAEN national study.

BACKGROUND: Physicians are at risk of anxiety and depression. OBJECTIVES: To determine the prevalence of anxiety and depression in a national sample of young physicians and their associated factors. METHODS: The study is a cross-sectional observational epidemiological national study. An online anonymous questionnaire was administered to the young physicians of all French medical faculties. Anxiety and depression were assessed with the Hamilton Anxiety & Depression scale subscores for anxiety and depression. Psychotropic drug consumption, psychotherapy follow-up and other variables were self-declared. RESULTS: Of the 2003 study participants, 32.3% reported a current anxiety disorder and 8.7% a current major depressive disorder according to their HAD scores and less than one on five of them was followed-up in psychotherapy or treated by antidepressant. Moral harassment, a bad quality of initial formation regarding dealing with disease and alcohol consumption were all associated with respectively anxiety disorder and major depression in multivariate analyses. Medical vocation was specifically associated with decreased major depression while being woman and increased coffee consumption were specifically associated with increased anxiety disorders. CONCLUSION: Almost one third of medical students reported anxiety disorder or major depression and less than one on five received the recommended treatment (psychotherapy or antidepressant). The prevention and treatment of psychiatric disorders should be improved in this population. Moral harassment exposure, alcohol and coffee consumptions, bad quality of initial formation regarding dealing with disease have been identified as modifiable factors associated with poor mental health. Despite the absence of causal associations, these results yield some clues to guide future mental health prevention strategies in this population.

Risk factors for burnout and depression in healthcare workers: The national AMADEUS study protocol.

CONTEXT: Burnout is an international phenomenon defined as a state of professional exhaustion. It can lead to depression and have major economic and organizational impacts. Previous studies of healthcare professionals in France have focused on physicians, but none to date have explored other healthcare professions. OBJECTIVES: The main objective of our study is to determine the prevalence of burnout among healthcare workers. The secondary objectives are to explore the associations of burnout with professional and psycho-social factors and the risk of depression, professional harassment, sexual harassment, sexual-orientation based discrimination, consumption of antidepressants, anxiolytics and also the lifestyle of the individual: smoking, alcohol consumption, coffee consumption, physical activity and sleep quality. MATERIALS AND METHODS: The survey will take the form of a voluntary and anonymous online questionnaire carried out on the FramaForm1® platform and will be disseminated via social networks, professional networks and mailings. STUDY POPULATION: Senior doctors, interns, directors of care, nurses, head nurses and senior head nurses, physiotherapists and occupational therapists, dieticians, radiology technicians, laboratory technicians, psychologists, nurses' aides, auxiliary nurses and midwives will be included. COLLECTED DATA: Burnout will be measured with the Maslach Inventory burnout (MBI) questionnaire, work environment with the Karasek questionnaire and anxiety, depression risk with the Center for Epidemiologic Studies- Depression (CES-D), physical activity with the Global Physical Activity Questionnaire (GPAQ) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). ETHICS: This protocol has been accepted by the ethical committee (IRB n°C08/21.01.06.93911, CNIL). EXPECTED RESULTS: Based on international studies, we expect a high rate of burnout with disparities according to profession, socio-demographic data, seniority and type of service. We also expect a significant rate of untreated depression. This study will provide evidence for policy makers to implement collective strategies to reduce burnout and depression in the different populations studied.

The Covid-19 infection: An opportunity to develop systematic vitamin D supplementation in psychiatry.

Psychiatric patients are at risk of hypovitaminosis D and Covid-19-related mortality. In addition to the mental health benefits, vitamin D supplementation may be potentially effective in preventing severe forms of Covid-19 infections. Vitamin D supplementation is not necessary and is not reimbursed in France for this indication. A monthly supplementation of 50,000 IU may be sufficient in most cases. Double the dose is recommended for obese patients. The risk of renal lithiasis is not increased at these doses, even when supplemented in a patient without vitamin D deficiency. The Covid-19 crisis is an opportunity to disseminate vitamin D supplementation in psychiatric patients, as it has been shown to be effective in other respiratory diseases such as mild upper respiratory tract infections and influenza.

Prevalence and associated factors of cannabis consumption in medical students: the BOURBON nationwide study.

France has been identified with one of the highest rates of cannabis consumption of Western European countries. Yet we lack data in medical students who are at risk of addictive behavior. The objective of the study is to determine the prevalence of cannabis consumption and cannabis use disorder (CUD) among French medical students and their association with psychotropic drug consumption and psychosocial factors. Medical students were recruited from 35 French universities of medicine through administration mailing lists and social networks, between December 2016 and May 2017. Cannabis consumption was self-declared by anonymous questionnaire and CUD was defined by a Cannabis Abuse Screening Test (CAST) score ≥ 3. 10,985 medical students with a mean age of 21.8 years (± 3.3) were included, 32% of which were men. Overall, 1642 [14.9 (14.3; 15.6)%] reported cannabis consumption and 622 [5.7 (5.2; 6.1)%] students were identified with CUD at screening. Men were at two-time higher risk of cannabis consumption and three-time higher risk of CUD (22.4% and 10.6% for men vs. 11.5% and 3.4%, respectively, for women). In multivariate analyses, men sex, alcohol use disorder, tobacco smoking, parents' divorce, and history of physical assault and lower rates of lower rates of ≥ 40 weekly worked hours were identified as common associated factors for cannabis consumption and CUD. Hypnotic consumption, psychiatric follow-up, and history of sexual assault were identified as factors associated specifically with CUD, suggesting that these factors were associated with more severe cannabis consumption. Only 17% of students identified with CUD reported a psychiatric follow-up. Altogether, these results suggest that health policies should target cannabis consumption in medical students that is frequent, especially in men, with low rates of psychiatric follow-up. We have identified psychological factors and increased hypnotic drug consumption in CUD participants suggesting that psychiatric follow-up should be systematically proposed to this group.

Hazardous drinking is associated with hypnotic consumption in medical students in the BOURBON nationwide study: psychological factors explored.

France has been identified with one of the highest rates of hazardous drinking and hypnotic consumption in Western countries. Medical students have been identified at risk for hazardous drinking yet we lacked of national data on their hypnotic consumption and associated factors to guide public health policies. To determine the prevalence of hazardous drinking and dependence among French medical students and their association with psychotropic drug consumption and psychosocial factors. Medical students were recruited from 35 French universities of medicine through administration mailing lists and social networks, between December 13, 2016 and May 15, 2017. Hazardous drinking was defined by an Alcohol Use Disorder Identification Test (AUDIT) score ≥ 7 for men and ≥ 6 for women. 10,985 medical students with a mean aged of 21.8 years (± 3.3) were included, 32% of which were male. Overall, 3713 (34%) students reported hazardous drinking (41% for men vs. 31% for women) and 820 participants (8%) reported alcohol dependence (12% for men vs. 6% for women). In multivariate analyses, hazardous drinking was independently associated with age, male gender, hypnotic consumption, psychiatric follow-up, mourning, parents divorce, exposure to sexual and physical assault. Alcohol dependence was associated with male gender, tobacco and cannabis consumption, and sexual and physical assault. Second year was reported as the year at higher risk for increased alcohol consumption vs. decreased risk in first and fourth year. Hazardous drinking identified in one third of medical students is associated with hypnotic consumption and some psychological factors suggesting self-medication behavior that could be targeted by psychological interventions.

Repeated bullying at the workplace in medical students and young doctors: the MESSIAEN national study.

Despite clues indicating high Bullying at the Work Place (BWP) rates in French hospitals, there has been no quantitative study so far. To determine the prevalence of repeated BWP in a national sample of French young physicians; its risk factors, and the mental health consequences of BWP. The study is a cross-sectional observational epidemiological national study addressed to young physicians. The online internet anonymous questionnaire was elaborated according to previous studies exploring BWP. In addition, we explored the quality of initial training. BWP was defined according to the French legal definition. Mental health was assessed by Hamilton Anxiety and Depression scale, psychotropic drug consumption and psychotherapy follow-up. A Structured Equation Modeling (SEM) was carried out to confirm our theoretical model. 2003 participants of the 37 French medical faculties were included. At least one history of BWP was identified in 41.7% of the participants. The SEM model showed good fit (RMSEA = 0.025, CFI = 0.93, TLI = 0.92, WRMR = 1.285). In the SEM model, BWP was associated with age and number of monthly night shifts and weekly worked hours. Obstetric gynecology, psychiatry, surgery, and medical specialties and low-quality initial training were associated with higher risk of BWP. BWP was associated with increased anxiety and depressive symptoms, daily antidepressant and anxiolytic consumption, and psychotherapy follow-up. Decreasing worked hours and night shifts and improving the quality of the initial training may help preventing BWP among medical students and young physicians. Obstetric gynecology, surgical and medical specialties, and psychiatry should be targeted with a focus on developing prevention programs.

[Exposure to professional violence by young physicians in the hospital: MESSIAEN national study]. / Exposition aux violences professionnelles à l'hôpital chez les jeunes médecins : l'étude nationale MESSIAEN.

BACKGROUND: Hospital professional violence is defined as hostile and aggressive behavior exerted by health professionals on other health professionals. No quantitative study has been carried out to date on French hospital professional violence among young physicians, while recent qualitative studies have suggested a potential high frequency. The main objective was to determine the prevalence of exposure of young doctors to hospital violence. The secondary objective was to determine their characteristics and consequences as well as to determine if students and young physicians (resident and young MD) differed. METHODS: The study was a national cross-sectional observational epidemiological study that included 4th-year medical students and young physicians (MD for less than 2 years). Thirty-seven French faculties of medicine were contacted for email recruitment of participants. Social networks were used to increase the visibility of the study. The questionnaire was developed after exhaustive review of the international literature dealing with professional violence in hospitals, its characteristics and its consequences in terms of mental health, addiction, personal and professional life. The report of these events was also explored. RESULTS: In total, 2003 participants have been included. More than nine out of ten participants were exposed to hospital violence at least once and nearly 42% to moral harassment as defined by the French law. This violence does not differ between the students and the residents/young MDs, suggesting that working time in the hospital does not seem to affect this risk. Nearly 80 % of interns and young MDs reported working more than the legal time. The perpetrators of violence include in almost all cases at least one man, often a senior doctor, but students reported the presence of at least one woman among the perpetrators in ¾ of cases. The victims are as often men as women. Compared to the undergraduate medical students, residents and young MDs more frequently reported poor outcomes on their mental health, addictive behavior, personal and professional lives. The majority of victims reported the event to a peer but fewer than 10% to the head of the department, a professor or an instance that could have acted. In almost all cases, participants reported the continuation of abusive behavior after the event. In total, 42% of students think that this is simple part of medical studies that they must endure. CONCLUSION: These results suggest the need to develop specific information and prevention programs for professional hospital violence in France.

Increased in-hospital mortality from COVID-19 in patients with schizophrenia.

BACKGROUND: There is limited information describing the presenting characteristics and outcomes of patients with schizophrenia (SCZ) requiring hospitalization for coronavirus disease 2019 (COVID-19). AIMS: We aimed to compare the clinical characteristics and outcomes of COVID-19 SCZ patients with those of non-SCZ patients. METHOD: This was a case-control study of COVID-19 patients admitted to 4 AP-HM/AMU acute care hospitals in Marseille, southern France. COVID-19 infection was confirmed by a positive result on polymerase chain reaction testing of a nasopharyngeal sample and/or on chest computed scan among patients requiring hospital admission. The primary outcome was in-hospital mortality. The secondary outcome was intensive care unit (ICU) admission. RESULTS: A total of 1092 patients were included. The overall in-hospital mortality rate was 9.0%. The SCZ patients had an increased mortality compared to the non-SCZ patients (26.7% vs. 8.7%, P=0.039), which was confirmed by the multivariable analysis after adjustment for age, sex, smoking status, obesity and comorbidity (adjusted odds ratio 4.36 [95% CI: 1.09-17.44]; P=0.038). In contrast, the SCZ patients were not more frequently admitted to the ICU than the non-SCZ patients. Importantly, the SCZ patients were mostly institutionalized (63.6%, 100% of those who died), and they were more likely to have cancers and respiratory comorbidities. CONCLUSIONS: This study suggests that SCZ is not overrepresented among COVID-19 hospitalized patients, but SCZ is associated with excess COVID-19 mortality, confirming the existence of health disparities described in other somatic diseases.

Increase of precuneus metabolism correlates with reduction of PTSD symptoms after EMDR therapy in military veterans: an 18F-FDG PET study during virtual reality exposure to war.

PURPOSE: The prevalence of posttraumatic stress disorder (PTSD) is higher among veterans, and can lead to disastrous consequences such as suicide. Eye movement desensitization and reprocessing (EMDR) is recommended in first-line psychotherapies for PTSD. Virtual reality exposure (VRE) coupled with 18F-FDG PET imaging can highlight the activated brain regions during stress exposure. The objective of this study is to identify, after EMDR therapy, the regions of brain metabolism that evolve during the stress exposure of a war scene with symptomatic remission in a group of military veterans suffering from PTSD, and to secondarily search for predictive metabolic features. METHODS: We recruited 15 military veterans suffering from PTSD who performed an 18F-FDG PET sensitized by the exposure to a virtual war scene, before (T0) and after (T1) EMDR therapy. Statistical parametric mapping was used to compare brain metabolism before and after treatment and to study correlations between metabolism and evolution scores on PTSD clinical scales (PTSD Checklist Scale, PCLS; Clinician-Administered PTSD Scale, CAPS). RESULTS: The metabolic activity of the precuneus was increased after EMDR therapy (p < 0.005 uncorrected, k > 180) and correlated with clinical improvement with the CAPS scale (r = -0.73 and p < 0.001). Moreover, the precuneus metabolic value before therapy predicted the clinical improvement on the PCLS scale (T1-T0) after EMDR (r = -0.667 and p < 0.006). CONCLUSION: The clinical improvement in military patients with PTSD after EMDR is related to increased precuneus metabolism upon VR stress exposure.

Hypovitaminosis D is associated with negative symptoms, suicide risk, agoraphobia, impaired functional remission, and antidepressant consumption in schizophrenia.

Hypovitaminosis D has been associated with, respectively, major depressive disorder, schizophrenia (SZ), and cognitive disorders in the general population, and with positive and negative symptoms and metabolic syndrome in schizophrenia. The objective was to determine the prevalence of hypovitaminosis D and associated factors in a non-selected multicentric sample of SZ subjects in day hospital. Hypovitaminosis D was defined by blood vitamin D level < 25 nM. Depressive symptoms were assessed by the Calgary Depression Rating Scale Score and Positive and Negative Syndrome Scale Score. Anxiety disorders and suicide risk were evaluated by the Structured Clinical Interview for Mental Disorders. Functioning was evaluated with the Functional Remission of General Schizophrenia Scale. Hypovitaminosis D has been found in 27.5% of the subjects. In multivariate analysis, hypovitaminosis D has been significantly associated with, respectively, higher suicide risk (aOR = 2.67 [1.31-5.46], p = 0.01), agoraphobia (aOR = 3.37 [1.66-6.85], p < 0.0001), antidepressant consumption (aOR = 2.52 [1.37-4.64], p < 0.001), negative symptoms (aOR = 1.04 [1.01-1.07], p = 0.04), decreased functioning (aOR = 0.97[0.95-0.99], p = 0.01), and increased leucocytosis (aOR = 1.17 [1.04-1.32], p = 0.01) independently of age and gender. No association with alcohol use disorder, metabolic syndrome, peripheral inflammation, insulin resistance, or thyroid disturbances has been found (all p > 0.05). Despite some slight abnormalities, no major cognitive impairment has been associated with hypovitaminosis D in the present sample (all p > 0.05 except for WAIS similarities score). Hypovitaminosis D is frequent and associated with suicide risk, agoraphobia and antidepressant consumption in schizophrenia, and more slightly with negative symptoms. Patients with agoraphobia, suicide risk and antidepressant consumption may, therefore, benefit in priority from vitamin D supplementation, given the benefit/risk profile of vitamin D. Further studies should evaluate the impact of vitamin D supplementation on clinical outcomes of SZ subjects.

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 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.

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.

[The 10-year findings from the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ): Review and recommendations for clinical practice]. / Centres Experts Schizophrénie, un outil pour le soin et la recherche : retour sur 10 ans d'expérience.

OBJECTIVES: The present article is a synthesis of the first 10 years of follow-up of the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ) cohort. METHODS: More than 700 community-dwelling stabilized subjects have been recruited and evaluated to date. The mean age was 32 years with 75 % males, the mean illness duration was 11 years, the mean age at illness onset was 21 years, the mean duration of untreated psychosis was 1.5 years and 55 % were current daily tobacco smokers. RESULTS: The major findings of the FACE-SZ cohort may be summarized as follows: the metabolic syndrome is twice more frequent in schizophrenia as compared to the general population and is not correctly assessed and treated; cognitive disturbances have been found in benzodiazepine consumers and in patients with chronic low-grade peripheral inflammation; major depressive disorder (MDD) is a common current comorbid condition in about 20% of the subjects at the evaluation. MDD is associated with impaired quality of life and with increased nicotine dependency in SZ daily tobacco smokers. Improving depression and negative symptoms may be the most effective strategies to improve quality of life in schizophrenia; the duration of untreated psychosis is much longer in cannabis smokers and in subjects with an age at illness onset<19 years. Adherence to treatment is diminished in subjects who report a subjective negative feeling after treatment intake independent of objective side effects (extrapyramidal syndrome and weight gain). Akathisia has been found in 18% of the subjects and has been associated with antipsychotic polytherapy. CONCLUSIONS: In the light of these results, some recommendations for clinical care may be suggested. The early detection of schizophrenia should be specifically increased in adolescents and/or cannabis smokers. All patients should be administered a comprehensive neuropsychological evaluation at the beginning of the illness and after stabilization under treatment. Improving metabolic parameters and lifestyle (diet and physical activity) should be reinforced. The benefit/risk ratio of benzodiazepine and antipsychotic polytherapy should be regularly reevaluated and withdrawn as soon as possible. If MDD remains underdiagnosed and undertreated, improving depression may strongly improve the quality of life of SZ subjects. In the end, Cognitive Remediation Therapy and anti-inflammatory strategies should be more frequently included in therapeutic strategies.

Relationships between low-grade peripheral inflammation and psychotropic drugs in schizophrenia: results from the national FACE-SZ cohort.

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

Making psychiatric semiology great again: A semiologic, not nosologic challenge.

This article analyzes whether psychiatric disorders can be considered different from non-psychiatric disorders on a nosologic or semiologic point of view. The supposed difference between psychiatric and non-psychiatric disorders relates to the fact that the individuation of psychiatric disorders seems more complex than for non-psychiatric disorders. This individuation process can be related to nosologic and semiologic considerations. The first part of the article analyzes whether the ways of constructing classifications of psychiatric disorders are different than for non-psychiatric disorders. The ways of establishing the boundaries between the normal and the pathologic, and of classifying the signs and symptoms in different categories of disorder, are analyzed. Rather than highlighting the specificity of psychiatric disorders, nosologic investigation reveals conceptual notions that apply to the entire field of medicine when we seek to establish the boundaries between the normal and the pathologic and between different disorders. Psychiatry is thus very important in medicine because it exemplifies the inherent problem of the construction of cognitive schemes imposed on clinical and scientific medical information to delineate a classification of disorders and increase its comprehensibility and utility. The second part of this article assesses whether the clinical manifestations of psychiatric disorders (semiology) are specific to the point that they are entities that are different from non-psychiatric disorders. The attribution of clinical manifestations in the different classifications (Research Diagnostic Criteria, Diagnostic Statistic Manual, Research Domain Criteria) is analyzed. Then the two principal models on signs and symptoms, i.e. the latent variable model and the causal network model, are assessed. Unlike nosologic investigation, semiologic analysis is able to reveal specific psychiatric features in a patient. The challenge, therefore, is to better define and classify signs and symptoms in psychiatry based on a dual and mutually interactive biological and psychological perspective, and to incorporate semiologic psychiatry into an integrative, multilevel and multisystem brain and cognitive approach.