Recommendations of the schizophrenia expert center network for the screening prevention and treatment of sleep disorders based on the results from the real-world schizophrenia FACE-SZ national cohort.

BACKGROUND: Sleep disorders associated factors are under explored in schizophrenia while the literature suggests high and heterogeneous frequency. AIMS: The objective of the present study was to determine the prevalence and risk factors of sleep disorders in the real-world FACE-SZ national cohort. METHOD: Stabilized schizophrenic outpatients were recruited in 10 expert centers for schizophrenia. Sleep quality was explored with the Pittsburgh Sleep Quality Index (PSQI) and sleep disorders was defined by a PSQI score > 5. Psychosis severity was measured with the Positive and Negative Syndrome Scale, current major depressive episode with the Calgary Depression Scale for Schizophrenia, verbal aggressiveness with the Buss-Perry Aggression Questionnaire, adherence to treatment with the Medication Adherence Rating Scale, akathisia with the Barnes Akathisia Scale. Current somatic comorbidities and body mass index were reported. Variables with P values <0.20 in univariate analysis were included in a multivariate regression model. RESULTS: Of the 562 included patients, 327 subjects (58.2%, IC95% [54.1% - 62.3%]) reported having sleep disorders. After adjustment, sleep disorders were significantly associated with migraine (adjusted odds ratio aOR = 2.23, p = 0.041), major depressive disorder (aOR 1.79, p = 0.030), poor adherence to treatment (aOR = 0.87, p = 0.006), akathisia (aOR = 1.29, p = 0.042) and verbal aggressiveness (aOR = 1.09, p = 0.002). CONCLUSIONS: More than one on two stabilized real-life outpatients with schizophrenia have been identified with sleep disorders. Combined with the literature data, we have yielded expert recommendations for the treatment and prevention of sleep disorders including treating undiagnosed comorbid depression and migraine and managing antipsychotic treatment to improve adherence and akathisia.

Major depression, sleep, hostility and body mass index are associated with impaired quality of life in schizophrenia. Results from the FACE-SZ cohort.

BACKGROUND: Impaired Quality of life (QoL) in schizophrenia has been mostly associated with psychotic and mood symptomatology, insight and functioning so far. AIMS: QoL levels remain unsatisfactory due to other factors we aim to explore. METHOD: We have explored sleep quality with the Pittsburgh Sleep Quality Index, hostility with the Buss&Perry questionnaire, major depression with the Positive and Negative Syndrome Scale depressive factor, functioning with the Global Assessment of Functioning scale and weight gain with body mass index in addition to other classical QoL-associated factors. RESULTS: 559 patients (mean age=31 (SD 9) years, 74% male sex) were included in the national FACE-SZ cohort. Impaired QoL has been significantly associated with respectively major depression, impaired sleep quality, increased hostility, impaired functioning and impaired insight independently of age, sex, treatments, tobacco smoking and body mass index. Major depression was associated with impaired psychological and physical well-being, and impaired self-esteem. Impaired sleep quality has been associated with impaired psychological and physical well-being and sentimental life. Hostility has been associated with impaired psychological well-being and self-esteem, impaired friends' relationships and impaired autonomy. Weight was associated with impaired physical well-being. Tobacco smoking was associated with higher level of friends' relationships. CONCLUSIONS: Major depression, sleep, hostility, and weight gain have been identified as potential targets to improve QoL in schizophrenia and should be implemented in the recommendations for good practice to optimize schizophrenia care.

[Health professionals facing the coronavirus disease 2019 (COVID-19) pandemic: What are the mental health risks?] / Les professionnels de santé face à la pandémie de la maladie à coronavirus (COVID-19) : quels risques pour leur santé mentale ?

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has caused major sanitary crisis worldwide. Half of the world has been placed in quarantine. In France, this large-scale health crisis urgently triggered the restructuring and reorganization of health service delivery to support emergency services, medical intensive care units and continuing care units. Health professionals mobilized all their resources to provide emergency aid in a general climate of uncertainty. Concerns about the mental health, psychological adjustment, and recovery of health care workers treating and caring for patients with COVID-19 are now arising. The goal of the present article is to provide up-to-date information on potential mental health risks associated with exposure of health professionals to the COVID-19 pandemic. METHODS: Authors performed a narrative review identifying relevant results in the scientific and medical literature considering previous epidemics of 2003 (SARS-CoV-1) and 2009 (H1N1) with the more recent data about the COVID-19 pandemic. We highlighted most relevant data concerning the disease characteristics, the organizational factors and personal factors that may contribute to developing psychological distress and other mental health symptoms. RESULTS: The disease characteristics of the current COVID-19 pandemic provoked a generalized climate of wariness and uncertainty, particularly among health professionals, due to a range of causes such as the rapid spread of COVID-19, the severity of symptoms it can cause in a segment of infected individuals, the lack of knowledge of the disease, and deaths among health professionals. Stress may also be caused by organizational factors, such as depletion of personal protection equipment, concerns about not being able to provide competent care if deployed to new area, concerns about rapidly changing information, lack of access to up-to-date information and communication, lack of specific drugs, the shortage of ventilators and intensive care unit beds necessary to care for the surge of critically ill patients, and significant change in their daily social and family life. Further risk factors have been identified, including feelings of being inadequately supported, concerns about health of self, fear of taking home infection to family members or others, and not having rapid access to testing through occupational health if needed, being isolated, feelings of uncertainty and social stigmatization, overwhelming workload, or insecure attachment. Additionally, we discussed positive social and organizational factors that contribute to enhance resilience in the face of the pandemic. There is a consensus in all the relevant literature that health care professionals are at an increased risk of high levels of stress, anxiety, depression, burnout, addiction and post-traumatic stress disorder, which could have long-term psychological implications. CONCLUSIONS: In the long run, this tragic health crisis should significantly enhance our understanding of the mental health risk factors among the health care professionals facing the COVID-19 pandemic. Reporting information such as this is essential to plan future prevention strategies. Protecting health care professionals is indeed an important component of public health measures to address large-scale health crisis. Thus, interventions to promote mental well-being in health care professionals exposed to COVID-19 need to be immediately implemented, and to strengthen prevention and response strategies by training health care professionals on mental help and crisis management.

Confirmations, advances and recommendations for the daily care of schizophrenia based on the French national FACE-SZ cohort.

BACKGROUND: The National FondaMental Centers of Expertise (FACE) for Schizophrenia (SZ) have been created to shorten the gap between research and clinical practice. OBJECTIVES: To synthetize in a review the 10-year findings issued from the FACE-SZ cohort analyses. METHODS: More than 1000 patients were evaluated in 10 expert centers since 2010 with a 2-day long comprehensive standardized battery including neuropsychological testes and physical health assessment and followed-up for 3 years. RESULTS: 1. The phase 0 cross-sectional analyses have confirmed well-known data: over-prescription of first-generation antipsychotics, antipsychotic polytherapy and long-term benzodiazepine and under-prescription of clozapine, 13% of drug-induced parkinsonism, 18% of akathisia, a mean duration of untreated psychosis of 18 months, one third of poorly-adherent patients, 24% of metabolic syndrome and 52% of current tobacco smokers with poor care for physical illnesses; a yearly mean financial cost of 15,000 euro/patient. 2. FACE-SZ also yielded additional data in insufficiently explored area: a half of major depression issues (among them one third of undiagnosed major depression and 44% of treated patients with unremitted depression), major depression having a strong impact on Quality of Life independently of negative symptoms, 22% of moderated to severe untreated physical pain. 3. FACE-SZ has explored emerging fields of research, including development of 4 stages- model of schizophrenia, chronic low-grade peripheral inflammation, latent Toxoplasma infection, hypovitaminosis D, and a model for relapse prediction at 2 years. DISCUSSION: The associated factors and implications for public health programs were discussed. Based on the FACE-SZ findings and literature, the FACE-SZ group has yielded recommendations to improve daily care for schizophrenia and for future research.

Sexual dysfunctions are associated with major depression, chronic inflammation and anticholinergic consumption in the real-world schizophrenia FACE-SZ national cohort.

BACKGROUND: Sexual dysfunctions (SD) are frequent in schizophrenia (SZ) and associated with treatment withdrawal, however they remain under-explored and under-treated. To date, most of the studies have focused on SD as antipsychotics' side effects in therapeutic trials. AIMS: The objectives of the present study were to determine the SD prevalence in stabilized SZ outpatients and their clinical, pharmacological and biological correlates. METHOD: Two hundred and thirty-seven participants (61.2% men) were consecutively included and received a thorough 2 days- clinical assessment including the self-reported Sexual Functioning Questionnaire (SFQ). SD was defined by a SFQ score ≥ 8. RESULTS: Two hundred and thirty-seven subjects were recruited in the FACE-SZ cohort, 41% of them reported sexual dysfunctions. In multivariate analyses, SD have been associated with current major depressive disorder (adjusted odd ratio aOR = 2.29[1.08-4.85], p = .03), anticholinergic prescription (aOR = 2.65, p = .02) and chronic low-grade inflammation (aOR = 2.09, p = .03) independently of age, gender, current cannabis use disorder and olanzapine prescription. No antipsychotic has been associated with increased or decreased SD rate. CONCLUSIONS: SD are frequent in SZ subjects. Major depression, anticholinergic prescription and chronic low-grade peripheral inflammation may be the three targets of interest for addressing this specific issue.

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.

Inflammatory DEpression Advances in Schizophrenia (IDEAS): A precision medicine approach of the national FACE-SZ cohort.

BACKGROUND: Major Depressive Disorder (MDD) is a therapeutic challenge in schizophrenia (SZ). Untangling different forms of MDD appears as the best current strategy to improve remission to treatment in the so-called precision medicine approach. AIMS: The objectives of the present study were to determine (i) the prevalence of Inflammatory Depression (ID) in stabilized SZ outpatients (ii) if ID was associated with clinical or cognitive profiles that may help clinicians detecting ID (iii) if antidepressants were effective in ID and (iv) the biological correlates of ID that may orientate personalized treatments. METHOD: Participants were consecutively included and received a thorough 2 days- clinical assessment. RESULTS: 785 subjects were recruited in the FACE-SZ cohort. 289 (36.8%) were diagnosed with MDD (remitted or unremitted), of them 57 with ID (19.7%). No clinical or cognitive features were associated with ID (all p > 0.05). ID has been associated with increased abdominal perimeter (aOR = 4.48, p = 0.002) and latent Toxoplasma infection (aOR = 2.19, p = 0.04). While antidepressants were associated with decreased depressive symptoms level in ID, 44% of the subjects remained unremitted under antidepressant, with no association with CRP blood levels. CONCLUSIONS: ID may not differ from other forms of depression by its clinical symptoms but by its aetiologies. ID is associated with increased perivisceral fat and latent Toxoplasma infection that are both potentially related to gut/microbiota disturbances. Specific anti-inflammatory drugs and microbiota-targeted therapeutics appear as promising strategies in the treatment of inflammatory depression in schizophrenia.

[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.

Machine learning for predicting psychotic relapse at 2 years in schizophrenia in the national FACE-SZ cohort.

BACKGROUND: Predicting psychotic relapse is one of the major challenges in the daily care of schizophrenia. OBJECTIVES: To determine the predictors of psychotic relapse and follow-up withdrawal in a non-selected national sample of stabilized community-dwelling SZ subjects with a machine learning approach. METHODS: Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical and cognitive assessment, including recording of current treatment. Relapse was defined by at least one acute psychotic episode of at least 7 days, reported by the patient, her/his relatives or by the treating psychiatrist, within the 2-year follow-up. A classification and regression tree (CART) was used to construct a predictive decision tree of relapse and follow-up withdrawal. RESULTS: Overall, 549 patients were evaluated in the expert centers at baseline and 315 (57.4%) (mean age = 32.6 years, 24% female gender) were followed-up at 2 years. On the 315 patients who received a visit at 2 years, 125(39.7%) patients had experienced psychotic relapse at least once within the 2 years of follow-up. High anger (Buss&Perry subscore), high physical aggressiveness (Buss&Perry scale subscore), high lifetime number of hospitalization in psychiatry, low education level, and high positive symptomatology at baseline (PANSS positive subscore) were found to be the best predictors of relapse at 2 years, with a percentage of correct prediction of 63.8%, sensitivity 71.0% and specificity 44.8%. High PANSS excited score, illness duration <2 years, low Buss&Perry hostility score, high CTQ score, low premorbid IQ and low medication adherence (BARS) score were found to be the best predictors of follow-up withdrawal with a percentage of correct prediction of 52.4%, sensitivity 62%, specificity 38.7%. CONCLUSION: Machine learning can help constructing predictive score. In the present sample, aggressiveness appears to be a good early warning sign of psychotic relapse and follow-up withdrawal and should be systematically assessed in SZ subjects. The other above-mentioned clinical variables may help clinicians to improve the prediction of psychotic relapse at 2 years.

Hypovitaminosis D is associated with depression and anxiety in schizophrenia: Results from the national FACE-SZ cohort.

OBJECTIVE: 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 objectives were (i) to determine the prevalence of hypovitaminosis D and associated factors (with a focus on depression and cognition) in a national non-selected multicentric sample of community-dwelling SZ subjects (ii) to determine the rate of SZ patients being administered vitamin D supplementation and associated factors. METHODS: A comprehensive 2 daylong clinical and neuropsychological battery was administered in 140 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Hypovitaminosis D was defined by blood vitamin D level <25 nM. Depressive symptoms were assessed by the Positive and Negative Syndrome Scale depressive subscore and current anxiety disorder by the Structured Clinical Interview for Mental Disorders. RESULTS: Hypovitaminosis D has been found in 21.4% of the subjects and none of them had received vitamin D supplementation in the previous 12 months. In multivariate analysis, hypovitaminosis D has been significantly associated with respectively higher depressive symptoms (aOR = 1.18 [1.03-1.35], p = 0.02) and current anxiety disorder (aOR = 6.18 [2.15-17.75], p = 0.001), independently of age and gender. No association of hypovitaminosis D with respectively positive and negative symptoms, cognitive scores or other biological variables has been found (all p > 0.05), however, a trend toward significance has been found for metabolic syndrome (p = 0.06). Vitamin D supplementation has been administered during the previous 12 months in only 8.5% of the subjects but was associated with lower depressive symptoms (aOR = 0.67 [0.46-0.98], p = 0.04) and lower rate of current anxiety disorder (aOR = 0.06 [0.01-0.66], p = 0.02) compared to patients with hypovitaminosis D. CONCLUSION: Hypovitaminosis D is frequent and associated with depressive symptoms and anxiety disorders in schizophrenia. Vitamin D supplementation is associated with lower depressive and anxiety symptoms, however patients with hypovitaminosis D remain insufficiently treated.

Latent toxoplasma infection in real-world schizophrenia: Results from the national FACE-SZ cohort.

OBJECTIVE: Latent Toxoplasma infection has been associated with widespread brain immune activation, increased blood brain barrier permeability, neural disruption, increased dopamine release in dopaminergic neurons, with NMDA activation and with schizophrenia (SZ) onset risk. Toxoplasma has been suggested to be a source of chronic low-grade inflammation and this inflammation has been associated with cognitive impairment in SZ. The objective of the present study were (i) to determine if latent Toxoplasma infection was associated with specific clinical features in stabilized SZ subjects, with cognitive impairment and with increased low-grade peripheral inflammation and (ii) to determine if Treatments with Anti-Toxoplasmic Activity (TATA) were associated with improved outcomes in subjects with latent Toxoplasma infection. METHODS: A comprehensive 2 daylong clinical and neuropsychological battery was administered in 250 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Solid phase-enzyme microplate immunoassay methods were used to measure IgG class of antibodies to T. gondii in blood sample. Latent Toxoplasma infection was defined by T. gondii IgG ratio ≥0.8, equivalent to ≥10 international units. Chronic peripheral inflammation was defined by highly sensitive C reactive protein blood level ≥ 3 mg/L. RESULTS: Latent Toxoplasma infection has been found in 184 (73.6%) of this national multicentric sample. In the multivariate analyses, latent Toxoplasma infection has been significantly associated with higher PANSS negative (aOR = 1.1 [1.1-1.1], p = 0.04) and excitement subscores (aOR = 1.3 [1.1-1.6], p = 0.01), with two specific symptoms (i.e., reference delusion (aOR = 3.6 [1.2-10.6] p = 0.01) and alogia (aOR = 16.7 [2.0-134.7], p = 0.008)) and with chronic low-grade peripheral inflammation (27.2% vs. 7.6%, aOR = 3.8 [1.4-10.3], p = 0.004). Extrapyramidal symptoms remained significantly associated with latent Toxoplasma infection. On the opposite, no significant association of latent Toxoplasma infection with age, gender, age at SZ onset, suicide behavior or cognitive deficits has been found in these models (all p > 0.05). TATA were associated with lower depressive symptoms (aOR = 0.8[0.7-0.9], p = 0.01), and with lower rates of chronic peripheral inflammation (20.9% vs. 48.6%, aOR = 3.5 [1.5-7.9], p = 0.003) but not with higher cognitive scores (p > 0.05). CONCLUSION: The present findings suggest that Toxoplasma is almost 3 times more frequent in SZ population compared to general population in France. The potential cerebral underpinnings of the association of latent Toxoplasma infection and the above-mentioned outcomes have been discussed. Future studies should confirm that TATA may be effective to reduce Toxoplasma-associated depressive symptoms and low-grade peripheral inflammation.

Risk factors for increased duration of untreated psychosis. Results from the FACE-SZ dataset.

OBJECTIVES: Reducing the duration of untreated psychosis (DUP) may improve the prognosis of schizophrenia. This study investigated the prevalence, and associated risk factors, of long DUP in a large, non-selected sample of community-dwelling schizophrenia patients (SZ). METHOD: 478 community-dwelling stable SZ participants (122 women and 356 men; mean age 32.37±9.86years) were recruited between 2010 and 2016. The mean retrospective DUP was evaluated from both patient and family reports, as well as hospital/psychiatrists records. Long DUP was defined as >2years. RESULTS: The mean DUP was 1.5years. 80 participants (16.7%) had a DUP>2years. In multivariate analyses, after adjustment for sex, education level, history of childhood trauma and history of maternal schizophrenia or bipolar disorder, long DUP was associated with a younger age of illness onset (19.3±6.67years vs. 22.0±6.51years, adjusted odd ratio aOR=0.91, 95%CI [0.86; 0.97], p=0.003) and cannabis use disorder (20.0% vs. 10.3%, aOR=2.41, 95%CI [1.14-5.09], p=0.02). CONCLUSION: A high proportion of SZ patients still have a long DUP. The present results suggest that illness onset before age 19years and cannabis use are associated with long DUP in schizophrenia patients. Early psychosis detection programs should prioritize the targeting of these populations.

Influence of Venus and Mars in the cognitive sky of schizophrenia. Results from the first-step national FACE-SZ cohort.

OBJECTIVES: Sex differences can yield important clues regarding illness pathophysiology and its treatment. Schizophrenia (SZ) has a lower incidence rate, and a better prognosis, in women versus men. The present study investigated the cognitive profiles of both sexes in a large multi-centre sample of community-dwelling SZ patients. METHOD: 544 community-dwelling stable SZ subjects (141 women and 403 men; mean age 34.5±12.1 and 31.6±8.7years, respectively) were tested with a comprehensive battery of neuropsychological tests. RESULTS: Although community-dwelling SZ men had more risk factors for impaired cognition (including first-generation antipsychotics administration and comorbid addictive disorders), women had lower scores on a wide range of cognitive functions, including current and premorbid intellectual functioning, working memory, semantic memory, non-verbal abstract thinking and aspects of visual exploration. However, women scored higher in tests of processing speed and verbal learning, as well as having a lower verbal learning bias. No sex difference were evident for visuospatial learning abilities, cued verbal recall, sustained attention and tests of executive functions, including cognitive flexibility, verbal abstract thinking, verbal fluency and planning abilities. CONCLUSION: Sex differences are evident in the cognitive profiles of SZ patients. The impact on daily functioning and prognosis, as well as longitudinal trajectory, should be further investigated in the FACE-SZ follow-up study. Sex differences in cognition have implications for precision-medicine determined therapeutic strategies. LIMITS: Given the restricted age range of the sample, future research will have to determine cognitive profiles across gender in late onset SZ.

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.

Cigarette smoking and schizophrenia: a specific clinical and therapeutic profile? Results from the FACE-Schizophrenia cohort.

BACKGROUND: Tobacco use is common in patients with schizophrenia (SZ) but little is known on the role of tobacco in the physiopathology or on the course of the disease. Only few studies embrace an extensive examination of clinical and therapeutic characteristics in stabilized patients. The objective of the present study was to determine the prevalence of tobacco smoking in stabilized SZ outpatients and the clinical and treatment characteristics associated with daily tobacco use in a large community-dwelling sample of patients. METHODS: Three-hundred-and-sixty-one patients were included in the network of the FondaMental Expert Centers for Schizophrenia. Current tobacco status was self-declared. RESULTS: 53.7% were smokers. Mean age at tobacco onset was 17.2years old. In multivariate analyses, after adjustment for confounding factors, positive symptoms and mean daily antipsychotic dose were associated with a higher frequency of tobacco use (OR=1.06 95%IC[1.02-1.12], for positive symptoms, OR=1.1, 95%IC[1.02-1.18] for daily antipsychotic dose). Education level, negative symptoms, anticholinergic agents, clozapine or aripiprazole administration were independently associated with a lower frequency of tobacco use (respectively OR=0.87, 95%IC [0.79, 0.95], OR=0.95, 95%IC[0.91-0.98], OR=0.41, 95%IC[0.22-0.76], OR=0.56, 95%IC=[0.32, 0.99] and OR=0.49, 95%IC [0.26-0.91]). CONCLUSION: The prevalence of current tobacco smoking in a French community-dwelling SZ patients is higher that observed in the general population. Patients with tobacco use present clinical and therapeutic specificities that may involve interaction between cholinergic-nicotinic and dopaminergic systems. The present study suggests that some therapeutics may improve daily smoking behavior in smokers. These results should be confirmed in longitudinal studies.

Predictors of rapid high weight gain in schizophrenia: Longitudinal analysis of the French FACE-SZ cohort.

Metabolic syndrome (MetS) is highly prevalent in schizophrenia. However very little is known about the time course of MetS and its components. The few longitudinal studies that have been carried out had small sample sizes and a short follow-up. The aim of our study was to evaluate the prevalence of MetS and its components, at baseline and one year later, and to investigate predictors of weight gain (WG) in a cohort of individuals with schizophrenia. We followed 167 schizophrenia patients from the FACE-SZ cohort for one year. The Structured Clinical Interview for DSM-IV (SCID) was used to confirm the diagnosis of schizophrenia. Data on socio-demographic and clinical characteristics, antipsychotic treatment, and comorbidities were collected, and a blood sample was drawn. We found that the prevalence of MetS increased from 21.0% to 26.6% after one year. Patients with baseline depressive symptoms had a 4.5-fold higher risk of WG at the one-year follow-up (p = 0.02) than those without depressive symptoms, after adjusting for confounding variables. WG also correlated with high levels of metabolic parameters and peripheral inflammation. These findings highlight the need to systematically diagnose depression in Schizophrenia. Future studies should determine whether specific pharmacological and non-pharmacological interventions for depression in SZ subjects are effective in preventing rapid high weight gain.

Chronic low-grade peripheral inflammation is associated with severe nicotine dependence in schizophrenia: results from the national multicentric FACE-SZ cohort.

Chronic peripheral inflammation (CPI) has been associated with cognitive impairment in schizophrenia (SZ). However, its sources remain unclear, more specifically it is not known whether tobacco smoking is a source of inflammation or not in SZ subjects. Moreover, nicotine (NIC), the major psychoactive compound of tobacco, shows strong anti-inflammatory properties in vitro, as well as inducing a severe biological dependence when administered repeatedly. The objective of the present study was to determine if CPI was associated with tobacco smoking and/or NIC dependence in schizophrenia. Three hundred and forty five stabilized community-dwelling SZ subjects aged 16 years or older (mean age = 32 years, 73% male) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and assessed with validated scales. CPI was defined by a highly sensitive C-reactive protein (hsCRP) ≥3 mg/L. Current tobacco status was self-declared. Severe NIC dependence was defined by a Fagerstrom Test for Nicotine Dependence score ≥7. Overall, 159 (46.1%) were non-smokers, 117 (33.9%) and 69 (20%) were current tobacco smokers with, respectively, low and severe nicotine dependence. In a multivariate model, CPI remained associated with severe NIC dependence (29 vs 15%, OR = 2.8, p = 0.003) and body mass index (OR = 1.1, p < 0.0001), independently of socio-demographic characteristics and antidepressant intake. No association of CPI with low to moderate tobacco smoking dependence, number of daily smoked cigarettes, cannabis use, alcohol use or illness characteristics was found (all p > 0.05). CPI was associated with severe NIC dependence but not with tobacco smoking with low to moderate NIC dependence in SZ, independently of socio-demographic variables, body mass index, alcohol consumption and antidepressant intake. This result highlights the potential CPI consequences of the high prevalence of heavy tobacco smoking in SZ, indicating the importance of new therapeutic strategies for tobacco cessation in SZ.

Childhood trauma, depression and negative symptoms are independently associated with impaired quality of life in schizophrenia. Results from the national FACE-SZ cohort.

OBJECTIVES: Depression and negative symptoms have been associated with impaired Quality of life (QoL) in schizophrenia (SZ). However, childhood trauma may influence both QoL and depression in SZ patients, with consequences for the management of impaired QoL in SZ patients. The aim of the present study was to determine if childhood trauma was associated with impaired QoL in schizophrenia. METHOD: A sample of 544 community-dwelling stabilized SZ patients enrolled in FACE-SZ cohort were utilized in this study (74.1% males, mean aged 32.3years, mean illness duration 10.6years). QoL was self-reported with the S-QoL18 questionnaire. Childhood trauma was self-reported with the Childhood Trauma Questionnaire. Depression was measured by the Calgary Depression Rating Scale for Schizophrenia. Psychotic severity was measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Other clinical factors, treatments, comorbidities, functioning and sociodemographical variables were also recorded, with validated scales. RESULTS: Overall, 151 participants (27.8%) had a current major depressive episode and 406 (82.5%) reported at least one episode of historical childhood trauma. In multivariate analyses, lower QoL total score was associated with a history of childhood trauma (ß=-0.21, p<0.0001), psychotic negative symptoms (ß=-0.11, p=0.04), current depression (ß=-0.0.38, p<0.0001) and male gender (ß=-0.16, p<0.0001). CONCLUSION: Impaired QoL is independently associated with negative symptoms, depression and childhood trauma in schizophrenia.