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Promoting the cessation of smoking in mental healthcare is a priority of international health organizations as it is the most cost-effective intervention in psychiatry.To explore the representations of psychiatrists on their role in active smoking cessation prevention in severe psychiatric disorders.Psychiatrists and residents in psychiatry were recruited at a national level by professional mailings.One thousand four hundred and sixty participants were included in the study, and only 46% reported actively promoting smoking cessation. In multivariate analyses, participants aged35years were more likely to promote cessation of tobacco smoking, as well as the two thirds who believe that psychiatry is a systemic discipline with complex interactions between brain, body and mind. Almost two thirds of those promoting tobacco cessation reported lacking time to combine psychiatric and physical examination during one session. The psychiatrists who reported not promoting tobacco smoking cessation also reported never dealing with physical health in case of the absence of a general practitioner and thinking that physical examination may have a negative impact on the therapeutic relationship. Almost all (96%) reported promoting the need for a general practitioner for their patients. We found no significant difference between the public and private sectors (P0.05).Young psychiatrists are more prone than their elders to promote smoking cessation but report lacking time to include it in their daily practice. Promotion of tobacco smoking cessation should be included in the components for quality evaluation for mental health services and specific sessions dedicated to this intervention.

It remains unknown to what degree resource prioritization toward SARS-CoV-2 (2019-nCoV) coronavirus (COVID-19) cases had disrupted usual acute care for non-COVID-19 patients, especially in the most vulnerable populations such as patients with schizophrenia. The objective was to establish whether the impact of the COVID-19 pandemic on non-COVID-19 hospital mortality and access to hospital care differed between patients with schizophrenia versus without severe mental disorder. We conducted a nationwide population-based cohort study of all non-COVID-19 acute hospitalizations in the pre-COVID-19 (March 1, 2019 through December 31, 2019) and COVID-19 (March 1, 2020 through December 31, 2020) periods in France. We divided the population into patients with schizophrenia and age/sex-matched patients without severe mental disorder (1:10). Using a difference-in-differences approach, we performed multivariate patient-level logistic regression models (adjusted odds ratio, aOR) with adjustment for complementary health insurance, smoking, alcohol and substance addiction, Charlson comorbidity score, origin of the patient, category of care, intensive care unit (ICU) care, major diagnosis groups and hospital characteristics. A total of 198,186 patients with schizophrenia were matched with 1,981,860 controls. The 90-day hospital mortality in patients with schizophrenia increased significantly more versus controls (aOR = 1.18; p p = 0.033), respiratory diseases (aOR = 1.19; p = 0.008) and for both surgery (aOR = 1.26; p = 0.008) and medical care settings (aOR = 1.16; p = 0.001). Significant changes in the case mix were noted with reduced admission in the ICU and for several somatic diseases including cancer, circulatory and digestive diseases and stroke for patients with schizophrenia compared to controls. These results suggest a greater deterioration in access to, effectiveness and safety of non-COVID-19 acute care in patients with schizophrenia compared to patients without severe mental disorders. These findings question hospitals’ resilience pertaining to patient safety and underline the importance of developing specific strategies for vulnerable patients in anticipation of future public health emergencies.

Women with schizophrenia and their newborns are at risk of adverse pregnancy, delivery, neonatal and child outcomes. However, robust and informative epidemiological estimates are lacking to guide health policies to prioritise and organise perinatal services. For the first time, we carried out a systematic review and meta-analysis to synthesise the accumulating evidence on pregnancy, delivery, neonatal complications, and infant mortality among women with schizophrenia and their newborns (N = 43,611) vs. controls (N = 40,948,272) between 1999 and 2021 (26 population-based studies from 11 high-income countries) using random effects. Women with schizophrenia had higher odds (OR) of gestational diabetes (2.35, 95% CI: [1.57-3.52]), gestational hypertension, pre-eclampsia/eclampsia (OR 1.55, 95% CI: [1.02-2.36]; 1.85, 95% CI: [1.52-2.25]), antepartum and postpartum haemorrhage (OR 2.28, 95% CI: [1.58-3.29]; 1.14, 95% CI: [1.04-1.24]), placenta abruption, threatened preterm labour, and premature rupture of membrane (OR 2.20, 95% CI: [2.02-2.39]; 2.91, 95% CI: [1.57-5.40]; 1.29, 95% CI: [1.06-1.58]), c-section (OR 1.33, 95% CI: [1.22-1.45]), foetal distress (OR 1.80, 95% CI: [1.43-2.26]), preterm and very preterm delivery (OR 1.79, 95% CI: [1.62-1.98]; 2.31, 95% CI: [1.78-2.98]), small for gestational age and low birth weight (OR 1.63, 95% CI: [1.48-1.80]; 1.75, 95% CI: [1.46-2.11]), congenital malformations (OR 1.86, 95% CI: [1.71-2.03]), and stillbirths (OR 2.06, 95% CI: [1.83-2.31]). Their newborns had higher odds of neonatal death (OR 1.41, 95% CI: [1.03-1.94]), post-neonatal death (OR 2.87, 95% CI: [2.11-3.89]) and infant mortality (OR 2.33, 95% CI: [1.81-3.01]). This large-scale meta-analysis confirms that schizophrenia is associated with a substantially increased risk of very preterm delivery, stillbirth, and infant mortality, and metabolic risk in mothers. No population-based study has been carried out in low- and middle-income countries in which health problems of women with schizophrenia are probably more pronounced. More research is needed to better understand the complex needs of women with schizophrenia and their newborns, determine how care delivery could be optimised, and define best practices. Study registration: PROSPERO CRD42020197446.

International audience; Caffeine is the most consumed psychoactive substance worldwide. Previous studies suggested higher caffeine consumption in subjects with schizophrenia spectrum disorders (SSD) as well as associations with symptoms, medication and medication side-effects. In a large and well-characterized sample of SSD subjects we explored the association between caffeine consumption and clinical (psychosis related, severity, general health) as well as pharmacological (antipsychotic treatment, sedation potential) variables. Eight hundred four subjects with data on their caffeine (coffee and tea) consumption successively recruited were included in this study. After controlling for potential confounders (demographic variables, smoking) only the negative dimension of psychosis was associated with the amount of caffeine ingested. Less severe negative symptoms were associated with higher caffeine consumption. The effect size of this association was small (partial correlation coefficient = −0.12) but significant.

Measuring the quality of information delivered to patients with severe mental illness (SMI), i.e., schizophrenia, bipolar disorders, and major depressive disorders, is essential to improve their quality of care. In this work, we described the different steps of the validation of the PREMIUM computerized adaptive testing (CAT) for measuring the quality of information delivered to patients with SMI. The PREMIUM item bank regarding information included 25 items. A total of 499 patients with schizophrenia (53%), bipolar disorders (26%), and major depressive disorders (22%) were recruited from numerous in- and outpatient settings in France. Unidimensionality, local independence, and monotonicity were verified for 19 items of the item bank. The psychometric properties were satisfactory for both internal (RMSEA = 0.069, CFI = 0.969, TLI = 0.963) and external validity (in particular, significant associations were found with age, educational level, and social functioning). The CAT exhibited satisfactory accuracy and precision (standard error of measurement

The aim of this study was to (1) calibrate an item bank to measure patients’ experience of drug therapy for adult patients with SMIs and (2) develop computerized adaptive testing (CAT) to improve its use in routine practice. This is a cross-sectional, multicentric study involving 541 patients with schizophrenia, bipolar disorder, and major depressive disorder. Analyses based on classical test and item response theories were performed. After 7 highly inter-correlated items and 4 items with low factor loadings were removed, the remaining 26 items were sufficiently unidimensional (RMSEA = 0.069, CFI = 0.969, TLI = 0.963) and showed adequate fit to the generalized partial credit model. There was no differential item functioning by gender, age, care setting, or diagnosis from moderate- to large-magnitude. The mean score was 46.0 ± 16.9 and was significantly higher for patients reporting good medication adherence. The resulting PREMIUM-DT item bank has strong psychometric properties, and CAT facilitates widespread use in clinical settings (an average of 8 items administered, corresponding to a reliability of >0.90). Our results suggest that practical information and information about the side effects of psychotropic treatments and how to cope with them should be targeted as a priority to improve patients’ experience of drug therapy.

Resume Les patients atteints de schizophrenie representent une population vulnerable qui a ete sous-etudiee dans le cadre de la recherche COVID-19. Nous avons cherche a etablir si les resultats et les soins de sante differaient entre les patients atteints de schizophrenie et les patients sans diagnostic de maladie mentale. Nous avons mene une etude basee sur la population de tous les patients presentant des symptomes respiratoires et une infection a COVID-19 identifies qui ont ete hospitalises en France entre fevrier et juin 2020. Au total, 50 750 patients ont ete inclus, dont 823 etaient des patients avec schizophrenie (1,6 %). Ces derniers ont connu une augmentation de la mortalite hospitaliere (25,6 % contre 21,7 % pour les autres patients) et une diminution du taux d’admission en unite de soins intensifs-reanimation (23,7 % contre 28,4 %) par rapport aux temoins. Les patients schizophrenes âges de 65 a 80 ans presentaient un risque de mortalite significativement plus eleve que les temoins du meme âge (+7,89 %) alors qu’ils ont ete moins admis en USI que les temoins du meme âge (−15,44 %). Cette etude montre l’existence de disparites en matiere de sante et d’acces aux soins entre les patients schizophrenes et les patients sans diagnostic de maladie mentale. Ces disparites different en fonction de l’âge et du profil clinique des patients, ce qui suggere l’importance d’une gestion clinique personnalisee du COVID-19 et de strategies de soins de sante avant, pendant et apres l’hospitalisation pour reduire les disparites de sante dans cette population vulnerable. Les patients schizophrenes âges de 65 a 80 ans etaient plus souvent envoyes par les hopitaux ou les institutions que les patients sans diagnostic de maladie mentale grave, ce qui peut expliquer les mauvais resultats de sante des patients schizophrenes. Une etude francaise a rapporte que la plupart des patients psychiatriques hospitalises avec un diagnostic COVID-19 etaient gardes dans des services psychiatriques specialises et non dans des hopitaux generaux. La division entre medecine physique et psychiatrique entraine une confusion quant au secteur du service de sante (c’est-a-dire les niveaux de soins primaires, de sante mentale ou de soins aigus) qui devrait assumer la responsabilite de la gestion des patients ayant des besoins de sante complexes. Nous manquons de donnees nationales sur le taux de patients âges schizophrenes qui sont institutionnalises, mais nous pouvons raisonnablement supposer que l’institutionnalisation est un facteur de risque d’infection grave par COVID-19 chez les patients âges avec schizophrenie. Nos resultats soutiennent une strategie de detection systematique chez les patients avec schizophrenie institutionnalises et d’intervention precoce dans cette population. Cela a deja ete fait dans un refuge pour sans-abri a Boston ou 36 % des residents ont ete testes positifs. Le taux d’admission en reanimation etait plus faible chez les patients schizophrenes que chez les patients sans diagnostic de maladie mentale grave, ce qui illustre parfaitement le debat entre les arguments fondes sur l’utilite et ceux fondes sur l’equite. Les patients schizophrenes presentaient l’un des plus mauvais indicateurs de pronostic justifiant le triage en reanimation. Cependant, ce triage base uniquement sur le pronostic exacerbe les inegalites existantes en matiere de sante, laissant les patients defavorises dans une situation plus difficile.

Background Tobacco smoking has been associated with suicide, impulsivity and depression in non-clinical populations with differences across sexes. Objective To determine the role of tobacco smoking in Treatment-Resistant Depression (TRD) according to sex in a precision-medicine approach. Method The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at 6 months. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at 6 months on their smoking and psychiatric hospitalization outcomes. Results 355 TRD participants were included (222 women). The smoking rate was much higher in TRD women compared to the French general population (34% vs 24%) while it was comparable for men (approximately 29%). In multivariate analyses, compared to non-smoking women, female smokers had significantly increased number of lifetime psychiatric hospitalizations (standardized beta B = 0.232, p = 0.014) and electro-convulsive therapy (adjusted odds ratio (aOR) = 2.748, p = 0.005), increased suicidal ideations (aOR = 4.047, p = 0.031), history of suicide attempt (aOR = 1.994, p = 0.033), and increased impulsivity (B = 0.210, p = 0.006) and were more frequently treated by benzodiazepines (aOR = 1.848, p = 0.035) and third- or fourth-line TRD treatments (antipsychotics aOR = 2.270, p = 0.006, mood stabilizers aOR = 2.067 p = 0.044). Tobacco smoking at baseline was predictive of psychiatric hospitalization within 6 months in persistent smoking women (aOR = 2.636, p = 0.031). These results were not replicated in men, for whom tobacco smoking was only associated with increased clinician-rated and self-reported depressive symptoms (respectively B = 0.207, p = 0.022 and B = 0.184, p = 0.048). The smoking cessation rate at 6 months was higher in women than in men (12% vs. 7%). No patient was administered nicotine substitute or varenicline at the two timepoints. Interpretation Combining these results and those of the literature, we recommend that active tobacco cessation should be promoted in TRD to improve depression, suicide and impulsivity especially in women. Female smokers appear as a specific population with heavier mental health outcomes that should be specifically addressed.

Comorbid major depressive disorder (MDD) in schizophrenia (SZ; SZ-MDD) has been identified as a major prognostic factor. However, the prevalence and associated factors of SZ-MDD have never been explored in a meta-analysis. All studies assessing the prevalence of SZ-MDD in stabilized outpatients with a standardized scale or with structured interviews were included. The Medline, Web of Science, PsycINFO, and Google Scholar databases were searched. Using random effects models, we calculated the pooled estimate of the prevalence of SZ-MDD. We used meta-regression and subgroup analyses to evaluate the potential moderators of the prevalence estimates, and we used the leave-one-out method for sensitivity analyses. Of the 5633 potentially eligible studies identified, 18 studies (n = 6140 SZ stabilized outpatients) were retrieved in the systematic review and included in the meta-analysis. The pooled estimate of the prevalence of SZ-MDD was 32.6% (95% CI: 27.9–37.6); there was high heterogeneity (I2 = 92.6%), and Egger’s test did not reveal publication bias (P = .122). The following factors were found to be sources of heterogeneity: publication in or after 2015, the inclusion of patients from larger studies, the assessment tools, the inclusion of patients with substance use disorder or somatic chronic diseases, age, education level, the lifetime number of hospitalizations, and antidepressant use. Two-thirds of the extracted variables could not be explored due to an insufficient amount of published data. The prevalence of MDD is high among SZ individuals. Healthcare providers and public health officials should have an increased awareness of the burden of SZ-MDD.

Background: Patients with schizophrenia (SCZ) represent a vulnerable population who have been understudied in COVID-19 research. We aimed to establish whether health outcomes and care differed between patients with SCZ and patients without a diagnosis of severe mental illness. Methods: We conducted a population-based cohort study of all patients with identified COVID-19 and respiratory symptoms who were hospitalized in France between February and June 2020. Cases were patients who had a diagnosis of SCZ. Controls were patients who did not have a diagnosis of severe mental illness. The outcomes were in-hospital mortality and intensive care unit (ICU) admission. Findings: A total of 50,750 patients were included, of whom 823 were SCZ patients (1.6%). The SCZ patients had an increased in-hospital mortality (25.6% vs. 21.7%; adjusted odds ratio (aOR) 1.30 [95% CI 1.08-1.56], p=0.0093) and a decreased ICU admission rate (23.7% vs. 28.4%; aOR 0.75 [95% CI 0.62-0.91], p=0.0062) compared to controls. Significant interactions between SCZ and age for mortality and ICU admission were observed (p=0.0006 and p

BackgroundThe determinants of quality of life (QoL) in schizophrenia are largely debated, mainly due to methodological discrepancies and divergence about the concepts concerned. As most studies have investigated bi- or tri-variate models, a multivariate model accounting for simultaneous potential mediations is necessary to have a comprehensive view of the determinants of QOL. We sought to estimate the associations between cognitive reserve, cognition, functioning, insight, depression, schizophrenic symptoms, and QoL in schizophrenia and their potential mediation relationships.MethodsWe used structural equation modeling with mediation analyses to test a model based on existing literature in a sample of 776 patients with schizophrenia from the FondaMental Foundation FACE-SZ cohort.ResultsOur model showed a good fit to the data. We found better functioning to be positively associated with a better QoL, whereas better cognition, better insight, higher levels of depression, and schizophrenic symptoms were associated with a lower QoL in our sample. Cognitive reserve is not directly linked to QoL, but indirectly in a negative manner via cognition. We confirm the negative relationship between cognition and subjective QoL which was previously evidenced by other studies; moreover, this relationship seems to be robust as it survived in our multivariate model. It was not explained by insight as some suggested, thus the mechanism at stake remains to be explained.ConclusionThe pathways to subjective QoL in schizophrenia are complex and the determinants largely influence each other. Longitudinal studies are warranted to confirm these cross-sectional findings.

Purpose The purpose of this study was to describe the association between adherence to antipsychotic medication and quality of life (QoL) in a sample of individuals diagnosed with schizophrenia. Methods Two hundred fifty-three patients were included from three public mental health services from Bolivia, Peru, and Chile. Data were collected using the Drug Attitude Inventory (DAI-10) and the Schizophrenia Quality of Life short-version questionnaire (SQoL-18), which considers 8 dimensions. Results Significant associations were found between adherence to antipsychotic medication treatment and QoL (S-QoL-18 index: β = 0.26, p = 0.004; self-esteem: β = 0.37, p = 0.000; and sentimental life: β = 0.20, p = 0.033). Associations of clinical and socio-demographic variables with QoL were identified: severity of psychotic symptoms, awareness of the disease, gender, age, and ethnicity were found to be associated with a lower level of QoL (β from 0.14 -0.56). Conclusion This study provides evidence of the association between adherence to treatment and quality of life in patients diagnosed with schizophrenia. Therefore, as in developed countries, improving adherence to antipsychotic medication would appear to be an important issue to address to improve patients' QoL in Latin American countries.

The S-QoL 18 is a self-administered questionnaire that assesses quality of life (QoL) among individuals with schizophrenia. This study aims to validate the S-QoL 18 in bipolar and depressive disorders for a more widespread use in psychiatric settings. This study was conducted in a non-selected sample of individuals with bipolar and depressive disorders in the day hospital of a regional psychiatric academic hospital. Two-hundred and seventy-two stable outpatients with bipolar (n = 73) and recurrent and persistent depressive (n = 199) disorders were recruited over a 12 month-period. The S-QoL 18 was tested for construct validity, reliability, and external validity. The eight-factor structure of the S-QoL 18 was confirmed by confirmatory factor analysis (RMSEA = 0.075 (0.064–0.086), CFI = 0.972, TLI = 0.961). Internal consistency and reliability were satisfactory. External validity was confirmed via correlations between S-QoL 18 dimension scores, symptomatology, and functioning. The percentage of missing data for the eight dimensions did not exceed 5%. INFIT statistics were ranged from 0.7 to 1.2, ensuring that all items of the scale measured the same QoL concept. In conclusion, the S-QoL 18 appears to be a valid and reliable instrument for measuring QoL in patients with bipolar and depressive disorders. The S-QoL 18 may be used by healthcare professionals in clinical settings to accurately assess QoL in individuals with bipolar and depressive disorders, as well as in schizophrenia.

International audience; Background: In people with schizophrenia, major areas of everyday life are impaired, including independent living, productive activities, social relationships and overall quality of life. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes.Aim: The goal of the present study was to identify factors associated with motivation deficits in real-life schizophrenia, and to assess its contribution to impaired functioning and quality of life.Methods: Based on previous literature and clinical experience, several factors were selected and grouped into factors potentially explaining motivation deficits. Some of these variables were never investigated before in relationship with motivation deficits.Results: In 561 patients with schizophrenia of the national FACE-SZ cohort living in the community, 235(41.9%) reported severe motivation deficits. These deficits were found to be significantly associated with impaired socially useful activities, psychological and physical quality of life (in almost all domains), alcohol use disorder (aOR =2.141, p = 0.021), severe nicotine dependence (aOR =2.906, p < 0.001) independently of age and sex. No significant association was found for body mass index, metabolic syndrome or physical activity level. In the second model, we identified the following modifiable factors associated with motivation deficits: history of suicide attempt (aOR =2.297, p = 0.001), positive symptoms (aOR =1.052, p = 0.006), current major depressive episode (aOR =2.627, p < 0.001), sleep disorders (aOR =1.474, p = 0.024) and lower medication adherence (aOR =0.836, p = 0.001) independently of gender, current alcohol use disorder, second-generation antipsychotics and akathisia. No significant association was found for negative symptoms, childhood trauma and inflammation. These results were maintained after removing patients with schizoaffective disorders or those with major depressive disorder.Interpretation: Motivation deficits are frequent and remain persistent unmet need in real-world schizophrenia that should be addressed in future guidelines. Based on our results, literature and clinical experience, we recommend to address in priority major depression, sleep, suicide, positive symptoms (when present and as early as possible) and medication adherence to improve motivation deficits of schizophrenia.

International audience; Background: Peripheral inflammation is associated with impaired prognosis in schizophrenia (SZ). Highly sensitive C-reactive protein (hs-CRP) is the most used inflammatory biomarker in daily practice. However, no consensual cut-off has been determined to date to discriminate patients with peripheral inflammation from those without.Aims: To determine if patients with peripheral inflammation between 1 and 3 mg/L had poorer outcomes compared to those with undetectable CRP ( 1 mg/L is a reliable marker to detect peripheral inflammation in patients with schizophrenia.

High rates of non-right-handedness (NRH) including mixed-handedness have been reported in neurodevelopmental disorders. In schizophrenia (SZ), atypical handedness has been inconsistently related to impaired features. We aimed to determine whether SZ subjects with NRH and mixed-handedness had poorer clinical and cognitive outcomes compared to their counterparts.667 participants were tested with a battery of neuropsychological tests, and assessed for laterality using the Edinburg Handedness Inventory. Clinical symptomatology was assessed. Learning disorders and obstetrical complications were recorded. Biological parameters were explored.The prevalence of NRH and mixed-handedness was high (respectively, 42.4% and 34.1%). In the multivariable analyses, NRH was associated with cannabis use disorder (Non-right and mixed-handedness are very high in patients with SZ, possibly reflecting a neurodevelopmental origin. NRH is associated with learning disorders and cannabis use. Mixed-handedness is associated with positive symptoms, current depressive disorder, cannabis use and less akathisia. However, this study did not confirm greater cognitive impairment in these patients.

Background. Fasting interventions have shown effectiveness in alleviating stress, anxiety and depressive symptoms. However, no quantitative analysis has been carried out thus far. The objective was to determine the effectiveness of fasting interventions on stress, anxiety and depression and if these interventions were associated with increased or decreased fatigue/energy. Methods. Overall, 11 studies and 1436 participants were included in the quantitative analyses. Results. After limiting analyses to randomized controlled trials with low risk of bias, we found that fasting groups had lower anxiety (b = −0.508, p = 0.038), depression levels (b= −0.281, p = 0.012) and body mass index compared to controls without increased fatigue. There was no publication bias and no heterogeneity for these results. These interventions were safe, even in patients with type 2 diabetes. Conclusions. These results should be taken with a caveat. These results are preliminary and encouraging and fasting appears to be a safe intervention. Data are not sufficient to recommend one fasting intervention more than the others. No study was carried out in psychiatric populations and further trials should be carried out in these populations that may be good candidates for fasting interventions.

Objectives The aim of this study was to adapt and validate the Schizophrenia Caregiver's Quality of Life Questionnaire (S-CGQoL) for use in the Hispanic-American population from the caregiver's perspective. Methods A cross-sectional instrumental model was used, with a sample of 253 caregivers of patients suffering of Schizophrenia in Bolivia, Peru and Chile. The psychometric properties of the S-CGQoL were tested through construct validity, reliability and some aspects of external validity. In addition, in order to assess the nature of the different items across the three countries, a Differential Performance Analysis (DPA) was conducted. Results A confirmatory factor analysis showed that the scale structure was well correlated to the initial structure of the QoL-MDS. The results confirmed the existence of adequate reliability indicators (α> .70 and ω> .80) and the absence of FIDs supporting the invariance of item calibrations among the three Latin American countries. Conclusions The adaptation and validation of the S-CGQoL questionnaire demonstrate adequate psychometric properties to assess the quality of life of caregivers in samples of middle-income countries in Latin America.

IMPORTANCE: Heterogeneous evidence exists for the association between COVID-19 and the clinical outcomes of patients with mental health disorders. It remains unknown whether patients with COVID-19 and mental health disorders are at increased risk of mortality and should thus be targeted as a high-risk population for severe forms of COVID-19. OBJECTIVE: To determine whether patients with mental health disorders were at increased risk of COVID-19 mortality compared with patients without mental health disorders. DATA SOURCES: For this systematic review and meta-analysis, MEDLINE, Web of Science, and Google Scholar were searched from inception to February 12, 2021. Bibliographies were also searched, and the corresponding authors were directly contacted. The search paradigm was based on the following combination: (mental, major[MeSH terms]) AND (COVID-19 mortality[MeSH terms]). To ensure exhaustivity, the term mental was replaced by psychiatric, schizophrenia, psychotic, bipolar disorder, mood disorders, major depressive disorder, anxiety disorder, personality disorder, eating disorder, alcohol abuse, alcohol misuse, substance abuse, and substance misuse. STUDY SELECTION: Eligible studies were population-based cohort studies of all patients with identified COVID-19 exploring the association between mental health disorders and mortality. DATA EXTRACTION AND SYNTHESIS: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. This systematic review is registered with PROSPERO. MAIN OUTCOMES AND MEASURES: Pooled crude and adjusted odds ratios (ORs) for the association of mental health disorders with mortality were calculated using a 3-level random-effects (study/country) approach with a hierarchical structure to assess effect size dependency. RESULTS: In total, 16 population-based cohort studies (data from medico-administrative health or electronic/medical records databases) across 7 countries (1 from Denmark, 2 from France, 1 from Israel, 3 from South Korea, 1 from Spain, 1 from the UK, and 7 from the US) and 19 086 patients with mental health disorders were included. The studies covered December 2019 to July 2020, were of good quality, and no publication bias was identified. COVID-19 mortality was associated with an increased risk among patients with mental health disorders compared with patients without mental health disorders according to both pooled crude OR (1.75 [95% CI, 1.40-2.20]; P

The aim of this study was to investigate the factors associated with violent behavior in a large multicenter sample of Homeless Schizophrenia (SZ) and Bipolar Disorder (BD) (HSB) subjects.This multicenter study was conducted in 4 French cities: Lille, Marseille, Paris and Toulouse. Violent behavior was defined by at least one episode of verbal or physical violence in the last 6 months.Overall, 675 HSB patients, mean aged 38 years and 82.5% men were included, 458 SZ (68.4%) and 212 BD (31.6%). During the 6 months before evaluation, 213 (34.3%) committed at least one physical or verbal violence. In multivariate analysis, violence has been associated with younger age (aOR = 0.96[0.94-0.99], p = .001), number of nights in the street (aOR = 1.01[1.01-1.01]), BD diagnosis (aOR = 1.63[1.01-2.65], p = .04), higher current illness severity (CGI score) (aOR = 1.32[1.07-1.64], p = .01), higher rates of current manic episode (aOR = 2.24[1.32-3.81], p = .002), current alcohol use disorder (aOR = 2.05 [1.33-3.15], p = .001), antisocial personality disorder (aOR = 2.51[1.55-4.07], p .001) and with antidepressant consumption (aOR = 2.01[1.01-4.04], p = .04). No specific antipsychotic or mood stabilizer has been associated with decreased rates of violent behavior, however clozapine, lithium and carbamazepine remained poorly prescribed.In case of violent behavior in HSB subjects, clinicians should focus in priority on the treatment of mania, antidepressant iatrogenic effect and alcohol use disorder by pharmacological and non-pharmacological treatments. Clozapine, lithium and carbamazepine should be chosen as the treatments of reference in this population but may be hard to manage in some cases. The current clinical trial number is NCT01570712.

Objective The aim of this study was to investigate the prevalence and associated factors of physical pain in a large multicenter sample of Homeless Schizophrenia and Bipolar (HSB) patients. Methods This multicenter study was conducted in 4 French cities: Lille, Marseille, Paris and Toulouse. Pain was measured by EQ5D-3 L questionnaire with no specified period or location. In addition, sociodemographic information, duration of homelessness, illness severity using the Modified Colorado Symptom Index (MCSI) and drug information were collected. Results Overall, 655 HSB patients, mean age 38.8 years and 82.6% men were included, 448 (68.9%) were diagnosed with schizophrenia and 202 (31.1%) with bipolar disorder. More than half patients (N = 337, 51.5%) reported moderate to extreme physical pain while only 2.7% were administered analgesic drugs. In the multivariate analysis, self-reported moderate to extreme physical pain was associated with antidepressant consumption (adjusted odd ratio aOR = 2.56[1.25;5.26], p = .01), female gender (aOR = 1.72[1.03;2.86], p = .04), bipolar disorders (vs. schizophrenia) (aOR = 1.81[1.19;2.77], p = .006), older age (aOR = 1.03 [1.01;1.05], p = .01), with higher MCSI psychotic score (a0R = 1.04[1.01;1.06],p = .002), independently of the number of days in the street during the last 180 days, MCSI depression score, alcohol and substance use disorders, psychotropic drugs and analgesic treatments. No association with education level, antipsychotics, mood stabilizers, anxiolytic, hypnotic or medication adherence was found (all p > .05). Conclusion Physical pain was highly reported in homeless patients with severe mental illness with insufficient care. Physical pain should be systematically explored and treated in this population. Bipolar disorders, antidepressant consumption and female gender may be targeted in priority. Age and psychotic symptomatology were found to influence self-reported pain in a marginal way.

The interest in social cognition in schizophrenia is justified by the relationship between deficits in these skills and negative functional outcomes. Although assessment batteries have already been described, there is no consensus about which measures are useful in predicting patient functioning or quality of life (QoL). We investigated a set of five measures of recognition of facial emotions, theory of mind (ToM), and empathy in a cohort of 143 patients with schizophrenia or schizoaffective disorder at inclusion and, amongst whom 79 were reassessed 1 year later. The distribution was satisfactory for the TREF (Facial Emotion Recognition Task), V-SIR (Versailles-Situational Intention Reading), and QCAE (Questionnaire of Cognitive and Affective Empathy). Internal consistency was satisfactory for the TREF, V-SIR, V-Comics (Versailles Intention Attribution Task), and QCAE. Sensitivity to change was acceptable for the TREF. The TREF and V-SIR showed a cross-sectional relationship with functioning beyond the clinical symptoms of schizophrenia but not beyond neurocognition. Moreover, the TREF and V-SIR at inclusion could not predict functioning one year later, whereas most neurocognitive and clinical dimensions at inclusion could. Finally, only affective QCAE showed a significant cross-sectional, but not longitudinal, association with QoL. In conclusion, the TREF had satisfactory psychometric properties and showed a cross-sectional, but not longitudinal, association with objective outcome measures, thus appearing to be reliable in clinical practice and research. The V-SIR also showed promising psychometric properties, despite a possible weakness to detect change. However, these measures should be interpreted within the context of the good predictive power of the neurocognitive and clinical status on the outcome.

Little is known on the end-of-life (EOL) care of terminal breast cancer in women with severe psychiatric disorder (SPD). The objective was to determine if women with SPD and terminal breast cancer received the same palliative and high-intensity care during their end-of-life than women without SPD. Study design, setting, participants. This population-based cohort study included all women aged 15 and older who died from breast cancer in hospitals in France (2014–2018). Key measurements/outcomes. Indicators of palliative care and high-intensity EOL care. Multivariable models were performed, adjusted for age at death, year of death, social deprivation, duration between cancer diagnosis and death, metastases, comorbidity, smoking addiction and hospital category. The analysis included 1742 women with SPD (287 with bipolar disorder, 1075 with major depression and 380 with schizophrenia) and 36,870 women without SPD. In multivariate analyses, women with SPD had more palliative care (adjusted odd ratio aOR 1.320, 95%CI [1.153–1.511], p p

Purpose. Peripheral inflammation is frequent in schizophrenia, and plays a major role in pathophysiology, prognosis, and persistence of psychotic symptomatology under treatment. Aim. To determine the correlation between peripheral inflammation and brain SPECT perfusion in stabilized antipsychotic-treated outpatients with schizophrenia, and to determine whether such perfusion changes are correlated to persistent symptoms. Methods. Highly sensitive C-reactive protein blood level (hs-CRP) and brain SPECT perfusion were assessed in 137 stabilized outpatients with schizophrenia. Whole-brain voxel-based associations were searched with SPM between SPECT perfusion and hs-CRP (correlation analysis to quantitative levels and between-group analysis according to a threshold of 3mg/L). The identified clusters were secondarily correlated with clinical symptoms.Results. After adjustment for age, sex, educational level, illness duration, antidepressant, chlorpromazine equivalent dose, tobacco smoking and obesity, a negative correlation was found between hs-CRP level and the perfusion of 4 brain areas: the right inferior frontal gyrus, the right middle/superior temporal gyrus, the left superior parietal lobe and the right postcentral/transverse temporal gyrus (p-voxel < 0.001, k > 80, uncorrected). An increased perfusion of the left amygdala was found in patients with hs-CRP ≥ 3 mg/L compared to those with hs-CRP level < 3mg/L. A negative correlation was found between perfusion of the right inferior frontal gyrus and the persistence of positive, negative and excitement symptoms under antipsychotic treatment. Conclusion. In stabilized patients with schizophrenia, peripheral inflammation is associated with brain perfusion changes that are correlated with the persistence of psychotic symptomatology.

International audience

Background: The objective of this study was to develop a conceptual framework to define a domain map describing the experience of patients with severe mental illnesses (SMIs) on the quality of mental health care. Methods: This study used an exploratory qualitative approach to examine the subjective experience of adult patients (18–65 years old) with SMIs, including schizophrenia (SZ), bipolar disorder (BD) and major depressive disorder (MDD). Participants were selected using a purposeful sampling method. Semistructured interviews were conducted with 37 psychiatric inpatients and outpatients recruited from the largest public hospital in southeastern France. Transcripts were subjected to an inductive analysis by using two complementary approaches (thematic analysis and computerized text analysis) to identify themes and subthemes. Results: Our analysis generated a conceptual model composed of 7 main themes, ranked from most important to least important as follows: interpersonal relationships, care environment, drug therapy, access and care coordination, respect and dignity, information and psychological care. The interpersonal relationships theme was divided into 3 subthemes: patient-staff relationships, relations with other patients and involvement of family and friends. All themes were spontaneously raised by respondents. Conclusion: This work provides a conceptual framework that will inform the subsequent development of a patient-reported experience measure to monitor and improve the performance of the mental health care system in France. The findings showed that patients with SMIs place an emphasis on the interpersonal component, which is one of the important predictors of therapeutic alliance. Trial registration: NCT02491866

International audience; Introduction: Deficits in theory of mind (ToM) can vary depending on the predominant schizophrenia symptoms, and though most neurocognitive functions are involved in ToM, all may not be associated with the same symptoms. With consideration to the relationships between symptoms, neurocognition and ToM, the aim of the present study is to identify the neurocognitive functions influencing ToM capacities according to symptomatic profile. Methods: The study is based on a sample of 124 adults with schizophrenia from a French national cohort. Patients were divided into two groups according to their scores on the five Wallwork factors of the Positive and Negative Syndrome Scale using hierarchical clustering before carrying out multivariable analyses. Results: The “disorganised group” (n = 89) showed high scores on the disorganised factor, and had a ToM associated with reasoning, visual recognition and speed of processing. The “positive group” (n = 35) showed high scores on the positive and depressive factors, and had a ToM associated with working memory. Conclusions: These results suggest that neurocognitive predictors of ToM in schizophrenia are different according to the predominant clinical dimension, thus refining our knowledge of the relationship between symptoms, neurocognition and ToM, and acknowledging their status as important predictors of patients’ functional status. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

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

Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics.

OBJECTIVE This study aimed to describe end-of-life (EOL) care in individuals with bipolar disorder (BD) who died of cancer compared with mentally healthy individuals. METHODS This was a nationwide cohort study of all adult individuals who died of cancer in hospitals in France between 2013 and 2016. Outcomes were compared between individuals with BD and mentally healthy individuals in the last month of life including palliative care and high-intensity EOL care (chemotherapy, artificial nutrition, and other interventions). A subanalysis explored differences between patients with BD and patients with schizophrenia. RESULTS The study included 2015 individuals with BD and 222,477 mentally healthy controls. Compared with the controls, individuals with BD died 5 years earlier, more often had comorbidities and thoracic cancer, and had fewer metastases, but did not have shorter delays from cancer diagnosis to death. After matching and adjustment for covariates, individuals with BD more often received palliative care in the last 3 days of life (25% versus 13%, p < .001) and less high-intensity care (e.g., chemotherapy 12% versus 15%, p = .004), but more artificial nutrition (6% versus 4.6%, p = .003). Compared with the schizophrenia comparison group, chemotherapy was received more by individuals with BD in the last 14 days of life (12.5% for BD versus 9.4%, p < .001). CONCLUSIONS Individuals with BD were more likely to receive palliative care and less likely to receive high-intensity EOL care, except for artificial nutrition. These results may not be specific to BD, as no difference was found between patients with BD and schizophrenia except for chemotherapy.

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.

Schizophrenia is marked by inequities in cancer treatment and associated with high smoking rates. Lung cancer patients with schizophrenia may thus be at risk of receiving poorer end-of-life care compared to those without mental disorder. The objective was to compare end-of-life care delivered to patients with schizophrenia and lung cancer with patients without severe mental disorder. This population-based cohort study included all patients aged 15 and older who died from their terminal lung cancer in hospital in France (2014–2016). Schizophrenia patients and controls without severe mental disorder were selected and indicators of palliative care and high-intensity end-of-life care were compared. Multivariable generalized log-linear models were performed, adjusted for sex, age, year of death, social deprivation, time between cancer diagnosis and death, metastases, comorbidity, smoking addiction and hospital category. The analysis included 633 schizophrenia patients and 66,469 controls. The schizophrenia patients died 6 years earlier, had almost twice more frequently smoking addiction (38.1%), had more frequently chronic pulmonary disease (32.5%) and a shorter duration from cancer diagnosis to death. In multivariate analysis, they were found to have more and earlier palliative care (adjusted Odds Ratio 1.27 [1.03;1.56]; p = 0.04), and less high-intensity end-of-life care (e.g., chemotherapy 0.53 [0.41;0.70]; p

Purpose The purpose of this study was to describe the association between adherence to antipsychotic medication and quality of life (QoL) in a sample of individuals diagnosed with schizophrenia. Methods Two hundred fifty-three patients were included from three public mental health services from Bolivia, Peru, and Chile. Data were collected using the Drug Attitude Inventory (DAI-10) and the Schizophrenia Quality of Life short-version questionnaire (SQoL-18), which considers 8 dimensions. Results Significant associations were found between adherence to antipsychotic medication treatment and QoL (S-QoL-18 index: β = 0.26, p = 0.004; self-esteem: β = 0.37, p = 0.000; and sentimental life: β = 0.20, p = 0.033). Associations of clinical and socio-demographic variables with QoL were identified: severity of psychotic symptoms, awareness of the disease, gender, age, and ethnicity were found to be associated with a lower level of QoL (β from 0.14 −0.56). Conclusion This study provides evidence of the association between adherence to treatment and quality of life in patients diagnosed with schizophrenia. Therefore, as in developed countries, improving adherence to antipsychotic medication would appear to be an important issue to address to improve patients’ QoL in Latin American countries.

International audience; Background and significance. There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy is thus needed to improve the SZ prognosis. Microbiota-orientated treatments are currently one of the most promising tracks. Method. This work is a systematic review synthetizing data of arguments to develop microbiota-orientated treatments (including fecal microbiota transplantation (FMT)) in major depression and schizophrenia. Results. The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments. Probiotics have yielded medium-to-large significant effects on depressive symptoms, but it is still unclear if the effect is maintained following probiotic discontinuation. Several factors may limit MD improvement when using probiotics, including the small number of bacterial strains administered in probiotic complementary agents, as well as the presence of a disturbed gut microbiota that probably limits the probiotics' impact. FMT is a safe technique enabling to improve microbiota in several gut disorders. The benefit/risk ratio of FMT has been discussed and has been recently improved by capsule administration. Conclusion. Cleaning up the gut microbiota by transplanting a totally new human gut microbiota in one shot, which is referred to as FMT, is likely to strongly improve the efficacy of microbiota-orientated treatments in MD and schizophrenia and maintain the effect over time. This hypothesis should be tested in future clinical trials.

While psychotic remission in schizophrenia (SZ) has been defined by consensus and associated with a rank of clinical predictive factors, there is a lack of data of factors associated with functional remission.To identify clinical and biological factors associated with impaired functional remission in a non-selected chronic stabilized SZ outpatients.This study was a cross-sectional study carried out on all admitted SZ stabilized outpatients in an academic daily care psychiatric hospital. Functional remission was defined by a global assessment of functioning score ≥61. Psychotic remission was defined according to international criteria. Depression was assessed with the Calgary Depression Rating scale for Schizophrenia. Sociodemographic variables, tobacco status, clozapine treatment and obesity were reported. Chronic peripheral inflammation was defined by a highly sensitive C-reactive protein serum level ≥3 mg/L and metabolic syndrome according to international recommendations.273 patients were included, among them 51 (18.7%) were classified in the functional remission group. In the multivariate analysis, higher rate of functional remission was associated with psychotic remission (adjusted Odd ratio = 18.2, p0.001), lower depressive symptoms (aOR=0.8, p = 0.018) and lower peripheral inflammation (aOR=0.4, p = 0.046). No association of functional remission with age, gender, illness duration, second-generation antipsychotics, clozapine treatment, tobacco smoking, obesity or metabolic syndrome has been found.Depressive symptoms and chronic peripheral inflammation are associated with impaired functional remission in SZ independently of psychotic remission. Future intervention studies should determine if improving depressive symptoms and chronic peripheral inflammation may improve SZ patients reaching functional remission.

Background C-reactive protein (CRP) is a general marker of peripheral inflammation and has been shown to be a good marker of neuroinflammation. CRP has been found to be elevated in patients with mood disorders (especially unipolar disorders (UD) and in schizophrenia (SZ)) but also to be lowered by antidepressants. Objective The objectives were (i) to determine the prevalence of major depression, antidepressant prescription and remission under antidepressant in a stabilized population of SZ and UD patients consulting in a daily hospital, and (ii) to determine if CRP was a marker of major depression and remission under antidepressant in these SZ and UD populations. Methods Abnormal CRP was defined by a CRP blood level ≥ 3 mg/L. Depressive symptoms were assessed by the Calgary Depression Rating Scale score. The clinicians were blinded of the CRP status of the patient. Results 411 patients were included (272 SZ and 139 UD). 171 (41.6%) were diagnosed with current major depression (74 (27.2%) for SZ and 97 (69.8%) for UD). 86 SZ (31.6%) and 119 UD (85.6%) were treated by antidepressant. Only 28/74 (37.8%) of the SZ subjects with major depression were administered antidepressants vs. 87/97 (89.7%) for UD. The non-remission rate under antidepressant was 28/86(32.6%) for SZ and 87/119 (73.1%) for UD. Overall, 105 (40.1%) of SZ and 39 (28.1%) of UD patients were found to have abnormal CRP blood levels. Abnormal CRP levels were significantly associated with increased MDD and more strongly with increased rates of non-remission under antidepressants in SZ patients, independently of age, gender, psychotic symptomatology, functioning, tobacco smoking and metabolic syndrome. This result was not replicated in UD patients, which suggests that CRP may be a specific marker of major depression and remission under antidepressant in SZ patients. Conclusion The development of biomarkers in psychiatry may orientate specific etiologic therapies in patients with mental disorders. The present findings suggest that major depression is frequent in SZ patients and that increased CRP levels are associated with non-remission under antidepressants in this population. Anti-inflammatory strategies may be particularly useful in this specific population.

Background Sexual dysfunctions (SD) in schizophrenia are frequent with strong impact on adherence and quality of life. Current recommendations stipulate to switch to prolactin-sparing antipsychotic in case of SD. Objectives To synthetize in a systematic review data on the SD prevalence and the associated risk factors in schizophrenia (SZ). Methods Medline, Google Scholar, PsychInfo, and Cochrane were explored, without any year or language restriction. Results Overall, 89 studies and 25,490 participants were included in the present review. SZ subjects aged 18–70 reported high SD frequency [30%–82%] (men [33%- 85%]; women [25%- 85%]). For SZ men erectile dysfunction [31%–95%] was the most frequent SD vs. loss of libido for women [31%–100%]. The following risk factors were associated with increased SD: 1. Illness severity (including psychotic symptomatology, early age at SZ onset, negative symptomatology, and continuous illness course), 2. Depressive symptomatology 3. Antipsychotics (especially first generation antipsychotics, risperidone and antipsychotic polytherapy). Switching to prolactin-sparing antipsychotics has shown effectiveness in some studies (especially aripiprazole). Antidepressants were not found to be associated with SD in SZ subjects. Conclusion The prevalence of SD is high in SZ subjects. In addition to the current guidelines, the present review suggests that treating depressive symptoms may be a major intervention to improve SD in SZ subjects. Sociodemographic variables, physical illnesses, metabolic syndrome and peripheral inflammation have been poorly or never explored and should be included in future studies.

Background: Inflammation plays a major role in the onset and maintenance of schizophrenia. The objective of the present work was to synthetize in a narrative review the recent findings in the field of inflammation in schizophrenia and their application in daily practice. Method: This review was based on the most recent meta-analyses and randomized controlled trials. Results: The disturbed cytokines depend on the phase of the illness. A meta-analysis of cytokines in schizophrenia found higher levels of pro-inflammatory and anti-inflammatory cytokines in the peripheral blood in both patients with first-episode schizophrenia and relapsed patients than in healthy controls. Exploring detailed data on immune-inflammatory disturbances in SZ reveals that IL-6 is one of the most consistently disturbed cytokines. Other cytokines, including IL1, TNF, and IFN, are also disturbed in schizophrenia. Choosing a broad spectrum anti-inflammatory agent that may inhibit subsequent pathways might be particularly useful for the treatment of inflammatory schizophrenia. Highly sensitive C-Reactive Protein is a useful screening marker for detecting inflammation in SZ subjects. Anti-inflammatory agents have shown effectiveness in recently published meta-analyses. Only one study found a significant difference between celecoxib and placebo, but two found a trend toward significance on illness severity and one on positive symptoms. In addition, other published and unpublished data were included in another meta-analysis that concluded the significant effect of add-on celecoxib in positive symptoms in first episode patients. There is a lack of data to determine if aspirin is truly effective in schizophrenia to date. Other anti-inflammatory agents have been explored, including hormonal therapies, antioxidants, omega 3 fatty acids, and minocycline, showing significant effects for reducing total, positive, and negative score symptoms and general functioning. However, each of these agents has multiple properties beyond inflammation and it remains unclear how these drugs improve schizophrenia. Conclusion: The next step is to tailor anti-inflammatory therapy in schizophrenia, with two main challenges: 1. To provide a more efficient anti-inflammatory therapeutic approach that targets specific pathways associated with the pathology of schizophrenia. 2. To develop a more personalized approach in targeting patients who have the best chance of successful treatment.