Patients' awareness of recovery mediates the link between clinical and level of functional remission in schizophrenia to a larger extent in those treated with long-acting antipsychotics.

Background: Clinical remission is a step towards functional remission for subjects with schizophrenia. While recovery is both a subjective personal journey and a clinical outcome to be targeted, data on patient self-rated outcomes are scarce. Objectives: (i) To determine the extent to which the association between clinical and functional remission is mediated by the subjective experience of recovery as reported by patients versus their relatives or their psychiatrist and (ii) to assess differences according to treatment, specifically with oral antipsychotics only versus long-acting injectable antipsychotics (LAIs). Design: Clinical observational study. Methods: Community-dwelling participants with schizophrenia enrolled in the EGOFORS cohort (N = 198) were included. Clinical symptoms and remission were assessed using the Positive and Negative Syndrome Scale. Functional remission was assessed with the Functional Remission of General Schizophrenia Scale. Awareness of recovery was assessed with one question 'What percentage of recovery do you think you have now (from 0% - no recovery - to 100% - full recovery)?', asked of the patient, also of the patient's close relative, and the psychiatrist. We used mediation analyses, taking into account the type of pharmacological treatment. Results: Remission criteria and perceived remission measures were significantly correlated, both within and between groups (r > 0.330). The patient's awareness of recovery mediated the relationship between clinical remission and level of functional remission, while the level of recovery according to psychiatrists or close relatives did not. The direct effect of clinical remission on the level of functional remission became non-significant when taking into account the mediator (patients' awareness of recovery) in the group of patients with LAI (t = 1.5, p = 0.150) but not in the group of patients with other treatments (t = 3.1, p = 0.003). Conclusion: Patients with LAIs may be more efficient in reporting their level of functional remission. Higher patient awareness could be an interesting candidate to explain this. However, as the study was cross-sectional, such a proposal should be tested with a more specifically designed protocol, such as a long-term cohort.

Clinical and cognitive characteristics of subjects with schizophrenia and childhood attention-deficit/hyperactivity disorder: Results from the multicentric FACE-SZ cross-sectional dataset.

BACKGROUND: Childhood Attention-deficit/hyperactivity disorder (C-ADHD) is a neurodevelopmental disorder, associated with an increased risk of subsequent schizophrenia. The objective of the present study was to determine the prevalence of C-ADHD in schizophrenia and the clinical and cognitive characteristics associated with C-ADHD history in schizophrenia. METHODS: 569 subjects with schizophrenia (74 % men, mean age 30.8) were included in ten expert centers at a national level and tested with a comprehensive battery of clinician-rated, patient-reported scales and cognitive tests. C-ADHD was assessed with the WURS (Wender Utah Rating Scale) self-report questionnaire. Multivariate, correlation, and principal component analyses (PCA) were conducted. RESULTS: Thirty-nine subjects (N = 39, 6.9 %) were classified in the C-ADHD group. Compared to those without C-ADHD, subjects with C-ADHD were more frequently male, had lower education levels, more severe positive clinical symptoms, more subjective cognitive deficits complaints, and lower medication adherence with small to medium effect sizes. Two cognitive components emerged from the PCA, one component including perceptual reasoning and working memory, and another component including visuospatial search and graphomotor speed, cognitive inhibition/flexibility and central executive functioning. Both components were associated with lower performances in the C-ADHD group. CONCLUSIONS: C-ADHD is frequent in schizophrenia and associated with more severe positive symptoms and impaired cognitive performances compared to those without C-ADHD. This suggests that the pathophysiological mechanisms contributing to these disorders may lead to the worsening of the cognitive functioning in patients with both disorders. C-ADHD is a relevant clinical marker to discriminate subgroups of schizophrenia with different profiles for a precision-psychiatry approach.

Poverty and inequality in real-world schizophrenia: a national study.

Background: Schizophrenia has high socioeconomic impact among severe psychiatric disorders. Aims: To explore clinician-reported and patient-reported inequities between patients under the poverty threshold vs. the others. Method: 916 patients consecutively recruited in 10 national centers received a comprehensive standardized evaluation of illness severity, addictions and patient-reported outcomes. Results: 739 (80.7%) of the patients were classified in the poverty group. This group had poorer objective illness outcomes (lower positive, negative, cognitive, excitement/aggressive and self-neglect symptoms and lifetime history of planned suicide) in multivariate analyses. While they had similar access to treatments and psychotherapy, they had lower access to socially useful activities, couple's life, housing and parenthood. They had also more disturbed metabolic parameters. On the contrary, the poverty group reported better self-esteem. No significant difference for depression, risky health behavior including addictions and sedentary behavior was found. Interpretation: The equity in access to care is attributed to the French social system. However, mental and physical health remain poorer in these patients, and they still experience poor access to social roles independently of illness severity and despite healthcare interventions. These patients may have paradoxically better self-esteem due to decreased contact with society and therefore lower stigma exposure (especially at work). Schizophrenia presents itself as a distinct impoverished population concerning health-related outcomes and social integration, warranting focus in public health initiatives and improved treatment, including tailored interventions, collaborative care models, accessible mental health services, housing support, vocational training and employment support, community integration, education and awareness, research and data collection, culturally competent approaches, and long-term support.

Predictors of medication adherence in a large 1-year prospective cohort of individuals with schizophrenia: insights from the multicentric FACE-SZ dataset.

Schizophrenia is characterized by the most salient medication adherence problems among severe mental disorders, but limited prospective data are available to predict and improve adherence in this population. This investigation aims to identify predictors of medication adherence over a 1-year period in a large national cohort using clustering analysis. Outpatients were recruited from ten Schizophrenia Expert Centers and were evaluated with a day-long standardized battery including clinician and patient-rated medication adherence measures. A two-step cluster analysis and multivariate logistic regression were conducted to identify medication adherence profiles based on the Medication Adherence rating Scale (MARS) and baseline predictors. A total of 485 participants were included in the study and medication adherence was significantly improved at the 1-year follow-up. Higher depressive scores, lower insight, history of suicide attempt, younger age and alcohol use disorder were all associated with poorer adherence at 1 year. Among the 203 patients with initially poor adherence, 86 (42%) switched to good adherence at the 1-year follow-up, whereas 117 patients (58%) remained poorly adherent. Targeting younger patients with low insight, history of suicide, alcohol use disorder and depressive disorders should be prioritized through literacy and educational therapy programs. Adherence is a construct that can vary considerably from year to year in schizophrenia, and therefore may be amenable to interventions for its improvement. However, caution is also warranted as nearly one in five patients with initially good adherence experienced worsened adherence 1 year later.

Adjunctive agents to antipsychotics in schizophrenia: a systematic umbrella review and recommendations for amino acids, hormonal therapies and anti-inflammatory drugs.

QUESTION: This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia. STUDY SELECTION AND ANALYSIS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed. FINDINGS: Provisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200-3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200-300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio. CONCLUSIONS: The results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.

Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: an individual participant data meta-analysis on 3053 individuals.

Background: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses use aggregated data discarding important confounding variables which is a source of bias. Methods: PubMed, ScienceDirect and PsycINFO were used to search for publications from inception to September 27, 2022. We contacted the authors of relevant studies to extract raw datasets and perform an Individual Participant Data meta-analysis (IPDMA). Inclusion criteria were: psychopathology of individuals with schizophrenia spectrum disorders assessed by the Positive and Negative Syndrome Scale (PANSS); cannabis-users had to either have a diagnosis of cannabis use disorder or use cannabis at least twice a week. The main outcomes were the PANSS subscores extracted via the 3-factor (positive, negative and general) and 5-factor (positive, negative, disorganization, depression, excitement) structures. Preregistration is accessible via Prospero: ID CRD42022329172. Findings: Among the 1149 identified studies, 65 were eligible and 21 datasets were shared, totaling 3677 IPD and 3053 complete cases. The adjusted multivariate analysis revealed that relative to non-use, cannabis use was associated with higher severity of positive dimension (3-factor: Adjusted Mean Difference, aMD = 0.34, 95% Confidence Interval, CI = [0.03; 0.66]; 5-factor: aMD = 0.38, 95% CI = [0.08; 0.63]), lower severity of negative dimension (3-factor: aMD = -0.49, 95% CI [-0.90; -0.09]; 5-factor: aMD = -0.50, 95% CI = [-0.91; -0.08]), higher severity of excitement dimension (aMD = 0.16, 95% CI = [0.03; 0.28]). No association was found between cannabis use and disorganization (aMD = -0.13, 95% CI = [-0.42; 0.17]) or depression (aMD = -0.14, 95% CI = [-0.34; 0.06]). Interpretation: No causal relationship can be inferred from the current results. The findings could be in favor of both a detrimental and beneficial effect of cannabis on positive and negative symptoms, respectively. Longitudinal designs are needed to understand the role of cannabis is this association. The reported effect sizes are small and CIs are wide, the interpretation of findings should be taken with caution. Funding: This research did not receive any specific grant or funding. Primary financial support for authors was provided by Le Vinatier Psychiatric Hospital.

Clinical and pharmacological correlates of caffeine consumption in subjects with schizophrenia - Data from the FACE-SZ cohort.

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.

Relationships between neuropsychological performance, insight, medication adherence, and social metacognition in schizophrenia.

BACKGROUND: Social metacognition is still poorly understood in schizophrenia, particularly its neuropsychological basis and its impact on insight and medication adherence. We therefore quantified social metacognition as the agreement between objective and subjective mentalization and assessed its correlates in a sample of individuals with schizophrenia spectrum disorders. METHODS: Participants consisted of 143 patients with schizophrenia or schizoaffective disorders who underwent a metacognitive version of a mentalization task, an extensive neuropsychological battery, and a clinical evaluation to assess their insight into illness and medication adherence. We studied potential interactions between confidence judgments and several neuropsychological and clinical variables on mentalization accuracy with mixed-effects multiple logistic regressions. RESULTS: Confidence judgments were closely associated with mentalization accuracy, indicative of good social metacognition in this task. Working memory, visual memory, and reasoning and problem-solving were the three neuropsychological dimensions positively associated with metacognition. By contrast, the two measures of medication adherence were associated with poorer metacognition, whereas no association was found between metacognition and clinical insight. The multiple regression model showed a significant positive impact of better working memory, older age at onset, longer duration of hospitalization, and worse medication adherence on social metacognition. CONCLUSIONS: We discuss possible mechanisms underlying the apparent association between social metacognition and working memory. Adherence should be monitored when remediating social metacognition, and psychoeducation should be given to patients with a high level of awareness of their capacity to mentalize.

History of learning disorders is associated with worse cognitive and functional outcomes in schizophrenia: results from the multicentric FACE-SZ cross-sectional dataset.

Schizophrenia is associated with early neurodevelopmental disorders, including most frequently learning disorders (LD), among them dyslexia and dyspraxia. Despite the demonstrated links between schizophrenia and LD, specific clinical patterns of the schizophrenia with a history of LD subgroup remain unknown. The aim of the present study was to investigate cognitive impairment, symptoms and functional outcome associated with a history of LD in a large cross-sectional, multicentric, sample of schizophrenia subjects. 492 community-dwelling subjects with schizophrenia (75.6% male, mean age 30.8 years) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. The 51 (10.4%) subjects identified with a history of LD had significantly impaired general cognitive ability (Wechsler Adult Intelligence Scale Full Scale Total IQ: Cohen's d = 0.50, p = 0.001), processing speed (d = 0.19), verbal comprehension (d = 0.29), working memory (d = 0.31), cognitive inhibition and flexibility (d = 0.26), central executive functioning (d = 0.26), phonemic verbal fluency (d = 0.22) and premorbid intellectual ability (d = 0.48), as well as with a worse functional outcome (Global Assessment of Functioning, d = 0.21), independently of age, sex, education level, symptoms, treatments, and addiction comorbidities. These results indicate that a history of LD is associated with later cognitive impairment and functional outcome in schizophrenia. This suggests that history of LD is a relevant clinical marker to discriminate subgroups of patients with schizophrenia with different profiles in a precision psychiatry framework.

Current (but not ex) cigarette smoking is associated with worse cognitive performances in schizophrenia: results from the FACE-SZ cohort.

BACKGROUND: Tobacco use is common in subjects with schizophrenia (SZ) and has sometimes been associated with better functioning in short-term studies. Only few studies embrace an extensive examination of tobacco influence on clinical, cognitive and therapeutic characteristics in stabilized SZ outpatients. The objective of the present study was to assess the association between cognitive performances and smoking status in SZ subjects. METHODS: In total, 1233 SZ participants (73.9% men, mean age 31.5) were included and tested with a comprehensive battery. Tobacco status was self-declared (never-, ex-, or current smokers). Multivariable analyses including principal component analyses (PCA) were used. RESULTS: In total, 53.7% were smokers with 33.7% of them nicotine-dependent. Multiple factor analysis revealed that current tobacco smoking was associated with impaired general intellectual ability and abstract reasoning (aOR 0.60, 95% IC 0.41-0.88, p = 0.01) and with a lifetime alcohol use disorder (p = 0.026) and a lifetime cannabis use disorder (p < 0.001). Ex- and never-smokers differed for age, mean outcome, cannabis history and medication [ex-smokers being older (p = 0.047), likely to have higher income (p = 0.026), a lifetime cannabis use disorder (p < 0.001) and higher CPZeq doses (p = 0.005)]. Premorbid IQ in the three groups significantly differed with, from higher to lower: ex-smokers, never-smoker, current smokers (all p < 0.001). CONCLUSIONS: This study is the largest to date providing strong evidence that chronic smoking is associated with cognitive impairment in SZ, arguing against the self-medication hypothesis as a contributor to the high prevalence of smoking in SZ. Ex-smokers may also represent a specific subgroup. Longitudinal studies are warranted to determine the developmental impact of tobacco on neurocognition.

[Mental health during the Covid pandemic, a narrative review]. / Santé mentale et Covid : toutes et tous concernés. Une revue narrative.

The COVID-19 pandemic (caused by the Sars-CoV-2 coronavirus) led to unprecedented challenges to public health, the healthcare system, and our daily lives (including work and education), particularly during the first wave in early 2020. In order to control infection of the virus, many countries have imposed restrictive measures to promote social distancing, ranging from curfews and school closures to widespread lockdown. At the beginning of 2022, there were 135,000 deaths from Sars-CoV-2 in France (nearly 6 million worldwide). Beyond the possible impact of Sars-CoV-2 on the brain, the pandemic has created complex human situations, with a possible impact on the mental health of populations. In this narrative review, we summarize current data on the impact of the pandemic on mental health in the general population and identify the most vulnerable groups. The goal is to provide more targeted prevention for these populations. Our review has identified several subgroups of subjects at higher risk of disorder in the context of the COVID-19 pandemic: those bereaved by COVID-19, adolescents, students, people with COVID (with potentially direct brain damages), and finally, health care workers. Gender disparities were accentuated, leading to more mental disorders in women. Longitudinal follow-up studies are needed to better identify the effects of the pandemic on the mental health of different populations, and also to define personalized prevention strategies. Screening and prevention measures must be taken to limit the impact of this pandemic on mental health. More generally, the "one health" approach, which places human health at the interface of environmental and animal health, seems essential to avoid the occurrence of this type of pandemic and its consequences in the future.

Attitudes towards Vaccines, Intent to Vaccinate and the Relationship with COVID-19 Vaccination Rates in Individuals with Schizophrenia.

Schizophrenia patients are at high risk of developing severe COVID-19 outcomes but recent evidence suggests that they are under-vaccinated. This study explored the role of potential attitudinal barriers by comparing schizophrenia patients with participants from the general population regarding COVID-19 vaccination rates, general attitudes towards vaccines, and willingness to take a COVID-19 vaccine. We conducted a cross-sectional study between April 2021 and October 2021. A total of 100 people with schizophrenia and 72 nonclinical controls were recruited. In our study, individuals with schizophrenia were under-vaccinated, despite similar general attitudes towards vaccination and higher willingness to be vaccinated against COVID-19 compared to nonclinical participants. In patients, negative attitudes toward vaccines were related to higher levels of negative psychotic symptoms and higher levels of paranoid ideation. As a whole, participants with more negative attitudes towards vaccines were less likely to be vaccinated against COVID-19 and had lower levels of trust in institutions. Vaccine hesitancy does not appear to be a major barrier for COVID-19 vaccine uptake amongst people with schizophrenia. This study suggests that disparities in COVID-19 vaccination rates in schizophrenia do not seem related to attitudinal but rather structural barriers.

Management of schizophrenia in women during the perinatal period: a synthesis of international recommendations.

INTRODUCTION: The perinatal period in schizophrenia is associated with high risk of psychotic relapse and pregnancy/child outcomes. The extent to which antipsychotics may potentially affect the fetus or the child development is unclear and debated. Even though guidelines have been developed, there is a lack of consensual recommendations regarding the optimal strategy to manage schizophrenia during the perinatal period. AREAS COVERED: This systematic review describes the current state of evidence with respect to the impact of recommended interventions for schizophrenia during the perinatal period, including childbearing age, pregnancy, and post-partum. It compares recent international treatment guidelines for this specific group of women. Last, this review presents a set of major points to be discussed with patients and relatives for shared-decision making and a summary of key recommendations from the international guidelines. EXPERT OPINION: Although treatment guidelines may be of significant help, discrepancies exist across them regarding the management of antipsychotics for schizophrenia women during the perinatal period. Shared decision-making and advance directives represent useful patient-centered approaches during this specific period. Further cohort-based evidence is needed to better identify maternal and fetal risks associated to antipsychotic treatment exposure.

Immuno-metabolic profile of patients with psychotic disorders and metabolic syndrome. Results from the FACE-SZ cohort.

Background: Metabolic syndrome (MetS) is a highly prevalent and harmful medical disorder often comorbid with psychosis where it can contribute to cardiovascular complications. As immune dysfunction is a key shared component of both MetS and schizophrenia (SZ), this study investigated the relationship between immune alterations and MetS in patients with SZ, whilst controlling the impact of confounding clinical characteristics including psychiatric symptoms and comorbidities, history of childhood maltreatment and psychotropic treatments. Method: A total of 310 patients meeting DSM-IV criteria for SZ or schizoaffective disorders (SZA), with or without MetS, were systematically assessed and included in the FondaMental Advanced Centers of Expertise for Schizophrenia (FACE-SZ) cohort. Detailed clinical characteristics of patients, including psychotic symptomatology, psychiatric comorbidities and history of childhood maltreatment were recorded and the serum levels of 18 cytokines were measured. A penalized regression method was performed to analyze associations between inflammation and MetS, whilst controlling for confounding factors. Results: Of the total sample, 25% of patients had MetS. Eight cytokines were above the lower limit of detection (LLOD) in more than 90% of the samples and retained in downstream analysis. Using a conservative Variable Inclusion Probability (VIP) of 75%, we found that elevated levels of interleukin (IL)-6, IL-7, IL-12/23 p40 and IL-16 and lower levels of tumor necrosis factor (TNF)-α were associated with MetS. As for clinical variables, age, sex, body mass index (BMI), diagnosis of SZ (not SZA), age at the first episode of psychosis (FEP), alcohol abuse, current tobacco smoking, and treatment with antidepressants and anxiolytics were all associated with MetS. Conclusion: We have identified five cytokines associated with MetS in SZ suggesting that patients with psychotic disorders and MetS are characterized by a specific "immuno-metabolic" profile. This may help to design tailored treatments for this subgroup of patients with both psychotic disorders and MetS, taking one more step towards precision medicine in psychiatry.

Recommendations of the Schizophrenia Expert Center network for adequate physical activity in real-world schizophrenia (FACE-SZ).

The World Health Organization (WHO) recommends adults complete 150-300 min per week of moderate physical activity or 75-150 min of vigorous physical activity or an equivalent combination of both, to optimize health. To explore the factors associated with adequate MVPA in stabilized outpatients with schizophrenia. 425 stabilized outpatients were recruited in the national FACE-SZ cohort between 2015 and 2018 were evaluated with the International Physical Activity Questionnaire and a 1-day long standardized battery. We explored in multivariate analyses the clinical and pharmacological factors associated with MVPA (model 1) and the biological factors and patient-reported outcomes (model 2). Overall, only 86 (20.2%) of the 425 participants achieved the recommended MVPA threshold. In model 1, the adequate MVPA group was associated with younger age, mood stabilizers prescription and adherence to treatment, independent of sex, positive and depressive symptoms, first-generation antipsychotics prescription, anxiolytic medication, and akathisia. In model 2, adequate MVPA was associated with better glycemic and lipidic profile and better physical and psychological well-being, self-esteem, sentimental life, and resilience independently of age, sex, and current psychotic severity. The expert centers recommend the importance of promoting promote effective MVPA programs for stabilized patients with schizophrenia. Interventions studies suggest that MVPA may be a useful strategy to maximize physical and psychological well-being and self-esteem and potentially to prevent or manage metabolic disturbances.

Precision-medicine findings from the FACE-SZ cohort to develop motivation-enhancing programs in real-world schizophrenia.

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.

The puzzle of quality of life in schizophrenia: putting the pieces together with the FACE-SZ cohort.

BACKGROUND: The 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. METHODS: We 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. RESULTS: Our 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. CONCLUSION: The 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.

Handedness in bipolar disorders is associated with specific neurodevelopmental features: results of the BD-FACE cohort.

OBJECTIVES: High rates of non-right-handedness (NRH) and mixed-handedness exist in neurodevelopmental disorders. Dysfunctional neurodevelopmental pathways may be implicated in the underlying pathophysiology of bipolar disorders (BD), at least in some subgroups. Yet little is known about correlates of NRH and mixed-handedness in BD. The objectives of this national study are to determine (i) the prevalence of NRH and mixed-handedness in a well-stabilized sample of BD individuals; (ii) if NRH/mixed-handedness in BD is associated with a different clinical, biological and neurocognitive profile. METHODS: We included 2174 stabilized individuals. Participants were tested with a comprehensive battery of neuropsychological tests. Handedness was assessed using a single oral question. Learning and/or language disorders and obstetrical complications were recorded using childhood records. Common environmental, clinical and biological parameters were assessed. RESULTS: The prevalence of NRH and mixed-handedness were, respectively, 11.6 and 2.4%. Learning/language disorders were found in 9.7% out of the total sample and were associated with atypical handedness (only dyslexia for mixed-handedness (p < 0.01), and dyslexia and dysphasia for NRH (p = 0.01 and p = 0.04, respectively). In multivariate analyses, NRH was associated with a younger age of BD onset (aOR 0.98 (95% CI 0.96-0.99) and lifetime substance use disorder (aOR 1.40 (95% CI 1.03-1.82) but not with any of the cognitive subtasks. Mixed-handedness was associated in univariate analyses with lifetime substance use disorder, lifetime cannabis use disorder (all p < 0.01) and less mood stabilizer prescription (p = 0.028). No association was found between NRH or mixed-handedness and the following parameters: trauma history, obstetrical complications, prior psychotic symptoms, bipolar subtype, attention deficit/hyperactivity disorder, peripheral inflammation or body mass index. CONCLUSIONS: Handedness may be associated with specific features in BD, possibly reflecting a specific subgroup with a neurodevelopmental load.

Relationship between neurocognition and theory of mind as a function of symptomatic profile in schizophrenia: results from the national FACE-SZ cohort.

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.

Handedness as a neurodevelopmental marker in schizophrenia: Results from the FACE-SZ cohort.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 (p = 0.045). Mixed-handedness was associated with positive symptoms (p = 0.041), current depressive disorder (p = 0.005)), current cannabis use (p = 0.024) and less akathisia (p = 0.019). A history of learning disorder was associated with NRH. No association was found with cognition, trauma history, obstetrical complications, psychotic symptoms, peripheral inflammation. CONCLUSIONS: 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.