Psychometric Assessment of an Item Bank for Adaptive Testing on Patient-Reported Experience of Care Environment for Severe Mental Illness: Validation Study.

BACKGROUND: The care environment significantly influences the experiences of patients with severe mental illness and the quality of their care. While a welcoming and stimulating environment enhances patient satisfaction and health outcomes, psychiatric facilities often prioritize staff workflow over patient needs. Addressing these challenges is crucial to improving patient experiences and outcomes in mental health care. OBJECTIVE: This study is part of the Patient-Reported Experience Measure for Improving Quality of Care in Mental Health (PREMIUM) project and aims to establish an item bank (PREMIUM-CE) and to develop computerized adaptive tests (CATs) to measure the experience of the care environment of adult patients with schizophrenia, bipolar disorder, or major depressive disorder. METHODS: We performed psychometric analyses including assessments of item response theory (IRT) model assumptions, IRT model fit, differential item functioning (DIF), item bank validity, and CAT simulations. RESULTS: In this multicenter cross-sectional study, 498 patients were recruited from outpatient and inpatient settings. The final PREMIUM-CE 13-item bank was sufficiently unidimensional (root mean square error of approximation=0.082, 95% CI 0.067-0.097; comparative fit index=0.974; Tucker-Lewis index=0.968) and showed an adequate fit to the IRT model (infit mean square statistic ranging between 0.7 and 1.0). DIF analysis revealed no item biases according to gender, health care settings, diagnosis, or mode of study participation. PREMIUM-CE scores correlated strongly with satisfaction measures (r=0.69-0.78; P<.001) and weakly with quality-of-life measures (r=0.11-0.21; P<.001). CAT simulations showed a strong correlation (r=0.98) between CAT scores and those of the full item bank, and around 79.5% (396/498) of the participants obtained a reliable score with the administration of an average of 7 items. CONCLUSIONS: The PREMIUM-CE item bank and its CAT version have shown excellent psychometric properties, making them reliable measures for evaluating the patient experience of the care environment among adults with severe mental illness in both outpatient and inpatient settings. These measures are a valuable addition to the existing landscape of patient experience assessment, capturing what truly matters to patients and enhancing the understanding of their care experiences. TRIAL REGISTRATION: ClinicalTrials.gov NCT02491866; https://clinicaltrials.gov/study/NCT02491866.

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.

Development of the PREMIUM computerized adaptive testing for measuring the access and care coordination for patients with severe mental illness.

Severe mental illness (SMI) patients often have complex health needs, which makes it difficult to access and coordinate their care. This study aimed to develop a computerized adaptive testing (CAT) tool, PREMIUM CAT-ACC, to measure SMI patients' experience with access and care coordination. This multicenter and cross-sectional study included 496 adult in- and out-patients with SMI (i.e., schizophrenia, bipolar disorder, or major depressive disorder). Psychometric analysis of the 13-item bank showed adequate properties, with preliminary evidence of external validity and no substantial differential item functioning for sex, age, care setting, and diagnosis, making it suitable for CAT administration. A post-hoc CAT simulation demonstrated that the tool was efficient and accurate, with an average of seven items, compared to the full item bank administration. Its use by clinicians can contribute to optimizing patient care pathways and transitioning towards more person-centered healthcare.

Long-term remission following esketamine nasal spray sessions in a patient with severe and highly treatment-resistant depression: a single-case report.

About 30% of patients with major depressive disorder have treatment-resistant depression (TRD). Recently, intranasal esketamine was approved as a treatment option after the failure of two antidepressant trials. We report a patient with multiresistant depression that was successfully and safely treated with esketamine nasal spray. This 31-year-old inpatient with severe, chronic, and multi-TRD received an acute course of intranasal esketamine (84 mg). Previously, 14 different antidepressants, alone or in potentiation, and several neurostimulation techniques had been unsuccessful. Over 20 bi-weekly sessions, she had no significant adverse effects and was stabilized into remission. During the maintenance phase and 1 year after, she continues to be stable. This case report provides an example of a patient with severe TRD that showed significant improvement after treatment with intranasal esketamine.

Long-term benzodiazepine prescription in treatment-resistant depression: A national FACE-TRD prospective study.

BACKGROUND: Benzodiazepine long-term use (BLTU) is a public health challenge. We lack data on the consequences of LBTU on the trajectory of treatment-resistant depression (TRD). OBJECTIVE: To determine the prevalence of BLTU in a nationwide non-selected population of patients with TRD, to determine the rate of patients succeeding at withdrawing benzodiazepines at one year and to determine if persistent BLTU is associated with poorer mental health outcomes. 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 one year. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at one year. RESULTS: At baseline, 45.2% of the patients were classified in the BLTU group. In multivariate analysis, compared to patients without BLTU, patients with BLTU were more frequently classified in the "low physical activity" group (adjusted odds ratio (aOR) = 1.885, p = 0.036), and had higher primary healthcare consumption (B = 0.158, p = 0.031) independently of age, sex and antipsychotic consumption. We found no significant difference for personality traits, suicidal ideation, impulsivity, childhood trauma exposure, earlier age at first major depressive episode, anxiety and sleep disorders (all p > 0.05). Despite recommendations for withdrawal, <5% of BLTU patients withdraw benzodiazepines during the one-year follow-up. Persistent BLTU at one-year was associated with higher depression severity (B = 0.189, p = 0.029), higher clinical global severity (B = 0.210, p = 0.016), higher state-anxiety (B = 0.266, p = 0.003), impaired sleep quality (B = 0.249, p = 0.008), increased peripheral inflammation (B = 0.241, p = 0.027), lower functioning level (B = -0.240, p = 0.006), decreased processing speed (B = -0.195, p = 0.020) and verbal episodic memory (B = -0.178, p = 0.048), higher absenteeism and productivity loss (B = 0.595, p = 0.016) and lower subjective global health status (B = -0.198, p = 0.028). CONCLUSION: Benzodiazepines are over-prescribed in TRD (in almost a half of the patients). Despite recommendations for withdrawal and psychiatric follow-up, <5% of patients successfully stopped taking benzodiazepines at one-year. Maintaining BLTU may contribute to the worsening of clinical and cognitive symptoms and of daily functioning in TRD patients. Progressive and planed withdrawal of benzodiazepines seems therefore strongly recommended in TRD patients with BLTU. Pharmacological and non-pharmacological alternatives should be promoted when possible.

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.

Mortality among inpatients with bipolar disorders and COVID-19: a propensity score matching analysis in a national French cohort study.

BACKGROUND: It remains unknown whether coronavirus disease 2019 (COVID-19) patients with bipolar disorders (BDs) are at an increased risk of mortality. We aimed to establish whether health outcomes and care differed between patients infected with COVID-19 with BD 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. The outcomes were in-hospital mortality and intensive care unit (ICU) admission. We used propensity score matching to control for confounding factors. RESULTS: In total, 50 407 patients were included, of whom 480 were patients with BD. Patients with BD were 2 years older, more frequently women and had more comorbidities than controls without a diagnosis of severe mental illness. Patients with BD had an increased in-hospital mortality rate (26.6% v. 21.9%; p = 0.034) and similar ICU admission rate (27.9% v. 28.4%, p = 0.799), as confirmed by propensity analysis [odds ratio, 95% confidence interval (OR, 95% CI) for mortality: 1.30 (1.16-1.45), p < 0.0001]. Significant interactions between BD and age and between BD and social deprivation were found, highlighting that the most important inequalities in mortality were observed in the youngest [OR, 95% CI 2.28 (1.18-4.41), p = 0.0015] and most deprived patients with BD [OR, 95% CI 1.60 (1.33-1.92), p < 0.001]. CONCLUSIONS: COVID-19 patients with BD were at an increased risk of mortality, which was exacerbated in the youngest and most deprived patients with BD. Patients with BD should thus be targeted as a high-risk population for severe forms of COVID-19, requiring enhanced preventive and disease management strategies.

Virtual reality cue exposure therapy for tobacco relapse prevention: a comparative study with standard intervention.

BACKGROUND: Successful interventions have been developed for smoking cessation although the success of smoking relapse prevention protocols has been limited. Cognitive behavioural therapy (CBT) in particular has been hampered by a high relapse rate. Because relapse can be due to conditions associated with tobacco consumption (such as drinking in bars with friends), virtual reality cue exposure therapy (VRCE) can be a potential tool to generate 3D interactive environments that simulate risk situations for relapse prevention procedures. METHODS: To assess the effectiveness of VRCE with CBT, a comparative trial involving 100 smoking abstinent participants was designed with all required virtual environments (VE) created with an inexpensive graphic engine/game level editor. RESULTS: Outcome measures confirmed the immersive and craving eliciting effect of these VEs. Results demonstrated that more participants in the VRCE group did not experience smoking relapse and that VRCE is at least as efficacious as traditional CBT in terms of craving reduction and decrease in nicotine dependence. Dropout and relapse rate in the VRCE group was noticeably lower than the CBT group. Aside from mood scores, no significant differences were found regarding the other scales. CONCLUSION: The present clinical trial provides evidence that VRCE was effective in preventing smoking relapse. Improvement in technology and methodology for future research and applications is delineated.

Effect of Psychiatric Advance Directives Facilitated by Peer Workers on Compulsory Admission Among People With Mental Illness: A Randomized Clinical Trial.

Importance: Reducing the use of coercion in mental health care is crucial from a human rights and public health perspective. Psychiatric advance directives (PADs) are promising tools that may reduce compulsory admissions. Assessments of PADs have included facilitation by health care agents but not facilitation by peer workers. Objective: To determine the efficacy of PADs facilitated by peer workers (PW-PAD) in people with mental disorders. Design, Setting, and Participants: A multicenter randomized clinical trial was conducted in 7 French mental health facilities. Adults with a DSM-5 diagnosis of schizophrenia, bipolar I disorder, or schizoaffective disorder who had a compulsory admission in the past 12 months and the capacity to consent were enrolled between January 2019 and June 2020 and followed up for 12 months. Interventions: The PW-PAD group was invited to fill out a PAD form and meet a peer worker who was trained to assist in completing and sharing the form with relatives and psychiatrists. Main Outcomes and Measures: The primary outcome was the rate of compulsory admission at 12 months after randomization. The overall psychiatric admission rate, therapeutic alliance, quality of life, mental health symptoms, empowerment, and recovery outcomes were also investigated. Results: Among 394 allocated participants (median age, 39 years; 39.3% female; 45% with schizophrenia, 36% bipolar I disorder, and 19% schizoaffective disorder), 196 were assigned to the PW-PAD group and 198 to the control group. In the PW-PAD group, 27.0% had compulsory admissions compared with 39.9% in the control group (risk difference, -0.13; 95% CI, -0.22 to -0.04; P = .007). No significant differences were found in the rate of overall admissions, therapeutic alliance score, and quality of life. Participants in the PW-PAD group exhibited fewer symptoms (effect size, -0.20; 95% CI, -0.40 to 0.00), greater empowerment (effect size, 0.30; 95% CI, 0.10 to 0.50), and a higher recovery score (effect size, 0.44; 95% CI, 0.24 to 0.65), compared with those in the control group. Conclusions and Relevance: Peer worker-facilitated PADs are effective in decreasing compulsory hospital admissions and increasing some mental health outcomes (self-perceived symptoms, empowerment, and recovery). Involving peer workers in the completion of PADs supports the current shift of mental health care from substitute decision-making to supported decision-making. Trial Registration: ClinicalTrials.gov Identifier: NCT03630822.

ADHD prevalence in patients with hypersexuality and paraphilic disorders: a systematic review and meta-analysis.

Hypersexuality and paraphilic disorders have been associated with increased ADHD in several studies. To determine the prevalence of ADHD in hypersexuality and paraphilic disorders. Three databases (Medline, Web of Science and Google Scholar) were explored. Using random effects models, we calculated the pooled estimate of ADHD prevalence. The leave-1-out method and subgroup analyses were carried out to identify sources of heterogeneity. Seven studies from three countries (N = 730 patients with hypersexuality) were included (including five US studies). The overall estimate of the prevalence of ADHD in patients with hypersexuality or paraphilic disorders was 22.6% (95% interval: 17-29.4) with high heterogeneity (I2 = 63%). No publication bias was observed according to Egger's test. We found no significant difference in ADHD prevalence between the following subgroups: hypersexuality vs. paraphilic disorders, studies exploring the history of childhood ADHD vs. adult ADHD, US studies vs. others. The French study was a source of heterogeneity with a much lower rate than others (4.5%) but did not significantly change the prevalence estimate. Removing this study increases the prevalence to 25%. We found no association between the year of publication and ADHD prevalence. ADHD is much more frequent in populations with hypersexuality or paraphilic disorders compared to the general population. It should be systematically screened. The subgroup analyses were not sufficient to identify all sources of heterogeneity, other sources should be explored in further studies.

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.

Development and Calibration of the PREMIUM Item Bank for Measuring Respect and Dignity for Patients with Severe Mental Illness.

Most patient-reported experience measures (PREMs) are paper-based, leading to a high burden for patients and care providers. The aim of this study was to (1) calibrate an item bank to measure patients' experience of respect and dignity for adult patients with serious mental illnesses and (2) develop computerized adaptive testing (CAT) to improve the use of this PREM in routine practice. Patients with schizophrenia, bipolar disorder, and major depressive disorder were enrolled in this multicenter and cross-sectional study. Psychometric analyses were based on classical test and item response theories and included evaluations of unidimensionality, local independence, and monotonicity; calibration and evaluation of model fit; analyses of differential item functioning (DIF); testing of external validity; and finally, CAT development. A total of 458 patients participated in the study. Of the 24 items, 2 highly inter-correlated items were deleted. Factor analysis showed that the remaining items met the unidimensional assumption (RMSEA = 0.054, CFI = 0.988, TLI = 0.986). DIF analyses revealed no biases by sex, age, care setting, or diagnosis. External validity testing has generally supported our assumptions. CAT showed satisfactory accuracy and precision. This work provides a more accurate and flexible measure of patients' experience of respect and dignity than that obtained from standard questionnaires.

The Validity of the SQoL-18 in Patients with Bipolar and Depressive Disorders: A Psychometric Study from the PREMIUM Project.

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.

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.

Perceived Changes in Sexual Interest and Distress About Discrepant Sexual Interest During the First Phase of COVID-19 Pandemic: A Multi-Country Assessment in Cohabiting Partnered Individuals.

Due to COVID-19 pandemic, different restrictive measures in terms of physical distancing and lockdowns have been introduced in most European countries, affecting all facets of social life. Currently, little is known about how partnered individuals perceive changes in their sexual life during this complex emergency. This study explored retrospectively assessed changes in sexual interest for one's partner and levels of distress related to perceived sexual interest discrepancy during the first phase of the pandemic in a large-scale online sample of partnered individuals (n = 4813; Mage = 38.5 years, SD = 10.74) recruited between May and July 2020 in seven European Union countries and Turkey. We also examined the possible role of approach/avoidance motives for sex in reported changes in sexual interest and associated distress. Most participants (53%) reported no change in their sexual interest during the pandemic, followed by those who reported an increase (28.5%). The pattern was similar across the eight countries. Distress about discrepant sexual interest, which was only weakly related to changes in sexual interest, was significantly associated with relationship quality and emotional closeness with a partner, coping with and worrying about the pandemic, and specific motivation for sex. In contrast to avoidant and relationship-focused approach motivation, ego-focused approach motivation was related to stable sexual interest during the pandemic. The current study contributes to the understanding of the link between sexual interest and complex emergencies. Considering that the COVID-19 pandemic continues, the reported experiences and perceptions are prone to change.

Psychometric properties of the BIRT Motivation Questionnaire (BMQ), a self-measure of avolition in individuals with schizophrenia.

AIMS: Avolition defined as a lack of interest or engagement in goal-directed behavior plays a key role in everyday functioning in schizophrenia and is considered as one of the main contributors to the burden of disease. The aim of this study was to 1) validate the self-report BIRT Motivation Questionnaire (BMQ-S) seldom used before in schizophrenia 2) examine the degree of agreement between the BMQ-S and its informant-report version 3) to assess its ability to predict real-world outcome at 12 month follow-up. METHODS: One hundred and twenty-two (51.9% inpatients) adults with a diagnosis of schizophrenia were included. Exploratory Factor analysis was performed on the BMQ-S to identify the underlying structure. Real life functioning was measured with the Global Assessment of Functioning scale (GAF). Convergent validity was assessed with the Scale for Assessment of Negative Symptom (SANS) and the Lille Apathy Rating Scale (LARS). RESULTS: The main psychometric properties of the BMQ-S (internal consistency, test-retest reliability) were satisfactory. Exploratory factorial analysis revealed a 4-factor model which explained 76% of the overall variance. The BMQ-S correlated significantly with the LARS and the SANS avolition subscore suggesting adequate convergent validity. The correlation between the BMQ-S and the clinician-report version was 0.48. The global score and in particular the Initiation/disorganisation dimension was a significant predictor of global functioning at 12-months even when adjusted for age, chlorpromazine intake and depression. CONCLUSION: Our findings indicate that the BMQ-S has satisfactory psychometric properties and that schizophrenia patients can reliably assess their lack of motivation. Self-evaluation of avolition should be considered in the overall prediction of real-world functioning in 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.

Peripheral inflammation is associated with brain SPECT perfusion changes in schizophrenia.

PURPOSE: Peripheral inflammation is frequent in schizophrenia and could play a role in the pathophysiology, prognosis, and persistence of psychotic symptomatology under treatment. We seek to determine the relationship between peripheral inflammation and brain SPECT perfusion in stabilized antipsychotic-treated outpatients with schizophrenia, and to determine whether such perfusion changes are correlated with 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 3 mg/L). The identified clusters were secondarily correlated with clinical symptoms. RESULTS: After adjustment for age, sex, educational level, illness duration, antidepressant use, 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). Increased perfusion of the left amygdala was found in patients with hs-CRP ≥ 3 mg/L compared to those with hs-CRP levels < 3 mg/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.

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.

Recommendations of the treatment-resistant depression expert center network for promoting tobacco smoking cessation based on the results from the real-world FACE-TRD national cohort.

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.