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.

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.

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.

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.

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.

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.

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.

Association between anhedonia and suicidal events in patients with mood disorders: A 3-year prospective study.

BACKGROUND: As almost all mental disorders are associated with increased suicidal-related behavior, anhedonia might be a trans-diagnostic dimension to target for suicide prevention. METHODS: For this 3-year-long prospective study, 2,839 outpatients with mood disorders were recruited. They were divided in: (a) two groups according to the occurrence or not of suicidal ideation during the follow-up, and (b) two groups according to the occurrence or not of suicide attempts during the follow-up. Anhedonia was assessed using a composite score (the French version of the 14-item Snaith-Hamilton Pleasure Scale and item 13 of the Quick Inventory of Depressive Symptomatology scale) at inclusion and at 6, 12, 24, and 36 months after inclusion. RESULTS: Patients with mood disorders and anhedonia at least at one follow-up visit had a 1.4-fold higher risk of suicidal ideation (adjusted odds ratio = 1.35; 95% confidence interval [1.07, 1.70]), even after adjustment for confounding factors of suicide risk (i.e., bipolar or unipolar disorder, sex, age, marital status, education level, antidepressant intake, personal history of suicide attempt, at least one childhood trauma, and mean of the maximum depression score during the follow-up). Conversely, association between anhedonia and suicide attempt did not remain significant after adjustment. CONCLUSIONS: The significant association between anhedonia and suicide ideation in patients with mood disorders stresses the need of targeting hedonia in mood disorders, and of research focusing on the position to pleasure in life through eudaimonia.

Palliative and high-intensity end-of-life care in schizophrenia patients with lung cancer: results from a French national population-based study.

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 < 0.0001; surgery 0.73 [0.59;0.90]; p < 0.01) than controls. Although the use and/or continuation of high-intensity end-of-life care is less important in schizophrenia patients with lung cancer, some findings suggest a loss of chance. Future studies should explore the expectations of patients with schizophrenia and lung cancer to define the optimal end-of-life care.

Positive and negative urgency as a single coherent construct: Evidence from a large-scale network analysis in clinical and non-clinical samples.

AIMS: Negative and positive urgency are emotion-related impulsivity traits that are thought to be transdiagnostic factors in psychopathology. However, it has recently been claimed that these two traits are closely related to each other and that considering them separately might have limited conceptual and methodological value. The present study aimed to examine whether positive and negative urgency constructs constitute separate impulsivity traits. METHODS: In contrast to previous studies that have used latent variable approaches, this study employed an item-based network analysis conducted in two different samples: a large sample of non-clinical participants (N = 18,568) and a sample of clinical participants with psychiatric disorders (N = 385). RESULTS: The network analysis demonstrated that items denoting both positive and negative urgency cohere as a single cluster of items termed "general urgency" in both clinical and non-clinical samples, thereby suggesting that differentiating positive and negative urgency as separate constructs is not necessary. CONCLUSION: These findings have important implications for the conceptualization and assessment of urgency and, more broadly, for future research on impulsivity, personality, and psychopathology.

[Mortality in schizophrenia: Towards a new health scandal? COVID-19 and schizophrenia]. / Mortalité dans la schizophrénie : vers un nouveau scandale sanitaire ? COVID-19 et schizophrénie.

Patients with schizophrenia 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 schizophrenia and patients without a diagnosis of severe mental illness. 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 schizophrenia. 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. A total of 50,750 patients were included, of whom 823 were schizophrenia patients (1.6%). The schizophrenia 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 schizophrenia and age for mortality and ICU admission were observed (p = 0.0006 and p < 0.0001). Schizophrenia patients between 65 and 80 years had a significantly higher risk of death than controls of the same age (+7.89%). schizophrenia patients younger than 55 years had more ICU admissions (+13.93%) and schizophrenia patients between 65 and 80 years and older than 80 years had less ICU admissions than controls of the same age (-15.44% and -5.93%, respectively). Our findings report the existence of disparities in health and health care between schizophrenia patients and patients without a diagnosis of severe mental illness. These disparities differed according to the age and clinical profile of schizophrenia patients, suggesting the importance of personalized COVID-19 clinical management and health care strategies before, during and after hospitalization for reducing health disparities in this vulnerable population.

End-of-Life Care Among Patients With Bipolar Disorder and Cancer: A Nationwide Cohort Study.

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.

Childhood maltreatment and clinical severity of treatment-resistant depression in a French cohort of outpatients (FACE-DR): One-year follow-up.

BACKGROUND: Childhood maltreatment is associated with major depressive disorder (MDD). It not only increases the risk of lifetime MDD, but it also aggravates its course. Among depressed patients, 20-30% of them experience treatment-resistance depression (TRD). We aimed to assess the association between childhood maltreatment, severity of depression in a unipolar TRD sample, and patient outcomes after one-year of follow-up. METHODS: Patients were recruited for a prospective cohort from the French network of TRD expert centers. Depressive symptom severity was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology self-report (QIDS-SR). Childhood maltreatment was evaluated with the Childhood Trauma Questionnaire (CTQ). RESULTS: In total, 256 patients filled in the CTQ at baseline between 2012 and 2019. At baseline, the MADRS score was associated with CTQ score (ß = .185; p = .004). QIDS was also associated with CTQ scores (ß = .27; p < .001). Regarding the different subtypes of childhood maltreatment, MADRS was associated with physical (ß = .21; p = .005) and sexual abuse (ß = .22; p = .002), while QIDS with physical abuse (ß = .304; p < .001) and physical neglect (ß = .254; p < .001). However, we did not find any significant association focusing on the other types of traumas. During a 1-year follow-up focusing on remission, CTQ scores (baseline) were less important in remittent patients [n = 38; CTQ score = 39.26 (9.68)] than in nonremittent ones [n = 92; CTQ score = 46.02 (17.53)] (p = .027). There was no significant difference among remitters and nonremitters based on trauma subtypes. At baseline, CTQ scores had a significant influence on remission at 1 year (χ2 (1) = 5.57; p < .05). We lost this influence adding MADRS scores at baseline in the model (p = .063). CONCLUSION: We highlighted a significant association between the severity of depressive disorders and childhood maltreatment in the TRD population. Information about a history of childhood maltreatment helps in identifying individuals who could be less likely to go into remission after treatment.

Assessing metacognitive and help-seeking strategies in schizophrenia: design and psychometric validation of the Versailles Metacognitive Strategies Evaluation Questionnaire.

OBJECTIVES: The aim of this study is to design a questionnaire, the Versailles Metacognitive Strategies Evaluation Questionnaire, for assessing the use of metacognitive and help-seeking strategies in three key-domains of impaired daily functioning in schizophrenia. To evaluate its psychometric properties (internal consistency, factor structure, convergent and divergent validity, and stability). DESIGN: Development of a questionnaire and psychometric validation procedure in patients with schizophrenia compared with healthy controls. Stability over one year was assessed in the patient group. SETTING: Schizophrenia Centers of Expertise (French FondaMental Network). SUBJECTS: A total of 141 patients with schizophrenia, among whom 77 participated in the second evaluation; 97 healthy subjects. MAIN MEASURES: The Versailles Metacognitive Strategies Evaluation Questionnaire, Positive and Negative Symptoms Scale, Personal and Social Performance Scale, Evaluation of Cognitive Processes involved in Disability in Schizophrenia Scale, Schizophrenia Quality of Life Questionnaire, and Stages of Recovery Instrument. RESULTS: From the 36-items version, stepwise exploratory factor analysis (oblimin) produced a 25-items scale which had a 3-factors structure (hygiene concern, social relationships, and hygiene help-seeking). Cronbach's were respectively equal to 0.91, 0.82, and 0.78. One-year stability was good (intra-class correlation coefficient = 0.7). The three factors showed good convergent validity with measures of quality of life (rho = 0.34, P ⩽ 0.001). The first two factors correlated with recovery (N = 34, rho = 0.53, P ⩽ 0.001). On the contrary, the factors exhibited divergent validity, with no significant correlation, with symptoms and cognitive and psychosocial functioning (P > 0.05). Factor structure in healthy controls did not match with that of patients, all items but one were found significantly different among groups. CONCLUSION: The Versailles Metacognitive Strategies Evaluation Questionnaire provides a simple and valid means to assess metacognitive strategies in individuals with schizophrenia.

[Climate impact on mental health]. / Les conséquences climatiques sur la santé mentale.

While many studies have looked into the consequences of climate change on physical health, its impact on mental health is still relatively unknown. Climate-related disasters lead to psychotrauma in populations, as well as sleeping disorders, anxiety and depression. Rising temperatures increase the level of agression and violence. Climate migration also leads to psychological disorders in migrants. Mental health professionals must be trained in these pathologies which are set to become more common over the decades to come.

The cognitive, affective motivational and clinical longitudinal determinants of apathy in schizophrenia.

Apathy is a frequent and debilitating condition with few treatment options available in schizophrenia patients. Despite evidence of its multidimensional structure, most of past studies have explored apathy through a categorical approach. The main objective of this study was to identify the cognitive, emotional, motivational, and clinical factors at baseline that best predicted the three subtypes of apathy dimensions at follow-up. In a longitudinal study, 137 participants diagnosed with schizophrenia underwent different assessments including clinical, motivational, affective and cognitive measurements, at 1-month (referred to as baseline) and 12-month follow-ups. Data were analyzed using partial least squares variance-based structural equation modeling. Three latent variables representing the three previously described domains of apathy reaching consensus in the literature were extracted from the Lille Apathy Rating Scale. Results showed that in addition to baseline apathy, positive symptoms, anticipatory pleasure and sensibility to punishment at baseline predicted cognitive apathy at follow-up. Likewise, both baseline apathy and sensibility to punishment predicted emotional apathy at follow-up. Finally, baseline anhedonia and episodic memory were the main variables the predicted behavioral apathy at follow-up. This is the first study to show specific associations between apathy subtypes and clinical and cognitive motivational dysfunction in individual with schizophrenia, indicating possible distinct underlying mechanisms to these demotivational symptoms. Treatment for apathy should address both types of processes. Importantly, our results demonstrate the interest of multidimensional approaches in the understanding of apathy in schizophrenia.

Psychiatric advance directives for people living with schizophrenia, bipolar I disorders, or schizoaffective disorders: Study protocol for a randomized controlled trial - DAiP study.

BACKGROUND: Compulsory admission to psychiatric hospital is rising despite serious ethical concerns. Among measures to reduce compulsory admissions, Psychiatric Advance Directives (PAD) are the most promising, with intensive PAD (i.e. facilitated and shared) being the most effective. The aim of the study is to experiment Psychiatric Advance Directives in France. METHODS: A multicentre randomized controlled trial and qualitative approach conducted from January 2019 to January 2021 with intent-to-treat analysis. SETTING: Seven hospitals in three French cities: Lyon, Marseille, and Paris. Research assistants meet each participant at baseline, 6 months and 12 months after inclusion for face-to-face interviews. PARTICIPANTS: 400 persons with a DSM-5 diagnosis of bipolar I disorder (BP1), schizophrenia (SCZ), or schizoaffective disorders (SCZaff), compulsorily admitted to hospital within the last 12 months, with capacity to consent (MacCAT-CR), over 18 years old, and able to understand French. INTERVENTIONS: The experimental group (PAD) (expected n = 200) is invited to fill in a document describing their crisis plan and their wishes in case of loss of mental capacity. Participants meet a facilitator, who is a peer support worker specially trained to help them. They are invited to nominate a healthcare agent, and to share the document with them, as well as with their psychiatrist. The Usual Care (UC) group (expected n = 200) receives routine care. MAIN OUTCOMES AND MEASURES: The primary outcome is the rate of compulsory admissions to hospital during the 12-month follow-up. Secondary outcomes include quality of life (S-QoL18), satisfaction (CSQ8), therapeutic alliance (4-PAS), mental health symptoms (MCSI), awareness of disorders (SUMD), severity of disease (ICG), empowerment (ES), recovery (RAS), and overall costs. DISCUSSION: Implication of peer support workers in PAD, potential barriers of supported-decision making, methodological issues of evaluating complex interventions, evidence-based policy making, and the importance of qualitative evaluation in the context of constraint are discussed. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03630822. Registered 14th August 2018.

A Multilevel Functional Study of a SNAP25 At-Risk Variant for Bipolar Disorder and Schizophrenia.

The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant in SNAP25, rs6039769, that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combined in vitro and in vivo approaches in humans to understand the functional impact of the at-risk allele. Thus, we showed in vitro that the rs6039769 C allele was sufficient to increase the SNAP25 transcription level. In a postmortem expression analysis of 33 individuals affected with schizophrenia and 30 unaffected control subjects, we showed that the SNAP25b/SNAP25a ratio was increased in schizophrenic patients carrying the rs6039769 at-risk allele. Last, using genetics imaging in a cohort of 71 subjects, we showed that male risk carriers had an increased amygdala-ventromedial prefrontal cortex functional connectivity and a larger amygdala than non-risk carriers. The latter association has been replicated in an independent cohort of 121 independent subjects. Altogether, results from these multilevel functional studies are bringing strong evidence for the functional consequences of this allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network, which therefore may increase the vulnerability to both early-onset bipolar disorder and schizophrenia.SIGNIFICANCE STATEMENT Functional characterization of disease-associated variants is a key challenge in understanding neuropsychiatric disorders and will open an avenue in the development of personalized treatments. Recent studies have accumulated evidence that the SNARE complex, and more specifically the SNAP25 protein, may be involved in psychiatric disorders. Here, our multilevel functional studies are bringing strong evidence for the functional consequences of an allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network. These results demonstrate a common genetically driven functional alteration of a synaptic mechanism both in schizophrenia and early-onset bipolar disorder and confirm the shared genetic vulnerability between these two disorders.

Remission of depression in patients with schizophrenia and comorbid major depressive disorder: results from the FACE-SZ cohort.

BACKGROUND: Major depressive disorder (MDD) is underdiagnosed and undertreated in schizophrenia, and has been strongly associated with impaired quality of life.AimsTo determine the prevalence and associated factors of MDD and unremitted MDD in schizophrenia, to compare treated and non-treated MDD. METHOD: Participants were included in the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment. MDD was defined by a Calgary score ≥6. Non-remitted MDD was defined by current antidepressant treatment (unchanged for >8 weeks) and current Calgary score ≥6. RESULTS: 613 patients were included and 175 (28.5%) were identified with current MDD. MDD has been significantly associated with respectively paranoid delusion (odds ratio 1.8; P = 0.01), avolition (odds ratio 1.8; P = 0.02), blunted affect (odds ratio 1.7; P = 0.04) and benzodiazepine consumption (odds ratio 1.8; P = 0.02). Antidepressants were associated with lower depressive symptoms score (5.4 v. 9.5; P < 0.0001); however, 44.1% of treated patients remained in non-remittance MDD. Nonremitters were found to have more paranoid delusion (odds ratio 2.3; P = 0.009) and more current alcohol misuse disorder (odds ratio 4.8; P = 0.04). No antidepressant class or specific antipsychotic were associated with higher or lower response to antidepressant treatment. MDD was associated with Metabolic syndrome (31.4 v. 20.2%; P = 0.006) but not with increased C-reactive protein. CONCLUSIONS: Antidepressant administration is associated with lower depressive symptom level in patients with schizophrenia and MDD. Paranoid delusions and alcohol misuse disorder should be specifically explored and treated in cases of non-remission under treatment. MetS may play a role in MDD onset and/or maintenance in patients with schizophrenia.Declaration of interestNone.