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.

Validation and refinement of the clinical staging model in a French cohort of outpatient with schizophrenia (FACE-SZ).

OBJECTIVE: Existing staging models have not been fully validated. Thus, after classifying patients with schizophrenia according to the staging model proposed by McGorry et al. (2010), we explored the validity of this staging model and its stability after one-year of follow-up. METHOD: Using unsupervised machine-learning algorithm, we classified 770 outpatients into 5 clinical stages, the highest being the most severe. Analyses of (co)variance were performed to compare each stage in regard to socio-demographics factors, clinical characteristics, co-morbidities, ongoing treatment and neuropsychological profiles. RESULTS: The precision of clinical staging can be improved by sub-dividing intermediate stages (II and III). Clinical validators of class IV include the presence of concomitant major depressive episode (42.6% in stage IV versus 3.4% in stage IIa), more severe cognitive profile, lower adherence to medication and prescription of >3 psychotropic medications. Follow-up at one-year showed good stability of each stage. CONCLUSION: Clinical staging in schizophrenia could be improved by adding clinical elements such as mood symptoms and cognition to severity, relapses and global functioning. In terms of therapeutic strategies, attention needs to be paid on the factors associated with the more stages of schizophrenia such as treatment of comorbid depression, reduction of the number of concomitant psychotropic medications, improvement of treatment adherence, and prescription of cognitive remediation.

Metabolic Syndrome and Illness Severity Predict Relapse at 1-Year Follow-Up in Schizophrenia: The FACE-SZ Cohort.

OBJECTIVE: Predicting relapse is a major challenge in schizophrenia from a clinical and medico-economic point of view. During recent decades, major psychiatric disorders have been found to be extensively associated with metabolic disorders, even before the illness onset, with a prevalence estimated to be 35% in this population. However, no study to date has, to our knowledge, explored the potential impact of metabolic syndrome (MetS) on relapse. METHODS: From 2010 to 2016, 185 patients (mean age = 32 years) with a DSM-IV-TR diagnosis of schizophrenia were included in the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) cohort and followed up for 1 year. Multivariable logistic regression was performed to estimate the adjusted odds ratio for relapse. RESULTS: Thirty-seven percent of stabilized outpatients with schizophrenia (mean illness duration = 11 years) experienced a relapse at least once during the 1 year of follow-up. MetS strongly predicted relapse at 1 year, independently of illness severity, insight into illness, and treatment characteristics (including medication compliance). Patients with MetS at baseline had a 3 times higher risk (95% CI, 1.1-8.4) of experiencing a new episode of psychosis during the 12 months of follow-up. CONCLUSIONS: Further studies should determine if reducing or preventing MetS could help to protect subjects with schizophrenia from relapse.