Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment in schizophrenia: results from the multicenter FACE-SZ cohort.

Aim: The anticholinergic properties of medications are associated with poorer cognitive performance in schizophrenia. Numerous scales have been developed to assess anticholinergic burden and yet, there is no consensus indicating which anticholinergic burden scale is more relevant for patients with schizophrenia. We aimed to identify valid scales for estimating the risk of iatrogenic cognitive impairment in schizophrenia. Methods: We identified 27 scales in a literature review. The responses to neuropsychological tests of 839 individuals with schizophrenia or schizoaffective disorder in the FACE-SZ database were collected between 2010 and 2021. We estimated the association between objective global cognitive performance and the 27 scales, the number of psychotropic drugs, and chlorpromazine and lorazepam equivalents in bivariable regressions in a cross-sectional design. We then adjusted the bivariable models with covariates: the predictors significantly associated with cognitive performance in multiple linear regressions were considered to have good concurrent validity to assess cognitive performance. Results: Eight scales, the number of psychotropic drugs, and drug equivalents were significantly associated with cognitive impairment. The number of psychotropic drugs, the most convenient predictor to compute, was associated with worse executive function (Standardized ß = -0.12, p = .004) and reasoning (Standardized ß = -0.08, p = .037). Conclusion: Anticholinergic burden, the number of psychotropic drugs, and drug equivalents were weakly associated with cognition, thus suggesting that cognitive impairment in schizophrenia and schizoaffective disorder is explained by factors other than medication. The number of psychotropic drugs was the most parsimonious method to assess the risk of iatrogenic cognitive impairment.

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.

Modeling the Longitudinal Effects of Insight on Depression, Quality of Life and Suicidality in Schizophrenia Spectrum Disorders: Results from the FACE-SZ Cohort.

BACKGROUND: Up to half of the patients with schizophrenia attempt suicide during their lifetime. Better insight is associated with better functioning but also with increased suicidality. The direction of the relationship between insight and suicidality is not clear, hence we aimed to provide new elements using structural equation modeling. METHODS: Insight, quality of life (QoL), depression, and suicidality were measured at baseline and at 12 months in individuals with schizophrenia spectrum disorders. The relationships between these variables were investigated by latent difference score models, controlling for chlorpromazine doses, positive and negative symptoms, and general psychopathology. RESULTS: 738 patients were included, and 370 completed the study. Baseline levels of insight predicted changes in suicidality, whereas baseline levels of suicidality did not predict changes in insight, suggesting that better insight underlies suicidality and predicts its worsening. Our results suggest this temporal sequence: better insight → worse QoL → increased depression → increased suicidality, while insight also affects the three variables in parallel. CONCLUSION: Better insight predicts a worsening of QoL, depression and suicidality. These findings contribute to our global understanding of the longitudinal influence of insight on suicidality. We advocate that insight-targeted interventions should not be proposed without the monitoring of depression and suicide prevention.