Assessment of risk factors of treatment discontinuation among patients on paliperidone palmitate and risperidone microspheres in France, Germany and Belgium

BACKGROUND: Long-acting antipsychotics (e.g. 1-monthly (PP1M) / 3-monthly (PP3M) injection forms of paliperidone palmitate) have been developed to improve treatment continuation in schizophrenia patients. We aim to assess risk factors of treatment discontinuation of patients on paliperidone palmitate and risperidone microsphere. Additionally, treatment discontinuation between patients with PP1M and PP3M was compared. METHODS: The IQVIA Longitudinal Prescription databases were used. Risk factors of treatment discontinuation were identified by a multilevel survival regression using Cox proportional hazards model. Kaplan Meier analyses were performed by identified significant risk factors. RESULTS: Twenty-five thousand three hundred sixty-one patients (France: 9,720; Germany: 14,461; Belgium: 1,180) were included. Over a one-year follow-up period, a significant lower treatment discontinuation was observed for patients newly initiated on paliperidone palmitate (53.8%) than those on risperidone microspheres (85.4%). Additionally, a significantly lower treatment discontinuation was found for ‘stable’ PP3M patients (19.2%) than ‘stable’ PP1M patients (37.1%). Patients were more likely to discontinue when drugs were prescribed by GP only (HR = 1.68, p  50 years: HR = 0.91, p < 0.001 vs. 18–30 years). CONCLUSIONS: This study demonstrates that patients stay significantly longer on treatment when initiated on paliperidone palmitate as compared to risperidone microspheres. It also indicated a higher treatment continuation of PP3M over PP1M. Treatment continuation is likely to be improved by empowering GPs with mental health knowledge and managing patients by a collaborative primary care-mental health model. Further research is needed to understand why females and younger patients have more treatment discontinuation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-022-03914-2

Etude de l'accessibilité à l'humour chez le sujet schizophrène (mécanismes, fonctions et application clinique)

La problématique des compétences sociales altérées dans la schizophrénie est en lien avec l'accessibilité à l'humour. L'humour est un comportement humain situé au centre des interactions sociales. Il est admis que les patients souffrant de schizophrénie présentent un déficit de perception de l'humour. Le domaine encore non exploré est l'étude du traitement du contexte dans les mécanismes d'accessibilité à l'humour. La première étage de notre projet a été de construite e de valider le matériel expérimental constitué de stimuli verbaux et visuels en faisant varier l'incongruité selon le modèle de Suls, puis de valider la tâche expérimentale auprès de participants sains. Le questionnaire de projet actuel pourra donc être transmis à des patients atteints de schizophrénie afin d'étudier les mécanismes de traitement de l'humour de ces personnes. En parallèle, des épreuves neuropsychologiques ainsi que des échelles symptomatiques et sociales seront réalisées. Il est fort possible que l'étude puisse donner des résultats concordants avec nos hypothèses de départ, c'est-à-dire que la perception des situations humoristiques diminuées dans la schizophrénie est en lien avec le traitement altéré des informations contextuelles en rapport avec la flexibilité mentale. Caractériser la nature d'éventuel déficit dans la perception de l'humour des ptients pourra avoir plusieurs conséquences. Tout d'abord, cela pourra s'intégrer dans la démarche diagnostique, cela permettra de déterminer les fonctions cognitives qui sous-tendent le déficit de perception de l'humour. Et enfin, des programmes de remédiation pourront être établis afin d'améliorer les interactions sociales du patientAIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Les troubles de l'émotion dans la schizophrénie

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Association between formal thought disorder and cannabis use: a systematic review and meta-analysis.

Formal thought disorder (FTD) is a multidimensional syndrome mainly occurring along the psychosis continuum. Cannabis use is known to increase symptoms of psychosis, particularly positive symptoms. However, the impact of cannabis use on FTD in individuals presenting symptoms along the psychosis continuum remains unclear. To address this knowledge gap, we conducted a meta-analysis examining the association between cannabis use and FTD in those individuals. We hypothesized that cannabis would worsen FTD. We conducted a systematic search of the PubMed, ScienceDirect, PsycINFO, Web of Science, Embase and Google Scholar databases up to July 2022. The results were collated through a random-effects model using the statistical software R. Reference lists of included studies were searched for additional relevant publications. Nineteen studies were included, totalling 1840 cannabis users and 3351 non-cannabis users. The severity of FTD was found to be higher in cannabis users. Subgroup analyses revealed that FTD severity was increased among cannabis users, regardless of the disorder severity: healthy individuals; patients with first-episode psychosis; patients with schizophrenia. Between-group differences were not significant. In line with its already known effect on positive symptoms in psychosis, cannabis use appears to be associated with increased FTD severity all along the psychosis continuum. Future research should consider potential confounding variables such as other substance use disorders and explore how FTD dimensions are impacted by cannabis use

Understanding the link between childhood trauma and schizophrenia: A systematic review of neuroimaging studies

International audienceIncreasing evidence suggests that childhood trauma (CT) is a major risk factor for schizophrenia but the underpinning mechanisms of their association remain unclear. Our aim is to review the literature on the association between CT and brain imaging measurements in adult schizophrenia subjects. We conducted a systematic review of the existing neuroimaging literature on CT and schizophrenia. We reviewed studies considering adult subjects with schizophrenia, schizoaffective disorder or first episode schizophrenia. A total of 15 studies were included. The most replicated result was the association in schizophrenia patients between CT and decreased total cerebral grey matter, particularly in the prefrontal cortex. In addition, studies suggest a different sensitivity to early stressors between schizophrenia subjects, their sibling and healthy unrelated subjects. In schizophrenia, CT is associated with alterations of white matter integrity in the inferior and superior longitudinal fasciculus, the inferior fronto-occipital fasciculus and the forceps major. Functional connectivity studies suggest an association between CT and a network including the amygdala, the anterior cingulate cortex, the precuneus/posterior cingulate cortex region and the temporo-parietal junction

Relation Between Facial Affect Recognition and Configural Face Processing in Antipsychotic-Free Schizophrenia

International audienceObjective: Deficit in facial affect recognition is a well-documented impairment in schizophrenia, closely connected to social outcome. This deficit could be related to psychopathology, but also to a broader dysfunction in processing facial information. In addition, patients with schizophrenia inadequately use configural information-a type of processing that relies on spatial relationships between facial features. To date, no study has specifically examined the link between symptoms and misuse of configural information in the deficit in facial affect recognition. Method: Unmedicated schizophrenia patients (n = 30) and matched healthy controls (n = 30) performed a facial affect recognition task and a face inversion task, which tests aptitude to rely on configural information. In patients, regressions were carried out between facial affect recognition, symptom dimensions and inversion effect. Results: Patients, compared with controls, showed a deficit in facial affect recognition and a lower inversion effect. Negative symptoms and lower inversion effect could account for 41.2% of the variance in facial affect recognition. Conclusion: This study confirms the presence of a deficit in facial affect recognition, and also of dysfunctional manipulation in configural information in antipsychotic-free patients. Negative symptoms and poor processing of configural information explained a substantial part of the deficient recognition of facial affect. We speculate that this deficit may be caused by several factors, among which independently stand psychopathology and failure in correctly manipulating configural information

Molecular mapping of a core transcriptional signature of microglia-specific genes in schizophrenia

International audienceBesides playing a central role in neuroinflammation, microglia regulate synaptic development and is involved in plasticity. Converging lines of evidence suggest that these different processes play a critical role in schizophrenia. Furthermore, previous studies reported altered transcription of microglia genes in schizophrenia, while microglia itself seems to be involved in the etiopathology of the disease. However, the regional specificity of these brain transcriptional abnormalities remains unclear. Moreover, it is unknown whether brain and peripheral expression of microglia genes are related. Thus, we investigated the expression of a pre-registered list of 10 genes from a core signature of human microglia both at brain and peripheral levels. We included 9 independent Gene Expression Omnibus datasets (764 samples obtained from 266 individuals with schizophrenia and 237 healthy controls) from 8 different brain regions and 3 peripheral tissues. We report evidence of a widespread transcriptional alteration of microglia genes both in brain tissues (we observed a decreased expression in the cerebellum, associative striatum, hippocampus, and parietal cortex of individuals with schizophrenia compared with healthy controls) and whole blood (characterized by a mixed altered expression pattern). Our results suggest that brain underexpression of microglia genes may represent a candidate transcriptional signature for schizophrenia. Moreover, the dual brain-whole blood transcriptional alterations of microglia/macrophage genes identified support the model of schizophrenia as a whole-body disorder and lend weight to the use of blood samples as a potential source of biological peripheral biomarkers

Association between formal thought disorder and cannabis use: a systematic review and meta-analysis

International audienceFormal thought disorder (FTD) is a multidimensional syndrome mainly occurring along the psychosis continuum. Cannabis use is known to increase symptoms of psychosis, particularly positive symptoms. However, the impact of cannabis use on FTD in individuals presenting symptoms along the psychosis continuum remains unclear. To address this knowledge gap, we conducted a meta-analysis examining the association between cannabis use and FTD in those individuals. We hypothesized that cannabis would worsen FTD. We conducted a systematic search of the PubMed, ScienceDirect, PsycINFO, Web of Science, Embase and Google Scholar databases up to July 2022. The results were collated through a random-effects model using the statistical software R. Reference lists of included studies were searched for additional relevant publications. Nineteen studies were included, totalling 1840 cannabis users and 3351 non-cannabis users. The severity of FTD was found to be higher in cannabis users (SMD = 0.21, 95% CI [0.12-0.29], p = 0.00009). Subgroup analyses revealed that FTD severity was increased among cannabis users, regardless of the disorder severity: healthy individuals (SMD = 0.19, 95%CI [0.05-0.33], p = 0.02); patients with first-episode psychosis (SMD = 0.21, 95%CI [0.01-0.41], p = 0.04); patients with schizophrenia (SMD = 0.25, 95%CI [0.11-0.38], p = 0.005). Between-group differences were not significant. In line with its already known effect on positive symptoms in psychosis, cannabis use appears to be associated with increased FTD severity all along the psychosis continuum. Future research should consider potential confounding variables such as other substance use disorders and explore how FTD dimensions are impacted by cannabis use