Hypovitaminosis D is associated with depression and anxiety in schizophrenia: results from the national FACE-SZ cohort. Running title: hypovitaminosis D, depression and anxiety in schizophrenia

International audienceBackground. Guidelines have been edited for the treatment of schizophrenia (SZ) and bipola

Poverty and inequality in real-world schizophrenia: a national study

BackgroundSchizophrenia has high socioeconomic impact among severe psychiatric disorders.AimsTo explore clinician-reported and patient-reported inequities between patients under the poverty threshold vs. the others.Method916 patients consecutively recruited in 10 national centers received a comprehensive standardized evaluation of illness severity, addictions and patient-reported outcomes.Results739 (80.7%) of the patients were classified in the poverty group. This group had poorer objective illness outcomes (lower positive, negative, cognitive, excitement/aggressive and self-neglect symptoms and lifetime history of planned suicide) in multivariate analyses. While they had similar access to treatments and psychotherapy, they had lower access to socially useful activities, couple’s life, housing and parenthood. They had also more disturbed metabolic parameters. On the contrary, the poverty group reported better self-esteem. No significant difference for depression, risky health behavior including addictions and sedentary behavior was found.InterpretationThe equity in access to care is attributed to the French social system. However, mental and physical health remain poorer in these patients, and they still experience poor access to social roles independently of illness severity and despite healthcare interventions. These patients may have paradoxically better self-esteem due to decreased contact with society and therefore lower stigma exposure (especially at work). Schizophrenia presents itself as a distinct impoverished population concerning health-related outcomes and social integration, warranting focus in public health initiatives and improved treatment, including tailored interventions, collaborative care models, accessible mental health services, housing support, vocational training and employment support, community integration, education and awareness, research and data collection, culturally competent approaches, and long-term support

Potential efficacy of dopaminergic antidepressants in treatment resistant anergic-anhedonic depression results of the chronic anergic-anhedonic depression open trial – CADOT

IntroductionAmong treatment-resistant depression (TRD), we identified anergic-anhedonic clinical presentations (TRAD) as putatively responsive to pro-dopaminergic strategies. Based on the literature, non-selective monoamine oxidase inhibitors (MAOI) and dopamine D2 receptor agonists (D2RAG) were sequentially introduced, frequently under the coverage of a mood stabilizer. This two-step therapeutic strategy will be referred to as the Dopaminergic Antidepressant Therapy Algorithm (DATA). We describe the short and long-term outcomes of TRAD managed according to DATA guidelines.MethodOut of 52 outpatients with TRAD treated with DATA in a single expert center, 48 were included in the analysis [severity – QIDS (Quick Inventory of Depressive Symptomatology) = 16 ± 3; episode duration = 4.1 ± 2.7 years; Thase and Rush resistance stage = 2.9 ± 0.6; functioning – GAF (Global Assessment of Functioning) = 41 ± 8]. These were followed-up for a median (1st – 3rd quartile) of 4 (1–9) months before being prescribed the first dopaminergic treatment and remitters were followed up 21 (11–33) months after remission.ResultsAt the end of DATA step 1, 25 patients were in remission (QIDS <6; 52% [38–66%]). After DATA step 2, 37 patients were in remission (77% [65–89%]) to whom 5 patients with a QIDS score = 6 could be added (88% [78–97%]). Many of these patients felt subjectively remitted (GAF = 74 ± 10). There was a significant benefit to combining MAOI with D2RAG which was maintained for at least 18 months in 30 patients (79% [62–95%]).ConclusionThese results support TRAD sensitivity to pro-dopaminergic interventions. However, some clinical heterogeneities remain in our sample and suggest some improvement in the description of dopamine-sensitive form(s)

Handedness as a neurodevelopmental marker in schizophrenia: Results from the FACE-SZ cohort

Objectives: High rates of non-right-handedness (NRH) including mixed-handedness have been reported in neurodevelopmental disorders. In schizophrenia (SZ), atypical handedness has been inconsistently related to impaired features. We aimed to determine whether SZ subjects with NRH and mixed-handedness had poorer clinical and cognitive outcomes compared to their counterparts. Methods: 667 participants were tested with a battery of neuropsychological tests, and assessed for laterality using the Edinburg Handedness Inventory. Clinical symptomatology was assessed. Learning disorders and obstetrical complications were recorded. Biological parameters were explored. Results: The prevalence of NRH and mixed-handedness was high (respectively, 42.4% and 34.1%). In the multivariable analyses, NRH was associated with cannabis use disorder (p = 0.045). Mixed-handedness was associated with positive symptoms (p = 0.041), current depressive disorder (p = 0.005)), current cannabis use (p = 0.024) and less akathisia (p = 0.019). A history of learning disorder was associated with NRH. No association was found with cognition, trauma history, obstetrical complications, psychotic symptoms, peripheral inflammation. Conclusions: Non-right and mixed-handedness are very high in patients with SZ, possibly reflecting a neurodevelopmental origin. NRH is associated with learning disorders and cannabis use. Mixed-handedness is associated with positive symptoms, current depressive disorder, cannabis use and less akathisia. However, this study did not confirm greater cognitive impairment in these patients. © 2021 Informa UK Limited, trading as Taylor & Francis Group.Sorbonne Universités à Paris pour l'Enseignement et la RechercheFondaMental-Cohorte

Schizophrenia Bulletin Open

Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics.Sorbonne Universités à Paris pour l'Enseignement et la RechercheFondaMental-Cohorte

Immuno-metabolic profile of patients with psychotic disorders and metabolic syndrome. Results from the FACE-SZ cohort

Background: Metabolic syndrome (MetS) is a highly prevalent and harmful medical disorder often comorbid with psychosis where it can contribute to cardiovascular complications. As immune dysfunction is a key shared component of both MetS and schizophrenia (SZ), this study investigated the relationship between immune alterations and MetS in patients with SZ, whilst controlling the impact of confounding clinical characteristics including psychiatric symptoms and comorbidities, history of childhood maltreatment and psychotropic treatments. Method: A total of 310 patients meeting DSM-IV criteria for SZ or schizoaffective disorders (SZA), with or without MetS, were systematically assessed and included in the FondaMental Advanced Centers of Expertise for Schizophrenia (FACE-SZ) cohort. Detailed clinical characteristics of patients, including psychotic symptomatology, psychiatric comorbidities and history of childhood maltreatment were recorded and the serum levels of 18 cytokines were measured. A penalized regression method was performed to analyze associations between inflammation and MetS, whilst controlling for confounding factors. Results: Of the total sample, 25% of patients had MetS. Eight cytokines were above the lower limit of detection (LLOD) in more than 90% of the samples and retained in downstream analysis. Using a conservative Variable Inclusion Probability (VIP) of 75%, we found that elevated levels of interleukin (IL)-6, IL-7, IL-12/23 p40 and IL-16 and lower levels of tumor necrosis factor (TNF)-α were associated with MetS. As for clinical variables, age, sex, body mass index (BMI), diagnosis of SZ (not SZA), age at the first episode of psychosis (FEP), alcohol abuse, current tobacco smoking, and treatment with antidepressants and anxiolytics were all associated with MetS. Conclusion: We have identified five cytokines associated with MetS in SZ suggesting that patients with psychotic disorders and MetS are characterized by a specific “immuno-metabolic” profile. This may help to design tailored treatments for this subgroup of patients with both psychotic disorders and MetS, taking one more step towards precision medicine in psychiatry. © 2022 The AuthorsImmuno-Génétique, Inflammation, retro-Virus, Environnement : de l'étiopathogénie des troubles psychotiques aux modèles animauxRéseau d'Innovation sur les Voies de Signalisation en Sciences de la Vi

Les troubles de la mémoire autobiographique et du self dans la schizophrénie : approche en psychopathologie cognitive et perspectives thérapeutiques

Médecin

Autobiographical memory and the self in schizophrenia

La schizophrénie est une maladie mentale qui s'accompagne de perturbations profondes de l'identité subjective (ou self). Nous avons cherché à préciser la nature de ces perturbations au moyen de cinq études portant sur la mémoire autobiographique. Nous nous sommes basés pour cela sur le modèle théorique de Conway (2005) qui établit des liens étroits et réciproques entre le self et la mémoire autobiographique. Ce modèle distingue un self conceptuel, porteur de connaissances sur soi (ou images de soi) et un self exécutif contrôlant la récupération des souvenirs en accord avec le self conceptuel. Nos résultats montrent que certains souvenirs en lien étroit avec le self (self-defining memories, souvenirs sous-tendant les images de soi) sont moins intégrés ou reliés de façon moins cohérente au self chez les patients schizophrènes. Les souvenirs sous-tendant les images de soi sont caractérisés par une altération du sentiment même de soi chez les patients. De plus, l'organisation de la mémoire autobiographique et en particulier des souvenirs sous-tendant les images de soi, est défaillante chez les patients. Nous avons exploré enfin l'influence de la maladie et des symptômes comme le délire sur la mémoire autobiographique et le self et montré que les souvenirs d'expériences psychotiques représentent une proportion significative des self-defining memories des patients. Ces résultats nous amènent à proposer un modèle cognitif basé sur la mémoire autobiographique expliquant la constitution d'un self anormal dans la schizophrénie et des croyances délirantes. Ce modèle sert de base pour guider l'application de thérapeutiques spécifiques découlant de nos travaux.Schizophrenia is a mental illness that profoundly alters the self. We conducted five autobiographical memory studies with the aim to better understand the nature of self disorders in patients. Our work was based on the theoretical model put forward by Conway (2005), which posits reciprocal relationships between autobiographical memory and the self. This model distinguishes a conceptual self, which contains self-knowledge as self-images from an executive self (working self), which controls memories retrieval with respect to the conceptual self. We found that some memories that are closely related to the self (as self-defining memories or memories grounding self-images) were less integrated or less coherently linked to the self in patients compared with control subjects. Memories grounding self-images were characterized by an alteration of the subjective sense of self. Moreover, the organization of autobiographical memory was deficient in patients, in particular that of memories related to self-images. Finally, we investigated how the illness and symptoms like delusion had an impact on autobiographical memory and the self and it showed that memories of psychotic episodes are often considered as self-defining in patients. Our results allowed us to put forward a cognitive model based on autobiographical memory, accounting for the constitution of an abnormal self and of delusional beliefs. Our work brings new findings on the nature of autobiographical memory deficits and self disorders in patients with schizophrenia, which may lead to specific therapeutical interventions in the future