Insight et schizophrénie : quels rôles dans le risque suicidaire ?

International audienceLe suicide constitue la première cause de mort prématurée chez les patients souffrant de schizophrénie. Le risque suicidaire serait majoré au cours des phases précoces de la maladie, en particulier la première année qui suit le diagnostic. La coexistence d'un trouble de l'humeur est un facteur de risque de suicide identifié dans cette population. Les données de la littérature sont consensuelles quant au lien entre un bon niveau d'insight et une augmentation du risque suicidaire. L'hypothèse selon laquelle l'association entre l'insight et le risque suicidaire serait liée à l'existence d'une symptomatologie dépressive ou un sentiment de désespoir reste à confirmer. Une étude auprès de 61patients a évalué les dimensions cliniques et cognitives de l'insight et confirme l'association entre un niveau d'insight élevé et le risque suicidaire. Les patients ayant bénéficié d'un programme psychoéducatif avaient un meilleur insight. Ces données soulèvent un paradoxe apparent. Si l'altération de l'insight est un facteur reconnu de mauvais pronostic dans la schizophrénie, améliorer la conscience de la maladie devrait constituer un des objectifs thérapeutiques principaux. Pourtant, un bon insight est également associé à des effets négatifs significatifs. Parmi les programmes d'éducation à la santé, des interventions dont l'objectif est de modifier les croyances négatives à propos des troubles psychotiques pourraient avoir un effet sur la réduction du risque suicidaire. Indépendamment du modèle d'intervention visant l'amélioration de l'insight, le maintien d'une alliance thérapeutique optimale est sans doute la meilleure façon de réduire le risque suicidaire

Psychiatric and psychological follow-up of undergraduate and postgraduate medical students: prevalence and associated factors. Results from the national BOURBON study. Running title: mental health and addictive behavior of medical students

International audienceBackground. Physicians are at risk of burnout, anxiety and depression. Prevention i

Evaluation of patients on sertindole treatment after failure of other antipsychotics: A retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Use of the atypical antipsychotic sertindole was suspended for four years due to safety concerns. During the suspension, the regulatory authorities required further studies, including this one, to be conducted. The purpose of this study was to determine if a subset of patients with psychotic illness exists which particularly benefits from sertindole treatment after failure of other antipsychotic drugs, including atypical antipsychotics.</p> <p>Methods</p> <p>This was a retrospective single-arm observational crossover study of 344 patients, who served as their own controls. Patients mainly from the Sertindole Safety Study who had shown good response to sertindole, and who had followed up to four alternating six month periods of treatment with sertindole and other antipsychotics, were included. (In Period 1 patients took non-sertindole treatment, in Period 2, sertindole was taken, in Period 3, patients reverted to non-sertindole treatment, and in Period 4, sertindole was taken again.) Patient records for each period of treatment were assessed for objective data: number and duration of hospitalizations due to worsening of psychotic symptoms; the amount of self-harming behaviour; indicators of social status. Retrospective evaluation of changes in clinical symptoms from the patients' records was also conducted. Dates and reasons for stopping and/or switching medication were also recorded.</p> <p>Results</p> <p>There was improvement in all objective measured parameters during the periods of sertindole treatment. In particular, the average number of hospitalizations per year due to worsening of psychotic symptoms was reduced in the following way in the group studied over four treatment periods: Period 1 (non-sertindole treatment) 3.4; Period 2 (sertindole treatment) 1.0; Period 3 (non-sertindole treatment) 2.0; Period 4 (sertindole treatment) 1.8. The duration of hospitalizations also decreased significantly during the periods of sertindole treatment. Results showed that patients improved in objective social parameters when switched to sertindole treatment; assessment of the patients' affective lives showed a significant increase in the number of patients having a stable relationship during sertindole treatment; and assessment of the number of patients employed showed an increase after the first and second switch to sertindole treatment (from Period 1 to Period 2 and from Period 3 to Period 4, respectively).</p> <p>Adverse events and lack of efficacy were the main reasons for switching to sertindole.</p> <p>Conclusion</p> <p>A group of patients benefited from sertindole after other antipsychotic treatments, including that with atypical antipsychotics, had failed. Further studies are needed to investigate if there is a specific patient profile that corresponds to these responders.</p

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

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

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. © 2022 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

Medication adherence in patients with psychotic disorders: an observational survey involving patients before they switch to long-acting injectable risperidone

Franck Jean Bayl&eacute;,1 Arnaud Tessier,2,3 Sophie Bouju,4 David Misdrahi2,3 1Sainte-Anne Hospital (SHU), Paris V-Descartes University, Paris, 2H&ocirc;pital Charles Perrens, P&ocirc;le de Psychiatrie Adulte, 3CNRS UMR 5287-INCIA, Bordeaux University, Bordeaux, 4Janssen-Cilag France, Issy Les Moulineaux, Paris, France Background: Maintaining antipsychotic therapy in psychosis is important in preventing relapse. Long-acting depot preparations can prevent covert non-adherence and thus potentially contribute to better patient outcomes. In this observational survey the main objective is to evaluate medication adherence and its determinants for oral treatment in a large sample of patients with psychosis.Methods: In this cross-sectional survey medication adherence for oral treatment was assessed by patients using the patient-rated Medication Adherence Questionnaire (MAQ). Data were collected by physicians on patients with a recent acute psychotic episode before switching to long-acting injectable risperidone. Other evaluations included disease severity (Clinical Global Impression &ndash; Severity), patients&rsquo; insight (Positive and Negative Syndrome Scale item G12), treatment acceptance (clinician-rated Compliance Rating Scale), and therapeutic alliance (patient-rated 4-Point ordinal Alliance Scale).Results: A total of 399 psychiatrists enrolled 1,887 patients (mean age 36.8&plusmn;11.9 years; 61.6% had schizophrenia). Adherence to oral medication was &ldquo;low&rdquo; in 53.2% of patients, &ldquo;medium&rdquo; in 29.5%, and &ldquo;high&rdquo; in 17.3%. Of patients with psychiatrist-rated active acceptance of treatment, 70% had &ldquo;medium&rdquo; or &ldquo;high&rdquo; MAQ scores (P&lt;0.0001). Medication adherence was significantly associated with therapeutic alliance (4-Point ordinal Alliance Scale score; P&lt;0.0001). Patient age was significantly associated with adherence: mean age increased with greater adherence (35.6, 36.7, and 38.6 years for patients with &ldquo;low&rdquo;, &ldquo;medium&rdquo;, and &ldquo;high&rdquo; levels of adherence, respectively; P=0.0007), while age &lt;40 years was associated with &ldquo;low&rdquo; MAQ classification (P=0.0003). Poor adherence was also associated with a diagnosis of schizophrenia (P=0.0083), more severe disease (Clinical Global Impression &ndash; Severity &ge;4; P&lt;0.0001), and lower insight (Positive and Negative Syndrome Scale-G12 &ge;4; P&lt;0.0001).Conclusion: Self-reported adherence was low in most patients, with a strong positive association between self-reported adherence and psychiatrists&rsquo; assessment of treatment acceptance. Understanding factors associated with poor medication adherence may help physicians to better manage their patients, thereby improving outcomes. Keywords: schizophrenia, long-acting antipsychotic, medication adherence, therapeutic allianc

Etude du mouvement dans les épreuves projectives à la lumière d'un cas de myasthénie gravis

International audienc