The Inhibitory Receptor CLEC12A Regulates PI3K-Akt Signaling to Inhibit Neutrophil Activation and Cytokine Release

The myeloid inhibitory C-type lectin receptor CLEC12A limits neutrophil activation, pro-inflammatory pathways and disease in mouse models of inflammatory arthritis by a molecular mechanism that remains poorly understood. We addressed how CLEC12A-mediated inhibitory signaling counteracts activating signaling by cross-linking CLEC12A in human neutrophils. CLEC12A cross-linking induced its translocation to flotillin-rich membrane domains where its ITIM was phosphorylated in a Src-dependent manner. Phosphoproteomic analysis identified candidate signaling molecules regulated by CLEC12A that include MAPKs, phosphoinositol kinases and members of the JAK-STAT pathway. Stimulating neutrophils with uric acid crystals, the etiological agent of gout, drove the hyperphosphorylation of p38 and Akt. Ultimately, one of the pathways through which CLEC12A regulates uric acid crystal-stimulated release of IL-8 by neutrophils is through a p38/PI3K-Akt signaling pathway. In summary this work defines early molecular events that underpin CLEC12A signaling in human neutrophils to modulate cytokine synthesis. Targeting this pathway could be useful therapeutically to dampen inflammation

Metabolic disturbances are risk factors for readmission to psychiatric hospitals in non-smokers but not in smokers: results from a Swiss psychiatric cohort and in first-episode psychosis patients

BackgroundPsychiatric patients are at high risk of readmission, and a high body mass index has previously been shown as a risk factor. We sought to replicate this finding and 1) to prospectively assess the association of metabolic syndrome and its five components with readmission in psychiatric hospitals and 2) to identify other clinical and sociodemographic predictors of readmission.MethodsBetween 2007 and 2019, data on 16727 admissions of 7786 adult and elderly patients admitted to the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to the International Diabetes Federation definition. Cox frailty models were used to investigate the associations between readmission and metabolic disturbances.ResultsA total of 2697 (35%) patients were readmitted to our psychiatric hospital. Novel risk factors for readmission in non-smokers were identified, including being overweight (HR=1.26; 95%CI=[1.05; 1.51]) or obese (HR=1.33; 95%CI=[1.08; 1.62]), displaying hypertriglyceridemia (HR=1.21; 95%CI=[1.04; 1.40]) and metabolic syndrome (HR=1.26; 95%CI=[1.02; 1.55]). Central obesity and hyperglycemia increased the risk of readmission when considering the Health of the Nation Outcome Scales variable. In first-episode psychosis patients, obesity (HR=2.23; 95%CI=[1.14; 4.30]) and high-density lipoprotein hypocholesterolemia (HR=1.90; 95%CI=[1.14; 3.20]) doubled the risk of readmission.ConclusionThe observed interaction between smoking and metabolic variables are compatible with a ceiling effect; metabolic variables increase the risk of readmission in non-smokers but not in smokers who are already at higher risk. Future studies should determine whether better metabolic monitoring and treatment can reduce readmission risk

Histoire des thérapies de choc en psychiatrie ou la naissance d'un nouveau paradigme (entre innovations thérapeutiques et controverses)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF

La question de l'insight

Par crainte et par méconnaissance, les approches psychothérapeutiques des troubles psychotiques sont trop souvent mises de côté, alors même que les patients témoignent de plus en plus de leur besoin vital d’être écoutés et compris dans leur recherche de sens à cette expérience. La position psychothérapeutique, qui met au centre du soin l’écoute de la personne, est essentielle dans tous les parcours en psychiatrie ; pourquoi est-elle souvent considérée comme impossible avec les patients présentant une psychose ? Bien au contraire, comme démontré tout au long de cet ouvrage, elle est indiquée dans la psychose, et la pensée psychothérapique peut et doit imprégner tous les actes thérapeutiques, quel que soit le lieu du soin. La psychothérapie dans ce sens ne se pratique pas seulement dans un cabinet de psychothérapeute : elle est aussi une approche relationnelle globale visant la construction d’un lien pour cheminer au quotidien. Ce guide de formation présente le vaste champ des approches psychothérapeutiques des psychoses en exposant les principales théories et leurs applications cliniques, illustrées de manière concrète en s’appuyant sur des exemples cliniques et des témoignages

Psychiatrie : Nouveautés en médecine 2020

The Covid-19 pandemic has a major impact on psychiatry by its social consequences and possible direct effect of certain forms of Covid-19 on mental health. During this crisis, the accessibility of technology meets a state of necessity, which has propelled telepsychiatry from the shadows into the light. The contribution of several technologies (i.e. virtual reality, actigraphy, computational psychiatry) combining clinical data and neuroscience underlines the great neurobehavioural variability even within the same diagnostic category, calling for greater precision in therapeutic offers as suggested e.g. by developments in neurofeedback. The place of intranasal esketamin in the panoply of antidepressent drug treatments for resistant depression has not yet been defined

Mild Depressive Symptoms Mediate the Impact of Childhood Trauma on Long-Term Functional Outcome in Early Psychosis Patients

Abstract Introduction The mechanism linking childhood trauma (CT) to the functional deficits observed in early psychosis (EP) patients is as yet unknown. We aim to examine the potential mediating effect of depressive symptoms in this well-established association. Methods Two hundred nine EP subjects aged 18-35 were assessed for functioning and psychopathology after 2, 6, 12, 18, 24, 30, and 36 months of treatment. Patients were classified into early trauma if they had faced at least one experience of abuse (physical, sexual, or emotional) or neglect (physical or emotional) before age 12, and late trauma if the exposure had occurred between ages 12 and 16. Diagnosis was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Psychopathology was assessed with the Positive and Negative Syndrome Scale and the Montgomery-Asberg Depression Rating Scale. Functioning was measured with the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS). Mediation analyses were performed in order to study whether the relationship between CT and functioning was mediated by depressive symptoms. Results When compared with nonexposed patients, early but not late trauma patients showed lower levels of GAF and SOFAS scores over all the time points, excepting after the first assessment. After 30 and 36 months, the effect of early trauma on functioning was completely mediated by depressive symptoms. No mediating effect of positive or negative symptoms was highlighted at those time points. Conclusion Mild depressive symptoms mediated the impact of early trauma on long-term functional outcome. Intensifying pharmacologic and/or psychotherapeutic treatment, focused on the depressive dimension, may help traumatized EP patients to improve their functioning

DataSheet_1_Metabolic disturbances are risk factors for readmission to psychiatric hospitals in non-smokers but not in smokers: results from a Swiss psychiatric cohort and in first-episode psychosis patients.docx

BackgroundPsychiatric patients are at high risk of readmission, and a high body mass index has previously been shown as a risk factor. We sought to replicate this finding and 1) to prospectively assess the association of metabolic syndrome and its five components with readmission in psychiatric hospitals and 2) to identify other clinical and sociodemographic predictors of readmission.MethodsBetween 2007 and 2019, data on 16727 admissions of 7786 adult and elderly patients admitted to the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to the International Diabetes Federation definition. Cox frailty models were used to investigate the associations between readmission and metabolic disturbances.ResultsA total of 2697 (35%) patients were readmitted to our psychiatric hospital. Novel risk factors for readmission in non-smokers were identified, including being overweight (HR=1.26; 95%CI=[1.05; 1.51]) or obese (HR=1.33; 95%CI=[1.08; 1.62]), displaying hypertriglyceridemia (HR=1.21; 95%CI=[1.04; 1.40]) and metabolic syndrome (HR=1.26; 95%CI=[1.02; 1.55]). Central obesity and hyperglycemia increased the risk of readmission when considering the Health of the Nation Outcome Scales variable. In first-episode psychosis patients, obesity (HR=2.23; 95%CI=[1.14; 4.30]) and high-density lipoprotein hypocholesterolemia (HR=1.90; 95%CI=[1.14; 3.20]) doubled the risk of readmission.ConclusionThe observed interaction between smoking and metabolic variables are compatible with a ceiling effect; metabolic variables increase the risk of readmission in non-smokers but not in smokers who are already at higher risk. Future studies should determine whether better metabolic monitoring and treatment can reduce readmission risk.</p