Overlap and Mutual Distinctions between Clinical Recovery and Personal Recovery in People with Schizophrenia in a One-Year Study

Recovery is a multidimensional construct that can be defined either from a clinical perspective or from a consumer-focused one, as a self-broadening process aimed at living a meaningful life beyond mental illness. We aimed to longitudinally examine the overlap and mutual distinctions between clinical and personal recovery. Of 1239 people with schizophrenia consecutively recruited from the FondaMental Advanced Centers of Expertise for SZ network, the 507 present at one-year did not differ from those lost to follow-up. Clinical recovery was defined as the combination of clinical remission and functional remission. Personal recovery was defined as being in the rebuilding or in the growth stage of the Stages of Recovery Instrument (STORI). Full recovery was defined as the combination of clinical recovery and personal recovery. First, we examined the factors at baseline associated with each aspect of recovery. Then, we conducted multivariable models on the correlates of stable clinical recovery, stable personal recovery, and stable full recovery after one year. At baseline, clinical recovery and personal recovery were characterized by distinct patterns of outcome (i.e. better objective outcomes but no difference in subjective outcomes for clinical recovery, the opposite pattern for personal recovery, and better overall outcomes for full recovery). We found that clinical recovery and personal recovery predicted each other over time (baseline personal recovery for stable clinical recovery at one year; P =. 026, OR = 4.94 [1.30-23.0]; baseline clinical recovery for stable personal recovery at one year; P =. 016, OR = 3.64 [1.31-11.2]). In short, given the interaction but also the degree of difference between clinical recovery and personal recovery, psychosocial treatment should target, beyond clinical recovery, subjective aspects such as personal recovery and depression to reach full recovery. © 2021 The Author(s). Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.Sorbonne Universités à Paris pour l'Enseignement et la RechercheFondaMental-Cohorte

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

ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders

A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.

BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.journal articleresearch support, non-u.s. gov't2016 Feb2015 10 26importe

Nephrocalcinosis (enamel renal syndrome) caused by autosomal recessive FAM20A mutations

Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood

Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

PURPOSE: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. METHODS: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. RESULTS: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10-18) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10-13). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. CONCLUSION: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing

Analyse de l'expression génétique dans des cellules humaines en réponse aux interférons

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Regulation of two interferon-inducible human genes by interferon, poly(rI)·poly(rC) and viruses

The IFI-56K and IFI-54K genes are transcriptionally stimulated when cells are treated by interferon. We have previously shown that the IFI-56K gene is in addition directly induced by poly(rI)·poly(rC), and inducer of interferon-β. Since the regulation of the IFI-56K and IFI-54K genes by interferon are very much alike, we tested whether the IFI-54K gene is also directly regulated by poly(rI)·poly(rC). Treatment of various cell lines with poly(rI)·poly(rC) leads to a clear accumulation of the IFI-54K mRNA to a level which sometimes even exceeds that obtained with high doses of interferon. Several interferon-resistant cell lines were investigated for the inducibility of both the IFI-56K and IFI-54K genes by interferons, poly(rI)·poly(rC) and viruses (which are the natural inducers of interferon-α and -β). Both genes appear to be coordinately regulated by these inducers. It was thus interesting to search for common regulatory element(s) in the control region of these two genes. The IFI-54K gene promoter region was isolated, from which a 520-base-pair segment was sequenced and compared with the promoter region of the IFI-56K gene that we had previously sequenced. The only homology found is a well conserved 19-bp segment located just upstream of the TATA box of these genes; interestingly, this sequence is also homologous to the minimal region needed for the inducibility by poly(rI)·poly(rC) of the interferon-β gene. This conserved sequence might be responsible for the coordinate induction of the IFI-56K and IFI-54K genes by interferon, poly(rI)·poly(rC) and viruses.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Post-transcriptional effect of ultraviolet light on gene expression in human cells. Stabilization of cytokine-induced and poly(I) · poly(C)-induced messenger RNA

It is well established that ultraviolet light modulates gene expression in mammalian cells, particularly at transcriptional and post-translational levels. The present study was undertaken to investigate whether the fate of mRNA is also altered in ultraviolet-light-irradiated human cells. In order to facilitate distinction between transcriptional and post-transcriptional effects, this analysis has focused on six genes whose transcription is conditional on the supply of exogenous inducers, interferon-α, interleukin-1α or the double-stranded RNA, poly(I) · poly(C). Human cells induced to express these genes were found to retain a significantly higher concentration of corresponding transcripts when irradiated with ultraviolet light at the end of the inducing treatment. This stimulation was due to dose-dependent ultraviolet-light stabilization of preformed mRNA, as shown by run-on and pulse/chase experiments. This work uncovers a new facet of the cellular response to genotoxic stresses, i.e. extension of the life-span of transcription products. Whether this stabilizing effect contributes to cell recovery by promoting gene expression remains to be determined.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

2-Aminopurine selectively blocks the transcriptional activation of cellular genes by virus, double-stranded RNA and interferons in human cells

Interferons, double-stranded RNA and viruses induce the transcription of partly overlapping sets of cellular genes. We have studied the regulation of 11 interferon-inducible genes by these agents and found that four of them were also directly inducible by virus and double-stranded RNA, and two by virus only. We have investigated whether an inhibitor of interferon-β gene activation, 2-aminopurine, would block this induction process. Induction of these genes by virus and double-stranded RNA was indeed blocked by 2-aminopurine. Since a single cis-acting element can confer inducibility both to interferons, and to virus and double-stranded RNA, we tested the effect of 2-aminopurine on gene activation by interferon-α and interferon-γ. Remarkably, in all the cell lines tested, these induction processes and the establishment of an antiviral state were blocked by the drug. These observations contrast with previous reports. The inhibitor effect of this drug on gene induction was exerted in a selective fashion and at the transcriptional level. This indicates that for the virus-, double-stranded-RNA-, and interferons-mediated gene induction, an early and similar step in signal transduction was affected by 2-aminopurine.SCOPUS: ar.jinfo:eu-repo/semantics/publishe