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1. Neurodevelopmental disorders (NDD) without boundaries: research and interventions beyond classifications

Author: Cécile Louveau, Pierre Ellul, Anton Iftimovici, Julien Dubreucq, Charles Laidi, Quentin Leyrolle, Diane Purper-Ouakil, Sebastien Jacquemont, Stanislas Lyonnet, Catherine Barthélémy, Marie-Odile Krebs, Jing Bai, Paul Olivier, Boris Chaumette, GHU Paris Psychiatrie et Neurosciences, AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Etienne, Child Mind Institute, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hôpital Saint Eloi (CHRU Montpellier), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), CHU Necker - Enfants Malades [AP-HP], GIS autisme et troubles du neuro-développement (GIS-Autisme et TND), Université de Tours (UT), McGill University = Université McGill [Montréal, Canada], Martinez Rico, Clara, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Psychiatry and Mental health, Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Biological Psychiatry
Abstract: International audience; On June 2022, the 2nd Webinar "Neurodevelopmental Disorders (NDD) without boundaries took place at the Imagine Institute in Paris and was broadcasted live and in replay. The aim of this webinar is to address NDD in a dimensional rather than in a categorical approach. Several speakers were invited to present their researches on the subject. Classifications in NDD were discussed: irritability in NDD, involvement of the immune system in neurodevelopment, nutrition and gut microbiota modulate brain inflammation and neurodevelopment, co-occurring conditions in autistic adolescents and adults without intellectual disability. Classifications in psychiatric disorders were asked: mapping the effect of genes on cognition and autism risk, epigenetics and symptomatic trajectory in neurodevelopmental disorders, the autism-schizophrenia continuum in two examples: minor neurological signs and EEG microstates, the cerebellum in schizophrenia and autism: from imaging to intervention perspectives. Both genetic and environmental factors, along with clinical and imaging features, argue toward a continnum between NDD but also with adult psychiatric presentations. This new paradigm could modify the therapeutic strategy, with the development of large-spectrum treatments or new psychotherapies addressing co-occuring symptoms. The complexity and the heterogeneity of NDD apply well to the next scientific and political challenges: developing international convergence to push back the frontiers of our knowledge. This article is a summary of the 2nd webinar "Neurodevelopmental Disorders (NDD) without boundaries: research and interventions beyond classifications" sponsored by the French National Academy of Medicine, the autism and neurodevelopmental disorders scientific interest group (GIS), the International Research Network Dev-O-Psy and the French Institute of Psychiatry (GDR3557). Oral presentations are available as a replay on the following website (in French): https://autisme-neurodev.org/evenements/2022/04/12/tnd-sans-frontieres-la-recherche-et-les-interventions-au-dela-des-classifications/ .
Published: 2023
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2. MRI spot sign in acute intracerebral hemorrhage: an independent biomarker of hematoma expansion and poor functional outcome

Author: Nefeli Valyraki, Adrien Goujon, Marjorie Mateos, Adrien Lecoeuvre, Augustin Lecler, Igor Raynouard, Candice Sabben, Michael Obadia, Julien Savatovsky, Pierre Seners, Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Martinez Rico, Clara
Subjects: Stroke, Neurology, Cerebral Hemorrhage Magnetic Resonance Imaging Stroke Prognosis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Prognosis, Magnetic Resonance Imaging, Cerebral Hemorrhage
Abstract: International audience; Background: In acute intracerebral hemorrhage (ICH), the prognostic value of the MRI spot sign on hematoma expansion (HE) and poor functional outcome is poorly known.Methods: We retrospectively included patients admitted over a 4-year period for an acute ICH in a single institution using MRI as the first-line imaging tool. The presence and number of MRI spot signs on contrast-enhanced T1-weighted imaging was evaluated by one neuroradiologist, blinded from outcomes. The primary outcome was HE, defined as > 6 mL or > 33% ICH volume growth from initial MRI to 24-48 h follow-up imaging; the secondary outcome was poor 3-month modified Rankin score (4-6).Results: Overall, 147 patients were included, and 62% had a spot sign. Among the 130 patients with follow-up imaging, 24% experienced HE. HE occurred in 6%, 21% and 43% patients with 0, 1 and ≥ 2 spots, respectively (P < 0.001). The MRI spot sign was independently associated with HE (adjusted OR 6.15 [95% CI 1.60-23.65]; P = 0.008), with a dose-dependent effect. The negative and positive predictive values of the spot sign for HE were 0.94 and 0.35, respectively. Poor functional outcome occurred in 27%, 32% and 71% patients with 0, 1 and ≥ 2 spots, respectively (P < 0.001). In multivariable analysis, the presence of ≥ 2 spots was independently associated with poor functional outcome (adjusted OR 3.67 [95% CI 1.21-11.10]; P = 0.024).Conclusion: The MRI spot sign is an independent biomarker of HE, and the presence of ≥ 2 spots is independently associated with poor 3-month outcome. The lack of spot sign is highly predictive of a favorable evolution.
Published: 2022
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3. Synthetic FLAIR as a Substitute for FLAIR Sequence in Acute Ischemic Stroke

Author: Joseph Benzakoun, Marc-Antoine Deslys, Laurence Legrand, Ghazi Hmeydia, Guillaume Turc, Wagih Ben Hassen, Sylvain Charron, Clément Debacker, Olivier Naggara, Jean-Claude Baron, Bertrand Thirion, Catherine Oppenheim, GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Saint-Anne (GHU Paris), Modèles et inférence pour les données de Neuroimagerie (MIND), IFR49 - Neurospin - CEA, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), MIND, and Martinez Rico, Clara
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Radiology, Nuclear Medicine and imaging, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background In acute ischemic stroke (AIS), fluid-attenuated inversion recovery (FLAIR) is used for treatment decisions when onset time is unknown. Synthetic FLAIR could be generated with deep learning from information embedded in diffusion-weighted imaging (DWI) and could replace acquired FLAIR sequence (real FLAIR) and shorten MRI duration. Purpose To compare performance of synthetic and real FLAIR for DWI-FLAIR mismatch estimation and identification of patients presenting within 4.5 hours from symptom onset. Materials and Methods In this retrospective study, all pretreatment and early follow-up ( .99). Conclusion Synthetic fluid-attenuated inversion recovery (FLAIR) had diagnostic performances similar to real FLAIR in depicting diffusion-weighted imaging-FLAIR mismatch and in helping to identify early acute ischemic stroke, and it may accelerate MRI protocols. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Carroll and Hurley in this issue.
Published: 2022
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4. Impact of Comorbid Affective Disorders on Longitudinal Clinical Outcomes in Individuals at Ultra-high Risk for Psychosis

Author: Nadine C van der Burg, Philip McGuire, Birte Glenthøj, Stephan Ruhrmann, Jim van Os, Bart P. F. Rutten, Neus Barrantes-Vidal, Patrick D. McGorry, Frederike Schirmbeck, Gabriele Sachs, Rodrigo A. Bressan, Barnaby Nelson, Marie-Odile Krebs, Jentien M Vermeulen, Anita Riecher-Rössler, G. Paul Amminger, Matthijs Blankers, Lucia Valmaggia, Mark van der Gaag, Christos Pantelis, Paolo Fusar-Poli, Merete Nordentoft, Lieuwe de Haan, Matthew J. Kempton, Adult Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, VU University Medical Center [Amsterdam], Arkin Institute for Mental Health [Amsterdam, The Netherlands] (AIMH), GGZ Centraal [Amersfoort, The Netherlands], Trimbos Institute, Netherlands Institute of Mental Health and Addiction, King‘s College London, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Psychosis Research Institute [The Hague, Netherlands], University of Basel (Unibas), Universidade Federal de São Paulo, Universitat Autònoma de Barcelona (UAB), Spanish Mental Health Research Network (CIBERSAM), Orygen [Parkville, Victoria], University of Melbourne, Melbourne Health [Carlton South, Victoria], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Groupement de recherche en Psychiatrie (GDR Psychiatrie (3557)), Centre National de la Recherche Scientifique (CNRS), University of Cologne, Medizinische Universität Wien = Medical University of Vienna, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University Medical Center [Utrecht], IT University of Copenhagen, South London and Maudsley NHS Foundation Trust, University of Pavia, EU-GEI High Risk Study Group Authors: Maria Calem, Stefania Tognin, Gemma Modinos, Sara Pisani, Emily Hedges, Eva Velthorst, Tamar C Kraan, Daniella S van Dam, Nadine Burger, Athena Politis, Joanne Goodall, Stefan Borgwardt, Erich Studerus, Ary Gadelha, Elisa Brietzke, Graccielle Asevedo, Elson Asevedo, Andre Zugman, Tecelli Domínguez-Martínez, Manel Monsonet, Lidia Hinojosa, Anna Racioppi, Thomas R Kwapil, Mathilde Kazes, Claire Daban, Julie Bourgin, Olivier Gay, Célia Mam-Lam-Fook, Dorte Nordholm, Lasse Randers, Kristine Krakauer, Louise Birkedal Glenthøj, Dominika Gebhard, Julia Arnhold, Joachim Klosterkötter, Iris Lasser, Bernadette Winklbaur, Philippe A Delespaul, VU University Amsterdam, Martinez Rico, Clara, Vrije Universiteit Amsterdam [Amsterdam] (VU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), IT University of Copenhagen (ITU), Università degli Studi di Pavia = University of Pavia (UNIPV), RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), RS: MHeNs - R2 - Mental Health, and MUMC+: Hersen en Zenuw Centrum (3)
Subjects: Male, Ultra-high risk, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Comorbid, Comorbidity, Anxiety, Logistic regression, 0302 clinical medicine, Longitudinal Studies, psychosis, Depression (differential diagnoses), Depression, anxiety, DEPRESSION, Anxiety Disorders, STATE, EXPERIENCES, CHILDHOOD TRAUMA, Europe, Psychiatry and Mental health, YOUTH, Schizophrenia, Female, medicine.symptom, Anxiety disorder, Adult, Risk, medicine.medical_specialty, Psychosis, Adolescent, AcademicSubjects/MED00810, Prodromal Symptoms, comorbid, Lower risk, ultra-high risk, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Risk factor, METAANALYSIS, Depressive Disorder, Mood Disorders, business.industry, PERSISTENCE, prediction, medicine.disease, 030227 psychiatry, schizophrenia, Psychotic Disorders, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, ONSET, Gene-Environment Interaction, business, Prediction, 030217 neurology & neurosurgery, AT-RISK, Regular Articles, Follow-Up Studies
Abstract: Introduction Diagnoses of anxiety and/or depression are common in subjects at Ultra-High Risk for Psychosis (UHR) and associated with extensive functional impairment. Less is known about the impact of affective comorbidities on the prospective course of attenuated psychotic symptoms (APS). Method Latent class mixed modelling identified APS trajectories in 331 UHR subjects assessed at baseline, 6, 12, and 24 months follow-up. The prognostic value of past, baseline, and one-year DSM-IV depressive or anxiety disorders on trajectories was investigated using logistic regression, controlling for confounders. Cox proportional hazard analyses investigated associations with transition risk. Results 46.8% of participants fulfilled the criteria for a past depressive disorder, 33.2% at baseline, and 15.1% at one-year follow-up. Any past, baseline, or one-year anxiety disorder was diagnosed in 42.9%, 37.2%, and 27.0%, respectively. Participants were classified into one of three latent APS trajectory groups: (1) persistently low, (2) increasing, and (3) decreasing. Past depression was associated with a higher risk of belonging to the increasing trajectory group, compared to the persistently low (OR = 3.149, [95%CI: 1.298–7.642]) or decreasing group (OR = 3.137, [1.165–8.450]). In contrast, past (OR = .443, [.179–1.094]) or current (OR = .414, [.156–1.094]) anxiety disorders showed a trend-level association with a lower risk of belonging to the increasing group compared to the persistently low group. Past depression was significantly associated with a higher risk of transitioning to psychosis (HR = 2.123, [1.178–3.828]). Conclusion A past depressive episode might be a particularly relevant risk factor for an unfavorable course of APS in UHR individuals. Early affective disturbances may be used to advance detection, prognostic, and clinical strategies.
Published: 2022
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5. NMOSD typical brain lesions after COVID-19 mRNA vaccination

Author: Julie Lévi-Strauss, Corentin Provost, Noémie Wane, Thomas Jacquemont, Nicolas Mélé, GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Martinez Rico, Clara
Subjects: Aquaporin 4, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Neurology, Neuromyelitis Optica, Vaccination, Brain, COVID-19, Humans, RNA, Messenger, Neurology (clinical), Nervous System Diseases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Autoantibodies
Abstract: International audience; No abstract available
Published: 2022
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6. A novel tablet-based application for assessment of manual dexterity and its components: a reliability and validity study in healthy subjects

Author: Ayah, Rabah, Quentin, Le Boterff, Loïc, Carment, Narjes, Bendjemaa, Maxime, Térémetz, Lucile, Dupin, Macarena, Cuenca, Jean-Louis, Mas, Marie-Odile, Krebs, Marc A, Maier, Påvel G, Lindberg, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Pôle hospitalo-universitaire d’Evaluation Prévention et Innovation Thérapeutique [Paris] (PEPIT), GHU Paris Psychiatrie & Neurosciences, Groupement de recherche en Psychiatrie (GDR Psychiatrie (3557)), Centre National de la Recherche Scientifique (CNRS), Centre Neurosciences intégratives et Cognition (INCC - UMR 8002), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Martinez Rico, Clara
Subjects: Adult, Measurement, Aging, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Digital medicine, Rehabilitation, Manual dexterity, Reproducibility of Results, Health Informatics, Tablet application, Middle Aged, Hand, Reliability, Healthy Volunteers, Validity, Stroke, Upper Extremity, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Inter-rater reliability, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background We developed five tablet-based tasks (applications) to measure multiple components of manual dexterity. Aim: to test reliability and validity of tablet-based dexterity measures in healthy participants. Methods Tasks included: (1) Finger recognition to assess mental rotation capacity. The subject taps with the finger indicated on a virtual hand in three orientations (reaction time, correct trials). (2) Rhythm tapping to evaluate timing of finger movements performed with, and subsequently without, an auditory cue (inter-stimulus interval). (3) Multi-finger tapping to assess independent finger movements (reaction time, correct trials, unwanted finger movements). (4) Sequence tapping to assess production and memorization of visually cued finger sequences (successful taps). (5) Line-tracking to assess movement speed and accuracy while tracking an unpredictably moving line on the screen with the fingertip (duration, error). To study inter-rater reliability, 34 healthy subjects (mean age 35 years) performed the tablet tasks twice with two raters. Relative reliability (Intra-class correlation, ICC) and absolute reliability (Standard error of measurement, SEM) were established. Task validity was evaluated in 54 healthy subjects (mean age 49 years, range: 20–78 years) by correlating tablet measures with age, clinical dexterity assessments (time taken to pick-up objects in Box and Block Test, BBT and Moberg Pick Up Test, MPUT) and with measures obtained using a finger force-sensor device. Results Most timing measures showed excellent reliability. Poor to excellent reliability was found for correct trials across tasks, and reliability was poor for unwanted movements. Inter-session learning occurred in some measures. Age correlated with slower and more variable reaction times in finger recognition, less correct trials in multi-finger tapping, and slower line-tracking. Reaction times correlated with those obtained using a finger force-sensor device. No significant correlations between tablet measures and BBT or MPUT were found. Inter-task correlation among tablet-derived measures was weak. Conclusions Most tablet-based dexterity measures showed good-to-excellent reliability (ICC ≥ 0.60) except for unwanted movements during multi-finger tapping. Age-related decline in performance and association with finger force-sensor measures support validity of tablet measures. Tablet-based components of dexterity complement conventional clinical dexterity assessments. Future work is required to establish measurement properties in patients with neurological and psychiatric disorders.
Published: 2022
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7. Versatile and automated workflow for the analysis of oligodendroglial calcium signals in preclinical mouse models of myelin repair

Author: Dorien A. Maas, Blandine Manot-Saillet, Philippe Bun, Chloé Habermacher, Corinne Poilbout, Filippo Rusconi, Maria Cecilia Angulo, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), SynapCell SAS, Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Plateforme d'Analyse Protéomique de Paris Sud Ouest (PAPPSO), GHU Paris Psychiatrie et Neurosciences, and Martinez Rico, Clara
Subjects: [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract: Intracellular Ca2+signals of oligodendroglia, the myelin-forming cells of the central nervous system, regulate vital cellular processes including myelination. However, studies on oligodendroglia Ca2+signal dynamics are still scarce, especially during myelin repair, and there are no software solutions to properly analyze the unique Ca2+signal characteristics in these cells. Here, we provide a comprehensive experimental and analytical workflow to acquire and analyze Ca2+imaging data of oligodendroglia at the population and single-cell levels in preclinical mouse models of myelin repair. We report diverseex vivoandin vivoexperimental protocols to obtain reproducible Ca2+imaging data from oligodendroglia in demyelinated lesions. Importantly, we provide an analytical pipeline containing two free, open source and cross-platform software programs, Occam and post-prOccam, that enable the fully automated analysis of one- and two-photon Ca2+imaging datasets from oligodendroglia obtained by eitherex vivoorin vivoCa2+imaging techniques. This versatile and accessible experimental and analytical framework, which revealed significant but uncorrelated spontaneous Ca2+activity in oligodendroglia inside demyelinated lesions, should facilitate the elucidation of Ca2+-mediated mechanisms underlying remyelination and therefore help to accelerate the development of therapeutic strategies for the many myelin-related disorders, such as multiple sclerosis.
Published: 2022

8. Efficacity of tDCS in catatonic patients with Phelan McDermid syndrome, a case series

Author: Mylène Moyal, Marion Plaze, Ambre Baruchet, David Attali, Cora Cravero, Marie Raffin, Angèle Consoli, David Cohen, Alexandre Haroche, Boris Chaumette, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Physique pour la médecine (PhysMed Paris), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité mobile interdépartementale pour les situations complexes en matière d'autisme [Paris] (UMI 75-92), Fondation l’Élan Retrouvé [Paris] (FER), Abord dimensionnel des épisodes psychotiques de l’enfant et de l’adolescent: implications génétiques, métaboliques et auto-immunes, Troubles psychiatriques et développement (GRC 15 PSYDEV), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut des Systèmes Intelligents et de Robotique (ISIR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Martinez Rico, Clara
Subjects: General Neuroscience, BFCRS, Biophysics, Catatonia, Neurodevelopmental disorder, tDCS, Phelan-McDermid syndrome, Transcranial direct current stimulation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Chronic catatonia, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Neurostimulation, SHANK3
Abstract: International audience; No abstract available
Published: 2022
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9. Motor inhibition and its contribution to recovery of dexterous hand use after stroke

Author: Jeanette Plantin, Alison K Godbolt, Gaia V Pennati, Evaldas Laurencikas, Peter Fransson, Jean Claude Baron, Marc A Maier, Jörgen Borg, Påvel G Lindberg, Karolinska Institutet [Stockholm], GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Neurosciences intégratives et Cognition (INCC - UMR 8002), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Martinez Rico, Clara
Subjects: recovery, General Engineering, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], hand, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], motor inhibition, stroke, MRI
Abstract: Recovery of dexterous hand use is critical for functional outcome after stroke. Grip force recordings can inform on maximal motor output and modulatory and inhibitory cerebral functions, but how these actually contribute to recovery of dexterous hand use is unclear. This cohort study used serially assessed measures of hand kinetics to test the hypothesis that behavioural measures of motor modulation and inhibition explain dexterity recovery beyond that explained by measures of motor output alone. We also investigated the structural and functional connectivity correlates of grip force control recovery. Eighty-nine adults (median age = 54 years, 26% females) with first-ever ischaemic or haemorrhagic stroke and persistent arm and hand paresis were assessed longitudinally, at 3 weeks, and at 3 and 6 months after stroke. Kinetic measures included: maximal grip force, accuracy of precision and power grip force control, and ability to release force abruptly. Dexterous hand use was assessed clinically with the Box and Block Test and motor impairment with the upper extremity Fugl-Meyer Assessment. Structural and functional MRI was used to assess weighted corticospinal tract lesion load, voxel-based lesion symptom mapping and interhemispheric resting-state functional connectivity. Fifty-three per cent of patients had severe initial motor impairment and a majority still had residual force control impairments at 6 months. Force release at 3 weeks explained 11% additional variance of Box and Block Test outcome at 6 months, above that explained by initial scores (67%). Other kinetic measures did not explain additional variance of recovery. The predictive value of force release remained significant when controlling for corticospinal tract lesion load and clinical measures. Corticospinal tract lesion load correlated with recovery in grip force control measures. Lesions involving the parietal operculum, insular cortex, putamen and fronto-striatal tracts were also related to poorer force modulation and release. Lesions to fronto-striatal tracts explained an additional 5% of variance in force release beyond the 43% explained by corticospinal injury alone. Interhemispheric functional connectivity did not relate to force control recovery. We conclude that not only voluntary force generation but also force release (reflecting motor inhibition) are important for recovery of dexterous hand use after stroke. Although corticospinal injury is a main determinant of recovery, lesions to integrative somatosensory areas and fronto-parietal white matter (involved in motor inhibition) explain additional variance in post-stroke force release recovery. Our findings indicate that post-stroke upper limb motor impairment profiling, which is essential for targeted treatment, should consider both voluntary grasp generation and inhibition.
Published: 2022
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10. Association Between FIASMAs and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID‐19: An Observational Multicenter Study

Author: Hoertel, Nicolas, Sánchez-Rico, Marina, Gulbins, Erich, Kornhuber, Johannes, Carpinteiro, Alexander, Lenze, Eric J., Reiersen, Angela M., Abellán, Miriam, de la Muela, Pedro, Vernet, Raphaël, Blanco, Carlos, Cougoule, Céline, Neuraz, Antoine, Gorwood, Philip, Alvarado, Jesús M., Meneton, Pierre, Limosin, Frédéric, Ancel, Pierre-Yves, Bauchet, Alain, Beeker, Nathanaël, Benoit, Vincent, Bernaux, Mélodie, Bellamine, Ali, Bey, Romain, Bourmaud, Aurélie, Breant, Stéphane, Burgun, Anita, Carrat, Fabrice, Caucheteux, Charlotte, Champ, Julien, Cormont, Sylvie, Daniel, Christel, Dubiel, Julien, Ducloas, Catherine, Esteve, Loic, Frank, Marie, Garcelon, Nicolas, Gramfort, Alexandre, Griffon, Nicolas, Grisel, Olivier, Guilbaud, Martin, Hassen-Khodja, Claire, Hemery, François, Hilka, Martin, Sophie Jannot, Anne, Lambert, Jerome, Layese, Richard, Leblanc, Judith, Lebouter, Léo, Lemaitre, Guillaume, Leprovost, Damien, Lerner, Ivan, Levi Sallah, Kankoe, Maire, Aurélien, Mamzer, Marie-France, Martel, Patricia, Mensch, Arthur, Moreau, Thomas, Orlova, Nina, Paris, Nicolas, Rance, Bastien, Ravera, Hélène, Rozes, Antoine, Salamanca, Elisa, Sandrin, Arnaud, Serre, Patricia, Tannier, Xavier, Treluyer, Jean-Marc, van Gysel, Damien, Varoquaux, Gaël, Vie, Jill Jen, Wack, Maxime, Wajsburt, Perceval, Wassermann, Demian, Zapletal, Eric, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Corentin Celton [Issy-les-Moulineaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), University of Duisburg-Essen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Hôpital Européen Georges Pompidou [APHP] (HEGP), National Institute on Drug Abuse [Bethesda] (NIDA), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, AP-HP / Université de Paris / INSERM COVID-19 research collaboration, AP-HP COVID CDR Initiative, 'Entrepôt de Données de Santé' AP-HP Consortium: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal, Martinez Rico, Clara, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), National Institute on Drug Abuse [Bethesda], Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Collaborators : AP-HP / Université de Paris / INSERM COVID-19 research collaboration, AP-HP COVID CDR Initiative, 'Entrepôt de Données de Santé' AP-HP Consortium: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien Van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Imagine - Institut des maladies génétiques (IMAGINE - U1163), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Medizin, law.invention, Cohort Studies, COVID-19 Testing, medications, Randomized controlled trial, law, Clinical endpoint, Intubation, Pharmacology (medical), Enzyme Inhibitors, acid sphingomyelinase, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, treatment, Inverse probability weighting, Hazard ratio, Middle Aged, 3. Good health, Hospitalization, [SDV] Life Sciences [q-bio], Sphingomyelin Phosphodiesterase, Female, FIASMA, Adult, medicine.medical_specialty, Adolescent, intubation, Young Adult, Internal medicine, Intubation, Intratracheal, medicine, Humans, ceramide, Aged, Retrospective Studies, Pharmacology, SARS-CoV-2, Proportional hazards model, business.industry, COVID-19, mortality, Confidence interval, COVID-19 Drug Treatment, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Collaborators : AP-HP / Université de Paris / INSERM COVID-19 research collaboration, AP-HP COVID CDR Initiative, “Entrepôt de Données de Santé” AP-HP Consortium: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien Van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal; International audience; Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS-CoV-2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID-19 in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) receiving a FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58-0.87; p
Published: 2021
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11. Obsessive-Compulsive Symptoms and Other Symptoms of the At-risk Mental State for Psychosis

Author: Ong, Hui Lin, Isvoranu, Adela-Maria, Schirmbeck, Frederike, McGuire, Philip, Valmaggia, Lucia, Kempton, Matthew J., van der Gaag, Mark, Riecher-Rössler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Nelson, Barnaby, Amminger, G. Paul, McGorry, Patrick, Pantelis, Christos, Krebs, Marie-Odile, Nordentoft, Merete, Glenthøj, Birte, Ruhrmann, Stephan, Sachs, Gabriele, Rutten, Bart P. F., van Os, Jim, de Haan, Lieuwe, Borsboom, Denny, Calem, Maria, Tognin, Stefania, Modinos, Gemma, Pisani, Sara, Hedges, Emily, Velthorst, Eva, Kraan, Tamar C., van Dam, Daniella S., Burger, Nadine, Politis, Athena, Goodall, Joanne, Borgwardt, Stefan, Studerus, Erich, Gadelha, Ary, Brietzke, Elisa, Asevedo, Graccielle, Asevedo, Elson, Zugman, Andre, Domínguez-Martínez, Tecelli, Monsonet, Manel, Hinojosa, Lidia, Racioppi, Anna, Kwapil, Thomas R., Kazes, Mathilde, Daban, Claire, Bourgin, Julie, Gay, Olivier, Mam-Lam-Fook, C. lia, Nordholm, Dorte, Randers, Lasse, Krakauer, Kristine, Glenthøj, Louise Birkedal, Gebhard, Dominika, Arnhold, Julia, Klosterkötter, Joachim, Lasser, Iris, Winklbaur, Bernadette, Delespaul, Philippe A., University of Amsterdam [Amsterdam] (UvA), Arkin Institute for Mental Health [Amsterdam, The Netherlands] (AIMH), King‘s College London, Vrije Universiteit Amsterdam [Amsterdam] (VU), Universitätsspital Basel [Switzerland], Universidade Federal de São Paulo, Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), University of Melbourne, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Copenhagen = Københavns Universitet (KU), University of Cologne, Medizinische Universität Wien = Medical University of Vienna, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Utrecht University [Utrecht], EU-GEI High Risk Study: Maria Calem, Stefania Tognin, Gemma Modinos, Sara Pisani, Emily Hedges, Eva Velthorst, Tamar C Kraan, Daniella S van Dam, Nadine Burger, Athena Politis, Joanne Goodall, Stefan Borgwardt, Erich Studerus, Ary Gadelha, Elisa Brietzke, Graccielle Asevedo, Elson Asevedo, Andre Zugman, Tecelli Domínguez-Martínez, Manel Monsonet, Lidia Hinojosa, Anna Racioppi, Thomas R Kwapil, Mathilde Kazes, Claire Daban, Julie Bourgin, Olivier Gay, Célia Mam-Lam-Fook, Dorte Nordholm, Lasse Randers, Kristine Krakauer, Louise Birkedal Glenthøj, Dominika Gebhard, Julia Arnhold, Joachim Klosterkötter, Iris Lasser, Bernadette Winklbaur, Philippe A Delespaul, Adult Psychiatry, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, ANS - Complex Trait Genetics, Psychologische Methodenleer (Psychologie, FMG), Clinical Psychology, RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), RS: MHeNs - R2 - Mental Health, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Copenhagen = Københavns Universitet (UCPH), and Martinez Rico, Clara
Subjects: Male, DISORDER, Obsessive-Compulsive Disorder, Ultra-high risk, obsessive-compulsive, Psychological intervention, clinical high risk, Anxiety, 0302 clinical medicine, SCHIZOPHRENIA, COMPREHENSIVE ASSESSMENT, psychosis, Social isolation, network analysis, Depression (differential diagnoses), ASSOCIATIONS, Psychiatry, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Obsessive-compulsive, Depression, Clinical high risk, anxiety, CHILDHOOD TRAUMA, Psychiatry and Mental health, Schizophrenia, depression, Blunted Affect, Female, Network analysis, medicine.symptom, Life Sciences & Biomedicine, Clinical psychology, Adult, Psychosis, AcademicSubjects/MED00810, Risk Assessment, ultra-high risk, 03 medical and health sciences, Young Adult, medicine, Humans, METAANALYSIS, VULNERABILITY, SPECTRUM, Science & Technology, business.industry, At risk mental state, medicine.disease, 030227 psychiatry, INDIVIDUALS, Psychotic Disorders, Case-Control Studies, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Regular Articles
Abstract: Background The high prevalence of obsessive-compulsive symptoms (OCS) among subjects at Ultra-High Risk (UHR) for psychosis is well documented. However, the network structure spanning the relations between OCS and symptoms of the at risk mental state for psychosis as assessed with the Comprehensive Assessment of At Risk Mental States (CAARMS) has not yet been investigated. This article aimed to use a network approach to investigate the associations between OCS and CAARMS symptoms in a large sample of individuals with different levels of risk for psychosis. Method Three hundred and forty-one UHR and 66 healthy participants were included, who participated in the EU-GEI study. Data analysis consisted of constructing a network of CAARMS symptoms, investigating central items in the network, and identifying the shortest pathways between OCS and positive symptoms. Results Strong associations between OCS and anxiety, social isolation and blunted affect were identified. Depression was the most central symptom in terms of the number of connections, and anxiety was a key item in bridging OCS to other symptoms. Shortest paths between OCS and positive symptoms revealed that unusual thought content and perceptual abnormalities were connected mainly via anxiety, while disorganized speech was connected via blunted affect and cognitive change. Conclusions Findings provide valuable insight into the central role of depression and the potential connective component of anxiety between OCS and other symptoms of the network. Interventions specifically aimed to reduce affective symptoms might be crucial for the development and prospective course of symptom co-occurrence.
Published: 2021
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12. Chronic lithium treatment alters the excitatory/inhibitory balance of synaptic networks and reduces mGluR5–PKC signalling in mouse cortical neurons

Author: Austen J. Milnerwood, Boris Chaumette, Patrick A. Dion, Anouar Khayachi, Guy A. Rouleau, Ariel R. Ase, Philippe Séguéla, Calwing Liao, Martin Alda, Anusha Kamesh, Lenka Schorova, Naila Kuhlmann, McGill University = Université McGill [Montréal, Canada], McGill University Health Center [Montreal] (MUHC), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Dalhousie University [Halifax], and Martinez Rico, Clara
Subjects: Bipolar Disorder, Lithium (medication), medicine.drug_class, Receptor, Metabotropic Glutamate 5, Inhibitory postsynaptic potential, Synapse, Mice, Glutamatergic, Calcium imaging, GSK-3, medicine, Animals, Pharmacology (medical), [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Bipolar disorder, Cells, Cultured, Protein Kinase C, Biological Psychiatry, Cerebral Cortex, Neurons, Chemistry, Neural Inhibition, Mood stabilizer, medicine.disease, Psychiatry and Mental health, Synapses, Lithium Compounds, Calcium, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, Signal Transduction, Research Paper, medicine.drug
Abstract: International audience; Background: Bipolar disorder is characterized by cyclical alternation between mania and depression, often comorbid with psychosis and suicide. Compared with other medications, the mood stabilizer lithium is the most effective treatment for the prevention of manic and depressive episodes. However, the pathophysiology of bipolar disorder and lithium’s mode of action are yet to be fully understood. Evidence suggests a change in the balance of excitatory and inhibitory activity, favouring excitation in bipolar disorder. In the present study, we sought to establish a holistic understanding of the neuronal consequences of lithium exposure in mouse cortical neurons, and to identify underlying mechanisms of action.Methods: We used a range of technical approaches to determine the effects of acute and chronic lithium treatment on mature mouse cortical neurons. We combined RNA screening and biochemical and electrophysiological approaches with confocal immunofluorescence and live-cell calcium imaging.Results: We found that only chronic lithium treatment significantly reduced intracellular calcium flux, specifically by activating metabotropic glutamatergic receptor 5. This was associated with altered phosphorylation of protein kinase C and glycogen synthase kinase 3, reduced neuronal excitability and several alterations to synapse function. Consequently, lithium treatment shifts the excitatory–inhibitory balance toward inhibition.Limitations: The mechanisms we identified should be validated in future by similar experiments in whole animals and human neurons.Conclusion: Together, the results revealed how lithium dampens neuronal excitability and the activity of the glutamatergic network, both of which are predicted to be overactive in the manic phase of bipolar disorder. Our working model of lithium action enables the development of targeted strategies to restore the balance of overactive networks, mimicking the therapeutic benefits of lithium but with reduced toxicity.
Published: 2021
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13. Meningioma in patients exposed to progestin drugs: results from a real-life screening program

Author: Thomas Samoyeau, Corentin Provost, Alexandre Roux, Laurence Legrand, Edouard Dezamis, Geneviève Plu-Bureau, Johan Pallud, Catherine Oppenheim, Joseph Benzakoun, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Martinez Rico, Clara
Subjects: Cancer Research, Cyproterone acetate, Chlormadinone acetate, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mass screening, Magnetic Resonance Imaging, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neurology, Oncology, Meningeal Neoplasms, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Prospective Studies, Progestins, Nomegestrol acetate, Meningioma, Aged
Abstract: Purpose: To report the results of systematic meningioma screening program implemented by French authorities in patients exposed to progestin therapies (cyproterone (CPA), nomegestrol (NA), and chlormadinone (CMA) acetate).Methods: We conducted a prospective monocentric study on patients who, between September 2018 and April 2021, underwent standardized MRI (injection of gadolinium, then a T2 axial FLAIR and a 3D-T1 gradient-echo sequence) for meningioma screening.Results: Of the 210 included patients, 15 (7.1%) had at least one meningioma; seven (7/15, 47%) had multiple meningiomas. Meningiomas were more frequent in older patients and after exposure to CPA (13/103, 13%) compared to NA (1/22, 4%) or CMA (1/85, 1%; P=0.005). After CPA exposure, meningiomas were associated with longer treatment duration (median=20 vs 7 years, P=0.001) and higher cumulative dose (median=91 g vs. 62 g, P=0.014). Similarly, their multiplicity was associated with higher dose of CPA (median=244 g vs 61 g, P=0.027). Most meningiomas were ≤1 cm3 (44/58, 76%) and were convexity meningiomas (36/58, 62%). At diagnosis, patients were non-symptomatic, and all were managed conservatively. Among 14 patients with meningioma who stopped progestin exposure, meningioma burden decreased in 11 (79%) cases with no case of progression during MR follow-up.Conclusion: Systematic MR screening in progestin-exposed patients uncovers small and multiple meningiomas, which can be managed conservatively, decreasing in size after progestin discontinuation. The high rate of meningiomas after CPA exposure reinforces the need for systematic screening. For NA and CMA, further studies are needed to identify patients most likely to benefit from screening.
Published: 2022
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14. Altered Neuronal Support and Inflammatory Response in Bipolar Disorder Patient-Derived Astrocytes

Author: Michael McCarthy, Maria C. Marchetto, Renata Santos, Maxim N. Shokhirev, Arianna Mei, Kelly J. Heard, Ruth Oefner, Galina Erikson, Krishna C. Vadodaria, Vipula Racha, Lisa T. Eyler, John R. Kelsoe, Ana P.D. Mendes, Fred H. Gage, The Salk Institute for Biological Studies, University of California [San Diego] (UC San Diego), University of California, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of California (UC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Martinez Rico, Clara
Subjects: 0301 basic medicine, Bipolar Disorder, glia, medicine.medical_treatment, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Interleukin-1beta, Biochemistry, neuronal activity, Transcriptome, 0302 clinical medicine, cytokine, Premovement neuronal activity, Induced pluripotent stem cell, Neurons, iPSC, biology, Phenotype, mood disorders, psychiatry, 3. Good health, Cytokine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Neuroglia, medicine.medical_specialty, Clinical Sciences, Induced Pluripotent Stem Cells, Inflammation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Neuropathology, Article, 03 medical and health sciences, Internal medicine, Genetics, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Interleukin 6, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, IL-6, Interleukin-6, astrocytes, Cell Biology, Coculture Techniques, IL-6 Stem Cell Reports, 030104 developmental biology, Endocrinology, inflammation, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, biology.protein, Biochemistry and Cell Biology, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Summary Bipolar disorder (BD) is characterized by cyclical mood shifts. Studies indicate that BD patients have a peripheral pro-inflammatory state and alterations in glial populations in the brain. We utilized an in vitro model to study inflammation-related phenotypes of astrocytes derived from induced pluripotent stem cells (iPSCs) generated from BD patients and healthy controls. BD astrocytes showed changes in transcriptome and induced a reduction in neuronal activity when co-cultured with neurons. IL-1β-stimulated BD astrocytes displayed a unique inflammatory gene expression signature and increased secretion of IL-6. Conditioned medium from stimulated BD astrocytes reduced neuronal activity, and this effect was partially blocked by IL-6 inactivating antibody. Our results suggest that BD astrocytes are functionally less supportive of neuronal excitability and this effect is partially mediated by IL-6. We confirmed higher IL-6 in blood in a distinct cohort of BD patients, highlighting the potential role of astrocyte-mediated inflammatory signaling in BD neuropathology., Highlights • Bipolar disorder astrocytes are functionally less supportive of neuronal activity • Bipolar disorder astrocytes response to IL-1β is transcriptionally distinct • IL-6 secretion in bipolar disorder astrocytes reduces neuronal activity • Bipolar disorder patients show higher circulating levels of IL-6 in blood, In this article, Gage and collaborators show that astrocytes differentiated from induced pluripotent stem cells generated from bipolar disorder patients are functionally less supportive of neuronal activity. Bipolar disorder astrocytes' response to pro-inflammatory cytokines is characterized by a unique transcriptional response and increased IL-6 secretion that directly and negatively impacted on neuronal activity. Increased peripheral IL-6 was confirmed in a distinct clinical cohort highlighting the potential role of astrocyte-mediated inflammatory signaling in the neuropathology of bipolar disorder.
Published: 2021
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15. Characterisation of early ultrastructural changes in the cerebral white matter of CADASIL small vessel disease using high‐pressure freezing/freeze‐substitution

Author: Nicolas Dupré, Rikesh M. Rajani, Guillaume van Niel, Valérie Domenga-Denier, Xavier Heiligenstein, Anne Joutel, Martinez Rico, Clara, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), and University of Vermont [Burlington]
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, small vessel disease, Histology, Freeze Substitution, inner tongue, Uranyl acetate, CADASIL, Corpus callosum, myelin splitting, Corpus Callosum, Pathology and Forensic Medicine, White matter, Mice, 03 medical and health sciences, chemistry.chemical_compound, Myelin, 0302 clinical medicine, Physiology (medical), medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Myelin Sheath, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Chemistry, CD68, high pressure freezing/freeze-substitution, medicine.disease, White Matter, Hyperintensity, 030104 developmental biology, medicine.anatomical_structure, Neurology, Freeze substitution, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; Aims: The objective of this study was to elucidate the early white matter changes in CADASIL small vessel disease.Methods: We used high-pressure freezing and freeze substitution (HPF/FS) in combination with high-resolution electron microscopy (EM), immunohistochemistry and confocal microscopy of brain specimens from control and CADASIL (TgNotch3R169C ) mice aged 4-15 months to study white matter lesions in the corpus callosum.Results: We first optimised the HPF/FS protocol in which samples were chemically prefixed, frozen in a sample carrier filled with 20% polyvinylpyrrolidone and freeze-substituted in a cocktail of tannic acid, osmium tetroxide and uranyl acetate dissolved in acetone. EM analysis showed that CADASIL mice exhibit significant splitting of myelin layers and enlargement of the inner tongue of small calibre axons from the age of 6 months, then vesiculation of the inner tongue and myelin sheath thinning at 15 months of age. Immunohistochemistry revealed an increased number of oligodendrocyte precursor cells, although only in older mice, but no reduction in the number of mature oligodendrocytes at any age. The number of Iba1 positive microglial cells was increased in older but not in younger CADASIL mice, but the number of activated microglial cells (Iba1 and CD68 positive) was unchanged at any age.Conclusion: We conclude that early WM lesions in CADASIL affect first and foremost the myelin sheath and the inner tongue, suggestive of a primary myelin injury. We propose that those defects are consistent with a hypoxic/ischaemic mechanism.
Published: 2021
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16. Prise en charge des comorbidités cardio-vasculaires chez les jeunes patients souffrant d’une psychose débutante : état des lieux et perspectives thérapeutiques

Author: Boris Chaumette, Oussama Kebir, Marie-Odile Krebs, V. Morin, A. Frajerman, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Groupement de recherche en Psychiatrie (GDR Psychiatrie (3557)), Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), GHU Paris Psychiatrie et Neurosciences, Department of Psychiatry [Montréal], McGill University = Université McGill [Montréal, Canada], Martinez Rico, Clara, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Université Paris Cité (UPCité)
Subjects: Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Diabète, Type 2 diabetes, Premier épisode psychotique, [SCCO]Cognitive science, 03 medical and health sciences, Diabetes mellitus, 0302 clinical medicine, Arts and Humanities (miscellaneous), Weight loss, Elevated blood pressure, Medicine, 2. Zero hunger, First episode, Psychotic disorders, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Trouble psychotique, [SCCO] Cognitive science, Odds ratio, medicine.disease, 3. Good health, 030227 psychiatry, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Drug-naïve, Dyslipidemia, First episode of psychosis, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Hypertension, medicine.symptom, Metabolic syndrome, business, Body mass index, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Dyslipidémie, medicine.drug
Abstract: International audience; Patients with psychiatric disorders have a decrease in their life expectancy. Excess mortality of patients with schizophrenia was demonstrated by a meta-analysis in the late 1990s and has not decreased for the past 30years. A recent meta-analysis including nearly 250,000 patients with schizophrenia found an average decrease in life expectancy of 14.5years (CI95: 11,2-17,8), more important for men than for women: 15.9 (CI95: 13,8-18,0) vs 13.6 (CI95: 11,4-15,8). A closer look at the somatic comorbidities, including metabolic syndrome, and investigation of causes of death of these patients highlighted already well-known factors, namely late diagnosis and insufficient treatment of physical diseases, side effects of antipsychotics, unhealthy lifestyle (poor diet, smoking, excessive alcohol consumption and lack of exercise), and higher risk of suicide and accident. Concerning ultra-high risk (UHR) patients, a 2016 meta-analysis of 47 studies evaluated the cardiovascular risk factors. They reported a higher prevalence of smoking in UHR (odds ratio 2,3) and a lower level of physical activity associated with a normal BMI (Body Mass Index) compared to the control population. A meta-analysis about patients with a first episode of psychosis (FEP) found reduced total and LDL cholesterol levels and an increased triglyceride level compared to the control population. One study found alteration of the fasting plasmatic levels of glucose and insulin, as well as insulin resistance in FEP patients, compared to controls albeit the HbA1c level was not significantly different. A meta-analysis reported a prevalence of metabolic syndrome of 10 % in FEP or drug naïve patients versus 35 % and 20 % in treated and untreated patients with chronic schizophrenia respectively. Somatic comorbidities usually appear during the first two years of the disease. Some interventions have proven their efficacy in reducing the occurrence of metabolic syndrome and other cardiovascular risk factors. For instance, metformin, a treatment for type 2 diabetes that is allowed from the age of 10, has shown benefits in children and adolescents receiving second-generation antipsychotics in a recent meta-analysis, with a mean weight loss of 3.23kg (IC95 % -5.59 -0.86) after 16 weeks. Dietary-hygienic interventions are also effective in reducing cardiovascular risk. Other interventions such as omega-3 supplementation, vitamin D, N-acetylcysteine, and fasting have not proven to be effective. Comprehensive care programs have been developed to promote somatic care in psychiatric patients, such as the Canadian HeAL (Healthy Active Lives) program. These programs are more effective when proposed from the beginning of the disease and the introduction of antipsychotics. In this review, because there is no French recommendation, we translate a tool for the prescription of metformin and the Canadian recommendations from the HeAL program. Generalization of these programs to all young psychotic patients could improve their life expectancy and reduce the overall mortality. Prevention of cardiovascular risk factors and cardio-metabolic monitoring of treatments must be part of the standard of care in early psychosis. These programs aim at providing patients with the quality of somatic and mental care they are entitled to. This requires the involvement of all stakeholders, including patients and their families but also psychiatrists and other caregivers.
Published: 2020
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17. A missense mutation in the CSTF2 gene that impairs the function of the RNA recognition motif and causes defects in 3′ end processing is associated with intellectual disability in humans

Author: Pierre Billuart, Clinton C. MacDonald, Vera M. Kalscheuer, Thierry Bienvenu, Michael P. Latham, Petar N. Grozdanov, Marie-Ange Delrue, Elahe Masoumzadeh, Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Max Planck Institute for Molecular Genetics (MPIMG), Max-Planck-Gesellschaft, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Sainte Justine [Montréal], Martinez Rico, Clara, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Male, Polyadenylation, AcademicSubjects/SCI00010, [SDV]Life Sciences [q-bio], Mutation, Missense, Biology, 03 medical and health sciences, Mice, 0302 clinical medicine, Intellectual Disability, Genetics, Missense mutation, Animals, Humans, Child, Gene, Molecular Biology, 3' Untranslated Regions, 030304 developmental biology, 0303 health sciences, Messenger RNA, RNA recognition motif, MRNA cleavage, Three prime untranslated region, RNA, Brain, Pedigree, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Cleavage Stimulation Factor, Female, 030217 neurology & neurosurgery, RNA Recognition Motif, HeLa Cells, Protein Binding
Abstract: CSTF2 encodes an RNA-binding protein that is essential for mRNA cleavage and polyadenylation (C/P). No disease-associated mutations have been described for this gene. Here, we report a mutation in the RNA recognition motif (RRM) of CSTF2 that changes an aspartic acid at position 50 to alanine (p.D50A), resulting in intellectual disability in male patients. In mice, this mutation was sufficient to alter polyadenylation sites in over 1300 genes critical for brain development. Using a reporter gene assay, we demonstrated that C/P efficiency of CSTF2D50A was lower than wild type. To account for this, we determined that p.D50A changed locations of amino acid side chains altering RNA binding sites in the RRM. The changes modified the electrostatic potential of the RRM leading to a greater affinity for RNA. These results highlight the significance of 3′ end mRNA processing in expression of genes important for brain plasticity and neuronal development.
Published: 2020
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18. Experience with postmortem computed tomography in the forensic analysis of the November 2015 Paris attacks

Author: Lilia Hamza, Catherine Oppenheim, Tania Delabarde, Myriam Edjlali, Bertrand Ludes, J.F. Meder, Laurence Legrand, Ghazi Hmeydia, Laura W de Jong, Joseph Benzakoun, Pôle Universitaire d'Imagerie Post-Mortem [Paris] (Université de Paris), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), GHU Paris Psychiatrie et Neurosciences, Institut de Médecine Légale - IML (Paris, France), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie, anthropologie, biométrie, épigénétique, lignées : De la diversité des populations à l'individu, de l'identification à l'identité (BABEL - FRE 2029), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Biologie, anthropologie, biométrie, épigénétique, lignées : De la diversité des populations à l'individu, de l'identification à l'identité (BABEL), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Martinez Rico, Clara
Subjects: medicine.medical_specialty, History, Short Communications, Computed tomography, 01 natural sciences, Biochemistry, Genetics and Molecular Biology (miscellaneous), Pathology and Forensic Medicine, Analytical Chemistry, 03 medical and health sciences, 0302 clinical medicine, medicine, Medical physics, 030216 legal & forensic medicine, Physical and Theoretical Chemistry, ComputingMilieux_MISCELLANEOUS, [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, K5000-5582, medicine.diagnostic_test, 010401 analytical chemistry, Tower (mathematics), respiratory tract diseases, 0104 chemical sciences, Criminal law and procedure, Forensic science, Psychiatry and Mental health, Anthropology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Other, Public aspects of medicine, RA1-1270, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Several reports discuss the added value of postmortem computed tomography (PMCT) in the forensic analysis of mass fatality incidents (MFIs), such as the 2009 Victorian bushfires, the Grenfell tower...
Published: 2020
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19. Perfusion Imaging to Select Patients with Large Ischemic Core for Mechanical Thrombectomy

Author: François Zhu, Aymeric Rouchaud, Wagih Benhassen, Joseph Benzakoun, Kevin Janot, Jean François Hak, Florent Gariel, Lili Detraz, Gaultier Marnat, Cyril Dargazanli, Gregoire Boulouis, Charline Perot, Basile Kerleroux, Romain Bourcier, Géraud Forestier, Dimitri Daly-Eraya, Johannes Kaesmacher, Pasquale Mordasini, Benjamin Gory, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], CHU Limoges, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Bern University Hospital [Berne] (Inselspital), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Martinez Rico, Clara
Subjects: medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, [SDV]Life Sciences [q-bio], 610 Medicine & health, Perfusion scanning, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, Internal medicine, Medicine, Acute stroke, Endovascular treatment, 030212 general & internal medicine, Prospective cohort study, Thrombectomy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Ischemic stroke, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Odds ratio, Perfusion imaging, Confidence interval, [SDV] Life Sciences [q-bio], lcsh:RC666-701, Cardiology, Original Article, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Perfusion, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Cohort study
Abstract: Background and Purpose Patients with acute ischemic stroke, proximal vessel occlusion and a large ischemic core at presentation are commonly not considered for mechanical thrombectomy (MT). We tested the hypothesis that in patients with baseline large infarct cores, identification of remaining penumbral tissue using perfusion imaging would translate to better outcomes after MT.Methods This was a multicenter, retrospective, core lab adjudicated, cohort study of adult patients with proximal vessel occlusion, a large ischemic core volume (diffusion weighted imaging volume ≥70 mL), with pre-treatment magnetic resonance imaging perfusion, treated with MT (2015 to 2018) or medical care alone (controls; before 2015). Primary outcome measure was 3-month favorable outcome (defined as a modified Rankin Scale of 0–3). Core perfusion mismatch ratio (CPMR) was defined as the volume of critically hypo-perfused tissue (Tmax >6 seconds) divided by the core volume. Multivariable logistic regression models were used to determine factors that were independently associated with clinical outcomes. Outputs are displayed as adjusted odds ratio (aOR) and 95% confidence interval (CI).Results A total of 172 patients were included (MT n=130; Control n=42; mean age 69.0±15.4 years; 36% females). Mean core-volume and CPMR were 102.3±36.7 and 1.8±0.7 mL, respectively. As hypothesized, receiving MT was associated with increased probability of favorable outcome and functional independence, as CPMR increased, a difference becoming statistically significant above a mismatch-ratio of 1.72. Similarly, receiving MT was also associated with favorable outcome in the subgroup of 74 patients with CPMR >1.7 (aOR, 8.12; 95% CI, 1.24 to 53.11; P=0.028). Overall (prior to stratification by CPMR) 73 (42.4%) patients had a favorable outcome at 3 months, with no difference amongst groups.Conclusions In patients currently deemed ineligible for MT due to large infarct ischemic cores at baseline, CPMR identifies a subgroup strongly benefiting from MT. Prospective studies are warranted.
Published: 2020
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20. The identification, assessment and management of difficult-to-treat depression: An international consensus statement

Author: Allan H. Young, Gin S Malhi, RH McAllister-Williams, Eduard Vieta, Philip Gorwood, Afzal Javed, Peter Falkai, Andrew Papadopoulos, A. J. Rush, Celso Arango, Jair C. Soares, Malcolm Hopwood, Pierre Blier, Koen Demyttenaere, Siegfried Kasper, Martinez Rico, Clara, Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Instituto de Investigación Sanitaria Gregorio Marañón [Madrid, Spain] ( IiSGM), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), University of Ottawa [Ottawa], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Ludwig Maximilian University [Munich] (LMU), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Melbourne, University of Warwick [Coventry], Medizinische Universität Wien = Medical University of Vienna, The University of Sydney, Royal North Shore Hospital (RNSH), The University of Texas Health Science Center at Houston (UTHealth), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), King‘s College London, South London and Maudsley NHS Foundation Trust, Somerset Partnership NHS Foundation Trust, Duke University [Durham], Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Duke-NUS Medical School [Singapore], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: VAGUS NERVE-STIMULATION, TRANSCRANIAL MAGNETIC STIMULATION, medicine.medical_specialty, Consensus, 2016 CLINICAL GUIDELINES, SEROTONIN REUPTAKE INHIBITORS, medicine.medical_treatment, Clinical Neurology, GENERALIZED ANXIETY DISORDER, Difficult-to-treat depression, Depressive Disorder, Treatment-Resistant, DOUBLE-BLIND, 03 medical and health sciences, POSTTRAUMATIC-STRESS-DISORDER, 0302 clinical medicine, Pharmacotherapy, Diagnosis, medicine, Humans, Symptom control, COGNITIVE-BEHAVIORAL THERAPY, Intensive care medicine, Neurostimulation, Psychiatry, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Science & Technology, Conceptualization, Depression, Clinical management, business.industry, Treatment options, MAJOR DEPRESSION, medicine.disease, 3. Good health, 030227 psychiatry, Psychotherapy, Psychiatry and Mental health, Clinical Psychology, Management implications, Quality of Life, TREATMENT-RESISTANT DEPRESSION, Neurosciences & Neurology, Treatment-resistant depression, business, Life Sciences & Biomedicine, Psychosocial, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: BACKGROUND: Many depressed patients are not able to achieve or sustain symptom remission despite serial treatment trials - often termed "treatment resistant depression". A broader, perhaps more empathic concept of "difficult-to-treat depression" (DTD) was considered. METHODS: A consensus group discussed the definition, clinical recognition, assessment and management implications of the DTD heuristic. RESULTS: The group proposed that DTD be defined as "depression that continues to cause significant burden despite usual treatment efforts". All depression management should include a thorough initial assessment. When DTD is recognized, a regular reassessment that employs a multi-dimensional framework to identify addressable barriers to successful treatment (including patient-, illness- and treatment-related factors) is advised, along with specific recommendations for addressing these factors. The emphasis of treatment, in the first instance, shifts from a goal of remission to optimal symptom control, daily psychosocial functional and quality of life, based on a patient-centred approach with shared decision-making to enhance the timely consideration of all treatment options (including pharmacotherapy, psychotherapy, neurostimulation, etc.) to optimize outcomes when sustained remission is elusive. LIMITATIONS: The recommended definition and management of DTD is based largely on expert consensus. While DTD would seem to have clinical utility, its specificity and objectivity may be insufficient to define clinical populations for regulatory trial purposes, though DTD could define populations for service provision or phase 4 trials. CONCLUSIONS: DTD provides a clinically useful conceptualization that implies a search for and remediation of specific patient-, illness- and treatment obstacles to optimizing outcomes of relevance to patients. ispartof: Journal of Affective Disorders vol:267 pages:264-282 ispartof: location:Netherlands status: published
Published: 2020
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21. Tool-use Extends Peripersonal Space Boundaries in Schizophrenic Patients

Author: Francesca Ferroni, Martina Ardizzi, Francesca Magnani, Francesca Ferri, Nunzio Langiulli, Francesca Rastelli, Valeria Lucarini, Francesca Giustozzi, Roberto Volpe, Carlo Marchesi, Matteo Tonna, Vittorio Gallese, Università degli studi di Parma = University of Parma (UNIPR), Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Local Health Service [Parma, Italy] (LHS), and Martinez Rico, Clara
Subjects: bodily self, Tool Use Behavior, multisensory integration, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Psychiatry and Mental health, self-disorder, Personal Space, Acoustic Stimulation, Touch, plasticity, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Physical Stimulation, Space Perception, Humans, self-other boundaries
Abstract: Background and Hypothesis A primary disruption of the bodily self is considered a core feature of schizophrenia (SCZ). The “disembodied” self might be underpinned by inefficient body-related multisensory integration processes, normally occurring in the peripersonal space (PPS), a plastic sector of space surrounding the body whose extent is altered in SCZ. Although PPS is a malleable interface marking the perceptual border between self and others, no study has addressed the potential alteration of its plasticity in SCZ. We investigated the plasticity of PPS in SCZ patients after a motor training with a tool in the far space. Study Design Twenty-seven SCZ patients and 32 healthy controls (HC) underwent an audio-tactile task to estimate PPS boundary before (Session 1) and after (Session 3) the tool-use. Parameters of PPS, including the size and the slope of the psychometric function describing audio-tactile RTs as a function of the audio-tactile distances, were estimated. Study Results Results confirm a narrow PPS extent in SCZ. Surprisingly, we found PPS expansion in both groups, thus showing for the first time a preserved PPS plasticity in SCZ. Patients experienced a weaker differentiation from others, as indicated by a shallower PPS slope at Session 1 that correlated positively with negative symptoms. However, at Session 3, patients marked their bodily boundary in a steeper way, suggesting a sharper demarcation of PPS boundaries after the action with the tool. Conclusions These findings highlight the importance of investigating the multisensory and motor roots of self-disorders, paving the way for future body-centred rehabilitation interventions that could improve patients’ altered body boundary.
Published: 2022
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22. Role of SNAREs in Unconventional Secretion—Focus on the VAMP7-Dependent Secretion

Author: Vats, Somya, Galli, Thierry, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, and Martinez Rico, Clara
Subjects: unconventional protein secretion, SNARE, neurodegeneration, VAMP7, cancer, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cell Biology, Developmental Biology
Abstract: International audience; Intracellular membrane protein trafficking is crucial for both normal cellular physiology and cell-cell communication. The conventional secretory route follows transport from the Endoplasmic reticulum (ER) to the plasma membrane via the Golgi apparatus. Alternative modes of secretion which can bypass the need for passage through the Golgi apparatus have been collectively termed as Unconventional protein secretion (UPS). UPS can comprise of cargo without a signal peptide or proteins which escape the Golgi in spite of entering the ER. UPS has been classified further depending on the mode of transport. Type I and Type II unconventional secretion are non-vesicular and non-SNARE protein dependent whereas Type III and Type IV dependent on vesicles and on SNARE proteins. In this review, we focus on the Type III UPS which involves the import of cytoplasmic proteins in membrane carriers of autophagosomal/endosomal origin and release in the extracellular space following SNARE-dependent intracellular membrane fusion. We discuss the role of vesicular SNAREs with a strong focus on VAMP7, a vesicular SNARE involved in exosome, lysosome and autophagy mediated secretion. We further extend our discussion to the role of unconventional secretion in health and disease with emphasis on cancer and neurodegeneration.
Published: 2022
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23. Feasibility of large-scale eOSCES: the simultaneous evaluation of 500 medical students during a mock examination

Author: Donia Bouzid, Tristan Mirault, Aiham Ghazali, Léonore Muller, Enrique Casalino, Nathan Peiffer Smadja, Baptiste Auber, Mathias Guerin, Charles Henri Sambet, Isabelle Etienne, Victoire De Lastours, Cécile Badoual, Cédric Lemogne, Philippe Ruszniewski, null Université Paris Cité’ OSCE study group, Albert Faye, Alexy Tran Dinh, Martinez Rico, Clara, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Account executive- Higher Education- Zoom [San José, CA, USA] (AEHEZ), Hôpital Beaujon [AP-HP], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Hôtel-Dieu [Paris], and Hôpital Robert Debré
Subjects: digital training, Students, Medical, COVID-19, medical students, General Medicine, Education, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Surveys and Questionnaires, Feasibility Studies, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Objective structured clinical examination, Pandemics, innovative
Abstract: International audience; The COVID-19 pandemic has led health schools to cancel many on-site training and exams. Teachers were looking for the best option to carry out online OSCEs, and Zoom was the obvious choice since many schools have used it to pursue education purposes. Methods: We conducted a feasibility study during the 2020-2021 college year divided into six pilot phases and the large-scale eOSCEs on Zoom on June 30th, 2021. We developed a specific application allowing us to mass create Zoom meetings and built an entire organization, including a technical support system (an SOS room and catching-up rooms) and teachers' training sessions. We assessed satisfaction via an online survey. Results: On June 30th, 531/794 fifthyear medical students (67%) participated in a large-scale mock exam distributed in 135 Zoom meeting rooms with the mobilization of 298 teachers who either participated in the Zoom meetings as standardized patients (N =135, 45%) or examiners (N =135, 45%) or as supervisors in the catching-up rooms (N =16, 6%) or the SOS room (N =12, 4%). In addition, 32/270 teachers (12%) experienced difficulties connecting to their Zoom meetings and sought the help of an SOS room member. Furthermore, 40/531 students (7%) were either late to their station or had technical difficulties and declared those issues online and were welcomed in one of the catching-up rooms to perform their eOSCE stations. Additionally, 518/531 students (98%) completed the entire circuit of three stations, and 225/531 students (42%) answered the online survey. Among them, 194/225 (86%) found eOSCES helpful for training and expressed their satisfaction with this experience. Conclusion: Organizing large-scale eOSCEs on Zoom is feasible with the appropriate tools. In addition, eOCSEs should be considered complementary to on-site OSCEs and to train medical students in telemedicine.
Published: 2022
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24. BRAIN ANOMALIES IN EARLY PSYCHOSIS: FROM SECONDARY TO PRIMARY PSYCHOSIS

Author: Iftimovici, Anton, Chaumette, Boris, Duchesnay, Edouard, Krebs, Marie-Odile, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), GHU Paris Psychiatrie et Neurosciences, and Martinez Rico, Clara
Subjects: Adult, Brain Diseases, Adolescent, Cognitive Neuroscience, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Brain, Brain anomalies, Neuroimaging, Pathophysiology, Behavioral Neuroscience, Young Adult, Neuropsychology and Physiological Psychology, Psychotic Disorders, Case-Control Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Primary and secondary early psychoses
Abstract: International audience; Brain anomalies are frequently found in early psychoses. Although they may remain undetected for many years, their interpretation is critical for differential diagnosis. In secondary psychoses, their identification may allow specific management. They may also shed light on various pathophysiological aspects of primary psychoses. Here we reviewed cases of secondary psychoses associated with brain anomalies, reported over a 20-year period in adolescents and young adults aged 13 to 30 years old. We considered age at first psychotic symptoms, relevant medical history, the nature of psychiatric symptoms, clinical red flags, the nature of the brain anomaly reported, and the underlying disease. We discuss the relevance of each brain area in light of normal brain function, recent case-control studies, and postulated pathophysiology. We show that anomalies in all regions, whether diffuse, multifocal, or highly localized, may lead to psychosis, without necessarily being associated with non-psychiatric symptoms. This underlines the interest of neuroimaging in the initial workup, and supports the hypothesis of psychosis as a global network dysfunction that involves many different regions.
Published: 2022
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25. Dopamine-induced pruning in monocyte-derived-neuronal-like cells (MDNCs) from patients with schizophrenia

Author: Alfredo Bellon, Vincent Feuillet, Alonso Cortez-Resendiz, Faycal Mouaffak, Lan Kong, L. Elliot Hong, Lilian De Godoy, Therese M. Jay, Anne Hosmalin, Marie-Odile Krebs, Penn State Health Milton S. Hershey Medical Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), EPS Ville-Evrard - Pavillon Provence [Saint-Denis], University of Maryland School of Medicine, University of Maryland System, Baptist Hospital [Miami, FL, USA] (BH), GHU Paris Psychiatrie et Neurosciences, Hosmalin, Anne, Pôle de Psychiatrie d'Adultes 93G04 [Saint-Denis] (PSA93G04), Pôle hospitalo-universitaire d’Evaluation Prévention et Innovation Thérapeutique [Paris] (PEPIT), GHU Paris Psychiatrie & Neurosciences, and Martinez Rico, Clara
Subjects: Neurons, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, Dopamine, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Reproducibility of Results, Monocytes, Cellular and Molecular Neuroscience, Psychiatry and Mental health, nervous system, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Schizophrenia, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular Biology
Abstract: The long lapse between the presumptive origin of schizophrenia (SCZ) during early development and its diagnosis in late adolescence has hindered the study of crucial neurodevelopmental processes directly in living patients. Dopamine, a neurotransmitter consistently associated with the pathophysiology of SCZ, participates in several aspects of brain development including pruning of neuronal extensions. Excessive pruning is considered the cause of the most consistent finding in SCZ, namely decreased brain volume. It is therefore possible that patients with SCZ carry an increased susceptibility to dopamine’s pruning effects and that this susceptibility would be more obvious in the early stages of neuronal development when dopamine pruning effects appear to be more prominent. Obtaining developing neurons from living patients is not feasible. Instead, we used Monocyte-Derived-Neuronal-like Cells (MDNCs) as these cells can be generated in only 20 days and deliver reproducible results. In this study, we expanded the number of individuals in whom we tested the reproducibility of MDNCs. We also deepened the characterization of MDNCs by comparing its neurostructure to that of human developing neurons. Moreover, we studied MDNCs from 12 controls and 13 patients with SCZ. Patients’ cells differentiate more efficiently, extend longer secondary neurites and grow more primary neurites. In addition, MDNCs from medicated patients expresses less D1R and prune more primary neurites when exposed to dopamine. Haloperidol did not influence our results but the role of other antipsychotics was not examined and thus, needs to be considered as a confounder.
Published: 2022
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26. Post-trauma behavioral phenotype predicts the degree of vulnerability to fear relapse after extinction in male rats

Author: Fanny Demars, Ralitsa Todorova, Gabriel Makdah, Antonin Forestier, Marie-Odile Krebs, Bill P. Godsil, Thérèse M. Jay, Sidney I. Wiener, Marco N. Pompili, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, École nationale vétérinaire - Alfort (ENVA), Martinez Rico, Clara, Institut de Neurosciences des Systèmes (INS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, [SDV.BA] Life Sciences [q-bio]/Animal biology, animal model, [SDV.BA]Life Sciences [q-bio]/Animal biology, Conditioning, Classical, vulnerability, Fear, interindividual differences, General Biochemistry, Genetics and Molecular Biology, Extinction, Psychological, Rats, Phenotype, ethological relevance, Recurrence, fear relapse, Animals, General Agricultural and Biological Sciences, transcriptional profiling
Abstract: International audience; Current treatments for trauma-related disorders remain ineffective for many patients.1,2 Fear extinction deficiency is a prominent feature of these diseases,3 and many behavioral treatments rely on extinction training.4,5 However, in many patients, therapy is followed by a relapse of symptoms, and the underpinnings of such interindividual variations in vulnerability to relapse remain unknown.6-8 Here, we modeled interindividual differences in post-therapy fear relapse with an ethologically relevant trauma recovery paradigm. After fear conditioning, male rats underwent fear extinction while foraging in a large enriched arena, permitting the expression of a wide spectrum of behaviors. An automated multidimensional behavioral assessment revealed that post-conditioning fear response profiles clustered into two groups: some animals expressed fear by freezing more, whereas others darted more, as if fleeing from danger. Remarkably, the tendency of an animal to dart or to freeze after CS presentation during the first extinction session was, respectively, associated with stronger or weaker fear renewal. Moreover, genome-wide transcriptional profiling revealed that these groups differentially regulated specific sets of genes, some of which were previously implicated in anxiety and trauma-related disorders. Our results suggest that post-trauma behavioral phenotypes and the associated gene expression landscapes can serve as markers of fear relapse susceptibility and thus may be instrumental for future development of more effective treatments for psychiatric patients.
Published: 2022
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27. Comparing Two Neurodevelopmental Disorders Linked to CK2: Okur-Chung Neurodevelopmental Syndrome and Poirier-Bienvenu Neurodevelopmental Syndrome—Two Sides of the Same Coin?

Author: Demetra Ballardin, Jose M. Cruz-Gamero, Thierry Bienvenu, Heike Rebholz, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Danube Private University [Krems, Autriche] (DPU), and Martinez Rico, Clara
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, autism-spectrum disorders (ASD), OCNDS, POBINDS, CK2 (casein kinase II), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biochemistry, Genetics and Molecular Biology (miscellaneous), Molecular Biology, Biochemistry, NDD-neurodevelopmental disorder, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: In recent years, variants in the catalytic and regulatory subunits of the kinase CK2 have been found to underlie two different, yet symptomatically overlapping neurodevelopmental disorders, termed Okur-Chung neurodevelopmental syndrome (OCNDS) and Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). Both conditions are predominantly caused by de novo missense or nonsense mono-allelic variants. They are characterized by a generalized developmental delay, intellectual disability, behavioral problems (hyperactivity, repetitive movements and social interaction deficits), hypotonia, motricity and verbalization deficits. One of the main features of POBINDS is epilepsies, which are present with much lower prevalence in patients with OCNDS. While a role for CK2 in brain functioning and development is well acknowledged, these findings for the first time clearly link CK2 to defined brain disorders. Our review will bring together patient data for both syndromes, aiming to link symptoms with genotypes, and to rationalize the symptoms through known cellular functions of CK2 that have been identified in preclinical and biochemical contexts. We will also compare the symptomatology and elaborate the specificities that distinguish the two syndromes.
Published: 2022
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28. COVID-19 pandemic's impact on French Health Students: A cross-sectional study during the third wave

Author: Ariel Frajerman, Franck Rolland, Bruno Falissard, Gilles Bertschy, Bertrand Diquet, Donata Marra, Hôpital Bicêtre, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Santé mentale et santé publique (SMSP - U1178), Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, CHU Strasbourg, Fédération de Médecine Translationelle de Strasbourg (FMTS), Institut de Biologie en Santé (PHB-IRIS) [CHU Angers] (IBS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Martinez Rico, Clara
Subjects: Male, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Students, Medical, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Health students, COVID-19, Psychological distress, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Humans, Mental health, Pandemics, COVID 19, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: COVID19 pandemic had a huge impact on global mental health. Health students, because of their age and status, are a more at-risk population. National survey during the first wave already found high levels of psychological distress. Objective: This nationwide study aimed to assess health's student mental health during the third wave in France. Methods: We did an online national cross-sectional study, which addressed all health students from April 4th to May 11th 2021. The questionnaire included sociodemographic and work conditions questions, Kessler 6 scale, and numeric scales. Results: 16,937 students answered, including 54% nurse and 16% medical students. Regarding K6 scale, 14% have moderate (8-12) and 83% high (≥13) level of psychological distress. In multivariate analysis, being a man (OR = 0.54, 95% CI [0.48; 0.60], p < 0.001) and not living alone (OR = 0.71, 95% CI [0.62; 0.82], p < 0.001), are associated with a reduced risk of psychological distress. Not having the ability to isolate themselves (OR = 1.58, 95% CI [1.39; 1.81], p < 0.001), and having low (OR = 2.31, 95% CI [2.08; 2.56], p < 0.001) or important (OR = 4.58, 95% CI [3.98; 5.29], p < 0.001) financial difficulties are associated with an increased risk of psychological distress. Limitations: The response rate was low regarding the target population (300,000 health students). Conclusion: Compared to the first national survey, we noticed mental health deterioration. Psychological distress (83% high level versus 21%), substance use (21% versus 13%), and psychotropic treatment use (18% versus 7.3%) hugely increased. These results highlighted the need to increase support actions for health students.
Published: 2022
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29. Mortality in people with schizophrenia: a systematic review and meta‐analysis of relative risk and aggravating or attenuating factors

Author: Christoph U. Correll, Marco Solmi, Giovanni Croatto, Lynne Kolton Schneider, S. Christy Rohani‐Montez, Leanne Fairley, Nathalie Smith, István Bitter, Philip Gorwood, Heidi Taipale, Jari Tiihonen, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Donald and Barbara Zucker School of Medicine at Hofstra/Northwell [Hempstead, NY, USA], Zucker Hillside Hospital [Glen Oaks, NY, USA] (ZHH), University of Ottawa [Ottawa], The Ottawa Hospital, AULSS 3 Serenissima [Venice, Italy] (Mestre), WebMD Global LLC [London, UK], Semmelweis University [Budapest], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Karolinska Institutet [Stockholm], University of Eastern Finland, and Martinez Rico, Clara
Subjects: cardiovascular disease, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, clozapine, substance use disorder, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, long-acting injectable antipsychotics, Research Reports, mortality, Psychiatry and Mental health, antipsychotics, comorbidity, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, first-episode schizophrenia, Schizophrenia, psychosis, Pshychiatric Mental Health, physical health, suicide, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; People with schizophrenia die 15-20 years prematurely. Understanding mortality risk and aggravating/attenuating factors is essential to reduce this gap. We conducted a systematic review and random-effects meta-analysis of prospective and retrospective, nationwide and targeted cohort studies assessing mortality risk in people with schizophrenia versus the general population or groups matched for physical comorbidities or groups with different psychiatric disorders, also assessing moderators. Primary outcome was all-cause mortality risk ratio (RR); key secondary outcomes were mortality due to suicide and natural causes. Other secondary outcomes included any other specific-cause mortality. Publication bias, subgroup and meta-regression analyses, and quality assessment (Newcastle-Ottawa Scale) were conducted. Across 135 studies spanning from 1957 to 2021 (schizophrenia: N=4,536,447; general population controls: N=1,115,600,059; other psychiatric illness controls: N=3,827,955), all-cause mortality was increased in people with schizophrenia versus any non-schizophrenia control group (RR=2.52, 95% CI: 2.38-2.68, n=79), with the largest risk in first-episode (RR=7.43, 95% CI: 4.02-13.75, n=2) and incident (i.e., earlier-phase) schizophrenia (RR=3.52, 95% CI: 3.09-4.00, n=7) versus the general population. Specific-cause mortality was highest for suicide or injury-poisoning or undetermined non-natural cause (RR=9.76-8.42), followed by pneumonia among natural causes (RR=7.00, 95% CI: 6.79-7.23), decreasing through infectious or endocrine or respiratory or urogenital or diabetes causes (RR=3 to 4), to alcohol or gastrointestinal or renal or nervous system or cardio-cerebrovascular or all natural causes (RR=2 to 3), and liver or cerebrovascular, or breast or colon or pancreas or any cancer causes (RR=1.33 to 1.96). All-cause mortality increased slightly but significantly with median study year (beta=0.0009, 95% CI: 0.001-0.02, p=0.02). Individuals with schizophrenia
Published: 2022
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30. Hippocampal Excitatory Synaptic Transmission and Plasticity Are Differentially Altered during Postnatal Development by Loss of the X-Linked Intellectual Disability Protein Oligophrenin-1

Author: Noemie Cresto, Nicolas Lebrun, Florent Dumont, Franck Letourneur, Pierre Billuart, Nathalie Rouach, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Ingénierie et Plateformes au Service de l'Innovation Thérapeutique (IPSIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Martinez Rico, Clara
Subjects: Mice, Knockout, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, intellectual disability, Oligophrenin-1, synaptic transmission, plasticity, hippocampus, development, GTPase-Activating Proteins, Nuclear Proteins, General Medicine, Cytoskeletal Proteins, Mice, Animals, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Oligophrenin-1 (OPHN1) is a Rho-GTPase-activating protein (RhoGAP), whose mutations are associated with X-linked intellectual disability (XLID). OPHN1 is enriched at the synapse in both pre- and postsynaptic compartments, where it regulates the RhoA/ROCK/MLC2 signaling pathway, playing a critical role in cytoskeleton remodeling and vesicle recycling. Ophn1 knockout (KO) adult mice display some behavioral deficits in multiple tasks, reminiscent of some symptoms in the human pathology. We also previously reported a reduction in dendritic spine density in the adult hippocampus of KO mice. Yet the nature of the deficits occurring in these mice during postnatal development remains elusive. Here, we show that juvenile KO mice present normal basal synaptic transmission, but altered synaptic plasticity, with a selective impairment in long-term depression, but no change in long-term potentiation. This contrasts with the functional deficits that these mice display at the adult stage, as we found that both basal synaptic transmission and long-term potentiation are reduced at later stages, due to presynaptic alterations. In addition, the number of excitatory synapses in adult is increased, suggesting some unsuccessful compensation. Altogether, these results suggest that OPHN1 function at synapses is differentially affected during maturation of the brain, which provides some therapeutic opportunities for early intervention.
Published: 2022
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31. Characterization of Depressive Symptoms Trajectories After Breast Cancer Diagnosis in Women in France

Author: Cécile Charles, Aurélie Bardet, Alicia Larive, Philip Gorwood, Nicolas Ramoz, Emilie Thomas, Alain Viari, Marina Rousseau-Tsangaris, Agnès Dumas, Gwenn Menvielle, Sibille Everhard, Anne-Laure Martin, Seyive-yvon-arnauld Gbenou, Julie Havas, Mayssam El-Mouhebb, Antonio Di Meglio, Fabrice André, Barbara Pistilli, Charles Coutant, Paul Cottu, Asma Mérimèche, Florence Lerebours, Olivier Tredan, Laurence Vanlemmens, Christelle Jouannaud, Christelle Levy, Ines Vaz-Luis, Stefan Michiels, Sarah Dauchy, Institut Bergonié [Bordeaux], UNICANCER, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut Curie [Paris], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut Curie - Saint Cloud (ICSC), Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut Jean Godinot [Reims], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Martinez Rico, Clara
Subjects: Male, Depression, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, Middle Aged, Cohort Studies, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Prevalence, Quality of Life, Humans, Female, Child
Abstract: International audience; Importance: Breast cancer (BC) diagnosis and treatment expose patients to a 5-fold higher risk of depression compared with the general population, with an estimated prevalence of 10% to 25%. A depressive episode in patients with BC has implications for the tolerance of and adherence to treatment, impairing quality of life and reducing life expectancy.Objective: To identify and characterize distinct longitudinal patterns of depressive symptoms in patients with BC from diagnosis to 3 years after treatment.Design, settings, and participants: The CANTO-DEePRESS (Deeper in the Understanding and Prevention of Depression in Breast Cancer Patients) cohort study included women in the French multicenter CANTO (CANcer TOxicities) cohort study (conducted between March 20, 2012 and December 11, 2018), who were 18 years or older with invasive stage I to III BC and no previous BC treatment. The study aimed to characterize toxicities over a 5-year period following stage I to III primary BC treatment. Assessments of depressive symptoms were performed on a subset of patients with available data at diagnosis and at least 2 other time points. All data were extracted from the CANTO database on October 1, 2020.Main outcomes and measures: The primary outcome was the level of depressive symptoms at each assessment time point measured with the Hospital Anxiety and Depression Scale and depression subscale at BC diagnosis and at 3 to 6, 12, and 36 months after the end of treatment. The group-based trajectory modeling was used to identify trajectory groups, and multinomial logistic regression models were used to characterize the following factors associated with trajectory group affiliation: demographic, socioeconomic, clinical, lifestyle, and quality-of-life data.Results: A total of 4803 women (mean [SD] age, 56.2 [11.2] years; 2441 patients [50.8%] with stage I BC) were included in the study. Six trajectory groups that described the heterogeneity in the expression of depressive symptoms were identified: noncases with no expression of symptoms (n = 2634 [54.8%]), intermediate worsening (1076 [22.4%]), intermediate improvement (480 [10.0%]), remission (261 [5.4%]), delayed occurrence (200 [4.2%]), and stable depression (152 [3.2%]). HADS-D scores at diagnosis were consistently associated with the 5 depressive trajectory group affiliations, with an estimated higher probability per point increase of experiencing subthreshold or clinically significant depressive symptoms between diagnosis and the 3 years after the end of BC treatment. The higher probabilities ranged from 1.49 (95% CI, 1.43-1.54) for the intermediate worsening group to 10.53 (95% CI, 8.84-12.55) for the stable depression group. Trajectory groups with depressive symptoms differed from the noncases group without symptoms by demographic and clinical factors, such as having dependent children, lower household income, cancer stage, family history of BC, previous psychiatric hospitalizations, obesity, smoking status, higher levels of fatigue, and depression at diagnosis.Conclusions and relevance: In this cohort study, nearly a third of patients with BC experienced temporary or lasting significant depressive symptoms during and after treatment. Improving early identification of women at risk of developing long-term or delayed depression is therefore critical to increase quality of life and overall survival. Subjected to validation, this study is an important first step toward personalized care of patients with BC at risk of depression.
Published: 2022
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32. Zebrafish Melanoma-Derived Interstitial EVs Are Carriers of ncRNAs That Induce Inflammation

Author: Valentina Biagini, Federica Busi, Viviana Anelli, Emanuela Kerschbamer, Marta Baghini, Elena Gurrieri, Michela Notarangelo, Isabella Pesce, Guillaume van Niel, Vito G. D’Agostino, Marina Mione, University of Trento [Trento], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Martinez Rico, Clara
Subjects: Inflammation, RNA, Untranslated, P and MRP RNAse, danio rerio, exosomes/extracellular vesicles, long ncRNA, melanoma, Organic Chemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, Catalysis, Computer Science Applications, Inorganic Chemistry, Extracellular Vesicles, [SDV.CAN] Life Sciences [q-bio]/Cancer, Animals, Physical and Theoretical Chemistry, Molecular Biology, Melanoma, Spectroscopy, Zebrafish
Abstract: International audience; Extracellular vesicles (EVs) are membranous particles released by all cell types. Their role as functional carrier of bioactive molecules is boosted by cells that actively secrete them in biological fluids or in the intercellular space (interstitial EVs, iEVs). Here we have optimised a method for the isolation and characterization of zebrafish iEVs from whole melanoma tissues. Zebrafish melanoma iEVs are around 140 nm in diameter, as determined by nanoparticle tracking and transmission electron microscopy (TEM) analysis. Western blot analysis shows enrichment for CD63 and Alix in the iEV fraction, but not in melanoma cell lysates. Super resolution and confocal microscopy reveal that purified zebrafish iEVs are green fluorescent protein positive (GFP+), indicating that they integrate the oncogene GFP-HRASV12G used to induce melanoma in this model within their vesicular membrane or luminal content. Analysis of RNA-Seq data found 118 non-coding (nc)RNAs differentially distributed between zebrafish melanoma and their iEVs, with only 17 of them being selectively enriched in iEVs. Among these, the RNA components of RNAses P and MRP, which process ribosomal RNA precursors, mitochondrial RNAs, and some mRNAs, were enriched in zebrafish and human melanoma EVs, but not in iEVs extracted from brain tumours. We found that melanoma iEVs induce an inflammatory response when injected in larvae, with increased expression of interferon responsive genes, and this effect is reproduced by MRP- or P-RNAs injected into circulation. This suggests that zebrafish melanoma iEVs are a source of MRP- and P-RNAs that can trigger inflammation in cells of the innate immune system.
Published: 2022
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33. LAMP2A regulates the loading of proteins into exosomes

Author: José C. Ramalho, Ana Sofia Carvalho, Henrique Girão, Petra Pintado, Paulo Pereira, Ana Soares, Joao Vasco Ferreira, Guillaume van Niel, Rune Matthiesen, Hans Christian Beck, Catarina Máximo Carvalho, Mónica Zuzarte, Maria Helena Cardoso, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Centro de Estudos de Doenças Crónicas (CEDOC), Martinez Rico, Clara, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Odense University Hospital (OUH), University of Coimbra [Portugal] (UC), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Endosome, BIOGENESIS, Cell Communication, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Exosomes, Exosome, Extracellular Vesicles, SYNTENIN, Lysosomal-Associated Membrane Protein 2, TSG101, LYSOSOMES, Transcription factor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, EXTRACELLULAR VESICLE, Multidisciplinary, Endosomal Sorting Complexes Required for Transport, Chemistry, DEGRADATION, Microvesicles, Autophagic Punctum, Cell biology, Cytosol, HIF1A, Membrane protein, SECRETION, Signal Transduction
Abstract: Exosomes are extracellular vesicles of endosomal origin released by virtually all cell types across metazoans. Exosomes are active vehicles of intercellular communication and can transfer lipids, RNAs and proteins between different cells, tissues or organs. However, the mechanisms that regulate the selective loading of cytosolic proteins into these vesicles are still largely unknow. Here we describe a mechanism whereby proteins containing a pentapeptide sequence, biochemically related to the KFERQ-motif, are loaded into a subpopulation of exosomes in a process that is dependent on the membrane protein LAMP2A. Moreover, this mechanism is independent of the ESCRT machinery components TSG101 and VPS4b and dependent on HSC70, CD63, Alix, Syntenin-1, Rab31 and ceramides. The transcription factor and master regulator of hypoxia HIF1A is loaded into exosomes by this mechanism to transport hypoxia signaling to normoxic cells. Additionally, by tagging fluorescent proteins with KFERQ-like sequences we were able to follow inter-organ transfer of exosomes in zebrafish larvae. Our findings identify LAMP2A as a key component in exosome biogenesis while opening new avenues for exosome engineering by allowing the loading of bioactive proteins by tagging them with KFERQ-like motifs.
Published: 2022
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34. Contributions of Andrée Tixier-Vidal (1923-2021) to modern cell biology

Author: Claude Tougard, Thierry Galli, Bruno Goud, Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL), and Martinez Rico, Clara
Subjects: secretion, electron microscopy, membrane transport, pituitary cells, education, Morphogenesis, Humans, brain/nervous system, Female, Cell Biology, General Medicine, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: International audience; This article illustrates the main stages of the scientific career of Dr Andrée Tixier-Vidal, a pioneer in cell biology research in France. She made important discoveries in the field of hormone secretion and neuronal morphogenesis. She played a key role in developing pituitary and neuronal cultures and using electron microscopy to study cellular structures. Her scientific influence continues to irradiate through her students and collaborators.
Published: 2022
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35. A Phosphosite Mutant Approach on LRRK2 Links Phosphorylation and Dephosphorylation to Protective and Deleterious Markers, Respectively

Author: Antoine Marchand, Alessia Sarchione, Panagiotis S. Athanasopoulos, Hélène Bauderlique-Le Roy, Liesel Goveas, Romain Magnez, Matthieu Drouyer, Marco Emanuele, Franz Y. Ho, Maxime Liberelle, Patricia Melnyk, Nicolas Lebègue, Xavier Thuru, R. Jeremy Nichols, Elisa Greggio, Arjan Kortholt, Thierry Galli, Marie-Christine Chartier-Harlin, Jean-Marc Taymans, Cell Biochemistry, CHU Lille, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Groningen [Groningen], Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Stanford University, Università degli Studi di Padova = University of Padua (Unipd), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Martinez Rico, Clara, ANR-16-CE16-0012,MeTDePaDi,Défauts de Traffic Membranaire dans la Maladie de Parkinson(2016), and ANR-20-CE16-0008,Synapark,Evaluation de l'implication de la fonction transcriptionnelle de la parkine dans le contrôle de l'alpha-synucléïne in vitro, in vivo et dans le sang de patients atteints de la Maladie de Parkinson(2020)
Subjects: LRRK2, phosphorylation, Parkinson’s disease, lysosome, RABs, [SDV]Life Sciences [q-bio], Parkinson's disease, Parkinson Disease, General Medicine, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, nervous system diseases, [SDV] Life Sciences [q-bio], Lysosome, Phosphorylation, Humans, Lysosomes, Signal Transduction
Abstract: International audience; The Leucine Rich Repeat Kinase 2 (LRRK2) gene is a major genetic determinant of Parkinson's disease (PD), encoding a homonymous multi-domain protein with two catalytic activities, GTPase and Kinase, involved in intracellular signaling and trafficking. LRRK2 is phosphorylated at multiple sites, including a cluster of autophosphorylation sites in the GTPase domain and a cluster of heterologous phosphorylation sites at residues 860 to 976. Phosphorylation at these latter sites is found to be modified in brains of PD patients, as well as for some disease mutant forms of LRRK2. The main aim of this study is to investigate the functional consequences of LRRK2 phosphorylation or dephosphorylation at LRRK2's heterologous phosphorylation sites. To this end, we generated LRRK2 phosphorylation site mutants and studied how these affected LRRK2 catalytic activity, neurite outgrowth and lysosomal physiology in cellular models. We show that phosphorylation of RAB8a and RAB10 substrates are reduced with phosphomimicking forms of LRRK2, while RAB29 induced activation of LRRK2 kinase activity is enhanced for phosphodead forms of LRRK2. Considering the hypothesis that PD pathology is associated to increased LRRK2 kinase activity, our results suggest that for its heterologous phosphorylation sites LRRK2 phosphorylation correlates to healthy phenotypes and LRRK2 dephosphorylation correlates to phenotypes associated to the PD pathological processes.
Published: 2022
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36. Sinful Foods: Measuring Implicit Associations Between Food Categories and Moral Attributes in Anorexic, Orthorexic, and Healthy Subjects

Author: Clara Lakritz, Lola Tournayre, Marilou Ouellet, Sylvain Iceta, Philibert Duriez, Vincent Masetti, Jérémie Lafraire, Centre de Recherche de l'Institut Paul Bocuse [Ecully] (CRIPB), Parcours santé systémique (P2S), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de Recherche de l’Institut Universitaire en Santé Mentale de Montréal (CRIUSMM), Groupe de Recherche Transdisciplinaire des Troubles du Comportement Alimentaire [Trois-Rivières, QC, Canada] (GR2TCA-Loricorps), Université du Québec à Trois-Rivières (UQTR), Hospices Civils de Lyon (HCL), Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Université Laval [Québec] (ULaval), GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Clinea Psychiatrie France [Paris] (CPF), and Martinez Rico, Clara
Subjects: cognition, orthorexia nervosa, food categorization, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, eating disorders, moral judgment, anorexia nervosa, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food Science
Abstract: International audience; Recently, neurocognitive studies have shown that food categorization is sensitive to both the properties of the food stimuli (e.g., calorie content) and the individual characteristics of subjects (e.g., BMI, eating disorders) asked to categorize these stimuli. Furthermore, groups of patients with eating disorders (ED) were described as relying more on moral criteria to form food categories than were control subjects. The present studies built on these seminal articles and aimed to determine whether certain food properties might trigger moral categories preferentially in subjects suffering from ED and in the general population. Using a Go/No-Go Association Task, Study 1 focused on the extent to which food categories are laden with moral attributes in ED patients compared to control subjects. Study 2 was a follow-up with a different design (an Implicit Association Test), another food variable (calorie content), and two non-clinical subgroups (orthorexic and healthy control subjects). Results revealed for the first time implicit associations between food variables cueing for energy density and moral attributes in the general population, the population suffering from anorexia nervosa, and subjects suffering from disordered eating such as orthorexia nervosa. These findings suggest that moralization of food is a pervasive phenomenon that can be measured with methods reputed to be less vulnerable to self-presentation or social desirability biases.
Published: 2022
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37. The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults): Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic

Author: Solmi, Marco, Estradé, Andrés, Thompson, Trevor, Agorastos, Agorastos, Radua, Joaquim, Cortese, Samuele, Dragioti, Elena, Leisch, Friedrich, Vancampfort, Davy, Thygesen, Lau Caspar, Aschauer, Harald, Schloegelhofer, Monika, Akimova, Elena, Schneeberger, Andres, Huber, Christian, Hasler, Gregor, Conus, Philippe, Cuénod, Kim, von Känel, Roland, Arrondo, Gonzalo, Fusar-Poli, Paolo, Gorwood, Philip, Llorca, Pierre-Michel, Krebs, Marie-Odile, Scanferla, Elisabetta, Kishimoto, Taishiro, Rabbani, Golam, Skonieczna-Żydecka, Karolina, Brambilla, Paolo, Favaro, Angela, Takamiya, Akihiro, Zoccante, Leonardo, Colizzi, Marco, Bourgin, Julie, Kamiński, Karol, Moghadasin, Maryam, Seedat, Soraya, Matthews, Evan, Wells, John, Vassilopoulou, Emilia, Gadelha, Ary, Su, Kuan-Pin, Kwon, Jun Soo, Kim, Minah, Lee, Tae Young, Papsuev, Oleg, Manková, Denisa, Boscutti, Andrea, Gerunda, Cristiano, Saccon, Diego, Righi, Elena, Monaco, Francesco, Croatto, Giovanni, Cereda, Guido, Demurtas, Jacopo, Brondino, Natascia, Veronese, Nicola, Enrico, Paolo, Politi, Pierluigi, Ciappolino, Valentina, Pfennig, Andrea, Bechdolf, Andreas, Meyer-Lindenberg, Andreas, Kahl, Kai, Domschke, Katharina, Bauer, Michael, Koutsouleris, Nikolaos, Winter, Sibylle, Borgwardt, Stefan, Bitter, Istvan, Balazs, Judit, Czobor, Pal, Unoka, Zsolt, Mavridis, Dimitris, Tsamakis, Konstantinos, Bozikas, Vasilios, Tunvirachaisakul, Chavit, Maes, Michael, Rungnirundorn, Teerayuth, Supasitthumrong, Thitiporn, Haque, Ariful, Brunoni, Andre, Costardi, Carlos Gustavo, Schuch, Felipe Barreto, Polanczyk, Guilherme, Luiz, Jhoanne Merlyn, Fonseca, Lais, Aparicio, Luana, Valvassori, Samira, Nordentoft, Merete, Vendsborg, Per, Hoffmann, Sofie Have, Sehli, Jihed, Sartorius, Norman, Heuss, Sabina, Guinart, Daniel, Hamilton, Jane, Kane, John, Rubio, Jose, Sand, Michael, Koyanagi, Ai, Solanes, Aleix, Andreu-Bernabeu, Alvaro, Cáceres, Antonia San José, Arango, Celso, Díaz-Caneja, Covadonga, Hidalgo-Mazzei, Diego, Vieta, Eduard, Gonzalez-Peñas, Javier, Fortea, Lydia, Parellada, Mara, Fullana, Miquel, Verdolini, Norma, Fárková, Eva, Janků, Karolina, Millan, Mark, Honciuc, Mihaela, Moniuszko-Malinowska, Anna, Łoniewski, Igor, Samochowiec, Jerzy, Kiszkiel, Łukasz, Marlicz, Maria, Sowa, Paweł, Marlicz, Wojciech, Spies, Georgina, Stubbs, Brendon, Firth, Joseph, Sullivan, Sarah, Darcin, Asli Enez, Aksu, Hatice, Dilbaz, Nesrin, Noyan, Onur, Kitazawa, Momoko, Kurokawa, Shunya, Tazawa, Yuki, Anselmi, Alejandro, Cracco, Cecilia, Machado, Ana Inés, Estrade, Natalia, de Leo, Diego, Curtis, Jackie, Berk, Michael, Ward, Philip, Teasdale, Scott, Rosenbaum, Simon, Marx, Wolfgang, Horodnic, Adrian Vasile, Oprea, Liviu, Alexinschi, Ovidiu, Ifteni, Petru, Turliuc, Serban, Ciuhodaru, Tudor, Bolos, Alexandra, Matei, Valentin, Nieman, Dorien, Sommer, Iris, van Os, Jim, van Amelsvoort, Therese, Sun, Ching-Fang, Guu, Ta-Wei, Jiao, Can, Zhang, Jieting, Fan, Jialin, Zou, Liye, Yu, Xin, Chi, Xinli, de Timary, Philippe, van Winke, Ruud, Ng, Bernardo, Pena, Edilberto, Arellano, Ramon, Roman, Raquel, Sanchez, Thelma, Movina, Larisa, Morgado, Pedro, Brissos, Sofia, Aizberg, Oleg, Mosina, Anna, Krinitski, Damir, Mugisha, James, Sadeghi-Bahmani, Dena, Sadeghi, Masoud, Hadi, Samira, Brand, Serge, Errazuriz, Antonia, Crossley, Nicolas, Ristic, Dragana Ignjatovic, López-Jaramillo, Carlos, Efthymiou, Dimitris, Kuttichira, Praveenlal, Kallivayalil, Roy Abraham, Javed, Afzal, Afridi, Muhammad Iqbal, James, Bawo, Seb-Akahomen, Omonefe Joy, Fiedorowicz, Jess, Carvalho, Andre, Daskalakis, Jeff, Yatham, Lakshmi, Yang, Lin, Okasha, Tarek, Dahdouh, Aïcha, Gerdle, Björn, Tiihonen, Jari, Shin, Jae Il, Lee, Jinhee, Mhalla, Ahmed, Gaha, Lotfi, Brahim, Takoua, Altynbekov, Kuanysh, Negay, Nikolay, Nurmagambetova, Saltanat, Jamei, Yasser Abu, Weiser, Mark, Correll, Christoph, Thygesen, Lau, Kwon, Jun, Lee, Tae, Costardi, Carlos, Schuch, Felipe, Luiz, Jhoanne, Hoffmann, Sofie, Cáceres, Antonia, Darcin, Asli, Machado, Ana, Horodnic, Adrian, Ristic, Dragana, Kallivayalil, Roy, Afridi, Muhammad, Seb-Akahomen, Omonefe, Shin, Jae, Jamei, Yasser, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Hôpital Sainte-Anne-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Clermont-Ferrand, Pathologies et épithéliums : prévention, innovation, traitements, évaluation (UR 4267) (PEPITE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Martinez Rico, Clara, Solmi, M., Estradé, A., Thompson, T., Agorastos, A., Radua, J., Cortese, S., Dragioti, E., Leisch, F., Vancampfort, D., Thygesen, L.C., Aschauer, H., Schloegelhofer, M., Akimova, E., Schneeberger, A., Huber, C.G., Hasler, G., Conus, P., Cuénod, K.Q.D., von Känel, R., Arrondo, G., Fusar-Poli, P., Gorwood, P., Llorca, P.-M., Krebs, M.-O., Scanferla, E., Kishimoto, T., Rabbani, G., Skonieczna-Żydecka, K., Brambilla, P., Favaro, A., Takamiya, A., Zoccante, L., Colizzi, M., Bourgin, J., Kamiński, K., Moghadasin, M., Seedat, S., Matthews, E., Wells, J., Vassilopoulou, E., Gadelha, A., Su, K.-P., Kwon, J.S., Kim, M., Lee, T.Y., Papsuev, O., Manková, D., Boscutti, A., Gerunda, C., Saccon, D., Righi, E., Monaco, F., Croatto, G., Cereda, G., Demurtas, J., Brondino, N., Veronese, N., Enrico, P., Politi, P., Ciappolino, V., Pfennig, A., Bechdolf, A., Meyer-Lindenberg, A., Kahl, K.G., Domschke, K., Bauer, M., Koutsouleris, N., Winter, S., Borgwardt, S., Bitter, I., Balazs, J., Czobor, P., Unoka, Z., Mavridis, D., Tsamakis, K., Bozikas, V.P., Tunvirachaisakul, C., Maes, M., Rungnirundorn, T., Supasitthumrong, T., Haque, A., Brunoni, A.R., Costardi, C.G., Schuch, F.B., Polanczyk, G., Luiz, J.M., Fonseca, L., Aparicio, L.V., Valvassori, S.S., Nordentoft, M., Vendsborg, P., Hoffmann, S.H., Sehli, J., Sartorius, N., Heuss, S., Guinart, D., Hamilton, J., Kane, J., Rubio, J., Sand, M., Koyanagi, A., Solanes, A., Andreu-Bernabeu, A., Cáceres, A.S.J., Arango, C., Díaz-Caneja, C.M., Hidalgo-Mazzei, D., Vieta, E., Gonzalez-Peñas, J., Fortea, L., Parellada, M., Fullana, M.A., Verdolini, N., Fárková, E., Janků, K., Millan, M., Honciuc, M., Moniuszko-Malinowska, A., Łoniewski, I., Samochowiec, J., Kiszkiel, Ł., Marlicz, M., Sowa, P., Marlicz, W., Spies, G., Stubbs, B., Firth, J., Sullivan, S., Darcin, A.E., Aksu, H., Dilbaz, N., Noyan, O., Kitazawa, M., Kurokawa, S., Tazawa, Y., Anselmi, A., Cracco, C., Machado, A.I., Estrade, N., De Leo, D., Curtis, J., Berk, M., Ward, P., Teasdale, S., Rosenbaum, S., Marx, W., Horodnic, A.V., Oprea, L., Alexinschi, O., Ifteni, P., Turliuc, S., Ciuhodaru, T., Bolos, A., Matei, V., Nieman, D.H., Sommer, I., van Os, J., van Amelsvoort, T., Sun, C.-F., Guu, T.-W., Jiao, C., Zhang, J., Fan, J., Zou, L., Yu, X., Chi, X., de Timary, P., van Winke, R., Ng, B., Pena, E., Arellano, R., Roman, R., Sanchez, T., Movina, L., Morgado, P., Brissos, S., Aizberg, O., Mosina, A., Krinitski, D., Mugisha, J., Sadeghi-Bahmani, D., Sadeghi, M., Hadi, S., Brand, S., Errazuriz, A., Crossley, N., Ristic, D.I., López-Jaramillo, C., Efthymiou, D., Kuttichira, P., Kallivayalil, R.A., Javed, A., Afridi, M.I., James, B., Seb-Akahomen, O.J., Fiedorowicz, J., Carvalho, A.F., Daskalakis, J., Yatham, L.N., Yang, L., Okasha, T., Dahdouh, A., Gerdle, B., Tiihonen, J., Shin, J.I., Lee, J., Mhalla, A., Gaha, L., Brahim, T., Altynbekov, K., Negay, N., Nurmagambetova, S., Jamei, Y.A., Weiser, M., Correll, C.U., Adult Psychiatry, APH - Mental Health, ANS - Compulsivity, Impulsivity & Attention, and ANS - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: Gerontology, DISORDER, STRESS, Outcome Assessment, IMPACT, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, RA0421, well-being, Pandemic, Health care, Outcome Assessment, Health Care, adults, Medicine, ANXIETY, COVID-19, mental health, functioning, physical health, representative, resilience, survey, international, psychiatry, depression, anxiety, post-traumatic, COH-FIT, children, adolescents, mental health, functioning, physical health, representative, well-being, resilience, survey, international, psychiatry, depression, anxiety, post-traumatic, COH-FIT, children, adolescents, adult, Child, SCALE, Psychiatry, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Public Health, Global Health, Social Medicine and Epidemiology, Psychiatry and Mental health, Clinical Psychology, Professional association, Life Sciences & Biomedicine, Psychopathology, Research Paper, Adult, Coronavirus disease 2019 (COVID-19), Adolescent, Population, Clinical Neurology, BF, Anxiety, Cross-Sectional Studies, Depression, Humans, Mental Health, SARS-CoV-2, Pandemics, Intervention (counseling), MANAGEMENT, VALIDITY, education, Science & Technology, business.industry, MORTALITY, CARE, Mental health, Health Care, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Neurosciences & Neurology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BACKGROUND: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. METHODS: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. RESULTS: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of ≥1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged ≥65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. LIMITATIONS: . Cross-sectional survey, preponderance of non-representative participants. CONCLUSIONS: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics. ispartof: JOURNAL OF AFFECTIVE DISORDERS vol:299 pages:393-407 ispartof: location:Netherlands status: published
Published: 2022
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38. Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times-Children and Adolescents (COH-FIT-C&A)

Author: Solmi, Marco, Estradé, Andrés, Thompson, Trevor, Agorastos, Agorastos, Radua, Joaquim, Cortese, Samuele, Dragioti, Elena, Leisch, Friedrich, Vancampfort, Davy, Thygesen, Lau Caspar, Aschauer, Harald, Schloegelhofer, Monika, Akimova, Elena, Schneeberger, Andres, Huber, Christian, Hasler, Gregor, Conus, Philippe, Cuénod, Kim, von Känel, Roland, Arrondo, Gonzalo, Fusar-Poli, Paolo, Gorwood, Philip, Llorca, Pierre-Michel, Krebs, Marie-Odile, Scanferla, Elisabetta, Kishimoto, Taishiro, Rabbani, Golam, Skonieczna-Żydecka, Karolina, Brambilla, Paolo, Favaro, Angela, Takamiya, Akihiro, Zoccante, Leonardo, Colizzi, Marco, Bourgin, Julie, Kamiński, Karol, Moghadasin, Maryam, Seedat, Soraya, Matthews, Evan, Wells, John, Vassilopoulou, Emilia, Gadelha, Ary, Su, Kuan-Pin, Kwon, Jun Soo, Kim, Minah, Lee, Tae Young, Papsuev, Oleg, Manková, Denisa, Boscutti, Andrea, Gerunda, Cristiano, Saccon, Diego, Righi, Elena, Monaco, Francesco, Croatto, Giovanni, Cereda, Guido, Demurtas, Jacopo, Brondino, Natascia, Veronese, Nicola, Enrico, Paolo, Politi, Pierluigi, Ciappolino, Valentina, Pfennig, Andrea, Bechdolf, Andreas, Meyer-Lindenberg, Andreas, Kahl, Kai, Domschke, Katharina, Bauer, Michael, Koutsouleris, Nikolaos, Winter, Sibylle, Borgwardt, Stefan, Bitter, Istvan, Balazs, Judit, Czobor, Pal, Unoka, Zsolt, Mavridis, Dimitris, Tsamakis, Konstantinos, Bozikas, Vasilios, Tunvirachaisakul, Chavit, Maes, Michael, Rungnirundorn, Teerayuth, Supasitthumrong, Thitiporn, Haque, Ariful, Brunoni, Andre, Costardi, Carlos Gustavo, Schuch, Felipe Barreto, Polanczyk, Guilherme, Luiz, Jhoanne Merlyn, Fonseca, Lais, Aparicio, Luana, Valvassori, Samira, Nordentoft, Merete, Vendsborg, Per, Hoffmann, Sofie Have, Sehli, Jihed, Sartorius, Norman, Heuss, Sabina, Guinart, Daniel, Hamilton, Jane, Kane, John, Rubio, Jose, Sand, Michael, Koyanagi, Ai, Solanes, Aleix, Andreu-Bernabeu, Alvaro, Cáceres, Antonia San José, Arango, Celso, Díaz-Caneja, Covadonga, Hidalgo-Mazzei, Diego, Vieta, Eduard, Gonzalez-Peñas, Javier, Fortea, Lydia, Parellada, Mara, Fullana, Miquel, Verdolini, Norma, Fárková, Eva, Janků, Karolina, Millan, Mark, Honciuc, Mihaela, Moniuszko-Malinowska, Anna, Łoniewski, Igor, Samochowiec, Jerzy, Kiszkiel, Łukasz, Marlicz, Maria, Sowa, Paweł, Marlicz, Wojciech, Spies, Georgina, Stubbs, Brendon, Firth, Joseph, Sullivan, Sarah, Darcin, Asli Enez, Aksu, Hatice, Dilbaz, Nesrin, Noyan, Onur, Kitazawa, Momoko, Kurokawa, Shunya, Tazawa, Yuki, Anselmi, Alejandro, Cracco, Cecilia, Machado, Ana Inés, Estrade, Natalia, de Leo, Diego, Curtis, Jackie, Berk, Michael, Ward, Philip, Teasdale, Scott, Rosenbaum, Simon, Marx, Wolfgang, Horodnic, Adrian Vasile, Oprea, Liviu, Alexinschi, Ovidiu, Ifteni, Petru, Turliuc, Serban, Ciuhodaru, Tudor, Bolos, Alexandra, Matei, Valentin, Nieman, Dorien, Sommer, Iris, van Os, Jim, van Amelsvoort, Therese, Sun, Ching-Fang, Guu, Ta-Wei, Jiao, Can, Zhang, Jieting, Fan, Jialin, Zou, Liye, Yu, Xin, Chi, Xinli, de Timary, Philippe, van Winke, Ruud, Ng, Bernardo, Pena, Edilberto, Arellano, Ramon, Roman, Raquel, Sanchez, Thelma, Movina, Larisa, Morgado, Pedro, Brissos, Sofia, Aizberg, Oleg, Mosina, Anna, Krinitski, Damir, Mugisha, James, Sadeghi-Bahmani, Dena, Sadeghi, Masoud, Hadi, Samira, Brand, Serge, Errazuriz, Antonia, Crossley, Nicolas, Ristic, Dragana Ignjatovic, López-Jaramillo, Carlos, Efthymiou, Dimitris, Kuttichira, Praveenlal, Kallivayalil, Roy Abraham, Javed, Afzal, Afridi, Muhammad Iqbal, James, Bawo, Seb-Akahomen, Omonefe Joy, Fiedorowicz, Jess, Carvalho, Andre, Daskalakis, Jeff, Yatham, Lakshmi, Yang, Lin, Okasha, Tarek, Dahdouh, Aïcha, Gerdle, Björn, Tiihonen, Jari, Shin, Jae Il, Lee, Jinhee, Mhalla, Ahmed, Gaha, Lotfi, Brahim, Takoua, Altynbekov, Kuanysh, Negay, Nikolay, Nurmagambetova, Saltanat, Jamei, Yasser Abu, Weiser, Mark, Correll, Christoph, Thygesen, Lau, Kwon, Jun, Lee, Tae, Costardi, Carlos, Schuch, Felipe, Luiz, Jhoanne, Hoffmann, Sofie, Cáceres, Antonia, Darcin, Asli, Machado, Ana, Horodnic, Adrian, Ristic, Dragana, Kallivayalil, Roy, Afridi, Muhammad, Seb-Akahomen, Omonefe, Shin, Jae, Jamei, Yasser, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Solmi, M., Estradé, A., Thompson, T., Agorastos, A., Radua, J., Cortese, S., Dragioti, E., Leisch, F., Vancampfort, D., Thygesen, L.C., Aschauer, H., Schloegelhofer, M., Akimova, E., Schneeberger, A., Huber, C.G., Hasler, G., Conus, P., Cuénod, K.Q.D., von Känel, R., Arrondo, G., Fusar-Poli, P., Gorwood, P., Llorca, P.-M., Krebs, M.-O., Scanferla, E., Kishimoto, T., Rabbani, G., Skonieczna-Żydecka, K., Brambilla, P., Favaro, A., Takamiya, A., Zoccante, L., Colizzi, M., Bourgin, J., Kamiński, K., Moghadasin, M., Seedat, S., Matthews, E., Wells, J., Vassilopoulou, E., Gadelha, A., Su, K.-P., Kwon, J.S., Kim, M., Lee, T.Y., Papsuev, O., Manková, D., Boscutti, A., Gerunda, C., Saccon, D., Righi, E., Monaco, F., Croatto, G., Cereda, G., Demurtas, J., Brondino, N., Veronese, N., Enrico, P., Politi, P., Ciappolino, V., Pfennig, A., Bechdolf, A., Meyer-Lindenberg, A., Kahl, K.G., Domschke, K., Bauer, M., Koutsouleris, N., Winter, S., Borgwardt, S., Bitter, I., Balazs, J., Czobor, P., Unoka, Z., Mavridis, D., Tsamakis, K., Bozikas, V.P., Tunvirachaisakul, C., Maes, M., Rungnirundorn, T., Supasitthumrong, T., Haque, A., Brunoni, A.R., Costardi, C.G., Schuch, F.B., Polanczyk, G., Luiz, J.M., Fonseca, L., Aparicio, L.V., Valvassori, S.S., Nordentoft, M., Vendsborg, P., Hoffmann, S.H., Sehli, J., Sartorius, N., Heuss, S., Guinart, D., Hamilton, J., Kane, J., Rubio, J., Sand, M., Koyanagi, A., Solanes, A., Andreu-Bernabeu, A., Cáceres, A.S.J., Arango, C., Díaz-Caneja, C.M., Hidalgo-Mazzei, D., Vieta, E., Gonzalez-Peñas, J., Fortea, L., Parellada, M., Fullana, M.A., Verdolini, N., Fárková, E., Janků, K., Millan, M., Honciuc, M., Moniuszko-Malinowska, A., Łoniewski, I., Samochowiec, J., Kiszkiel, Ł., Marlicz, M., Sowa, P., Marlicz, W., Spies, G., Stubbs, B., Firth, J., Sullivan, S., Darcin, A.E., Aksu, H., Dilbaz, N., Noyan, O., Kitazawa, M., Kurokawa, S., Tazawa, Y., Anselmi, A., Cracco, C., Machado, A.I., Estrade, N., De Leo, D., Curtis, J., Berk, M., Ward, P., Teasdale, S., Rosenbaum, S., Marx, W., Horodnic, A.V., Oprea, L., Alexinschi, O., Ifteni, P., Turliuc, S., Ciuhodaru, T., Bolos, A., Matei, V., Nieman, D.H., Sommer, I., van Os, J., van Amelsvoort, T., Sun, C.-F., Guu, T.-W., Jiao, C., Zhang, J., Fan, J., Zou, L., Yu, X., Chi, X., de Timary, P., van Winke, R., Ng, B., Pena, E., Arellano, R., Roman, R., Sanchez, T., Movina, L., Morgado, P., Brissos, S., Aizberg, O., Mosina, A., Krinitski, D., Mugisha, J., Sadeghi-Bahmani, D., Sadeghi, M., Hadi, S., Brand, S., Errazuriz, A., Crossley, N., Ristic, D.I., López-Jaramillo, C., Efthymiou, D., Kuttichira, P., Kallivayalil, R.A., Javed, A., Afridi, M.I., James, B., Seb-Akahomen, O.J., Fiedorowicz, J., Carvalho, A.F., Daskalakis, J., Yatham, L.N., Yang, L., Okasha, T., Dahdouh, A., Gerdle, B., Tiihonen, J., Shin, J.I., Lee, J., Mhalla, A., Gaha, L., Brahim, T., Altynbekov, K., Negay, N., Nurmagambetova, S., Jamei, Y.A., Weiser, M., Correll, C.U., Adult Psychiatry, APH - Mental Health, ANS - Compulsivity, Impulsivity & Attention, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Martinez Rico, Clara, Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Hôpital Sainte-Anne-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Clermont-Ferrand, Pathologies et épithéliums : prévention, innovation, traitements, évaluation (UR 4267) (PEPITE), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Gerontology, DISORDER, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Psychological intervention, Physical health, Adolescents, HV, Children, Covid-19, Mental health, Pandemic, Resilience, RA0421, Medicine, Adolescent, Adult, Child, Cross-Sectional Studies, Health Promotion, Humans, Mental Health, Pandemics, Quality of Life, SARS-CoV-2, COVID-19, SCALE, media_common, Psychiatry, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Public Health, Global Health, Social Medicine and Epidemiology, Psychiatry and Mental health, Clinical Psychology, Professional association, Psychological resilience, Life Sciences & Biomedicine, Psychopathology, Covid-19, Pandemic, Mental health, Physical health, Resilience, Children, Adolescents, media_common.quotation_subject, Clinical Neurology, BF, Article, Quality of life (healthcare), Intervention (counseling), VALIDITY, Science & Technology, business.industry, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Neurosciences & Neurology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BACKGROUND: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. METHODS: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www.coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via non-probability/snowball and representative sampling and assessed via self-rating and parental rating. Non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co-primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. RESULTS: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COH-FIT project, with representative samples from eleven countries. LIMITATIONS: Cross-sectional and anonymous design. CONCLUSIONS: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on children's, adolescents' and families', mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth. ispartof: JOURNAL OF AFFECTIVE DISORDERS vol:299 pages:367-376 ispartof: location:Netherlands status: published
Published: 2022
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39. Clinical Utility of a Unique Genome-Wide DNA Methylation Signature for KMT2A-Related Syndrome

Author: Aidin Foroutan, Sadegheh Haghshenas, Pratibha Bhai, Michael A. Levy, Jennifer Kerkhof, Haley McConkey, Marcello Niceta, Andrea Ciolfi, Lucia Pedace, Evelina Miele, David Genevieve, Solveig Heide, Mariëlle Alders, Giuseppe Zampino, Giuseppe Merla, Mélanie Fradin, Eric Bieth, Dominique Bonneau, Klaus Dieterich, Patricia Fergelot, Elise Schaefer, Laurence Faivre, Antonio Vitobello, Silvia Maitz, Rita Fischetto, Cristina Gervasini, Maria Piccione, Ingrid van de Laar, Marco Tartaglia, Bekim Sadikovic, Anne-Sophie Lebre, Foroutan A., Haghshenas S., Bhai P., Levy M.A., Kerkhof J., McConkey H., Niceta M., Ciolfi A., Pedace L., Miele E., Genevieve D., Heide S., Alders M., Zampino G., Merla G., Fradin M., Bieth E., Bonneau D., Dieterich K., Fergelot P., Schaefer E., Faivre L., Vitobello A., Maitz S., Fischetto R., Gervasini C., Piccione M., van de Laar I., Tartaglia M., Sadikovic B., Lebre A.-S., Human Genetics, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, University of Western Ontario (UWO), London Health Sciences Center (LHSC), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Amsterdam UMC - Amsterdam University Medical Center, University of Amsterdam [Amsterdam] (UvA), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University of Naples Federico II = Università degli studi di Napoli Federico II, Fondazione Casa Sollievo della Sofferenza [San Giovanni Rotondo, Italy] (FC2S), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), San Gerardo Hospital [Monza, Italy] (SGH), Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Università degli Studi di Milano = University of Milan (UNIMI), Università degli studi di Palermo - University of Palermo, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de génétique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Foroutan, A., Haghshenas, S., Bhai, P., Levy, M. A., Kerkhof, J., Mcconkey, H., Niceta, M., Ciolfi, A., Pedace, L., Miele, E., Genevieve, D., Heide, S., Alders, M., Zampino, G., Merla, G., Fradin, M., Bieth, E., Bonneau, D., Dieterich, K., Fergelot, P., Schaefer, E., Faivre, L., Vitobello, A., Maitz, S., Fischetto, R., Gervasini, C., Piccione, M., van de Laar, I., Tartaglia, M., Sadikovic, B., Lebre, A. -S., Martinez Rico, Clara, and Clinical Genetics
Subjects: Wiedemann–Steiner syndrome, QH301-705.5, Intellectual disability, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Catalysis, Inorganic Chemistry, KMT2A gene, Neurodevelopmental disorder, Growth Disorder, Abnormalities, Multiple, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biology (General), Physical and Theoretical Chemistry, Episignature, QD1-999, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, Spectroscopy, DNA methylation, Organic Chemistry, Neurodevelopmental disorders, Craniofacial Abnormalitie, Epigenetic, Hypertrichosi, General Medicine, Facie, Computer Science Applications, Chemistry, epigenetics, episignature, intellectual disability, neurodevelopmental disorders, Phenotype, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Epigenetics, Human
Abstract: Wiedemann–Steiner syndrome (WDSTS) is a Mendelian syndromic intellectual disability (ID) condition associated with hypertrichosis cubiti, short stature, and characteristic facies caused by pathogenic variants in the KMT2A gene. Clinical features can be inconclusive in mild and unusual WDSTS presentations with variable ID (mild to severe), facies (typical or not) and other associated malformations (bone, cerebral, renal, cardiac and ophthalmological anomalies). Interpretation and classification of rare KMT2A variants can be challenging. A genome-wide DNA methylation episignature for KMT2A-related syndrome could allow functional classification of variants and provide insights into the pathophysiology of WDSTS. Therefore, we assessed genome-wide DNA methylation profiles in a cohort of 60 patients with clinical diagnosis for WDSTS or Kabuki and identified a unique highly sensitive and specific DNA methylation episignature as a molecular biomarker of WDSTS. WDSTS episignature enabled classification of variants of uncertain significance in the KMT2A gene as well as confirmation of diagnosis in patients with clinical presentation of WDSTS without known genetic variants. The changes in the methylation profile resulting from KMT2A mutations involve global reduction in methylation in various genes, including homeobox gene promoters. These findings provide novel insights into the molecular etiology of WDSTS and explain the broad phenotypic spectrum of the disease.
Published: 2022
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40. Impact of the first wave of the COVID-19 pandemic on French Health students

Author: F. Rolland, A. Frajerman, B. Falissard, G. Bertschy, B. Diquet, D. Marra, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Bicêtre, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, CHU Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Institut de Biologie en Santé (PHB-IRIS) [CHU Angers] (IBS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), and Martinez Rico, Clara
Subjects: Santé mentale, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, anté mentale, education, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Health students, Étudiant en santé, COVID-19, Psychological distress, Article, Psychiatry and Mental health, Arts and Humanities (miscellaneous), [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Détresse psychologique, Mental health, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Context: In France, care workers and health students have been intensely mobilized during the first wave of the COVID-19 pandemic. But few studies have evaluated psychological distress on non-medical health students, in addition to the challenges posed by pedagogical continuity while universities are closed following health and safety regulations.Objectives: This study aims to assess COVID-19's impact on health students in France on different levels: psychological, educational and social.Methods: An online national cross-sectional study, from April 11 to May 30 2020, included sociodemographic, work conditions and numeric scales.Results: A total of 4411 students answered. Regarding the K6 scale, 39% of students had moderate distress, and 21% had a high level of distress. Risk factors of psychological distress included being a woman (P
Published: 2022
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41. Functional connectivity correlates of reduced goal-directed behaviors in behavioural variant frontotemporal dementia

Author: Valérie Godefroy, Bénédicte Batrancourt, Sylvain Charron, Arabella Bouzigues, David Bendetowicz, Guilhem Carle, Armelle Rametti-Lacroux, Stéphanie Bombois, Emmanuel Cognat, Raffaella Migliaccio, Richard Levy, Martinez Rico, Clara, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144))
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Histology, Resting-state functional connectivity, General Neuroscience, Apathy, fMRI, Brain, Ecological design, Magnetic Resonance Imaging, Cognition, Goal-directed behavior, Frontotemporal Dementia, Parietal Lobe, Humans, Anatomy, Goals, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: INTRODUCTION: We explored the resting state functional connectivity correlates of apathy assessed as a multidimensional construct, using behavioral metrics, in behavioral variant frontotemporal dementia (bvFTD).METHODS: We recorded the behavior of 20 bvFTD patients and 16 healthy controls (HC) in a close-to-real-life situation including a free phase (FP – in which actions were self-initiated) and a guided phase (GP – in which initiation of actions was facilitated by external guidance). We investigated the activity time and walking episode features as quantifiers of apathy. We used the means ((FP+GP)/2) and the differences (FP-GP) calculated for these metrics as well as measures by questionnaires to extract apathy dimensions by factor analysis. We assessed two types of connectivity measures (local low-frequency signal power and distant seed-based functional connectivity) and explored their relationship with extracted apathy dimensions. RESULTS: Apathy in bvFTD was associated with lower time spent in activity combined with walking episodes of higher frequency, lower acceleration and higher duration. Using these behavioral metrics and apathy measures by questionnaires, we disentangled two dimensions: the global reduction of goal-directed behaviors and the specific deficit of selfinitiation. Global apathy was associated with lower resting state activity within prefrontal cortex and lower connectivity of salience network hubs while the decrease in self-initiation was related to increased connectivity of parietal default-mode network hubs. DISCUSSION: Through a new dimensional approach of apathy, we dissociated the functional connectivity correlates of global apathy and self-initiation deficit. This contributes to better understand the role of functional networks in the production of goal-directed behaviors.
Published: 2022
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42. The role of neurotrophin genes involved in the vulnerability to gambling disorder

Author: Neus Solé-Morata, Isabel Baenas, Mikel Etxandi, Roser Granero, Sonia V. Forcales, Manel Gené, Carme Barrot, Mónica Gómez-Peña, José M. Menchón, Nicolás Ramoz, Philip Gorwood, Fernando Fernández-Aranda, Susana Jiménez-Murcia, Martinez Rico, Clara, Bellvitge University Hospital [Barcelona, Spain], Bellvitge Biomedical Research Institute [Barcelona, Spain] ((IDIBELL)), L’Hospitalet de Llobregat [Barcelona, Spain], Instituto de Salud Carlos III [Madrid] (ISC), Universitat Autònoma de Barcelona (UAB), University of Barcelona, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, Multidisciplinary, Addiction, Proteins, Joc compulsiu, [SDV.GEN] Life Sciences [q-bio]/Genetics, Predictive markers, Polymorphism, Single Nucleotide, Gene Frequency, Haplotypes, Gambling, Genetics, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Nerve Growth Factors, Compulsive gambling, Proteïnes, Genètica
Abstract: Altres ajuts: Delegación del Gobierno para el Plan Nacional sobre Drogas (2021I031 and 2019I47), EU Grant Eat2beNice (H2020-SFS-2016-2; Ref728018), PRIME (H2020-SC1-BHC-2018-2020, ref.847879) and COST Action (CA19115). Evidence about the involvement of genetic factors in the development of gambling disorder (GD) has been assessed. Among studies assessing heritability and biological vulnerability for GD, neurotrophin (NTF) genes have emerged as promising targets, since a growing literature showed a possible link between NTF and addiction-related disorders. Thus, we aimed to explore the role of NTF genes and GD with the hypothesis that some NTF gene polymorphisms could constitute biological risk factors. The sample included 166 patients with GD and 191 healthy controls. 36 single nucleotide polymorphisms (SNPs) from NTFs (NGF, NGFR, NTRK1, BDNF, NTRK2, NTF3, NTRK3, NTF4, CNTF and CNTFR) were selected and genotyped. Linkage disequilibrium (LD) and haplotype constructions were analyzed, in relationship with the presence of GD. Finally, regulatory elements overlapping the identified SNPs variants associated with GD were searched. The between groups comparisons of allele frequencies indicated that 6 SNPs were potentially associated with GD. Single and multiple-marker analyses showed a strong association between both NTF3 and NTRK2 genes, and GD. The present study supports the involvement of the NTF family in the aetiopathogenesis of GD. An altered cross-regulation of different NTF members signalling pathways might be considered as a biological vulnerability factor for GD.
Published: 2022
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43. Mental health-related risk factors and interventions in patients with heart failure: a position paper endorsed by the European Association of Preventive Cardiology (EAPC)

Author: Karl-Heinz Ladwig, Thomas C Baghai, Frank Doyle, Mark Hamer, Christoph Herrmann-Lingen, Evelyn Kunschitz, Cédric Lemogne, Margarita Beresnevaite, Angelo Compare, Roland von Känel, Hendrik B Sager, Willem Johan Kop, University of Zurich, Ladwig, Karl-Heinz, Technische Universität München = Technical University of Munich (TUM), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Regensburg, Royal College of Surgeons in Ireland (RCSI), University College of London [London] (UCL), Georg-August-University = Georg-August-Universität Göttingen, Hanusch Krankenhaus [Vienna, Austria] (HK), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lithuanian University of health Sciences [Kaunas], University of Bergamo, Centro Diagnostico Italiano (CDI), Universität Zürich [Zürich] = University of Zurich (UZH), Tilburg University [Tilburg], Netspar, and Martinez Rico, Clara
Subjects: Heart failure, psychological factors, depression, anxiety, palliative care, review, risk factors, psychosocial, Epidemiology, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cardiology, ATHEROSCLEROSIS RISK, 610 Medicine & health, Review, Anxiety, 2705 Cardiology and Cardiovascular Medicine, IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS, Risk Factors, Settore M-PSI/08 - Psicologia Clinica, ANTIDEPRESSANT USE, Humans, Prospective Studies, COGNITIVE-BEHAVIORAL THERAPY, ALL-CAUSE MORTALITY, Heart Failure, Depression, Palliative Care, Psychological Factors, DISEASE MANAGEMENT, Mental Health, 10057 Klinik für Konsiliarpsychiatrie und Psychosomatik, MYOCARDIAL-INFARCTION, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, DEPRESSIVE SYMPTOMS, Chronic Disease, VENTRICULAR ASSIST DEVICES, Cardiology and Cardiovascular Medicine, Psychosocial, 2713 Epidemiology
Abstract: The prevalence and public health burden of chronic heart failure (CHF) in Europe is steadily increasing mainly caused by the ageing population and prolonged survival of patients with CHF. Frequent hospitalizations, high morbidity and mortality rates, and enormous healthcare costs contribute to the health-related burden. However, multidisciplinary frameworks that emphasize effective long-term management and the psychological needs of the patients are sparse. The present position paper endorsed by the European Association of Preventive Cardiology (EAPC) provides a comprehensive overview on the scientific evidence of psychosocial aspects of heart failure (HF). In order to synthesize newly available information and reinforce best medical practice, information was gathered via literature reviews and consultations of experts. It covers the evidence for aetiological and prospective psychosocial risk factors and major underlying psycho-biological mechanisms. The paper elucidates the need to include psychosocial aspects in self-care concepts and critically reviews the current shortcomings of psychotherapeutic and psycho-pharmacological interventions. It also highlights the need for involvement of psychological support in device therapy for patients with HF and finally calls for better palliative care in the final stage of HF progression.
Published: 2022
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44. Interplay of tactile and motor information in constructing spatial self-perception

Author: Cataldo, Antonio, Dupin, Lucile, Dempsey-Jones, Harriet, Haggard, Patrick, hiroaki, gomi, Cataldo, Antonio, Dupin, Lucile, Dempsey-Jones, Harriet, Haggard, Patrick, Gomi, Hiroaki, University of London [London], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Queensland [Brisbane], Nippon Telegraph & Telephone Corporation - NTT, University College of London [London] (UCL), and Martinez Rico, Clara
Subjects: self-generated touch, tool-mediated self-touch, genetic structures, touchant-touché, InformationSystems_INFORMATIONINTERFACESANDPRESENTATION(e.g.,HCI), Movement, General Biochemistry, Genetics and Molecular Biology, InformationSystems_MODELSANDPRINCIPLES, self-touch, Humans, sensorimotor interaction, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], spatial perception, motor dominance, Hand, Self Concept, voluntary action, optimal integration, Touch Perception, Touch, Space Perception, agency, ComputingMilieux_COMPUTERSANDSOCIETY, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], General Agricultural and Biological Sciences, psychological phenomena and processes
Abstract: International audience; During active movement, there is normally a tight relation between motor command and sensory representation about the resulting spatial displacement of the body. Indeed, some theories of space perception emphasize the topographic layout of sensory receptor surfaces, while others emphasize implicit spatial information provided by the intensity of motor command signals. To identify which has the primary role in spatial perception, we developed experiments based on everyday self-touch, in which the right hand strokes the left arm. We used a robot-mediated form of self-touch to decouple the spatial extent of active or passive right hand movements from their tactile consequences. Participants made active movements of the right hand between unpredictable, haptically defined start and stop positions, or the hand was passively moved between the same positions. These movements caused a stroking tactile motion by a brush along the left forearm, with minimal delay, but with an unpredictable spatial gain factor. Participants judged the spatial extent of either the right hand's movement, or of the resulting tactile stimulation to their left forearm. Across five experiments, we found that movement extent strongly interfered with tactile extent perception, and vice versa. Crucially, interference in both directions was stronger during active than passive movements. Thus, voluntary motor commands produced stronger integration of multiple sensorimotor signals underpinning the perception of personal space. Our results prompt a reappraisal of classical theories that reduce space perception to motor command information.
Published: 2022
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45. European Stroke Organisation (ESO)-European Society for Minimally Invasive Neurological Therapy (ESMINT) expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischemic stroke and anterior circulation large vessel occlusion

Author: Guillaume Turc, Georgios Tsivgoulis, Heinrich J Audebert, Hieronymus Boogaarts, Pervinder Bhogal, Gian Marco De Marchis, Ana Catarina Fonseca, Pooja Khatri, Mikaël Mazighi, Natalia Pérez de la Ossa, Peter D Schellinger, Daniel Strbian, Danilo Toni, Philip White, William Whiteley, Andrea Zini, Wim van Zwam, Jens Fiehler, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: Carim - B05 Cerebral small vessel disease, RS: Carim - B06 Imaging, GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University General Hospital ' Attikon ' [Athens, Greece], The University of Tennessee Health Science Center [Memphis] (UTHSC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Radboud University Medical Center [Nijmegen], Royal Free Hospital [London, UK], University of Basel (Unibas), Universidade de Lisboa = University of Lisbon (ULISBOA), University of Cincinnati (UC), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospital Germans Trias i Pujol [Barcelona, Spain], Ruhr-Universität Bochum [Bochum], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Newcastle Upon Tyne Hospitals NHS Foundation Trust, University of Edinburgh, Maggiore-Bellaria Hospital [Bologna], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), and Martinez Rico, Clara
Subjects: thrombolysis, Mechanical Thrombolysis, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], RECANALIZATION, GUIDELINES, Brain Ischemia, EARLY MANAGEMENT, All institutes and research themes of the Radboud University Medical Center, Fibrinolytic Agents, Thrombolytic Therapy/methods, ALTEPLASE, Humans, Thrombolytic Therapy, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], PLASMINOGEN-ACTIVATOR, Ischemic Stroke, HEALTH-CARE PROFESSIONALS, OUTCOMES, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Fibrinolytic Agents/therapeutic use, Mechanical Thrombolysis/methods, Brain Ischemia/drug therapy, General Medicine, stroke, ARTERY-OCCLUSION, Treatment Outcome, Thrombectomy/methods, thrombectomy, ENDOVASCULAR TREATMENT, standards, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Surgery, TRIAL, Neurology (clinical), Stroke/drug therapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Six randomized controlled clinical trials have assessed whether mechanical thrombectomy (MT) alone is non-inferior to intravenous thrombolysis (IVT) plus MT within 4.5 hours of symptom onset in patients with anterior circulation large vessel occlusion (LVO) ischemic stroke and no contraindication to IVT. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted with the European Society of Minimally Invasive Neurological Therapy (ESMINT) according to ESO standard operating procedure based on the GRADE system. We identified two relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert opinion was provided if insufficient evidence was available to provide recommendations based on the GRADE approach.For stroke patients with anterior circulation LVO directly admitted to a MT-capable center (‘mothership’) within 4.5 hours of symptom onset and eligible for both treatments, we recommend IVT plus MT over MT alone (moderate evidence, strong recommendation). MT should not prevent the initiation of IVT, nor should IVT delay MT. In stroke patients with anterior circulation LVO admitted to a center without MT facilities and eligible for IVT ≤4.5 hours and MT, we recommend IVT followed by rapid transfer to a MT capable-center (‘drip-and-ship’) in preference to omitting IVT (low evidence, strong recommendation). Expert consensus statements on ischemic stroke on awakening from sleep are also provided. Patients with anterior circulation LVO stroke should receive IVT in addition to MT if they have no contraindications to either treatment.
Published: 2022
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46. Risk of death in individuals hospitalized for COVID-19 with and without psychiatric disorders: an observational multicenter study in France

Author: Nicolas Hoertel, Marina Sánchez-Rico, Pedro de la Muela, Miriam Abellán, Carlos Blanco, Marion Leboyer, Céline Cougoule, Erich Gulbins, Johannes Kornhuber, Alexander Carpinteiro, Katrin Anne Becker, Raphaël Vernet, Nathanaël Beeker, Antoine Neuraz, Jesús M. Alvarado, Juan José Herrera-Morueco, Guillaume Airagnes, Cédric Lemogne, Frédéric Limosin, Pierre-Yves Ancel, Alain Bauchet, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien Van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal, DMU Psychiatrie et Addictologie [Hôpital Corentin Celton, Issy-les-Moulineaux], Hôpital Corentin Celton [Issy-les-Moulineaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), National Institute on Drug Abuse [Bethesda] (NIDA), DMU psychiatrie et addictologie [CHU Henri Mondor], Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Duisburg-Essen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University Hospital [Essen, Germany], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), AP-HP / Université de Paris / INSERM COVID-19 research collaboration and AP-HP COVID CDR Initiative, 'Entrepôt de Données de Santé' AP-HP Consortium, Martinez Rico, Clara, IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Imagine - Institut des maladies génétiques (IMAGINE - U1163), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: obesity, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV]Life Sciences [q-bio], COVID-19, risk of death, General Medicine, SARS-COV-2, mood disorders, mortality, mental disorders, Archival Report, comorbidity, psychiatric disorders, antidepressants, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BackgroundPrior research suggests that psychiatric disorders could be linked to increased mortality among patients with COVID-19. However, whether all or specific psychiatric disorders are intrinsic risk factors of death in COVID-19 or whether these associations reflect the greater prevalence of medical risk factors in people with psychiatric disorders has yet to be evaluated.MethodsWe performed an observational, multicenter, retrospective cohort study to examine the association between psychiatric disorders and mortality among patients hospitalized for laboratory-confirmed COVID-19 at 36 Greater Paris University hospitals.ResultsOf 15,168 adult patients, 857 (5.7%) had an ICD-10 diagnosis of psychiatric disorder. Over a mean follow-up period of 14.6 days (SD = 17.9), 326 of 857 (38.0%) patients with a diagnosis of psychiatric disorder died compared with 1276 of 14,311 (8.9%) patients without such a diagnosis (odds ratio 6.27, 95% CI 5.40–7.28, p < .01). When adjusting for age, sex, hospital, current smoking status, and medications according to compassionate use or as part of a clinical trial, this association remained significant (adjusted odds ratio 3.27, 95% CI 2.78–3.85, p < .01). However, additional adjustments for obesity and number of medical conditions resulted in a nonsignificant association (adjusted odds ratio 1.02, 95% CI 0.84–1.23, p = .86). Exploratory analyses after the same adjustments suggested that a diagnosis of mood disorders was significantly associated with reduced mortality, which might be explained by the use of antidepressants.ConclusionsThese findings suggest that the increased risk of COVID-19–related mortality in individuals with psychiatric disorders hospitalized for COVID-19 might be explained by the greater number of medical conditions and the higher prevalence of obesity in this population and not by the underlying psychiatric disease.
Published: 2022
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47. Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions

Author: Eszter Császár, Nikolett Lénárt, Csaba Cserép, Zsuzsanna Környei, Rebeka Fekete, Balázs Pósfai, Diána Balázsfi, Balázs Hangya, Anett D. Schwarcz, Eszter Szabadits, Dávid Szöllősi, Krisztián Szigeti, Domokos Máthé, Brian L. West, Katalin Sviatkó, Ana Rita Brás, Jean-Charles Mariani, Andrea Kliewer, Zsolt Lenkei, László Hricisák, Zoltán Benyó, Mária Baranyi, Beáta Sperlágh, Ákos Menyhárt, Eszter Farkas, Ádám Dénes, Institute of Experimental Medicine [Budapest] (KOKI), Hungarian Academy of Sciences (MTA), Semmelweis University [Budapest], Hungarian Centre of Excellence for Molecular Medicine [Szeged, Hungary] (HCE2M), Plexxikon Inc. [Berkeley, CA, USA] (PI), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Szeged [Szeged], and Martinez Rico, Clara
Subjects: Adult, Carotid Artery Diseases, Male, Immunology, Mice, Transgenic, Hypercapnia, Mice, Immunology and Allergy, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Calcium Signaling, Evoked Potentials, Aged, Receptors, Purinergic, Brain, 03.01. Általános orvostudomány, Receptors, Purinergic P2Y12, Mice, Inbred C57BL, Vasodilation, nervous system, Cerebrovascular Circulation, Vibrissae, Neurovascular Coupling, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Microglia, circulatory and respiratory physiology
Abstract: International audience; Microglia, the main immunocompetent cells of the brain, regulate neuronal function, but their contribution to cerebral blood flow (CBF) regulation has remained elusive. Here, we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. Microglia establish direct, dynamic purinergic contacts with cells in the neurovascular unit that shape CBF in both mice and humans. Surprisingly, the absence of microglia or blockade of microglial P2Y12 receptor (P2Y12R) substantially impairs neurovascular coupling in mice, which is reiterated by chemogenetically induced microglial dysfunction associated with impaired ATP sensitivity. Hypercapnia induces rapid microglial calcium changes, P2Y12R-mediated formation of perivascular phylopodia, and microglial adenosine production, while depletion of microglia reduces brain pH and impairs hypercapnia-induced vasodilation. Microglial actions modulate vascular cyclic GMP levels but are partially independent of nitric oxide. Finally, microglial dysfunction markedly impairs P2Y12R-mediated cerebrovascular adaptation to common carotid artery occlusion resulting in hypoperfusion. Thus, our data reveal a previously unrecognized role for microglia in CBF regulation, with broad implications for common neurological diseases.
Published: 2022
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48. European Stroke Organisation (ESO) guidelines on mobile stroke units for prehospital stroke management

Author: Silke Walter, Heinrich J Audebert, Aristeidis H Katsanos, Karianne Larsen, Simona Sacco, Thorsten Steiner, Guillaume Turc, Georgios Tsivgoulis, Martinez Rico, Clara, Saarland University Medical Center [Homburg, Germany] (SUMC), Berlin Institute of Health (BIH), Humboldt University Of Berlin, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], McMaster University [Hamilton, Ontario], National and Kapodistrian University of Athens (NKUA), University of Oslo (UiO), University of L'Aquila [Italy] (UNIVAQ), Heidelberg University Hospital [Heidelberg], Universitätsklinikum Frankfurt, GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), and The University of Tennessee Health Science Center [Memphis] (UTHSC)
Subjects: thrombolysis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Guidelines, prehospital, stroke, Mobile Stroke Unit, large vessel occlusion, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), cardiovascular diseases, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cardiology and Cardiovascular Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The safety and efficacy of mobile stroke units (MSUs) in prehospital stroke management has recently been investigated in different clinical studies. MSUs are ambulances equipped with a CT scanner, point-of-care lab, telemedicine and are staffed with a stroke specialised medical team. This European Stroke Organisation (ESO) guideline provides an up-to-date evidence-based recommendation to assist decision-makers in their choice on using MSUs for prehospital management of suspected stroke, which includes patients with acute ischaemic stroke (AIS), intracranial haemorrhage (ICH) and stroke mimics. The guidelines were developed according to the ESO standard operating procedure and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and aggregated data meta-analyses of the literature, assessed the quality of the available evidence and made specific recommendations. Expert consensus statements are provided where sufficient evidence was not available to provide recommendations based on the GRADE approach. We found moderate evidence for suggesting MSU management for patients with suspected stroke. The patient group diagnosed with AIS shows an improvement of functional outcomes at 90 days, reduced onset to treatment times and increased proportion receiving IVT within 60 min from onset. MSU management might be beneficial for patients with ICH as MSU management was associated with a higher proportion of ICH patients being primarily transported to tertiary care stroke centres. No safety concerns (all-cause mortality, proportion of stroke mimics treated with IVT, symptomatic intracranial bleeding and major extracranial bleeding) could be identified for all patients managed with a MSU compared to conventional care. We suggest MSU management to improve prehospital management of suspected stroke patients.
Published: 2022
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49. Off-Label Use of Tenecteplase for the Treatment of Acute Ischemic Stroke A Systematic Review and Meta-analysis

Author: Katsanos, Aristeidis H, Psychogios, Klearchos, Turc, Guillaume, Sacco, Simona, de Sousa, Diana Aguiar, De Marchis, Gian Marco, Palaiodimou, Lina, Filippou, Dimitrios K, Ahmed, Niaz, Sarraj, Amrou, Menon, Bijoy K, Tsivgoulis, Georgios, Martinez Rico, Clara, McMaster University [Hamilton, Ontario], Metropolitan Hospital [Piraeus, Greece] (MH), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), University of L'Aquila [Italy] (UNIVAQ), Lusófona University [Lisbon], University of Basel (Unibas), National and Kapodistrian University of Athens (NKUA), Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], The University of Texas Health Science Center at Houston (UTHealth), University of Calgary, and The University of Tennessee Health Science Center [Memphis] (UTHSC)
Subjects: Stroke, Observational Studies as Topic, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Tenecteplase, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Off-Label Use, General Medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Brain Ischemia, Ischemic Stroke
Abstract: International audience; Importance: Tenecteplase is being evaluated as an alternative thrombolytic agent for the treatment of acute ischemic stroke (AIS) within ongoing randomized clinical trials (RCTs). In addition, nonrandomized clinical experiences with off-label use of tenecteplase vs alteplase for AIS treatment are being published.Objective: To evaluate the available evidence on the safety and efficacy of intravenous tenecteplase compared with intravenous alteplase provided by nonrandomized studies.Data sources: Eligible studies were identified by searching MEDLINE and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 12, 2021. This meta-analysis used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal.Study selection: Nonrandomized studies (prospective or retrospective) comparing intravenous tenecteplase (at any dose) with intravenous alteplase in patients with AIS were included in the analysis.Data extraction and synthesis: The crude odds ratios (ORs) and 95% CIs were calculated for the association of tenecteplase vs alteplase with the outcomes of interest and adjusted ORs were extracted if provided. Estimates using random-effects models were pooled.Main outcomes and measures: The primary outcome was the probability of good functional outcome (modified Rankin scale [mRS] score, 0-2) at 90 days.Results: Six studies were identified including a total of 1820 patients (618 [34%] treated with tenecteplase). Patients receiving tenecteplase had higher odds of 3-month good functional outcome (crude odds ratio [OR], 1.22; 95% CI, 0.90-1.66; adjusted OR, 1.60, 95% CI, 1.08-2.37), successful recanalization (crude OR, 2.82; 95% CI, 1.12-7.10; adjusted OR, 2.38; 95% CI, 1.18-4.81), and early neurological improvement (crude OR, 4.88; 95% CI, 2.03-11.71; adjusted OR, 7.60; 95% CI, 1.97-29.41). No significant differences were detected in 3-month excellent functional outcome proportions (mRS score 0-1; crude OR, 1.53; 95% CI, 0.81-2.91; adjusted OR, 2.51; 95% CI, 0.66- 9.49), symptomatic intracranial hemorrhage (crude OR, 0.97; 95% CI, 0.44-2.16; adjusted OR, 1.16; 95% CI, 0.13-10.50), or parenchymal hematoma (crude OR, 1.20; 95% CI, 0.24-5.95).Conclusions and relevance: Evidence from nonrandomized studies suggests tenecteplase is as safe as alteplase and potentially associated with improved functional outcomes compared with alteplase. Based on these findings, enrollment in the ongoing RCTs appears to be appropriate.
Published: 2022
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50. Improving upper-limb and trunk kinematics by interactive gaming in individuals with chronic stroke: a single-blinded RCT

Author: Maxime Térémetz, Alicia Garcia Alvarez, Sylvain Hanneton, Agnès Roby-Brami, Nicolas Roche, Djamel Bensmail, Påvel Lindberg, Johanna V.G. Robertson, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences du Sport-Santé de Paris (I3SP - URP3625), Université de Paris (UP), Institut des Systèmes Intelligents et de Robotique (ISIR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance aux Gestes et Applications THErapeutiques (AGATHE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut des Systèmes Intelligents et de Robotique (ISIR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Raymond Poincaré [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris Cité (UPCité), This study was funded by a PHRIP grant from APHP., and Martinez Rico, Clara
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, elbow extension, Rehabilitation, Stroke Rehabilitation, compensatory strategies, Biomechanical Phenomena, Upper Extremity, wii-therapy, Stroke, Treatment Outcome, Video Games, trunk movement, Humans, Brain Damage, Chronic, Orthopedics and Sports Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], gaming
Abstract: International audience; Background: . Commercial gaming systems are increasingly being used for stroke rehabilitation; however, their effect on upper-limb recovery versus compensation is unknown.Objectives: . We aimed to compare the effect of upper-limb rehabilitation using interactive gaming (Nintendo Wii) with dose-matched conventional therapy on elbow extension (recovery) and forward trunk motion (compensation) in individuals with chronic stroke. Secondary aims were to compare the effect on 1) clinical tests of impairment and activity, pain and effort, and 2) trajectory kinematics. We also explored arm and trunk motion (acceleration) during Wii sessions to understand how participants performed movements during Wii gaming.Methods: . This single-centre, randomized controlled trial compared 12 hourly sessions over 4 weeks of upper-limb Wii therapy to conventional therapy. Outcomes were evaluated at baseline and 4 weeks. The change in elbow extension and trunk motion during a reaching task was evaluated by electromagnetic sensors. Secondary outcomes were change in Fugl-Meyer assessment, Box and Block test, Action Research Arm Test, Motor Activity Log, and Stroke Impact Scale scores. Arm and trunk acceleration during Wii therapy was evaluated by using inertial sensors. A healthy control group was included for reference data.Results: . Nineteen participants completed Wii therapy and 21 conventional therapy (mean [SD] time post-stroke 66.4 [57.2] months). The intervention and control groups did not differ in mean change in elbow extension angle (Wii: +4.5°, 95% confidence interval [CI] 0.1; 9.1; conventional therapy: +6.4°, 95%CI 0.6; 12.2) and forward trunk position (Wii: -3.3 cm, 95%CI -6.2;-0.4]; conventional therapy: -4.1 cm, 95%CI -6.6; -1.6) (effect size: elbow, d=0.16, p=0.61; trunk, d=0.13, p=0.65). Clinical scores improved similarly but to a small extent in both groups. The amount of arm but not trunk acceleration produced during Wii sessions increased with training.Conclusions: . Supervised upper-limb gaming therapy induced similar recovery of elbow extension as conventional therapy and did not enhance the development of compensatory forward trunk movement in individuals with chronic stroke. More sessions may be necessary to induce greater improvements.
Published: 2021
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