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101. Pharmacological treatment profiles in the FACE-BD cohort: An unsupervised machine learning study, applied to a nationwide bipolar cohort✰

Author: Emilie Olié, Sébastien Brodeur, Chantal Henry, Jean-Luc Bosson, Paul Roux, Emmanuel Haffen, Bruno Aouizerate, Thierry Bougerol, Sébastien Gard, Hugo Terrisse, Frank Bellivier, Ludovic Samalin, Ophélia Godin, Raoul Belzeaux, Arnaud Pouchon, Caroline Dubertret, Raymund Schwan, Valerie Aubin, Bruno Etain, Marion Leboyer, Philippe Courtet, Mircea Polosan, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Louis Mourier - AP-HP [Colombes], Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Centre Hospitalier Universitaire [Grenoble] (CHU), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Bordeaux [Bordeaux], Centre Hospitalier Princesse Grace, Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Centre Hospitalier de Versailles André Mignot (CHV), CHU Clermont-Ferrand, and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: medicine.medical_specialty, Longitudinal study, Bipolar Disorder, Lithium (medication), [SDV]Life Sciences [q-bio], Disease, Lamotrigine, Pharmacological treatment, 03 medical and health sciences, 0302 clinical medicine, Antimanic Agents, Mood stabilizers, Internal medicine, medicine, Humans, Functioning, Longitudinal Studies, Bipolar disorder, ComputingMilieux_MISCELLANEOUS, Maintenance treatment, business.industry, Valproic Acid, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Mood, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, 030217 neurology & neurosurgery, Unsupervised Machine Learning, medicine.drug
Abstract: Background Despite thorough and validated clinical guidelines based on bipolar disorders subtypes, large pharmacological treatment heterogeneity remains in these patients. There is limited knowledge about the different treatment combinations used and their influence on patient outcomes. We attempted to determine profiles of patients based on their treatments and to understand the clinical characteristics associated with these treatment profiles. Methods This multicentre longitudinal study was performed on a French nationwide bipolar cohort database. We performed hierarchical agglomerative clustering to search for clusters of individuals based on their treatments during the first year following inclusion. We then compared patient clinical characteristics according to these clusters. Results Four groups were identified among the 1795 included patients: group 1 (“heterogeneous” n = 1099), group 2 (“lithium” n = 265), group 3 (“valproate” n = 268), and group 4 (“lamotrigine” n = 163). Proportion of bipolar 1 disorder, in groups 1 to 4 were: 48.2%, 57.0%, 48.9% and 32.5%. Groups 1 and 4 had greater functional impact at baseline and a less favorable clinical and functioning evolution at one-year follow-up, especially on GAF and FAST scales. Limitations The one-year period used for the analysis of mood stabilizing treatments remains short in the evolution of bipolar disorder. Conclusions Treatment profiles are associated with functional evolution of patients and were not clearly determined by bipolar subtypes. These profiles seem to group together common patient phenotypes. These findings do not seem to be influenced by the duration of disease prior to inclusion and neither by the number of treatments used during the follow-up period.
Published: 2021
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102. Immuno-psychiatrie et pandémie de SARS-CoV-2 : liens et possibles conséquences

Author: Ryad Tamouza, Marion Leboyer, and Jacques Daaboul
Subjects: Autism Spectrum Disorder, autism spectrum disorders, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Article, 03 medical and health sciences, 0302 clinical medicine, Arts and Humanities (miscellaneous), Pregnancy, Risk Factors, Political science, Immunopsychiatry, Humans, Mass Screening, immunopsychiatrie, troubles du spectre de l’autisme, Depressive Disorder, SARS-CoV-2, Mood Disorders, Infant, Newborn, COVID-19, Prenatal Care, Anxiety Disorders, 030227 psychiatry, Psychiatry and Mental health, schizophrénie, Neurodevelopmental Disorders, Prenatal Exposure Delayed Effects, immunopsychiatry, Schizophrenia, Female, troubles de l’humeur, Humanities, Stress, Psychological
Abstract: Resume Objectif La pandemie de SARS-CoV-2 (ou COVID-19) se propage depuis decembre 2019, et a ete, comme attendu, accompagnee d’une augmentation drastique de la prevalence des troubles anxieux et depressifs dans la population generale. Les traumatismes psychologiques peuvent bien sur, expliquer une partie de ces troubles. Cependant, dans la mesure ou les troubles psychiatriques sont egalement associes a une composante immuno-inflammatoire, les effets directs du virus sur le systeme immunitaire de l’hote, avec une reponse inflammatoire marquee, mais egalement l’inflammation secondaire a ces facteurs de stress psychosociaux, peuvent entrainer l’apparition ou l’aggravation de pathologies psychiatriques. Cet article vise donc a identifier les possibles consequences immuno-psychiatriques de la pandemie de SARS-CoV-2 qui pourraient etre utiles en termes de depistage et/ou de prise en charge. Methode Nous nous sommes appuyes sur les donnees issues des precedentes pandemies et les donnees existantes a ce jour sur les consequences psychopathologiques de la pandemie de SARS-CoV-2, pour realiser une revue de la litterature narrative sur les possibles consequences immuno-psychiatriques de la pandemie de SARS-CoV-2. Nous avons cible l’environnement gestationnel en raison des risques de troubles neuro-developpementaux pour le fœtus, d’une part, et les enfants et adultes directement infectes avec les risques de developper des troubles psychiatriques, d’autre part. Resultats Comme durant les precedentes pandemies, l’activation du systeme immunitaire due au stress et/ou a l’infection pendant la grossesse pourrait conduire a un risque accru de troubles du neuro-developpement chez le fœtus (schizophrenie et troubles du spectre de l’autisme). De plus, chez les individus exposes a des traumatismes psychologiques et/ou infectes par le virus, le risque de troubles psychiatriques, notamment de troubles de l’humeur, est probable. Conclusion Dans ce contexte, des mesures de depistage et de prise en charge dediees sont indispensables. Il est, de fait, important de proposer aux individus ayant ete infectes par le virus, un suivi rapproche afin de mettre en place une prise en charge la plus precoce possible. De meme chez les femmes enceintes, le depistage de troubles de l’humeur pendant la grossesse ou en post-partum doit etre facilite. Le suivi des bebes nes pendant la periode pandemique doit etre renforce afin de depister et de prendre en charge d’eventuels troubles du neuro-developpement.
Published: 2021
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103. Brain-immune crosstalk in the treatment of major depressive disorder

Author: Marion Leboyer, Lucile Capuron, Hemmo A. Drexhage, Francesco Benedetti, Sara Poletti, Brenda W.J.H. Penninx, Carmine M. Pariante, Igor Branchi, S. Poggini, Ryad Tamouza, Branchi, I., Poggini, S., Capuron, L., Benedetti, F., Poletti, S., Tamouza, R., Drexhage, H. A., Penninx, B. W. J. H., Pariante, C. M., Istituto Superiore di Sanita [Rome], 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), 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), CLinical Psychology, Division of Psychological Medicine, PO51, Immunology, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and APH - Digital Health
Subjects: Kynurenine pathway, Brain-body, T cell, Inflammation, Immunopsychiatry, 03 medical and health sciences, 0302 clinical medicine, Immune system, SDG 3 - Good Health and Well-being, Humans, Medicine, Pharmacology (medical), Neural plasticity, Kynurenine, Biological Psychiatry, Pharmacology, Depressive Disorder, Major, Neuronal Plasticity, business.industry, Brain, Antidepressants, medicine.disease, Mental illness, Antidepressive Agents, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Crosstalk (biology), Metabolism, medicine.anatomical_structure, Neurology, [SDE]Environmental Sciences, Major depressive disorder, Antidepressant, Neurology (clinical), medicine.symptom, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; A growing number of studies are pointing out the need for a conceptual shift from a brain-centered to a body-inclusive approach in mental health research. In this perspective, the link between the immune and the nervous system, which are deeply interconnected and continuously interacting, is one of the most important novel theoretical framework to investigate the biological bases of major depressive disorder and, more in general, mental illness. Indeed, depressed patients show high levels of inflammatory markers, administration of pro-inflammatory drugs triggers a depressive symptomatology and antidepressant efficacy is reduced by excessive immune system activation. A number of molecular and cellular mechanisms have been hypothesized to act as a link between the immune and brain function, thus representing potential pharmacologically targetable processes for the development of novel and effective therapeutic strategies. These include the modulation of the kynurenine pathway, the crosstalk between metabolic and inflammatory processes, the imbalance in acquired immune responses, in particular T cell responses, and the interplay between neural plasticity and immune system activation. In the personalized medicine approach, the assessment and regulation of these processes have the potential to lead, respectively, to novel diagnostic approaches for the prediction of treatment outcome according to the patient's immunological profile, and to improved efficacy of antidepressant compounds through immune modulation.
Published: 2021
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104. Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

Author: Rajagopal Krishnamoorthy, Philippe Beaune, Marion Leboyer, Ryad Tamouza, Bruno O. Villoutreix, Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), 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), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Drug, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), media_common.quotation_subject, [SDV]Life Sciences [q-bio], phenothiazine, Drug resistance, Disease, Bioinformatics, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, chemoinformatics, high-throughput screening, antihistamine, 03 medical and health sciences, 0302 clinical medicine, Medicine, Adverse effect, 030304 developmental biology, media_common, Original Research, 0303 health sciences, drug repurposing, business.industry, COVID-19, Computer Science Applications, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], Drug repositioning, 030104 developmental biology, Chemistry (miscellaneous), Advances and Applications in Bioinformatics and Chemistry, 030220 oncology & carcinogenesis, Antihistaminic drugs, prophylaxis, business, 030217 neurology & neurosurgery
Abstract: Bruno O Villoutreix,1 Rajagopal Krishnamoorthy,2 Ryad Tamouza,2 Marion Leboyer,2 Philippe Beaune3 1INSERM U1141, NeuroDiderot, Université de Paris, Hôpital Robert-Debré, Paris, F-75019, France; 2Université Paris Est Créteil, INSERM U955, IMRB, Laboratoire Neuropsychiatrie Translationnelle, AP-HP, Département Medico-Universitaire de Psychiatrie et d’Addictologie (DMU ADAPT), Hôpital Henri Mondor, Fondation FondaMental, Créteil, F-94010, France; 3INSERM U1138, Centre de Recherche des Cordeliers, Université de Paris, Paris, 75006, FranceCorrespondence: Bruno O Villoutreix Email bruno.villoutreix@inserm.frIntroduction: There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients.Objective: Based upon clinical observations, we proposed that some psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection. This observation is investigated in the light of experimental in vitro data on SARS-CoV-2.Methods: SARS-CoV-2 high-throughput screening results are available at the NCATS COVID-19 portal. We investigated the in vitro anti-viral activity of many psychotropic and antihistaminic drugs using chemoinformatics approaches.Results and Discussion: We analyze our clinical observations in the light of SARS-CoV-2 experimental screening results and propose that several cationic amphiphilic psychotropic and antihistaminic drugs could protect people from SARS-CoV-2 infection; some of these molecules have very limited adverse effects and could be used as prophylactic drugs. Other cationic amphiphilic drugs used in other disease areas are also highlighted. Recent analyses of patient electronic health records reported by several research groups indicate that some of these molecules could be of interest at different stages of the disease progression. In addition, recently reported drug combination studies further suggest that it might be valuable to associate several cationic amphiphilic drugs. Taken together, these observations underline the need for clinical trials to fully evaluate the potentials of these molecules, some fitting in the so-called category of broad-spectrum antiviral agents. Repositioning orally available drugs that have moderate side effects and should act on molecular mechanisms less prone to drug resistance would indeed be of utmost importance to deal with COVID-19.Keywords: chemoinformatics, COVID-19, high-throughput screening, phenothiazine, prophylaxis, antihistamine, drug repurposing
Published: 2021
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105. DNA hydrolysing IgG catalytic antibodies: an emerging link between psychoses and autoimmunity

Author: Ryad Tamouza, Marion Leboyer, Ravi Philip Rajkumar, Aparna Sundaresh, Rajendran Ramesh, M A Vijayalakshmi, Vir Singh Negi, A S Kamalanathan, and Rajagopal Krishnamoorthy
Subjects: 0301 basic medicine, RC435-571, medicine.disease_cause, Article, Autoimmunity, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, mental disorders, medicine, Psychology, Bipolar disorder, Psychiatry, Lupus erythematosus, biology, business.industry, medicine.disease, Comorbidity, Psychiatry and Mental health, 030104 developmental biology, chemistry, Polyclonal antibodies, Schizophrenia, Immunology, biology.protein, Antibody, Psychiatric disorders, business, 030217 neurology & neurosurgery, DNA
Abstract: It is not uncommon to observe autoimmune comorbidities in a significant subset of patients with psychotic disorders, namely schizophrenia (SCZ) and bipolar disorder (BPD). To understand the autoimmune basis, the DNA abyzme activity mediated by serum polyclonal IgG Abs were examined in psychoses patients, quantitatively, by an in-house optimized DNase assay. A similar activity exhibited by IgG Abs from neuropsychiatric-systemic lupus erythematosus (NP-SLE) patients was used as a comparator. Our data revealed that the IgG DNase activity of SCZ was close to that of NP-SLE and it was twofold higher than the healthy controls. Interestingly, the association between DNase activity with PANSS (positive, general and total scores) and MADRS were noted in a subgroup of SCZ and BPD patients, respectively. In our study group, the levels of IL-6 and total IgG in BPD patients were higher than SCZ and healthy controls, indicating a relatively inflammatory nature in BPD, while autoimmune comorbidity was mainly observed in SCZ patients.
Published: 2021

106. IMMUNO-PSYCHIATRY AND INFLAMMATION

Author: Marion Leboyer
Subjects: Pharmacology, Psychiatry and Mental health, Neurology, Pharmacology (medical), Neurology (clinical), Biological Psychiatry
Published: 2022
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107. TLR2 genetic diversity and the risk of Schizophrenia

Author: fayza Ayari, Arij Ben Chaaben, Hajer Abbaza, Ons Mihoub, Nesrine Ouni, Amani Mankai, Wahid Boukouaci, Maher kharat, Marion Leboyer, and Ryad Tamouza
Abstract: Objectives: Schizophrenia (SZ) is a multifactorial disorder involving complex interactions between genetic and environmental factors, where immune dysfunction plays a key etiopathogenic role. In order to explore the control of innate immune responses in SZ, we aimed to investigate the potential association of two TLR2 polymorphisms (rs3804099T>C and rs3804100T>C) with susceptibility to SZ in a Tunisian population. Methods: TLR2 genotyping was done using a TaqMan 5’-nuclease assay for 150 SZ patients and 201 healthy controls (HC) with no history of psychiatric illness.Results: we did not observe any significant differences in genotypes and alleles frequencies between the SZ patient and control groups (p>0.05).Conclusion: The results indicate that rs3804099T>C and rs3804100T>C in TLR 2 polymorphisms are unlikely to have a significant impact on the genetic predisposition to SZ in the presently studied population-group.
Published: 2022
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108. Direct medical cost of bipolar disorder: Insights from the FACE-BD longitudinal cohort

Author: Charles Laidi, Ophélia Godin, Bruno Etain, Frank Bellivier, Yannis Elandaloussi, Emilie Olié, Bruno Aouizerate, Sébastien Gard, Joséphine Loftus, Raoul Belzeaux, Caroline Dubertret, Hakim Laouamri, Christine Passerieux, Agnès Pelletier, Mircea Polosan, Raymund Schwan, Ludovic Samalin, Pierre-Michel Llorca, Philippe Courtet, Isabelle Durand-Zaleski, Marion Leboyer, 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), CHU Henri Mondor [Créteil], Fondation FondaMental [Créteil], Centre hospitalier Charles Perrens [Bordeaux], Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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 Princesse Grace, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Hôpital Louis Mourier - AP-HP [Colombes], Centre Hospitalier de Versailles André Mignot (CHV), Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), 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-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 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 Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Clermont-Ferrand, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Hôpital Hôtel-Dieu [Paris], 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), Authors express all our thanks to the nurses, and to the patients who were included in the present study. The authors thank Hakim Laouamri and his team (Seif Ben Salem, Karmène Souyris, Victor Barteau and Mohamed Laaidi) for the development of the FACE-BD computer interface (eBipolar©), data management, quality control and regulatory aspects., CHU Henri Mondor, Guerineau, Nathalie C., and Hôpital Charles Perrens
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, Bipolar disorder, Cost, Cost-Benefit Analysis, [SDV]Life Sciences [q-bio], Medico-economic, MESH: Health Care Costs, Health Care Costs, Cohort Studies, [SDV] Life Sciences [q-bio], Hospitalization, Psychiatry and Mental health, Clinical Psychology, MESH: Bipolar Disorder, 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], MESH: Cohort Studies, health care economics and organizations, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Cost-Benefit Analysis
Abstract: International audience; Background: Bipolar disorder (BD) is a severe chronic psychiatric disorder affecting 0.5 to 1% of the population worldwide. To date, most studies have estimated the cost of BD via information sourced from insurance claims with limited information on clinical characteristics and course of BD. The aims of this study are (i) to estimate the direct healthcare cost associated with BD and to identify contributing factors and (ii) to study the evolution of cost during a two-year follow-up period.Method: We analyzed a sample of 1116 individuals with BD included in the Advanced Centers of Expertise in Bipolar Disorder cohort. We estimated the direct healthcare cost per year and per patient, and we identified the clinical features of patients with BD associated with higher direct healthcare costs. In a subsample of patients followed up for two years centers of expertise for BD, we studied the evolution of direct healthcare cost.Results: The average cost of bipolar disorder was € 6910 per year and per patient. Clinical features of BD, sociodemographic characteristics, and associated addiction were associated with higher direct healthcare costs. In the subsample of patients followed-up for two years, direct healthcare cost dropped by more than 50%, strongly suggesting the beneficial effect of specialized care organization.Limitation: We did not estimate indirect healthcare and intangible costs.Conclusion: Our study investigates the cost of BD and its evolution in a deeply phenotyped longitudinal sample. Cost-utility and cost-effectiveness analyses are required to inform resource allocation decisions and to promote innovative healthcare organizations.
Published: 2022
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109. TLR2 genetic diversity associated with the risk of Schizophrenia development in a Tunisian population

Author: fayza Ayari, Arij Ben Chaaben, Hajer Abbaza, Ons Mihoub, Nesrine Ouni, Amani Mankai, Wahid Boukouaci, Maher kharat, Marion Leboyer, and Ryad Tamouza
Abstract: Objectives: Schizophrenia (SZ) is a multifactorial disorder involving complex interactions between genetic and environmental factors, where immune dysfunction plays a key etiopathogenic role. In order to explore the control of innate immune responses in SZ, we aimed to investigate the potential association of nine TLR2/TLR4 polymorphisms (TLR2: rs4696480T>A, rs3804099T>C, rs3804100T>C; TLR4: rs1927914G>A, rs10759932T>C, rs4986790A>G, rs4986791T>C, rs11536889G>C and rs11536891T>C) with susceptibility to SZ in a Tunisian population. Methods: TLR2-4 genotyping was done using a TaqMan 5’-nuclease assay for 150 SZ patients and 201 healthy controls (HC) with no history of psychiatric illness.Results: We found that only the TLR2 rs4696480T>A polymorphism was significantly associated with SZ. Indeed, the AA genotype was significantly associated with an increased risk of SZ (46% versus 31%, p= 4.7*10-3, OR =1.87 and 95% CI [1.18-2.97]). The frequency of the TA genotype was significantly more prevalent in HC than in SZ patients (27% versus 43%, p=2.1*10-3) and may be associated with protection against SZ (OR = 0.49 and 95% CI [0.30- 0.80]). The ACT haplotype of the TLR2 gene was identified as a risk haplotype for SZ. Moreover, we found a significant association between AA genotype and domestic violence (AA versus TT+AT; 71% versus 49%; p= 0.036, OR = 3.24, 95% CI = 1.20–10.80). Concerning the other polymorphisms no significant association was found.Conclusion: The results indicate that TLR2 genetic diversity may play a role in genetic vulnerability to SZ.
Published: 2022
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110. Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach - CORRIGENDUM

Author: Micah, Cearns, Azmeraw T, Amare, Klaus Oliver, Schubert, Anbupalam, Thalamuthu, Joseph, Frank, Fabian, Streit, Mazda, Adli, Nirmala, Akula, Kazufumi, Akiyama, Raffaella, Ardau, Bárbara, Arias, JeanMichel, Aubry, Lena, Backlund, Abesh Kumar, Bhattacharjee, Frank, Bellivier, Antonio, Benabarre, Susanne, Bengesser, Joanna M, Biernacka, Armin, Birner, Clara, Brichant-Petitjean, Pablo, Cervantes, HsiChung, Chen, Caterina, Chillotti, Sven, Cichon, Cristiana, Cruceanu, Piotr M, Czerski, Nina, Dalkner, Alexandre, Dayer, Franziska, Degenhardt, Maria Del, Zompo, J Raymond, DePaulo, Bruno, Étain, Peter, Falkai, Andreas J, Forstner, Louise, Frisen, Mark A, Frye, Janice M, Fullerton, Sébastien, Gard, Julie S, Garnham, Fernando S, Goes, Maria, Grigoroiu-Serbanescu, Paul, Grof, Ryota, Hashimoto, Joanna, Hauser, Urs, Heilbronner, Stefan, Herms, Per, Hoffmann, Andrea, Hofmann, Liping, Hou, Yi-Hsiang, Hsu, Stephane, Jamain, Esther, Jiménez, Jean-Pierre, Kahn, Layla, Kassem, Po-Hsiu, Kuo, Tadafumi, Kato, John, Kelsoe, Sarah, Kittel-Schneider, Sebastian, Kliwicki, Barbara, König, Ichiro, Kusumi, Gonzalo, Laje, Mikael, Landén, Catharina, Lavebratt, Marion, Leboyer, Susan G, Leckband, Mario, Maj, Mirko, Manchia, Lina, Martinsson, Michael J, McCarthy, Susan, McElroy, Francesc, Colom, Marina, Mitjans, Francis M, Mondimore, Palmiero, Monteleone, Caroline M, Nievergelt, Markus M, Nöthen, Tomas, Novák, Claire, O'Donovan, Norio, Ozaki, Vincent, Millischer, Sergi, Papiol, Andrea, Pfennig, Claudia, Pisanu, James B, Potash, Andreas, Reif, Eva, Reininghaus, Guy A, Rouleau, Janusz K, Rybakowski, Martin, Schalling, Peter R, Schofield, Barbara W, Schweizer, Giovanni, Severino, Tatyana, Shekhtman, Paul D, Shilling, Katzutaka, Shimoda, Christian, Simhandl, Claire M, Slaney, Alessio, Squassina, Thomas, Stamm, Pavla, Stopkova, Fasil, TekolaAyele, Alfonso, Tortorella, Gustavo, Turecki, Julia, Veeh, Eduard, Vieta, Stephanie H, Witt, Gloria, Roberts, Peter P, Zandi, Martin, Alda, Michael, Bauer, Francis J, McMahon, Philip B, Mitchell, Thomas G, Schulze, Marcella, Rietschel, Scott R, Clark, and Bernhard T, Baune
Subjects: Machine Learning, Psychiatry and Mental health, Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant, Bipolar Disorder, Humans, Lithium
Published: 2022

111. Association between childhood maltreatment and the clinical course of bipolar disorders: a survival analysis of mood recurrences

Author: Diane, Grillault Laroche, Ophélia, Godin, Raoul, Belzeaux, Katia, M'Bailara, Joséphine, Loftus, Philippe, Courtet, Caroline, Dubertret, Emmanuel, Haffen, Pierre Michel, Llorca, Emilie, Olie, Christine, Passerieux, Mircea, Polosan, Raymund, Schwan, Marion, Leboyer, Frank, Bellivier, Cynthia, Marie-Claire, Bruno, Etain, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Henri Mondor, Fondation FondaMental [Créteil], 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), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Charles Perrens [Bordeaux], Laboratoire de psychologie (LabPsy), Université de Bordeaux (UB), 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 Princesse Grace, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hôpital Louis Mourier - AP-HP [Colombes], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre Hospitalier de Versailles André Mignot (CHV), 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 Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Université de Lorraine (UL), 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, Université Paris Cité (UPCité), This research was supported by the Foundation FondaMental, Institut National de la Santé et de la Recherche Médicale (INSERM), AP- HP, and by the Investissements d’Avenir program managed by the ANR under reference ANR- 11- IDEX- 0004- 02 and ANR- 10-COHO- 10- 01. This work was supported by the Agence Nationale de la Recherche (ANR- 18-CE37- 0002). We thank INSERM and Labex BioPsy for the PhD funding (Poste Accueil) to DGL. CMC is supported by the Centre National pour la Recherche Scientifique (CNRS). These funding sources had no role in the study design, data collection, analysis, preparation of the manuscript, or decision to submit the manuscript for publication., FACE-BD collaborators, ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010), ANR-18-CE37-0002,CT-ScarBip,MicroARNs et réseaux de gènes co-exprimés associés aux traumatismes dans l'enfance: de la cicatrice moléculaire aux pistes thérapeutiques dans les troubles bipolaires(2018), Hôpital Charles Perrens, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Guerineau, Nathalie C., Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, Cohortes - FondaMental-Cohortes - - Psy-COH2010 - ANR-10-COHO-0010 - COHO - VALID, and APPEL À PROJETS GÉNÉRIQUE 2018 - MicroARNs et réseaux de gènes co-exprimés associés aux traumatismes dans l'enfance: de la cicatrice moléculaire aux pistes thérapeutiques dans les troubles bipolaires - - CT-ScarBip2018 - ANR-18-CE37-0002 - AAPG2018 - VALID
Subjects: mood recurrence, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, childhood trauma, survival analyses, Bipolar disorder, [SDV]Life Sciences [q-bio], childhood maltreatment, Survival Analysis, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Recurrence, physical abuse, Surveys and Questionnaires, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Child Abuse, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Child, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Retrospective Studies
Abstract: International audience; Objectives: Childhood maltreatment, also referred as childhood trauma, increases the severity of Bipolar Disorders (BD). Childhood maltreatment has been associated with more frequent mood recurrences, however mostly in retrospective studies. Since scarce, further prospective studies are required to identify whether childhood maltreatment may be associated with the time to recurrence in BD.Methods: Individuals with BD (N=2008) were assessed clinically and for childhood maltreatment at baseline, and followed-up for two years. The cumulative probability of mood recurrence over time was estimated with the Turnbull's extension of the Kaplan-Meier analysis for interval-censored data, including childhood maltreatment as a whole, and then maltreatment subtypes as predictors. Analyses were adjusted for potential confounding factors.Results: The median duration of follow-up was 22.3 month (IQR:12.0-24.8). Univariable analyses showed associations between childhood maltreatment, in particular all types of abuses (emotional, physical and sexual) or emotional neglect, and a shorter time to recurrence (all p values
Published: 2022
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112. Automatic fiber bundle segmentation in massive tractography datasets using a multi-subject bundle atlas.

Author: Pamela Guevara, Delphine Duclap, Cyril Poupon, Linda Marrakchi-Kacem, Pierre Fillard, Denis Le Bihan, Marion Leboyer, Josselin Houenou, and Jean-François Mangin
Published: 2012
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113. Measuring the Patient Experience of Mental Health Care: A Systematic and Critical Review of Patient-Reported Experience Measures

Author: Franck Schürhoff, Ludovic Samalin, Guillaume Fond, Marion Leboyer, Sara Fernandes, Bruno Aouizerate, Chantal Henry, Magali Coldefy, Pierre-Michel Llorca, Xavier Zendjidjian, Karine Baumstarck, Bruno Etain, Fabrice Berna, Christophe Lançon, Pascal Auquier, and Laurent Boyer
Subjects: medicine.medical_specialty, business.industry, Health Policy, media_common.quotation_subject, 05 social sciences, Health services research, Medicine (miscellaneous), 0506 political science, 03 medical and health sciences, Interpersonal relationship, 0302 clinical medicine, Patient satisfaction, Systematic review, Family medicine, Item response theory, Patient experience, 050602 political science & public administration, medicine, Quality (business), 030212 general & internal medicine, Computerized adaptive testing, business, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Social Sciences (miscellaneous), media_common
Abstract: Background There is growing concern about measuring patient experience with mental health care. There are currently numerous patient-reported experience measures (PREMs) available for mental health care, but there is little guidance for selecting the most suitable instruments. The objective of this systematic review was to provide an overview of the psychometric properties and the content of available PREMs. Methods A comprehensive review following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines was conducted using the MEDLINE database with no date restrictions. The content of PREMs was analyzed using an inductive qualitative approach, and the methodological quality was assessed according to Pesudovs quality criteria. Results A total of 86 articles examining 75 PREMs and totaling 1932 items were included. Only four PREMs used statistical methods from item response theory (IRT). The 1932 items covered seven key mental health care domains: interpersonal relationships (22.6%), followed by respect and dignity (19.3%), access and care coordination (14.9%), drug therapy (14.1%), information (9.6%), psychological care (6.8%) and care environment (6.1%). Additionally, a few items focused on patient satisfaction (6.7%) rather than patient experience. No instrument covered the latent trait continuum of patient experience, as defined by the inductive qualitative approach, and the psychometric properties of the instruments were heterogeneous. Conclusion This work is a critical step in the creation of an item library to measure mental health care patient-reported experience that will be used in France to develop, validate, and standardize item banks and computerized adaptive testing (CAT) based on IRT. It will also provide internationally replicable measures that will allow direct comparisons of mental health care systems. Trial registration NCT02491866.
Published: 2020
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114. A Brain Capital Grand Strategy: toward economic reimagination

Author: Marion Leboyer, Charles F. Reynolds, Erin Smith, Ioannis Tarnanas, Ernestine Fu, Julio Licinio, Chee H. Ng, Dilip V. Jeste, Sarah Caddick, Sandra B. Chapman, Michael Berk, Zoe Wainer, Harris A. Eyre, Husseini K. Manji, William Hynes, Ian H. Robertson, Eric A. Storch, Howard Fillit, Rhoda Au, Ryan Abbott, Jair C. Soares, Andrew W. Lo, Agustín Ibáñez, Gowri Aragam, Walter D. Dawson, Diab Ali, Facundo Manes, Patrick Brannelly, Helen Lavretsky, Cara M. Altimus, Jeffrey L. Cummings, Bill Wilkerson, and Kunmi Sobowale
Subjects: Employment, 0301 basic medicine, Aging, Work, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), media_common.quotation_subject, BRAIN SKILLS, Efficiency, Medical and Health Sciences, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cognition, 0302 clinical medicine, Humans, ECONOMIC RESILIENCE, Investments, Molecular Biology, media_common, Psychiatry, Resilience, Extramural, Psychology and Cognitive Sciences, Neurosciences, Brain, COVID-19, purl.org/becyt/ford/3.1 [https], Art, Resilience, Psychological, Biological Sciences, BRAIN CAPITAL, Capital (architecture), Psychiatry and Mental health, Mental Health, 030104 developmental biology, Neurology, Socioeconomic Factors, Workforce, Psychological, purl.org/becyt/ford/3 [https], Quality-Adjusted Life Years, Humanities, 030217 neurology & neurosurgery
Abstract: The time is now to catalyze a Grand Strategy. Brain Capital can be a key component in shaping economic resilience?linked to our digitalized, globalized, complex, and interconnected yet fragile global economy. Brain Capital resonates with existing efforts and helps build long-term globaleconomic recovery that promotes brain health and brain skills helping address urgent challenges caused and exacerbated by COVID. Current policies, concepts and economic measures neither account for the neuroscientific drivers of productivity nor the increasingly brain skills focused workforce demands of the twenty-first century.Furthermore, current approaches are insufficient to combat the rising complexity of challenges brought about by COVID. The preservation and development of Brain Capital positively impacts educational, social, health, institutional, and economic dimensions at the individual andcollective level. Hence, it should be considered a strategic resource for a country, corporations, and public policies in a brain-based world. Fil: Smith, Erin. University of Stanford; Estados Unidos Fil: Ali, Diab. Ochsner Clinical School; Estados Unidos. University of Queensland; Australia Fil: Wilkerson, Bill. Mental Health International; Canadá Fil: Dawson, Walter D.. Oregon Health and Science University; Estados Unidos. Portland State University; Estados Unidos. Trinity College Dublin; Irlanda. University of California; Estados Unidos Fil: Sobowale, Kunmi. University of California; Estados Unidos Fil: Reynolds, Charles. Univeristy of Pittsburgh. School of Medicine; Estados Unidos Fil: Berk, Michael. Deakin University; Australia. University of Melbourne; Australia Fil: Lavretsky, Helen. University of California; Estados Unidos Fil: Jeste, Dilip. University of California at San Diego; Estados Unidos Fil: Ng, Chee H.. University of Melbourne; Australia Fil: Soares, Jair C.. University of Texas Health Science Center at Houston; Estados Unidos Fil: Aragam, Gowri. University of Stanford; Estados Unidos Fil: Wainer, Zoe. University of Melbourne; Australia Fil: Manji, Husseini K.. Johnson & Johnson; Estados Unidos. University of Duke; Estados Unidos Fil: Licinio, Julio. SUNY Upstate Medical University; Estados Unidos Fil: Lo, Andrew W.. Massachusetts Institute of Technology; Estados Unidos Fil: Storch, Eric. Baylor College of Medicine; Fil: Fu, Ernestine. University of Stanford; Estados Unidos Fil: Leboyer, Marion. University Paris Est Créteil; Francia Fil: Tarnanas, Ioannis. Trinity College Dublin; Irlanda. University of California; Estados Unidos Fil: Ibañez, Agustin Mariano. Trinity College Dublin; Irlanda. Universidad Autónoma del Caribe; Colombia. University of California; Estados Unidos. Universidad Adolfo Ibañez; Chile. Universidad de San Andrés. Departamento de Matemáticas y Ciencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Manes, Facundo Francisco. Universidad Favaloro; Argentina. Instituto de Neurología Cognitiva; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Caddick, Sarah. Thalamic; Reino Unido Fil: Fillit, Howard. The Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Abbott, Ryan. University of California; Estados Unidos. University of Surrey; Reino Unido Fil: Robertson, Ian H.. University of Texas; Estados Unidos. Trinity College Dublin; Irlanda. University of California; Estados Unidos Fil: Chapman, Sandra B.. University of Texas; Estados Unidos Fil: Au, Rhoda. University of Boston. School of Medicine; Estados Unidos Fil: Altimus, Cara M.. Milken Institute; Estados Unidos Fil: Hynes, William. Organisation for Economic Cooperation and Development. New Approaches to Economic Challenges Unit; Francia Fil: Brannelly, Patrick. Rainwater Charitable Foundation; Estados Unidos Fil: Cummings, Jeffrey. Cleveland Clinic Lou Ruvo Center for Brain Health; Estados Unidos. University Of Nevada, Las Vegas; Estados Unidos Fil: Eyre, Harris A.. Deakin University; Australia. University of Melbourne; Australia. University of Stanford; Estados Unidos. University of Adelaide; Australia
Published: 2020
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115. Psychotic, Mood, and Anxiety Disorders and Venous Thromboembolism: A Systematic Review and Meta-Analysis

Author: Marion Leboyer, Célia Kowal, Hugo Peyre, Antoine Pelissolo, Baptiste Pignon, Franck Schürhoff, and Ali Amad
Subjects: medicine.medical_specialty, Deep vein, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Odds Ratio, medicine, Humans, cardiovascular diseases, Bipolar disorder, Applied Psychology, Depression (differential diagnoses), Venous Thrombosis, business.industry, Venous Thromboembolism, Odds ratio, equipment and supplies, medicine.disease, Anxiety Disorders, 3. Good health, 030227 psychiatry, Pulmonary embolism, Psychiatry and Mental health, medicine.anatomical_structure, Mood, Meta-analysis, Anxiety, medicine.symptom, Pulmonary Embolism, business, 030217 neurology & neurosurgery
Abstract: OBJECTIVE Several studies have shown that psychiatric disorders can be associated with venous thromboembolism (VTE) risk, that is, pulmonary embolism (PE) and/or deep vein thrombosis (DVT). In this study, we provide a systematic review and meta-analyses of the studies addressing this issue. METHODS All studies addressing the risk of VTE phenomena (whole VTE, PE, DVT, fatal VTE) in individuals with psychotic, mood, and anxiety disorders published between 1998 and 2019 were reviewed and included in the meta-analyses. Main characteristics of the studies and data concerning VTE risk were extracted. The methodological qualities of the studies were also analyzed. A random-effects meta-analysis model was used. A meta-analysis was conducted separately for each disorder, as well as separately for unadjusted and adjusted studies. Meta-analyses were repeated considering only good-quality studies. Heterogeneity was assessed. RESULTS Sixteen studies were reviewed and 15 included in the meta-analyses. Psychotic and bipolar disorders were significantly associated with VTE risk (VTE, DVT, PE, and fatal VTE for psychotic disorder: odds ratios [ORs] between 1.29 and 2.20; VTE, DVT, and PE for bipolar disorder: ORs between 1.22 and 2.14). Depression and anxiety disorders were associated with VTE risk only in adjusted analyses (DVT and PE for depression: ORs = 1.29; VTE and PE for anxiety disorders: ORs between 1.14 and 1.49). CONCLUSIONS The risk of VTE among individuals with psychiatric disorders may be explained by hypercoagulability and stasis, with both being related to, and independent of, treatment adverse effects. VTE risk should be taken into consideration in the treatment for people with psychiatric disorders.
Published: 2020
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116. 'Reading the Mind in the Eyes' in Autistic Adults is Modulated by Valence and Difficulty: An InFoR Study

Author: Manuel Bouvard, Richard Delorme, Matias Baltazar, Myriam Ly Le-Moal, Anouck Amestoy, Daniel Umbricht, Isabelle Scheid, Sandrine Couffin-Cadiergues, Eleonora Murzi, Marion Leboyer, David Monnet, Axelle Martinez Teruel, Lorraine Murtagh, Marie-Maude Geoffray, and Christopher H. Chatham
Subjects: Adult, medicine.medical_specialty, genetic structures, difficulty, Autism Spectrum Disorder, media_common.quotation_subject, autism spectrum disorders, Emotions, Audiology, High functioning, behavioral disciplines and activities, PSYCHOLOGY, 03 medical and health sciences, 0302 clinical medicine, mental disorders, medicine, Reading the Mind in the Eyes, Humans, 0501 psychology and cognitive sciences, Generalized Linear Mixed Model, Valence (psychology), valence, Genetics (clinical), Research Articles, media_common, General Neuroscience, 05 social sciences, medicine.disease, Feeling, Cohort, Autism, Very low risk, Neurology (clinical), Psychology, 030217 neurology & neurosurgery, Neurotypical, 050104 developmental & child psychology, Research Article
Abstract: Autism spectrum disorders (ASD) are heterogeneous and complex neurodevelopmental conditions that urgently need reliable and sensitive measures to inform diagnosis properly. The Reading the Mind in the Eyes Task (or Eyes Test from now on) is widely used for this purpose. A recent study showed that subcategories of items of the children version of the Eyes Test could be especially discriminative to distinguish ASD and control children. Here, we analyzed the performance on the Eyes Test of 30 high functioning (IQ > 70) adults with ASD and 29 controls from the InFoR cohort multicentric study, using a Generalized Linear Mixed Model. We found that valence and difficulty modulate the performance on the Eyes Test, with easy and positive items being the most discriminative to distinguish ASD and controls. In particular, we suggest this result might be actionable to discriminate ASD patients from controls in subgroups where their overall scores show less difference with controls. We propose for future research the computation of two additional indexes when using the Eyes Test: the first focusing on the easy and positive items (applying a threshold of 70% of correct responses for these items, above which people are at very low risk of having ASD) and the second focusing on the performance gain from difficult to easy items (with a progression of less than 15% showing high risk of having ASD). Our findings open the possibility for a major change in how the Eyes Test is used to inform diagnosis in ASD. LAY SUMMARY: The Eyes Test is used worldwide to inform autism spectrum disorders (ASD) diagnosis. We show here that ASD and neurotypical adults show the most difference in performance on subgroups of items: ASD adults do not improve as expected when comparing easy and difficult items, and they do not show an improvement for items displaying a positive feeling. We advise clinicians to focus on these comparisons to increase the property of the test to distinguish people with ASD from neurotypical adults.
Published: 2020

117. An Association Between Serotonin <scp>1A</scp> Receptor, Gray Matter Volume, and Sociability in Healthy Subjects and in Autism Spectrum Disorder

Author: Arthur Lefevre, Raphaelle Mottolese, Marion Leboyer, Nathalie Richard, and Angela Sirigu
Subjects: Male, Autism Spectrum Disorder, media_common.quotation_subject, Serotonergic, Revised NEO Personality Inventory, 03 medical and health sciences, 0302 clinical medicine, mental disorders, medicine, Humans, Personality, 0501 psychology and cognitive sciences, Gray Matter, Genetics (clinical), media_common, business.industry, General Neuroscience, Putamen, 05 social sciences, Brain, medicine.disease, Magnetic Resonance Imaging, Healthy Volunteers, Autism spectrum disorder, Receptor, Serotonin, 5-HT1A, Autism, Female, Neurology (clinical), Serotonin, business, 030217 neurology & neurosurgery, Neurotypical, 050104 developmental & child psychology, Clinical psychology
Abstract: Central serotonin is an important molecular pathway, involved in the regulation of social behavior and gray matter volume (GMV). In men with autism spectrum disorders (ASD), the serotonergic system and the GMV have been found disrupted. Here, we investigated the relation between serotonin, GMV, and social personality in men with typical development (TD) and in men with ASD. We combined anatomical magnetic resonance imaging, Positron emission tomography scan with 2'-methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine radioligand and revised NEO personality inventory personality questionnaire to examine the association between serotonin 1A receptor (5-HT1A R) binding potential, GMV and social personality in 24 adult male TD subjects and 18 male men with ASD. In both groups, we found a positive correlation between 5-HT1A R binding potential and GMV in a region dependent manner. In the TD group, we observed a negative correlation between 5-HT1A R and GMV in the left and right posterior putamen. 5HT1A R binding and GMV in the putamen further correlated with social personality scores in the TD group. None of these associations were found in men with ASD, although no differences were observed for 5-HT1A R concentration among the two groups. Our findings point to a deregulation of 5-HT1A R density in the striatum of men with ASD, a failure that might contribute to their social disturbances. Serotonin is suspected to be involved in the pathophysiology of autism. We provide evidence for a role of serotonin 1A receptor in social behavior through a specific regulation of GMV in the putamen region in neurotypical subjects but not in men with autism. This suggests a potential impairment of the serotonergic system in men with autism which may contribute to patients' social disturbances. Our findings suggest further investigation on the role of serotonin 1A receptor and its activity in the striatum to regulate social behavior. Autism Res 2020, 13: 1843-1855. © 2020 International Society for Autism Research and Wiley Periodicals LLC LAY SUMMARY: Serotonin is suspected to be involved in the pathophysiology of autism. We provide evidence for a role of serotonin 1A receptor in social behavior through a specific regulation of gray matter volume in the putamen region in neurotypical subjects but not in men with autism. This suggests a potential impairment of the serotonergic system in men with autism which may contribute to patients' social disturbances. Our findings suggest further investigation on the role of serotonin 1A receptor and its activity in the striatum to regulate social behavior.
Published: 2020
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118. Precision psychiatry with immunological and cognitive biomarkers: a multi-domain prediction for the diagnosis of bipolar disorder or schizophrenia using machine learning

Author: Marion Leboyer, Nora Hamdani, Svetha Venkatesh, Jean Romain Richard, John Yearwood, Truyen Tran, Chandan Karmakar, Robert H. Yolken, Ryad Tamouza, Brisa Simoes Fernandes, H. Laouamri, and Michael Berk
Subjects: medicine.medical_specialty, Bipolar Disorder, Neuropsychological Tests, Molecular neuroscience, Machine learning, computer.software_genre, Article, lcsh:RC321-571, Machine Learning, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cognition, 0302 clinical medicine, medicine, Humans, Bipolar disorder, Psychiatry, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, business.industry, Diagnostic markers, medicine.disease, Inflammatory biomarkers, Peripheral blood, 030227 psychiatry, Psychiatry and Mental health, Multi domain, Immunological Factors, Schizophrenia, Artificial intelligence, Differential diagnosis, business, computer, Biomarkers, 030217 neurology & neurosurgery
Abstract: Precision psychiatry is attracting increasing attention lately as a recognized priority. One of the goals of precision psychiatry is to develop tools capable of aiding a clinically informed psychiatric diagnosis objectively. Cognitive, inflammatory and immunological factors are altered in both bipolar disorder (BD) and schizophrenia (SZ), however, most of these alterations do not respect diagnostic boundaries from a phenomenological perspective and possess great variability in different individuals with the same phenotypic diagnosis and, consequently, none so far has proven to have the ability of reliably aiding in the differential diagnosis of BD and SZ. We developed a probabilistic multi-domain data integration model consisting of immune and inflammatory biomarkers in peripheral blood and cognitive biomarkers using machine learning to predict diagnosis of BD and SZ. A total of 416 participants, being 323, 372, and 279 subjects for blood, cognition and combined biomarkers analysis, respectively. Our multi-domain model performances for the BD vs. control (sensitivity 80% and specificity 71%) and for the SZ vs. control (sensitivity 84% and specificity 81%) pairs were high in general, however, our multi-domain model had only moderate performance for the differential diagnosis of BD and SZ (sensitivity 71% and specificity 73%). In conclusion, our results show that the diagnosis of BD and of SZ, and that the differential diagnosis of BD and SZ can be predicted with possible clinical utility by a computational machine learning algorithm employing blood and cognitive biomarkers, and that their integration in a multi-domain outperforms algorithms based in only one domain. Independent studies are needed to validate these findings.
Published: 2020
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119. Psychiatric comorbidities in bipolar disorders: An examination of the prevalence and chronology of onset according to sex and bipolar subtype

Author: Joséphine Loftus, Jean-Pierre Kahn, Marion Leboyer, Bruno Étain, Florence Vorspan, Franck Bellivier, S Gard, Jan Scott, Chantal Henry, and Romain Icick
Subjects: Adult, Male, medicine.medical_specialty, Bipolar Disorder, Psychological intervention, Prevalence, Comorbidity, 03 medical and health sciences, 0302 clinical medicine, Recall bias, mental disorders, medicine, Humans, Bipolar disorder, Psychiatry, Retrospective Studies, business.industry, Panic disorder, medicine.disease, Anxiety Disorders, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Eating disorders, Anxiety, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Agoraphobia
Abstract: Objectives Bipolar Disorder (BD) is frequently comorbid with other psychiatric disorders. However, few studies systematically examine which disorders are more likely to occur pre- or post-BD onset. We examine the prevalence and Age At Onset (AAO) of psychiatric conditions in adults with BD. Methods A structured clinical interview was used to assess lifetime history and AAO of alcohol and cannabis misuse, suicide attempts, anxiety and eating disorders in a French sample of euthymic patients with BD (n = 739). Regression analyses were used to test for statistically significant associations between rates and AAO of comorbidities in BD groups stratified by sex or subtype. Results Prevalence of alcohol and cannabis misuse was associated with male sex and BD-I subtype; whilst most anxiety and eating disorders were associated with female sex. The AAO of most comorbid conditions preceded that of BD, except for panic disorder, agoraphobia and alcohol misuse. Few variations were observed in AAO of comorbidities according to groups. Limitations All assessments were retrospective, so estimates of prevalence rates and especially exact AAO of some comorbidities are at risk of recall bias. Conclusions Sex and BD subtype are associated with different rates of comorbid disorders. However, there were minimal between group differences in median AAO of comorbidities. By describing the chronological sequence of comorbidities in BD we were able to demonstrate that a minority of comorbidities typically occurred post-onset of BD. This is noteworthy as these disorders might be amenable to interventions aimed at early secondary prevention.
Published: 2020
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120. Contribution of common and rare damaging variants in familial forms of bipolar disorder and phenotypic outcome

Author: Elisa Courtois, Mark Schmid, Orly Wajsbrot, Caroline Barau, Philippe Le Corvoisier, Bruno Aouizerate, Frank Bellivier, Raoul Belzeaux, Caroline Dubertret, Jean-Pierre Kahn, Marion Leboyer, Emilie Olie, Christine Passerieux, Mircea Polosan, Bruno Etain, Stéphane Jamain, and and the FondaMental Advanced Centers of Expertise in Bipolar Disorders (FACE-BD)
Subjects: lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:RC321-571
Abstract: Genome-wide association studies on bipolar disorders (BD) have revealed an additive polygenic contribution of common single-nucleotide polymorphisms (SNPs). However, these SNPs explain only 25% of the overall genetic variance and suggest a role of rare variants in BD vulnerability. Here, we combined high-throughput genotyping data and whole-exome sequencing in cohorts of individuals with BD as well as in multiplex families with a high density of affected individuals in order to determine the contribution of both common and rare variants to BD genetic vulnerability. Using polygenic risk scores (PRS), we showed a strong contribution of common polymorphisms previously associated with BD and schizophrenia (SZ) and noticed that those specifically associated with SZ contributed more in familial forms of BD than in non-familial ones. The analysis of rare damaging variants shared by affected individuals in multiplex families with BD revealed a single interaction network enriched in neuronal and developmental biological pathways, as well as in the regulation of gene expression. We identified four genes with a higher mutation rate in individuals with BD than in the general population and showed that mutations in two of them were associated with specific clinical manifestations. In addition, we showed a significant negative correlation between PRS and the number of rare damaging variants specifically in unaffected individuals of multiplex families. Altogether, our results suggest that common and rare genetic variants both contribute to the familial aggregation of BD and this genetic architecture may explain the heterogeneity of clinical manifestations in multiplex families.
Published: 2020
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121. A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort)

Author: René S. Kahn, Marion Leboyer, Dick Schijven, Christiaan H. Vinkers, Sinan Guloksuz, Mark K Bakker, Sophie E Ter Hark, Stéphane Jamain, Jean-François Deleuze, Bochao D. Lin, Bjørn H Ebdrup, Réjane Troudet, Jurjen J. Luykx, Anne Boland-Auge, Anil K. Malhotra, Utrecht University [Utrecht], 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), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], Centre National de Recherche en Génomique Humaine [Évry] (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut de Biologie François JACOB (JACOB), 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), Donald and Barbara Zucker School of Medicine at Hofstra/Northwell [Hempstead, NY, USA], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Yale School of Medicine [New Haven, Connecticut] (YSM), Amsterdam UMC - Amsterdam University Medical Center, Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research [Glostrup, Denmark] (CCINSR), University of Copenhagen = Københavns Universitet (UCPH), University Medical Center [Utrecht], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, GGNet Mental Health [Apeldoorn, The Netherlands], Yale University School of Medicine, Amsterdam UMC, University of Copenhagen = Københavns Universitet (KU), Jamain, Stéphane, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Psychiatry, and Anatomy and neurosciences
Subjects: Hydroxymethylglutaryl-CoA Synthase, Male, medicine.medical_treatment, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Genome-wide association study, VARIANTS, Weight Gain, Bioinformatics, Cohort Studies, 0302 clinical medicine, GWAS, Pharmacology (medical), 2. Zero hunger, 0303 health sciences, ASSOCIATION, Original Papers, INSULIN, 3. Good health, Psychiatry and Mental health, Schizophrenia, Cohort, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], schizophrenia, Female, Amisulpride, CLOZAPINE, GROWTH-HORMONE, medicine.symptom, SELENOPROTEIN-P, Antipsychotic Agents, medicine.drug, Adult, amisulpride-induced weight gain, body mass index, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Polymorphism, Single Nucleotide, Young Adult, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], SEPP1, medicine, Humans, Antipsychotic, Alleles, 030304 developmental biology, Genetic association, Pharmacology, business.industry, MEDICATIONS, PROFILES, medicine.disease, antipsychotics, Psychotic Disorders, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genetic Loci, Pharmacogenetics, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, business, Weight gain, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Background: Antipsychotic-induced weight gain is a common and debilitating side effect of antipsychotics. Although genome-wide association studies of antipsychotic-induced weight gain have been performed, few genome-wide loci have been discovered. Moreover, these genome-wide association studies have included a wide variety of antipsychotic compounds. Aims: We aim to gain more insight in the genomic loci affecting antipsychotic-induced weight gain. Given the variable pharmacological properties of antipsychotics, we hypothesized that targeting a single antipsychotic compound would provide new clues about genomic loci affecting antipsychotic-induced weight gain. Methods: All subjects included for this genome-wide association study ( n=339) were first-episode schizophrenia spectrum disorder patients treated with amisulpride and were minimally medicated (defined as antipsychotic use Results: Our genome-wide association analyses for antipsychotic-induced weight gain yielded one genome-wide significant hit (rs78310016; β=1.05; p=3.66 × 10−08; n=206) in a locus not previously associated with antipsychotic-induced weight gain or body mass index. Minor allele carriers had an odds ratio of 3.98 ( p=1.0 × 10−03) for clinically meaningful antipsychotic-induced weight gain (⩾7% of baseline weight). In silico analysis elucidated a chromatin interaction with 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. In an attempt to replicate single-nucleotide polymorphisms previously associated with antipsychotic-induced weight gain, we found none were associated with amisulpride-induced weight gain. Conclusion: Our findings suggest the involvement of rs78310016 and possibly 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 in antipsychotic-induced weight gain. In line with the unique binding profile of this atypical antipsychotic, our findings furthermore hint that biological mechanisms underlying amisulpride-induced weight gain differ from antipsychotic-induced weight gain by other atypical antipsychotics.
Published: 2020
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122. Childhood maltreatment and polygenic risk in bipolar disorders

Author: Monica Aas, Marion Leboyer, Francesco Bettella, Ingrid Melle, Jean-Pierre Kahn, Chantal Henry, Stéphane Jamain, Sébastien Gard, Trine Vik Lagerberg, Bruno Etain, Ole A. Andreassen, Frank Bellivier, and Sofie R. Aminoff
Subjects: Adult, Male, Multifactorial Inheritance, Bipolar Disorder, Poison control, Suicide, Attempted, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Surveys and Questionnaires, Injury prevention, Humans, Medicine, Child Abuse, Bipolar disorder, Age of Onset, Risk factor, Child, Psychological abuse, Biological Psychiatry, Framingham Risk Score, business.industry, Adult Survivors of Child Abuse, CTQ tree, Middle Aged, medicine.disease, 030227 psychiatry, Affect, Psychiatry and Mental health, Mood, Psychotic Disorders, Female, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Background Childhood maltreatment is a well-known risk factor for developing a more severe and complex form of bipolar disorders (BD). However, knowledge is scarce about the interactions between childhood maltreatment and underlying genetic vulnerability on the clinical expression of BD. Method We assigned a BD-polygenic risk score (BD-PRS), calculated from the Psychiatric Genomics Consortium, to each individual in a sample of 402 cases with BD. The lifetime clinical expression of BD was characterized using structured interviews and patients completed the Childhood Trauma Questionnaire (CTQ) to assess the severity of childhood maltreatment. Results Cases who reported more severe childhood maltreatment had a lower BD-PRS (rho = -0.12, P = .01), especially when considering emotional abuse (rho = -0.16, P = .001). An interaction between BD-PRS and childhood maltreatment was observed for the risk of rapid cycling (P = .01). No further interactions between BD-PRS and childhood maltreatment were observed for other clinical characteristics (age at onset, suicide attempts, number of mood episodes, mixed features, substance use disorders and psychotic symptoms). Conclusion Our study is the first to show that less genetic risk may be needed to develop a more unstable form of BD when exposed to childhood maltreatment. Our study supports childhood trauma as an independent risk factor for BD.
Published: 2020
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123. Drugs used to treat bipolar disorder act via microRNAs to regulate expression of genes involved in neurite outgrowth

Author: Laura J. Gray, Marion Leboyer, Bruna Panizzutti, Ben Wade, Briana Spolding, Stéphane Jamain, Tamsyn M. Crowley, Ken Walder, Michael Berk, Timothy Connor, Srisaiyini Kidnapillai, and Chiara C. Bortolasci
Subjects: Neurite, Neuronal Outgrowth, Gene Expression, Disease, Lamotrigine, Bioinformatics, Quetiapine Fumarate, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Pharmacology (medical), Bipolar disorder, Cells, Cultured, 030304 developmental biology, Pharmacology, 0303 health sciences, Valproic Acid, Drug discovery, business.industry, Drug Synergism, medicine.disease, MicroRNAs, Psychiatry and Mental health, medicine.symptom, Lithium Chloride, business, Mania, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background:The drugs commonly used to treat bipolar disorder have limited efficacy and drug discovery is hampered by the paucity of knowledge of the pathophysiology of this disease. This study aims to explore the role of microRNAs in bipolar disorder and understand the molecular mechanisms of action of commonly used bipolar disorder drugs.Methods:The transcriptional effects of bipolar disorder drug combination (lithium, valproate, lamotrigine and quetiapine) in cultured human neuronal cells were studied using next generation sequencing. Differential expression of genes ( n=20) and microRNAs ( n=6) was assessed and the differentially expressed microRNAs were confirmed with TaqMan MicroRNA Assays. The expression of the differentially expressed microRNAs were inhibited to determine bipolar disorder drug effects on their target genes ( n=8). Independent samples t-test was used for normally distributed data and Kruskal-Wallis/Mann-Whitney U test was used for data not distributed normally. Significance levels were set at pResults:We found that bipolar disorder drugs tended to increase the expression of miR-128 and miR-378 ( pConclusions:We conclude that at a transcriptional level, bipolar disorder drugs affect several genes in concert that would increase neurite outgrowth and neurogenesis and hence neural plasticity, and that this effect is mediated (at least in part) by modulation of the expression of these two key microRNAs.
Published: 2020
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124. PM2.5 and PM10 air pollution peaks are associated with emergency department visits for psychotic and mood disorders: an eleven-year study

Author: Baptiste Pignon, Cynthia Borel, Mohamed Lajnef, Jean-Romain Richard, Andrei Szöke, François Hemery, Marion Leboyer, Gilles Foret, and Franck Schürhoff
Abstract: Particulate matter with a diameter of less than 10 µm (PM 10 ) or less than 2.5 µm (PM 2.5 ) are major air pollutants poorly studies regarding psychiatric disorders. We aimed to explore the association between PM 10 and PM 2.5 air pollution peaks and the daily number of emergency visits for psychotic and mood disorders. Clinical data were collected from the Emergency department of the Centre Hospitalo-Universitaire Henri-Mondor (Créteil, France) from 2008 to 2018. Air pollution data were collected from public databases. Pollution peaks periods were defined as days for which the daily mean level of PM was above nationally predefined warning thresholds (20 µg/m 3 for PM 2.5 , and 50 µg/m 3 for PM 10 ), and the 6 following days. Multivariable analyses compared the number of daily visits for psychotic and mood disorders according to pollution peak period. After adjustment on meteorological variables, the daily number of emergency visits for psychotic disorders was significantly higher during with PM 2.5 and PM 10 air pollution peaks periods; while the number of visits for unipolar depressive disorders was higher only during PM 10 peaks periods (β=0.059, p-value=0.034). There was no significant differences concerning bipolar disorders. Differences in the effects of PM air pollution on psychotic and mood disorders should be analyzed in further studies.
Published: 2022
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125. Reader Response: Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis

Author: Ludger Tebartz van Elst, Kimon Runge, Dominique Endres, Marion Leboyer, and Janet L. Cunningham
Subjects: Psychotic Disorders, Neuroimmunomodulation, Humans, Neurology (clinical)
Published: 2022

126. Predictors of functional impairment in bipolar disorder: Results from 13 cohorts from seven countries by the global bipolar cohort collaborative

Author: Katherine E. Burdick, Caitlin E. Millett, Anastasia K. Yocum, Cara M. Altimus, Ole A. Andreassen, Valerie Aubin, Raoul Belzeaux, Michael Berk, Joanna M. Biernacka, Hilary P. Blumberg, Anthony J. Cleare, Claudia Diaz‐Byrd, Caroline Dubertret, Bruno Etain, Lisa T. Eyler, Brent P. Forester, Janice M. Fullerton, Mark A. Frye, Sébastien Gard, Ophelia Godin, Emmanuel Haffen, Federica Klaus, Trine Vik Lagerberg, Marion Leboyer, Anabel Martinez‐Aran, Susan McElroy, Philip B. Mitchell, Emilie Olie, Phebe Olorunfemi, Christine Passerieux, Amy T. Peters, Daniel L. Pham, Mircea Polosan, Julia R. Potter, Martha Sajatovic, Ludovic Samalin, Raymund Schwan, Megan Shanahan, Brisa Solé, Rebecca Strawbridge, Amanda L. Stuart, Ivan Torres, Torrill Ueland, Eduard Vieta, Lana J. Williams, Anna L. Wrobel, Lakshmi N. Yatham, Allan H. Young, Andrew A. Nierenberg, Melvin G. McInnis, Centre Hospitalier Princesse Grace, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-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), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), 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), CHU Henri Mondor, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (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, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Université de Lorraine (UL), Harvard Medical School [Boston] (HMS), University of Michigan [Ann Arbor], University of Michigan System, Milken Institute School of Public Health, The George Washington University (GW), Norwegian Centre for Mental Disorders Research [Oslo] (NORMENT), University of Oslo (UiO)-Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB)-Oslo University Hospital [Oslo], Assistance Publique - Hôpitaux de Marseille (APHM), Deakin University [Burwood], Orygen Youth Health Research Centre [Melbourne], University of Melbourne, Mayo Clinic [Rochester], Yale School of Medicine [New Haven, Connecticut] (YSM), King‘s College London, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lariboisière-Fernand-Widal [APHP], University of California [San Diego] (UC San Diego), University of California (UC), McLean Hospital [Belmont, Ma.], University of New South Wales [Sydney] (UNSW), Centre hospitalier Charles Perrens [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], Université Bourgogne Franche-Comté [COMUE] (UBFC), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), University of Cincinnati College of Medicine, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Massachusetts General Hospital [Boston], Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Universitaire [Grenoble] (CHU), Case Western Reserve University [Cleveland], CHU Clermont-Ferrand, University of British Columbia (UBC), University of Oslo (UiO), IMPACT Strategic Research Centre [VIC, Australia] (Barwon Health), Guerineau, Nathalie C., CHU Henri Mondor [Créteil], and Hôpital Charles Perrens
Subjects: Bipolar Disorder, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV]Life Sciences [q-bio], Cohort Studies, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Affect, [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], Prospective Studies, Longitudinal Studies, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biological Psychiatry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objectives: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD.Methods: Thirteen cohorts from 7 countries included n=5,882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived "higher versus lower function" as the dependent variable and selected clinical and demographic variables as predictors.Results: We found high rates of functional impairment, ranging from 41-75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning.Conclusions: The bipolar clinical research community is poised to work together to characterize the multi-dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large-scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness.
Published: 2022
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127. PM

Author: Baptiste, Pignon, Cynthia, Borel, Mohamed, Lajnef, Jean-Romain, Richard, Andrei, Szöke, François, Hemery, Marion, Leboyer, Gilles, Foret, and Franck, Schürhoff
Subjects: Air Pollutants, Mood Disorders, Air Pollution, Humans, Particulate Matter, Emergency Service, Hospital
Abstract: Particulate matters with a diameter of less than 10 µm (PM
Published: 2022

128. Association between mental disorders and COVID-19 outcomes among inpatients in France: A retrospective nationwide population-based study

Author: Alexandre Descamps, Jérôme Frenkiel, Kevin Zarca, Charles Laidi, Ophélia Godin, Odile Launay, Marion Leboyer, and Isabelle Durand-Zaleski
Subjects: Adult, Hospitalization, Psychiatry and Mental health, Inpatients, Mental Disorders, COVID-19, Humans, Dementia, Biological Psychiatry, Retrospective Studies
Abstract: Mental disorders are at-risk of severe COVID-19 outcomes. There is limited and heterogeneous national data in hospital settings evaluating the risks associated with any pre-existing mental disorder, and susceptible subgroups. Our study aimed to investigate the association between pre-existing psychiatric disorders and outcomes of adults hospitalised for COVID-19.We used data obtained from the French national hospital database linked to the state-level psychiatric registry. The primary outcome was 30-days in-hospital mortality. Secondary outcomes were to compare the length of hospital stay, Intensive Care Unit (ICU) admission and ICU length. Propensity score matching analysis was used to control for COVID-19 confounding factors between patients with or without mental disorder and stratified by psychiatric subgroups.Among 97 302 adults hospitalised for COVID-19 from March to September 2020, 10 083 (10.3%) had a pre-existing mental disorder, mainly dementia (3581 [35.5%]), mood disorders (1298 [12.9%]), anxiety disorders (995 [9.9%]), psychoactive substance use disorders (960 [9.5%]), and psychotic disorders (866 [8.6%]). In propensity-matched analysis, 30-days in-hospital mortality was increased among those with at least one pre-existing mental disorder (hazard ratio (HR) 1.15, 95% CI 1.08-1.23), psychotic disorder (1.90, 1.24-2.90), and psychoactive substance disorders (1.53, 1.10-2.14). The odds of ICU admission were consistently decreased for patients with any pre-existing mental disorder (OR 0.83, 95% CI 0.76-0.92) and for those with dementia (0.64, 0.53-0.76).Pre-existing mental disorders were independently associated with in-hospital mortality. These findings underscore the important need for adequate care and targeted interventions for at-risk individuals with severe mental illness.
Published: 2022

129. Recommendations of the treatment-resistant depression expert center network for promoting tobacco smoking cessation based on the results from the real-world FACE-TRD national cohort

Author: Alexandra Garosi, Christelle Andrieu-Haller, Olivier Doumy, Nicolas Suc, Julia Maruani, J.-B. Genty, Martin Breyton, Raphaëlle Richieri, Frank Bellivierid, Antoine Yrondid, Mathilde Horn, T Korchia, Guillaume Fond, Laurent Boyers, Rémi Moirand, Bruno Aouizerate, Jean Petrucci, Christophe Arbus, Michel Walter, Thierry Bougerol, Jérôme Holtzmann, Philippe Courtet, Vincent Camus, Christophe Lançon, Guillaume Vaiva, Pierre-Michel Llorca, Fanny Moliere, Djamila Bennabi, Wissam El-Hage, Florian Stephan, Mélanie Faugere, Ludovic Samalin, Romain Rey, Ophélia Godin, Marion Leboyer, Emmanuel Haffen, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Fondation FondaMental [Créteil], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Bourgogne Franche-Comté [COMUE] (UBFC), Neurobiologie et Psychiatrie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_treatment, MESH: Tobacco Smoking, Suicide, Attempted, tobacco, MESH: Nicotine, Cohort Studies, Depressive Disorder, Treatment-Resistant, chemistry.chemical_compound, Surveys and Questionnaires, Medicine, Precision Medicine, Varenicline, MESH: Cohort Studies, Depression (differential diagnoses), health care economics and organizations, education.field_of_study, public mental health, MESH: Middle Aged, MESH: Suicidal Ideation, public health, Middle Aged, MESH: Smoking Cessation, psychiatry, Cohort, depression, MESH: Suicide, Attempted, Female, mental health, Nicotine, medicine.medical_specialty, Population, education, MESH: Precision Medicine, smoking, Suicidal Ideation, MESH: Depressive Disorder, Treatment-Resistant, Sex Factors, MESH: Sex Factors, Tobacco Smoking, Humans, MESH: Surveys and Questionnaires, Psychiatry, Biological Psychiatry, Pharmacology, MESH: Humans, Suicide attempt, business.industry, Odds ratio, medicine.disease, MESH: Male, schizophrenia, chemistry, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Smoking cessation, Smoking Cessation, business, Treatment-resistant depression, MESH: Female
Abstract: Background Tobacco smoking has been associated with suicide, impulsivity and depression in non-clinical populations with differences across sexes. Objective To determine the role of tobacco smoking in Treatment-Resistant Depression (TRD) according to sex in a precision-medicine approach. Method The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at 6 months. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at 6 months on their smoking and psychiatric hospitalization outcomes. Results 355 TRD participants were included (222 women). The smoking rate was much higher in TRD women compared to the French general population (34% vs 24%) while it was comparable for men (approximately 29%). In multivariate analyses, compared to non-smoking women, female smokers had significantly increased number of lifetime psychiatric hospitalizations (standardized beta B = 0.232, p = 0.014) and electro-convulsive therapy (adjusted odds ratio (aOR) = 2.748, p = 0.005), increased suicidal ideations (aOR = 4.047, p = 0.031), history of suicide attempt (aOR = 1.994, p = 0.033), and increased impulsivity (B = 0.210, p = 0.006) and were more frequently treated by benzodiazepines (aOR = 1.848, p = 0.035) and third- or fourth-line TRD treatments (antipsychotics aOR = 2.270, p = 0.006, mood stabilizers aOR = 2.067 p = 0.044). Tobacco smoking at baseline was predictive of psychiatric hospitalization within 6 months in persistent smoking women (aOR = 2.636, p = 0.031). These results were not replicated in men, for whom tobacco smoking was only associated with increased clinician-rated and self-reported depressive symptoms (respectively B = 0.207, p = 0.022 and B = 0.184, p = 0.048). The smoking cessation rate at 6 months was higher in women than in men (12% vs. 7%). No patient was administered nicotine substitute or varenicline at the two timepoints. Interpretation Combining these results and those of the literature, we recommend that active tobacco cessation should be promoted in TRD to improve depression, suicide and impulsivity especially in women. Female smokers appear as a specific population with heavier mental health outcomes that should be specifically addressed.
Published: 2022
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130. A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Author: Luca Sforzini, Courtney Worrell, Melisa Kose, Ian M. Anderson, Bruno Aouizerate, Volker Arolt, Michael Bauer, Bernhard T. Baune, Pierre Blier, Anthony J. Cleare, Philip J. Cowen, Timothy G. Dinan, Andrea Fagiolini, I. Nicol Ferrier, Ulrich Hegerl, Andrew D. Krystal, Marion Leboyer, R. Hamish McAllister-Williams, Roger S. McIntyre, Andreas Meyer-Lindenberg, Andrew H. Miller, Charles B. Nemeroff, Claus Normann, David Nutt, Stefano Pallanti, Luca Pani, Brenda W. J. H. Penninx, Alan F. Schatzberg, Richard C. Shelton, Lakshmi N. Yatham, Allan H. Young, Roland Zahn, Georgios Aislaitner, Florence Butlen-Ducuing, Christine Fletcher, Marion Haberkamp, Thomas Laughren, Fanni-Laura Mäntylä, Koen Schruers, Andrew Thomson, Gara Arteaga-Henríquez, Francesco Benedetti, Lucinda Cash-Gibson, Woo Ri Chae, Heidi De Smedt, Stefan M. Gold, Witte J. G. Hoogendijk, Valeria Jordán Mondragón, Eduard Maron, Jadwiga Martynowicz, Elisa Melloni, Christian Otte, Gabriela Perez-Fuentes, Sara Poletti, Mark E. Schmidt, Edwin van de Ketterij, Katherine Woo, Yanina Flossbach, J. Antoni Ramos-Quiroga, Adam J. Savitz, Carmine M. Pariante, Sforzini, L., Worrell, C., Kose, M., Anderson, I. M., Aouizerate, B., Arolt, V., Bauer, M., Baune, B. T., Blier, P., Cleare, A. J., Cowen, P. J., Dinan, T. G., Fagiolini, A., Ferrier, I. N., Hegerl, U., Krystal, A. D., Leboyer, M., McAllister-Williams, R. H., Mcintyre, R. S., Meyer-Lindenberg, A., Miller, A. H., Nemeroff, C. B., Normann, C., Nutt, D., Pallanti, S., Pani, L., Penninx, B. W. J. H., Schatzberg, A. F., Shelton, R. C., Yatham, L. N., Young, A. H., Zahn, R., Aislaitner, G., Butlen-Ducuing, F., Fletcher, C., Haberkamp, M., Laughren, T., Mantyla, F. -L., Schruers, K., Thomson, A., Arteaga-Henriquez, G., Benedetti, F., Cash-Gibson, L., Chae, W. R., De Smedt, H., Gold, S. M., Hoogendijk, W. J. G., Mondragon, V. J., Maron, E., Martynowicz, J., Melloni, E., Otte, C., Perez-Fuentes, G., Poletti, S., Schmidt, M. E., van de Ketterij, E., Woo, K., Flossbach, Y., Ramos-Quiroga, J. A., Savitz, A. J., Pariante, C. M., Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, 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), Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden = Dresden University of Technology (TU Dresden), The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 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), and European Project: (grant No 116060),IMPRiND
Subjects: Depression, Diagnostic markers, DISORDER, STIMULATION, STAR-ASTERISK-D, SEROTONIN REUPTAKE INHIBITORS, Major Depressive Disorder, Clinical Trials and Supportive Activities, Medical and Health Sciences, Depressive Disorder, Treatment-Resistant, Cellular and Molecular Neuroscience, REPORT QIDS-SR, SDG 3 - Good Health and Well-being, Clinical Research, Humans, RATING-SCALE, Molecular Biology, METAANALYSIS, Psychiatry, Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant, Psychology and Cognitive Sciences, Major, REMISSION, Biological Sciences, Serious Mental Illness, Brain Disorders, Psychiatry and Mental health, QUICK INVENTORY, Mental Health, Good Health and Well Being, SYMPTOMATOLOGY, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract: Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.
Published: 2022
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131. Low omega-3 polyunsaturated fatty acids predict reduced response to standard antidepressants in patients with major depressive disorder

Author: Sofia Cussotto, Inês Delgado, Giovanni Oriolo, Jonas Kemper, Diane Begarie, Sandra Dexpert, Julie Sauvant, Marion Leboyer, Bruno Aouizerate, Rocío Martin‐Santos, Martin Schaefer, and Lucile Capuron
Subjects: Psychiatry and Mental health, Clinical Psychology, Depressive Disorder, Major, Docosahexaenoic Acids, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Humans, Antidepressive Agents
Abstract: Major depressive disorder (MDD) is characterized by a high rate of treatment resistance. Omega (ω)-3 polyunsaturated fatty acids (PUFAs) were shown to correlate with depressive phenotype both in rodents and in humans. However, few studies to date have investigated the role of PUFAs in antidepressant response. The primary aim of this study was to assess the link between baseline PUFA composition and changes in depressive symptoms as well as antidepressant response in a multicenter study of depressed patients.Sixty depressed adults who met criteria for MDD according to DSM-IV-TR were recruited. Neuropsychiatric evaluations occurred at baseline and after 4 and 8 weeks of treatment with standard antidepressants, including escitalopram (N = 45), sertraline (N = 13) and venlafaxine (N = 2). At study endpoint, patients were stratified into responders (R) or non-responders (NR) based on their MADRS (Montgomery-Åsberg Depression Rating Scale) score. Baseline PUFA levels were assessed and their association with clinical response was determined.Lower ω-3 PUFA levels were associated to worse baseline symptomatology. Baseline levels of PUFAs were significantly different between R and NR, with R exhibiting lower docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and ω-3 index; and higher ω-6/ω-3 ratio than NR before the start of antidepressant treatment. DHA levels as well as the ω-3 index and ω-6/ω-3 ratio significantly predicted response to antidepressants at study endpoint.These results show that baseline levels of PUFAs predict later response to standard antidepressants in depressed subjects. They suggest that PUFA intake and/or metabolism represent a novel modifiable tool for the management of unresponsive depressed patients.
Published: 2022

132. Violent suicide attempt history in elderly patients with bipolar disorder: The role of sex, abdominal obesity, and verbal memory: Results from the FACE-BD cohort (FondaMental Advanced center of Expertise for Bipolar Disorders)

Author: Raoul Belzeaux, Mircea Polosan, Aiste Lengvenyte, Paul Roux, Joséphine Loftus, Sébastien Gard, Christine Passerieux, Emeline Marlinge, Emmanuel Haffen, Emilie Olié, Valerie Aubin, Bruno Aouizerate, Caroline Dubertret, Raymund Schwan, Bruno Etain, Philippe Courtet, Pierre-Michel Llorca, Marion Leboyer, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Fondation FondaMental [Créteil], Vilnius University [Vilnius], Centre hospitalier Charles Perrens [Bordeaux], Hôpital Princesse Grace [Monaco], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Louis Mourier - AP-HP [Colombes], Université Paris Cité (UPCité), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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 Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre Hospitalier de Versailles André Mignot (CHV), 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, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), This work was supported (in part) by the Fondation FondaMental, Créteil, France and by the Investissements d'Avenir programs managed by the ANR under references ANR-11- IDEX-0004-02 and ANR-10-COHO-10-01, Hôpital Charles Perrens, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Université Paris-Saclay, Guerineau, Nathalie C., and Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: Male, Bipolar disorder, [SDV]Life Sciences [q-bio], Suicide, Attempted, 03 medical and health sciences, 0302 clinical medicine, Memory, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Obesity, Abdominal obesity, Aged, Retrospective Studies, California Verbal Learning Test, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Suicide attempt, business.industry, Cohort, Cognition, Middle Aged, medicine.disease, Middle age, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Suicide, Cross-Sectional Studies, Obesity, Abdominal, Quantitative Biology - Neurons and Cognition, FOS: Biological sciences, Female, Neurons and Cognition (q-bio.NC), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cognitive function, medicine.symptom, Verbal memory, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Clinical psychology
Abstract: International audience; Background: Bipolar disorder (BD) is a chronic, lifelong condition, associated with increased risk of obesity, cognitive impairment, and suicidal behaviors. Abdominal obesity and a higher risk of violent suicide attempt (SA) seem to be shared correlates with older age, BD, and male sex until middle age when menopause-related female body changes occur. This study aimed at assessing the role of abdominal obesity and cognition in the violent SA burden of individuals with BD.Methods: From the well-defined nationwide cohort FACE-BD (FondaMental Advanced center of Expertise for Bipolar Disorders), we extracted data on 619 euthymic BD patients that were 50 years or older at inclusion. Cross-sectional clinical, cognitive, and metabolic assessments were performed. SA history was based on self-report.Results: Violent SA, in contrast to non-violent and no SA, was associated with higher waist circumference, abdominal obesity and poorer California Verbal Learning Test short-delay free recall (CVLT-SDFR) (ANOVA, p < .001, p = .014, and p = .006). Waist circumference and abdominal obesity were associated with violent SA history independently of sex, BD type and anxiety disorder (Exp(B) 1.02, CI 1.00-1.05, p = .018; Exp(B) 2.16, CI 1.00-4.64, p = .009, accordingly). In an exploratory model, waist circumference and CVLT-SDFR performance mediated the association between male sex and violent SA.Limitations: Cross-sectional design and retrospective reporting.Conclusions: Violent SA history was associated with abdominal obesity and poorer verbal memory in older age BD patients. These factors were interlinked and might mediate the association between male sex and violent SA.
Published: 2022
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133. Cerebellar Atypicalities in Autism?

Author: Charles Laidi, Dorothea L. Floris, Julian Tillmann, Yannis Elandaloussi, Mariam Zabihi, Tony Charman, Thomas Wolfers, Sarah Durston, Carolin Moessnang, Flavio Dell’Acqua, Christine Ecker, Eva Loth, Declan Murphy, Simon Baron-Cohen, Jan K. Buitelaar, Andre F. Marquand, Christian F. Beckmann, Vincent Frouin, Marion Leboyer, Edouard Duchesnay, Pierrick Coupé, Josselin Houenou, null Tobias Banaschewski, Antonio Persico, Antonia San Jose Caceres, Hannah Hayward, Daisy Crawley, Jessica Faulkner, Jessica Sabet, Claire Ellis, Bethany Oakley, Rosemary Holt, Sara Ambrosino, Nico Bast, Sarah Baumeister, Annika Rausch, Carsten Bours, Ineke Cornelissen, Daniel von Rhein, Larry O’Dwyer, Jumana Ahmad, Emily Simonoff, 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), 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), Radboud University [Nijmegen], IMRB - 'NeuroPsychologie Interventionnelle' [Créteil] (U955 Inserm - UPEC), University of Oslo (UiO), University Medical Center [Utrecht], Universität Heidelberg [Heidelberg] = Heidelberg University, King‘s College London, Goethe-Universität Frankfurt am Main, University of Cambridge [UK] (CAM), Radboud University Medical Center [Nijmegen], Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Patch-based processing for medical and natural images (PICTURA), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg], Coupé, Pierrick, Baron-Cohen, Simon [0000-0001-9217-2544], and Apollo - University of Cambridge Repository
Subjects: [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Parcellation, Normative Modelling, Autism Spectrum Disorder, Autism, 220 Statistical Imaging Neuroscience, behavioral disciplines and activities, Magnetic Resonance Imaging, Cohort Studies, Volumetry, nervous system, 130 000 Cognitive Neurology & Memory, Cerebellum, mental disorders, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], 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], Autistic Disorder, Gray Matter, Biological Psychiatry, Normative modeling, MRI
Abstract: Contains fulltext : 288245.pdf (Publisher’s version ) (Open Access) BACKGROUND: The cerebellum contains more than 50% of the brain's neurons and is involved in social cognition. Cerebellar anatomical atypicalities have repeatedly been reported in individuals with autism. However, studies have yielded inconsistent findings, likely because of a lack of statistical power, and did not capture the clinical and neuroanatomical diversity of autism. Our aim was to better understand cerebellar anatomy and its diversity in autism. METHODS: We studied cerebellar gray matter morphology in 274 individuals with autism and 219 control subjects of a multicenter European cohort, EU-AIMS LEAP (European Autism Interventions-A Multicentre Study for Developing New Medications; Longitudinal European Autism Project). To ensure the robustness of our results, we conducted lobular parcellation of the cerebellum with 2 different pipelines in addition to voxel-based morphometry. We performed statistical analyses with linear, multivariate (including normative modeling), and meta-analytic approaches to capture the diversity of cerebellar anatomy in individuals with autism and control subjects. Finally, we performed a dimensional analysis of cerebellar anatomy in an independent cohort of 352 individuals with autism-related symptoms. RESULTS: We did not find any significant difference in the cerebellum when comparing individuals with autism and control subjects using linear models. In addition, there were no significant deviations in our normative models in the cerebellum in individuals with autism. Finally, we found no evidence of cerebellar atypicalities related to age, IQ, sex, or social functioning in individuals with autism. CONCLUSIONS: Despite positive results published in the last decade from relatively small samples, our results suggest that there is no striking difference in cerebellar anatomy of individuals with autism.
Published: 2022
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134. Strategies and foundations for scientific discovery in longitudinal studies of bipolar disorder

Author: Melvin G. McInnis, Ole A. Andreassen, Ana C. Andreazza, Uri Alon, Michael Berk, Teri Brister, Katherine E. Burdick, Donghong Cui, Mark Frye, Marion Leboyer, Philip B. Mitchell, Kathleen Merikangas, Andrew A. Nierenberg, John I. Nurnberger, Daniel Pham, Eduard Vieta, Lakshmi N. Yatham, and Allan H. Young
Subjects: Adult, Psychiatry and Mental health, Bipolar Disorder, Cross-Sectional Studies, Adolescent, Humans, Comorbidity, Longitudinal Studies, Biological Psychiatry, Personality
Abstract: Bipolar disorder (BD) is a complex and dynamic condition with a typical onset in late adolescence or early adulthood followed by an episodic course with intervening periods of subthreshold symptoms or euthymia. It is complicated by the accumulation of comorbid medical and psychiatric disorders. The etiology of BD remains unknown and no reliable biological markers have yet been identified. This is likely due to lack of comprehensive ontological framework and, most importantly, the fact that most studies have been based on small nonrepresentative clinical samples with cross-sectional designs. We propose to establish large, global longitudinal cohorts of BD studied consistently in a multidimensional and multidisciplinary manner to determine etiology and help improve treatment. Herein we propose collection of a broad range of data that reflect the heterogenic phenotypic manifestations of BD that include dimensional and categorical measures of mood, neurocognitive, personality, behavior, sleep and circadian, life-story, and outcomes domains. In combination with genetic and biological information such an approach promotes the integrating and harmonizing of data within and across current ontology systems while supporting a paradigm shift that will facilitate discovery and become the basis for novel hypotheses.
Published: 2022
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135. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author: Gabriëlla A.M. Blokland, Jakob Grove, Chia-Yen Chen, Chris Cotsapas, Stuart Tobet, Robert Handa, David St Clair, Todd Lencz, Bryan J. Mowry, Sathish Periyasamy, Murray J. Cairns, Paul A. Tooney, Jing Qin Wu, Brian Kelly, George Kirov, Patrick F. Sullivan, Aiden Corvin, Brien P. Riley, Tõnu Esko, Lili Milani, Erik G. Jönsson, Aarno Palotie, Hannelore Ehrenreich, Martin Begemann, Agnes Steixner-Kumar, Pak C. Sham, Nakao Iwata, Daniel R. Weinberger, Pablo V. Gejman, Alan R. Sanders, Joseph D. Buxbaum, Dan Rujescu, Ina Giegling, Bettina Konte, Annette M. Hartmann, Elvira Bramon, Robin M. Murray, Michele T. Pato, Jimmy Lee, Ingrid Melle, Espen Molden, Roel A. Ophoff, Andrew McQuillin, Nicholas J. Bass, Rolf Adolfsson, Anil K. Malhotra, Nicholas G. Martin, Janice M. Fullerton, Philip B. Mitchell, Peter R. Schofield, Andreas J. Forstner, Franziska Degenhardt, Sabrina Schaupp, Ashley L. Comes, Manolis Kogevinas, José Guzman-Parra, Andreas Reif, Fabian Streit, Lea Sirignano, Sven Cichon, Maria Grigoroiu-Serbanescu, Joanna Hauser, Jolanta Lissowska, Fermin Mayoral, Bertram Müller-Myhsok, Beata Świątkowska, Thomas G. Schulze, Markus M. Nöthen, Marcella Rietschel, John Kelsoe, Marion Leboyer, Stéphane Jamain, Bruno Etain, Frank Bellivier, John B. Vincent, Martin Alda, Claire O’Donovan, Pablo Cervantes, Joanna M. Biernacka, Mark Frye, Susan L. McElroy, Laura J. Scott, Eli A. Stahl, Mikael Landén, Marian L. Hamshere, Olav B. Smeland, Srdjan Djurovic, Arne E. Vaaler, Ole A. Andreassen, Bernhard T. Baune, Tracy Air, Martin Preisig, Rudolf Uher, Douglas F. Levinson, Myrna M. Weissman, James B. Potash, Jianxin Shi, James A. Knowles, Roy H. Perlis, Susanne Lucae, Dorret I. Boomsma, Brenda W.J.H. Penninx, Jouke-Jan Hottenga, Eco J.C. de Geus, Gonneke Willemsen, Yuri Milaneschi, Henning Tiemeier, Hans J. Grabe, Alexander Teumer, Sandra Van der Auwera, Uwe Völker, Steven P. Hamilton, Patrik K.E. Magnusson, Alexander Viktorin, Divya Mehta, Niamh Mullins, Mark J. Adams, Gerome Breen, Andrew M. McIntosh, Cathryn M. Lewis, David M. Hougaard, Merete Nordentoft, Ole Mors, Preben B. Mortensen, Thomas Werge, Thomas D. Als, Anders D. Børglum, Tracey L. Petryshen, Jordan W. Smoller, Jill M. Goldstein, Stephan Ripke, Benjamin M. Neale, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberly D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee Chee Keong, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Sandra Meier, Carin J. Meijer, Bela Melegh, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Vihra Milanova, Younes Mokrab, Derek W. Morris, Kieran C. Murphy, Inez Myin-Germeys, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Ulrich Schall, Christian R. Schubert, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Hon-Cheong So, Chris C.A. Spencer, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kari Stefansson, Peter M. Visscher, Douglas H.R. Blackwood, Ariel Darvasi, Enrico Domenici, Michael Gill, Hugh Gurling, Christina M. Hultman, Assen V. Jablensky, Kenneth S. Kendler, Jo Knight, Qingqin S. Li, Jianjun Liu, Steven A. McCarroll, Jennifer L. Moran, Michael J. Owen, Carlos N. Pato, Danielle Posthuma, Pamela Sklar, Jens R. Wendland, Mark J. Daly, Michael C. O’Donovan, Peter Donnelly, Ines Barroso, Jenefer M. Blackwell, Matthew A. Brown, Juan P. Casas, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Colin N.A. Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas W. Wood, Gavin Band, Céline Bellenguez, Colin Freeman, Eleni Giannoulatou, Garrett Hellenthal, Richard Pearson, Matti Pirinen, Amy Strange, Zhan Su, Damjan Vukcevic, Cordelia Langford, Hannah Blackburn, Suzannah J. Bumpstead, Serge Dronov, Sarah Edkins, Matthew Gillman, Emma Gray, Rhian Gwilliam, Naomi Hammond, Sarah E. Hunt, Alagurevathi Jayakumar, Jennifer Liddle, Owen T. McCann, Simon C. Potter, Radhi Ravindrarajah, Michelle Ricketts, Avazeh Tashakkori-Ghanbaria, Matthew Waller, Paul Weston, Pamela Whittaker, Sara Widaa, Mark I. McCarthy, Maria J. Arranz, Steven Bakker, Stephan Bender, Benedicto Crespo-Facorro, Jeremy Hall, Conrad Iyegbe, Stephen Lawrie, Kuang Lin, Don H. Linszen, Ignacio Mata, Muriel Walshe, Matthias Weisbrod, Durk Wiersma, Vassily Trubetskoy, Yunpeng Wang, Jonathan R.I. Coleman, Héléna A. Gaspar, Christiaan A. de Leeuw, Jennifer M. Whitehead Pavlides, Maciej Trzaskowski, Enda M. Byrne, Liam Abbott, Huda Akil, Diego Albani, Ney Alliey-Rodriguez, Adebayo Anjorin, Verneri Antilla, Swapnil Awasthi, Judith A. Badner, Marie Bækvad-Hansen, Jack D. Barchas, Nicholas Bass, Michael Bauer, Richard Belliveau, Carsten Bøcker Pedersen, Erlend Bøen, Marco P. Boks, James Boocock, Monika Budde, William Bunney, Margit Burmeister, Jonas Bybjerg-Grauholm, Miquel Casas, Felecia Cerrato, Kimberly Chambert, Alexander W. Charney, Danfeng Chen, Claire Churchhouse, Toni-Kim Clarke, William Coryell, David W. Craig, Cristiana Cruceanu, Piotr M. Czerski, Anders M. Dale, Simone de Jong, Jurgen Del-Favero, J. Raymond DePaulo, Amanda L. Dobbyn, Ashley Dumont, Torbjørn Elvsåshagen, Chun Chieh Fan, Sascha B. Fischer, Matthew Flickinger, Tatiana M. Foroud, Liz Forty, Christine Fraser, Katrin Gade, Diane Gage, Julie Garnham, Claudia Giambartolomei, Marianne Giørtz Pedersen, Jaqueline Goldstein, Scott D. Gordon, Katherine Gordon-Smith, Elaine K. Green, Melissa J. Green, Tiffany A. Greenwood, Weihua Guan, Martin Hautzinger, Urs Heilbronner, Maria Hipolito, Dominic Holland, Laura Huckins, Jessica S. Johnson, Radhika Kandaswamy, Robert Karlsson, Sarah Kittel-Schneider, Anna C. Koller, Ralph Kupka, Catharina Lavebratt, Jacob Lawrence, William B. Lawson, Markus Leber, Phil H. Lee, Shawn E. Levy, Jun Z. Li, Chunyu Liu, Anna Maaser, Donald J. MacIntyre, Pamela B. Mahon, Lina Martinsson, Steve McCarroll, Peter McGuffin, Melvin G. McInnis, James D. McKay, Helena Medeiros, Sarah E. Medland, Fan Meng, Grant W. Montgomery, Thomas W. Mühleisen, Hoang Nguyen, Caroline M. Nievergelt, Annelie Nordin Adolfsson, Evaristus A. Nwulia, Claire O'Donovan, Loes M. Olde Loohuis, Anil P.S. Ori, Lilijana Oruc, Urban Ösby, Amy Perry, Andrea Pfennig, Eline J. Regeer, Céline S. Reinbold, John P. Rice, Fabio Rivas, Margarita Rivera, Euijung Ryu, Cristina Sánchez-Mora, Alan F. Schatzberg, William A. Scheftner, Nicholas J. Schork, Cynthia Shannon Weickert, Tatyana Shehktman, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Christine Søholm Hansen, Anne T. Spijker, Michael Steffens, John S. Strauss, Szabolcs Szelinger, Robert C. Thompson, Thorgeir E. Thorgeirsson, Jens Treutlein, Helmut Vedder, Weiqing Wang, Stanley J. Watson, Thomas W. Weickert, Simon Xi, Wei Xu, Allan H. Young, Peter Zandi, Peng Zhang, Sebastian Zöllner, Abdel Abdellaoui, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Aartjan T.F. Beekman, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Gregory E. Crawford, Gail Davies, Ian J. Deary, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Fernando S. Goes, Lynsey S. Hall, Thomas F. Hansen, Ian B. Hickie, Georg Homuth, Carsten Horn, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Dean F. MacKinnon, Robert M. Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Christel M. Middeldorp, Evelin Mihailov, Francis M. Mondimore, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O'Reilly, Hogni Oskarsson, Jodie N. Painter, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Jorge A. Quiroz, Per Qvist, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Stanley I. Shyn, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Katherine E. Tansey, Henning Teismann, Wesley Thompson, Pippa A. Thomson, Matthew Traylor, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Shantel Marie Weinsheimer, Jürgen Wellmann, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Klaus Berger, Udo Dannlowski, Katharina Domschke, Caroline Hayward, Andrew C. Heath, Stefan Kloiber, Glyn Lewis, Pamela AF. Madden, Patrik K. Magnusson, Preben Bo Mortensen, Michael C. O'Donovan, Sara A. Paciga, Nancy L. Pedersen, David J. Porteous, Catherine Schaefer, Henry Völzke, Marco Bortolato, Janita Bralten, Cynthia M. Bulik, Christie L. Burton, Caitlin E. Carey, Lea K. Davis, Laramie E. Duncan, Howard J. Edenberg, Lauren Erdman, Stephen V. Faraone, Slavina B. Goleva, Wei Guo, Christopher Hübel, Laura M. Huckins, Ekaterina A. Khramtsova, Joanna Martin, Carol A. Mathews, Elise Robinson, Eli Stahl, Barbara E. Stranger, Michela Traglia, Raymond K. Walters, Lauren A. Weiss, Stacey J. Winham, Yin Yao, Kristjar Skajaa, Markus Nöthen, Michael Owen, Robert H. Yolken, Niels Plath, Jonathan Mill, Daniel Geschwind, Psychiatry 1, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Functional Genomics, Biological Psychology, APH - Mental Health, APH - Methodology, Sociology and Social Gerontology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Blokland, Gabriella AM, Grove, Jakob, Chen, Chia Yen, Cotsapas, Chris, Tobet, Stuart, Handa, Robert, Lee, Sang Hong, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium, iPSYCH, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, ANS - Complex Trait Genetics, and ANS - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: 0301 basic medicine, Male, Bipolar Disorder, Schizophrenia/genetics, LD SCORE REGRESSION, Genome-wide association study, 0302 clinical medicine, Receptors, SCHIZOPHRENIA, Psychotic Disorders/genetics, KYNURENINE PATHWAY METABOLISM, Genetics, RISK, Sex Characteristics, Vascular Endothelial Growth Factor, Bipolar Disorder/genetics, Major/genetics, Single Nucleotide, AFFECTIVE STIMULI IMPACT, Schizophrenia, Sulfurtransferases, Major depressive disorder, Female, Depressive Disorder, Major/genetics, Bipolar disorder, Locus (genetics), Genomics, Biology, Polymorphism, Single Nucleotide, Article, DYSPHORIC MOOD, 03 medical and health sciences, Sex differences, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Polymorphism, GENOME-WIDE ASSOCIATION, Genotype-by-sex interaction, Biological Psychiatry, Depressive Disorder, Major, Depressive Disorder, GENDER-DIFFERENCES, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], PARAVENTRICULAR NUCLEUS, 3112 Neurosciences, Endothelial Cells, MAJOR DEPRESSION, medicine.disease, Genetic architecture, 030104 developmental biology, Mood, Receptors, Vascular Endothelial Growth Factor, Psychotic Disorders, 3111 Biomedicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Contains fulltext : 248656.pdf (Publisher’s version ) (Closed access) BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10(-8)), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10(-6)) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10(-7); rs73033497, p = 8.8 × 10(-7); rs7914279, p = 6.4 × 10(-7)), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10(-7)) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10(-7)), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10(-7)) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
Published: 2022
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136. Precision-medicine findings from the FACE-SZ cohort to develop motivation-enhancing programs in real-world schizophrenia

Author: Théo Korchia, Maud Tastevin, Pierre-Louis Sunhary de Verville, Ridha Joober, Christelle Andrieu-Haller, Mélanie Faugere, Ophélia Godin, Damien Etchecopar-Etchart, Fabrice Berna, Bruno Aouizerate, Delphine Capdevielle, Isabelle Chereau, Julie Clauss-Kobayashi, Nathalie Coulon, Jean-Michel Dorey, Caroline Dubertret, Julien Dubreucq, Jasmina Mallet, David Misdrahi, Christine Passerieux, Romain Rey, Frank Schürhoff, Andrei Szoke, Mathieu Urbach, Marion Leboyer, Pierre-Michel Llorca, Christophe Lançon, Raphaelle Richieri, Laurent Boyer, Guillaume Fond, Fondation FondaMental [Créteil], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], 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, Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Charles Perrens, 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), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Versailles André Mignot (CHV), 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 Henri Mondor, 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)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPC), Centre hospitalier Charles Perrens [Bordeaux], Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)
Subjects: Depressive Disorder, Major, Motivation, [SDV]Life Sciences [q-bio], mood disorders, psychiatry, schizophrenia, Psychiatry and Mental health, Alcoholism, quality of life, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Precision Medicine, depressive disorders, Biological Psychiatry, mental health, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: In people with schizophrenia, major areas of everyday life are impaired, including independent living, productive activities, social relationships and overall quality of life. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes.Aim: The goal of the present study was to identify factors associated with motivation deficits in real-life schizophrenia, and to assess its contribution to impaired functioning and quality of life.Methods: Based on previous literature and clinical experience, several factors were selected and grouped into factors potentially explaining motivation deficits. Some of these variables were never investigated before in relationship with motivation deficits.Results: In 561 patients with schizophrenia of the national FACE-SZ cohort living in the community, 235(41.9%) reported severe motivation deficits. These deficits were found to be significantly associated with impaired socially useful activities, psychological and physical quality of life (in almost all domains), alcohol use disorder (aOR =2.141, p = 0.021), severe nicotine dependence (aOR =2.906, p < 0.001) independently of age and sex. No significant association was found for body mass index, metabolic syndrome or physical activity level. In the second model, we identified the following modifiable factors associated with motivation deficits: history of suicide attempt (aOR =2.297, p = 0.001), positive symptoms (aOR =1.052, p = 0.006), current major depressive episode (aOR =2.627, p < 0.001), sleep disorders (aOR =1.474, p = 0.024) and lower medication adherence (aOR =0.836, p = 0.001) independently of gender, current alcohol use disorder, second-generation antipsychotics and akathisia. No significant association was found for negative symptoms, childhood trauma and inflammation. These results were maintained after removing patients with schizoaffective disorders or those with major depressive disorder.Interpretation: Motivation deficits are frequent and remain persistent unmet need in real-world schizophrenia that should be addressed in future guidelines. Based on our results, literature and clinical experience, we recommend to address in priority major depression, sleep, suicide, positive symptoms (when present and as early as possible) and medication adherence to improve motivation deficits of schizophrenia.
Published: 2022
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137. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author: Andreas J. Forstner, Martin Alda, Manolis Kogevinas, Pak C. Sham, Patrick F. Sullivan, Michele T. Pato, John R. Kelsoe, Paul A. Tooney, Steven P. Hamilton, Dorret I. Boomsma, Gerome Breen, Tracy Air, Hannelore Ehrenreich, Nakao Iwata, Jill M. Goldstein, Olav B. Smeland, Daniel R. Weinberger, Andrew McQuillin, Stuart A. Tobet, Elvira Bramon, Gabriëlla A.M. Blokland, Jing Qin Wu, Erik G. Jönsson, Peter R. Schofield, Fabian Streit, Nicholas Bass, Aarno Palotie, Brian Kelly, Cathryn M. Lewis, Srdjan Djurovic, Thomas Damm Als, Chia-Yen Chen, Bettina Konte, Joanna Hauser, Claire O'Donovan, Laura J. Scott, Hans J. Grabe, Murray J. Cairns, Rudolf Uher, Pablo Cervantes, Nicholas G. Martin, James A. Knowles, Aiden Corvin, Espen Molden, Lili Milani, Andreas Reif, Maria Grigoroiu-Serbanescu, George Kirov, Yuri Milaneschi, David St Clair, Eco J. C. de Geus, Robert Handa, Tõnu Esko, Alexander Teumer, Anders D. Børglum, Divya Mehta, Roel A. Ophoff, Susanne Lucae, Henning Tiemeier, Marion Leboyer, Ina Giegling, Alan R. Sanders, Jouke-Jan Hottenga, Pablo V. Gejman, Bernhard T. Baune, Brenda W.J.H. Penninx, Chris Cotsapas, Martin Preisig, Thomas Werge, Jakob Grove, Ingrid Melle, Jordan W. Smoller, Marcella Rietschel, Myrna M. Weissman, Preben Bo Mortensen, Philip B. Mitchell, Jolanta Lissowska, Andrew M. McIntosh, Annette M. Hartmann, Ole A. Andreassen, Lea Sirignano, John B. Vincent, Niamh Mullins, Jimmy Lee, Gonneke Willemsen, Marian L. Hamshere, Rolf Adolfsson, Mark A. Frye, Markus M. Nöthen, Jianxin Shi, Ashley L. Comes, Robin M. Murray, Patrik K. E. Magnusson, Frank Bellivier, Stéphane Jamain, Ole Mors, Sven Cichon, Uwe Völker, Fermín Mayoral, Bryan J. Mowry, Bruno Etain, James B. Potash, Beata Świątkowska, Bertram Müller-Myhsok, Mikael Landén, Tracey L. Petryshen, Franziska Degenhardt, Mark Adams, Dan Rujescu, Jose Guzman-Parra, Thomas G. Schulze, Merete Nordentoft, Joseph D. Buxbaum, Janice M. Fullerton, Brien P. Riley, Roy H. Perlis, Arne E. Vaaler, David M. Hougaard, Eli A. Stahl, Susan L. McElroy, Sabrina K. Schaupp, Martin Begemann, Sandra Van der Auwera, Todd Lencz, Joanna M. Biernacka, Agnes A. Steixner-Kumar, Douglas F. Levinson, Sathish Periyasamy, Alexander Viktorin, and Anil K. Malhotra
Subjects: Genetics, 0303 health sciences, Medizin, Locus (genetics), Genomics, Biology, medicine.disease, Genetic architecture, 03 medical and health sciences, 0302 clinical medicine, Mood, medicine, Major depressive disorder, Bipolar disorder, Gene, NKAIN2 Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: BACKGROUNDSex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk.METHODSWe conducted the largest to date genome-wide genotype–by–sex (GxS) interaction of risk for these disorders, using 85,735 cases (33,403 SCZ, 19,924 BIP, 32,408 MDD) and 109,946 controls from the Psychiatric Genomics Consortium (PGC) and iPSYCH.RESULTSAcross disorders, genome-wide significant SNP-by-sex interaction was detected for a locus encompassingNKAIN2(rs117780815;p=3.2×10−8), that interacts with sodium/potassium-transporting ATPase enzymes implicating neuronal excitability. Three additional loci showed evidence (p−6) for cross-disorder GxS interaction (rs7302529,p=1.6×10−7; rs73033497,p=8.8×10−7; rs7914279,p=6.4×10−7) implicating various functions. Gene-based analyses identified GxS interaction across disorders (p=8.97×10−7) with transcriptional inhibitorSLTM. Most significant in SCZ was aMOCOSgene locus (rs11665282;p=1.5×10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509;p=1.1×10−7) in a locus containingIDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant GxS of genes regulating vascular endothelial growth factor (VEGF) receptor signaling in MDD (pFDRCONCLUSIONSIn the largest genome-wide GxS analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development, immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway enrichment levels.
Published: 2022

138. Self-Reported Pain and Emotional Reactivity in Bipolar Disorder: A Prospective FACE-BD Study

Author: Nathan Risch, Jonathan Dubois, Katia M’bailara, Irena Cussac, Bruno Etain, Raoul Belzeaux, Caroline Dubertret, Emmanuel Haffen, Raymund Schwan, Ludovic Samalin, Paul Roux, Mircea Polosan, Marion Leboyer, Philippe Courtet, Emilie Olié, on behalf of the FondaMental Advanced Centers of Expertise in Bipolar Disorders (FACE-BD) Collaborators, Guerineau, Nathalie C., Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, Cohortes - Maladie Rénale Chronique - Réseau Epidémiologie et Information en Néphrologie - - CKD-REIN2010 - ANR-10-COHO-0001 - COHO - VALID, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Fondation FondaMental [Créteil], Laboratoire de psychologie (LabPsy), Université de Bordeaux (UB), Centre hospitalier Charles Perrens [Bordeaux], Centre Hospitalier Princesse Grace, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Mourier - AP-HP [Colombes], Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Lorraine (UL), CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre Hospitalier de Versailles André Mignot (CHV), 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, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Henri Mondor, 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), ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-10-COHO-0001,CKD-REIN,Maladie Rénale Chronique - Réseau Epidémiologie et Information en Néphrologie(2010), Hôpital Charles Perrens, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and CHU Henri Mondor [Créteil]
Subjects: bipolar disorder, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, pain, depression, affective symptoms, [SDV]Life Sciences [q-bio], General Medicine, [SDV] Life Sciences [q-bio], Medicine, [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; In patients with bipolar disorder (BD), pain prevalence is close to 30%. It is important to determine whether pain influences BD course and to identify factors associated with pain in BD in order to guide BD management. This naturalistic, prospective study used data on 880 patients with BD from the French FACE-BD cohort who were divided into two groups according to the presence or absence of pain. Multivariate models were used to test whether pain was associated with affective states and personality traits while controlling for confounders. Then, multivariate models were used to test whether pain at baseline predicted global life functioning and depressive symptomatology at one year. At baseline, 22% of patients self-reported pain. The pain was associated with depressive symptomatology, levels of emotional reactivity in a quadratic relationship, and a composite variable of personality traits (affective lability, affective intensity, hostility/anger, and impulsivity). At one year, the pain was predictive of depression and lower global life functioning. Pain worsens mental health and well-being in patients with BD. The role of emotions, depression, and personality traits in pain has to be elucidated to better understand the high prevalence of pain in BD and to promote specific therapeutic strategies for patients experiencing pain.
Published: 2022
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139. 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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140. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author: Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. O’Connell, Brandon Coombes, Zhen Qiao, Thomas D. Als, Sigrid Børte, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Verneri Antilla, Anastasia Antoniou, Ji Hyun Baek, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Erlend Bøen, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Ian R. Gizer, Katherine Gordon-Smith, Tiffany A. Greenwood, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Peter A. Holmans, Laura Huckins, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, Sarah Kittel-Schneider, Maria Koromina, Thorsten M. Kranz, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Markus Leber, Heon-Jeong Lee, Shawn E. Levy, Catrin Lewis, Martin Lundberg, Sigurdur H. Magnusson, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Nathaniel W. McGregor, James D. McKay, Helena Medeiros, Vincent Millischer, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. Reininghaus, Takeo Saito, Ulrich Schall, Martin Schalling, Rodney J. Scott, Eystein Stordal, Arne E. Vaaler, Eduard Vieta, Irwin D. Waldman, John-Anker Zwart, John I. Nurnberger, Arianna Di Florio, Roger A.H. Adan, Tetsuya Ando, Harald Aschauer, Jessica H. Baker, Vladimir Bencko, Andreas Birgegård, Joseph M. Boden, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Laura Carlberg, Matteo Cassina, Maurizio Clementi, Roger D. Cone, Philippe Courtet, James J. Crowley, Unna N. Danner, Oliver S.P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo Martinez, Laramie E. Duncan, Karin Egberts, Morten Mattingsdal, Sara McDevitt, Ingrid Meulenbelt, Nadia Micali, James Mitchell, Karen Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Melissa A. Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Richard Parker, John F. Pearson, Stefan Ehrlich, Geòrgia Escaramís, Thomas Espeseth, Xavier Estivill, Anne Farmer, Angela Favaro, Krista Fischer, James A.B. Floyd, Manuel Föcker, Lenka Foretova, Monica Forzan, Christopher S. Franklin, Giovanni Gambaro, Johanna Giuranna, Paola Giusti-Rodríquez, Fragiskos Gonidakis, Scott Gordon, Monica Gratacos Mayora, Sébastien Guillaume, Ken B. Hanscombe, Konstantinos Hatzikotoulas, Johannes Hebebrand, Sietske G. Helder, Anjali K. Henders, Beate Herpertz-Dahlmann, Wolfgang Herzog, Anke Hinney, L. John Horwood, Christopher Hübel, Liselotte V. Petersen, Kirstin L. Purves, Anu Raevuori, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Filip Rybakowski, Paolo Santonastaso, André Scherag, Ulrike Schmidt, Nicholas J. Schork, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P. Eline Slagboom, Margarita C.T. Slof-Op ‘t Landt, Agnieszka Slopien, Nicole Soranzo, Sandro Sorbi, Lorraine Southam, Vidar W. Steen, Laura M. Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Jennifer Jordan, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J.H. Kas, Martin A. Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Katherine M. Kirk, Lars Klareskog, Gun Peggy S. Knudsen, Janne T. Larsen, Stephanie Le Hellard, Virpi M. Leppä, Paul Lichtenstein, Bochao Danae Lin, Astri Lundervold, Jurjen Luykx, Mario Maj, Katrin Mannik, Sara Marsal, Garret D. Stuber, Jin P. Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Tracey D. Wade, Gudrun Wagner, Esther Walton, H. Erich Wichmann, Elisabeth Widen, Shuyang Yao, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Martin Jungkunz, Lydie Dietl, Cornelia E. Schwarze, Norbert Dahmen, Björn H. Schott, Arian Mobascher, Silvia Crivelli, Michelle F. Dennis, Phillip D. Harvey, Bruce W. Carter, Jennifer E. Huffman, Daniel Jacobson, Ravi Madduri, Maren K. Olsen, John Pestian, J. Michael Gaziano, Sumitra Muralidhar, Rachel Ramoni, Jean Beckham, Kyong-Mi Chang, Christopher J. O’Donnell, Philip S. Tsao, James Breeling, Grant Huang, J.P. Casas Romero, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, Mihaela Aslan, Todd Connor, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Luis E. Selva, Nhan Do, Shahpoor Shayan, Kelly Cho, Saiju Pyarajan, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, Kristin Mattocks, John Harley, Clement J. Zablocki, Jeffrey Whittle, Frank Jacono, Salvador Gutierrez, Gretchen Gibson, Kimberly Hammer, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Roy Mathew, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Douglas Ivins, Stephen Mastorides, Jonathan Moorman, Saib Gappy, Jon Klein, Nora Ratcliffe, Hermes Florez, Olaoluwa Okusaga, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Neeraj Tandon, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, Suthat Liangpunsakul, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Joseph Constans, Paul Meyer, Jennifer Greco, Michael Rauchman, Richard Servatius, Melinda Gaddy, Agnes Wallbom, Timothy Morgan, Todd Stapley, Scott Sherman, George Ross, Philip Tsao, Patrick Strollo, Edward Boyko, Laurence Meyer, Samir Gupta, Mostaqul Huq, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, Robert Striker, Dietl, Lydie, Schwarze, Cornelia E., Dahmen, Norbert, Schott, Björn H., Nöthen, Markus M., Ripke, Stephan, Mobascher, Arian, Rujescu, Dan, Lieb, Klaus, Roepke, Stefan, Schmahl, Christian, Bohus, Martin, Rietschel, Marcella, Crivelli, Silvia, Dennis, Michelle F., Harvey, Phillip D., Carter, Bruce W., Huffman, Jennifer E., Jacobson, Daniel, Madduri, Ravi, Olsen, Maren K., Pestian, John, Gaziano, J. Michael, Muralidhar, Sumitra, Ramoni, Rachel, Beckham, Jean, Chang, Kyong-Mi, O'Donnell, Christopher J., Tsao, Philip S., Breeling, James, Huang, Grant, Romero, J. P. Casas, Moser, Jennifer, Whitbourne, Stacey B., Brewer, Jessica V., Aslan, Mihaela, Connor, Todd, Argyres, Dean P., Stephens, Brady, Brophy, Mary T., Humphries, Donald E., Selva, Luis E., Do, Nhan, Shayan, Shahpoor, Cho, Kelly, Pyarajan, Saiju, Hauser, Elizabeth, Sun, Yan, Zhao, Hongyu, Wilson, Peter, McArdle, Rachel, Dellitalia, Louis, Mattocks, Kristin, Harley, John, Zablocki, Clement J., Whittle, Jeffrey, Jacono, Frank, Gutierrez, Salvador, Gibson, Gretchen, Hammer, Kimberly, Kaminsky, Laurence, Villareal, Gerardo, Kinlay, Scott, Xu, Junzhe, Hamner, Mark, Mathew, Roy, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Ballas, Zuhair, Ivins, Douglas, Mastorides, Stephen, Moorman, Jonathan, Gappy, Saib, Klein, Jon, Ratcliffe, Nora, Florez, Hermes, Okusaga, Olaoluwa, Murdoch, Maureen, Sriram, Peruvemba, Yeh, Shing Shing, Tandon, Neeraj, Jhala, Darshana, Aguayo, Samuel, Cohen, David, Sharma, Satish, Liangpunsakul, Suthat, Oursler, Kris Ann, Whooley, Mary, Ahuja, Sunil, Constans, Joseph, Meyer, Paul, Greco, Jennifer, Rauchman, Michael, Servatius, Richard, Gaddy, Melinda, Wallbom, Agnes, Morgan, Timothy, Stapley, Todd, Sherman, Scott, Ross, George, Tsao, Philip, Strollo, Patrick, Boyko, Edward, Meyer, Laurence, Gupta, Samir, Huq, Mostaqul, Fayad, Joseph, Hung, Adriana, Lichy, Jack, Hurley, Robin, Robey, Brooks, Striker, Robert, Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F. M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T. F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R. I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A. F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C. B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Penninx, Brenda W. J. H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., O'Connell, Kevin S., Coombes, Brandon, Qiao, Zhen, Als, Thomas D., Børte, Sigrid, Charney, Alexander W., Drange, Ole Kristian, Gandal, Michael J., Hagenaars, Saskia P., Ikeda, Masashi, Kamitaki, Nolan, Kim, Minsoo, Krebs, Kristi, Panagiotaropoulou, Georgia, Schilder, Brian M., Sloofman, Laura G., Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Bøen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsåshagen, Torbjørn, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frei, Oleksandr, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Gizer, Ian R., Gordon-Smith, Katherine, Greenwood, Tiffany A., Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Holmans, Peter A., Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Kogevinas, Manolis, Koromina, Maria, Kranz, Thorsten M., Kranzler, Henry R., Kubo, Michiaki, Kupka, Ralph, Kushner, Steven A., Lavebratt, Catharina, Lawrence, Jacob, Leber, Markus, Lee, Heon-Jeong, Lee, Phil H., Levy, Shawn E., Lewis, Catrin, Liao, Calwing, Lundberg, Martin, Magnusson, Sigurdur H., Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, McGregor, Nathaniel W., McKay, James D., Medeiros, Helena, Millischer, Vincent, Moran, Jennifer L., Morris, Derek W., Mühleisen, Thomas W., O'Brien, Niamh, O'Donovan, Claire, Olde Loohuis, Loes M., Oruc, Lilijana, Papiol, Sergi, Pardiñas, Antonio F., Perry, Amy, Pfennig, Andrea, Porichi, Evgenia, Quested, Digby, Raj, Towfique, Rapaport, Mark H., Regeer, Eline J., Rivas, Fabio, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sánchez-Mora, Cristina, Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Sobell, Janet L., Artigas, Maria Soler, Spijker, Anne T., Stein, Dan J., Strauss, John S., Świątkowska, Beata, Terao, Chikashi, Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Xi, Simon, Xu, Wei, Kay Yang, Jessica Mei, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dikeos, Dimitris, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen V., Kahn, René S., Kelsoe, John R., Kirov, George, Landén, Mikael, Leboyer, Marion, Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Mitchell, Philip B., Morken, Gunnar, Mowry, Bryan, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Oedegaard, Ketil J., Olsson, Tomas, Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Weickert, Cynthia Shannon, Stordal, Eystein, Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Zwart, John-Anker, Biernacka, Joanna M., Nurnberger, John I., Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., Andreassen, Ole A., Adan, Roger A. H., Ando, Tetsuya, Aschauer, Harald, Baker, Jessica H., Bencko, Vladimir, Bergen, Andrew W., Birgegård, Andreas, Boden, Joseph M., Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Brandt, Harry, Buehren, Katharina, Bulik, Cynthia M., Burghardt, Roland, Carlberg, Laura, Cassina, Matteo, Clementi, Maurizio, Cone, Roger D., Courtet, Philippe, Crawford, Steven, Crow, Scott, Crowley, James J., Danner, Unna N., Davis, Oliver S. P., de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E., Dick, Danielle M., Dina, Christian, Dmitrzak-Weglarz, Monika, Martinez, Elisa Docampo, Duncan, Laramie E., Egberts, Karin, Marshall, Christian R., Mattingsdal, Morten, McDevitt, Sara, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, James, Mitchell, Karen, Monteleone, Palmiero, Monteleone, Alessio Maria, Munn-Chernoff, Melissa A., Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, Olsen, Catherine M., O'Toole, Julie K., Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Parker, Richard, Pearson, John F., Ehrlich, Stefan, Escaramís, Geòrgia, Espeseth, Thomas, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M., Fischer, Krista, Floyd, James A. B., Föcker, Manuel, Foretova, Lenka, Forzan, Monica, Franklin, Christopher S., Gallinger, Steven, Gambaro, Giovanni, Giegling, Ina, Giuranna, Johanna, Giusti-Rodríquez, Paola, Gonidakis, Fragiskos, Gordon, Scott, Gorwood, Philip, Mayora, Monica Gratacos, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine A., Hanscombe, Ken B., Hatzikotoulas, Konstantinos, Hebebrand, Johannes, Helder, Sietske G., Henders, Anjali K., Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Hinney, Anke, Horwood, L. John, Hübel, Christopher, Petersen, Liselotte V., Pinto, Dalila, Purves, Kirstin L., Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen W., Schmidt, Ulrike, Schork, Nicholas J., Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P. Eline, Slof-Op 't Landt, Margarita C. T., Slopien, Agnieszka, Soranzo, Nicole, Sorbi, Sandro, Southam, Lorraine, Steen, Vidar W., Strober, Michael, Huckins, Laura M., Hudson, James I., Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Johnson, Craig, Jordan, Jennifer, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Kaplan, Allan S., Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J. H., Kaye, Walter H., Kennedy, Martin A., Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Kirk, Katherine M., Klareskog, Lars, Klump, Kelly L., Knudsen, Gun Peggy S., Larsen, Janne T., Le Hellard, Stephanie, Leppä, Virpi M., Li, Dong, Lichtenstein, Paul, Lilenfeld, Lisa, Lin, Bochao Danae, Lundervold, Astri, Luykx, Jurjen, Magistretti, Pierre J., Maj, Mario, Mannik, Katrin, Marsal, Sara, Stuber, Garret D., Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Thornton, Laura M., Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A., van Furth, Eric F., Wade, Tracey D., Wagner, Gudrun, Walton, Esther, Watson, Hunna J., Whiteman, David C., Wichmann, H. Erich, Widen, Elisabeth, Woodside, D. Blake, Yao, Shuyang, Yilmaz, Zeynep, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Jungkunz, Martin, Mullins, N., Kang, J., Campos, A. I., Coleman, J. R. I., Edwards, A. C., Galfalvy, H., Levey, D. F., Lori, A., Shabalin, A., Starnawska, A., Su, M. -H., Watson, H. J., Adams, M., Awasthi, S., Gandal, M., Hafferty, J. D., Hishimoto, A., Kim, M., Okazaki, S., Otsuka, I., Ripke, S., Ware, E. B., Bergen, A. W., Berrettini, W. H., Bohus, M., Brandt, H., Chang, X., Chen, W. J., Chen, H. -C., Crawford, S., Crow, S., Diblasi, E., Duriez, P., Fernandez-Aranda, F., Fichter, M. M., Gallinger, S., Glatt, S. J., Gorwood, P., Guo, Y., Hakonarson, H., Halmi, K. A., Hwu, H. -G., Jain, S., Jamain, S., Jimenez-Murcia, S., Johnson, C., Kaplan, A. S., Kaye, W. H., Keel, P. K., Kennedy, J. L., Klump, K. L., Li, D., Liao, S. -C., Lieb, K., Lilenfeld, L., Liu, C. -M., Magistretti, P. J., Marshall, C. R., Mitchell, J. E., Monson, E. T., Myers, R. M., Pinto, D., Powers, A., Ramoz, N., Roepke, S., Rozanov, V., Scherer, S. W., Schmahl, C., Sokolowski, M., Strober, M., Thornton, L. M., Treasure, J., Tsuang, M. T., Witt, S. H., Woodside, D. B., Yilmaz, Z., Zillich, L., Adolfsson, R., Agartz, I., Air, T. M., Alda, M., Alfredsson, L., Andreassen, O. A., Anjorin, A., Appadurai, V., Soler Artigas, M., Van der Auwera, S., Azevedo, M. H., Bass, N., Bau, C. H. D., Baune, B. T., Bellivier, F., Berger, K., Biernacka, J. M., Bigdeli, T. B., Binder, E. B., Boehnke, M., Boks, M. P., Bosch, R., Braff, D. L., Bryant, R., Budde, M., Byrne, E. M., Cahn, W., Casas, M., Castelao, E., Cervilla, J. A., Chaumette, B., Cichon, S., Corvin, A., Craddock, N., Craig, D., Degenhardt, F., Djurovic, S., Edenberg, H. J., Fanous, A. H., Foo, J. C., Forstner, A. J., Frye, M., Fullerton, J. M., Gatt, J. M., Gejman, P. V., Giegling, I., Grabe, H. J., Green, M. J., Grevet, E. H., Grigoroiu-Serbanescu, M., Gutierrez, B., Guzman-Parra, J., Hamilton, S. P., Hamshere, M. L., Hartmann, A., Hauser, J., Heilmann-Heimbach, S., Hoffmann, P., Ising, M., Jones, I., Jones, L. A., Jonsson, L., Kahn, R. S., Kelsoe, J. R., Kendler, K. S., Kloiber, S., Koenen, K. C., Kogevinas, M., Konte, B., Krebs, M. -O., Landen, M., Lawrence, J., Leboyer, M., Lee, P. H., Levinson, D. F., Liao, C., Lissowska, J., Lucae, S., Mayoral, F., Mcelroy, S. L., Mcgrath, P., Mcguffin, P., Mcquillin, A., Medland, S. E., Mehta, D., Melle, I., Milaneschi, Y., Mitchell, P. B., Molina, E., Morken, G., Mortensen, P. B., Muller-Myhsok, B., Nievergelt, C., Nimgaonkar, V., Nothen, M. M., O'Donovan, M. C., Ophoff, R. A., Owen, M. J., Pato, C., Pato, M. T., Penninx, B. W. J. H., Pimm, J., Pistis, G., Potash, J. B., Power, R. A., Preisig, M., Quested, D., Ramos-Quiroga, J. A., Reif, A., Ribases, M., Richarte, V., Rietschel, M., Rivera, M., Roberts, A., Roberts, G., Rouleau, G. A., Rovaris, D. L., Rujescu, D., Sanchez-Mora, C., Sanders, A. R., Schofield, P. R., Schulze, T. G., Scott, L. J., Serretti, A., Shi, J., Shyn, S. I., Sirignano, L., Sklar, P., Smeland, O. B., Smoller, J. W., Sonuga-Barke, E. J. S., Spalletta, G., Strauss, J. S., Swiatkowska, B., Trzaskowski, M., Turecki, G., Vilar-Ribo, L., Vincent, J. B., Volzke, H., Walters, J. T. R., Shannon Weickert, C., Weickert, T. W., Weissman, M. M., Williams, L. M., Wray, N. R., Zai, C. C., Ashley-Koch, A. E., Beckham, J. C., Hauser, E. R., Hauser, M. A., Kimbrel, N. A., Lindquist, J. H., Mcmahon, B., Oslin, D. W., Qin, X., Mattheisen, M., Abdellaoui, A., Adams, M. J., Agerbo, E., Andlauer, T. F. M., Bacanu, S. -A., Baekvad-Hansen, M., Beekman, A. T. F., Bryois, J., Buttenschon, H. N., Bybjerg-Grauholm, J., Cai, N., Christensen, J. H., Clarke, T. -K., Colodro-Conde, L., Couvy-Duchesne, B., Crawford, G. E., Davies, G., Derks, E. M., Direk, N., Dolan, C. V., Dunn, E. C., Eley, T. C., Escott-Price, V., Hassan Kiadeh, F. F., Finucane, H. K., Frank, J., Gaspar, H. A., Gill, M., Goes, F. S., Gordon, S. D., Weinsheimer, S. M., Wellmann, J., Willemsen, G., Wu, Y., Xi, H. S., Yang, J., Zhang, F., Arolt, V., Boomsma, D. I., Dannlowski, U., Depaulo, J. 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A., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Kirk, K. M., Klareskog, L., Knudsen, G. P. S., Larsen, J. T., Le Hellard, S., Leppa, V. M., Lichtenstein, P., Lin, B. D., Lundervold, A., Luykx, J., Maj, M., Mannik, K., Marsal, S., Stuber, G. D., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wade, T. D., Wagner, G., Walton, E., Whiteman, D. C., Wichmann, H. E., Widen, E., Yao, S., Zeggini, E., Zerwas, S., Zipfel, S., Jungkunz, M., Dietl, L., Schwarze, C. E., Dahmen, N., Schott, B. H., Mobascher, A., Crivelli, S., Dennis, M. F., Harvey, P. D., Carter, B. W., Huffman, J. E., Jacobson, D., Madduri, R., Olsen, M. K., Pestian, J., Gaziano, J. M., Muralidhar, S., Ramoni, R., Beckham, J., Chang, K. -M., O'Donnell, C. J., Tsao, P. S., Breeling, J., Huang, G., Romero, J. P. C., Moser, J., Whitbourne, S. B., Brewer, J. V., Aslan, M., Connor, T., Argyres, D. P., Stephens, B., Brophy, M. T., Humphries, D. E., Selva, L. E., Do, N., Shayan, S., Cho, K., Pyarajan, S., Hauser, E., Sun, Y., Zhao, H., Wilson, P., Mcardle, R., Dellitalia, L., Mattocks, K., Harley, J., Zablocki, C. J., Whittle, J., Jacono, F., Gutierrez, S., Gibson, G., Hammer, K., Kaminsky, L., Villareal, G., Kinlay, S., Xu, J., Hamner, M., Mathew, R., Bhushan, S., Iruvanti, P., Godschalk, M., Ballas, Z., Ivins, D., Mastorides, S., Moorman, J., Gappy, S., Klein, J., Ratcliffe, N., Florez, H., Okusaga, O., Murdoch, M., Sriram, P., Yeh, S. S., Tandon, N., Jhala, D., Aguayo, S., Cohen, D., Sharma, S., Liangpunsakul, S., Oursler, K. A., Whooley, M., Ahuja, S., Constans, J., Meyer, P., Greco, J., Rauchman, M., Servatius, R., Gaddy, M., Wallbom, A., Morgan, T., Stapley, T., Sherman, S., Ross, G., Tsao, P., Strollo, P., Boyko, E., Meyer, L., Gupta, S., Huq, M., Fayad, J., Hung, A., Lichy, J., Hurley, R., Robey, B., Striker, R., Erlangsen, A., Kessler, R. C., Porteous, D., Ursano, R. J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards 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Maratou E., Martinsson L., McGregor N.W., McKay J.D., Medeiros H., Millischer V., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Raj T., Rapaport M.H., Regeer E.J., Rivas F., Roth J., Roussos P., Ruderfer D.M., Senner F., Sharp S., Shilling P.D., Slaney C., Sobell J.L., Artigas M.S., Spijker A.T., Stein D.J., Terao C., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Xi S., Xu W., Kay Yang J.M., Young A.H., Young H., Zandi P.P., Zhou H., HUNT All-In Psychiatry, Babadjanova G., Backlund L., Bengesser S., Blackwood D.H.R., Carr V.J., Catts S., Dikeos D., Etain B., Ferentinos P., Gawlik M., Gershon E.S., Henskens F., Hillert J., Hong K.S., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Kirov G., Lochner C., Loughland C., Mathews C.A., McMahon F.J., Michie P., Mowry B., Neale B.M., Nievergelt C.M., Oedegaard K.J., Olsson T., Pantelis C., Patrinos G.P., Reininghaus E.Z., Saito T., Schall U., Schalling M., Scott R.J., Weickert C.S., Stordal E., Vaaler A.E., Vieta E., Waldman I.D., Zwart J.-A., Nurnberger J.I., Stahl E.A., Di Florio A., Adan R.A.H., Ando T., Aschauer H., Baker J.H., Bencko V., Birgegard A., Boden J.M., Boehm I., Boni C., Perica V.B., Buehren K., Bulik C.M., Burghardt R., Carlberg L., Cassina M., Clementi M., Cone R.D., Courtet P., Crowley J.J., Danner U.N., Davis O.S.P., de Zwaan M., Dedoussis G., Degortes D., DeSocio J.E., Dick D.M., Dina C., Dmitrzak-Weglarz M., Martinez E.D., Duncan L.E., Egberts K., Mattingsdal M., McDevitt S., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., Ntalla I., Olsen C.M., O'Toole J.K., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J.F., Ehrlich S., Escaramis G., Espeseth T., Estivill X., Farmer A., Favaro A., Fischer K., Floyd J.A.B., Focker M., Foretova L., Forzan M., Franklin C.S., Gambaro G., Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Mayora M.G., Guillaume S., Hanscombe K.B., Hatzikotoulas K., Hebebrand J., Helder S.G., Henders A.K., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L.J., Hubel C., Petersen L.V., Purves K.L., Raevuori A., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ritschel F., Roberts M., Rybakowski F., Santonastaso P., Scherag A., Schmidt U., Schork N.J., Schosser A., Seitz J., Slachtova L., Slagboom P.E., Slof-Op 't Landt M.C.T., Slopien A., Soranzo N., Sorbi S., Southam L., Steen V.W., Huckins L.M., Hudson J.I., Imgart H., Inoko H., Janout V., Jordan J., Julia A., Kalsi G., Kaminska D., Kaprio J., Karhunen L., Karwautz A., Kas M.J.H., Kennedy M.A., Keski-Rahkonen A., Kiezebrink K., Kim Y.-R., Kirk K.M., Klareskog L., Knudsen G.P.S., Larsen J.T., Le Hellard S., Leppa V.M., Lichtenstein P., Lin B.D., Lundervold A., Luykx J., Maj M., Mannik K., Marsal S., Stuber G.D., Szatkiewicz J.P., Tachmazidou I., Tenconi E., Tortorella A., Tozzi F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V.
Subjects: LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract: Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551
Published: 2022
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141. Preserved Navigation abilities and Spatio-Temporal Memory in individuals with Autism Spectrum Disorder

Author: Charles Laidi, Nathan Neu, Aurélie Watilliaux, Axelle Martinez‐Teruel, Mihoby Razafinimanana, Jennifer Boisgontier, Sevan Hotier, Marc‐Antoine d'Albis, Richard Delorme, Anouck Amestoy, Štefan Holiga, Myriam Ly‐Le Moal, Pierrick Coupé, Marion Leboyer, Josselin Houenou, Laure Rondi‐Reig, Anne‐Lise Paradis, 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), Unité de recherche en NeuroImagerie Applicative Clinique et Translationnelle (UNIACT), 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)-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), Cerebellum Navigation and Memory Team [IBPS] (CeZaMe), Neurosciences Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Robert Debré, Institut Roche [Boulogne-Billancourt, France], Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Investissements d'Avenir programs managed by the ANR under references ANR-11-IDEX-004-02 (Labex BioPsy) and ANR-10-COHO-10-01 and CNRS, and via collaboration with the Roche Institute for Research and Translational Medicine., CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Neuroscience Paris Seine (NPS), Fondation FondaMental [Créteil], Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Charles PERRENS, Patch-based processing for medical and natural images (PICTURA), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Autism Spectrum Disorder, Memory, General Neuroscience, Cerebellum, [SCCO.NEUR]Cognitive science/Neuroscience, Adults, Neurology (clinical), Genetics (clinical), Spatial Navigation
Abstract: International audience; Cerebellar abnormalities have been reported in autism spectrum disorder (ASD). Beyond its role in hallmark features of ASD, the cerebellum and its connectivity with forebrain structures also play a role in navigation. However, the current understanding of navigation abilities in ASD is equivocal, as is the impact of the disorder on the functional anatomy of the cerebellum. In the present study, we investigated the navigation behavior of a population of ASD and typically developing (TD) adults related to their brain anatomy as assessed by structural and functional MRI at rest. We used the Starmaze task, which permits assessing and distinguishing two complex navigation behaviors, one based on allocentric and the other on egocentric learning of a route with multiple decision points. Compared to TD controls, individuals with ASD showed similar exploration, learning, and strategy performance and preference. In addition, there was no difference in the structural or functional anatomy of the cerebellar circuits involved in navigation between the two groups. The findings of our work suggest that navigation abilities, spatio-temporal memory, and their underlying circuits are preserved in individuals with ASD.
Published: 2022
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142. A mind-reading puzzle: Autistic people are more efficient at a theory-of-mind task

Author: Estefania Loza, Frédérique Amsellem, Tiziana Zalla, Ariane Cartigny, Marion Leboyer, Richard Delorme, Franck Ramus, and Baudouin Forgeot d′Arc
Subjects: Psychiatry and Mental health, Clinical Psychology, Developmental and Educational Psychology
Published: 2023
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143. Viewpoint | European COVID-19 exit strategy for people with severe mental disorders: Too little, but not yet too late

Author: Robert H. Yolken, Benedetta Vai, Juan C. Leza, Michael E. Benros, Thomas A Pollak, Livia De Picker, Igor Branchi, Anthony C. Vernon, Marion Leboyer, Alessandra Borsini, Francesco Benedetti, Paolo Fusar-Poli, Carmine M. Pariante, and Ryad Tamouza
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Exit strategy, Severe Mental Disorders, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, Endocrine and Autonomic Systems, business.industry, Mental Disorders, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, COVID-19, Behavioral Neuroscience, Immunopsychiatry, medicine, Humans, Psychiatry, business
Published: 2021
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144. Redefining peripheral inflammation signature in schizophrenia based on the real-world FACE-SZ cohort

Author: Christophe Lançon, Baptiste Pignon, T Korchia, Guillaume Fond, Damien Etchecopar-Etchart, Raphaëlle Richieri, Christine Passerieux, Jasmina Mallet, David Misdrahi, Delphine Capdevielle, Mélanie Faugere, Mathieu Urbach, F. Schürhoff, N Coulon, Bruno Aouizerate, Romain Rey, Ophélia Godin, L. Boyer, Julien Dubreucq, P.L. Sunhary de Verville, Isabelle Chereau, Jean-Michel Dorey, Marion Leboyer, Julie Clauss-Kobayashi, Caroline Dubertret, Fabrice Berna, P.-M. Llorca, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Fondation FondaMental [Créteil], 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), Hôpital Henri Mondor, 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, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Les Hôpitaux Universitaires de Strasbourg (HUS), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier Charles Perrens [Bordeaux], 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), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], 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 Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur (HANDIReSP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier de Versailles André Mignot (CHV), FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) Group: P M Llorca, C Lançon, L Boyer, Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Quality of life, medicine.medical_specialty, Inflammation, Overweight, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, Biological Psychiatry, Pharmacology, Psychiatry, business.industry, Patient Acuity, medicine.disease, Physical activity level, 3. Good health, 030227 psychiatry, Peripheral, C-Reactive Protein, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, Inflammatory biomarker, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers
Abstract: International audience; Background: Peripheral inflammation is associated with impaired prognosis in schizophrenia (SZ). Highly sensitive C-reactive protein (hs-CRP) is the most used inflammatory biomarker in daily practice. However, no consensual cut-off has been determined to date to discriminate patients with peripheral inflammation from those without.Aims: To determine if patients with peripheral inflammation between 1 and 3 mg/L had poorer outcomes compared to those with undetectable CRP ( 1 mg/L is a reliable marker to detect peripheral inflammation in patients with schizophrenia.
Published: 2021
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145. Monocyte mitochondrial dysfunction, inflammaging, and inflammatory pyroptosis in major depression

Author: Sara Poletti, Marion Leboyer, Bartholomeus C M Haarman, Gara Arteaga-Henríquez, Maria S Simon, Annemarie J. M. Wijkhuijs, Carmen Schiweck, Olya Mikova, Richard Musil, Volker Arolt, Elske Vrieze, Stephan Claes, Francesco Benedetti, Raf Berghmans, W A Dik, Silke Joergens, Roberto Furlan, Bernhard T. Baune, Hemmo A. Drexhage, Markus J. Schwarz, Harm de Wit, Norbert Müller, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Immunology, Simon, M. S., Schiweck, C., Arteaga-Henriquez, G., Poletti, S., Haarman, B. C. M., Dik, W. A., Schwarz, M., Vrieze, E., Mikova, O., Joergens, S., Musil, R., Claes, S., Baune, B. T., Leboyer, M., Benedetti, F., Furlan, R., Berghmans, R., de Wit, H., Wijkhuijs, A., Arolt, V., Muller, N., and Drexhage, H. A.
Subjects: Male, DISORDER, STRESS, Gene Expression, Apoptosis, Monocytes, PATHWAY, 0302 clinical medicine, Adverse Childhood Experiences, Gene cluster, HISTORY, Medicine, Pharmacology & Pharmacy, GENE-EXPRESSION, Psychiatry, Microglia, CHOLESTEROL, Pyroptosis, Mitochondria, medicine.anatomical_structure, PCR, Female, medicine.symptom, Life Sciences & Biomedicine, Adult, Premature aging, Clinical Neurology, Inflammation, Major depressive disorder, DIAGNOSIS, 03 medical and health sciences, Downregulation and upregulation, Cholesterol pathway, Humans, Biological Psychiatry, METAANALYSIS, Pharmacology, Depressive Disorder, Major, Science & Technology, business.industry, Macrophages, Monocyte, Neurosciences, 030227 psychiatry, Cross-Sectional Studies, Immunology, Childhood adversity, Neurosciences & Neurology, business, CD163
Abstract: BACKGROUND: The macrophage theory of depression states that macrophages play an important role in Major Depressive Disorder (MDD). METHODS: MDD patients (N = 140) and healthy controls (N = 120) participated in a cross-sectional study investigating the expression of apoptosis/growth and lipid/cholesterol pathway genes (BAX, BCL10, EGR1, EGR2, HB-EGF, NR1H3, ABCA1, ABCG1, MVK, CD163, HMOX1) in monocytes (macrophage/microglia precursors). Gene expressions were correlated to a set of previously determined and reported inflammation-regulating genes and analyzed with respect to various clinical parameters. RESULTS: MDD monocytes showed an overexpression of the apoptosis/growth/cholesterol and the TNF genes forming an inter-correlating gene cluster (cluster 3) separate from the previously described inflammation-related gene clusters (containing IL1 and IL6). While upregulation of monocyte gene cluster 3 was a hallmark of monocytes of all MDD patients, upregulation of the inflammation-related clusters was confirmed to be found only in the monocytes of patients with childhood adversity. The latter group also showed a downregulation of the cholesterol metabolism gene MVK, which is known to play an important role in trained immunity and proneness to inflammation. CONCLUSIONS: The upregulation of cluster 3 genes in monocytes of all MDD patients suggests a premature aging of the cells, i.e. mitochondrial apoptotic dysfunction and TNF "inflammaging", as a general feature of MDD. The overexpression of the IL-1/IL-6 containing inflammation clusters and the downregulation of MVK in monocytes of patients with childhood adversity indicates a shift in this condition to a more severe inflammation form (pyroptosis) of the cells, additional to the signs of premature aging and inflammaging. ispartof: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY vol:111 ispartof: location:England status: published
Published: 2021
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146. Hypo- and hyper- sensory processing heterogeneity in Autism Spectrum Disorder

Author: Aline Lefebvre, Julian Tillmann, Freddy Cliquet, Frederique Amsellem, Anna Maruani, Claire Leblond, Anita Beggiato, David Germanaud, Anouck Amestoy, Myriam Ly-Le Moal, Daniel Umbricht, Christopher Chattam, Lorraine Murtagh, Manuel Bouvard, Marion Leboyer, Tony Charman, Thomas Bourgeron, Richard Delorme, and Guillaume Dumas
Abstract: Background. Sensory processing atypicalities are part of the core symptoms of autism spectrum disorder (ASD) and could result from an excitation/inhibition imbalance. Yet, the convergence level of phenotypic sensory processing atypicalities with genetic alterations in GABA-ergic and glutamatergic pathways remains poorly understood. This study aimed to characterize the distribution of hypo/hyper-sensory profile among individuals with ASD and investigate the role of deleterious mutations in GABAergic and glutamatergic pathways related genes in sensory processing atypicalities. Method. From the Short Sensory Profile (SSP) questionnaire, we defined and explored a score – the differential Short Sensory Profile (dSSP) - as a normalized and centralized hypo/hypersensitivity ratio for 1136 participants (533 with ASD, 210 first-degree relatives, and 267 controls) from two independent study samples (PARIS and LEAP). We also performed an unsupervised item-based clustering analysis on SSP items scores to validate this new categorization in terms of hypo and hyper sensitivity. We then explored the link between the dSSP score and the burden of deleterious mutations in a subset of individuals for which whole-genome sequencing data were available. Results. We observed a mean dSSP score difference between ASD and controls, driven mostly by a high dSSP score variability among groups (PARIS: p2 = 0.0001, LEAP: p2 = 0.02; LEAP: p=0.01, η2 = 0.01). Clusters were similarly characterized by hypo- and hyper-sensitivity items in both study samples (Cramer's V from 0.64 to 0.69, pLimitations. The major limitation was the dSSP score difficulty to discriminate subjects with a similar quantum of hypo- and hyper- sensory symptoms to those with no such symptoms, resulting both in a similar ratio score of 0.Conclusion. The dSSP score could be a relevant clinical score of the hypo/hyper-sensory individual profile in subjects with ASD. Combined with additional sensory domain characteristics, genetics and endophenotypic substrates, the dSSP score will offer new avenues to explore the underlying neurobiological mechanisms of sensory processing atypicalities in ASD.
Published: 2021
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147. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

Author: Michael McCarthy, Claire O'Donovan, Urs Heilbronner, Ichiro Kusumi, Eduard Vieta, Liping Hou, Hsi-Chung Chen, Claire Slaney, Maria Grigoroiu-Serbanescu, Kazufumi Akiyama, Michael Bauer, Janusz K. Rybakowski, Frank Bellivier, Marion Leboyer, Katzutaka Shimoda, Palmiero Monteleone, Cristiana Cruceanu, Alessio Squassina, Stephanie H. Witt, Tadafumi Kato, Giovanni Severino, Alfonso Tortorella, J. Raymond DePaulo, Martin Alda, Louise Frisén, Mazda Adl, Martin Schalling, Per Hoffmann, Susan G. Leckband, Jean-Pierre Kahn, Jean-Michel Aubry, Francis J. McMahon, Sven Cichon, Alexandre Dayer, Tatyana Shekhtman, Franziska Degenhardt, James B. Potash, Bruno Etain, Joseph Frank, Antonio Benabarre, Bernhard T. Baune, Gloria Roberts, Ryota Hashimoto, Tomas Novak, Paul D. Shilling, Julia Veeh, Joanna M. Biernacka, Barbara König, Peter Falkai, Philip B. Mitchell, Urban Ösby, Esther Jiménez, Sébastien Gard, Mark A. Frye, Sarah Kittel-Schneider, Layla Kassem, Fasil Tekola-Ayele, Armin Birner, Cynthia Marie-Claire, Raffaella Ardau, Abesh Kumar Bhattacharjee, Stéphane Jamain, Julie Garnham, Guy A. Rouleau, Caterina Chillotti, Piotr M. Czerski, Thomas G. Schulze, Gustavo Turecki, Anbupalam Thalamuthu, Claudia Pisanu, Azmeraw T. Amare, Marina Mitjans, Sergi Papiol, Mario Maj, Bárbara Arias, Janice M. Fullerton, Nina Dalkner, Peter R. Schofield, Susanne Bengesser, Stefan Herms, Klaus Oliver Schubert, Francis M. Mondimore, Eva Z. Reininghaus, Fernando S. Goes, Lena Backlund, Francesc Colom, Catharina Lavebratt, Christian Simhandl, Marcella Rietschel, Micah Cearns, Mikael Landén, Norio Ozaki, Gonzalo Laje, Barbara W. Schweizer, Nirmala Akula, Andrea Pfennig, Yi-Hsiang Hsu, John R. Kelsoe, Lina Martinsson, Markus M. Nöthen, Caroline M. Nievergelt, Pavla Stopkova, Mirko Manchia, Susan L. McElroy, Peter P. Zandi, Scott R. Clark, Joanna Hauser, Andreas J. Forstner, Po-Hsiu Kuo, Andreas Reif, Maria Del Zompo, Paul Grof, Fabian Streit, Ewa Ferensztajn-Rochowiak, Pablo Cervantes, Thomas Stamm, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Digital Health, Schubert, K. O., Thalamuthu, A., Amare, A. T., Frank, J., Streit, F., Adl, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J. -M., Backlund, L., Bhattacharjee, A. K., Bellivier, F., Benabarre, A., Bengesser, S., Biernacka, J. M., Birner, A., Marie-Claire, C., Cearns, M., Cervantes, P., Chen, H. -C., Chillotti, C., Cichon, S., Clark, S. R., Cruceanu, C., Czerski, P. M., Dalkner, N., Dayer, A., Degenhardt, F., Del Zompo, M., Depaulo, J. R., Etain, B., Falkai, P., Forstner, A. J., Frisen, L., Frye, M. A., Fullerton, J. M., Gard, S., Garnham, J. S., Goes, F. S., Grigoroiu-Serbanescu, M., Grof, P., Hashimoto, R., Hauser, J., Heilbronner, U., Herms, S., Hoffmann, P., Hou, L., Hsu, Y. -H., Jamain, S., Jimenez, E., Kahn, J. -P., Kassem, L., Kuo, P. -H., Kato, T., Kelsoe, J., Kittel-Schneider, S., Ferensztajn-Rochowiak, E., Konig, B., Kusumi, I., Laje, G., Landen, M., Lavebratt, C., Leboyer, M., Leckband, S. G., Maj, M., Manchia, M., Martinsson, L., Mccarthy, M. J., Mcelroy, S., Colom, F., Mitjans, M., Mondimore, F. M., Monteleone, P., Nievergelt, C. M., Nothen, M. M., Novak, T., O'Donovan, C., Ozaki, N., Osby, U., Papiol, S., Pfennig, A., Pisanu, C., Potash, J. B., Reif, A., Reininghaus, E., Rouleau, G. A., Rybakowski, J. K., Schalling, M., Schofield, P. R., Schweizer, B. W., Severino, G., Shekhtman, T., Shilling, P. D., Shimoda, K., Simhandl, C., Slaney, C. M., Squassina, A., Stamm, T., Stopkova, P., Tekola-Ayele, F., Tortorella, A., Turecki, G., Veeh, J., Vieta, E., Witt, S. H., Roberts, G., Zandi, P. P., Alda, M., Bauer, M., Mcmahon, F. J., Mitchell, P. B., Schulze, T. G., Rietschel, M., and Baune, B. T.
Subjects: Oncology, Multifactorial Inheritance, Treatment response, medicine.medical_specialty, Lithium (medication), Bipolar disorder, Poor responder, Neurosciences. Biological psychiatry. Neuropsychiatry, Lithium, DISEASE, Article, Cellular and Molecular Neuroscience, Risk Factors, Internal medicine, medicine, Humans, Manic-depressive illness, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Depressió psíquica, METAANALYSIS, Biological Psychiatry, Depression (differential diagnoses), MANIA, Depressive Disorder, Depressive Disorder, Major, Trastorn bipolar, Depression, business.industry, Major, medicine.disease, Pathway analysis, Liti, COMPARATIVE EFFICACY, Psychiatry and Mental health, Mental depression, Schizophrenia, Polygenic risk score, Esquizofrènia, Pharmacogenomics, business, RC321-571, medicine.drug
Abstract: Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium’s therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.
Published: 2021
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148. Visual attention and inhibitory control in children, teenagers and adults with autism without intellectual disability: results of oculomotor tasks from a 2-year longitudinal follow-up study (InFoR)

Author: Daniel Umbricht, Richard Delorme, Josselin Houenou, Lorraine Murtagh, Giulia Bucchioni, Tiziana Zalla, Marion Leboyer, Anouck Amestoy, Jean-René Cazalets, Manuel Bouvard, Christopher H. Chatham, Etienne Guillaud, and Miriam Ly-Le Moal
Subjects: Adult, medicine.medical_specialty, Neurology, Adolescent, Eye Movements, genetic structures, Autism Spectrum Disorder, Audiology, behavioral disciplines and activities, Developmental Neuroscience, Intellectual Disability, Intellectual disability, mental disorders, medicine, Humans, Autistic Disorder, Child, RC346-429, Inhibitory control, Molecular Biology, Oculomotor behavior, Gap–Overlap–Step tasks, Research, Neuropsychology, Cognition, Executive functions, medicine.disease, Comorbidity, Autism spectrum disorders (ASD), Attention shifting, Psychiatry and Mental health, Attention Deficit Disorder with Hyperactivity, Antisaccade task, Autism, Neurology. Diseases of the nervous system, Eye-tracking, Psychology, Developmental Biology, Follow-Up Studies
Abstract: Background Inhibitory control and attention processing atypicalities are implicated in various diseases, including autism spectrum disorders (ASD). These cognitive functions can be tested by using visually guided saccade-based paradigms in children, adolescents and adults to determine the time course of such disorders. Methods In this study, using Gap, Step, Overlap and Antisaccade tasks, we analyzed the oculomotor behavior of 82 children, teenagers and adults with high functioning ASD and their peer typically developing (TD) controls in a two-year follow-up study under the auspices of the InFoR-Autism project. Analysis of correlations between oculomotors task measurements and diagnostic assessment of attentional (ADHD-RS and ADHD comorbidity indices) and executive functioning (BRIEF scales) were conducted in order to evaluate their relationship with the oculomotor performance of participants with ASD. Results As indicated by the presence of a Gap and Overlap effects in all age groups, the oculomotor performances of ASD participants showed a preserved capability in overt attention switching. In contrast, the difference in performances of ASD participants in the Antisaccade task, compared to their TD peers, indicated an atypical development of inhibition and executive functions. From correlation analysis between our oculomotor data and ADHD comorbidity index, and scores of attention and executive function difficulties, our findings support the hypothesis that a specific dysfunction of inhibition skills occurs in ASD participants that is independent of the presence of ADHD comorbidity. Limitations These include the relatively small sample size of the ASD group over the study’s two-year period, the absence of an ADHD-only control group and the evaluation of a TD control group solely at the study’s inception. Conclusions Children and teenagers with ASD have greater difficulty in attention switching and inhibiting prepotent stimuli. Adults with ASD can overcome these difficulties, but, similar to teenagers and children with ASD, they make more erroneous and anticipatory saccades and display a greater trial-to-trial variability in all oculomotor tasks compared to their peers. Our results are indicative of a developmental delay in the maturation of executive and attentional functioning in ASD and of a specific impairment in inhibitory control.
Published: 2021

149. Temporal preparation in adults with autistic spectrum disorder: The variable foreperiod effect

Author: Marion Leboyer, Tiziana Zalla, Sylvie Chokron, Laura Gabriela Fernandez, Giovanna Girardi, Alice Latimier, Laboratoire d'informatique de l'école normale supérieure (LIENS), Département d'informatique - ENS Paris (DI-ENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, medicine.medical_specialty, genetic structures, Autistic spectrum disorder, Warning tone, autism spectrum disorder, Stimulus (physiology), Audiology, 050105 experimental psychology, Arousal, 03 medical and health sciences, [SCCO]Cognitive science, Cognition, 0302 clinical medicine, arousal, Reaction Time, timing, medicine, Humans, Attention, 0501 psychology and cognitive sciences, implicit temporal preparation, Temporal information, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, General Neuroscience, 05 social sciences, medicine.disease, foreperiod, Autism spectrum disorder, Time Perception, conditional probability, Autism, Neurology (clinical), Psychology, 030217 neurology & neurosurgery
Abstract: Research suggested the possibility that temporal cognition may be different in autistic spectrum disorder (ASD). Although there are some empirical studies examining timing ability in these individuals, to our knowledge, no one directly assessed the ability to predict when an event will occur. Here, we report a study on implicit temporal preparation in individuals with ASD as indexed by the variable foreperiod (FP) effect. We compared a group of adult ASD participants to a group of typically-developed (TD) controls, for their respective abilities to utilize implicit temporal information in a simple detection task with three different preparatory intervals (FP, short, middle and long). Participants were given a warning tone to signal an imminent stimulus, and asked to press a key as quickly as they could upon detection of the stimulus. Both groups were able to use implicit temporal information, as revealed by both the variable-FP effect (i.e., faster response for targets appearing after a long FP) and asymmetric sequential effects (i.e., slower response in short-FP trials following a previous long-FP trial). The TD group exhibited a faster response in a long-FP trial that was preceded by short-FP one, whereas the ASD group did not, as reflected in their higher percentage of response omissions for a target that appeared later than in the previous trial. The reduced ability of ASD participants to modulate their responses under these conditions might reflect a difficulty in time-based monitoring of stimulus occurrence. LAY SUMMARY: Time-processing may be different in autistic spectrum disorder (ASD). This study addressed the ability to anticipate a relevant stimulus's onset according to predictable interstimulus intervals comparing adults with ASD and typically developed controls. We found that ASD participants did not benefit from temporal preparation when stimulus appeared later than previously attended. This suggests a reduced ability in detecting implicit temporal regularities between events.
Published: 2021
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150. Genome-wide association study identifies new locus associated with OCD

Author: Danielle Posthuma, Bernie Devlin, Edna Grünblatt, Ying Wang, Daniele Cusi, Stephan Ruhrmann, Steven A. Rasmussen, Michael S. Breen, Julia Klawohn, Ana Gabriela Hounie, Aline S. Sampaio, Cristina Barlassina, Marta Ribasés, Jackson G. Thorp, Cynthia M. Bulik, Marco A. Grados, Dan J. Stein, Abby Fyer, Vladimir Coric, Martha J. Falkenstein, Stephanie Le Hellard, Behrang Mahjani, Nathaniel McGregor, Homero Vallada, Miguel Casas, Laurent F. Thomas, Janice Krasnow, Abraham Reichenberg, Donald W. Black, Gwyneth Zai, Norbert Kathmann, Manuel Mattheisen, Nicholas G. Martin, Jason W. Krompinger, Josep Antoni Ramos-Quiroga, Judith Becker Nissen, Helga Ask, Damiaan Denys, Carolina Cappi, Euripedes Constantino Miguel, O. Joseph Bienvenu, Bengt T. Fundin, Lisa Osiecki, Karin J. H. Verweij, Paul Sandor, Jeremy Veenstra-VanderWeele, Maureen Mulhern, Sarah E. Medland, David M. Hougaard, Lauren Erdman, Jan Haavik, James L. Kennedy, Christopher P. Walker, Jurjen J. Luykx, Tim B. Bigdeli, Ian M. Hickie, Nienke Vulink, Maurizio Turiel, Peter Falkai, Enda M. Byrne, Valentina Ciullo, Daniel A. Geller, Liang Kung-Yee, Miriam A. Schiele, Lambertus Klei, Götz Berberich, Thomas Werge, Brion S. Maher, Christie L. Burton, Julia M. Sealock, Sandra Meier, Bernadette Cullen, Stephan Ripke, Dorothy E. Grice, Richard Delorme, Ted Reichborn-Kjennerud, Dongmei Yu, Danielle C. Cath, Lili Milani, Abdel Abdellaoui, Andres Metspalu, María Soler Artigas, Maria Conceição do Rosário, Ole Mors, Brian P. Brennan, Barbara E. Stranger, Ann E. Pulver, Nora I. Strom, Joseph D. Buxbaum, Hans J. Grabe, Jens R. Wendland, Michael H. Bloch, Srdjan Djurovic, Raquel Rabionet, Angel Carracedo, Carlos N. Pato, Erika L. Nurmi, Janet L. Sobell, Kevin S. O’Connell, Michael Wagner, David R. Rosenberg, Jonathan R. I. Coleman, Jeremiah M. Scharf, Kerry J. Ressler, Jaakko Kaprio, Edwin H. Cook, Scott L. Rauch, Federica Piras, Merete Nordentoft, Christian Rück, Fabrizio Piras, John-Anker Zwart, Jason A. Elias, Christopher Pittenger, Lea K. Davis, Margaret A. Richter, Evonne McArthur, Bendik S. Winsvold, Yin Yao, James J. Crowley, David L. Pauls, Rosa Bosch, Xavier Estivil, Matthew Halvorsen, Adrian Camarena, Nancy L. Pedersen, Pino Alonso, Eric A. Storch, Bjarne Hansen, Helena Brentani, James T. McCracken, Jan Maerten Smit, Donald Hucks, Alexandra Havdahl, Gerome Breen, Christina M. Hultman, Benjamin M. Neale, Gregory L. Hanna, Mikael Landén, Christine Lochner, Dirk J.A. Smit, Fabio Macciardi, Carol A. Mathews, Nuria Lanzagorta, Laura G. Sloofman, Cristina Rodriguez-Fontenla, Michael A. Jenike, Michele T. Pato, Marion Leboyer, Humberto Nicolini, Anders D. Børglum, Maria Cristina Cavallini, Wei Guo, Benjamin D. Greenberg, Maiken Elvestad Gabrielsen, Magdalena Janecka, Mark A. Riddle, Paul S. Nestadt, Beatriz Camarena, Valsamma Eapen, Susanne Walitza, Jack Samuels, Fernando S. Goes, Nicole C.R. McLaughlin, S. Evelyn Stewart, Jennifer Reichert, Sven Sandin, Gerd Kvale, Katharina Domschke, Ole A. Andreassen, Elles de Schipper, Paul D. Arnold, Kristi Krebs, Zachary Gerring, Teemu Palviainen, Kathleen D. Askland, Alfredo Ramirez, James A. Knowles, Laura Bellodi, Kristen Hagen, Julia Boberg, Thomas V. Fernandez, Gerald Nestadt, John Piacentini, Jakob Grove, Eske M. Derks, Preben Bo Mortensen, Elinor K. Karlsson, Gianfranco Spalletta, David Mataix-Cols, Katharina Bey, and Jonas Bybjerg-Grauholm
Subjects: Genetics, business.industry, Locus (genetics), Genome-wide association study, Single-nucleotide polymorphism, Heritability, behavioral disciplines and activities, humanities, Genetic architecture, Anorexia nervosa (differential diagnoses), mental disorders, medicine, Anxiety, SNP, medicine.symptom, business
Abstract: Obsessive-compulsive disorder (OCD) is a heritable disorder, but no definitive, replicated OCD susceptibility loci have yet been identified by any genome-wide association study (GWAS). Here, we report results from a GWAS in the largest OCD case-control sample (N = 14,140 OCD cases and N = 562,117 controls) to date. We explored the genetic architecture of OCD, including its genetic relationships to other psychiatric and non-psychiatric phenotypes. In the GWAS analysis, we identified one SNP associated with OCD at a genome-wide significant level. Subsequent gene-based analyses identified additional two genes as potentially implicated in OCD pathogenesis. All SNPs combined explained 16% of the heritability of OCD. We show sub-stantial positive genetic correlations between OCD and a range of psychiatric disorders, including anxiety disorders, anorexia nervosa, and major depression. We thus for the first time provide evidence of a genome-wide locus implicated in OCD and strengthen previous literature suggesting a polygenic nature of this disorder.
Published: 2021
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