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1. Clinical features and outcomes of COVID-19 patients hospitalized for psychiatric disorders: a French multi-centered prospective observational study

Author

Claire Jansen, Pierre Thomas, Djamila Bennabi, Dominique Drapier, Thomas Schwitzer, Delphine Capdevielle, Noe Teboul, Pascal Delamillieure, Emmanuelle Corruble, Christophe Schmitt, Daniela Dobre, Olivier C. Martin, Pierre Abdel Ahad, Antoine Pelissolo, Clément Vansteene, Benjamin Rolland, Marion Leboyer, Raymund Schwan, Fabienne Ligier, Wanda Yekhlef, Antoine Yrondi, Raphaël Gaillard, William Lecoeur, Radoine Haoui, Mathilde Roser, Vincent Laprevote, Catherine Massoubre, Sonia Dollfus, Fabien Joubert, Philip Gorwood, 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, Centre Psychothérapique de Nancy [Laxou] (CPN), Faculté de Médecine [Nancy], Université de Lorraine (UL), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), 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), Hospices Civils de Lyon (HCL), GHU Paris Psychiatrie et Neurosciences, 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), Département de psychiatrie adulte, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital La Colombière, 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, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Imagerie et Stratégies Thérapeutiques de la Schizophrénie (ISTS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier le Vinatier [Bron], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), 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 hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Hôpital Sainte-Anne-Université Paris Cité (UPCité), Service Psychiatrie et psychologie médicale [CHU Toulouse], Pôle Psychiatrie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Gérard Marchant, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Psychiatrie et Neurosciences (U894), Centre Psychothérapique de Nancy (CPN), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, HAL UR1, Admin, Centre de recherche en neurosciences de Lyon (CRNL), 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), Service Universitaire d’Addictologie de Lyon [CH Le Vinatier, Bron] (Pôle MOPHA - SUAL), 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 Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Etablissement Public de Santé Alsace Nord, Partenaires INRAE, Hôpital Sainte-Anne-Université de Paris (UP), Etablissement public de santé de Ville-Evrard (EPS), Service Psychiatrie et psychologie médicale [CHU Purpan], CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Population, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Confusional state, Logistic regression, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Organic mental disorders, Intensive care, medicine, Psychiatry, Prospective cohort study, education, Applied Psychology, Univariate analysis, education.field_of_study, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, Medical record, COVID-19, Odds ratio, medicine.disease, Mental health, Confidence interval, 030227 psychiatry, 3. Good health, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Original Article, Observational study, business, 030217 neurology & neurosurgery
Abstract

Background: At the beginning of COVID-19 pandemic, specific COVID/PSY wards were created in France to provide care for inpatients with COVID-19 and psychiatric disorders. In this multi-center prospective study, we set out to assess the clinical features and risk factors of somatic aggravation in patients hospitalized in COVID/PSY wards. Methods: Data were collected between 28 February and 30 May, 2020. We collected demographic data, psychiatric diagnoses, medical data and COVID-19-related clinical data. Somatic aggravation was estimated by the number of patients transferred to intensive care or medicine units, the number of deaths and the number of patients presenting a confusional state. A multivariate logistic model was used to assess the risk factors of confusional state and transfer to intensive care or medicine units. The risk of death was analysed by the univariate predictors of this outcome. Outcomes: 350 patients were included in the study. The number of inclusions peaked one week after that of the general population and declined more slowly. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit (OR 17.1; CI 4.9-59.3). Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age > 55 (OR 4.9; CI 2.1-11.4), an affective disorder (OR 4.1; CI 1.6-10.9), and severe respiratory symptoms (OR 4.6; CI 2.2-9.7) predicted a higher risk, while smoking (OR 0.3; CI 0.1-0.9) predicted a lower risk of a confusional state. Interpretation: COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and a high risk of confusion. COVID/PSY wards may play a role in reducing the mortality of COVID-19 in patients with psychiatric disorders. Funding Statement: There was no funding source for this study. Declaration of Interests: There are no conflicts of interest to be declared. Ethics Approval Statement: This observational study was conducted according to the principles of the Declaration of Helsinki. In accordance with French bioethics laws, it was classified as a non- interventional study, since it concerned anonymized clinical data that are routinely compiled in medical records. Compliance with French regulations on personal data collection was supervised by the personal data referent of the Centre Psychotherapique de Nancy. Patients, and their legal guardian when appropriate, were informed in writing, in agreement with national regulations for observational studies.

Published
2023

2. Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation

Author

Jung Goo Lee, Elisa Brietzke, Mehala Subramaniapillai, Rodrigo B. Mansur, Michael E. Thase, Yena Lee, James W. Murrough, George I. Papakostas, Charles B. Nemeroff, Philip Gorwood, Roger Ho, Leanna M.W. Lui, Gerard Sanacora, Siegfried Kasper, Carlos A. Zarate, Eduard Vieta, Kevin Kratiuk, Carlos López Jaramillo, Seetal Dodd, Stephen M. Stahl, Michael Berk, Allan H. Young, Joshua D. Rosenblat, Dan V. Iosifescu, and Roger S. McIntyre

Subjects
medicine.medical_specialty, business.industry, medicine.disease, Article, 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Mood, Tolerability, Mood disorders, medicine, Major depressive disorder, Antidepressant, Bipolar disorder, medicine.symptom, business, Psychiatry, Suicidal ideation, Treatment-resistant depression, 030217 neurology & neurosurgery
Abstract

Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent pharmacologically novel treatment avenues for adults with treatment-resistant depression. In addition to providing hope to affected persons, these agents represent the first non-monoaminergic agents with proven rapid-onset efficacy in major depressive disorder. Nevertheless, concerns remain about the safety and tolerability of ketamine and esketamine in mood disorders. Moreover, there is uncertainty about the appropriate position of these agents in treatment algorithms, their comparative effectiveness, and the appropriate setting, infrastructure, and personnel required for their competent and safe implementation. In this article, an international group of mood disorder experts provides a synthesis of the literature with respect to the efficacy, safety, and tolerability of ketamine and esketamine in adults with treatment-resistant depression. The authors also provide guidance for the implementation of these agents in clinical practice, with particular attention to practice parameters at point of care. Areas of consensus and future research vistas are discussed.

Published
2021

3. Lower leptin level at discharge in acute anorexia nervosa is associated with early weight‐loss

Author

Philip Gorwood, Nebal Alanbar, Philibert Duriez, Jacques Epelbaum, Dominique Grouselle, Roland Dardennes, Virginie Tolle, Nicolas Ramoz, Guillaume Lavoisy, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Hôpital Sainte-Anne-Université de Paris (UP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Mécanismes Adaptatifs et Evolution (MECADEV), and Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Leptin, 050103 clinical psychology, medicine.medical_specialty, Anorexia Nervosa, [SDV]Life Sciences [q-bio], Aftercare, Gastroenterology, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Weight loss, Internal medicine, Weight Loss, medicine, Humans, 0501 psychology and cognitive sciences, Risk factor, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, business.industry, digestive, oral, and skin physiology, 05 social sciences, Obestatin, Patient Discharge, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Anorexia nervosa (differential diagnoses), Biomarker (medicine), Ghrelin, medicine.symptom, business, Body mass index, hormones, hormone substitutes, and hormone antagonists
Abstract

OBJECTIVE Predictive values of acute phase metabolic abnormalities of anorexia nervosa (AN) have seldom been studied. As early postrestoration weight loss is associated with poor outcome, discharge biologic parameters were assessed to detect an association with 2-month follow-up weight loss as a proxy to poor outcome. METHOD Fasting plasma levels of leptin, acyl-ghrelin, obestatin, PYY, oxytocin and BDNF were measured in 26 inpatients, at inclusion, at discharge and 2 months later. A body mass index less than 18 2-month postdischarge was considered a poor outcome. RESULTS Nineteen patients (73%) had a fair outcome and seven (27%) had a poor one with a mean loss of 0.69 versus 4.54 kg, respectively. Only discharge leptin levels were significantly higher in fair versus poor outcome patients (14.1 vs. 7.0 ng/ml, p = 0.006). The logistic regression model using discharge leptin, acyl-ghrelin, obestatin, oxytocin, PYY and BDNF levels as predictors of outcome disclosed a nearly significant effect of leptin (p

Published
2021

4. Depressive-, Cognitive- or Stroke-Related Risk Factors of Post-Stroke Depression: Which One Could Better Help Clinicians and Patients?

Author

David Calvet, Lila Mekaoui, Rebecca Perrain, Jean-Louis Mas, Philip Gorwood, and Vincent Guiraud

Subjects
medicine.medical_specialty, Neuropsychiatric Disease and Treatment, 03 medical and health sciences, 0302 clinical medicine, prevention, Internal medicine, mental disorders, History of depression, medicine, Post-stroke depression, risk factors, Risk factor, Major depressive episode, Prospective cohort study, Stroke, Depression (differential diagnoses), Original Research, post-stroke depression, business.industry, cohort, medicine.disease, stroke, 030227 psychiatry, nervous system, Cohort, depression, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Rebecca Perrain,1,2 David Calvet,3– 5 Vincent Guiraud,3– 5 Lila Mekaoui,1 Jean-Louis Mas,3– 5 Philip Gorwood1,2,5 1GHU Paris Psychiatrie et Neurosciences, CMME, Hôpital Sainte-Anne, Paris, France; 2University of Paris, Paris, France; 3GHU Paris Psychiatrie et Neurosciences, Department of Neurology, Hôpital Sainte-Anne, Paris, France; 4University of Paris, FHU Neurovasc, Paris, France; 5Institute of Psychiatry and Neuroscience of Paris, INSERMU1266, Paris, FranceCorrespondence: Rebecca PerrainClinique des Maladies Mentales et de l’Encéphale, Sainte-Anne Hospital, GHU Paris– Psychiatrie & Neurosciences, 100 rue de la Santé 75674 Paris Cedex 14, Paris, FranceTel +33 1 45 65 83 64Fax +33 1 45 65 76 56Email r.perrain@ghu-paris.frPurpose: Post-stroke depression (PSD) affects one third of stroke survivors, with multiple severe negative consequences. We aim to assess the weight of four different types of clinical risk factors for PSD.Patients and Methods: We conducted a prospective cohort study in a stroke centre. After stroke, patients were assessed for cognitive performances, psychiatric standardized questionnaires and socio-demographic features. They were called three months after and assessed for major depressive episode using DSM criteria.Results: PSD was diagnosed in 8 of the 59 (13.6%) patients enrolled in the study. After multivariate analysis, only “previous history of depressive episode” remained a significant predictive factor for PSD, the model explaining 19% of the total variance (OR=18.0; p=0.002). Patients with a previous history of depression had a 10-fold increased risk for PSD.Conclusion: Previous history of depression is confirmed as a strong risk factor for PDS and allow the identification of an at-risk sub-group of patients.Keywords: post-stroke depression, depression, stroke, risk factors, prevention, cohort

Published
2021

5. Cholinergic dysfunction in the dorsal striatum promotes habit formation and maladaptive eating

Author

Damian Justo, Marc G. Caron, Luc Moquin, Ornela Kljakic, Xiang Qi Meng, Pedro Rosa Neto, Erika Vigneault, Philibert Duriez, Helena Janickova, Tharick A. Pascoal, Jun-II Kang, Mark P. Brandon, Jacob P. R. Jacobsen, Marco A. M. Prado, Salah El Mestikawy, Vania F. Prado, Philip Gorwood, Jürgen Germann, Alain Gratton, Léonie Runtz, Mathieu Favier, Sanda Raulic, M. Mallar Chakravarty, Christina Antinora, Daniel Gallino, Joman Y. Natsheh, and Mohammad M. Herzallah

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Vesicular Acetylcholine Transport Proteins, Glutamic Acid, Striatum, Biology, Feeding and Eating Disorders, Levodopa, Mice, 03 medical and health sciences, 0302 clinical medicine, Interneurons, Dopamine, Internal medicine, medicine, Animals, Humans, Donepezil, Mice, Knockout, Phenocopy, Glutamate receptor, Feeding Behavior, General Medicine, Middle Aged, medicine.disease, Acetylcholine, Corpus Striatum, Eating disorders, 030104 developmental biology, Endocrinology, nervous system, 030220 oncology & carcinogenesis, Cholinergic, Female, Research Article, medicine.drug
Abstract

Dysregulation of habit formation has been recently proposed as pivotal to eating disorders. Here, we report that a subset of patients suffering from restrictive anorexia nervosa have enhanced habit formation compared with healthy controls. Habit formation is modulated by striatal cholinergic interneurons. These interneurons express vesicular transporters for acetylcholine (VAChT) and glutamate (VGLUT3) and use acetylcholine/glutamate cotransmission to regulate striatal functions. Using mice with genetically silenced VAChT (VAChT conditional KO, VAChTcKO) or VGLUT3 (VGLUT3cKO), we investigated the roles that acetylcholine and glutamate released by cholinergic interneurons play in habit formation and maladaptive eating. Silencing glutamate favored goal-directed behaviors and had no impact on eating behavior. In contrast, VAChTcKO mice were more prone to habits and maladaptive eating. Specific deletion of VAChT in the dorsomedial striatum of adult mice was sufficient to phenocopy maladaptive eating behaviors of VAChTcKO mice. Interestingly, VAChTcKO mice had reduced dopamine release in the dorsomedial striatum but not in the dorsolateral striatum. The dysfunctional eating behavior of VAChTcKO mice was alleviated by donepezil and by l-DOPA, confirming an acetylcholine/dopamine deficit. Our study reveals that loss of acetylcholine leads to a dopamine imbalance in striatal compartments, thereby promoting habits and vulnerability to maladaptive eating in mice.

Published
2020

6. 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. 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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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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., de Geus E.J.C., Depaulo J.R., Domenici E., Domschke K., Esko T., Grove J., Hall L.S., Hansen C.S., Hansen T.F., Herms S., Hickie I.B., Homuth G., Horn C., Hottenga J.-J., Hougaard D.M., Howard D.M., Jansen R., Jorgenson E., Knowles J.A., Kohane I.S., Kraft J., Kretzschmar W.W., Kutalik Z., Li Y., Lind P.A., MacIntyre D.J., MacKinnon D.F., Maier R.M., Maier W., Marchini J., Mbarek H., Middeldorp C.M., Mihailov E., Milani L., Mondimore F.M., Montgomery G.W., Mostafavi S., Nauck M., Ng B., Nivard M.G., Nyholt D.R., O'Reilly P.F., Oskarsson H., Hayward C., Heath A.C., Lewis G., Li Q.S., Madden P.A.F., Magnusson P.K., Martin N.G., McIntosh A.M., Metspalu A., Mors O., Nordentoft M., Paciga S.A., Pedersen N.L., Painter J.N., Pedersen C.B., Pedersen M.G., Peterson R.E., Peyrot W.J., Posthuma D., Quiroz J.A., Qvist P., Rice J.P., Riley B.P., Mirza S.S., Schoevers R., Schulte E.C., Shen L., Sigurdsson E., Sinnamon G.C.B., Smit J.H., Smith D.J., Stefansson H., Steinberg S., Streit F., Strohmaier J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Treutlein J., Trubetskoy V., Uitterlinden A.G., Umbricht D., der Auwera S.V., van Hemert A.M., Viktorin A., Visscher P.M., Wang Y., Webb B.T., Perlis R.H., Porteous D.J., Schaefer C., Stefansson K., Tiemeier H., Uher R., Werge T., Lewis C.M., Breen G., Borglum A.D., Sullivan P.F., O'Connell K.S., Coombes B., Qiao Z., Als T.D., Borte S., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Al Eissa M., Albani D., Alliey-Rodriguez N., Antilla V., Antoniou A., Baek J.H., Bauer M., Beins E.C., Bergen S.E., Birner A., Boen E., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Byerley W., Cairns M., Cervantes P., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Dobbyn A.L., Douzenis A., Elvsashagen T., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Gizer I.R., Gordon-Smith K., Greenwood T.A., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Holmans P.A., Huckins L., Johnson J.S., Kalman J.L., Kamatani Y., Kittel-Schneider S., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Leber M., Lee H.-J., Levy S.E., Lewis C., Lundberg M., Magnusson S.H., Maihofer A., Malaspina D., 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

7. The identification, assessment and management of difficult-to-treat depression: An international consensus statement

Author

Allan H. Young, Gin S Malhi, RH McAllister-Williams, Eduard Vieta, Philip Gorwood, Afzal Javed, Peter Falkai, Andrew Papadopoulos, A. J. Rush, Celso Arango, Jair C. Soares, Malcolm Hopwood, Pierre Blier, Koen Demyttenaere, Siegfried Kasper, Martinez Rico, Clara, Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Instituto de Investigación Sanitaria Gregorio Marañón [Madrid, Spain] ( IiSGM), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), University of Ottawa [Ottawa], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Ludwig Maximilian University [Munich] (LMU), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Melbourne, University of Warwick [Coventry], Medizinische Universität Wien = Medical University of Vienna, The University of Sydney, Royal North Shore Hospital (RNSH), The University of Texas Health Science Center at Houston (UTHealth), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), King‘s College London, South London and Maudsley NHS Foundation Trust, Somerset Partnership NHS Foundation Trust, Duke University [Durham], Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Duke-NUS Medical School [Singapore], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
VAGUS NERVE-STIMULATION, TRANSCRANIAL MAGNETIC STIMULATION, medicine.medical_specialty, Consensus, 2016 CLINICAL GUIDELINES, SEROTONIN REUPTAKE INHIBITORS, medicine.medical_treatment, Clinical Neurology, GENERALIZED ANXIETY DISORDER, Difficult-to-treat depression, Depressive Disorder, Treatment-Resistant, DOUBLE-BLIND, 03 medical and health sciences, POSTTRAUMATIC-STRESS-DISORDER, 0302 clinical medicine, Pharmacotherapy, Diagnosis, medicine, Humans, Symptom control, COGNITIVE-BEHAVIORAL THERAPY, Intensive care medicine, Neurostimulation, Psychiatry, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Science & Technology, Conceptualization, Depression, Clinical management, business.industry, Treatment options, MAJOR DEPRESSION, medicine.disease, 3. Good health, 030227 psychiatry, Psychotherapy, Psychiatry and Mental health, Clinical Psychology, Management implications, Quality of Life, TREATMENT-RESISTANT DEPRESSION, Neurosciences & Neurology, Treatment-resistant depression, business, Life Sciences & Biomedicine, Psychosocial, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract

BACKGROUND: Many depressed patients are not able to achieve or sustain symptom remission despite serial treatment trials - often termed "treatment resistant depression". A broader, perhaps more empathic concept of "difficult-to-treat depression" (DTD) was considered. METHODS: A consensus group discussed the definition, clinical recognition, assessment and management implications of the DTD heuristic. RESULTS: The group proposed that DTD be defined as "depression that continues to cause significant burden despite usual treatment efforts". All depression management should include a thorough initial assessment. When DTD is recognized, a regular reassessment that employs a multi-dimensional framework to identify addressable barriers to successful treatment (including patient-, illness- and treatment-related factors) is advised, along with specific recommendations for addressing these factors. The emphasis of treatment, in the first instance, shifts from a goal of remission to optimal symptom control, daily psychosocial functional and quality of life, based on a patient-centred approach with shared decision-making to enhance the timely consideration of all treatment options (including pharmacotherapy, psychotherapy, neurostimulation, etc.) to optimize outcomes when sustained remission is elusive. LIMITATIONS: The recommended definition and management of DTD is based largely on expert consensus. While DTD would seem to have clinical utility, its specificity and objectivity may be insufficient to define clinical populations for regulatory trial purposes, though DTD could define populations for service provision or phase 4 trials. CONCLUSIONS: DTD provides a clinically useful conceptualization that implies a search for and remediation of specific patient-, illness- and treatment obstacles to optimizing outcomes of relevance to patients. ispartof: Journal of Affective Disorders vol:267 pages:264-282 ispartof: location:Netherlands status: published

Published
2020

8. A meta-analysis of poststroke depression risk factors comparing depressive-related factors versus others

Author

Jean-Louis Mas, Rebecca Perrain, Lila Mekaoui, Philip Gorwood, and David Calvet

Subjects
medicine.medical_specialty, Time Factors, Alcohol Drinking, Apathy, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, History of depression, Humans, Post-stroke depression, Medicine, Cognitive Dysfunction, Stroke, Depression (differential diagnoses), Depression, business.industry, Smoking, Stroke Rehabilitation, Social Support, medicine.disease, Confidence interval, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Sample size determination, Relative risk, Meta-analysis, Geriatrics and Gerontology, business, Gerontology, 030217 neurology & neurosurgery
Abstract

Objectives:Poststroke depression (PSD) is a public health issue, affecting one-third of stroke survivors, and is associated with multiple negative consequences. Reviews tried to identify PSD risk factors with discrepant results, highlighting the lack of comparability of the analyzed studies. We carried out a meta-analysis in order to identify clinical risk factors that can predict PSD.Design:PubMed and Web of Science were searched for papers. Only papers with a strictly defined Diagnostic and Statistical Manual of Mental Disorders depression assessment, at least 2 weeks after stroke, were selected. Two authors independently evaluated potentially eligible studies that were identified by our search and independently extracted data using standardized spreadsheets. Analyses were performed using MetaWin®, the role of each variable being given as a risk ratio (RR).Results:Eighteen studies were included in the meta-analysis. Identified risk factors for PSD with RR significantly above 1 were previous history of depression (RR 2.19, confidence interval (CI) 1.52–3.15), disability (RR 2.00, CI 1.58–2.52), previous history of stroke (RR 1.68, CI 1.06–2.66), aphasia (RR 1.47, CI 1.13–1.91), and female gender (RR 1.35, CI 1.14–1.61). Fixed effects model leads to identification of two more risk factors: early depressive symptoms with an RR of 2.32 (CI 1.43–3.79) and tobacco consumption (RR 1.40, CI 1.09–1.81). Time bias was found for alcohol consumption. Sample size was significantly involved to explain the role of “alcohol consumption” and “cognitive impairment.”Conclusion:Five items were significantly predictive of PSD. It might be of clinical interest that depressive-related risk factors (such as past depressive episodes) were having the largest impact.

Published
2020

9. Association Between the A118G Polymorphism of the OPRM1 Gene and Suicidal Depression in a Large Cohort of Outpatients with Depression

Author

Emilie Olié, Sébastien Guillaume, Jonathan Dubois, Philippe Courtet, Bénédicte Nobile, Nicolas Ramoz, Philip Gorwood, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), 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), Fondation FondaMental [Créteil], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Guerineau, Nathalie C., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
medicine.medical_specialty, OPRM1, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Hospital Anxiety and Depression Scale, 03 medical and health sciences, 0302 clinical medicine, opioid system, Polymorphism (computer science), Rating scale, Internal medicine, Genotype, medicine, Allele, Suicidal ideation, Depression (differential diagnoses), A118G, suicide, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], business.industry, 030227 psychiatry, 3. Good health, suicidal ideation, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: Growing evidences suggest that depression with suicidal ideation (SI) could be a specific phenotype with its own characteristics. Moreover, opioid system deregulation might be implicated in suicidal behaviour (SB). The aim of this study was to determine whether the A118G polymorphism (rs1799971) in ORPM1 (the gene encoding opioid receptor mu 1) is associated with suicidal depression (ie, moderate to severe depression with SI) in a large cohort of outpatients with depression.Methods: GENESE is a large, prospective, naturalistic cohort of French adult outpatients with depression (DSM-IV criteria), treated and followed for 6 weeks. Depression severity was assessed with the Hospital Anxiety and Depression Scale (HADS), and SI with the suicidal item of the Montgomery-Åsberg Depression Rating Scale (MADRS-SI). From this cohort, patients with moderate or severe depression (HADS-D subscale score >11) were selected and classified as without SI (MADRS-SI < 2), or with SI (MADRS-SI ≥ 2).Results: The AA/AG genotypes of the A118G polymorphism were significantly associated with suicidal depression in the non-adjusted (OR = 2.32, 95% CI = [1.28; 4.18]; p-value = 0.005) and in the adjusted models (OR = 2.54, 95% CI = [1.35; 4.78]; p-value = 0.004).Conclusion: Outpatients with depression harbouring the A allele are at higher risk of SI (and possibly SB) than those carrying the G allele. More studies are needed to better understand the link between this polymorphism and SB.

Published
2021

10. Value of treatment for eating disorders

Author

Janet Treasure, Philip Gorwood, and Fernando Fernández-Aranda

Subjects
Feeding and Eating Disorders, Psychiatry and Mental health, Clinical Psychology, Eating disorders, medicine.medical_specialty, business.industry, medicine, MEDLINE, Humans, medicine.disease, business, Psychiatry, Value (mathematics)
Published
2021

11. Characteristics and treatment outcome of suicidal depression: Two large naturalistic cohorts of depressed outpatients

Author

Philippe Courtet, Emilie Olié, Sébastien Guillaume, Jonathan Dubois, Bénédicte Nobile, Philip Gorwood, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), 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), Fondation FondaMental [Créteil], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
Moderate to severe, suicide attempt, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Treatment outcome, suicidal depression, Suicidal Ideation, 03 medical and health sciences, 0302 clinical medicine, antisuicidal therapeutics, Outpatients, medicine, Humans, Prospective Studies, Psychiatry, Suicidal ideation, Depression (differential diagnoses), Psychiatric Status Rating Scales, antidepressant, Suicide attempt, business.industry, Depression, SUICIDAL DEPRESSION, General Medicine, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Treatment Outcome, Concomitant, Antidepressant, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Objective: The emergence of new drugs for managing suicidal ideation (e.g. ketamine) raises the question of whether suicidal depression (i.e. moderate to severe depression with concomitant suicidal ideation) is a specific depression phenotype. Therefore, this study characterized patients with suicidal depression (baseline clinical characteristics, suicidal ideation and depression evolutions, suicide risk) in two large cohorts of outpatients with depression. Methods: LUEUR and GENESE are two large, prospective, naturalistic cohorts of French adult outpatients with depression (Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria), treated and followed up for 6 weeks. Depression severity was assessed with the Hospital Anxiety and Depression Scale, and suicidal ideation with the suicidal item of the Montgomery–Åsberg Depression Rating Scale. Patients with moderate or severe depression (Hospital Anxiety and Depression Scale–Depression subscale score >11) were selected and classified as without suicidal ideation (suicidal item of the Montgomery–Åsberg Depression Rating Scale Results: Baseline clinical features were more severe (e.g. higher anxiety and depression scores) in depressed patients with moderate/severe suicidal ideation. Depression remission after treatment was less frequent among patients with severe suicidal ideation. The risk of suicide attempt during the follow-up was threefold higher in patients with suicidal ideation among those 10% had persistent suicidal ideation. Conclusion: Suicidal depression could be a specific depression phenotype with more severe clinical characteristics, less frequent depression remission, suicidal ideation persistence and higher suicide attempt risk, despite antidepressant treatment. It seems that novel therapeutic strategies could be needed.

Published
2021

12. Expert Consensus on Screening and Assessment of Cognition in Psychiatry

Author

Philip D. Harvey, Allan H. Young, Joshua D. Rosenblat, Bernhard T. Baune, Katherine E. Burdick, Phillipe Fossati, Rodrigo B. Mansur, John Harrison, Philip Gorwood, Elisa Brietzke, Alice Medalia, Carola Rong, Nicole D. Anderson, Kamilla W. Miskowiak, Catherine J. Harmer, Stephen M. Stahl, Tanya Ramey, and Roger S. McIntyre

Subjects
medicine.medical_specialty, Population ageing, Consensus, business.industry, Mental Disorders, MEDLINE, Expert consensus, Cognition, Disease, Neuropsychological Tests, Psychiatry and Mental health, Practice Guidelines as Topic, Humans, Medicine, Antidepressant, Neurology (clinical), Risk factor, Differential diagnosis, business, Psychiatry
Abstract

During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.

Published
2019

13. Burnout in medical students before residency: A systematic review and meta-analysis

Author

Boris Chaumette, Marie-Odile Krebs, Philip Gorwood, A. Frajerman, and Yannick Morvan

Subjects
medicine.medical_specialty, Students, Medical, 020205 medical informatics, Emotions, Population, MEDLINE, 02 engineering and technology, Burnout, Psychological, Burnout, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Depersonalization, Prevalence, 0202 electrical engineering, electronic engineering, information engineering, medicine, Humans, 030212 general & internal medicine, education, Emotional exhaustion, Depression (differential diagnoses), education.field_of_study, business.industry, Internship and Residency, Psychiatry and Mental health, Distress, Family medicine, Meta-analysis, medicine.symptom, business
Abstract

Background:Applying the concept of burnout to medical students before residency is relatively recent. Its estimated prevalence varies significantly between studies. Our objective was to estimate the prevalence of burnout in medical students worldwide.Methods:We systematically searched Medline for English-language articles published between January 1, 2010 and December 31, 2017. We selected all the original studies about the prevalence of burnout in medical students before residency, using validated questionnaires for burnout. Statistical analyses were conducted using the OpenMetaAnalyst software.Results:Prevalence of current burnout was extracted from 24 studies encompassing 17,431 medical students. Among them, 8060 suffered from burnout and we estimated the prevalence to be 44.2% [33.4%–55.0%]. The information about the prevalence of each subset of burnout dimensions was given in nine studies including 7588 students. Current prevalence was estimated to be 40.8% for ‘emotional exhaustion’ [32.8%–48.9%], 35.1% [27.2%–43.0%] for ‘depersonalization’ and 27.4% [20.5%–34.3%] for ‘personal accomplishment’. There is no significant gender difference in burnout. The prevalence of burnout is slightly different across countries with a higher prevalence in Oceania and the Middle East than in other continents.Conclusions:The results of this meta-analysis suggest that one student out of two is suffering from burnout, even before residency. Again, our findings highlight the high level of distress in the medical population. These results should encourage the development of preventive strategies.

Published
2019

14. Bright Light Therapy in the Morning or at Mid-Day in the Treatment of Non-Seasonal Bipolar Depressive Episodes (LuBi): Study Protocol for a Dose Research Phase I / II Trial

Author

Michel Lejoyeux, Philip Gorwood, Frank Bellivier, Julia Maruani, Ali Amad, Guillaume Vaiva, Bruno Etain, Sylvie Chevret, Caroline Dubertret, Philippe Courtet, Pierre-Alexis Geoffroy, El Mountacer Billah El Abbassi, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint Louis [APHP], Fondation FondaMental [Créteil], GHU Paris Psychiatrie et Neurosciences, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Diderot - Paris 7 (UPD7), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hopital Louis Mourier - AP-HP [Colombes], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Université Paris Diderot - Paris 7 (UPD7)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Sainte-Anne-Université Paris Descartes - Paris 5 (UPD5), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Centre de Psychiatrie et Neurosciences (U894), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)

Subjects
Pediatrics, medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], Bipolar depression, Major depressive episode, Placebo, Study Protocol, 03 medical and health sciences, 0302 clinical medicine, Bipolar disorders, medicine, Circadian rhythms, Bipolar disorder, Bright light therapy, Biological Psychiatry, Morning, business.industry, Mood stabilizer, Phototherapy, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Phase i ii, Cohort, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Objective This study protocol aims to determine, using a rigorous approach in patients with bipolar disorder (BD) and non-seasonal major depressive episode (MDE), the characteristics of bright light therapy (BLT) administration (duration, escalation, morning and mid-day exposures) depending on the tolerance (hypomanic symptoms). Methods Patients with BD I or II and treated by a mood stabilizer are eligible. After 1 week of placebo, patients are randomized between either morning or mid-day exposure for 10 weeks of active BLT with glasses using a dose escalation at 7.5, 10, 15, 30 and 45 minutes/day. A further follow-up visit is planned 6 months after inclusion. Patients will be included by cohorts of 3, with at least 3 days of delay between them, and 1 week between cohorts. If none meet a dose limiting toxicity (DLT; i.e hypomanic symptoms), the initiation dose of the next cohort will be increased. If one patient meet a DLT, an additionnal cohort will start at the same dose. If 2 or 3 patients meet a DLT, from the same cohort or from two cohorts at the same dose initiation, the maximum tolerated dose is defined. This dose escalation will also take into account DLTs observed during the intra-subject escalation on previous cohorts, with a "Target Ceiling Dose" defined if 2 DLTs occured at a dose. Discussion Using an innovative and more ergonomic device in the form of glasses, this study aims to better codify the use of BLT in BD to ensure a good initiation and tolerance. Trial registrationaaClinicalTrials.gov Identifier: NCT03396744.

Published
2018

15. Association between Functional Inhibitors of Acid Sphingomyelinase and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID-19: results from an observational multicenter study

Author

Marina Sánchez-Rico, Miriam Abellán, Frédéric Limosin, Eric J. Lenze, Jesús M. Alvarado, Carlos Blanco, Angela M. Reiersen, Antoine Neuraz, Raphaël Vernet, Pedro de la Muela, Philip Gorwood, Alexander Carpinteiro, Nicolas Hoertel, Johannes Kornhuber, Pierre Meneton, Ap-Hp Covid Cdr Initiative, Erich Gulbins, and Nathanaël Beeker

Subjects
medicine.medical_specialty, business.industry, Proportional hazards model, medicine.medical_treatment, Inverse probability weighting, Retrospective cohort study, law.invention, Randomized controlled trial, law, Internal medicine, Clinical endpoint, Medicine, Intubation, Observational study, Acid sphingomyelinase, business, medicine.drug
Abstract

Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS-CoV-2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID-19 in an observational multicenter retrospective study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) who were taking a FIASMA medication, and 1,060 patients (41.4%) who were not. Taking a FIASMA medication was associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58-0.87; p

Published
2021

16. The impact of duration of illness on treatment nonresponse and drop-out: Exploring the relevance of enduring eating disorder concept

Author

Roser Granero, Georgios Paslakis, Zaida Agüera, Fernando Fernández-Aranda, Susana Jiménez-Murcia, Mónica Giménez, Eduardo Serrano-Troncoso, Beate Herpertz-Dahlmann, Eva-Maria Bonin, Isabel Sánchez, Janet Treasure, Palmiero Monteleone, and Philip Gorwood

Subjects
050103 clinical psychology, medicine.medical_specialty, Anorexia Nervosa, Psychological intervention, Dysfunctional family, Feeding and Eating Disorders, 03 medical and health sciences, 0302 clinical medicine, Binge-eating disorder, binge eating disorder, Medicine, Humans, 0501 psychology and cognitive sciences, Duration (project management), Big Five personality traits, Psychiatry, Bulimia Nervosa, other specified feeding and eating disorders, business.industry, Bulimia nervosa, 05 social sciences, medicine.disease, drop-out, 030227 psychiatry, Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, Clinical Psychology, Eating disorders, enduring, Anorexia nervosa (differential diagnoses), anorexia nervosa, bulimia nervosa, treatment nonresponders, business, Binge-Eating Disorder
Abstract

Objective There are no generally accepted definitions or markers of treatment nonresponse in eating disorders (EDs). The aim of this paper was to examine how the duration of illness and other potential prognostic markers impacted on nonresponse and drop-out from treatment across different EDs subtypes. Methods A total sample of 1199 consecutively treated patients with EDs, according to Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria, participated in this study. Kaplan-Meier curves were calculated for each ED diagnosis in which the probability of recovery was plotted against the duration of illness. Results Full remission was more likely for people with binge eating disorder (BED; 47.4%) and anorexia nervosa (AN; 43.9%) compared to bulimia nervosa (BN; 25.2%) and other specified feeding and EDs (OSFED; 23.2%). The cut-off points for the duration of the illness related with high likelihoods of poor response was 6-8 years among OSFED, 12-14 years among AN and BN and 20-21 years among BED. Other variables predicting nonresponse included dysfunctional personality traits. Conclusions Nonresponse to treatment is associated with duration of illness which is in turn associated with poor response to previous treatment. However, there was no evidence for staging the illness using specific duration of illness criteria. Nevertheless, the shorter temporal trajectory for OSFED suggests that early interventions may be of importance for this group.

Published
2021

17. Identification and management of cardiometabolic risk in subjects with schizophrenia spectrum disorders: A Delphi expert consensus study

Author

Stefan Leucht, Andrea Fagiolini, Aldo P. Maggioni, Celso Arango, Philip Gorwood, Marc De Hert, Stefano Del Prato, Silvana Galderisi, Armida Mucci, Galderisi, S., De Hert, M., Del Prato, S., Fagiolini, A., Gorwood, P., Leucht, S., Maggioni, A. P., Mucci, A., Arango, C., University of the Study of Campania Luigi Vanvitelli, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Universiteit Antwerpen [Antwerpen], University of Pisa - Università di Pisa, University of Siena (University of Siena), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Maria Cecilia Hospital [Cotignola], Hospital General Universitario 'Gregorio Marañón' [Madrid], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Martinez Rico, Clara, Universiteit Antwerpen = University of Antwerpen [Antwerpen], Università degli Studi di Siena = University of Siena (UNISI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Technische Universität München [München] (TUM)

Subjects
medicine.medical_specialty, Consensus, medicine.medical_treatment, Population, Delphi method, schizophrenia spectrum disorder, antipsychotic cardiometabolic profile, antipsychotics, cardiometabolic risk, monitoring of cardiometabolic risk, prevention, schizophrenia spectrum disorders, smoking cessation, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Medicine, Humans, Psychiatry, education, Risk management, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, medicine.disease, 030227 psychiatry, 3. Good health, ddc, Psychiatry and Mental health, Schizophrenia, Cardiovascular Diseases, Life expectancy, Smoking cessation, Position paper, Human medicine, business, Risk assessment, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article, Antipsychotic Agents
Abstract

Background Patients with schizophrenia spectrum disorders (SSD) have worse physical health and reduced life expectancy compared to the general population. In 2009, the European Psychiatric Association, the European Society of Cardiology and the European Association for the Study of Diabetes published a position paper aimed to improve cardiovascular and diabetes care in patients with severe mental illnesses. However, the initiative did not produce the expected results. Experts in SSD or in cardiovascular and metabolic diseases convened to identify main issues relevant to management of cardiometabolic risk factors in schizophrenia patients and to seek consensus through the Delphi method. Methods The steering committee identified four topics: 1) cardiometabolic risk factors in schizophrenia patients; 2) cardiometabolic risk factors related to antipsychotic treatment; 3) differences in antipsychotic cardiometabolic profiles; 4) management of cardiometabolic risk. Twelve key statements were included in a Delphi questionnaire delivered to a panel of expert European psychiatrists. Results Consensus was reached for all statements with positive agreement higher than 85% in the first round. European psychiatrists agreed on: 1) high cardiometabolic risk in patients with SSD, 2) importance of correct risk management of cardiometabolic diseases, from lifestyle modification to treatment of risk factors, including the choice of antipsychotic drugs with a favourable cardiometabolic profile. The expert panel identified the psychiatrist as the central coordinating figure of management, possibly assisted by other specialists and general practitioners. Conclusions This study demonstrates high level of agreement among European psychiatrists regarding the importance of cardiovascular risk assessment and management in subjects with SSD.

Published
2021

18. Reconceptualising treatment-resistant depression as difficult-to-treat depression

Author

R. Hamish McAllister-Williams, Andreas Papadopoulos, Pierre Blier, Eduard Vieta, Peter Falkai, Afzal Javed, Koen Demyttenaere, Augustus J Rush, Siegfried Kasper, Philip Gorwood, Malcolm Hopwood, Celso Arango, Allan H. Young, Jair C. Soares, and Gurjhinder S Malhi

Subjects
Psychiatry, medicine.medical_specialty, Science & Technology, business.industry, Depression, MEDLINE, medicine.disease, Psychiatry and Mental health, Depressive Disorder, Treatment-Resistant, Mental depression, Drug resistance, Medicine, Humans, Depressió psíquica, business, Treatment-resistant depression, Treatment resistant, Life Sciences & Biomedicine, Biological Psychiatry, Depression (differential diagnoses), Resistència als medicaments
Abstract

We are heartened that our consensus statement1 on difficult-to-treat depression has provoked robust debate. As pointed out by Lisa Cosgrove and colleagues,2 our proposed definition and model of care for difficult-to-treat depression is not derived from a systematic review or a Delphi technique. The term difficult-to-treat depression had previously been proposed to address semantic and conceptual issues with the so-called treatment-resistant depression model, for patients where achieving sustained remission proves elusive.3 We aimed to extend the discussion regarding this proposal, focusing on practical clinical advice. As the concept of difficult-to-treat depression is new, there is no literature to systematically review. The literature around the management of so-called treatment-resistant depression has been reviewed on many occasions, but this literature was only of partial relevance to our aims. Not only is there no universally accepted definition of treatment-resistant depression, but those that are used rarely if ever take into account psychotherapeutic or neurostimulatory treatments, or how to account for differential efficacy among treatments.4, 5 At the core of the proposed difficult-to-treat depression model is the importance of taking a holistic approach and considering all treatment options available. A systematic review of all treatments for depression was not practical. As a result, our consensus was based on the culmination of extensive discussion and deliberation among 15 international experts in the management of depression from across three continents, and the national guidelines for the treatment of depression from the countries represented. Rather than through a Delphi technique, we arrived at a consensus through many iterative reviews of the manuscript until all 15 contributors were comfortable with all the statements being discussed. However, we wish to clarify two key points that we feel Cosgrove and colleagues might have misunderstood.

Published
2020

19. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Author

Stephan Zipfel, Hidetoshi Inoko, K. Fischer, Laramie E. Duncan, Jochen Seitz, Lars Klareskog, Ina Giegling, Grant W. Montgomery, Manuel Föcker, Colin A. Johnson, Agnieszka Słopień, Dong Li, M. C. T. Slof-Op 't Landt, Thomas Werge, Janiece E. DeSocio, Stefan Ehrlich, Joseph M. Boden, Patrick F. Sullivan, M. La Via, Bochao Danae Lin, Andreas Karwautz, Ilka Boehm, Lenka Foretová, Stephen W. Scherer, Anders Juréus, Jolanta Lissowska, Janne Tidselbak Larsen, Antonio Julià, A. Metspalu, Roger A.H. Adan, George Dedoussis, Stefan Herms, Franziska Ritschel, Martin A. Kennedy, Vesna Boraska Perica, S.D. Gordon, Johanna Giuranna, Janet Treasure, Youl-Ri Kim, Joanna Hauser, Manfred M. Fichter, P.E. Slagboom, Wade H. Berrettini, Kirstin L. Purves, Fernando Fernández-Aranda, Eleftheria Zeggini, Nadia Micali, Anne Farmer, Beata Swiatkowska, Tracey D. Wade, Claudette Boni, Fragiskos Gonidakis, Ioanna Ntalla, Johannes Pantel, Raquel Rabionet, Pierre J. Magistretti, Johannes Hebebrand, Mario Maj, Sietske G. Helder, Roland Burghardt, Sarah E. Medland, Maurizio Clementi, John F. Pearson, Gerd Wagner, V. Janout, Susana Jiménez-Murcia, Mikael Landén, Samuli Ripatti, Sandro Sorbi, Martien J H Kas, Leonid Padyukov, Zeynep Yilmaz, Kelly L. Klump, Paul Lichtenstein, Shuyang Yao, Dan Rujescu, James J. Crowley, Valdo Ricca, Palmiero Monteleone, Steve Crawford, Sébastien Guillaume, Liselotte Petersen, Yiran Guo, Stephan Ripke, Beate Herpertz-Dahlmann, Marie Navratilova, S. Gallinger, Anjali K. Henders, Cynthia M. Bulik, Wolfgang Herzog, Alfonso Tortorella, Christian Dina, Garret D. Stuber, A. A. van Elburg, Manuel Mattheisen, Harry Brandt, Hunna J. Watson, Alessandro Rotondo, Roel A. Ophoff, Artemis Tsitsika, Nicholas G. Martin, Sara Marsal, Konstantinos Tziouvas, Ken B. Hanscombe, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Anu Raevuori, Lars Alfredsson, E. F. van Furth, Hartmut Imgart, Esther Walton, Julie K. O'Toole, Katharina Buehren, Unna N. Danner, Hana Papezova, Katherine M. Kirk, Deborah Kaminská, Lisa R. Lilenfeld, Aarno Palotie, Paola Giusti-Rodríguez, Jennifer Jordan, Gun Peggy Knudsen, L. Slachtova, Ole A. Andreassen, Monica Gratacos Mayora, Elisabeth Widen, Benedetta Nacmias, Nicholas J. Schork, Monika Dmitrzak-Weglarz, Jurjen J. Luykx, André Scherag, Christopher Hübel, Laura M. Thornton, Marion Roberts, Angela Favaro, Catherine M. Olsen, Jaakko Kaprio, S Le Hellard, Federica Tozzi, Monica Forzan, Claes Norring, Leila Karhunen, Karin Egberts, Dalila Pinto, Geòrgia Escaramís, Nicolas Ramoz, Robert D. Levitan, Laura M. Huckins, Ulrike Schmidt, Gerome Breen, Kirsty Kiezebrink, Andreas J. Forstner, Scott J. Crow, Ingrid Meulenbelt, Dimitris Dikeos, Sven Cichon, Daniela Degortes, L. J. Horwood, Tetsuya Ando, Jonathan R. I. Coleman, Stephanie Zerwas, Katherine A. Halmi, Helena Gaspar, Andrew W. Bergen, Elena Tenconi, Katrin Männik, Christopher S. Franklin, Anna Keski-Rahkonen, Sara McDevitt, Marta Tyszkiewicz-Nwafor, Jakob Grove, Philip Gorwood, Christian R. Marshall, Preben Bo Mortensen, Melissa A. Munn-Chernoff, Hakon Hakonarson, Roger D. Cone, Allan S. Kaplan, Paolo Santonastaso, James I. Hudson, M. de Zwaan, Xavier Estivill, James E. Mitchell, Danielle M. Dick, Jessica H. Baker, Peter McGuffin, Walter H. Kaye, Michael Strober, D. B. Woodside, Oliver S. P. Davis, Karen S. Mitchell, David C. Whiteman, Julien Bryois, Nancy L. Pedersen, Philippe Courtet, Virpi M. Leppä, Konstantinos Hatzikotoulas, T Esko, Matteo Cassina, Andreas Birgegård, Anke Hinney, Richard Parker, James L. Kennedy, Elisa Docampo, Ioanna Tachmazidou, Jin P. Szatkiewicz, Alexandra Schosser, Filip Rybakowski, Morten Mattingsdal, and Gursharan Kalsi

Subjects
medicine.medical_specialty, Anorexia nervosa (differential diagnoses), business.industry, medicine, Genome-wide association study, Psychiatry, business
Published
2020

20. Does physical activity associated with chronic food restriction alleviate anxiety like behaviour, in female mice?

Author

David Blum, Suzanne L. Dickson, Sabiha Eddarkaoui, Virginie Tolle, Philibert Duriez, Philip Gorwood, Odile Viltart, GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Sahlgrenska Academy at University of Gothenburg [Göteborg], Martinez Rico, Clara, Université de Lille, CNRS, CHU Lille, Lille Neurosciences & Cognition (LilNCog) - U 1172, Institut de psychiatrie et neurosciences de Paris [IPNP - U1266 Inserm], Institut de psychiatrie et neurosciences de Paris [IPNP - U1266 Inserm - Paris Descartes], University of Gothenburg [GU], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC))

Subjects
Time Factors, Anxiety, Anorexia nervosa, Open field, Marble burying, Mice, Behavioral Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Corticosterone, Medicine, Acute stress, 2. Zero hunger, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Behavior, Animal, Food restriction, 3. Good health, Female, medicine.symptom, Restraint, Physical, Elevated plus maze, medicine.medical_specialty, Animals, Anorexia Nervosa, Caloric Restriction, Food Deprivation, Humans, Mice, Inbred C57BL, Physical Conditioning, Animal, Stress, Psychological, Physical activity, Context (language use), 03 medical and health sciences, Internal medicine, Endocrine and Autonomic Systems, business.industry, medicine.disease, 030227 psychiatry, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Anxiogenic, chemistry, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Anorexia nervosa (AN) is an eating disorder characterized by excessive weight loss, persistent food restriction and inappropriate physical activity relative to declining energy balance. The comorbidity with depression and/ or anxiety disorders might contribute to the "chronicization" of the disease. We aimed here to question first the link between physical activity and anxiety from a clinical investigation of AN patients (n = 206). Then, using a rodent model mimicking numerous physiological and metabolic alterations commonly seen in AN patients, we examined whether 1) chronic food restriction increased anxiety-like behaviour and 2) physical activity plays a role in regulating anxiety levels. To this end, we exposed young female mice to a chronic food restriction (FR, n = 8) paradigm combined or not with access to a running wheel (FRW, n = 8) for two weeks. The mice were compared to a group of mice fed ad libitum without (AL, n = 6) or with running wheel access (ALW, n = 8). We explored anxiety-like behaviour of all mice in the following tests: hyponeophagia, marble burying, elevated plus maze, open field, and the light and dark box. On the last day, we used a restraint test of 30 min duration and measured their stress reactivity by assaying plasma corticosterone. In the open field and the elevated plus-maze, we found that FRW mice behaved similarly to AL and ALW mice whereas FR mice did not express anxiety-like behaviour. The FRW mice displayed the lowest latency to reach the food in the hyponeophagia test. Regarding stress reactivity, FRW mice exhibited corticosterone reactivity after acute stress that was similar to the control mice, while FR mice did not fully return to basal corticosterone at one hour after the restraint stress. Taken together, these data demonstrate a differential reactivity to acute stress in FR conditions and a beneficial effect of running wheel activity in ALW and FRW conditions. Moreover, we report the absence of a typical anxiety-like behaviour associated with the food restriction (FR and FRW groups). We conclude that this model (FR and FRW mice) did not express typical anxiety-like behaviour, but that physical activity linked to food restriction improved coping strategies in an anxiogenic context.

Published
2020

21. The consequences of the COVID-19 pandemic on mental health and implications for clinical practice

Author

Philip Gorwood, Andrea Fiorillo, Università degli studi della Campania 'Luigi Vanvitelli', GHU Paris Psychiatrie et Neurosciences, Clinique des Maladies Mentales et de l'Encéphale [Paris] (CMME), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Fiorillo, A., Gorwood, P., Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Bodescot, Myriam

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Pneumonia, Viral, MEDLINE, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, Pandemic, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, Pandemics, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Psychiatry, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Betacoronaviru, biology, SARS-CoV-2, Coronavirus Infection, COVID-19, biology.organism_classification, medicine.disease, Mental health, 3. Good health, Clinical Practice, Psychiatry and Mental health, Pneumonia, Editorial, Mental Health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Coronavirus Infections, Psychology, 030217 neurology & neurosurgery, Human
Abstract

International audience

Published
2020

22. What distinguish patients with compulsory treatment for severely undernourished anorexia nervosa

Author

Damien Ringuenet, Philip Gorwood, Mouna Hanachi, M. Duquesnoy, Nathalie Godart, Jean-Claude Melchior, L. Di Lodovico, and Marika Dicembre

Subjects
050103 clinical psychology, Pediatrics, medicine.medical_specialty, Multivariate analysis, Anorexia Nervosa, Endocrinology, Diabetes and Metabolism, Population, Compulsory treatment, Logistic regression, Feeding and Eating Disorders, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 0501 psychology and cognitive sciences, education, Retrospective Studies, education.field_of_study, Nutrition and Dietetics, Binge eating, business.industry, 05 social sciences, Malnutrition, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Eating disorders, Treatment Refusal, Anorexia nervosa (differential diagnoses), medicine.symptom, business, Binge-Eating Disorder
Abstract

OBJECTIVE Anorexia nervosa (AN) is a mental disorder potentially leading to severe malnutrition and life-threatening complications, with high mortality rates and dropouts from treatment. In the most severe cases, treatment refusal associated with acute nutritional disorders may require compulsory admission in specialised units. The aim of this study was to investigate clinical and nutritional parameters associated with the use of compulsory treatment for severely ill AN patients requiring intensive nutritional care. METHODS This retrospective, single-centre study performed in a unit of specialised nutritional care compared severely undernourished inpatients, compulsorily admitted for AN, with a population of sex- and age-matched voluntarily admitted patients. Socio-demographic and clinical variables were collected for univariate comparison and logistic regression. RESULTS Compulsory treatment in AN was mainly associated with lower socio-economic status (p < 0.01), history of lower weight (p < 0.05), more frequently prescribed psychotropic medication (p = 0.02), more previous admissions for AN, longer hospitalisations (p < 0.01) and binge eating/purging subtype (p = 0.02). Binge eating/purging subtype and the number of past admissions showed the strongest odds of compulsory treatment in multivariate analysis. CONCLUSION The knowledge of factors associated with compulsory treatment may help practitioners of all fields to better evaluate its pertinence and indications in AN.

Published
2020

23. Genetics of substance use disorders

Author

Nicolas Ramoz, Yann Le Strat, and Philip Gorwood

Subjects
medicine.medical_specialty, business.industry, mental disorders, behavior and behavior mechanisms, Medicine, Substance use, business, Psychiatry, behavioral disciplines and activities, health care economics and organizations, humanities
Abstract

The literature on the existing evidence for a genetic component is reviewed for substance use disorders (SUD), formerly known as substance abuse and substance dependence. The chapter provides a historical perspective of the evolution of genetic understanding in the field. It also discusses the most recent methods of studying genetic factors in SUD, as well as the related discoveries of genes involved in SUD. It concludes on the possible role of genetics in the evolution of the concept and the mechanisms of SUD.

Published
2020

24. Activation syndrome induced by the antidepressant tianeptine and suicidal ideation: Evidence from a large depressed outpatient sample

Author

Philip Gorwood, Philippe Courtet, Isabelle Jaussent, Jorge Lopez-Castroman, 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), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Hôpital Sainte-Anne-Université de Paris (UP), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CCSD, Accord Elsevier, and Hôpital Sainte-Anne-Université Paris Cité (UPCité)

Subjects
Male, MESH: Thiazepines, Time Factors, Thiazepines, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Antidepressive Agents, Tricyclic, Anxiety, Benzodiazepines, 0302 clinical medicine, Sleep Initiation and Maintenance Disorders, Outpatients, Tianeptine, MESH: Syndrome, Suicidal ideation, Psychomotor Agitation, MESH: Middle Aged, MESH: Suicidal Ideation, Confounding, MESH: Psychomotor Agitation, Syndrome, Middle Aged, 3. Good health, Suicidal behavior, Activation syndrome, Antidepressant, Drug Therapy, Combination, Female, MESH: Impulsive Behavior, medicine.symptom, medicine.drug, medicine.medical_specialty, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, MESH: Depressive Disorder, Major, Impulsivity, Suicidal Ideation, 03 medical and health sciences, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, MESH: Sleep Initiation and Maintenance Disorders, medicine, Humans, Psychiatry, Biological Psychiatry, Jitteriness, Pharmacology, Depressive Disorder, Major, MESH: Humans, MESH: Anxiety, business.industry, MESH: Time Factors, medicine.disease, MESH: Male, 030227 psychiatry, MESH: Antidepressive Agents, Tricyclic, MESH: Outpatients, MESH: Drug Therapy, Combination, MESH: Benzodiazepines, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Impulsive Behavior, business, Sleep, MESH: Female
Abstract

Objective To determine the characteristics of the activation syndrome (AS) that predict the emergence or worsening of suicidal ideation (SI) in the first month of antidepressant treatment with tianeptine, as well as the temporal relationship between both conditions. Method A naturalistic sample of 2422 depressed outpatients starting a new antidepressant treatment with tianeptine was assessed at 2, 4 and 6 weeks of follow-up using validated questionnaires. Four main dimensions of AS were examined: impulsivity, sleep problems, anxiety and agitation. Results The emergence of an AS was more likely in long-lasting depressive episodes, but less likely if the patient responded to the antidepressant or benzodiazepines were added as an add-on treatment. Treatment-emergent SI was strongly associated to the presence of an AS, particularly in case of sleep problems (OR = 8.42) or impulsivity upsurges (OR = 3.89), even after adjustment for all relevant confounding factors. Conclusions Our findings suggest a dose-effect mechanism modulating the relationship between treatment-related SI and AS. AS symptoms may need to be monitored closely in the weeks that follow the introduction of an antidepressant treatment.

Published
2020

25. Structural correlates of COMT Val158Met polymorphism in childhood ADHD: a voxel-based morphometry study

Author

Hichem Slama, Stéphane S. De Brito, Simon Baijot, Mathilde Septier, Isabelle Massat, Philippe Peigneux, Danielle Balériaux, Martin Kavec, Thomas Villemonteix, Alison Mary, Philip Gorwood, Nicolas Ramoz, and Thierry Metens

Subjects
Male, medicine.medical_specialty, Genotype, Inferior frontal gyrus, Prefrontal Cortex, Grey matter, Audiology, computer.software_genre, Impulsivity, Catechol O-Methyltransferase, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Temporal lobe, Voxel, mental disorders, medicine, Humans, Gray Matter, Psychiatry, Child, Biological Psychiatry, Alleles, Homozygote, Voxel-based morphometry, Antisocial Personality Disorder, Magnetic Resonance Imaging, Temporal Lobe, Psychiatry and Mental health, medicine.anatomical_structure, Attention Deficit Disorder with Hyperactivity, Female, medicine.symptom, Caudate Nucleus, Psychology, computer, rs4680
Abstract

Objectives. The Val158-allele of the catechol-O-methyltransferase (COMT) Val158Met (rs4680) functional polymorphism has been identified as a risk factor for antisocial behaviour in attention-deficit/hyperactivity disorder (ADHD). Here, we used voxel-based morphometry to investigate the effects of Val158Met polymorphism on grey matter (GM) volumes in a sample of 7–13-year-old children. Methods. MRI and genotype data were obtained for 38 children with combined-type ADHD and 24 typically developing (TD) children. Four regions of interest were identified: striatum, cerebellum, temporal lobe and inferior frontal gyrus (IFG). Results. When compared to TD children, those with ADHD had a significant decrease of GM volume in the IFG. Volume in this region was negatively correlated with ratings of hyperactivity/impulsivity symptoms. Furthermore, the smaller GM volume in the IFG was attributed to the presence of the Met158-allele, as only children with ADHD carrying a Met158-allele exhibited such decrease in the IFG. Children with ADHD homozygotes for the Val158-allele presented increased GM volume in the caudate nucleus when compared with TD children. Conclusions. This study provides the first evidence of a modulation of ADHD-related GM volume alterations by Val158Met in two key regions, possibly mediating the relationship between Val158Met polymorphism and antisocial behaviour in children with ADHD.

Published
2020
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26. Agomelatine in Standard Medical Practice in Depressed Patients: Results of a 1-Year Multicentre Observational Study In France

Author

Jacques Benichou, Marie-Cécile Secouard, Philip Gorwood, Xavier Desobry, F. Picarel-Blanchot, Christian de Bodinat, Nicolas Moore, Marine Wattez, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Unité de biostatistiques [CHU Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Servier Affaires Médicales, Institut de Recherches Internationales Servier [Suresnes] (IRIS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Martinez Rico, Clara

Subjects
Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Rating scale, Internal medicine, Acetamides, Outpatients, Medicine, Agomelatine, Humans, Pharmacology (medical), Original Research Article, Adverse effect, Depression (differential diagnoses), Aged, Psychiatric Status Rating Scales, PharmacoEpi-Drugs, Depressive Disorder, Major, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, General Medicine, Middle Aged, Antidepressive Agents, 3. Good health, [SDV] Life Sciences [q-bio], Clinical trial, Treatment Outcome, Tolerability, Quality of Life, Observational study, Female, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

Background and Objectives Non-interventional studies are a valuable source of evidence that is complementary to traditional randomised, blinded and controlled clinical trials, for evaluating antidepressants in a real-world setting. The aim of the present study was to document the use of agomelatine in current medical practice and evaluate its effectiveness and safety in outpatients prescribed agomelatine to treat their current depressive episode. Methods This 12-month observational French study included patients initiating agomelatine treatment. The intensity and severity of depression were assessed using the 17-item Hamilton Depression Rating Scale (HAM-D17) total score and the Clinical Global Impression-Severity of Illness (CGI-S) scale. Patients’ quality of life and functioning were measured using the Quality of Life in Depression Scale and the Sheehan Disability Scale, respectively. The safety measures included emergent adverse events and biological samplings, with a focus on liver acceptability. Results A total of 1484 patients (70% of women; 49.6 ± 15.4 years of age) were enrolled in the study. Most patients (62.3%) were treated with agomelatine for at least 6 months and 28.8% were treated for at least 1 year. Mean HAM-D17 total score and mean CGI-S scores decreased by 13.6 ± 8.1 and 2.1 ± 1.5 points, respectively, from baseline to last visit on agomelatine. Rates of responders (i.e. with a decrease in HAM-D17 total score by at least 50%) and remitters (HAM-D total score

Published
2020

27. La faible estime de soi est corrélée à l’intentionnalité suicidaire, indépendamment de la sévérité de la dépression

Author

C. Perrot, Philip Gorwood, and L. Vera

Subjects
Gynecology, medicine.medical_specialty, Injury control, Accident prevention, Poison control, 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Arts and Humanities (miscellaneous), medicine, Suicide Risk, Psychology, 030217 neurology & neurosurgery
Abstract

Resume Le suicide est un probleme de sante publique majeur et l’estime de soi pourrait y avoir une place determinante. Notre objectif principal est d’evaluer s’il existe un lien entre l’intentionnalite suicidaire et l’estime de soi, en se focalisant plus specifiquement sur ses differentes dimensions (generale, familiale, professionnelle et sociale). Notre second objectif est d’etudier le role potentiel du syndrome depressif dans la relation entre estime de soi et risque suicidaire. Nous avons realise une etude retrospective transversale de 2008 a 2010, au sein d’un service d’accueil des patients suicidants a l’hopital Sainte-Anne a Paris. Les criteres d’inclusion etaient : âge > 15 ans ; hospitalise suite a une tentative de suicide. L’estime de soi etait evaluee via l’echelle de Coopersmith (SEI) et les patients ayant un score SEI mensonge > 5 etaient exclus. Notre critere de jugement principal etait la correlation entre l’estime de soi et l’intentionnalite suicidaire. Notre critere de jugement secondaire concernait le poids du facteur « intensite du syndrome depressif » (echelle d’Hamilton) dans cette correlation. Cent trente-deux patients ont ete inclus. L’intentionnalite suicidaire etait correlee a l’estime de soi totale (r = −0,227, p = 0,009), sociale (r = −0,331, p

Published
2018

28. Stability of the diagnosis of seasonal affective disorder in a long-term prospective study

Author

Serge Friedman, Christian Even, Philip Gorwood, and Marie-Laure Cléry-Melin

Subjects
Adult, Male, Predictive validity, Pediatrics, medicine.medical_specialty, Time Factors, Craving, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Recurrence, mental disorders, medicine, Humans, Prospective Studies, Family history, Prospective cohort study, Depression (differential diagnoses), Suicide attempt, Seasonal Affective Disorder, Middle Aged, Phototherapy, Prognosis, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Mood, Cohort, behavior and behavior mechanisms, Female, medicine.symptom, Psychology, psychological phenomena and processes, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Background Seasonal affective disorder (SAD) is mainly characterized by a seasonal pattern of depressive recurrences over the years. However, few studies have been conducted on the long-term course of patients with SAD, whose findings raised questions about the diagnosis stability over time. This study aimed to better characterize the diagnosis evolution, and determine prognosis markers. Methods An initial cohort of 225 outpatients diagnosed as having a SAD, was assessed at baseline (T1) for clinical symptoms and response to bright light therapy. One hundred and nineteen patients (53%) were interviewed 2–12 years after (T2). Results Of 119 patients reached at follow-up (T2), only 32 patients (27%) still fulfilled the DSM-IV criteria for a stable SAD (S-SAD). A large proportion (59%) of the follow up cohort was in remission and 14% still suffered from a non-seasonal mood disorder. Family history of depression, previous suicide attempt, carbohydrate craving and HAD-depression score at baseline were associated with a stable SAD (S-SAD) diagnosis at T2, the HAD-depression score being the only one still significantly predictive (p=0.025) of a later stable SAD, with a multivariate approach. Carbohydrate craving, a core symptom of SAD, showed a trend (p=0.100) to predict diagnosis stability. Limitations Only 53% patients from the initial cohort were assessed at follow-up. Conclusions Patients with eventual stable SAD show more subjective severity (higher HAD-Depression score) and carbohydrate craving at baseline. A low predictive validity of diagnosis criteria suggests that SAD is a temporary expression of a mood disorder rather than a specific disorder.

Published
2018

29. Progress in Elucidating Biomarkers of Antidepressant Pharmacological Treatment Response: A Systematic Review and Meta-analysis of the Last 15 Years

Author

G. Voegeli, Nicolas Ramoz, M. L. Cléry-Melin, and Philip Gorwood

Subjects
Treatment response, medicine.medical_specialty, Depression, business.industry, Theta activity, MEDLINE, Cognition, Bioinformatics, Antidepressive Agents, Biomarkers, Pharmacological, 030227 psychiatry, Pharmacological treatment, 03 medical and health sciences, 0302 clinical medicine, Sample size determination, Meta-analysis, Humans, Medicine, Antidepressant, Pharmacology (medical), business, Psychiatry, 030217 neurology & neurosurgery
Abstract

Antidepressant drugs are widely prescribed, but response rates after 3 months are only around one-third, explaining the importance of the search of objectively measurable markers predicting positive treatment response. These markers are being developed in different fields, with different techniques, sample sizes, costs, and efficiency. It is therefore difficult to know which ones are the most promising. Our purpose was to compute comparable (i.e., standardized) effect sizes, at study level but also at marker level, in order to conclude on the efficacy of each technique used and all analyzed markers. We conducted a systematic search on the PubMed database to gather all articles published since 2000 using objectively measurable markers to predict antidepressant response from five domains, namely cognition, electrophysiology, imaging, genetics, and transcriptomics/proteomics/epigenetics. A manual screening of the abstracts and the reference lists of these articles completed the search process. Executive functioning, theta activity in the rostral Anterior Cingular Cortex (rACC), and polysomnographic sleep measures could be considered as belonging to the best objectively measured markers, with a combined d around 1 and at least four positive studies. For inter-category comparisons, the approaches that showed the highest effect sizes are, in descending order, imaging (combined d between 0.703 and 1.353), electrophysiology (0.294–1.138), cognition (0.929–1.022), proteins/nucleotides (0.520–1.18), and genetics (0.021–0.515). Markers of antidepressant treatment outcome are numerous, but with a discrepant level of accuracy. Many biomarkers and cognitions have sufficient predictive value (d ≥ 1) to be potentially useful for clinicians to predict outcome and personalize antidepressant treatment.

Published
2017

30. The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial

Author

Anne G. Lever, Jürgen Deckert, Andreas Reif, Michael Browning, Judit Simon, Andreas Menke, Henricus G. Ruhé, J Kingslake, Guy M. Goodwin, Anneke van Schaik, Rebecca Dias, Gerard R Dawson, Richard Morriss, Géraldine Voegeli, Boliang Guo, Michael Stäblein, Dick J. Veltman, Susan Brown, Catherine J. Harmer, Colin T. Dourish, Philip Gorwood, Víctor Pérez, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Anatomy and neurosciences, and Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE)

Subjects
Research design, Male, Time Factors, Cost-Benefit Analysis, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Medicine (miscellaneous), Antidepressant, law.invention, Study Protocol, 0302 clinical medicine, Cognition, Randomized controlled trial, Clinical Protocols, law, Risk Factors, Surveys and Questionnaires, ANXIETY, Pharmacology (medical), 030212 general & internal medicine, Young adult, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Depression (differential diagnoses), SCALE, lcsh:R5-920, Depression, Health Care Costs, Middle Aged, Primary care, SR, Antidepressive Agents, 3. Good health, Europe, Treatment Outcome, Research Design, Predictive value of tests, Anxiety, Female, medicine.symptom, lcsh:Medicine (General), Adult, medicine.medical_specialty, Adolescent, Clinical Decision-Making, Decision Support Techniques, Time-to-Treatment, 03 medical and health sciences, Young Adult, Pharmacotherapy, Predictive Value of Tests, MENTAL-DISORDERS, medicine, Humans, ddc:610, Psychiatry, Aged, Primary Health Care, business.industry, Patient Selection, Treatment, Regimen, Affect, Physical therapy, business, Prediction, 030217 neurology & neurosurgery
Abstract

Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depression measured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients. Trial registration ClinicalTrials.gov, ID: NCT02790970. Registered on 30 March 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2247-2) contains supplementary material, which is available to authorized users.

Published
2017

31. Netrin G1: its downregulation in the nucleus accumbens of cocaine-conditioned mice and genetic association in human cocaine dependence

Author

J. M. Moalic, Naguib Mechawar, Gustavo Turecki, Florence Noble, Michel Simonneau, Sandrine Imbeaud, Philip Gorwood, Gilles Maussion, Sabah Kelaï, and Nicolas Ramoz

Subjects
0301 basic medicine, Pharmacology, medicine.medical_specialty, Addiction, media_common.quotation_subject, Medicine (miscellaneous), Single-nucleotide polymorphism, Context (language use), Epigenetics of cocaine addiction, Nucleus accumbens, Biology, medicine.disease, Cocaine dependence, 03 medical and health sciences, Psychiatry and Mental health, 030104 developmental biology, 0302 clinical medicine, Endocrinology, Internal medicine, Netrin, medicine, Allele, 030217 neurology & neurosurgery, media_common
Abstract

Netrin G1 is a presynaptic ligand involved in axonal projection. Although molecular mechanisms underlying cocaine addiction are still poorly understood, Netrin G1 might have a role as a regulator of anxiety, fear and spatial memory, behavioural traits impaired in the context of cocaine exposure. In this study, the Netrin G1 (Ntng1) expression was investigated in the nucleus accumbens of mice primarily conditioned to cocaine using a place preference paradigm. A genetic association study was then conducted on 146 multiplex families of the Collaborative study on Genetics of Alcoholism, in which seven single nucleotide polymorphisms located in the NTNG1 gene were genotyped. NTNG1 expression levels were also quantified in BA10, BA46 and the cerebellum of healthy controls (with no Axis 1 psychopathology). Decreased Ntng1 expression was initially observed in the nucleus accumbens of mice conditioned to cocaine. Significant genetic family-based associations were detected between NTNG1 polymorphisms and cocaine dependence. NTNG1 expression in BA10, BA46 and the cerebellum, however, were not significantly associated with any allele or haplotype of this gene. These results confirm that Ntng1 expression is disturbed in the nucleus accumbens of mice, after cocaine conditioning. A haplotype of NTNG1 was found to constitute a vulnerability factor for cocaine use disorder in patients, although none of its single nucleotide polymorphisms were associated with a differential expression pattern in healthy controls. The data suggest that change in the Ntng1 expression is a consequence of cocaine exposure, and that some of its genetic markers are associated with a greater risk for cocaine use disorder.

Published
2017

32. A simple attention test in the acute phase of a major depressive episode is predictive of later functional remission

Author

Philip Gorwood and Marie-Laure Cléry-Melin

Subjects
Pediatrics, medicine.medical_specialty, Trail Making Test, Poison control, Cognition, 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, Clinical Psychology, 0302 clinical medicine, Injury prevention, medicine, D2 Test of Attention, Agomelatine, medicine.symptom, Major depressive episode, Psychology, Psychiatry, 030217 neurology & neurosurgery, Depression (differential diagnoses), medicine.drug
Abstract

Background Functional recovery after a major depressive episode (MDE) requires both clinical remission and preservation of cognitive skills. As attentional deficit may persist after remission, leading to functional impairment, its role as a prognosis marker needs to be considered. Methods Five hundred eight depressed outpatients (DSM-IV) were assessed at baseline for clinical symptoms (QIDS-SR), social functioning (Sheehan Disability Scale, SDS) and attention through the d2 test of attention and the trail making test, simple tests, respectively, requiring to quote or to interconnect relevant items. All patients were treated by agomelatine, and examined 6 to 8 weeks after baseline to assess clinical remission (QIDS-SR ≤ 5) and/or functional remission (SDS ≤ 6). Results At follow up, 154 patients (31%) were in clinical and functional remission. Shorter cumulative duration of prior depression, shorter present MDE, and two parameters of the d2 test of attention were predictive of such positive outcome, the number of omission mistakes (F1) being the only one still significantly predictive (P < .05) with a multivariate approach. F1 was unchanged after remission, patients with less than 11 mistakes had a 2.27 times increased chance to reach full remission, and a dose–response relationship was observed, with a regular increase of positive outcome for less mistakes. Conclusions The number of omission mistakes (F1) of the d2 test of attention was a stable marker, being predictive of, and with a dose-effect for, clinical plus functional remission. It may constitute a specific marker of attentional deficit, involved in the resilience process that enables individuals to develop more adequate strategies to cope with everyday functional activities.

Published
2016

33. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Author

Leila Karhunen, Geòrgia Escaramís, Ingrid Meulenbelt, Yiran Guo, Matteo Cassina, Stephan Ripke, Alessandro Rotondo, Harry Brandt, Nicholas G. Martin, Andreas Birgegård, Cynthia M. Bulik, Sietske G. Helder, Julie K. O'Toole, Martien J H Kas, Julien Bryois, Nancy L. Pedersen, Philippe Courtet, Virpi M. Leppä, Konstantinos Hatzikotoulas, Liselotte Petersen, Paola Giusti-Rodríguez, André Scherag, Roger A.H. Adan, George Dedoussis, Laramie E. Duncan, John F. Pearson, Helena Gaspar, Andrew W. Bergen, Jurjen J. Luykx, Paul Lichtenstein, Jin P. Szatkiewicz, Lisa R. Lilenfeld, James L. Kennedy, Sébastien Guillaume, Angela Favaro, Artemis Tsitsika, Sara Marsal, Tõnu Esko, Joseph M. Boden, Janiece E. DeSocio, Stefan Ehrlich, Michael Strober, Laura M. Huckins, Alexandra Schosser, Katherine M. Kirk, Gun Peggy Knudsen, Dalila Pinto, Garret D. Stuber, Nicolas Ramoz, Dimitris Dikeos, Jochen Seitz, Stephanie Zerwas, Jolanta Lissowska, Jacques Pantel, Palmiero Monteleone, Katherine A. Halmi, Alessio Maria Monteleone, Scott D. Gordon, Ulrike Schmidt, Franziska Ritschel, Ted Reichborn-Kjennerud, Jennifer Jordan, Ina Giegling, Grant W. Montgomery, Morten Mattingsdal, Esther Walton, Andreas Karwautz, Federica Tozzi, Marion Roberts, Vladimir Janout, P. Eline Slagboom, Laura M. Thornton, Hana Papezova, Mikael Landén, Deborah Kaminská, Robert D. Levitan, Daniela Degortes, Manuel Föcker, Kirsty Kiezebrink, Wolfgang Herzog, Katharina Buehren, Benedetta Nacmias, Christopher Hübel, Eleftheria Zeggini, L. John Horwood, Maria La Via, Claes Norring, Karin Egberts, Nadia Micali, Filip Rybakowski, Monica Forzan, Katrin Männik, Konstantinos Tziouvas, Ioanna Tachmazidou, Thomas Werge, Tracey D. Wade, Raquel Rabionet, Scott J. Crow, Antonio Julià, Jonathan R. I. Coleman, Susana Jiménez-Murcia, Claudette Boni, Roland Burghardt, Christopher S. Franklin, Alfonso Tortorella, Fragiskos Gonidakis, Ioanna Ntalla, Anke Hinney, Jaakko Kaprio, Lenka Slachtova, Anu Raevuori, Sandro Sorbi, Richard Parker, Johanna Giuranna, Kirstin L. Purves, Stephan Zipfel, James J. Crowley, Hidetoshi Inoko, Janet Treasure, Shuyang Yao, Leonid Padyukov, Youl-Ri Kim, Monica Gratacos Mayora, Joanna Hauser, Manfred M. Fichter, Samuli Ripatti, Zeynep Yilmaz, Stephanie Le Hellard, Bochao Danae Lin, Wade H. Berrettini, Gursharan Kalsi, Anders Juréus, Oliver S. P. Davis, Ilka Boehm, Lars Klareskog, Lenka Foretova, Ken B. Hanscombe, Janne Tidselbak Larsen, Hunna J. Watson, Beate Herpertz-Dahlmann, Krista Fischer, Xavier Estivill, Vesna Boraska Perica, Karen S. Mitchell, Andreas J. Forstner, Stefan Herms, Eric F. van Furth, Kelly L. Klump, Anjali K. Henders, Fernando Fernández-Aranda, David C. Whiteman, Catherine M. Olsen, James E. Mitchell, Martina de Zwaan, Johannes Hebebrand, Manuel Mattheisen, Anne Farmer, Agnieszka Słopień, Christian Dina, Dong Li, Marie Navratilova, Sarah E. Medland, Steven Crawford, Elisa Docampo, Craig Johnson, Tetsuya Ando, Elena Tenconi, Roger D. Cone, Sara McDevitt, Allan S. Kaplan, Patrick F. Sullivan, Paolo Santonastaso, Gudrun Wagner, James I. Hudson, Mario Maj, Margarita C T Slof-Op 't Landt, Anna Keski-Rahkonen, Annemarie A. van Elburg, Marta Tyszkiewicz-Nwafor, Danielle M. Dick, Beata Świątkowska, Sven Cichon, Jessica H. Baker, Peter McGuffin, Walter H. Kaye, Stephen W. Scherer, Maurizio Clementi, Valdo Ricca, D. Blake Woodside, Roel A. Ophoff, Unna N. Danner, Aarno Palotie, Elisabeth Widen, Nicholas J. Schork, Jakob Grove, Philip Gorwood, Christian R. Marshall, Preben Bo Mortensen, Melissa A. Munn-Chernoff, Hakon Hakonarson, Martin A. Kennedy, Dan Rujescu, Gerome Breen, Lars Alfredsson, Hartmut Imgart, Steven Gallinger, Ole A. Andreassen, Monika Dmitrzak-Weglarz, Pierre J. Magistretti, Andres Metspalu, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Azienda Ospedaliera di Padova, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Athens Medical School [Athens], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Universitätsklinikum Bonn (UKB), National and Kapodistrian University of Athens (NKUA), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Universität Duisburg-Essen [Essen], Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Tokai University, Department of Optics [Univ Palacký], Faculty of Science [Univ Palacký], Palacky University Olomouc-Palacky University Olomouc, Vall d'Hebron University Hospital [Barcelona], National Institute for Health and Welfare [Helsinki], Medizinische Universität Wien = Medical University of Vienna, University of Helsinki, Rheumatology Unit, Karolinska Institutet [Stockholm], University of Bergen (UiB), The M Sklodowska-Curie Cancer Center and Institute of Oncology, Università degli studi della Campania 'Luigi Vanvitelli', Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Estonian Genome and Medicine, University of Tartu, Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, Università degli Studi di Salerno (UNISA), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Masaryk Memorial Cancer Institute (RECAMO), Department of Psychiatry, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Vanderbilt University School of Medicine [Nashville], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm - Paris Descartes), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Charles University [Prague] (CU), Norwegian Institute of Public Health [Oslo] (NIPH), Department of Medical Epidemiology and Biostatistics (MEB), Medstar Research Institute, Institute of Medical Informatics, Biometry and Epidemiology, The Scripps Translational Science Institute and The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Molecular Epidemiology, The Jackson Laboratory [Bar Harbor] (JAX), Università degli Studi di Perugia (UNIPG), Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Utrecht University [Utrecht], Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], Oregon Research Institute (ORI), Weill Medical College of Cornell University [New York], Institute for Marine and Antarctic Studies [Horbat] (IMAS), University of Tasmania [Hobart, Australia] (UTAS), University of California [San Diego] (UC San Diego), University of California, QIMR Berghofer Medical Research Institute, Department of Physics and Astronomy [Leicester], University of Leicester, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Aarhus University [Aarhus], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K, National Centre for Register-based Research, School of Computing [Dublin], Dublin City University [Dublin] (DCU), Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Queensland Institute of Medical Research, Department of Genomics, Leiden University Medical Center (LUMC), Watson, H. J., Yilmaz, Z., Thornton, L. M., Hubel, C., Coleman, J. R. I., Gaspar, H. A., Bryois, J., Hinney, A., Leppa, V. M., Mattheisen, M., Medland, S. E., Ripke, S., Yao, S., Giusti-Rodriguez, P., Hanscombe, K. B., Purves, K. L., Adan, R. A. H., Alfredsson, L., Ando, T., Andreassen, O. A., Baker, J. H., Berrettini, W. H., Boehm, I., Boni, C., Perica, V. B., Buehren, K., Burghardt, R., Cassina, M., Cichon, S., Clementi, M., Cone, R. D., Courtet, P., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J. E., Dick, D. M., Dikeos, D., Dina, C., Dmitrzak-Weglarz, M., Docampo, E., Duncan, L. E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Farmer, A., Favaro, A., Fernandez-Aranda, F., Fichter, M. M., Fischer, K., Focker, M., Foretova, L., Forstner, A. J., Forzan, M., Franklin, C. S., Gallinger, S., Giegling, I., Giuranna, J., Gonidakis, F., Gorwood, P., Mayora, M. G., Guillaume, S., Guo, Y., Hakonarson, H., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S. G., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Huckins, L. M., Hudson, J. I., Imgart, H., Inoko, H., Janout, V., Jimenez-Murcia, S., Julia, A., Kalsi, G., Kaminska, D., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M. J. H., Kennedy, J. L., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klareskog, L., Klump, K. L., Knudsen, G. P. S., La Via, M. C., Le Hellard, S., Levitan, R. D., Li, D., Lilenfeld, L., Lin, B. D., Lissowska, J., Luykx, J., Magistretti, P. J., Maj, M., Mannik, K., Marsal, S., Marshall, C. R., Mattingsdal, M., Mcdevitt, S., Mcguffin, P., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, K., Monteleone, A. M., Monteleone, P., Munn-Chernoff, M. A., Nacmias, B., Navratilova, M., Ntalla, I., O'Toole, J. K., Ophoff, R. A., Padyukov, L., Palotie, A., Pantel, J., Papezova, H., Pinto, D., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ritschel, F., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S. W., Schmidt, U., Schork, N. J., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op 't Landt, M. C. T., Slopien, A., Sorbi, S., Swiatkowska, B., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wagner, G., Walton, E., Widen, E., Zeggini, E., Zerwas, S., Zipfel, S., Bergen, A. W., Boden, J. M., Brandt, H., Crawford, S., Halmi, K. A., Horwood, L. J., Johnson, C., Kaplan, A. S., Kaye, W. H., Mitchell, J. E., Olsen, C. M., Pearson, J. F., Pedersen, N. L., Strober, M., Werge, T., Whiteman, D. C., Woodside, D. B., Stuber, G. D., Gordon, S., Grove, J., Henders, A. K., Jureus, A., Kirk, K. M., Larsen, J. T., Parker, R., Petersen, L., Jordan, J., Kennedy, M., Montgomery, G. W., Wade, T. D., Birgegard, A., Lichtenstein, P., Norring, C., Landen, M., Martin, N. G., Mortensen, P. B., Sullivan, P. F., Breen, G., Bulik, C. M., and Kas lab

Subjects
Male, Anorexia Nervosa, LD SCORE REGRESSION, Medizin, Genome-wide association study, MYC, VARIANTS, Body Mass Index, ddc:616.89, 0302 clinical medicine, POLYGENIC RISK, genetics, molecular biology, anorexia nervosa, Anorexia Nervosa/etiology/genetics/pathology, 0303 health sciences, Metabolic Diseases/complications/genetics, HERITABILITY, Mental Disorders, Anorèxia nerviosa, Genomics, metabo-psychiatric origins, Prognosis, 3. Good health, PREVALENCE, Eating disorders, INSIGHTS, Phenotype, Anorexia nervosa (differential diagnoses), Medical genetics, Female, GENETIC CORRELATIONS, Adult, medicine.medical_specialty, Quantitative Trait Loci, Biology, Article, 03 medical and health sciences, Metabolic Diseases, mental disorders, medicine, Genetics, Journal Article, Humans, Genetic Predisposition to Disease, Psychiatry, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Case-control study, EATING-DISORDERS, Anorexia nervosa, medicine.disease, Comorbidity, Genetic architecture, Genomics/methods, Genòmica, Case-Control Studies, Mental Disorders/complications/genetics, COMORBIDITY, Body mass index, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness 1, affecting 0.9–4% of women and 0.3% of men 2–4, with twin-based heritability estimates of 50–60% 5. Mortality rates are higher than those in other psychiatric disorders 6, and outcomes are unacceptably poor 7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI) 8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

Published
2019

34. Exome sequencing in a familial form of anorexia nervosa supports multigenic etiology

Author

Philip Gorwood, Philibert Duriez, Nicolas Lebrun, Thierry Bienvenu, Julia Clarke, and Nicolas Ramoz

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, Neurology, Anorexia Nervosa, Adolescent, 03 medical and health sciences, 0302 clinical medicine, Exome Sequencing, Medicine, Humans, Exome, Biological Psychiatry, Exome sequencing, Genetic association, Genetics, Familial form, business.industry, Pedigree, Psychiatry and Mental health, 030104 developmental biology, Anorexia nervosa (differential diagnoses), Etiology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Anorexia nervosa (AN) is a severe debilitating eating disorder. To date, only very few genes that predispose to AN have been identified. An alternative to association studies is to characterize ultra-rare variants in familial forms of AN. Here, we have implemented this approach to identify pathways that contribute to the development of AN through the analysis of a family with three members suffering from AN by exome analysis. We identified three ultra-rare deleterious variants in three genes (DRD4, CCKAR, NMS), already connected to the reward pathway, that co-segregate with AN, suggesting that this pathway might be playing a predisposing role in AN at least in familial forms.

Published
2019

35. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author

Laura M. Thornton, Paul Lichtenstein, Verneri Anttila, Diego Albani, Josep Antoni Ramos-Quiroga, Roger A.H. Adan, Monika Schlögelhofer, Stephen Sanders, Enrique Castelao, Klaus Berger, Nina Dalkner, Urs Heilbronner, Engilbert Sigurdsson, Pablo Mir, Fuquan Zhang, James T.R. Walters, Patrick F. Sullivan, Fragiskos Gonidakis, F. Kyle Satterstrom, Sara Marsal, Per Hoffmann, Amy Perry, Valentina Ciullo, Beate Herpertz-Dahlmann, Catharina Lavebratt, Kieran C. Murphy, Tammy Hedderly, Hyun Ju Hong, Evald Saemundsen, Sascha B. Fischer, Hailiang Huang, Andrew D. Grotzinger, Nienke Vulink, Murray B. Stein, Mark A. Frye, Laura J. Scott, David Curtis, Todd Lencz, Janiece E. DeSocio, Richard A. Belliveau, Eduard Vieta, Andrea Dietrich, Wade H. Berrettini, Kenneth S. Kendler, Marquis P. Vawter, Paul S. Nestadt, Michael E. Talkowski, Manuel Mattheisen, Ingrid Agartz, Elisa Docampo, Bernhard T. Baune, Stefan Ehrlich, Jolanta Lissowska, Felecia Cerrato, Terje Nærland, Robin M. Murray, Jennifer Reichert, Annette M. Hartmann, Hannelore Ehrenreich, Howard J. Edenberg, Katherine A. Halmi, Qingqin S. Li, Peristera Paschou, Marie Bækvad-Hansen, Esther Walton, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Frank Bellivier, Jungeun Song, D. Blake Woodside, Young Shin Kim, Jochen Seitz, Jacques Pantel, Palmiero Monteleone, Erika L. Nurmi, Rodney J. Scott, Kang Sim, Ekaterina A. Khramtsova, Udo Dannlowski, Rolf Adolfsson, Danielle Posthuma, Melissa J. Green, Laura Ibanez-Gomez, Jakob Grove, Elvira Bramon, Gregory L. Hanna, Cynthia M. Bulik, Yiran Guo, Stephan Ripke, Mary M. Robertson, Harald N. Aschauer, Adebayo Anjorin, Joanna Martin, Bertram Müller-Myhsok, Deborah Kaminská, Jose Guzman-Parra, Benedetta Nacmias, Erik G. Jönsson, Jonathan R. I. Coleman, Douglas F. Levinson, Hamdi Mbarek, Gun Peggy Knudsen, Karin Egberts, Mette Nyegaard, Patrik K. E. Magnusson, Mark Adams, Douglas Blackwood, Elisabeth B. Binder, Marcus Ising, Anna R. Docherty, Jim van Os, Nese Direk, Lina Martinsson, Maria Arranz, Christel M. Middeldorp, Stefan Kloiber, Sintia Iole Belangero, Eske M. Derks, Ingrid Melle, Erlend Bøen, Jan Haavik, Federica Piras, Unna N. Danner, Anil K. Malhotra, Gerome Breen, Stephen V. Faraone, Amanda B Zheutlin, Timothy Poterba, Stephan Ruhrmann, Inge Joa, Ulrik Fredrik Malt, Sarah E. Bergen, Federica Tozzi, Lauren A. Weiss, Hana Papezova, Dominic Holland, Elliot S. Gershon, Jaakko Kaprio, Merete Nordentoft, Scott D. Gordon, Christopher Pittenger, Keun-Ah Cheon, Jennifer Jordan, Philip Gorwood, Myrna M. Weissman, Preben Bo Mortensen, Melissa A. Munn-Chernoff, Isobel Heyman, Eun-Young Shin, Christie L. Burton, Katherine Gordon-Smith, Sietske G. Helder, Peter Nagy, Till F. M. Andlauer, Yunpeng Wang, Young Key Kim, Kate Langley, Søren Dalsgaard, Richard Delorme, Torbjørn Elvsåshagen, Bennett L. Leventhal, Giovanni Gambaro, Christos Androutsos, Jennifer Tübing, Marion Roberts, Annelie Nordin Adolfsson, Hakon Hakonarson, Dorothy E. Grice, Vaughan J. Carr, Konstantinos Tziouvas, Stephanie Zerwas, Cathy L. Barr, Michael Conlon O'Donovan, Per Qvist, Beate St Pourcain, Samuel Kuperman, Leila Karhunen, Jack Samuels, Markus M. Nöthen, Martien J H Kas, Alfonso Tortorella, Mikael Landén, Jennifer Crosbie, Marco A. Grados, Joanna M. Biernacka, Paul D. Arnold, Irene A. Malaty, Jurjen J. Luykx, Nicholas Bass, Naomi R. Wray, Catharina A. Hartman, Christina M. Hultman, Michael S. Okun, Brandon Wormley, Michael Bauer, Daniel J. Smith, Ian Jones, Kathryn Roeder, Brien P. Riley, Caroline M. Nievergelt, Katrin Gade, Sarah Kittel-Schneider, Roy H. Perlis, James R. Mitchell, Ziarih Hawi, James Lee, Liz Forty, William E. Bunney, Thomas Damm Als, Catherine Schaefer, Digby Quested, Matteo Cassina, Anna C. Koller, Patrick Turley, Agnes A. Steixner, Anu Raevuori, Assen Jablensky, Peter Holmans, Dong-Ho Song, S. Evelyn Stewart, Jan K. Buitelaar, Fernando S. Goes, Alexander Münchau, Ayman H. Fanous, Nicolas Ramoz, James B. Potash, Monica Gratacos Mayora, Tobias Banaschewski, Céline S. Reinbold, Renata Rizzo, Arianna Di Florio, Lenka Foretova, Gianfranco Spalletta, Aarno Palotie, Eleftheria Zeggini, Lawrence W. Brown, Julie K. O'Toole, Lynn E. DeLisi, Ulrich Schall, Mary Roberson, Barbara J. Coffey, Bryan J. Mowry, Murray J. Cairns, Dan J. Stein, Glyn Lewis, Marta Ribasés, C. Robert Cloninger, Bettina Konte, John B. Vincent, Duncan S. Palmer, Radhika Kandaswamy, Christine Ladd-Acosta, Lars Alfredsson, Frank Visscher, Ulrike Schmidt, Aiden Corvin, Susan L. Santangelo, Brenda W.J.H. Penninx, David J. Porteous, Tetsuya Ando, Arne E. Vaaler, Bru Cormand, Laura Carlberg, Claire Churchhouse, Manfred Stuhrmann, Niamh Mullins, Christine Søholm Hansen, Cathy L. Budman, Hartmut Imgart, Dan E. Arking, James J. McGough, Michael Gill, Christel Depienne, Roland Burghardt, Antonio Julià, Anders M. Dale, Sven Sandin, Katharina Domschke, Maria Grigoroiu-Serbanescu, Susana Jiménez-Murcia, Marianne Giørtz Pedersen, Zsanett Tarnok, Gisli Baldursson, Michele T. Pato, David M. Hougaard, Thorgeir E. Thorgeirsson, Katharina Bey, Kerstin J. Plessen, Margaret A. Richter, Ole A. Andreassen, Claudine Laurent-Levinson, Leonid Padyukov, Jacques Mallet, Daniela Degortes, John R. Kelsoe, Robert D. Levitan, Andreas Reif, Chaim Huyser, Derek W. Morris, Sina Wanderer, William Byerley, Edna Grünblatt, E.J.C. de Geus, Hyejung Won, Josephine Elia, Rudolf Uher, Jay A. Tischfield, Andreas Karwautz, Gustavo Turecki, Pieter J. Hoekstra, Dorret I. Boomsma, Jacob Rosenthal, Daniele Cusi, Michael C. Neale, Sara Mostafavi, Gwyneth Zai, F. Anthony O'Neill, Gary Donohoe, Karola Rehnström, Harry Brandt, Helena Gaspar, Francis J. McMahon, H-Erich Wichmann, Andrew W. Bergen, Giovanni Coppola, Lea K. 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O., Lucae, S., Maaser, A., Malt, U. F., Martin, N. G., Martinsson, L., Mcelroy, S. L., Mcmahon, F. J., Mcquillin, A., Melle, I., Metspalu, A., Millischer, V., Mitchell, P. B., Montgomery, G. W., Morken, G., Morris, D. W., Muller-Myhsok, B., Mullins, N., Myers, R. M., Nievergelt, C. M., Nordentoft, M., Adolfsson, A. N., Nothen, M. M., Ophoff, R. A., Owen, M. J., Paciga, S. A., Pato, C. N., Pato, M. T., Perlis, R. H., Perry, A., Potash, J. B., Reinbold, C. S., Rietschel, M., Rivera, M., Roberson, M., Schalling, M., Schofield, P. R., Schulze, T. G., Scott, L. J., Serretti, A., Sigurdsson, E., Smeland, O. B., Stordal, E., Streit, F., Strohmaier, J., Thorgeirsson, T. E., Treutlein, J., Turecki, G., Vaaler, A. E., Vieta, E., Vincent, J. B., Wang, Y., Witt, S. H., Zandi, P., Adan, R. A. H., Alfredsson, L., Ando, T., Aschauer, H., Baker, J. H., Bencko, V., Bergen, A. W., Birgegard, A., Perica, V. B., Brandt, H., Burghardt, R., Carlberg, L., Cassina, M., Clementi, M., Courtet, P., Crawford, S., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., Degortes, D., Desocio, J. E., Dick, D. M., Dina, C., Docampo, E., Egberts, K., Ehrlich, S., Espeseth, T., Fernandez-Aranda, F., Fichter, M. M., Foretova, L., Forzan, M., Gambaro, G., Giegling, I., Gonidakis, F., Gorwood, P., Mayora, M. G., Guo, Y., Halmi, K. A., Hatzikotoulas, K., Hebebrand, J., Helder, S. G., Herpertz-Dahlmann, B., Herzog, W., Hinney, A., Imgart, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Julia, A., Kaminska, D., Karhunen, L., Karwautz, A., Kas, M. J. H., Kaye, W. H., Kennedy, M. A., Kim, Y. -R., Klareskog, L., Klump, K. L., Knudsen, G. P. S., Landen, M., Le Hellard, S., Levitan, R. D., Li, D., Lichtenstein, P., Maj, M., Marsal, S., Mcdevitt, S., Mitchell, J., Monteleone, P., Monteleone, A. M., Munn-Chernoff, M. A., Nacmias, B., Navratilova, M., O'Toole, J. K., Padyukov, L., Pantel, J., Papezova, H., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Roberts, M., Rujescu, D., Rybakowski, F., Scherag, A., Schmidt, U., Seitz, J., Slachtova, L., Slof-Op't Landt, M. C. T., Slopien, A., Sorbi, S., Southam, L., Strober, M., Tortorella, A., Tozzi, F., Treasure, J., Tziouvas, K., van Elburg, A. A., Wade, T. D., Wagner, G., Walton, E., Watson, H. J., Wichmann, H. -E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Adams, M. J., Andlauer, T. F. M., Berger, K., Binder, E. B., Boomsma, D. I., Castelao, E., Colodro-Conde, L., Direk, N., Docherty, A. R., Domenici, E., Domschke, K., Dunn, E. C., Foo, J. C., D, e. Geus E. J. C., Grabe, H. J., Hamilton, S. P., Horn, C., Hottenga, J. -J., Howard, D., Ising, M., Kloiber, S., Levinson, D. F., Lewis, G., Magnusson, P. K. E., Mbarek, H., Middeldorp, C. M., Mostafavi, S., Nyholt, D. R., Penninx, B. W., Peterson, R. E., Pistis, G., Porteous, D. J., Preisig, M., Quiroz, J. A., Schaefer, C., Schulte, E. C., Shi, J., Smith, D. J., Thomson, P. A., Tiemeier, H., Uher, R., van der Auwera, S., Weissman, M. M., Alexander, M., Begemann, M., Bramon, E., Buccola, N. G., Cairns, M. J., Campion, D., Carr, V. J., Cloninger, C. R., Cohen, D., Collier, D. A., Corvin, A., Delisi, L. E., Donohoe, G., Dudbridge, F., Duan, J., Freedman, R., Gejman, P. V., Golimbet, V., Godard, S., Ehrenreich, H., Hartmann, A. M., Henskens, F. A., Ikeda, M., Iwata, N., Jablensky, A. V., Joa, I., Jonsson, E. G., Kelly, B. J., Knight, J., Konte, B., Laurent-Levinson, C., Lee, J., Lencz, T., Lerer, B., Loughland, C. M., Malhotra, A. K., Mallet, J., Mcdonald, C., Mitjans, M., Mowry, B. J., Murphy, K. C., Murray, R. M., O'Neill, F. A., Oh, S. -Y., Palotie, A., Pantelis, C., Pulver, A. E., Petryshen, T. L., Quested, D. J., Riley, B., Sanders, A. R., Schall, U., Schwab, S. G., Scott, R. J., Sham, P. C., Silverman, J. M., Sim, K., Steixner, A. A., Tooney, P. A., van Os, J., Vawter, M. P., Walsh, D., Weiser, M., Wildenauer, D. B., Williams, N. M., Wormley, B. K., Zhang, F., Androutsos, C., Arnold, P. D., Barr, C. L., Barta, C., Bey, K., Bienvenu, O. J., Black, D. W., Brown, L. W., Budman, C., Cath, D., Cheon, K. -A., Ciullo, V., Coffey, B. J., Cusi, D., Davis, L. K., Denys, D., Depienne, C., Dietrich, A., Eapen, V., Falkai, P., Fernandez, T. V., Garcia-Delgar, B., Geller, D. A., Gilbert, D. L., Grados, M. A., Greenberg, E., Grunblatt, E., Hagstrom, J., Hanna, G. L., Hartmann, A., Hedderly, T., Heiman, G. A., Heyman, I., Hong, H. J., Huang, A., Huyser, C., Ibanez-Gomez, L., Khramtsova, E. A., Kim, Y. K., Kim, Y. -S., King, R. A., Koh, Y. -J., Konstantinidis, A., Kook, S., Kuperman, S., Leventhal, B. L., Lochner, C., Ludolph, A. G., Madruga-Garrido, M., Malaty, I., Maras, A., Mccracken, J. T., Meijer, I. A., Mir, P., Morer, A., Muller-Vahl, K. R., Munchau, A., Murphy, T. L., Naarden, A., Nagy, P., Nestadt, G., Nestadt, P. S., Nicolini, H., Nurmi, E. L., Okun, M. S., Paschou, P., Piras, F., Pittenger, C., Plessen, K. J., Richter, M. A., Rizzo, R., Robertson, M., Roessner, V., Ruhrmann, S., Samuels, J. F., Sandor, P., Schlogelhofer, M., Shin, E. -Y., Singer, H., Song, D. -H., Song, J., Spalletta, G., Stein, D. J., Stewart, S. E., Storch, E. A., Stranger, B., Stuhrmann, M., Tarnok, Z., Tischfield, J. A., Tubing, J., Visscher, F., Vulink, N., Wagner, M., Walitza, S., Wanderer, S., Woods, M., Worbe, Y., Zai, G., Zinner, S. H., Sullivan, P. F., Franke, B., Daly, M. J., Bulik, C. M., Mcintosh, A. M., O'Donovan, M. C., Zheutlin, A., Andreassen, O. A., Borglum, A. D., Breen, G., Edenberg, H. J., Fanous, A. H., Faraone, S. V., Gelernter, J., Mathews, C. A., Mattheisen, M., Mitchell, K. S., Neale, M. C., Nurnberger, J. I., Ripke, S., Santangelo, S. L., Scharf, J. M., Stein, M. B., Thornton, L. M., Walters, J. T. R., Wray, N. R., Geschwind, D. H., Neale, B. M., Kendler, K. S., and Smoller, J. W.

Subjects
Netherlands Twin Register (NTR), cross-disorder genetics, Medizin, Genome-wide association study, Tourette syndrome, functional genomics, gene expression, genetic architecture, genetic correlation, GWAS, neurodevelopment, pleiotropy, psychiatric disorders, Psychiatric genetics, 0302 clinical medicine, Pleiotropy, functional genomic, WIDE ASSOCIATION, cross-disorder genetic, 0303 health sciences, Mental Disorders, Genetic Pleiotropy, HUMAN BRAIN, INSIGHTS, Autism spectrum disorder, Schizophrenia, DISEASES, GENETIC CORRELATIONS, medicine.medical_specialty, Neurogenesis, Quantitative Trait Loci, BF, Biology, GENOTYPE IMPUTATION, Psychiatric geneticscross-disorder geneticspsychiatric disorderspleiotropyneurodevelopmentGWASgenetic correlationgene expressiongenetic architecturefunctional genomics, Article, General Biochemistry, Genetics and Molecular Biology, psychiatric disorder, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, TRANSCRIPTOME, Psychiatry, 030304 developmental biology, Gwas, Psychiatric Genetics, Cross-disorder Genetics, Functional Genomics, Gene Expression, Genetic Architecture, Genetic Correlation, Neurodevelopment, Psychiatric Disorders, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], IDENTIFICATION, MUTATIONS, medicine.disease, Genetic architecture, DEMETHYLASE, RC0321, 1182 Biochemistry, cell and molecular biology, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

Published
2019

36. Altered DNA methylation associated with nervosa anorexia in males

Author

Marie Rose Moro, Franck Letourneur, Nicolas Lebrun, Corinne Blanchet, Marie de Tayrac, Philip Gorwood, Nicolas Ramoz, Thierry Bienvenu, Artem Kim, and Brigitte Izac

Subjects
medicine.medical_specialty, Endocrinology, business.industry, Internal medicine, DNA methylation, medicine, Anorexia, medicine.symptom, business
Published
2019

37. The number of past manic episodes is the best predictor of antidepressant-emergent manic switch in a cohort of bipolar depressed patients

Author

Stéphane Richard-Devantoy, Jean Pierre Olié, Othman Sentissi, Philip Gorwood, and Yann Le Strat

Subjects
Adult, medicine.medical_specialty, Bipolar Disorder, Lithium, Logistic regression, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Antimanic Agents, Rating scale, mental disorders, medicine, Humans, In patient, Bipolar disorder, Psychiatry, Biological Psychiatry, Depression (differential diagnoses), Aged, Depression, Mood Disorders, Middle Aged, medicine.disease, Antidepressive Agents, 030227 psychiatry, Affect, Psychiatry and Mental health, Carbamazepine, Mood, Cohort, Antidepressant, Female, Psychology, 030217 neurology & neurosurgery
Abstract

The present study sought to identify factors associated with the onset of a manic or hypomanic episode during the month following a new antidepressant therapy in depressed bipolar patients. Patients receiving mood stabilizers for ≥3 months were screened from 400 French centers and were assessed for a 4-week period following prescription of a first or a new antidepressant. Of the 1242 included participants, 4.8% (n=60) experienced antidepressant-emergent manic switch (AEMS). AEMS was more frequently associated with lifetime manic, depressive, and total mood episodes, and with past AEMS. A higher score at two items of the Montgomery-Åsberg Depression Rating Scale (pessimistic and suicidal thoughts) were significantly associated with AEMS. Logistic regression analysis showed that the number of lifetime manic episodes and past AEMS were the two most factors associated with an AEMS. Having more than four past manic episodes was associated with a 2.84 fold increased risk of AEMS. Cumulative number of past mood episodes seems to be the most important factor for switching to a manic episode following antidepressants in patients with bipolar disorder. Longer-term studies are required to further delineate antidepressant causality from natural disease course.

Published
2016

38. SUICIDAL DEPRESSED PATIENTS RESPOND LESS WELL TO ANTIDEPRESSANTS IN THE SHORT TERM

Author

Isabelle Jaussent, Jorge Lopez-Castroman, Philip Gorwood, and Philippe Courtet

Subjects
medicine.medical_specialty, Suicide attempt, Poison control, Odds ratio, Hospital Anxiety and Depression Scale, Confidence interval, 030227 psychiatry, 3. Good health, law.invention, 03 medical and health sciences, Psychiatry and Mental health, Clinical Psychology, 0302 clinical medicine, Randomized controlled trial, law, medicine, medicine.symptom, Psychiatry, Psychology, Suicidal ideation, 030217 neurology & neurosurgery, Depression (differential diagnoses)
Abstract

BACKGROUND: Suicidal thoughts and behaviors could be associated to a poor response to antidepressant treatment, but the exclusion of suicidal patients from randomized clinical trials restricts the available knowledge. In this study, we aimed at defining more precisely the response to antidepressants among suicidal patients and the threshold of suicidality that best predicts a poor response. METHOD: We investigated the short-term response to a new antidepressant treatment of 4,041 depressed outpatients depending on their suicidal status (passive or active suicidal ideation (SI), history of suicide attempts [SAs]), either self-rated or clinician-rated. Depression outcomes, measured with the Hospital Anxiety and Depression Scale, and remission rates were compared depending on suicidal status at baseline using logistic regression models. RESULTS: Using either a qualitative or a quantitative approach to measure SI, we found that suicidal patients were less likely to improve or attain remission, but not more likely to worsen, than nonsuicidal patients. In the multivariate analyses, SI (odds ratio [OR] = 1.40; 95% confidence interval [CI]: 1.18-1.65) and a history of SA (OR = 1.39; 95% CI: 1.16-1.66) were the best predictors of nonremission, independently of the class of antidepressant treatment. CONCLUSION: Antidepressant treatment seems to be less effective among those patients that need it most. Clinical trials including suicidal patients are needed to investigate specific treatment options. Language: en

Published
2016

39. Early Symptom Improvement as a Predictor of Response to Extended Release Quetiapine in Major Depressive Disorder

Author

Michael Bauer, Dhaval Desai, Charlie Liss, Michael E. Thase, Roger S. McIntyre, Philip Gorwood, and Ji Chen

Subjects
Adult, medicine.medical_specialty, early predictors, extended release quetiapine fumarate, Placebo, Quetiapine Fumarate, Rating scale, Internal medicine, Outcome Assessment, Health Care, medicine, Humans, Multicenter Studies as Topic, Pharmacology (medical), Psychiatry, Major depressive episode, Randomized Controlled Trials as Topic, Depressive Disorder, Major, major depressive disorder, symptom improvement, Hamilton Rating Scale for Depression, medicine.disease, Psychiatry and Mental health, Delayed-Action Preparations, Meta-analysis, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Major depressive disorder, Quetiapine, Brief Reports, medicine.symptom, Psychology, Antipsychotic Agents, medicine.drug
Abstract

Supplemental digital content is available in the text., The aim of this post-hoc analysis was to determine whether early symptom improvement with extended release quetiapine (quetiapine XR) may predict treatment outcome in patients with major depressive disorder. Data were from 6, double-blind, placebo-controlled studies of quetiapine XR (2 fixed-dose and 2 flexible-dose monotherapy and 2 adjunct studies) in adult patients with major depressive disorder. Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression-Severity Score (CGI-S) were assessed at baseline, weeks 2, 4, and 6. Hamilton Rating Scale for Depression (HAM-D) was assessed at baseline and week 6. The MADRS improvement at week 2 (15%, 20%, 25%, 30%) was used to predict response and remission, based on MADRS (50% improvement; total score ≤ 12) or HAM-D (50% improvement; total score ≤ 7). The CGI-S improvement (1 point) at week 2 was used to predict final outcome (CGI-S score ≤ 2). The predictive value for early improvement with quetiapine XR was found to be “very strong” (Yule’s Q coefficient, a combined measure of sensitivity and specificity) using 30% MADRS improvement as the threshold. This was relatively comparable for response and remission and for fixed-dose, flexible-dose, and adjunct studies. This was also observed for placebo. Exceptions were: adjunct studies (where predictivity was lower for ongoing antidepressant/placebo), and for remission (predictivity for remission appeared lower than for response with placebo). In conclusion, outcome at week 6 with quetiapine XR for a major depressive episode could be predicted by 30% improvement after 2 weeks, a finding that could give doctors confidence to continue treatment and may facilitate adherence in patients.

Published
2015

40. Paliperidone palmitate versus oral antipsychotics in recently diagnosed schizophrenia

Author

Marjolein Lahaye, Juan Schronen, A. Carlo Altamura, Adam Janik, Alp Üçok, Pierre Cherubin, Nikolaj G. Neznanov, Andreas Schreiner, Manuel Franco, Kaire Aadamsoo, Mathias Zink, Ludger Hargarter, and Philip Gorwood

Subjects
Adult, Male, Relative risk reduction, medicine.medical_specialty, Time Factors, Adolescent, Long-acting injectable and oral antipsychotics, medicine.medical_treatment, Administration, Oral, Kaplan-Meier Estimate, Relapse prevention, law.invention, Young Adult, Randomized controlled trial, law, Internal medicine, Paliperidone Palmitate, Humans, Medicine, Psychiatry, Antipsychotic, Biological Psychiatry, Aged, Psychiatric Status Rating Scales, Positive and Negative Syndrome Scale, business.industry, Recently diagnosed, Middle Aged, medicine.disease, Psychiatry and Mental health, Treatment Outcome, Tolerability, Schizophrenia, Female, business, Antipsychotic Agents
Abstract

Objective Relapse and acute exacerbation are common in schizophrenia and may impact treatment response and outcome. Evidence is conflicting in respect to superiority of long-acting injectable antipsychotic therapies versus oral antipsychotics in relapse prevention. This randomized controlled study assessed the efficacy of paliperidone palmitate versus oral antipsychotics for relapse prevention. Method Eligible patients with a recent diagnosis of schizophrenia (within 1–5 years) were randomized 1:1 to paliperidone palmitate (n = 376) or oral antipsychotic monotherapy (n = 388) and entered a 2-week initial acute oral treatment phase. Patients who met predefined response criteria were eligible to enter the 24-month rater-blinded core treatment phase. Patients were evaluated for relapse, symptoms, functioning, quality of life, treatment satisfaction, and tolerability. Results In the core treatment phase, time to relapse was significantly longer in the paliperidone palmitate (n = 352) compared with the oral antipsychotics arm (n = 363): 85% of patients were relapse-free at 469 versus 249 days ( P = 0.019). Significantly fewer patients receiving paliperidone palmitate met the relapse criteria (52 [14.8%] versus 76 [20.9%, oral antipsychotics]; P = 0.032), representing a 29.4% relative risk reduction. For paliperidone palmitate, a significantly greater improvement in Positive and Negative Syndrome Scale total score on Day 8 ( P = 0.021) and a trend at endpoint ( P = 0.075) were observed. Functioning improvements were comparable between treatment arms. No new safety signals were identified. Conclusion The observed time to relapse superiority of paliperidone palmitate over oral antipsychotics provides further evidence for the value of long-acting injectable antipsychotic therapies in the treatment of schizophrenia, including during the early stages of illness.

Published
2015
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41. Association study between reward dependence and a functional BDNF polymorphism in adult women offspring of alcohol-dependent probands

Author

Frédéric Limosin, Delphine Raucher-Chéné, Fabien Gierski, Philip Gorwood, Farid Benzerouk, Arthur Kaladjian, and Nicolas Ramoz

Subjects
Adult, Proband, medicine.medical_specialty, Offspring, media_common.quotation_subject, Personality Assessment, Polymorphism, Single Nucleotide, Asian People, Reward, Neurotrophic factors, Internal medicine, Genetics, Humans, Personality, Medicine, Genetic Predisposition to Disease, Allele, Association (psychology), Genetic Association Studies, Biological Psychiatry, Genetics (clinical), media_common, business.industry, Brain-Derived Neurotrophic Factor, Middle Aged, Alcoholism, Psychiatry and Mental health, Endocrinology, Reward dependence, Case-Control Studies, Female, Temperament and Character Inventory, business
Abstract

Thirty-five healthy adult women offspring of alcohol-dependent probands (AWOA) were compared with 63 healthy controls to test whether personality dimensions on the Temperament and Character Inventory questionnaire were associated with the brain-derived neurotrophic factor Val66Met polymorphism in offspring. We found a significantly lower reward dependence score in AWOA compared with the controls. The brain-derived neurotrophic factor Val66Met polymorphism may be involved in this difference as the lower reward dependence score was found only in AWOA carrying the Val allele.

Published
2015

42. FKBP5 gene variants and borderline personality disorder

Author

Pierre Thomas, Nicolas Ramoz, Hugo Peyre, Philip Gorwood, Ali Amad, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm - Paris Descartes), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Descartes - Paris 5 (UPD5), Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Genotyping Techniques, [SDV]Life Sciences [q-bio], Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Tacrolimus Binding Proteins, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Borderline Personality Disorder, Internal medicine, medicine, SNP, Humans, Child Abuse, Psychological abuse, Child, Borderline personality disorder, business.industry, medicine.disease, FKBP5 Gene, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Physical abuse, Multiple comparisons problem, Female, FKBP5, business, 030217 neurology & neurosurgery
Abstract

Background Genes associated with the physiological response to stress in the hypothalamic-pituitary-adrenal axis are considered as good candidates for genetic research in borderline personality disorder (BPD). Methods In this study, five FKBP5 (a co-chaperone of the glucocorticoid receptor) SNPs (rs3800373, rs9296158, rs737054, rs1360780, rs9470080) were genotyped in a sample of 101 unrelated Caucasian patients with BPD and 111 ethnically matched healthy controls. The interaction between FKBP5 polymorphisms and childhood trauma was also tested. Results All FKBP5 polymorphisms genotyped showed significant associations with BPD. A main effect of rs9470080 (p = 0.01) and gene x environment (physical abuse) interaction (p = 0.01) was found. A gene x environment (emotional abuse) interaction was also found for rs3800373 (p = 0.03). However, these interactions did not remain significant after multiple testing corrections. Limitations In this study, only 5 genetic variants were tested and thus tagging of the FKBP5 gene was incomplete. Moreover, the sample size is moderate. Conclusion BPD is associated with FKBP5 polymorphisms and several types of childhood abuse may modulate the effect between FKBP5 SNPs and this disorder.

Published
2018

43. Predictive factors of functional remission in patients with early to mid-stage schizophrenia treated by long acting antipsychotics and the specific role of clinical remission

Author

Catherine Delva, S. Bouju, Cécile Deal, Charlotte Gary, Pierre-Michel Llorca, Philip Gorwood, Sylvie Lancrenon, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), Service de Psychiatrie de l'Adulte B [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Hôpital Sainte-Anne-Université Paris Cité (UPCité), Janssen-Cilag [Issy-les-Moulineaux], Sylia-Stat [Bourg-La-Reine, France], and CCSD, Accord Elsevier

Subjects
Adult, Male, Psychosis, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Symptomatic treatment, Clinical remission, Long-acting injectable antipsychotics, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Outcome Assessment, Health Care, Antipsychotics, Humans, Medicine, In patient, Functioning, Prospective Studies, Stage (cooking), Biological Psychiatry, business.industry, Remission Induction, medicine.disease, 030227 psychiatry, 3. Good health, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Long acting, Functional remission, Schizophrenia, Delayed-Action Preparations, Female, Observational study, business, 030217 neurology & neurosurgery, Antipsychotic Agents
Abstract

International audience; Background: Functional remission has become a major therapeutic objective in schizophrenia, but the probability of such positive outcome has a large variability, ranging from 15% to 51%. Additionally, how clinical remission constitutes a prerequisite for functional remission also remains unclear.Methods: A prospective observational study was conducted in French schizophrenic patients who initiated treatment with a long-acting injectable (LAI) after an acute episode. Functional and clinical remissions were assessed using the FROGS and the Andreasen criteria, and the role of clinical remission and predictive factors of functional remission was evaluated.Results: Three hundred three patients with schizophrenia (DSM-IV criteria) were followed for 12 months. At 12 months, 45.1% of the patients reached functional remission while 55.1% obtained clinical remission. Clinical remission facilitated functional remission (OR = 14.74), especially in patients with psychosis for less than 5 years (OR = 23.73). Other predictive factors concerned the family environment, education level, employment status, baseline functioning levels and level of insight.Conclusions: About half of patients treated with LAI reached functional remission after one year of follow-up. Reduced clinical symptoms and reaching clinical remission largely favored functional remission. These results stress the importance of continuous and appropriate symptomatic treatment to reach functional remission and maximize recovery chances.

Published
2019

44. Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity

Author

Nektarios Tavernarakis, Mireia Niso-Santano, Lorenzo Galluzzi, Violeta Raverdy, Friedemann Loos, Guido Kroemer, François Pattou, Céline Cruciani-Guglielmacci, Patricia Boya, Justine Lallement, Frank Madeo, Jessica Denom, Ignacio Ramírez-Pardo, Karine Clément, Christophe Magnan, Isabelle Martins, Sylvère Durand, Raphaël G. P. Denis, Noélie Bossut, Maria Chiara Maiuri, Véronique Pelloux, Robert Caiazzo, Valentina Sica, Erwan Boedec, Alili Rohia, Stéphanie Migrenne-Li, José Manuel Bravo-San Pedro, Jonathan Pol, Nicolas Ramoz, Fernando Aranda, Philip Gorwood, Gerasimos Anagnostopoulos, Fanny Aprahamian, Carlos López-Otín, 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)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Université Paris-Saclay, Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigaciones Biológicas (CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Hôpital Sainte-Anne-Université Paris Descartes - Paris 5 (UPD5), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Apoptose, cancer et immunité (U848), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Weill Medical College of Cornell University [New York], Sandra and Edward Meyer Cancer Center [New-York], Yale University School of Medicine, BioTechMed-Graz, Graz University of Technology [Graz] (TU Graz)-Medical University Graz-Karl-Franzens-Universität [Graz, Autriche], Institute of Molecular Biosciences, Karl-Franzens-Universität [Graz, Autriche], University of Crete [Heraklion] (UOC), Institute of Molecular Biology and Biotechnology (IMBB-FORTH), Foundation for Research and Technology - Hellas (FORTH), Universidad de Oviedo [Oviedo], 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), University of Science & Technology of China [Suzhou], Karolinska Institutet [Stockholm], The authors thank CRC Core Facilities (CGB, CHIC, and CEF). G.K. is supported by the Ligue Contre le Cancer (équipe labelisée), Agence National de la Recherche (ANR) – projets blancs, Cancéropôle Île-de-France, Chancelerie Des universités de Paris (Legs Poix), the European Research Council (ERC), Inserm Transfert, Fondation Carrefour, Institut National du Cancer (INCa), Inserm (HTE), Institut Universitaire de France, Leducq Foundation, the Labex immuno-Oncology, the RHU Torino Lumière, the Seattle Foundation, and the SIRICs SOCRATE and CARPEM. C.M. and C.C.-G. are supported by Agence National de la Recherche (ANR-16-CE14-0026, fat4brain proposal), C.L.-O. is supported by 'Juan de Madariaga fellowship', S.B. is supported by the Swedish Research Council Vetenskapsrådet (2015-05468) and the Austrian Science Fund FWF (P27183-B24), and F.M. is supported by the Austrian Science Fund FWF (grants P23490-B20, P29262, P24381, P29203, and P27893), DKplus Metabolic and Cardiovascular Diseases (W1226), Austrian Science Ministry, Karl Franzens University ('Unkonventionelle Forschung' and 'flysleep'), NAWI Graz, and BioTechMed-Graz flagship project 'EPIAge.' K.C. is supported by ANR MICRO-Obes and AP/HP (PHRC Microbaria). L.G. is supported by an intramural startup from the Department of Radiation Oncology of Weill Cornell Medical College (New York, US) and by Sotio a.c. (Prague, Czech Republic)., The authors thank PreclinICAN (Institute of Cardiometabolism and Nutrition, IHU-ICAN, Paris, France) and 'Plateforme Imageries du Vivant' INSERM UMR 970 (PARCC-HEGP) for analyses of mouse whole-body composition and Functional & Physiological Exploration Platform (FPE) of the Unit 'Biologie Fonctionnelle et Adaptative' (University Paris Diderot, Sorbonne Paris Cité, BFA, UMR 8251 CNRS, Paris, France) for metabolic analyses., Ligue Nationale contre le Cancer (France), Agence Nationale de la Recherche (France), Chancellerie des Universités de Paris, European Research Council, Institut National du Cancer (France), Fondation Leducq, Swedish Research Council, Austrian Science Fund, Federal Ministry of Science, Research and Economy (Austria), Bravo-San-Pedro, José Manuel [0000-0002-5781-1133], Sica, Valentina [0000-0003-2770-5847], Martins, Isabelle [0000-0003-0885-613X], Pol, Jonathan G. [0000-0002-8355-7562], Loos, Friedemann [0000-0002-5976-5978], Maiuri, Maria Chiara [0000-0001-9760-7674], Niso-Santano, Mireia [0000-0002-6506-422X], Aranda, Fernando [0000-0002-9364-474X], Gorwood, Philip [0000-0003-1845-3676], Ramoz, Nicolas [0000-0002-8070-9938], Cleḿent, Karine [0000-0002-2489-3355], Pelloux, Véronique [0000-0003-3630-4746], Raverdy, Violeta [0000-0001-5754-2028], Denis, Raphaël G.P. [0000-0002-7677-7460], Boya, Patricia [0000-0003-3045-951X], Galluzzi, Lorenzo [0000-0003-2257-8500 ], Madeo, Frank [0000-0002-5070-1329], Cruciani-Guglielmacci, Céline [0000-0002-2562-5360], Tavernarakis, Nektarios [0000-0002-5253-1466 ], López-Otín, Carlos [0000-0001-6964-1904], Magnan, Christophe [0000-0002-7044-2571], Kroemer, Guido [0000-0002-9334-4405], CCSD, Accord Elsevier, Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Yale School of Medicine [New Haven, Connecticut] (YSM), Graz University of Technology [Graz] (TU Graz)-Karl-Franzens-Universität Graz-Medical University Graz, Karl-Franzens-Universität Graz, École Pratique des Hautes Études (EPHE), Centre de Psychiatrie et Neurosciences (U894), ANR-16-CE14-0026,Fat4Brain,Le métabolisme des lipides dans le cerveau est un regulateur essentiel de l'homéostasie énergétique(2016), Bravo-San Pedro, J. M., Sica, V., Martins, I., Pol, J., Loos, F., Maiuri, M. C., Durand, S., Bossut, N., Aprahamian, F., Anagnostopoulos, G., Niso-Santano, M., Aranda, F., Ramirez-Pardo, I., Lallement, J., Denom, J., Boedec, E., Gorwood, P., Ramoz, N., Clement, K., Pelloux, V., Rohia, A., Pattou, F., Raverdy, V., Caiazzo, R., Denis, R. G. P., Boya, P., Galluzzi, L., Madeo, F., Migrenne-Li, S., Cruciani-Guglielmacci, C., Tavernarakis, N., Lopez-Otin, C., Magnan, C., Kroemer, G., Bravo-San-Pedro, José Manuel, Sica, Valentina, Martins, Isabelle, Pol, Jonathan G., Loos, Friedemann, Maiuri, Maria Chiara, Niso-Santano, Mireia, Aranda, Fernando, Gorwood, Philip, Ramoz, Nicolas, Cleḿent, Karine, Pelloux, Véronique, Raverdy, Violeta, Denis, Raphaël G.P., Boya, Patricia, Galluzzi, Lorenzo, Madeo, Frank, Cruciani-Guglielmacci, Céline, Tavernarakis, Nektarios, López-Otín, Carlos, Magnan, Christophe, and Kroemer, Guido

Subjects
Male, 0301 basic medicine, obesity, Anorexia Nervosa, Physiology, Mice, Obese, Weight Gain, Eating, Mice, 0302 clinical medicine, lipid metabolism, Acyl-CoA-binding protein, Beta oxidation, media_common, Diazepam Binding Inhibitor, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, 0303 health sciences, Leptin Deficiency, Chemistry, Fatty Acids, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Anorexia, 3. Good health, anorexia, Lipogenesis, Female, medicine.symptom, Human, autophagy, medicine.medical_specialty, media_common.quotation_subject, Context (language use), Cell Line, 03 medical and health sciences, Internal medicine, Macroautophagy, Weight Loss, Autophagy, medicine, Animals, Humans, Obesity, Molecular Biology, 030304 developmental biology, Animal, Lipogenesi, Appetite, Cell Biology, Weight Lo, Mice, Inbred C57BL, Lipid metabolism, 030104 developmental biology, Endocrinology, Fatty Acid, 030217 neurology & neurosurgery
Abstract

24 p.-6 fig.-1 tab.-1 graph. abst., Autophagy facilitates the adaptation to nutritional stress. Here, we show that short-term starvation of cultured cells or mice caused the autophagy-dependent cellular release of acyl-CoA-binding protein (ACBP, also known as diazepam-binding inhibitor, DBI) and consequent ACBP-mediated feedback inhibition of autophagy. Importantly, ACBP levels were elevated in obese patients and reduced in anorexia nervosa. In mice, systemic injection of ACBP protein inhibited autophagy, induced lipogenesis, reduced glycemia, and stimulated appetite as well as weight gain. We designed three approaches to neutralize ACBP, namely, inducible whole-body knockout, systemic administration of neutralizing antibodies, and induction of antiACBP autoantibodies in mice. ACBP neutralization enhanced autophagy, stimulated fatty acid oxidation, inhibited appetite, reduced weight gain in the context of a high-fat diet or leptin deficiency, and accelerated weight loss in response to dietary changes. In conclusion, neutralization of ACBP might constitute a strategy for treating obesity and its co-morbidities., G.K. is supported by the Ligue Contre le Cancer (équipe labelisée); Agence National de la Recherche (ANR) – projets blancs; Cancéropôle Île-de-France; Chancelerie Des universités de Paris (Legs Poix); the European Research Council (ERC); Inserm Transfert, Fondation Carrefour; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; Leducq Foundation; the Labex immuno-Oncology; the RHU Torino Lumière; the Seattle Foundation; and the SIRICs SOCRATE and CARPEM. C.M. and C.C.-G. are supported by Agence National de la Recherche (ANR-16-CE14-0026, fat4brain proposal); C.L.-O. is supported by “Juan de Madariaga fellowship”; S.B. is supported by the Swedish Research Council Vetenskapsrådet (2015-05468) and the Austrian Science Fund FWF (P27183-B24); and F.M. is supported by the Austrian Science Fund FWF (grants P23490-B20, P29262, P24381, P29203, and P27893), DKplus Metabolic and Cardiovascular Diseases (W1226), Austrian Science Ministry, Karl Franzens University (“Unkonventionelle Forschung” and “flysleep”), NAWI Graz, and BioTechMed-Graz flagship project “EPIAge.” K.C. is supported by ANR MICRO-Obes and AP/HP (PHRC Microbaria). L.G. is supported by an intramural startup from the Department of Radiation Oncology of Weill Cornell Medical College (New York, US) and by Sotio a.c. (Prague, Czech Republic).

Published
2019

45. Letter: Long-Term Follow-up Study of MRI-Guided Bilateral Anterior Capsulotomy in Patients With Refractory Anorexia Nervosa

Author

Tarek Sharshar, Philip Gorwood, Philibert Duriez, Johan Pallud, Alexandre Roux, Marc Zanello, and Bertrand Devaux

Subjects
medicine.medical_specialty, Anorexia Nervosa, business.industry, Long term follow up, Magnetic Resonance Imaging, 030227 psychiatry, Surgery, Stereotaxic Techniques, 03 medical and health sciences, 0302 clinical medicine, Refractory, Anorexia nervosa (differential diagnoses), medicine, Humans, In patient, Neurology (clinical), business, 030217 neurology & neurosurgery, Mri guided, Anterior capsulotomy, Follow-Up Studies
Published
2018

46. Increased expression of BDNF mRNA in the frontal cortex of autistic patients

Author

J. M. Moalic, Philip Gorwood, Gilles Maussion, Michel Simonneau, and Nicolas Ramoz

Subjects
Adult, Male, medicine.medical_specialty, Candidate gene, Adolescent, Genotype, Single-nucleotide polymorphism, Context (language use), Nerve Tissue Proteins, Laser Capture Microdissection, Biology, Synapse, 03 medical and health sciences, Behavioral Neuroscience, Young Adult, 0302 clinical medicine, GTP-Binding Proteins, Internal medicine, Brodmann area 46, Diagnosis, medicine, CAMK2A, Humans, RNA, Messenger, Autistic Disorder, Child, 030304 developmental biology, 0303 health sciences, Brain-Derived Neurotrophic Factor, Middle Aged, medicine.disease, Frontal Lobe, Endocrinology, nervous system, Gene Expression Regulation, Child, Preschool, Linear Models, Autism, Female, Calcium-Calmodulin-Dependent Protein Kinase Type 2, rs6265, Cell Adhesion Molecules, 030217 neurology & neurosurgery
Abstract

Autistic spectrum disorders (ASDs) are neurodevelopmental disorders for which genetic components have been well defined. However, specific gene deregulations related to synapse function in the autistic brain have not been as extensively described. Based on a candidate genes approach, we present in this study the expression data of 4 transcripts of interest (BDNF, CAMK2a, NR-CAM and RIMS1) located at the synapse in two regions of interest in the context of the ASDs; the lobule VI of cerebellum and the Brodmann area 46. We have also genotyped in our cohort the coding single nucleotide polymorphism rs6265, located in the BDNF gene. After correction for age and sex, whereas no change was observed in the lobule VI between controls and autistic patients, we found a significant increase of BDNF expression level in the BA46 from autistic patients. No significant interaction between the rs6265 genotype and autism was observed for the BDNF expression. However, “A” allele carriers are more likely to have increased BDNF levels. Finally, we found a significant positive correlation between BDNF and RIMS1 expression levels. Our data suggest that these two molecules which are involved in cell signalling at the synapse, might have coordinated expressions and, that BDNF regulation in the brain has to be investigated further in the context of ASDs.

Published
2018

47. 5-HT2A Receptors in Eating Disorders

Author

Philip Gorwood, Laurence Lanfumey, Nicolas Ramoz, and Odile Viltart

Subjects
0301 basic medicine, medicine.medical_specialty, Binge eating, Bulimia nervosa, business.industry, media_common.quotation_subject, digestive, oral, and skin physiology, Appetite, Impulsivity, medicine.disease, Serotonin pathway, 03 medical and health sciences, Eating disorders, 030104 developmental biology, 0302 clinical medicine, Endocrinology, Anorexia nervosa (differential diagnoses), Binge-eating disorder, Internal medicine, medicine, medicine.symptom, business, 030217 neurology & neurosurgery, media_common
Abstract

Eating disorders consist in anorexia nervosa (lack of energy intake and/or excess of caloric consumption) bulimia nervosa (episodes of binge eating associated with compensatory behaviors, such as self-induced vomiting, misuse of laxative, diuretics, fasting or excessive exercise) and binge eating disorder (recurrent episodes of binge eating without compensatory behavior). The biological mechanisms of these eating disorders have been extensively studied, both in human and animal models, mainly focusing on neuropeptides regulating appetite and on neurotransmitters that may also be involved in mood, appetite and weight, but also impulsivity and rewarding aspects of behavior. Although early preclinical data described a clear role of 5-HT2A receptors in food regulation, the use of specific 5-HT2 ligands did not confirm these first data. Most of the ligands initially used acted actually through 5-HT2C receptors, and, at least at preclinical level, it is now clearly established that these 5-HT2C receptors are those which regulated food intake. The gene coding for 5-HT2A receptor was the very first gene associated with eating disorders, mainly in anorexia nervosa, raising the scientific interest in the serotonin pathway to explain their genetic vulnerability. The A allele of −1438G/A HTR2A polymorphism was reported as being associated to AN and BN, but with many discrepancies, the association being insufficiently strong to survive the performed meta-analyses. This does not mean that the 5-HT2A receptor is having no role in any eating disorder, but that its contribution, if any, might be too small to be detectable when many types of patients are being gathered.

Published
2018

48. Validation of a four items version of the Functional Remission of General Schizophrenia scale (the mini-FROGS) to capture the functional benefits of clinical remission

Author

F. Bayle, C. Lançon, Jasmina Mallet, Philip Gorwood, Sylvie Lancrenon, Pierre-Michel Llorca, Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Analyse Phenotypique, Developpementale et Genetique des Comportements Addictifs, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Psychometrics, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Culture, Prospective data, 03 medical and health sciences, 0302 clinical medicine, Recurrence, medicine, Humans, Multicenter Studies as Topic, ComputingMilieux_MISCELLANEOUS, Social functioning, Psychiatric Status Rating Scales, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SCCO.NEUR]Cognitive science/Neuroscience, Reproducibility of Results, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, medicine.disease, Self Concept, 030227 psychiatry, Europe, Psychiatry and Mental health, Observational Studies as Topic, Cross-Sectional Studies, Schizophrenia, Scale (social sciences), Multicenter survey, Observational study, Female, Schizophrenic Psychology, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract

ObjectivesWe previously developed the Functional Remission Of General Schizophrenia (FROGS) scale demonstrating first, reliable assessment in a cross-sectional study and second, good time-stability. The purpose of the present analysis was to propose a shorter version (mini-FROGS), more compatible with the limited time available in a psychiatric visit, focusing on the functional domains that have higher likelihood of being improved with higher and/or longer symptomatic remission in different cultural backgrounds.MethodsWe used multiple regressions to find the most informative items explaining increased length of symptomatic remission, using prospective data from a national observational multicenter survey. Then, the mini-FROGS was used in different European countries to test its between-center reliability, compared to other scales.ResultsFour domains were retained as capturing the maximum of symptomatic remission, namely (1) travel and communication, (2) management of illness and treatment, (3) self-esteem and sense of independence and (4) respect of biological rhythms. First, the mini-FROG was evaluated in 443 French patients with clinical remission and 22 without, and 12/18 months later in 140 patients still in clinical remission and 23 in relapse. In Europe, 295 schizophrenia patients were assessed with the mini-FROGS and other scales devoted to functional remission, allowing comparisons. The mini-FROGS showed good correlations with other scales in different countries and demonstrated good psychometric properties.ConclusionThese results give evidence that a 4 items-only version of the FROGS scale may be useful to assess important aspects of functional remission, tightly linked to the length of clinical remission.

Published
2018

49. Impaired decision-making in symptomatic anorexia and bulimia nervosa patients: a meta-analysis

Author

Sébastien Guillaume, F. van den Eynde, Philippe Courtet, Philip Gorwood, Fabrice Jollant, Stéphane Richard-Devantoy, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Hôpital Sainte-Anne-Université Paris Descartes - Paris 5 (UPD5), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Psychiatry [Montréal], McGill University = Université McGill [Montréal, Canada], Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, and McGill University

Subjects
medicine.medical_specialty, Anorexia Nervosa, Decision Making, eating disorders, Anorexia, Neuropsychological Tests, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Binge-eating disorder, Internal medicine, Task Performance and Analysis, Iowa gambling task, medicine, Humans, Bulimia Nervosa, Psychiatry, Applied Psychology, 2. Zero hunger, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Bulimia nervosa, 1. No poverty, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Eating disorders, Anorexia nervosa (differential diagnoses), [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Meta-analysis, medicine.symptom, Psychology, Body mass index, Binge-Eating Disorder, 030217 neurology & neurosurgery, Decision-making
Abstract

Background.Impaired decision-making is a potential neurocognitive phenotype of eating disorders. It is therefore important to disentangle the decision-making deficits associated with the eating disorder subtypes and determine whether this putative impairment is a state or trait marker of the disease or more related to starvation. We systematically reviewed the literature on decision-making in eating disorders and conducted a meta-analysis to explore its role in anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED).Method.A search of the Medline and EMBASE databases and article references was performed. A total of 23 studies (2044 participants) met the selection criteria. When the Iowa gambling task (IGT) was used in at least three of the studies, a meta-analysis was run.Results.IGT performance was significantly worse in patients with an eating disorder diagnosis (AN, BN or BED) compared with healthy controls, indicating that eating disorders have a negative effect on decision-making. Hedges’ g effect sizes were moderate to large (−0.72 in AN, −0.62 in BN, and −1.26 in BED). Recovered AN patients had IGT scores similar to those of healthy controls. Restrictive AN patients had significantly lower IGT net scores than purging AN patients, and both AN subtypes had worse performances than healthy controls. Age and body mass index did not explain results.Conclusions.Decision-making was significantly altered in patients with eating disorders. Poor decision-making was more pronounced during the acute phase than in the recovered state of AN. Nutritional status during the acute phase of the disease did not seem to influence decision-making skills.

Published
2015

50. Cognitive control and schizophrenia: The greatest reliability of the Stroop task

Author

Stéphane Richard-Devantoy, Philip Gorwood, Manuel Orsat, Jean-Paul Lhuillier, Didier Le Gall, and Charlotte Laurenson

Subjects
Adult, Male, medicine.medical_specialty, Trail Making Test, Audiology, behavioral disciplines and activities, Sentence completion tests, Developmental psychology, Executive Function, Young Adult, Cognition, mental disorders, medicine, Humans, Attention, Biological Psychiatry, Aged, Psychiatric Status Rating Scales, Positive and Negative Syndrome Scale, Depression, Beck Depression Inventory, Reproducibility of Results, Middle Aged, medicine.disease, Inhibition, Psychological, Psychiatry and Mental health, Cognitive inhibition, Schizophrenia, Stroop Test, Female, Schizophrenic Psychology, Psychology, Stroop effect
Abstract

Three components of cognitive inhibition were compared in patients with schizophrenia and healthy controls. Nineteen patients with schizophrenia were compared to 30 healthy controls, matched for age, sex, and educational level. Cognitive inhibition was examined by (i) access to relevant information (Reading with distraction task), (ii) suppression of no longer relevant information (Trail Making Test B), and (iii) restraint of cognitive resources to relevant information (Stroop Test, Hayling Sentence Completion Test, Go/No-Go Test). Beck Depression Inventory, and Positive and Negative Syndrome Scale were also used. Compared to healthy controls, patients with schizophrenia and stabilized for at least 6 months were slower in the inhibition condition at the Stroop task, read more distractors at the RWD, and made more perseverative errors at the TMT, even after controlling for age, Mini-Mental State Examination score, information speed processing, and accuracy. This difference remained significant after taking into account the level of depressive symptoms and the severity of psychotic symptoms. In multivariate analyses, only the Stroop interference index explained cognitive inhibition deficit in patients with schizophrenia. The abnormal cognitive inhibition process observed in patients with schizophrenia could therefore concerns the ability to restraint, rather than the access or the suppression processes.

Published
2015

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