Abstract
Tic disorders have a strong male predominance, with a male-to-female ratio of 4:1 in Tourette syndrome (TS) and 2:1 in persistent tic disorders. In other neurodevelopmental conditions, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), the disparity in sex distribution has been partially related to differences in symptom presentation between males and females. In tic disorders, however, little research has been conducted on this topic, probably due to the limited access to large samples with a significant proportion of females. The aim of this study was to describe sex differences in the clinical presentation of tic disorders in children and adolescents in one of the largest pediatric samples with TS/persistent tic disorders (n = 709, 23.3% females) recruited as part of the European Multicenter Tics in Children Study (EMTICS). Validated measures assessed the severity of tics and comorbid psychiatric symptoms. Using mixed-effect models, we found that sex had a significant influence on the severity of tics, ADHD symptoms, ASD symptoms, and emotional problems. Males had more severe symptoms than females, except for emotional problems. We also observed a statistically significant interaction between sex and age on the severity of tics and compulsions, with females showing higher symptom severity with increasing age than males. These findings indicate that the clinical presentation of TS/persistent tic disorders varies with sex. Males seem to exhibit a more noticeable pattern of clinical symptoms at a younger age that may contribute to their earlier detection in comparison to females.
Original language | English |
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Pages (from-to) | 1539-1548 |
Number of pages | 10 |
Journal | European Child and Adolescent Psychiatry |
Volume | 31 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2022 |
Bibliographical note
Publisher Copyright:© 2021, Springer-Verlag GmbH Germany, part of Springer Nature.
Funding
Coffey is on the Scientific Advisory Board of Abide Therapeutics and Teva/ Nuvelution, has received honoraria from the American Academy of Child and Adolescent Psychiatry, Partners Healthcare, Harvard Medical School, Teva, CME Outfitters, University of Cincinnati, University of Texas Medical Branch, and University of Florida, and has received research support from Teva/ Nuvelution, Inc., Neurocrine Biosciences, Emalex, the National Institute of Mental Health (Grant No. 5R01MH115959-02), and University of California San Francisco. Müller-Vahl received funding for research from the EU (FP7-PEOPLE-2012-ITN No. 316978), the German Research Society (DFG: GZ MU 1527/3–1), the German Ministry of Education and Research (BMBF: 01KG1421), the National Institute of Mental Health (NIMH), GW, Almirall, Abide Therapeutics, and Therapix Biosiences, and consultant’s honoraria from Abide Therapeutics, Fundacion Canna, and Therapix Biosiences. On behalf of all other authors, the corresponding author declares that the other authors have no conflict of interest. This project has received funding from the European Union's Seventh Framework Program for Research, technological development and demonstration under grant agreement no 278367. The authors are deeply grateful to all children and their parents who willingly participated to make this research possible. This research was supported by the Deutsche Forschungsgemeinschaft (DFG): projects 1692/3-1, 4-1, SFB 936, and FOR 2698 (project numbers 396914663, 396577296, 396474989) (Münchau). We thank all colleagues at the various study centers who contributed to data collection: Julie E. Bruun, Judy Grejsen, Christine L. Ommundsen, Mette Rubæk (Capital Region Psychiatry, Copenhagen, Denmark); Benjamin Bodmer, Stephanie Enghardt (TUD Dresden, Germany); Stefanie Bokemeyer, Christiane Driedger-Garbe, Cornelia Reichert (MHH Hannover, Germany); Jenny Schmalfeld (Lübeck University, Germany); Victoria L. Turner, Martin L. Woods (Evelina London Children’s Hospital, United Kingdom); Franciska Gergye, Margit Kovacs, Reka Vidomusz (Vadaskert Budapest, Hungary); Silvana Fennig, Ella Gev, Matan Nahon, Danny Horesh, Chen Regev, Tomer Simcha, (Tel Aviv, Petah-Tikva, Israel); Els van den Ban, Sebastian F.T.M. de Bruijn, Nicole Driessen, Andreas Lamerz, Marieke Messchendorp, Judith J.G. Rath, Nadine Schalk, Deborah Sival, Noor Tromp, Frank Visscher and the Stichting Gilles de la Tourettes (UMCG Groningen, Netherlands); Maria Teresa Cáceres, Fátima Carrillo, Pilar Gómez-Garre, Laura Vargas, Ángela Periañez Vasco (Hospital Virgen del Rocío, Seville, Spain); Giuseppe Gagliardi (ASL Bari, Italy); Paolo Roazzi, Marco Tallon (ISS Rome, Italy); Maria Gariup, Marina Redondo (Hospital Clinic Barcelona, Spain); and all who may not have been mentioned. EMTICS group authorship/appendix: EMTICS group members are Alan Apter, Valentina Baglioni, Juliane Ball, Noa Benaroya-Milshtein, Emese Bognar, Bianka Burger, Judith Buse, Francesco Cardona, Marta Correa Vela, Nanette M. Debes, Andrea Dietrich, Maria Cristina Ferro, Carolin Fremer, Blanca Garcia-Delgar, Mariangela Gulisano, Annelieke Hagen, Julie Hagstrøm, Tammy J. Hedderly, Isobel Heyman, Pieter J. Hoekstra, Chaim Huyser, Marcos Madruga-Garrido, Anna Marotta, Davide Martino, Pablo Mir, Astrid Morer, Norbert Müller, Kirsten Müller-Vahl, Alexander Münchau, Peter Nagy, Valeria Neri, Thaïra J.C. Openneer, Alessandra Pellico, Kerstin J. Plessen, Cesare Porcelli, Renata Rizzo, Veit Roessner, Daphna Ruhrman, Jaana M.L. Schnell, Paola Rosaria Silvestri, Liselotte Skov, Tamar Steinberg, Friederike Tagwerker Gloor, Zsanett Tarnok, Susanne Walitza Elif Weidinger . Child and Adolescent Psychiatry Department, Schneider Children's Medical Center of Israel, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Petah-Tikva, Israel. University La Sapienza of Rome, Department of Human Neurosciences, Rome, Italy. Clinic of Child and Adolescent Psychiatry and Psychotherapy, University of Zurich, Zurich, Switzerland. Vadaskert Child and Adolescent Psychiatric Hospital, Budapest, Hungary. Semmelweis University, Bókay Children's Clinic, Budapest, Hungary. Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany. Marion von Tessin Memory-Zentrum gGmbH, Munich, Germany. Department of Child and Adolescent Psychiatry, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany. Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clinica. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain. Paediatric Department, Herlev University Hospital, Herlev, Denmark. University of Groningen, University Medical Center Groningen, Department of Child and Adolescent Psychiatry, Groningen, The Netherlands. Child Neuropsychiatry Section, Department of Clinical and Experimental Medicine, School of Medicine, Catania University, Catania, Italy. Clinic of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany. Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic Universitari, Barcelona, Spain. De Bascule, Academic Center for Child and Adolescent Psychiatry, Amsterdam, The Netherlands. Academic Medical Center, Department of Child and Adolescent Psychiatry, Amsterdam, The Netherlands. Child and Adolescent Mental Health Center, Mental Health Services, Capital Region of Denmark and University of Copenhagen, Copenhagen, Denmark. Evelina London Children’s Hospital GSTT, Kings Health Partners AHSC, London, UK. Great Ormond Street Hospital for Children, and UCL Institute of Child Health, London, UK. Sección de Neuropediatría, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain. Azienda Sanitaria Locale di Bari, Mental Health Department, Child and Adolescent Service of Bari Metropolitan Area, Bari, Italy. Department of Clinical Neurosciences, University of Calgary, Calgary, Canada. Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Centro de Investigacion en Red de Salud Mental (CIBERSAM), Instituto Carlos III, Spain. Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany. Bethesda Children's Hospital, Budapest, Hungary. Division of Child and Adolescent Psychiatry, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland 1 2 3 1 4,5 6,7 8 2 9 10 11 12 13 14 12 15,16 17 18 19 11 15,16 20 21 22 9 14,23,24 6,7 13 25 4,26 2 11 12 17,27 21 12 8 1 6 2 10 1 3 4 3 , 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 The authors are deeply grateful to all children and their parents who willingly participated to make this research possible. This research was supported by the Deutsche Forschungsgemeinschaft (DFG): projects 1692/3-1, 4-1, SFB 936, and FOR 2698 (project numbers 396914663, 396577296, 396474989) (Münchau). We thank all colleagues at the various study centers who contributed to data collection: Julie E. Bruun, Judy Grejsen, Christine L. Ommundsen, Mette Rubæk (Capital Region Psychiatry, Copenhagen, Denmark); Benjamin Bodmer, Stephanie Enghardt (TUD Dresden, Germany); Stefanie Bokemeyer, Christiane Driedger-Garbe, Cornelia Reichert (MHH Hannover, Germany); Jenny Schmalfeld (Lübeck University, Germany); Victoria L. Turner, Martin L. Woods (Evelina London Children’s Hospital, United Kingdom); Franciska Gergye, Margit Kovacs, Reka Vidomusz (Vadaskert Budapest, Hungary); Silvana Fennig, Ella Gev, Matan Nahon, Danny Horesh, Chen Regev, Tomer Simcha, (Tel Aviv, Petah-Tikva, Israel); Els van den Ban, Sebastian F.T.M. de Bruijn, Nicole Driessen, Andreas Lamerz, Marieke Messchendorp, Judith J.G. Rath, Nadine Schalk, Deborah Sival, Noor Tromp, Frank Visscher and the Stichting Gilles de la Tourettes (UMCG Groningen, Netherlands); Maria Teresa Cáceres, Fátima Carrillo, Pilar Gómez-Garre, Laura Vargas, Ángela Periañez Vasco (Hospital Virgen del Rocío, Seville, Spain); Giuseppe Gagliardi (ASL Bari, Italy); Paolo Roazzi, Marco Tallon (ISS Rome, Italy); Maria Gariup, Marina Redondo (Hospital Clinic Barcelona, Spain); and all who may not have been mentioned. EMTICS group authorship/appendix: EMTICS group members are Alan Apter1, Valentina Baglioni2, Juliane Ball3, Noa Benaroya-Milshtein1, Emese Bognar4,5, Bianka Burger6,7, Judith Buse8, Francesco Cardona2, Marta Correa Vela9, Nanette M. Debes10, Andrea Dietrich11, Maria Cristina Ferro12, Carolin Fremer13, Blanca Garcia-Delgar14, Mariangela Gulisano12, Annelieke Hagen15,16, Julie Hagstrøm17, Tammy J. Hedderly18, Isobel Heyman19, Pieter J. Hoekstra11, Chaim Huyser15,16, Marcos Madruga-Garrido20, Anna Marotta21, Davide Martino22, Pablo Mir9, Astrid Morer14,23,24, Norbert Müller6,7, Kirsten Müller-Vahl13, Alexander Münchau25, Peter Nagy4,26, Valeria Neri2, Thaïra J.C. Openneer11, Alessandra Pellico12, Kerstin J. Plessen17,27, Cesare Porcelli21, Renata Rizzo12, Veit Roessner8, Daphna Ruhrman1, Jaana M.L. Schnell6, Paola Rosaria Silvestri2, Liselotte Skov10, Tamar Steinberg1, Friederike Tagwerker Gloor3, Zsanett Tarnok4, Susanne Walitza3, Elif Weidinger6.1Child and Adolescent Psychiatry Department, Schneider Children's Medical Center of Israel, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Petah-Tikva, Israel.2University La Sapienza of Rome, Department of Human Neurosciences, Rome, Italy.3Clinic of Child and Adolescent Psychiatry and Psychotherapy, University of Zurich, Zurich, Switzerland.4Vadaskert Child and Adolescent Psychiatric Hospital, Budapest, Hungary.5Semmelweis University, Bókay Children's Clinic, Budapest, Hungary.6Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.7Marion von Tessin Memory-Zentrum gGmbH, Munich, Germany.8Department of Child and Adolescent Psychiatry, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany.9Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clinica. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain.10Paediatric Department, Herlev University Hospital, Herlev, Denmark.11University of Groningen, University Medical Center Groningen, Department of Child and Adolescent Psychiatry, Groningen, The Netherlands.12Child Neuropsychiatry Section, Department of Clinical and Experimental Medicine, School of Medicine, Catania University, Catania, Italy.13Clinic of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.14Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic Universitari, Barcelona, Spain.15De Bascule, Academic Center for Child and Adolescent Psychiatry, Amsterdam, The Netherlands.16Academic Medical Center, Department of Child and Adolescent Psychiatry, Amsterdam, The Netherlands.17Child and Adolescent Mental Health Center, Mental Health Services, Capital Region of Denmark and University of Copenhagen, Copenhagen, Denmark.18Evelina London Children’s Hospital GSTT, Kings Health Partners AHSC, London, UK.19Great Ormond Street Hospital for Children, and UCL Institute of Child Health, London, UK.20Sección de Neuropediatría, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.21Azienda Sanitaria Locale di Bari, Mental Health Department, Child and Adolescent Service of Bari Metropolitan Area, Bari, Italy.22Department of Clinical Neurosciences, University of Calgary, Calgary, Canada.23Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.24Centro de Investigacion en Red de Salud Mental (CIBERSAM), Instituto Carlos III, Spain.25Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany.26Bethesda Children's Hospital, Budapest, Hungary.27Division of Child and Adolescent Psychiatry, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland
Funders | Funder number |
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Abide Therapeutics | |
Adolescent Service of Bari Metropolitan Area | |
CME Outfitters | |
Department of Clinical and Experimental Medicine, School of Medicine, Catania University | |
European Union's Seventh Framework Program for research, technological development and demonstration | |
Evelina London Children’s Hospital | |
Fundacion Canna | |
GSTT | |
Instituto de Biomedicina de Sevilla | |
Kings Health Partners AHSC | |
Maria Teresa Cáceres | |
Marta Correa Vela9 | |
Mental Health Services | |
Servicio de Neurología y Neurofisiología Clinica | |
Silvana Fennig | |
Therapix Biosiences | |
UCL Institute of Child Health | |
National Institute of Mental Health | 5R01MH115959-02 |
Teva Pharmaceutical Industries | |
Harvard Medical School | |
University of Florida | |
University of Texas Medical Branch | |
University of California, San Francisco | |
University of Cincinnati | |
Seventh Framework Programme | 278367 |
University Hospitals | |
European Commission | 316978, FP7-PEOPLE-2012-ITN |
Deutsche Forschungsgemeinschaft | SFB 936, 1692/3-1, 396914663, 396474989, FOR 2698, 396577296, GZ MU 1527/3–1 |
Københavns Universitet | |
Bundesministerium für Bildung und Forschung | 01KG1421 |
Great Ormond Street Hospital for Children | |
Universität zu Lübeck | |
Tel Aviv University | |
Instituto de Salud Carlos III | |
Region Hovedstaden | |
Medizinischen Hochschule Hannover | |
Ludwig-Maximilians-Universität München | |
Centre Hospitalier Universitaire Vaudois | |
Universität Zürich | |
Centro de Investigación Biomédica en Red de Salud Mental |
Keywords
- Adolescents
- Children
- Sex differences
- Tourette syndrome