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1. Genome-Wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome

Author

Barr, Cathy L., Batterson, James R., Berlin, Cheston, Budman, Cathy L., Coppola, Giovanni, Cox, Nancy J., Darrow, Sabrina, Dion, Yves, Freimer, Nelson B., Grados, Marco A., Greenberg, Erica, Hirschtritt, Matthew E., Huang, Alden Y., Illmann, Cornelia, King, Robert A., Kurlan, Roger, Leckman, James F., Lyon, Gholson J., Malaty, Irene A., McMahon, William M., Neale, Benjamin M., Okun, Michael S., Osiecki, Lisa, Robertson, Mary M., Rouleau, Guy A., Sandor, Paul, Singer, Harvey S., Smit, Jan H., Sul, Jae Hoon, Androutsos, Christos, Basha, Entela, Farkas, Luca, Fichna, Jakub, Janik, Piotr, Kapisyzi, Mira, Karagiannidis, Iordanis, Koumoula, Anastasia, Nagy, Peter, Puchala, Joanna, Szejko, Natalia, Szymanska, Urszula, Tsironi, Vaia, Apter, Alan, Ball, Juliane, Bodmer, Benjamin, Bognar, Emese, Buse, Judith, Vela, Marta Correa, Fremer, Carolin, Garcia-Delgar, Blanca, Gulisano, Mariangela, Hagen, Annelieke, Hagstrøm, Julie, Madruga-Garrido, Marcos, Pellico, Alessandra, Ruhrman, Daphna, Schnell, Jaana, Silvestri, Paola Rosaria, Skov, Liselotte, Steinberg, Tamar, Gloor, Friederike Tagwerker, Turner, Victoria L., Weidinger, Elif, Alexander, John, Aranyi, Tamas, Buisman, Wim R., Buitelaar, Jan K., Driessen, Nicole, Drineas, Petros, Fan, Siyan, Forde, Natalie J., Gerasch, Sarah, van den Heuvel, Odile A., Jespersgaard, Cathrine, Kanaan, Ahmad S., Möller, Harald E., Nawaz, Muhammad S., Nespoli, Ester, Pagliaroli, Luca, Poelmans, Geert, Pouwels, Petra J.W., Rizzo, Francesca, Veltman, Dick J., van der Werf, Ysbrand D., Widomska, Joanna, Zilhäo, Nuno R., Brown, Lawrence W., Cheon, Keun-Ah, Coffey, Barbara J., Fernandez, Thomas V., Gilbert, Donald L., Hong, Hyun Ju, Ibanez-Gomez, Laura, Kim, Eun-Joo, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett L., Maras, Athanasios, Murphy, Tara L., Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, State, Matthew W., Visscher, Frank, Wang, Sheng, Zinner, Samuel H., Tsetsos, Fotis, Topaloudi, Apostolia, Jain, Pritesh, Yang, Zhiyu, Yu, Dongmei, Kolovos, Petros, Tumer, Zeynep, Rizzo, Renata, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Müller-Vahl, Kirsten R., Cath, Danielle C., Boomsma, Dorret I., Wolanczyk, Tomasz, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Padmanabhuni, Shanmukha S., Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Yannaki, Evangelia, Stamatoyannopoulos, John A., Benaroya-Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Mir, Pablo, Morer, Astrid, Mueller, Norbert, Munchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Roessner, Veit, Walitza, Susanne, Schrag, Anette, Martino, Davide, Tischfield, Jay A., Heiman, Gary A., Willsey, A. Jeremy, Dietrich, Andrea, Davis, Lea K., Crowley, James J., Mathews, Carol A., Scharf, Jeremiah M., Georgitsi, Marianthi, Hoekstra, Pieter J., and Paschou, Peristera

Published
2024
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2. Genome-Wide Association Study Meta-Analysis of 9619 Cases With Tic Disorders

Author

Yu, Dongmei, Sul, Jae Hoon, Tsetsos, Fotis, Nawaz, Muhammad S., Huang, Alden Y., Zelaya, Ivette, Illmann, Cornelia, Osiecki, Lisa, Darrow, Sabrina M., Hirschtritt, Matthew E., Greenberg, Erica, Muller-Vahl, Kirsten R., Stuhrmann, Manfred, Dion, Yves, Rouleau, Guy, Aschauer, Harald, Stamenkovic, Mara, Schlögelhofer, Monika, Sandor, Paul, Barr, Cathy L., Grados, Marco, Singer, Harvey S., Nöthen, Markus M., Hebebrand, Johannes, Hinney, Anke, King, Robert A., Fernandez, Thomas V., Barta, Csaba, Tarnok, Zsanett, Nagy, Peter, Depienne, Christel, Worbe, Yulia, Hartmann, Andreas, Budman, Cathy L., Rizzo, Renata, Lyon, Gholson J., McMahon, William M., Batterson, James R., Cath, Danielle C., Malaty, Irene A., Okun, Michael S., Berlin, Cheston, Woods, Douglas W., Lee, Paul C., Jankovic, Joseph, Robertson, Mary M., Gilbert, Donald L., Brown, Lawrence W., Coffey, Barbara J., Dietrich, Andrea, Hoekstra, Pieter J., Kuperman, Samuel, Zinner, Samuel H., Luðvigsson, Pétur, Sæmundsen, Evald, Thorarensen, Ólafur, Atzmon, Gil, Barzilai, Nir, Wagner, Michael, Moessner, Rainald, Ophoff, Roel, Pato, Carlos N., Pato, Michele T., Knowles, James A., Roffman, Joshua L., Smoller, Jordan W., Buckner, Randy L., Willsey, Jeremy A., Tischfield, Jay A., Heiman, Gary A., Stefansson, Hreinn, Stefansson, Kári, Posthuma, Danielle, Cox, Nancy J., Pauls, David L., Freimer, Nelson B., Neale, Benjamin M., Davis, Lea K., Paschou, Peristera, Coppola, Giovanni, Mathews, Carol A., Scharf, Jeremiah M., Agee, Michelle, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Hicks, Barry, Huber, Karen E., Jewett, Ethan M., Jiang, Yunxuan, Kleinman, Aaron, Lin, Keng-Han, Litterman, Nadia K., McCreight, Jey C., McIntyre, Matthew H., McManus, Kimberly F., Mountain, Joanna L., Noblin, Elizabeth S., Northover, Carrie A.M., Pitts, Steven J., Poznik, G. David, Sathirapongsasuti, J. Fah, Shelton, Janie F., Shringarpure, Suyash, Tung, Joyce Y., Vacic, Vladimir, Wang, Xin, Strom, Nora I., Halvorsen, Matthew W., Grove, Jakob, Ásbjörnsdóttir, Bergrún, Luðvígsson, Pétur, de Schipper, Elles, Bäckmann, Julia, Andrén, Per, Tian, Chao, Als, Thomas Damm, Nissen, Judith Becker, Meier, Sandra M., Bybjerg-Grauholm, Jonas, Hougaard, David M., Werge, Thomas, Børglum, Anders D., Hinds, David A., Rück, Christian, Mataix-Cols, David, Stefánsson, Hreinn, Stefansson, Kari, Crowley, James J., and Mattheisen, Manuel

Published
2024
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3. Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

Author

Claudio‐Campos, Karla, Stevens, Daniel, Koo, Sang‐Wahn, Valko, Alexa, Bienvenu, Oscar Joseph, Budman, Cathy B, Cath, Danielle C, Darrow, Sabrina, Geller, Daniel, Goes, Fernando S, Grados, Marco A, Greenberg, Benjamin D, Greenberg, Erica, Hirschtritt, Matthew E, Illmann, Cornelia, Ivankovic, Franjo, King, Robert A, Knowles, James A, Krasnow, Janice, Lee, Paul C, Lyon, Gholson J, McCracken, James T, Robertson, Mary M, Osiecki, Lisa, Riddle, Mark A, Rouleau, Guy, Sandor, Paul, Nestadt, Gerald, Samuels, Jack, Scharf, Jeremiah M, Mathews, Carol A, and Study, for the Tourette Association of America International Consortium for Genetics and the OCD Collaborative Genetics Association

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Behavioral and Social Science, Anxiety Disorders, Tourette Syndrome, Neurodegenerative, Serious Mental Illness, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Mental health, Attention Deficit Disorder with Hyperactivity, Comorbidity, Humans, Obsessive-Compulsive Disorder, Tic Disorders, Tics, chronic tics, meta&#8208, analysis, severity, Tourette, Tourette Association of America International Consortium for Genetics (TAAICG) and the OCD Collaborative Genetics Association Study, meta-analysis, Human Movement and Sports Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

BackgroundPersistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation.ObjectiveThe goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT.MethodsWe analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature.ResultsRates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates.ConclusionsOur findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Published
2021

4. Synaptic processes and immune-related pathways implicated in Tourette syndrome.

Author

Tsetsos, Fotis, Yu, Dongmei, Sul, Jae Hoon, Huang, Alden Y, Illmann, Cornelia, Osiecki, Lisa, Darrow, Sabrina M, Hirschtritt, Matthew E, Greenberg, Erica, Muller-Vahl, Kirsten R, Stuhrmann, Manfred, Dion, Yves, Rouleau, Guy A, Aschauer, Harald, Stamenkovic, Mara, Schlögelhofer, Monika, Sandor, Paul, Barr, Cathy L, Grados, Marco A, Singer, Harvey S, Nöthen, Markus M, Hebebrand, Johannes, Hinney, Anke, King, Robert A, Fernandez, Thomas V, Barta, Csaba, Tarnok, Zsanett, Nagy, Peter, Depienne, Christel, Worbe, Yulia, Hartmann, Andreas, Budman, Cathy L, Rizzo, Renata, Lyon, Gholson J, McMahon, William M, Batterson, James R, Cath, Danielle C, Malaty, Irene A, Okun, Michael S, Berlin, Cheston, Woods, Douglas W, Lee, Paul C, Jankovic, Joseph, Robertson, Mary M, Gilbert, Donald L, Brown, Lawrence W, Coffey, Barbara J, Dietrich, Andrea, Hoekstra, Pieter J, Kuperman, Samuel, Zinner, Samuel H, Wagner, Michael, Knowles, James A, Jeremy Willsey, A, Tischfield, Jay A, Heiman, Gary A, Cox, Nancy J, Freimer, Nelson B, Neale, Benjamin M, Davis, Lea K, Coppola, Giovanni, Mathews, Carol A, Scharf, Jeremiah M, Paschou, Peristera, Tourette Association of America International Consortium for Genetics, Darrow, Sabrina, Kurlan, Roger, Leckman, James F, Smit, Jan H, and Gilles de la Tourette GWAS Replication Initiative

Subjects
Tourette Association of America International Consortium for Genetics, Gilles de la Tourette GWAS Replication Initiative, Tourette International Collaborative Genetics Study, Psychiatric Genomics Consortium Tourette Syndrome Working Group, Neurons, Humans, Tourette Syndrome, Genotype, Genome-Wide Association Study, Mental Health, Genetics, Neurosciences, Human Genome, Brain Disorders, Biotechnology, Neurodegenerative, 2.1 Biological and endogenous factors, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.

Published
2021

5. Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies

Author

Yu, Dongmei, Sul, Jae Hoon, Tsetsos, Fotis, Nawaz, Muhammad S, Huang, Alden Y, Zelaya, Ivette, Illmann, Cornelia, Osiecki, Lisa, Darrow, Sabrina M, Hirschtritt, Matthew E, Greenberg, Erica, Muller-Vahl, Kirsten R, Stuhrmann, Manfred, Dion, Yves, Rouleau, Guy, Aschauer, Harald, Stamenkovic, Mara, Schlögelhofer, Monika, Sandor, Paul, Barr, Cathy L, Grados, Marco, Singer, Harvey S, Nöthen, Markus M, Hebebrand, Johannes, Hinney, Anke, King, Robert A, Fernandez, Thomas V, Barta, Csaba, Tarnok, Zsanett, Nagy, Peter, Depienne, Christel, Worbe, Yulia, Hartmann, Andreas, Budman, Cathy L, Rizzo, Renata, Lyon, Gholson J, McMahon, William M, Batterson, James R, Cath, Danielle C, Malaty, Irene A, Okun, Michael S, Berlin, Cheston, Woods, Douglas W, Lee, Paul C, Jankovic, Joseph, Robertson, Mary M, Gilbert, Donald L, Brown, Lawrence W, Coffey, Barbara J, Dietrich, Andrea, Hoekstra, Pieter J, Kuperman, Samuel, Zinner, Samuel H, Luðvigsson, Pétur, Sæmundsen, Evald, Thorarensen, Ólafur, Atzmon, Gil, Barzilai, Nir, Wagner, Michael, Moessner, Rainald, Ophoff, Roel, Pato, Carlos N, Pato, Michele T, Knowles, James A, Roffman, Joshua L, Smoller, Jordan W, Buckner, Randy L, Willsey, A Jeremy, Tischfield, Jay A, Heiman, Gary A, Stefansson, Hreinn, Stefansson, Kári, Posthuma, Danielle, Cox, Nancy J, Pauls, David L, Freimer, Nelson B, Neale, Benjamin M, Davis, Lea K, Paschou, Peristera, Coppola, Giovanni, Mathews, Carol A, and Scharf, Jeremiah M

Subjects
Mental Health, Prevention, Brain Disorders, Human Genome, Neurosciences, Neurodegenerative, Serious Mental Illness, Tourette Syndrome, Genetics, Aetiology, 2.1 Biological and endogenous factors, Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Factors, Severity of Illness Index, Tic Disorders, fms-Like Tyrosine Kinase 3, Tourette Association of America International Consortium for Genetics, the Gilles de la Tourette GWAS Replication Initiative, the Tourette International Collaborative Genetics Study, and the Psychiatric Genomics Consortium Tourette Syndrome Working Group, Child Psychiatry, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

ObjectiveTourette's syndrome is polygenic and highly heritable. Genome-wide association study (GWAS) approaches are useful for interrogating the genetic architecture and determinants of Tourette's syndrome and other tic disorders. The authors conducted a GWAS meta-analysis and probed aggregated Tourette's syndrome polygenic risk to test whether Tourette's and related tic disorders have an underlying shared genetic etiology and whether Tourette's polygenic risk scores correlate with worst-ever tic severity and may represent a potential predictor of disease severity.MethodsGWAS meta-analysis, gene-based association, and genetic enrichment analyses were conducted in 4,819 Tourette's syndrome case subjects and 9,488 control subjects. Replication of top loci was conducted in an independent population-based sample (706 case subjects, 6,068 control subjects). Relationships between Tourette's polygenic risk scores (PRSs), other tic disorders, ascertainment, and tic severity were examined.ResultsGWAS and gene-based analyses identified one genome-wide significant locus within FLT3 on chromosome 13, rs2504235, although this association was not replicated in the population-based sample. Genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette's syndrome heritability. Tourette's-associated genes were significantly preferentially expressed in dorsolateral prefrontal cortex. Tourette's PRS significantly predicted both Tourette's syndrome and tic spectrum disorders status in the population-based sample. Tourette's PRS also significantly correlated with worst-ever tic severity and was higher in case subjects with a family history of tics than in simplex case subjects.ConclusionsModulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette's syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette's syndrome and other tic disorders in future diagnostic schemata. Tourette's PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity.

Published
2019

7. A Functional Neuroanatomy of Tics in Tourette Syndrome

Author

Stern, Emily, primary, Silbersweig, David A., additional, Chee, Kit-Yun, additional, Holmes, Andrew, additional, Robertson, Mary M., additional, Trimble, Michael, additional, Frith, Christopher D., additional, Frackowiak, Richard S. J., additional, and Dolan, Raymond J., additional

Published
2022
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8. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome.

Author

Hirschtritt, Matthew E, Lee, Paul C, Pauls, David L, Dion, Yves, Grados, Marco A, Illmann, Cornelia, King, Robert A, Sandor, Paul, McMahon, William M, Lyon, Gholson J, Cath, Danielle C, Kurlan, Roger, Robertson, Mary M, Osiecki, Lisa, Scharf, Jeremiah M, Mathews, Carol A, and Tourette Syndrome Association International Consortium for Genetics

Subjects
Tourette Syndrome Association International Consortium for Genetics, Humans, Tourette Syndrome, Prevalence, Risk Factors, Mental Disorders, Age Factors, Age of Onset, Comorbidity, Age Distribution, Adolescent, Child, Child, Preschool, Canada, United States, Netherlands, Female, Male, Young Adult, United Kingdom, Brain Disorders, Neurodegenerative, Clinical Research, Anxiety Disorders, Behavioral and Social Science, Serious Mental Illness, Genetics, Attention Deficit Hyperactivity Disorder (ADHD), Pediatric, Neurosciences, Prevention, Mental Health, Aetiology, 2.3 Psychological, social and economic factors, Mental health, Other Medical and Health Sciences, Psychology, Cognitive Sciences
Abstract

ImportanceTourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (

Published
2015

9. Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study

Author

McGrath, Lauren M, Yu, Dongmei, Marshall, Christian, Davis, Lea K, Thiruvahindrapuram, Bhooma, Li, Bingbin, Cappi, Carolina, Gerber, Gloria, Wolf, Aaron, Schroeder, Frederick A, Osiecki, Lisa, O'Dushlaine, Colm, Kirby, Andrew, Illmann, Cornelia, Haddad, Stephen, Gallagher, Patience, Fagerness, Jesen A, Barr, Cathy L, Bellodi, Laura, Benarroch, Fortu, Bienvenu, O Joseph, Black, Donald W, Bloch, Michael H, Bruun, Ruth D, Budman, Cathy L, Camarena, Beatriz, Cath, Danielle C, Cavallini, Maria C, Chouinard, Sylvain, Coric, Vladimir, Cullen, Bernadette, Delorme, Richard, Denys, Damiaan, Derks, Eske M, Dion, Yves, Rosário, Maria C, Eapen, Valsama, Evans, Patrick, Falkai, Peter, Fernandez, Thomas V, Garrido, Helena, Geller, Daniel, Grabe, Hans J, Grados, Marco A, Greenberg, Benjamin D, Gross-Tsur, Varda, Grünblatt, Edna, Heiman, Gary A, Hemmings, Sian MJ, Herrera, Luis D, Hounie, Ana G, Jankovic, Joseph, Kennedy, James L, King, Robert A, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F, Lennertz, Leonhard, Lochner, Christine, Lowe, Thomas L, Lyon, Gholson J, Macciardi, Fabio, Maier, Wolfgang, McCracken, James T, McMahon, William, Murphy, Dennis L, Naarden, Allan L, Neale, Benjamin M, Nurmi, Erika, Pakstis, Andrew J, Pato, Michele T, Pato, Carlos N, Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Reus, Victor I, Richter, Margaret A, Riddle, Mark, Robertson, Mary M, Rosenberg, David, Rouleau, Guy A, Ruhrmann, Stephan, Sampaio, Aline S, Samuels, Jack, Sandor, Paul, Sheppard, Brooke, Singer, Harvey S, Smit, Jan H, Stein, Dan J, Tischfield, Jay A, Vallada, Homero, Veenstra-VanderWeele, Jeremy, Walitza, Susanne, Wang, Ying, Wendland, Jens R, Shugart, Yin Yao, Miguel, Euripedes C, Nicolini, Humberto, and Oostra, Ben A

Subjects
Human Genome, Genetics, Brain Disorders, Serious Mental Illness, Neurodegenerative, Mental Health, Tourette Syndrome, Neurosciences, Intellectual and Developmental Disabilities (IDD), Aetiology, 2.1 Biological and endogenous factors, Mental health, Adolescent, DNA Copy Number Variations, Diagnostic and Statistical Manual of Mental Disorders, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Obsessive-Compulsive Disorder, Polymorphism, Single Nucleotide, Tourette syndrome, obsessive-compulsive disorder, copy number variation, genetics, 16p13.11, Medical and Health Sciences, Psychology and Cognitive Sciences, Developmental & Child Psychology
Abstract

ObjectiveObsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (

Published
2014

10. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

Author

Abdulkadir, Mohamed, Arbelaez, Juan, Bodmer, Benjamin, Bromberg, Yana, Brown, Lawrence W., Cheon, Keun-Ah, Coffey, Barbara J., Deng, Li, Dietrich, Andrea, Dong, Shan, Duhn, Clif, Elzerman, Lonneke, Fernandez, Thomas V., Fremer, Carolin, Garcia-Delgar, Blanca, Gilbert, Donald L., Grice, Dorothy E., Hagstrøm, Julie, Hedderly, Tammy, Heiman, Gary A., Heyman, Isobel, Hoekstra, Pieter J., Hong, Hyun Ju, Huyser, Chaim, Kim, Eun-Joo, Kim, Young Key, Kim, Young-Shin, King, Robert A., Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett L, Ludolph, Andrea G., Madruga-Garrido, Marcos, Mandell, Jeffrey D., Maras, Athanasios, Mir, Pablo, Morer, Astrid, Morris, Montana T, Müller-Vahl, Kirsten, Münchau, Alexander, Murphy, Tara L., Nasello, Cara, Plessen, Kerstin J., Poisner, Hannah, Roessner, Veit, Sanders, Stephan J., Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, State, Matthew W., Sun, Nawei, Thackray, Joshua K., Tischfield, Jay A., Tübing, Jennifer, Visscher, Frank, Wanderer, Sina, Wang, Sheng, Willsey, A Jeremy, Woods, Martin, Xing, Jinchuan, Zhang, Yeting, Zhao, Xin, Zinner, Samuel H., Androutsos, Christos, Barta, Csaba, Farkas, Luca, Fichna, Jakub, Georgitsi, Marianthi, Janik, Piotr, Karagiannidis, Iordanis, Koumoula, Anastasia, Nagy, Peter, Paschou, Peristera, Puchala, Joanna, Rizzo, Renata, Szejko, Natalia, Szymanska, Urszula, Tarnok, Zsanett, Tsironi, Vaia, Wolanczyk, Tomasz, Zekanowski, Cezary, Barr, Cathy L., Batterson, James R., Berlin, Cheston, Bruun, Ruth D., Budman, Cathy L., Cath, Danielle C., Chouinard, Sylvain, Coppola, Giovanni, Cox, Nancy J., Darrow, Sabrina, Davis, Lea K., Dion, Yves, Freimer, Nelson B., Grados, Marco A., Hirschtritt, Matthew E., Huang, Alden Y., Illmann, Cornelia, Kurlan, Roger, Leckman, James F., Lyon, Gholson J., Malaty, Irene A., Mathews, Carol A., MacMahon, William M., Neale, Benjamin M., Okun, Michael S., Osiecki, Lisa, Pauls, David L., Posthuma, Danielle, Ramensky, Vasily, Robertson, Mary M., Rouleau, Guy A., Sandor, Paul, Scharf, Jeremiah M., Singer, Harvey S., Smit, Jan, Sul, Jae-Hoon, Yu, Dongmei, Kumar, Yogesh, Morris, Montana T., Yang, Zhiyu, Padmanabhuni, Shanmukha S., Khalifa, Najah, Dahl, Niklas, Buxbaum, Joseph D., De Rubeis, Silvia, and Willsey, A. Jeremy

Published
2018
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11. Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

Author

Davis, Lea K, Yu, Dongmei, Keenan, Clare L, Gamazon, Eric R, Konkashbaev, Anuar I, Derks, Eske M, Neale, Benjamin M, Yang, Jian, Lee, S. Hong, Evans, Patrick, Barr, Cathy L, Bellodi, Laura, Benarroch, Fortu, Berrio, Gabriel Bedoya, Bienvenu, Oscar J, Bloch, Michael H, Blom, Rianne M, Bruun, Ruth D, Budman, Cathy L, Camarena, Beatriz, Campbell, Desmond, Cappi, Carolina, Cardona Silgado, Julio C, Cath, Danielle C, Cavallini, Maria C, Chavira, Denise A, Chouinard, Sylvain, Conti, David V, Cook, Edwin H, Coric, Vladimir, Cullen, Bernadette A, Deforce, Dieter, Delorme, Richard, Dion, Yves, Edlund, Christopher K, Egberts, Karin, Falkai, Peter, Fernandez, Thomas V, Gallagher, Patience J, Garrido, Helena, Geller, Daniel, Girard, Simon L, Grabe, Hans J, Grados, Marco A, Greenberg, Benjamin D, Gross-Tsur, Varda, Haddad, Stephen, Heiman, Gary A, Hemmings, Sian M. J, Hounie, Ana G, Illmann, Cornelia, Jankovic, Joseph, Jenike, Michael A, Kennedy, James L, King, Robert A, Kremeyer, Barbara, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F, Lennertz, Leonhard, Liu, Chunyu, Lochner, Christine, Lowe, Thomas L, Macciardi, Fabio, McCracken, James T, McGrath, Lauren M, Mesa Restrepo, Sandra C, Moessner, Rainald, Morgan, Jubel, Muller, Heike, Murphy, Dennis L, Naarden, Allan L, Ochoa, William Cornejo, Ophoff, Roel A, Osiecki, Lisa, Pakstis, Andrew J, Pato, Michele T, Pato, Carlos N, Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Rauch, Scott L, Renner, Tobias J, Reus, Victor I, Richter, Margaret A, Riddle, Mark A, Robertson, Mary M, Romero, Roxana, Rosàrio, Maria C, Rosenberg, David, Rouleau, Guy A, Ruhrmann, Stephan, Ruiz-Linares, Andres, Sampaio, Aline S, Samuels, Jack, Sandor, Paul, Sheppard, Brooke, Singer, Harvey S, and Smit, Jan H

Subjects
Missing Heritability, Tic Disorders, Neuropsychiatric Disorders, Complex Diseases, Common Snps, Gilles, Family, Brain, Expression, Autism
Published
2013

12. De Novo Coding Variants Are Strongly Associated with Tourette Disorder

Author

Willsey, A. Jeremy, Fernandez, Thomas V., Yu, Dongmei, King, Robert A., Dietrich, Andrea, Xing, Jinchuan, Sanders, Stephan J., Mandell, Jeffrey D., Huang, Alden Y., Richer, Petra, Smith, Louw, Dong, Shan, Samocha, Kaitlin E., Neale, Benjamin M., Coppola, Giovanni, Mathews, Carol A., Tischfield, Jay A., Scharf, Jeremiah M., State, Matthew W., Heiman, Gary A., Abdulkadir, Mohamed, Bohnenpoll, Julia, Bromberg, Yana, Brown, Lawrence W., Cheon, Keun-Ah, Coffey, Barbara J., Deng, Li, Elzerman, Lonneke, Fründt, Odette, Garcia-Delgar, Blanca, Gedvilaite, Erika, Gilbert, Donald L., Grice, Dorothy E., Hagstrøm, Julie, Hedderly, Tammy, Heyman, Isobel, Hoekstra, Pieter J., Hong, Hyun Ju, Huyser, Chaim, Ibanez-Gomez, Laura, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Lamerz, Andreas, Leventhal, Bennett, Ludolph, Andrea G., Lühr da Silva, Claudia, Madruga-Garrido, Marcos, Maras, Athanasios, Mir, Pablo, Morer, Astrid, Münchau, Alexander, Murphy, Tara L., Nasello, Cara, Openneer, Thaïra J.C., Plessen, Kerstin J., Roessner, Veit, Sanders, Stephan, Shin, Eun-Young, Sival, Deborah A., Song, Dong-Ho, Song, Jungeun, Stolte, Anne Marie, Sun, Nawei, Tübing, Jennifer, Visscher, Frank, Walker, Michael F., Wanderer, Sina, Wang, Shuoguo, Woods, Martin, Zhang, Yeting, Zhou, Anbo, Zinner, Samuel H., Barr, Cathy L., Batterson, James R., Berlin, Cheston, Bruun, Ruth D., Budman, Cathy L., Cath, Danielle C., Chouinard, Sylvain, Cox, Nancy J., Darrow, Sabrina, Davis, Lea K., Dion, Yves, Freimer, Nelson B., Grados, Marco A., Hirschtritt, Matthew E., Illmann, Cornelia, Kurlan, Roger, Leckman, James F., Lyon, Gholson J., Malaty, Irene A., MaMahon, William M., Okun, Michael S., Osiecki, Lisa, Pauls, David L., Posthuma, Danielle, Ramensky, Vasily, Robertson, Mary M., Rouleau, Guy A., Sandor, Paul, Singer, Harvey S., Smit, Jan, and Sul, Jae-Hoon

Published
2017
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17. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Author

Jain, Pritesh, Miller-Fleming, Tyne, Topaloudi, Apostolia, Yu, Dongmei, Drineas, Petros, Georgitsi, Marianthi, Yang, Zhiyu, Rizzo, Renata, Müller-Vahl, Kirsten R., Tumer, Zeynep, Mol Debes, Nanette, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Mir, Pablo, Cath, Danielle C., Boomsma, Dorret I., Roessner, Veit, Wolanczyk, Tomasz, Janik, Piotr, Szejko, Natalia, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Benaroya-Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Morer, Astrid, Mueller, Norbert, Munchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Walitza, Susanne, Schrag, Anette, Martino, Davide, Dietrich, Andrea, Mathews, Carol A., Scharf, Jeremiah M., Hoekstra, Pieter J., Davis, Lea K., Paschou, Peristera, Als, Thomas D., Aschauer, Harald, Atzmon, Gil, Bækvad-Hansen, Matie, Barr, Cathy L., Barzilai, Nir, Batterson, James R., Batterson, Robert, Benarroch, Fortu, Berlin, Cheston, Boberg, Julia, Bodmer, Benjamin, Bohnenpoll, Julia, Børglum, Anders D., Brown, Lawrence W., Bruun, Ruth, Budman, Cathy L., Buckner, Randy L., Bybjerg-Grauholm, Jonas, Cheon, Keun-Ah, Chouinard, Sylvain, Coffey, Barbara J., Coppola, Giovanni, Crowley, James J., Dahl, Niklas, Darrow, Sabrina M., Daly, Mark J., De Rubeis, Silvia, Dion, Yves, Djurfeldt, Diana R., Domenech-Salgado, Laura, Eapen, Valsamma, Elzerman, Lonneke, Fernandez, Thomas V., Freimer Carolin Fremer, Nelson B., Garcia-Delgar, Blanca, Garrido, Marcos, Gilbert, Donald L., Giusti-Rodriguez, Paola, Grados, Marco, Greenberg, Erica, Grove, Jakob, Hagstrom, Julie, Halvorsen, Matt, Hansen, Bjarne, Haavik, Jan, Hebebrand, Johannes, Heiman, Gary A., Herrera, Luis, Hinney, Anke, Hirschtritt, Matthew E., Sul, Jae Hoon, Hong, Hyun Ju, Hougaard, David M., Huang, Alden Y., Ibanez-Gomez, Laura, Ivankovic, Franjo, Jankovic, Joseph, Karlsson, Elinor K., Kaprio, Jakko A., Kim, Young Key, Kim, Young-Shin, King, Robert A., Knowles, James A., Koh, Yun-Joo, Kook, Sodham, Khalifa, Najah, Konstantinidis, Anastasios, Kuperman, Samuel, Kurlan, Roger, Kvale, Gerd, Leckman, James, Lee, Paul C., Leventhal, Bennett, Lichtenstein, Paul, Lindbald-Toh, Kerstin, Lowe, Thomas, Ludolph, Andrea, da Silva, Claudia Luhrs, Luðvigsson, Pétur, Luykx, Jurjen, Lyon, Gholson J., Mahjani, Behrang, Maras, Athanasios, Mataix-Cols, David, Mattheisen, Manuel, Malaty, Irene A., McMahon, William M., McQuillin, Andrew, Meier, Sandra M., Moessner, Rainald, Mortensen, Preben B., Mors, Ole, Mudgal, Poorva, Nagy, Peter, Naarden, Allan, Neale, Benjamin M., Nawaz, Muhammad S., Nissen, Judith Becker, Nöthen Merete Nordentoft, Markus M., Nordsletten, Ashley E., Okun, Michael S., Ophoff, Roel, Osiecki, Lisa, Palotie, Aarno, Palviainen, Teemu P., Pato Michele T. Pato, Carlos N., Pittenger, Christopher, Pollak, Yehuda, Posthuma, Danielle, Ramos, Eliana, Reichert, Jennifer, Robertson, Mary M., Roffman, Joshua L., Rouleau, Guy, Rück, Christian, Sæmundsen, Evald, Samuels, Jack, Sandin, Sven, Sandor, Paul, Schlögelhofer, Monika, Shin, Eun-Young, Singer, Harvey S., Smit, Jan, Smoller, Jordan W., State, Matthew, Solem, Stian, Song, Dong-Ho, Song, Jungeun, Stamenkovic, Mara, Stefansson, Kári, Strom, Nora, Stuhrmann, Manfred, Szatkiewicz, Jin, Szymanska, Urszula, Tischfield, Jay A., Tsetsos, Fotis, Thorarensen, Ólafur, Tubing, Jennifer, Visscher, Frank, Wagner, Michael, Wanderer, Sina, Wang, Sheng, Werge, Thomas, Willsey, Jeremy A., Wolancyk, Tomasz, Woods, Douglas W., Woods, Martin, Zelaya, Ivette, Zinner, Samuel H., Apter, Alan, Ball, Juliane, Bognar, Emese, Buse, Judith, Vela, Marta Correa, Fremer, Carolin, Gulisano, Mariangela, Hagen, Annelieke, Hagstrøm, Julie, Madruga-Garrido, Marcos, Pellico, Alessandra, Ruhrman, Daphna, Schnell, Jaana, Silvestri, Paola Rosaria, Skov, Liselotte, Steinberg, Tamar, Gloor, Friederike Tagwerker, Turner, Victoria L., Weidinger, Elif, Alexander, John, Aranyi, Tamas, Buisman, Wim R., Buitelaar, Jan K., Driessen, Nicole, Fan, Siyan, Forde, Natalie J., Gerasch, Sarah, van den Heuvel, Odile A., Jespersgaard, Cathrine, Kanaan, Ahmad S., Möller, Harald E., Nespoli, Ester, Pagliaroli, Luca, Poelmans, Geert, Pouwels, Petra J. W., Rizzo, Francesca, Veltman, Dick J., van der Werf, Ysbrand D., Widomska, Joanna, Zilhäo, Nuno R., Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Dynamic Earth and Resources, and Clinical Cognitive Neuropsychiatry Research Program (CCNP)

Subjects
Male, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Medizin, Autism Spectrum Disorder/genetics, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Diabetes Mellitus, Type 2, Risk Factors, Diabetes Mellitus, Tourette Syndrome/genetics, Humans, Female, Attention Deficit Disorder with Hyperactivity/genetics, Type 2, Biological Psychiatry
Abstract

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders. Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.

Published
2023
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18. Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome

Author

Tsetsos, Fotis, primary, Topaloudi, Apostolia, additional, Jain, Pritesh, additional, Yang, Zhiyu, additional, Yu, Dongmei, additional, Kolovos, Petros, additional, Tumer, Zeynep, additional, Rizzo, Renata, additional, Hartmann, Andreas, additional, Depienne, Christel, additional, Worbe, Yulia, additional, Müller-Vahl, Kirsten R., additional, Cath, Danielle C., additional, Boomsma, Dorret I., additional, Wolanczyk, Tomasz, additional, Zekanowski, Cezary, additional, Barta, Csaba, additional, Nemoda, Zsofia, additional, Tarnok, Zsanett, additional, Padmanabhuni, Shanmukha S., additional, Buxbaum, Joseph D., additional, Grice, Dorothy, additional, Glennon, Jeffrey, additional, Stefansson, Hreinn, additional, Hengerer, Bastian, additional, Yannaki, Evangelia, additional, Stamatoyannopoulos, John A., additional, Benaroya-Milshtein, Noa, additional, Cardona, Francesco, additional, Hedderly, Tammy, additional, Heyman, Isobel, additional, Huyser, Chaim, additional, Mir, Pablo, additional, Morer, Astrid, additional, Mueller, Norbert, additional, Munchau, Alexander, additional, Plessen, Kerstin J., additional, Porcelli, Cesare, additional, Roessner, Veit, additional, Walitza, Susanne, additional, Schrag, Anette, additional, Martino, Davide, additional, Tischfield, Jay A., additional, Heiman, Gary A., additional, Willsey, A. Jeremy, additional, Dietrich, Andrea, additional, Davis, Lea K., additional, Crowley, James J., additional, Mathews, Carol A., additional, Scharf, Jeremiah M., additional, Georgitsi, Marianthi, additional, Hoekstra, Pieter J., additional, Paschou, Peristera, additional, Barr, Cathy L., additional, Batterson, James R., additional, Berlin, Cheston, additional, Budman, Cathy L., additional, Coppola, Giovanni, additional, Cox, Nancy J., additional, Darrow, Sabrina, additional, Dion, Yves, additional, Freimer, Nelson B., additional, Grados, Marco A., additional, Greenberg, Erica, additional, Hirschtritt, Matthew E., additional, Huang, Alden Y., additional, Illmann, Cornelia, additional, King, Robert A., additional, Kurlan, Roger, additional, Leckman, James F., additional, Lyon, Gholson J., additional, Malaty, Irene A., additional, McMahon, William M., additional, Neale, Benjamin M., additional, Okun, Michael S., additional, Osiecki, Lisa, additional, Robertson, Mary M., additional, Rouleau, Guy A., additional, Sandor, Paul, additional, Singer, Harvey S., additional, Smit, Jan H., additional, Sul, Jae Hoon, additional, Androutsos, Christos, additional, Basha, Entela, additional, Farkas, Luca, additional, Fichna, Jakub, additional, Janik, Piotr, additional, Kapisyzi, Mira, additional, Karagiannidis, Iordanis, additional, Koumoula, Anastasia, additional, Nagy, Peter, additional, Puchala, Joanna, additional, Szejko, Natalia, additional, Szymanska, Urszula, additional, Tsironi, Vaia, additional, Apter, Alan, additional, Ball, Juliane, additional, Bodmer, Benjamin, additional, Bognar, Emese, additional, Buse, Judith, additional, Vela, Marta Correa, additional, Fremer, Carolin, additional, Garcia-Delgar, Blanca, additional, Gulisano, Mariangela, additional, Hagen, Annelieke, additional, Hagstrøm, Julie, additional, Madruga-Garrido, Marcos, additional, Pellico, Alessandra, additional, Ruhrman, Daphna, additional, Schnell, Jaana, additional, Silvestri, Paola Rosaria, additional, Skov, Liselotte, additional, Steinberg, Tamar, additional, Gloor, Friederike Tagwerker, additional, Turner, Victoria L., additional, Weidinger, Elif, additional, Alexander, John, additional, Aranyi, Tamas, additional, Buisman, Wim R., additional, Buitelaar, Jan K., additional, Driessen, Nicole, additional, Drineas, Petros, additional, Fan, Siyan, additional, Forde, Natalie J., additional, Gerasch, Sarah, additional, van den Heuvel, Odile A., additional, Jespersgaard, Cathrine, additional, Kanaan, Ahmad S., additional, Möller, Harald E., additional, Nawaz, Muhammad S., additional, Nespoli, Ester, additional, Pagliaroli, Luca, additional, Poelmans, Geert, additional, Pouwels, Petra J.W., additional, Rizzo, Francesca, additional, Veltman, Dick J., additional, van der Werf, Ysbrand D., additional, Widomska, Joanna, additional, Zilhäo, Nuno R., additional, Brown, Lawrence W., additional, Cheon, Keun-Ah, additional, Coffey, Barbara J., additional, Fernandez, Thomas V., additional, Gilbert, Donald L., additional, Hong, Hyun Ju, additional, Ibanez-Gomez, Laura, additional, Kim, Eun-Joo, additional, Kim, Young Key, additional, Kim, Young-Shin, additional, Koh, Yun-Joo, additional, Kook, Sodahm, additional, Kuperman, Samuel, additional, Leventhal, Bennett L., additional, Maras, Athanasios, additional, Murphy, Tara L., additional, Shin, Eun-Young, additional, Song, Dong-Ho, additional, Song, Jungeun, additional, State, Matthew W., additional, Visscher, Frank, additional, Wang, Sheng, additional, and Zinner, Samuel H., additional

Published
2023
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20. List of Contributors

Author

Acquaviva, Eric, primary, Barrett, Elizabeth, additional, Benarous, Xavier, additional, Berg, Astrid, additional, Bonvanie, Irma J., additional, Brown, Rebecca C., additional, de Vries, Petrus J., additional, Dominguez, Mari, additional, Eapen, Valsamma, additional, Ellul, Pierre, additional, Essau, Cecilia A., additional, Fegert, Joerg M., additional, Garralda, Elena M., additional, Goetz, Michal, additional, Haemmerle, Patrick, additional, Harper, Gordon, additional, Hodes, Matthew, additional, Hunt, Xanthe, additional, Jacobs, Brian W., additional, Klasen, Henrikje, additional, Koydemir, Selda, additional, Lachman, Anusha, additional, Malhotra, Savita, additional, Malik, Salma, additional, Malik, Sasha, additional, Mayordomo-Aranda, Angels, additional, Mohaplova, Marketa, additional, Namerow, Lisa, additional, Novak, Tomas, additional, Rask, Charlotte Ulrikka, additional, Remschmidt, Helmut, additional, Robertson, Mary M., additional, Robertson, Paul, additional, Sebela, Antonin, additional, Shah, Ruchita, additional, Shur-Fen Gau, Susan, additional, Šnircová, Eva, additional, Sönmez, Ekin, additional, Sukale, Thorsten, additional, Tomlinson, Mark, additional, Vašková, Lucia, additional, Voges, Juané, additional, Walker, Sophia A., additional, and Walter, Amelia, additional

Published
2018
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22. Tourette's Syndrome: Performance on Tests of Behavioural Inhibition, Working Memory and Gambling

Author

Crawford, Sarah, Channon, Shelley, and Robertson, Mary M.

Abstract

Background: Tourette's syndrome (TS) is a neurodevelopmental disorder associated with fronto-striatal dysfunction. There is debate as to the extent to which TS is associated with cognitive impairment. Some authors argue that any impairments seen are attributable to comorbid psychiatric symptomatology, whilst others have suggested that uncomplicated TS is associated with mild deficits limited primarily to inhibitory processes. The present study was designed to examine this issue using carefully screened participants with TS and experimental measures thought to involve different areas of the frontal lobes. Methods: Adolescents with TS who were screened for comorbid psychiatric disorder were compared with a healthy control group on a set of executive measures. Two tasks involving behavioural inhibition were used: a Sentence Completion task in which sentences had to be completed first with straightforward and then with nonsensical endings, and a Flanker task in which a central stimulus was surrounded by either compatible or incompatible flankers. Working memory was assessed using an N-back task, and reward learning was assessed using a Gambling task. Both accuracy and reaction times were measured for each task. Results: The TS group differed significantly from the control group on both the Sentence Completion task and on the Flanker task. On the Sentence Completion task, they were slower to make both sensible and nonsensical completions, and they had higher error scores on the nonsensical completions. On the Flanker task, the TS participants were less accurate than the control group, since they were poorer on the incompatible but not the compatible trials. A similar interaction with trial type was found for speed, where the TS participants were slowed more by the incompatible versus compatible trials, although overall their performance tended to be faster than the controls. The TS group did not differ significantly from the control group on measures of working memory or reward learning. Conclusions: The findings provide further evidence that uncomplicated TS is not associated with widespread executive impairments. However, it was not clear that any differences between the groups could be attributed solely to selective inhibitory impairment.

Published
2005
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23. Social Cognition in Tourette's Syndrome: Intact Theory of Mind and Impaired Inhibitory Functioning

Author

Channon, Shelley, Sinclair, Elizabeth, Waller, Denise, Healey, Louise, and Robertson, Mary M.

Abstract

Although associations between social cognition involving theory of mind and non-social executive skills have frequently been reported, dissociations in performance have also been found. The present study was designed to examine social and non-social cognition in uncomplicated Tourette Syndrome (TS). Adult TS participants without comorbid diagnoses were compared to matched healthy control participants on social cognition measures involving theory of mind and empathy, and on non-social executive tasks. Participants with TS were found to make more errors than a matched control group on an inhibitory task, but did not differ on other executive measures or on the social cognition measures. The implications of the findings for our understanding of TS and of the relationship between social cognition and executive skills are discussed.

Published
2004
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26. Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

Author

Claudio-Campos, Karla, Stevens, Daniel, Koo, Sang-Wahn, Valko, Alexa, Bienvenu, Oscar Joseph, Budman, Cathy B, Cath, Danielle C, Darrow, Sabrina, Geller, Daniel, Goes, Fernando S, Grados, Marco A, Greenberg, Benjamin D, Greenberg, Erica, Hirschtritt, Matthew E, Illmann, Cornelia, Ivankovic, Franjo, King, Robert A, Knowles, James A, Krasnow, Janice, Lee, Paul C, Lyon, Gholson J, McCracken, James T, Robertson, Mary M, Osiecki, Lisa, Riddle, Mark A, Rouleau, Guy, Sandor, Paul, Nestadt, Gerald, Samuels, Jack, Scharf, Jeremiah M, Mathews, Carol A, and Tourette Association of America International Consortium for Genetics (TAAICG) and the OCD Collaborative Genetics Association Study (OCGAS)

Subjects
Obsessive-Compulsive Disorder, analysis, Clinical Sciences, severity, Comorbidity, Neurodegenerative, Tourette Association of America International Consortium for Genetics (TAAICG) and the OCD Collaborative Genetics Association Study, chronic tics, Behavioral and Social Science, Humans, 2.1 Biological and endogenous factors, Aetiology, Neurology & Neurosurgery, Tourette, Neurosciences, meta&#8208, Human Movement and Sports Sciences, Serious Mental Illness, Anxiety Disorders, Brain Disorders, meta-analysis, Mental Health, Attention Deficit Disorder with Hyperactivity, Tic Disorders, Tics, Tourette Syndrome
Abstract

BackgroundPersistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation.ObjectiveThe goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT.MethodsWe analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature.ResultsRates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates.ConclusionsOur findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Published
2021

31. Tics, twitches, tales: the experiences of Gilles de la Tourette's syndrome

Author

Turtle, Lance and Robertson, Mary M.

Subjects
Tourette's syndrome -- Social aspects, Tourette's syndrome -- Diagnosis, Medical literature -- Research, Tic disorders -- Research, Health, Psychology and mental health
Abstract

Gilles de la Tourette's syndrome (GTS) is well described and although many clinicians are aware of the condition, misunderstandings about the disorder still persist. There have been few accounts of the experiences of people with GTS, and none from affected medical practitioners. The first personal account in the medical literature was over 25 years ago. This is the first personal account of having GTS written by a practicing physician. The sensation of having a tic is a peculiar one and is difficult to describe to those who have not experienced them for themselves. Tics are distinctly voluntary, though not wanted. The desire to tic stems from the relief of a physical sensation (that is distinct from a conventional somatic sensation) that builds up prior to the tic and is relieved by it. However, akin to scratching a mosquito bite, tics lead to more tics. The sensation leading to the tic is paradoxically relieved yet restimulated by the tic itself. The effect of GTS on a personal life story is recounted, and the condition briefly reviewed. Keywords: Tourette, Gilles de la Tourette's syndrome

Published
2008

45. Synaptic processes and immune-related pathways implicated in Tourette Syndrome

Author

Tsetsos, Fotis, primary, Yu, Dongmei, additional, Sul, Jae Hoon, additional, Huang, Alden Y., additional, Illmann, Cornelia, additional, Osiecki, Lisa, additional, Darrow, Sabrina M., additional, Hirschtritt, Matthew E., additional, Greenberg, Erica, additional, Muller-Vahl, Kirsten R., additional, Stuhrmann, Manfred, additional, Dion, Yves, additional, Rouleau, Guy A., additional, Aschauer, Harald, additional, Stamenkovic, Mara, additional, Schlögelhofer, Monika, additional, Sandor, Paul, additional, Barr, Cathy L., additional, Grados, Marco A., additional, Singer, Harvey S., additional, Nöthen, Markus M., additional, Hebebrand, Johannes, additional, Hinney, Anke, additional, King, Robert A., additional, Fernandez, Thomas V., additional, Barta, Csaba, additional, Tarnok, Zsanett, additional, Nagy, Peter, additional, Depienne, Christel, additional, Worbe, Yulia, additional, Hartmann, Andreas, additional, Budman, Cathy L., additional, Rizzo, Renata, additional, Lyon, Gholson J., additional, McMahon, William M., additional, Batterson, James R., additional, Cath, Danielle C., additional, Malaty, Irene A., additional, Okun, Michael S., additional, Berlin, Cheston, additional, Woods, Douglas W., additional, Lee, Paul C., additional, Jankovic, Joseph, additional, Robertson, Mary M., additional, Gilbert, Donald L., additional, Brown, Lawrence W., additional, Coffey, Barbara J., additional, Dietrich, Andrea, additional, Hoekstra, Pieter J., additional, Kuperman, Samuel, additional, Zinner, Samuel H., additional, Wagner, Michael, additional, Knowles, James A, additional, Willsey, A. Jeremy, additional, Tischfield, Jay A., additional, Heiman, Gary A., additional, Cox, Nancy J., additional, Freimer, Nelson B., additional, Neale, Benjamin M., additional, Davis, Lea K., additional, Coppola, Giovanni, additional, Mathews, Carol A., additional, Scharf, Jeremiah M., additional, and Paschou, Peristera, additional

Published
2020
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