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1. Yale Global Tic Severity Scale (YGTSS): Psychometric Quality of the Gold Standard for Tic Assessment Based on the Large-Scale EMTICS Study

Author

Martina Haas, Ewgeni Jakubovski, Carolin Fremer, Andrea Dietrich, Pieter J. Hoekstra, Burkard Jäger, Kirsten R. Müller-Vahl, The EMTICS Collaborative Group, Alan Apter, Valentina Baglioni, Juliane Ball, Noa Benaroya-Milshtein, Benjamin Bodmer, Emese Bognar, Bianka Burger, Judith Buse, Francesco Cardona, Marta Correa Vela, Nanette M. Debes, Maria Cristina Ferro, Blanca Garcia-Delgar, Mariangela Gulisano, Annelieke Hagen, Julie Hagstrøm, Tammy J. Hedderly, Isobel Heyman, Chaim Huyser, Marcos Madruga-Garrido, Anna Marotta, Davide Martino, Pablo Mir, Astrid Morer, Norbert Müller, Alexander Münchau, Peter Nagy, Valeria Neri, Thaïra J.C. Openneer, Alessandra Pellico, Ángela Periañez Vasco, Kerstin J. Plessen, Cesare Porcelli, Marina Redondo, Renata Rizzo, Veit Roessner, Daphna Ruhrman, Jaana M.L. Schnell, Anette Schrag, Paola Rosaria Silvestri, Liselotte Skov, Tamar Steinberg, Friederike Tagwerker Gloor, Zsanett Tarnok, Jennifer Tübing, Victoria L. Turner, Susanne Walitza, and Elif Weidinger

Subjects
Tourette's syndrome (TS), YGTSS = Yale Global Tic Severity Scale, psychometric properties, internal consistency, confirmatory factor analysis, Psychiatry, RC435-571
Abstract

The Yale Global Tic Severity Scale (YGTSS) is a clinician-rated instrument considered as the gold standard for assessing tics in patients with Tourette's Syndrome and other tic disorders. Previous psychometric investigations of the YGTSS exhibit different limitations such as small sample sizes and insufficient methods. To overcome these shortcomings, we used a subsample of the large-scale “European Multicentre Tics in Children Study” (EMTICS) including 706 children and adolescents with a chronic tic disorder and investigated convergent, discriminant and factorial validity, as well as internal consistency of the YGTSS. Our results confirm acceptable convergent and good to very good discriminant validity, respectively, indicated by a sufficiently high correlation of the YGTSS total tic score with the Clinical Global Impression Scale for tics (rs = 0.65) and only low to medium correlations with clinical severity ratings of attention deficit/hyperactivity symptoms (rs = 0.24), obsessive–compulsive symptoms (rs = 27) as well as internalizing symptoms (rs = 0.27). Internal consistency was found to be acceptable (Ω = 0.58 for YGTSS total tic score). A confirmatory factor analysis supports the concept of the two factors “motor tics” and “phonic tics,” but still demonstrated just a marginal model fit (root mean square error of approximation = 0.09 [0.08; 0.10], comparative fit index = 0.90, and Tucker Lewis index = 0.87). A subsequent analysis of local misspecifications revealed correlated measurement errors, suggesting opportunities for improvement regarding the item wording. In conclusion, our results indicate acceptable psychometric quality of the YGTSS. However, taking the wide use and importance of the YGTSS into account, our results suggest the need for further investigations and improvements of the YGTSS. In addition, our results show limitations of the global severity score as a sum score indicating that the separate use of the total tic score and the impairment rating is more beneficial.

Published
2021
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2. Vitamin D levels in children and adolescents with chronic tic disorders: a multicentre study

Author

Molly, Bond, Natalie, Moll, Alicia, Rosello, Rod, Bond, Jaana, Schnell, Bianka, Burger, Pieter, J Hoekstra, Andrea, Dietrich, Anette, Schrag, Eva, Kocovska, Martino, Davide, Norbert, Mueller, Markus, Schwarz, Ute-Christiane, Meier, EMTICS Collaborative Group: Alan Apter, Baglioni, Valentina, Juliane, Ball, Noa, Benaroya-Milshtein, Benjamin, Bodmer, Emese, Bognar, Judith, Buse, Cardona, Francesco Carmelo Giovanni, Marta Correa Vela, Nanette, M Debes, Maria Cristina Ferro, Carolin, Fremer, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Tammy, J Hedderly, Isobel, Heyman, Chaim, Huyser, Marcos, Madruga-Garrido, Anna, Marotta, Pablo, Mir, Astrid, Morer, Norbert, Müller, Kirsten, R Müller-Vahl, Alexander, Münchau, Peter, Nagy, Neri, Valeria, Thaïra Jc Openneer, Pellico, Alessandra, Ángela Periañez Vasco, Kerstin, J Plessen, Cesare, Porcelli, Marina, Redondo, Rizzo, Renata, Veit, Roessner, Daphna, Ruhrman, Jaana Ml Schnell, Silvestri, PAOLA ROSARIA, Liselotte, Skov, Tamar, Steinberg, Friederike Tagwerker Gloor, Zsanett, Tarnok, Jennifer, Tübing, Victoria, L Turner, Susanne, Walitza, Elif, Weidinger, Clinical Cognitive Neuropsychiatry Research Program (CCNP), EMTICS Collaborative Group, Bruun, J.E., Grejsen, J., Ommundsen, C.L., Rubæk, M., Enghardt, S., Bokemeyer, S., Driedger-Garbe, C., Reichert, C., Schmalfeld, J., Duffield, T., Gergye, F., Kovacs, M., Vidomusz, R., Carmel, M., Fennig, S., Gev, E., Keller, N., Michaelovsky, E., Nahon, M., Regev, C., Simcha, T., Smollan, G., Weizman, A., Gagliardi, G., Tallon, M., Roazzi, P., van den Ban, E., de Bruijn, SFTM, Driessen, N., Lamerz, A., Messchendorp, M., Rath, JJG, Sival, NSD, Tromp, N., Visscher, F., de la Tourettes, S.G., Cáceres, M.T., Carrillo, F., Gómez-Garre, P., Vargas, L., Gariup, M., Stöber, S., Apter, A., Baglioni, V., Ball, J., Benaroya-Milshtein, N., Bodmer, B., Bond, M., Bognar, E., Burger, B., Buse, J., Cardona, F., Vela, M.C., Dietrich, A., Debes, N.M., Ferro, M.C., Fremer, C., Garcia-Delgar, B., Gulisano, M., Hagen, A., Hagstrøm, J., Hedderly, T.J., Heyman, I., Hoekstra, P.J., Huyser, C., Madruga-Garrido, M., Marotta, A., Martino, D., Meier, U.C., Mir, P., Moll, N., Morer, A., Mueller, N., Müller-Vahl, K., Münchau, A., Nagy, P., Neri, V., Openneer, TJC, Pellico, A., Vasco, Á.P., Plessen, K.J., Porcelli, C., Redondo, M., Rizzo, R., Roessner, V., Ruhrman, D., Schnell, JML, Schrag, A., Schwarz, M.J., Silvestri, P.R., Skov, L., Steinberg, T., Gloor, F.T., Tarnok, Z., Tübing, J., Turner, V.L., Walitza, S., Weidinger, E., and Woods, M.L.

Subjects
Obsessive-Compulsive Disorder, Tic disorder, medicine.medical_specialty, Adolescent, Tics, Comorbidity, Severity of Illness Index, Pediatrics, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, Developmental and Educational Psychology, medicine, Child and adolescent psychiatry, Vitamin D and neurology, Humans, ADHD, Vitamin D, Child, OCD, business.industry, Tourette, Symptom severity, General Medicine, Attention Deficit Disorder with Hyperactivity/psychology, Cross-Sectional Studies, Obsessive-Compulsive Disorder/epidemiology, Obsessive-Compulsive Disorder/psychology, Tic Disorders/metabolism, Tic Disorders/psychology, Tics/complications, Tics/metabolism, Tourette Syndrome/psychology, Vitamin D/metabolism, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Attention Deficit Disorder with Hyperactivity, Tic Disorders, Pediatrics, Perinatology and Child Health, Cohort, CTD, business, 030217 neurology & neurosurgery, Tourette Syndrome
Abstract

This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3–16 years) with CTD (n = 327); first-degree relatives (3–10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27–3.42, p p = 0.01) and was inversely associated with ADHD symptom severity (β = − 2.52, 95% CI − 4.16–0.88, p

Published
2022

3. Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study

Author

Anette-Eleonore, Schrag, Martino, Davide, Hanyuying, Wang, Gareth, Ambler, Noa, Benaroya-Milstein, Maura, Buttiglione, Cardona, Francesco Carmelo Giovanni, Roberta, Creti, Androulla, Efstratiou, Tammy, Hedderly, Isobel, Heyman, Chaim, Huyser, Pablo, Mir, Astrid, Morer, Natalie, Moll, Norbert, E Müller, Kirsten, R Müller-Vahl, Kerstin, J Plessen, Cesare, Porcelli, Rizzo, Renata, Veit, Roessner, Markus, Schwarz, Zsanett, Tarnok, Susanne, Walitza, Andrea, Dietrich, Pieter, J Hoekstra Alan Apter, Baglioni, Valentina, Juliane, Ball, Noa, Benaroya-Milshtein, Benjamin, Bodmer, Emese, Bognar, Bianka, Burger, Judith, Buse, Marta Correa Vela, Nanette, M Debes, Maria Cristina Ferro, Carolin, Fremer, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Tammy, J Hedderly, Pieter, J Hoekstra, Marcos, Madruga-Garrido, Anna, Marotta, Norbert, Müller, Alexander, Münchau, Peter, Nagy, Neri, Valeria, Thaïra Jc Openneer, Pellico, Alessandra, Ángela Periañez Vasco, Marina, Redondo, Daphna, Ruhrman, Jaana Ml Schnell, Anette, Schrag, Silvestri, PAOLA ROSARIA, Liselotte, Skov, Tamar, Steinberg, Friederike Tagwerker Gloor, Jennifer, Tübing, Victoria, L Turner, and Elif, Weidinger

Subjects
Neuroimmunity, Neuroinflammation, Tic Disorders, Streptococcal infections
Published
2022

4. Clinical precursors of tics: an EMTICS study

Author

Openneer, Tha€ıra J. C., Chaim, Huyser, Martino, Davide, Anette, Schrag, Alan, Apter, Baglioni, Valentina, Juliane, Ball, Noa, Benaroya-Milshtein, Emese, Bognar, Bianka, Burger, Judith, Buse, Cardona, Francesco Carmelo Giovanni, 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, Marcos, Madruga-Garrido, Pablo, Mir, Astrid, Morer, Norbert, Müller, Kirsten, Müller-Vahl, Alexander, Münchau, Peter, Nagy, Neri, Valeria, Thaïra J, C Openneer, Pellico, Alessandra, Kerstin, J Plessen, Cesare, Porcelli, Rizzo, Renata, Veit, Roessner, Daphna, Ruhrman, Jaana M, L Schnell, Silvestri, PAOLA ROSARIA, Liselotte, Skov, Tamar, Steinberg, Friederike Tagwerker Gloor, Zsanett, Tarnok, Susanne, Walitza, Elif, Weidinger, Hoekstra, Pieter J., Child Psychiatry, Child and Adolescent Psychiatry & Psychosocial Care, ANS - Cellular & Molecular Mechanisms, and Clinical Cognitive Neuropsychiatry Research Program (CCNP)

Subjects
Male, sex differences, Pediatrics, Longitudinal study, SYMPTOMS, Autism Spectrum Disorder, Comorbidity, Logistic regression, Tourette syndrome, 0302 clinical medicine, Developmental and Educational Psychology, Obsessive compulsive scale, Spectrum disorder, Longitudinal Studies, Child, 05 social sciences, PSYCHIATRIC-DISORDERS, clinical precursors, PREVALENCE, Psychiatry and Mental health, Autism spectrum disorder, Child, Preschool, Compulsions, Tics, Female, Psychology, 050104 developmental & child psychology, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, conduct problems, 03 medical and health sciences, OBSESSIVE-COMPULSIVE SCALE, mental disorders, medicine, Humans, ADHD, 0501 psychology and cognitive sciences, tic onset, SPECTRUM DISORDER, TOURETTE-SYNDROME, medicine.disease, nervous system diseases, body regions, PSYCHOMETRIC PROPERTIES, SEVERITY, Attention Deficit Disorder with Hyperactivity, Tic Disorders, Pediatrics, Perinatology and Child Health, Selection operator, human activities, 030217 neurology & neurosurgery, DISRUPTIVE BEHAVIOR, Tourette Syndrome
Abstract

Background: Children with Tourette syndrome (TS) often have comorbid disorders, particularly attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). While subtle premorbid symptoms have been described in various psychiatric disorders, the presence of clinical precursors that may exist before the onset of tics is unknown. This longitudinal study aimed to find clinical precursors of tics by assessing a range of clinical characteristics prior to tic onset in comparison with children without onset of tics.Methods: A sample of 187 3- to 10-year-old first-degree unaffected relatives of children with TS were followed up to 7 years in the European Multicentre Tics in Children Study (EMTICS). We investigated whether clinical characteristics assessed at baseline predicted tic onset, comparing 126 children without tic onset to 61 children who developed tics. We used the least absolute shrinkage and selection operator (LASSO) method, a penalised logistic regression approach. We also explored sex differences and repeated our analyses in an age- and sex-matched subsample.Results: Children with tic onset were more frequently male (beta = -0.36), had higher baseline severity of conduct problems (beta = 0.23), autism spectrum disorder symptoms (ASD; beta = 0.08), compulsions (beta = 0.02) and emotional problems (beta = 0.03) compared to children without tic onset. Conduct and ASD problems were male-specific predictors, whereas severity of compulsions and oppositional (beta = 0.39) and emotional problems were female-specific predictors.Conclusion: This study supports the presence of clinical precursors prior to tic onset and highlights the need of sex-specific monitoring of children at risk of developing tics. This may aid in the earlier detection of tics, particularly in females. We moreover found that tics most often persisted one year after tic onset, in contrast to the common belief that tics are mostly transient.

Published
2021

5. Antibodies to neuronal surface proteins in Tourette Syndrome: Lack of evidence in a European paediatric cohort

Author

V. Baglioni, E. Coutinho, D.A. Menassa, M.P. Giannoccaro, L. Jacobson, M. Buttiglione, O. Petruzzelli, F. Cardona, A. Vincent, Zacharias Anastasiou, Alan Apter, Erika Bartolini, Noa Benaroya-Milshtein, Benjamin Bodmer, Emese Bognar, Bianka Burger, Marta Correa Vela, Roberta Creti, Andrea Dietrich, Nanette M. Debes, Androulla Efstratiou, Maria Cristina Ferro, Carolin Fremer, Blanca Garcia-Delgar, Maria Gariup, Marianthi Georgitsi, Mariangela Gulisano, Annelieke Hagen, Julie Hagstrøm, Tammy J. Hedderly, Isobel Heyman, Pieter J. Hoekstra, Chaim Huyser, Monica Imperi, Iordanis Karagiannidis, Giovanni Laviola, Simone Macri, Marcos Madruga-Garrido, Immaculada Margarit, Anna Marotta, Davide Martino, Ute C. Meier, Pablo Mir, Natalie Moll, Astrid Morer, Kirsten Müller-Vahl, Alexander Münchau, Peter Nagy, Valeria Neri, Thaïra J.C. Openneer, Graziella Orefici, Peristera Paschou, Alessandra Pellico, Cesare Porcelli, Marina Redondo, Renata Rizzo, Paolo Roazzi, Veit Roessner, Daphna Ruhrman, Jaana M.L. Schnell, Anette Schrag, Gregor A. Schütze, Markus J. Schwarz, Paola Rosaria Silvestri, Liselotte Skov, Tamar Steinberg, Sara Stöber, Marco Tallon, Zsanett Tarnok, Baglioni V., Coutinho E., Menassa D.A., Giannoccaro M.P., Jacobson L., Buttiglione M., Petruzzelli O., Cardona F., Vincent A., and Clinical Cognitive Neuropsychiatry Research Program (CCNP)

Subjects
0301 basic medicine, Male, Tics, Adolescent, DISORDERS, CNTNAP2, Immunology, Primary Cell Culture, CHILDREN, Hippocampal formation, Tourette syndrome, Hippocampus, Receptors, N-Methyl-D-Aspartate, Epitope, White People, Cohort Studies, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Antigen, medicine, Animals, Humans, Child, Autoantibodies, Neurons, antibodies to neuronal antigens, movement disorders, biology, RECEPTOR, Endocrine and Autonomic Systems, business.industry, Dentate gyrus, Autoantibody, Brain, Membrane Proteins, medicine.disease, Rats, Tourette Syndrome, Tic Disorders, Neurodevelopmental Disorders, Neuronal- Surface Antibodies, Antineuronal Antibodies, Voltage-Gated Potassium Channels Antibodies, CASPR2, NMDAR, 030104 developmental biology, nervous system, Child, Preschool, Dentate Gyrus, biology.protein, Female, Antibody, business, 030217 neurology & neurosurgery
Abstract

The EMTICS collaborative group: Anastasiou, Zacharias; Apter, Alan; Baglioni, Valentina; Bartolini, Erika; Benaroya-Milshtein, Noa; Bodmer, Benjamin; Bognar, Emese; Burger', Bianka; Buttiglione, Maura; Cardona, Francesco; Vela, Marta Correa; Creti, Roberta; Dietrich, Andrea; Debes, Nanette M.; Efstratiou, Androulla; Ferro, Maria Cristina; Fremer, Carolin; Garcia-Delgar, Blanca; Gariup, Maria; Georgitsi, Marianthi; Gulisano, Mariangela; Hagen, Annelieke; Hagstrom, Julie; Hedderly, Tammy J.; Heyman, Isobel; Hoekstra, Pieter J.; Huyser, Chaim; Imperi, Monica; Karagiannidis, Iordanis; Laviola, Giovanni; Macri, Simone; Madruga-Garrido, Marcos; Margarit, Immaculada; Marotta, Anna; Martino, Davide; Meier, Ute C.; Mir, Pablo; Mo, Natalie; More, Astrid; Mueller-Vahl, Kirsten; Muenchau, Alexander; Nagy, Peter; Neri, Valeria; Openneer, Thafra J. C.; Orefici, Graziella; Paschou, Peristera; Pellico, Alessandra; Petruzzelli, Onofrio; Porcelli, Cesare; Redondo, Marina; Rizzo, Renata; Roazzi, Paolo; Roessner, Veit; Ruhrman, Daphna; Schnell, Jaana M. L.; Schrag, Anette; Schutze, Gregor A.; Schwarz, Markus J.; Silvestri, Paola Rosaria; Skov, Liselotte; Steinberg, Tamar; Stober, Sara; Tallon, Marco; Tarnok, Zsanett, In Tourette Syndrome (TS) a role for autoantibodies directed against neuronal proteins has long been suspected, but so far results are still inconsistent. The aim of this study was to look for antibodies to specific or undefined neuronal proteins that could be involved in the aetiology of the disease. Sera from children with Tourette Syndrome or another chronic tic disorder (TS/TD), collected as part of the longitudinal European Multicenter Tics in Children Study, were investigated. Participants included 30 siblings of patients with TS/TD prior to developing tics (preclinical stage) and the same children after the first tic onset (onset), and 158 patients in the chronic phase undergoing an acute relapse (exacerbation). Presence of antibodies binding to rodent brain tissue was assessed by immunohistology on rat brain sections and by immunofluorescent staining of live hippocampal neurons. Live cell-based assays were used to screen for antibodies to NMDAR, CASPR2, LGI1, AMPAR and GABAAR. Immunohistology indicated evidence of antibodies reactive with brain tissue, binding mainly to the hippocampus, the basal ganglia or the cerebellum in 26/218 (12%), with 8% of the preclinical or onset sera binding to the dentate gyrus/CA3 region or cerebellum. Only two individuals (one pre-clinical, one chronic) had antibodies binding the NMDAR and the binding was only weakly positive. No other specific antibodies were detected. Despite some immunoreactivity towards neuronal antigens on brain tissue, this was not mirrored by antibodies binding to live neurons, suggesting the presence of non-specific antibodies or those that bind non-pathogenic intracellular epitopes. NMDAR or the other neuronal surface antibodies tested were very infrequent in these patients. The evidence for pathogenic antibodies that could be causative of TS is weak.

Published
2019

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