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1. Genome-wide association study of Tourettes syndrome.

Author

Neale, B, Stewart, S, Fagerness, J, Evans, P, Gamazon, E, Edlund, C, Service, S, Tikhomirov, A, Osiecki, L, Illmann, C, Pluzhnikov, A, Konkashbaev, A, Davis, L, Han, B, Crane, J, Scharf, J, Yu, D, Rangel-Lugo, M, Chouinard, S, Dion, Y, Girard, S, Cath, D, Smit, J, King, R, Fernandez, T, Leckman, J, Kidd, K, Kidd, J, Pakstis, A, Herrera, L, Romero, R, Fournier, E, Sandor, P, Barr, C, Phan, N, Gross-Tsur, V, Benarroch, F, Pollak, Y, Budman, C, Bruun, R, Erenberg, G, Naarden, A, Lee, P, Weiss, N, Kremeyer, B, Berrío, G, Campbell, D, Cardona Silgado, J, Ochoa, W, Mesa Restrepo, S, Muller, H, Valencia Duarte, A, Lyon, G, Leppert, M, Morgan, J, Weiss, R, Grados, M, Anderson, K, Davarya, S, Singer, H, Walkup, J, Jankovic, J, Tischfield, J, Heiman, G, Gilbert, D, Hoekstra, P, Robertson, M, Kurlan, R, Liu, C, Gibbs, J, Singleton, A, Hardy, J, Strengman, E, Crenshaw, A, Parkin, M, Wagner, M, Moessner, R, Mirel, D, Posthuma, D, Sabatti, C, Conti, D, Knowles, J, Ruiz-Linares, A, Rouleau, G, Purcell, S, Heutink, P, Oostra, B, McMahon, W, Cox, N, Pauls, D, Reus, Victor, State, Matthew, Eskin, Eleazar, Mathews, Carol, Lowe, Thomas, Freimer, Nelson, Ophoff, Roel, and Moorjani, Priya

Subjects
Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Case-Control Studies, Chromosomes, Human, Pair 9, Female, Fibrillar Collagens, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, International Cooperation, Male, Meta-Analysis as Topic, Obsessive-Compulsive Disorder, Polymorphism, Single Nucleotide, Tourette Syndrome, White People, Young Adult
Abstract

Tourettes syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P

Published
2013

2. Genome-wide association study of Tourette's syndrome

Author

Scharf, J M, Yu, D, Mathews, C A, Neale, B M, Stewart, S E, Fagerness, J A, Evans, P, Gamazon, E, Edlund, C K, Service, S K, Tikhomirov, A, Osiecki, L, Illmann, C, Pluzhnikov, A, Konkashbaev, A, Davis, L K, Han, B, Crane, J, Moorjani, P, Crenshaw, A T, Parkin, M A, Reus, V I, Lowe, T L, Rangel-Lugo, M, Chouinard, S, Dion, Y, Girard, S, Cath, D C, Smit, J H, King, R A, Fernandez, T V, Leckman, J F, Kidd, K K, Kidd, J R, Pakstis, A J, State, M W, Herrera, L D, Romero, R, Fournier, E, Sandor, P, Barr, C L, Phan, N, Gross-Tsur, V, Benarroch, F, Pollak, Y, Budman, C L, Bruun, R D, Erenberg, G, Naarden, A L, Lee, P C, Weiss, N, Kremeyer, B, Berrío, G B, Campbell, D D, Cardona Silgado, J C, Ochoa, W C, Mesa Restrepo, S C, Muller, H, Valencia Duarte, A V, Lyon, G J, Leppert, M, Morgan, J, Weiss, R, Grados, M A, Anderson, K, Davarya, S, Singer, H, Walkup, J, Jankovic, J, Tischfield, J A, Heiman, G A, Gilbert, D L, Hoekstra, P J, Robertson, M M, Kurlan, R, Liu, C, Gibbs, J R, Singleton, A, Hardy, J, Strengman, E, Ophoff, R A, Wagner, M, Moessner, R, Mirel, D B, Posthuma, D, Sabatti, C, Eskin, E, Conti, D V, Knowles, J A, Ruiz-Linares, A, Rouleau, G A, Purcell, S, Heutink, P, Oostra, B A, McMahon, W M, Freimer, N B, Cox, N J, and Pauls, D L

Published
2013
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5. Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome

Author

Hirschtritt, M. E., primary, Darrow, S. M., additional, Illmann, C., additional, Osiecki, L., additional, Grados, M., additional, Sandor, P., additional, Dion, Y., additional, King, R. A., additional, Pauls, D., additional, Budman, C. L., additional, Cath, D. C., additional, Greenberg, E., additional, Lyon, G. J., additional, Yu, D., additional, McGrath, L. M., additional, McMahon, W. M., additional, Lee, P. C., additional, Delucchi, K. L., additional, Scharf, J. M., additional, and Mathews, C. A., additional

Published
2017
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6. Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome.

Author

Hirschtritt, M. E., Darrow, S. M., Illmann, C., Osiecki, L., Grados, M., Sandor, P., Dion, Y., King, R. A., Pauls, D., Budman, C. L., Cath, D. C., Greenberg, E., Lyon, G. J., Yu, D., McGrath, L. M., McMahon, W. M., Lee, P. C., Delucchi, K. L., Scharf, J. M., and Mathews, C. A.

Subjects
OBSESSIVE-compulsive disorder, ATTENTION-deficit hyperactivity disorder, FACTOR analysis, FEAR, RESEARCH, PHENOTYPES, TOURETTE syndrome, COMORBIDITY, EXTENDED families, HARM reduction, COMPULSIVE hoarding, SYMPTOMS, GENETICS
Abstract

Background. The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families. Method. OCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed. Results. EFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (550% for all disorders). Conclusions. Symmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders. [ABSTRACT FROM AUTHOR]

Published
2018
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7. Developmental psychopathology of children and adolescents with Tourette syndrome--impact of ADHD

Author

Roessner, V., Becker, A., Banaschewski, T., Freeman, R. D., Rothenberger, A., Aabech, H., Allaghband Rad, J., Berlin, C., Bruun, R., Budman, C., Burd, L., Cardona, Francesco Carmelo Giovanni, Cardoso, F., Castillo, J., Chien, S., Chouinard, S., Dion, Y., Eisenberg, J., Erfan, N., Fast, D., Fayyed, J., Fernandez Alvarez, E., Gadow, K., Gershanik, O., Gil, M., Gilbert, D., Hannesdottir, H., Higgins, D., Janik, P., Jankovic, J., Kadesjo, B., Kano, Y., Kerbeshian, J., Kessler, A., Knudsen, U. F., Korsgaard, A., Lang, A., Lichter, D., Lindback, T., Liu, Z., Lobel, D., Magor, A., Miguel, E., Mueller Vahl, K., O'Connor, K., Oesterheld, J., Pancer, L., Rickards, H., Robertson, M., Rubin, J., Ruzicka, E., S. t. John K., Sandor, P., Scamvougeras, A., Shady, G., Spinner, M., Stamenkovic, M., Sverd, J., Tarnok, Z., Van Der Linden, C., Voutilainen, A., Yazgan, Y., Yi, Z., and Zinner, S.

Subjects
Male, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Tics, Adolescent, Comorbidity, Tourette syndrome, Neurodevelopmental disorder, Child Development, mental disorders, Developmental and Educational Psychology, medicine, Humans, Psychiatry, Child, Mental Disorders, General Medicine, Adolescent Development, medicine.disease, Child development, nervous system diseases, Psychiatry and Mental health, Cross-Sectional Studies, Attention Deficit Disorder with Hyperactivity, Child, Preschool, Pediatrics, Perinatology and Child Health, Regression Analysis, Female, Psychology, human activities, Psychosocial, Developmental psychopathology, Psychopathology, Tourette Syndrome
Abstract

In Tourette syndrome (TS) as a neurodevelopmental disorder not only the tics but also the comorbid conditions change with increasing age. ADHD is highly comorbid with TS and usually impairs psychosocial functioning more than the tics. Its impact on further comorbidity during development is important for clinical practice and still a matter of debate.Aspects of developmental psychopathology considering the impact of ADHD were examined by logistic regression (year wisely) in a cross-sectional sample of children and adolescents (n = 5060) from the TIC database.In TS+ADHD (compared to TS-ADHD) higher rates of comorbid conditions like OCD, anxiety disorders, CD/ODD and mood disorders were found in children (5-10 years). In adolescents (11-17 years) higher comorbidity rates in TS+ADHD remained only for CD/ODD and mood disorders. Accordingly, for OCD and anxiety disorders there was a steeper year wise increase of these comorbidities in TS-ADHD while it was a similar for CD/ODD and mood disorders in TS-ADHD as well as TS+ADHD.Children with TS+ADHD have more comorbidities than the TS-ADHD group, whereas in both adolescent groups this did no longer hold for OCD and anxiety disorders. These findings indicate that in TS comorbid ADHD is associated with high rates of externalizing and internalizing problems, whereas TS without ADHD is associated only with internalizing problems in adolescence.

Published
2008

8. Tic disorders and ADHD: answers from a world-wide clinical dataset on Tourette syndrome

Author

Freeman, R. D., Aabech, H., Allaghband Rad, J., Berlin, C., Bruun, R., Budman, C., Burd, L., Cardona, Francesco Carmelo Giovanni, Cardoso, F., Castillo, J., Chien, S., Chouinard, S., Dion, Y., Eisenberg, J., Erfan, N., Fast, D., Fayyed, J., Fernandez Alvarez, E., Gadow, K., Gershanik, O., Gil, M., Gilbert, D., Hannesdottir, H., Higgins, D., Janik, P., Jankovic, J., Kadesjo, B., Kano, Y., Kerbeshian, J., Kessler, A., Knudsen, U. F., Korsgaard, A., Lang, A., Lichter, D., Lindback, T., Liu, Z., Lobel, D., Magor, A., Miguel, E., Mueller Vahl, K., O'Connor, K., Oesterheld, J., Pancer, L., Rickards, H., Robertson, M., Roessner, V., Rothenberger, A., Rubin, J., Ruzicka, E., S. t. John K., Sandor, P., Scamvougeras, A., Shady, G., Spinner, M., Stamenkovic, M., Sverd, J., Tarnok, Z., Van Der Linden, C., Voutilainen, A., Yazgan, Y., Yi, Z., and Zinner, S.

Subjects
Male, medicine.medical_specialty, Adolescent, Databases, Factual, Comorbidity, Neurological disorder, Tourette syndrome, Neurodevelopmental disorder, mental disorders, Prevalence, Developmental and Educational Psychology, medicine, Child and adolescent psychiatry, Humans, Attention deficit hyperactivity disorder, Age of Onset, Child, Psychiatry, Mental Disorders, General Medicine, medicine.disease, Psychiatry and Mental health, Attention Deficit Disorder with Hyperactivity, Conduct disorder, Pediatrics, Perinatology and Child Health, Female, Psychology, Anxiety disorder, Tourette Syndrome
Abstract

Tourette syndrome (TS) is a neurodevelopmental disorder with frequent comorbidity with Attention- deficit-Hyperactivity disorder (ADHD). The impact of this association is still a matter of debate.Using the TIC database containing 6,805 cases, the clinical differences were ascertained between subjects with and without ADHD.The reported prevalence of ADHD in TS was 55%, within the range of many other reports. If the proband was diagnosed with ADHD, a family history of ADHD was much more likely. ADHD was associated with earlier diagnosis of TS and a much higher rate of anger control problems, sleep problems, specific learning disability, OCD, Oppositional-defiant disorder, mood disorder, social skill deficits, sexually inappropriate behaviour, and self-injurious behaviour. Subjects with seizures and with Developmental Coordination Disorder also had high rates of ADHD. Anxiety disorder, however, was not more frequent. Preliminary data suggest that most behavioural difficulties in ADHD are associated with the Combined or Hyperactive-Impulsive Subtypes of ADHD. Every large site (200 cases) had a significantly increased rate of anger control problems in cases with ADHD.Subjects with TS have high rates of ADHD and complex associations with other disorders. Clinically the findings confirm other research indicating the importance of ADHD in understanding the behavioural problems often associated with the diagnosis of TS. Additional ADHD comorbidity should be taken into account in diagnosis, management, and training.

Published
2007

9. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture

Author

Davis, L. K., Yu, D., Keenan, C. L., Gamazon, E. R., Konkashbaev, A. I., Derks, E. M., Neale, B. M., Yang, J., Lee, S. H., Evans, P., Barr, C. L., Bellodi, L., Benarroch, F., Berrio, G. B., Bienvenu, O. J., Bloch, M. H., Blom, R. M., Bruun, R. D., Budman, C. L., Camarena, B., Campbell, D., Cappi, C., Cardona Silgado, J. C., Cath, D. C., Cavallini, M. C., Chavira, D. A., Chouinard, S., Conti, D. V., Cook, E. H., Coric, V., Cullen, B. A., Deforce, D., Delorme, R., Dion, Y., Edlund, C. K., Egberts, K., Falkai, P., Fernandez, T. V., Gallagher, P. J., Garrido, H., Geller, D., Girard, Simon, Grabe, H. J., Grados, M. A., Greenberg, B. D., Gross-Tsur, V., Haddad, S., Heiman, G. A., Hemmings, S. M.J., Hounie, A. G., Illmann, C., Jankovic, J., Jenike, M. A., Kennedy, J. L., King, R. A., Kremeyer, B., Kurlan, R., Lanzagorta, N., Leboyer, M., Leckman, J. F., Lennertz, L., Liu, C., Lochner, C., Lowe, T. L., Macciardi, F., McCracken, J. T., McGrath, L. M., Mesa Restrepo, S. C., Moessner, R., Morgan, J., Muller, H., Murphy, D. L., Naarden, A. L., Ochoa, W. C., Ophoff, R. A., Osiecki, L., Pakstis, A. J., Pato, M. T., Pato, C. N., Piacentini, J., Pittenger, C., Pollak, Y., Rauch, S. L., Renner, T. J., Reus, V. I., Richter, M. A., Riddle, M. A., Robertson, M. M., Romero, R., Rosario, M. C., Rosenberg, D., Rouleau, G. A., Ruhrmann, S., Ruiz-Linares, A., Sampaio, A. S., Samuels, J., Sandor, P., Sheppard, B., Singer, H. S., Smit, J. H., Stein, D. J., Strengman, E., Tischfield, J. A., Valencia Duarte, A. V., Vallada, H., Van Nieuwerburgh, F., Veenstra-Vanderweele, J., Walitza, S., Wang, Y., Wendland, J. R., Westenberg, H. G.M., Shugart, Y. Y., Miguel, E. C., McMahon, W., Wagner, M., Nicolini, H., Posthuma, D., Hanna, G. L., Heutink, P., Denys, D., Arnold, P. D., Oostra, B. A., Nestadt, G., Freimer, N. B., Pauls, D. L., Wray, N. R., Stewart, S. E., Mathews, C. A., Knowles, J. A., Cox, N. J., Scharf, J. M., Davis, L. K., Yu, D., Keenan, C. L., Gamazon, E. R., Konkashbaev, A. I., Derks, E. M., Neale, B. M., Yang, J., Lee, S. H., Evans, P., Barr, C. L., Bellodi, L., Benarroch, F., Berrio, G. B., Bienvenu, O. J., Bloch, M. H., Blom, R. M., Bruun, R. D., Budman, C. L., Camarena, B., Campbell, D., Cappi, C., Cardona Silgado, J. C., Cath, D. C., Cavallini, M. C., Chavira, D. A., Chouinard, S., Conti, D. V., Cook, E. H., Coric, V., Cullen, B. A., Deforce, D., Delorme, R., Dion, Y., Edlund, C. K., Egberts, K., Falkai, P., Fernandez, T. V., Gallagher, P. J., Garrido, H., Geller, D., Girard, Simon, Grabe, H. J., Grados, M. A., Greenberg, B. D., Gross-Tsur, V., Haddad, S., Heiman, G. A., Hemmings, S. M.J., Hounie, A. G., Illmann, C., Jankovic, J., Jenike, M. A., Kennedy, J. L., King, R. A., Kremeyer, B., Kurlan, R., Lanzagorta, N., Leboyer, M., Leckman, J. F., Lennertz, L., Liu, C., Lochner, C., Lowe, T. L., Macciardi, F., McCracken, J. T., McGrath, L. M., Mesa Restrepo, S. C., Moessner, R., Morgan, J., Muller, H., Murphy, D. L., Naarden, A. L., Ochoa, W. C., Ophoff, R. A., Osiecki, L., Pakstis, A. J., Pato, M. T., Pato, C. N., Piacentini, J., Pittenger, C., Pollak, Y., Rauch, S. L., Renner, T. J., Reus, V. I., Richter, M. A., Riddle, M. A., Robertson, M. M., Romero, R., Rosario, M. C., Rosenberg, D., Rouleau, G. A., Ruhrmann, S., Ruiz-Linares, A., Sampaio, A. S., Samuels, J., Sandor, P., Sheppard, B., Singer, H. S., Smit, J. H., Stein, D. J., Strengman, E., Tischfield, J. A., Valencia Duarte, A. V., Vallada, H., Van Nieuwerburgh, F., Veenstra-Vanderweele, J., Walitza, S., Wang, Y., Wendland, J. R., Westenberg, H. G.M., Shugart, Y. Y., Miguel, E. C., McMahon, W., Wagner, M., Nicolini, H., Posthuma, D., Hanna, G. L., Heutink, P., Denys, D., Arnold, P. D., Oostra, B. A., Nestadt, G., Freimer, N. B., Pauls, D. L., Wray, N. R., Stewart, S. E., Mathews, C. A., Knowles, J. A., Cox, N. J., and Scharf, J. M.

Abstract

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.

Published
2013

11. Genome-Wide Association Study of Gilles de la Tourette Syndrome (IN10-1.002)

Author

Scharf, J., primary, Yu, D., additional, Mathews, C., additional, Neale, B., additional, Stewart, E., additional, Fagerness, J., additional, Evans, P., additional, Gamazon, E., additional, Service, S., additional, Osiecki, L., additional, Illmann, C., additional, Cath, D., additional, King, R., additional, Dion, Y., additional, Sandor, P., additional, Barr, C., additional, Budman, C., additional, Lyon, G., additional, Grados, M., additional, Singer, H., additional, Jankovic, J., additional, Gilbert, D., additional, Hoekstra, P., additional, Heiman, G., additional, Tischfield, J., additional, State, M., additional, Robertson, M., additional, Kurlan, R., additional, Ophoff, R., additional, Gibbs, J. R., additional, Cookson, M., additional, Hardy, J., additional, Singleton, A., additional, Ruiz-Linares, A., additional, Rouleau, G., additional, Heutink, P., additional, Oostra, B., additional, McMahon, W., additional, Freimer, N., additional, COX, N., additional, and Pauls, D., additional

Published
2012
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12. Genome-Wide Association Study of Gilles de la Tourette Syndrome (S32.006)

Author

Scharf, J., primary, Yu, D., additional, Mathews, C., additional, Neale, B., additional, Stewart, E., additional, Fagerness, J., additional, Evans, P., additional, Gamazon, E., additional, Service, S., additional, Osiecki, L., additional, Illmann, C., additional, Cath, D., additional, King, R., additional, Dion, Y., additional, Sandor, P., additional, Barr, C., additional, Budman, C., additional, Lyon, G., additional, Grados, M., additional, Singer, H., additional, Jankovic, J., additional, Gilbert, D., additional, Hoekstra, P., additional, Heiman, G., additional, Tischfield, J., additional, State, M., additional, Robertson, M., additional, Kurlan, R., additional, Ophoff, R., additional, Gibbs, J. R., additional, Cookson, M., additional, Hardy, J., additional, Singleton, A., additional, Ruiz-Linares, A., additional, Rouleau, G., additional, Heutink, P., additional, Oostra, B., additional, McMahon, W., additional, Freimer, N., additional, COX, N., additional, and Pauls, D., additional

Published
2012
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13. ATOMOXETINE TREATMENT OF ADHD IN CHILDREN WITH COMORBID TOURETTE SYNDROME

Author

Spencer, T, primary, Sallee, FR, additional, Dunn, D, additional, McCracken, J, additional, Coffey, B, additional, Budman, C, additional, Ricardi, R, additional, Leonard, H, additional, Allen, AJ, additional, Gilbert, D, additional, Geller, D, additional, Linder, S, additional, Lewis, D, additional, Winner, P, additional, Kurlan, R, additional, Mintz, M, additional, Milton, D, additional, Feldman, P, additional, and Kelsey, D, additional

Published
2006
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18. Persistent dyskinesia in a patient receiving fluoxetine.

Author

Budman, Cathy L., Bruun, Ruth D., Budman, C L, and Bruun, R D

Subjects
LETTERS to the editor, MOVEMENT disorders, BASAL ganglia diseases, MENTAL depression, FLUOXETINE, TARDIVE dyskinesia
Abstract

A letter to the editor is presented in response to an article on movement disorders in a patient receiving fluoxetine.

Published
1991
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19. 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. 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R., Mcgough, J. J., Medland, S. E., Moran, J. L., Mors, O., Mortensen, P. B., Oades, R. D., Palmer, D. S., Pedersen, C. B., Pedersen, M. G., Peters, T., Poterba, T., Poulsen, J. B., Ramos-Quiroga, J. A., Reif, A., Ribases, M., Rothenberger, A., Rovira, P., Sanchez-Mora, C., Satterstrom, F. K., Schachar, R., Artigas, M. S., Steinberg, S., Stefansson, H., Turley, P., Walters, G. B., Werge, T., Zayats, T., Arking, D. E., Bettella, F., Buxbaum, J. D., Christensen, J. H., Collins, R. L., Coon, H., De Rubeis, S., Delorme, R., Grice, D. E., Hansen, T. F., Holmans, P. A., Hope, S., Hultman, C. M., Klei, L., Ladd-Acosta, C., Magnusson, P., Naerland, T., Nyegaard, M., Pinto, D., Qvist, P., Rehnstrom, K., Reichenberg, A., Reichert, J., Roeder, K., Rouleau, G. A., Saemundsen, E., Sanders, S. J., Sandin, S., St Pourcain, B., Stefansson, K., Sutcliffe, J. S., Talkowski, M. E., Weiss, L. A., Willsey, A. J., Agartz, I., Akil, H., Albani, D., Alda, M., Als, T. D., Anjorin, A., Backlund, L., Bass, N., Bauer, M., Baune, B. T., Bellivier, F., Bergen, S. E., Berrettini, W. H., Biernacka, J. M., Blackwood, D. H. R., Boen, E., Budde, M., Bunney, W., Burmeister, M., Byerley, W., Byrne, E. M., Cichon, S., Clarke, T. -K., Coleman, J. R. I., Craddock, N., Curtis, D., Czerski, P. M., Dale, A. M., Dalkner, N., Dannlowski, U., Degenhardt, F., Di Florio, A., Elvsashagen, T., Etain, B., Fischer, S. B., Forstner, A. J., Forty, L., Frank, J., Frye, M., Fullerton, J. M., Gade, K., Gaspar, H. A., Gershon, E. S., Gill, M., Goes, F. S., Gordon, S. D., Gordon-Smith, K., Green, M. J., Greenwood, T. A., Grigoroiu-Serbanescu, M., Guzman-Parra, J., Hauser, J., Hautzinger, M., Heilbronner, U., Herms, S., Hoffmann, P., Holland, D., Jamain, S., Jones, I., Jones, L. A., Kandaswamy, R., Kelsoe, J. R., Kennedy, J. L., Joachim, O. K., Kittel-Schneider, S., Kogevinas, M., Koller, A. C., Lavebratt, C., Lewis, C. M., Li, Q. S., Lissowska, J., Loohuis, L. M. 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

20. Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree

Author

Andrew McQuillin, Dongmei Yu, Jeremiah M. Scharf, Poorva Mudgal, Matthew Halvorsen, David Mataix-Cols, James J. Crowley, Mary M. Robertson, Ashley E. Nordsletten, Manuel Mattheisen, Jin P. Szatkiewicz, Carol A. Mathews, Psychiatric Genomics Consortium TS/OCD Working Group, Aschauer, H., Atzmon, G., Barr, C., Barta, C., Barzilai, N., Batterson, J., Berlin, C., Bodmer, B., Bohnenpoll, J., Brown, L., Bruun, R., Buckner, R., Budman, C., Cath, D., Cheon, K.A., Chouinard, S., Coffey, B., Coppola, G., Cox, N., Crowley, J., Darrow, S., Davis, L., Depienne, C., Dietrich, A., Dion, Y., Elzerman, L., Fernandez, T., Freimer, N., Fremer, C., Fründt, O., Garcia-Delgar, B., Gilbert, D., Grados, M., Greenberg, E., Grice, D., Hagstrøm, J., Halvorsen, M., Hartmann, A., Hebebrand, J., Hedderly, T., Heiman, G., Heyman, I., Hinney, A., Hirschtritt, M., Hoekstra, P., Hong, H., Huang, A., Huyser, C., Ibanez-Gomez, L., Illmann, C., Jankovic, J., Kim, Y., Kim, Y.S., King, R., Knowles, J., Koh, Y.J., Konstantinidis, A., Kook, S., Kuperman, S., Kurlan, R., Leckman, J., Lee, P., Leventhal, B., Ludolph, A., Luðvigsson, P., Lyon, G., Madruga-Garrido, M., Malaty, I., Maras, A., Mataix-Cols, D., Mathews, C., Mattheisen, M., McMahon, W., McQuillin, A., Mir, P., Moessner, R., Morer, A., Mudgal, P., Mueller-Vahl, K., Murphy, T., Münchau, A., Nagy, P., Nawaz, M., Neale, B., Nordsletten, A., Nöthen, M., Okun, M., Ophoff, R., Osiecki, L., Paschou, P., Pato, C., Pato, M., Pauls, D., Plessen, K., Posthuma, D., Richer, P., Rizzo, R., Robertson, M., Roessner, V., Roffman, J., Rouleau, G., Sandor, P., Sæmundsen, E., Scharf, J., Schlögelhofer, M., Shin, E.Y., Singer, H., Smit, J., Smoller, J., Song, D.H., Song, J., Stamenkovic, M., State, M., Stefansson, H., Stefansson, K., Stuhrmann, M., Sul, J., Szatkiewicz, J., Tarnok, Z., Thorarensen, Ó., Tischfield, J., Tsetsos, F., Tübing, J., Visscher, F., Wagner, M., Wanderer, S., Wang, S., Willsey, J., Wolanczyk, T., Woods, D., Woods, M., Worbe, Y., Yu, D., Zelaya, I., Zinner, S., Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Plastic, Reconstructive and Hand Surgery, and Complex Trait Genetics

Subjects
Genetics, Tics, Single-nucleotide polymorphism, Biology, medicine.disease, Tourette syndrome, Genome, Identity by descent, Polymorphism, Single Nucleotide, Pedigree, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Risk Factors, Tic Disorders, medicine, SNP, Humans, Copy-number variation, Polymorphism, Single Nucleotide/genetics, Tourette Syndrome/genetics, Indel, Molecular Biology, Tourette Syndrome
Abstract

Tourette syndrome (TS) is a highly heritable neuropsychiatric disorder with complex patterns of genetic inheritance. Recent genetic findings in TS have highlighted both numerous common variants with small effects and a few rare variants with moderate or large effects. Here we searched for genetic causes of TS in a large, densely-affected British pedigree using a systematic genomic approach. This pedigree spans six generations and includes 122 members, 85 of whom were individually interviewed, and 53 of whom were diagnosed as "cases" (consisting of 28 with definite or probable TS, 20 with chronic multiple tics [CMT], and five with obsessive-compulsive behaviors [OCB]). A total of 66 DNA samples were available (25 TS, 15 CMT, 4 OCB cases, and 22 unaffecteds) and all were genotyped using a dense single nucleotide polymorphism (SNP) array to identify shared segments, copy number variants (CNVs), and to calculate genetic risk scores. Eight cases were also whole genome sequenced to test whether any rare variants were shared identical by descent. While we did not identify any notable CNVs, single nucleotide variants, indels or repeat expansions of near-Mendelian effect, the most distinctive feature of this family proved to be an unusually high load of common risk alleles for TS. We found that cases within this family carried a higher load of TS common variant risk similar to that previously found in unrelated TS cases. Thus far, the strongest evidence from genetic data for contribution to TS risk in this family comes from multiple common risk variants rather than one or a few variants of strong effect.

Published
2021

21. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

Author

Mary M. Robertson, Peter Heutink, Leonhard Lennertz, Victor I. Reus, John Hardy, Mark A. Riddle, Beatriz Camarena, Helena Garrido, Robert A. King, Simon Girard, Christine Lochner, Michael H. Bloch, Patrick Evans, Anuar Konkashbaev, Jack Samuels, Priya Moorjani, Chiara Sabatti, Andrew J. Pakstis, Ying Wang, O. Joseph Bienvenu, Richard Delorme, David L. Pauls, Rainald Moessner, Gary A. Heiman, Daniel A. Geller, Marco A. Grados, Eric R. Gamazon, John Piacentini, Dan J. Stein, William Cornejo Ochoa, Maria Conceição do Rosário, Karin Egberts, Thomas L. Lowe, Christopher K. Edlund, Jan Smit, Christopher Pittenger, Denise A. Chavira, Marion Leboyer, Homero Vallada, Sandra Catalina Mesa Restrepo, Jacquelyn Crane, Donald W. Black, David V. Conti, Paul Sandor, Humberto Nicolini, Lisa Osiecki, Jeremy Veenstra-VanderWeele, Catherine Mayerfeld, Danielle Posthuma, Edna Grünblatt, Carolina Cappi, Robert B. Weiss, Cristina Barlassina, Sara Lupoli, Chunyu Liu, Sian M. J. Hemmings, Ben A. Oostra, D. Denys, Susanne Walitza, Lea K. Davis, Stephen A. Haddad, Luis Diego Herrera, Jubel Morgan, Hans Joergen Grabe, Benjamin M. Neale, Thomas V. Fernandez, Yehuda Pollak, Roel A. Ophoff, Gerald Nestadt, Harvey S. Singer, Stephan Ruhrmann, Bernadette Cullen, Michael Wagner, Nuria Lanzagorta, Jeremiah M. Scharf, Cathy L. Budman, Ruth D. Bruun, R. Kurlan, Valsama Eapen, Jesen Fagerness, Desmond Campbell, James L. Kennedy, Carlos N. Pato, Nancy J. Cox, Pieter J. Hoekstra, Joseph Jankovic, Cathy L. Barr, Peter Falkai, Donald L. Gilbert, Fortu Benarroch, Dianne M. Hezel, Maria Cristina Cavallini, Brooke Sheppard, Fabio Macciardi, William M. McMahon, Laura Bellodi, Maurizio Turiel, Wolfgang Maier, Varda Gross-Tsur, Helena Brentani, Dongmei Yu, Danielle C. Cath, Ana V. Valencia Duarte, Eduardo Fournier, James A. Knowles, Tobias J. Renner, Erika L. Nurmi, Guy A. Rouleau, Benjamin D. Greenberg, Nelson B. Freimer, Shaun Purcell, Patience J. Gallagher, Roxana Romero, Gregory L. Hanna, Paolo Manunta, Edwin H. Cook, Michele T. Pato, Sylvain Chouinard, Scott L. Rauch, James T. McCracken, Gloria Gerber, Carol A. Mathews, Jens R. Wendland, Sampath Arepalli, Dennis L. Murphy, Daniele Cusi, Barbara Kremeyer, Vladimir Coric, Aline S. Sampaio, Erika Salvi, Julio C. Cardona Silgado, Cornelia Illmann, James F. Leckman, Euripedes Constantino Miguel, H. Müller, Yin Yao Shugart, Eric Strengman, Ana Gabriela Hounie, Michael E. Weale, Gabriel Bedoya Berrió, Margaret A. Richter, Maurizio Marconi, Allan L. Naarden, Michael A. Jenike, M.R. Cookson, David R. Rosenberg, Andres Ruiz-Linares, S. Evelyn Stewart, Paul D. Arnold, H.G.M. Westenberg, Yves Dion, Jay A. Tischfield, Eske M. Derks, Lauren M. McGrath, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Yu, D., Mathews, C. A., Scharf, J. M., Neale, B. M., Davis, L. K., Gamazon, E. R., Derks, E. M., Evans, P., Edlund, C. K., Crane, J., Fagerness, J. A., Osiecki, L., Gallagher, P., Gerber, G., Haddad, S., Illmann, C., Mcgrath, L. M., Mayerfeld, C., Arepalli, S., Barlassina, C., Barr, C. L., Bellodi, L., Benarroch, F., Berrio, G. B., Bienvenu, O. J., Black, D., Bloch, M. H., Brentani, H., Bruun, R. D., Budman, C. L., Camarena, B., Campbell, D. D., Cappi, C., Cardona Silgado, J. C., Cavallini, M. C., Chavira, D. A., Chouinard, S., Cook, E. H., Cookson, M. R., Coric, V., Cullen, B., Cusi, D., Delorme, R., Denys, D., Dion, Y., Eapen, V., Egberts, K., Falkai, P., Fernandez, T., Fournier, E., Garrido, H., Geller, D., Gilbert, D., Girard, S. L., Grabe, H. J., Grados, M. A., Greenberg, B. D., Gross-Tsur, V., Grunblatt, E., Hardy, J., Heiman, G. A., Hemmings, S. M. J., Herrera, L. D., Hezel, D. M., Hoekstra, P. J., Jankovic, J., Kennedy, J. L., King, R. A., Konkashbaev, A. I., Kremeyer, B., Kurlan, R., Lanzagorta, N., Leboyer, M., Leckman, J. F., Lennertz, L., Liu, C., Lochner, C., Lowe, T. L., Lupoli, S., Macciardi, F., Maier, W., Manunta, P., Marconi, M., Mccracken, J. T., Mesa Restrepo, S. C., Moessner, R., Moorjani, P., Morgan, J., Muller, H., Murphy, D. L., Naarden, A. L., Ochoa, W. C., Ophoff, R. A., Pakstis, A. J., Pato, M. T., Pato, C. N., Piacentini, J., Pittenger, C., Pollak, Y., Rauch, S. L., Renner, T., Reus, V. I., Richter, M. A., Riddle, M. A., Robertson, M. M., Romero, R., Rosario, M. C., Rosenberg, D., Ruhrmann, S., Sabatti, C., Salvi, E., Sampaio, A. S., Samuels, J., Sandor, P., Service, S. K., Sheppard, B., Singer, H. S., Smit, J. H., Stein, D. J., Strengman, E., Tischfield, J. A., Turiel, M., Valencia Duarte, A. V., Vallada, H., Veenstra-VanderWeele, J., Walitza, S., Walkup, J., Wang, Y., Weale, M., Weiss, R., Wendland, J. R., Westenberg, H. G. M., Yao, Y., Hounie, A. G., Miguel, E. C., Nicolini, H., Wagner, M., Ruiz-Linares, A., Cath, D. C., Mcmahon, W., Posthuma, D., Oostra, B. A., Nestadt, G., Rouleau, G. A., Purcell, S., Jenike, M. A., Heutink, P., Hanna, G. L., Conti, D. V., Arnold, P. D., Freimer, N., Stewart, S. E., Knowles, J. A., Cox, N. J., Pauls, D. L., Netherlands Institute for Neuroscience (NIN), Sub String Theory Cosmology and ElemPart, Leerstoel Hout, Experimental psychopathology, Psychiatry, Human genetics, NCA - Neurobiology of mental health, EMGO - Mental health, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Other departments, ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Adult Psychiatry, Complex Trait Genetics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, and EMGO+ - Mental Health

Subjects
Adult, Male, Obsessive-Compulsive Disorder, diagnosis [Tourette Syndrome], Tics, Single-nucleotide polymorphism, Genome-wide association study, Comorbidity, VARIANTS, Tourette syndrome, Polymorphism, Single Nucleotide, Severity of Illness Index, ASSOCIATION SCANS, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Polymorphism (computer science), Severity of illness, mental disorders, medicine, TICS, Humans, ddc:610, Polymorphism, 030304 developmental biology, Genetics, Psychiatric Status Rating Scales, genetics [Obsessive-Compulsive Disorder], 0303 health sciences, GENERALIST GENES, Single Nucleotide, OBSESSIVE-COMPULSIVE DISORDER, epidemiology [Tourette Syndrome], medicine.disease, Genetic architecture, Psychiatry and Mental health, genetics [Tourette Syndrome], Female, epidemiology [Obsessive-Compulsive Disorder], Psychology, 030217 neurology & neurosurgery, diagnosis [Obsessive-Compulsive Disorder], Genome-Wide Association Study, Tourette Syndrome
Abstract

Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.Method: The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders.Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders Polygenic score analyses identified a significant polygenic component for OCD (p=2x10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01).Conclusions: Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring burette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.

Published
2015

22. Ticked Off: Anger Outbursts and Aggressive Symptoms in Tourette Disorder.

Author

Ashurova M, Budman C, and Coffey BJ

Subjects
Aggression, Anger, Comorbidity, Humans, Tourette Syndrome diagnosis, Tourette Syndrome epidemiology, Tourette Syndrome therapy
Abstract

Tourette disorder is a complex neuropsychiatric syndrome of childhood onset characterized by multiple motor and phonic tics and is associated with high rates of psychiatric comorbidity. Symptoms of impulsive aggression (explosive outbursts or "rage") are commonly encountered in the clinical setting, cause significant morbidity, and pose diagnostic and treatment challenges. These symptoms may be multifactorial in etiology and result from a complex interplay of illness severity and psychosocial factors. Treatment strategies require careful differential diagnostic evaluation and include both behavioral and pharmacologic interventions., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Published
2021
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23. Deutetrabenazine in Tics Associated with Tourette Syndrome.

Author

Jankovic J, Jimenez-Shahed J, Budman C, Coffey B, Murphy T, Shprecher D, and Stamler D

Abstract

Background: Deutetrabenazine, an inhibitor of vesicular monoamine transporter type 2 (VMAT2) depletes presynaptic dopamine and is useful in the treatment of hyperkinetic movement disorders. This study explored the safety, tolerability, and preliminary efficacy of deutetrabenazine in adolescents with moderate-to-severe tics associated with Tourette syndrome (TS)., Methods: In this open-label study of 12-18-year-old patients with TS-related tics, deutetrabenazine was titrated up to 36 mg/day over 6 weeks to adequately suppress tics without bothersome adverse effects (AEs), followed by maintenance at optimal dose for 2 weeks. An independent blinded rater assessed tic severity using the Yale Global Tic Severity Scale (YGTSS), which was the primary outcome measure. Secondary outcome measures included the TS Clinical Global Impression (TS-CGI) and TS Patient Global Impression of Change (TS-PGIC)., Results: Twenty-three enrolled patients received deutetrabenazine and had at least 1 post-baseline YGTSS assessment. The mean (SD [standard deviation]) baseline YGTSS Total Tic Severity Score (TTS) was 31.6 (7.9) and had decreased by 11.6 (8.2) points at week 8, a 37.6% reduction in tic severity (p<0.0001). The TS-CGI score improved by 1.2 (0.81) points (p<0.0001) and the TS-PGIC results at week 8 indicated that 76% of patients were much improved or very much improved compared with baseline. The mean (SD) daily deutetrabenazine dose at week 8 was 32.1 (6.6) mg (range 18-36 mg). One week after withdrawal of deutetrabenazine, the TTS scores increased by 5.6 (8.4) points, providing confirmation of the drug effect. No serious or severe adverse events were reported., Discussion: The results of this open-label 8-week study suggest that deutetrabenazine is safe and associated with improvement in tic severity in adolescents with TS and troublesome tics., Competing Interests: Funding: This report describes a study funded by Auspex, a wholly owned subsidiary of Teva Pharmaceutical Industries, Petah Tikva, Israel. Conflict of Interest: The authors report no conflict of interest. Ethics Statement: The study was conducted in accordance with the principles of Good Clinical Practice, and with the FDA guidelines on safety monitoring by Institutional Review Boards for Human Research. Written informed consent by parent/guardian and assent of the adolescent was obtained before study participation. This study was performed in accordance with the ethical standards detailed in the Declaration of Helsinki. The authors’ institutional ethics committee has approved this study and all patients have provided written informed consent.

Published
2016
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24. Exploring the impact of chronic tic disorders on youth: results from the Tourette Syndrome Impact Survey.

Author

Conelea CA, Woods DW, Zinner SH, Budman C, Murphy T, Scahill LD, Compton SN, and Walkup J

Subjects
Adolescent, Anxiety psychology, Child, Emotions, Female, Health Surveys, Humans, Male, Psychometrics, Severity of Illness Index, Surveys and Questionnaires, Cost of Illness, Quality of Life psychology, Tic Disorders psychology
Abstract

Prior research has demonstrated that chronic tic disorders (CTD) are associated with functional impairment across several domains. However, methodological limitations, such as data acquired by parental report, datasets aggregated across child and adult samples, and small treatment-seeking samples, curtail interpretation. The current study explored the functional impact of tics among youth in a large, "virtual" community sample. An Internet-based survey was completed by families with children who had CTD. The sample included 740 parents and 232 of their children (ages 10-17 years). The survey assessed impact across five functional domains: physical, social, familial, academic, and psychological. Health-related quality of life and perceptions of discrimination resulting from tics were also assessed. Results suggest that (1) youth with CTD experience mild to moderate functional impairment, (2) impairment is generally positively correlated with tic severity, (3) children with CTD plus one or more co-occurring psychiatric conditions tend to have greater functional impairment, and (4) a notable portion of youth with CTD experience discrimination due to tics. Implications and limitations of these findings are discussed.

Published
2011
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25. Coprophenomena in Tourette syndrome.

Author

Freeman RD, Zinner SH, Müller-Vahl KR, Fast DK, Burd LJ, Kano Y, Rothenberger A, Roessner V, Kerbeshian J, Stern JS, Jankovic J, Loughin T, Janik P, Shady G, Robertson MM, Lang AE, Budman C, Magor A, Bruun R, and Berlin CM Jr

Subjects
Child, Child, Preschool, Female, Humans, Male, Tics complications, Behavioral Symptoms complications, Language, Social Behavior, Tourette Syndrome complications, Tourette Syndrome psychology, Verbal Behavior
Abstract

The aims of this descriptive study were to examine the prevalence and associations of coprophenomena (involuntary expression of socially unacceptable words or gestures) in individuals with Tourette syndrome. Participant data were obtained from the Tourette Syndrome International Database Consortium. A specialized data collection form was completed for each of a subset of 597 consecutive new patients with Tourette syndrome from 15 sites in seven countries. Coprolalia occurred at some point in the lifetime of 19.3% of males and 14.6% of females, and copropraxia in 5.9% of males and 4.9% of females. Coprolalia was three times as frequent as copropraxia, with a mean onset of each at about 11 years, 5 years after the onset of tics. In 11% of those with coprolalia and 12% of those with copropraxia these coprophenomena were one of the initial symptoms of Tourette syndrome. The onsets of tics, coprophenomena, smelling of non-food objects, and spitting were strongly intercorrelated. Early onset of coprophenomena was not associated with its longer persistence. The most robust associations of coprophenomena were with the number of non-tic repetitive behaviors, spitting, and inappropriate sexual behavior. Although coprophenomena are a frequently feared possibility in the course of Tourette syndrome, their emergence occurs in only about one in five referred patients. Because the course and actual impact of coprophenomena are variable, additional prospective research is needed to provide better counseling and prognostic information.

Published
2009
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26. Aripiprazole in children and adolescents with Tourette disorder with and without explosive outbursts.

Author

Budman C, Coffey BJ, Shechter R, Schrock M, Wieland N, Spirgel A, and Simon E

Subjects
Adolescent, Aggression drug effects, Antipsychotic Agents administration & dosage, Antipsychotic Agents adverse effects, Aripiprazole, Attention Deficit Disorder with Hyperactivity complications, Child, Child Behavior Disorders complications, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Male, Obsessive-Compulsive Disorder complications, Piperazines administration & dosage, Piperazines adverse effects, Psychiatric Status Rating Scales, Quinolones administration & dosage, Quinolones adverse effects, Retrospective Studies, Severity of Illness Index, Tourette Syndrome complications, Treatment Outcome, Antipsychotic Agents therapeutic use, Child Behavior Disorders drug therapy, Piperazines therapeutic use, Quinolones therapeutic use, Tourette Syndrome drug therapy
Abstract

Objective: We conducted a retrospective, observational study of aripiprazole for the treatment of tics and/or co-morbid explosive outbursts in 37 children and adolescents with Tourette disorder (TD)., Method: Thirty seven children and adolescents with TD, with and without explosive outbursts, and refractory to previous treatment were treated at one of two university affiliated specialty clinics. All diagnoses were made using Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) criteria. Tic severity was rated using the Clinical Global Impressions Scale for tics (CGI-Tics) and frequency of explosive outbursts was assessed using the CGI-Rage; both measures were obtained at pretreatment baseline and at posttreatment follow up., Results: High rates of psychiatric co-morbidity were observed in these subjects: 31 of 37 (84%) subjects met criteria for obsessive-compulsive disorder (OCD), and 31 of 37 (84%) met criteria for attention-deficit/hyperactivity disorder (ADHD). Twenty nine of 37 (78%) subjects met criteria for intermittent explosive disorder (IED) minus criterion C; the remaining 8 subjects had TD only. Eight subjects (22%) discontinued treatment before 12 weeks due to inability to tolerate the drug. At follow up, tics reduced at a mean daily dose of 12.3 (7.50) mg in 29 of 29 (100%) subjects who completed the study, and explosive outbursts improved in 24/25 subjects (96%) who completed the study. Aripiprazole was tolerated reasonably well, although 8/37 (22%) subjects discontinued treatment; most common side effects included weight gain, akathisia, and sedation., Conclusion: Aripiprazole should be investigated further as a treatment option for TD with and without co-morbid explosive outbursts.

Published
2008
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27. Rage attacks and aggressive symptoms in Japanese adolescents with tourette syndrome.

Author

Kano Y, Ohta M, Nagai Y, Spector I, and Budman C

Subjects
Adolescent, Child, Comorbidity, Cross-Sectional Studies, Female, Humans, Japan, Male, Mental Disorders diagnosis, Mental Disorders epidemiology, Mental Disorders psychology, Personality Assessment, Tourette Syndrome epidemiology, Tourette Syndrome psychology, Aggression psychology, Rage, Tourette Syndrome diagnosis
Abstract

Objective: This study was conducted to explore possible causes of rage attacks as well as clinically significant aggressive symptoms in Japanese adolescents with Tourette syndrome (TS)., Methods: The subjects included 29 adolescents (23 males, 6 females; mean age: 13.5+/-3.7 years). Eighteen subjects (62.1%) were diagnosed with TS only, 11 (37.9%) with TS and comorbidities, including attention-deficit/hyperactivity disorder and obsessive-compulsive disorder. Parents completed the Child Behavior Checklist. Clinically significant aggressive symptoms were assessed using two pilot tools, the Rage Screen and Questionnaire and the Clinical Rating of Aggression., Results: Thirteen subjects (44.8%) were judged to have clinically significant aggressive symptoms, according to the Clinical Rating of Aggression. Twelve met criteria for recurrent rage attacks, according to the Rage Screen and Questionnaire. Between the 13 aggressive and 16 non-aggressive subjects, no significant differences were found in age, gender, psychiatric comorbidities, or concurrent medication. Child Behavior Checklist ratings to compare 11 aggressive and 12 non-aggressive subjects <16 years of age revealed elevated t-test scores on the anxious/depressed, thought problems, aggressive, internalizing, externalizing subscales, and total scale in the aggressive group versus the non-aggressive group., Conclusion: Rage attacks and clinically significant aggressive symptoms are common problems in Japanese TS youth. Psychiatric morbidity appears associated with impulsive-aggressive symptoms. Treatment implications from these findings need to be explored further.

Published
2008
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28. Contemporary assessment and pharmacotherapy of Tourette syndrome.

Author

Scahill L, Erenberg G, Berlin CM Jr, Budman C, Coffey BJ, Jankovic J, Kiessling L, King RA, Kurlan R, Lang A, Mink J, Murphy T, Zinner S, and Walkup J

Subjects
Attention Deficit Disorder with Hyperactivity diagnosis, Attention Deficit Disorder with Hyperactivity drug therapy, Humans, Obsessive-Compulsive Disorder diagnosis, Obsessive-Compulsive Disorder drug therapy, Tics diagnosis, Neurology trends, Tourette Syndrome diagnosis, Tourette Syndrome drug therapy
Abstract

To develop a guide to clinical assessment and pharmacotherapy for children and adults with Tourette syndrome (TS), we reviewed published literature over the past 25 years to identify original articles and reviews on the assessment and pharmacological treatment of Tourette syndrome, attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The literature search also included a survey of reviews published in book chapters. The assessment section was compiled from several reviews. Pharmacological treatments were classified into those with strong empirical support (as evidenced by two positive placebo-controlled studies for tics, OCD, or ADHD in TS samples); modest empirical support (one positive placebo-controlled study), or minimal support (open-label data only). We conclude that accurate diagnosis, including identification of comorbid conditions, is an essential step toward appropriate treatment for patients with TS. In many patients with TS, symptom management requires pharmacotherapy for tics or coexisting conditions. The evidence supporting efficacy and safety for medications used in patients with TS varies. But this evidence offers the best guide to clinical practice.

Published
2006
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29. An Unusual Case of Motor and Vocal Tics With Obsessive-Compulsive Symptoms in a Young Adult With Behcet's Syndrome.

Author

Budman C and Sarcevic A

Abstract

Behcet's disease is a chronic relapsing-remitting, multi-system inflammatory disorder of unknown etiology, characterized by recurrent oral and genital ulcers, uveitis, and skin lesions. The most common central nervous system findings are demyelization and perivascular cell infiltration; meningoencephalitis, cerebral atrophy, and vascular thrombosis may also occur. Neuropsychiatric symptoms may include: paroxysmal dystonia, parkinsonism, delirium, hallucinations, and behavioral disturbances. We report an unusual case of explosive onset of motor and vocal tics with obsessive-compulsive symptoms in a 22-year-old male with Behcet's disease. The putative roles of infection and autoimmune mechanisms in the pathogenesis of tics and obsessive-compulsive symptoms are explored.

Published
2002
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30. Can steroid use be a precipitant in the development of an eating disorder?

Author

Fornari V, Dancyger I, La Monaca G, Budman C, Goodman B, Kabo L, and Katz JL

Subjects
Adolescent, Adrenal Cortex Hormones therapeutic use, Adult, Body Image, Chronic Disease, Female, Humans, Risk Factors, Weight Gain, Adrenal Cortex Hormones adverse effects, Feeding and Eating Disorders etiology
Abstract

Objective: Corticosteroids have a wide range of clinical indications in the treatment of both acute and chronic medical illnesses, and weight gain is a well-documented side effect of their use. In this paper, we describe eight individuals with an eating disorder, which appeared following steroid administration for a medical condition., Method: These findings, support the possibility that the excessive weight gain resulting from steroid use can be a precipitating factor in the development of an eating disorder, particularly among female adolescents and young women who are preoccupied with their appearance and weight., Results: Physicians caring for women receiving corticosteroids should therefore familiarize themselves with these patients' pre-morbid and current eating habits, as well as their weight, dieting and body image histories., Discussion: The relevance of these cases for furthering our understanding of the development and treatment of eating disorder is also discussed., (Copyright 2001 by John Wiley & Sons, Inc.)

Published
2001
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31. An open-label study of the treatment efficacy of olanzapine for Tourette's disorder.

Author

Budman CL, Gayer A, Lesser M, Shi Q, and Bruun RD

Subjects
Adult, Antipsychotic Agents administration & dosage, Attention Deficit Disorder with Hyperactivity diagnosis, Attention Deficit Disorder with Hyperactivity epidemiology, Benzodiazepines, Comorbidity, Drug Administration Schedule, Female, Humans, Male, Olanzapine, Pirenzepine administration & dosage, Psychiatric Status Rating Scales statistics & numerical data, Severity of Illness Index, Tourette Syndrome diagnosis, Tourette Syndrome epidemiology, Treatment Outcome, Antipsychotic Agents therapeutic use, Pirenzepine analogs & derivatives, Pirenzepine therapeutic use, Tourette Syndrome drug therapy
Abstract

Background: An open-label trial was performed to explore efficacy and safety of olanzapine, an atypical neuroleptic with diverse receptor activity including both dopamine-2 and serotonin-2A and -2C antagonism, for treatment of Tourette's disorder., Method: Ten adult patients aged 20 to 44 years with Tourette's disorder were treated using an open-label, flexible dosing schedule for 8 weeks. Three patients who continued olanzapine were reevaluated after 6 months. Three subjects were psychotropic medication naive, 5 patients experienced intolerable side effects with conventional neuroleptics, and 2 patients had remote (> or = 10 years) successful response to conventional neuroleptics. Tic severity was rated by the Yale Global Tic Severity Scale; weight, vital signs, and adverse effects were assessed weekly. Electrocardiogram, laboratory studies, and comorbid symptoms, assessed by the Yale-Brown Obsessive Compulsive Scale and ADHD Behavior Checklist for Adults, were measured at baseline and at week 8., Results: Two of 10 patients prematurely discontinued olanzapine owing to excessive sedation. Of 8 patients who completed the 8-week trial, 4 (50%) demonstrated reduction of global tic severity scores by > or = 20 points, and 6 (75%) demonstrated reductions by > or = 10 points. No significant changes in comorbid symptoms were demonstrated. Sedation, weight gain, increased appetite, dry mouth, and transient asymptomatic hypoglycemia were the most common side effects. Tic improvements were maintained in 3 patients reassessed 6 months later. Final olanzapine dosages ranged from 2.5 mg to 20 mg daily (mean = 10.9 mg/day)., Conclusion: This open-label study suggests that olanzapine should be explored as a potential alternative to conventional neuroleptic medications for treatment of motor tics and Tourette's disorder.

Published
2001
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32. Explosive outbursts in children with Tourette's disorder.

Author

Budman CL, Bruun RD, Park KS, Lesser M, and Olson M

Subjects
Adolescent, Aggression psychology, Anger, Child, Child Behavior Disorders psychology, Comorbidity, Female, Follow-Up Studies, Humans, Male, Obsessive-Compulsive Disorder diagnosis, Obsessive-Compulsive Disorder psychology, Personality Assessment, Tourette Syndrome psychology, Child Behavior Disorders diagnosis, Tourette Syndrome diagnosis
Abstract

Objective: Sudden, explosive outbursts of behavior occur in some children with Tourette's disorder (TD). The etiology of these symptoms is unknown. This study investigated the relationship between explosive outbursts, TD, and its comorbid disorders., Method: Tic type and severity and the presence of specific comorbid disorders were compared in 37 children with TD and explosive outbursts and 31 children with TD who did not have such symptoms., Results: Children with TD and explosive outbursts were more likely to demonstrate significant comorbid conditions, particularly attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and oppositional defiant disorder. Tic type and severity did not appear related to the presence of explosive outbursts. A highly significant relationship was demonstrated between the number of comorbid psychiatric diagnoses and explosive outbursts., Conclusions: Explosive outbursts in children with TD resemble intermittent explosive disorder and may reflect dysregulation of diverse domains of brain function. The presence of such symptoms should alert the clinician to underlying comorbid conditions.

Published
2000
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33. Hallucinations in nonpsychotic children.

Author

Bruun RD and Budman CL

Subjects
Auditory Perception, Child, Hallucinations epidemiology, Hallucinations psychology, Humans, Incidence, Tourette Syndrome psychology, Visual Perception, Hallucinations etiology, Tourette Syndrome complications
Published
1999
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34. Neuropsychological testing in adult attention deficit hyperactivity disorder: a pilot study.

Author

Kovner R, Budman C, Frank Y, Sison C, Lesser M, and Halperin J

Subjects
Adolescent, Adult, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Pilot Projects, Reaction Time, Statistics, Nonparametric, Attention Deficit Disorder with Hyperactivity diagnosis, Neuropsychological Tests
Abstract

Diagnosing adult ADHD is frequently problematic because behavioral information from the patient's childhood, and multiple informants who can delineate the patient's current behavior, are often unavailable. This preliminary study was designed to explore whether objective neuropsychological testing may be a useful adjunct in the diagnosis of adult ADHD. Nineteen adults diagnosed with ADHD according to DSM-IV criteria, along with 10 controls, were assessed using a neuropsychological battery which comprised tests assessing linguistic, visual-spatial perceptual, academic, attentional and inhibitory control, mnestic and executive functions. Following preliminary analyses, designed to determine which variables best discriminated the groups, receiver operating characteristic (ROC) curves were constructed to determine the sensitivity and specificity of the best measures both alone and in combination. Only three measures significantly (p < 0.01) distinguished the groups; Digits Backwards from the WAIS-R and two reaction time measures from a computerized task modeled after Luria's Competing Motor Programs. ROC curve analyses indicated that in combination these measures had greater than 90% accuracy for classifying ADHD and non-ADHD patients. While further research is necessary these preliminary findings suggest that neuropsychological testing may be a useful adjunct in the differential diagnosis of adult ADHD.

Published
1998
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35. Rage attacks in children and adolescents with Tourette's disorder: a pilot study.

Author

Budman CL, Bruun RD, Park KS, and Olson ME

Subjects
Adolescent, Attention Deficit Disorder with Hyperactivity epidemiology, Attention Deficit and Disruptive Behavior Disorders diagnosis, Attention Deficit and Disruptive Behavior Disorders epidemiology, Attention Deficit and Disruptive Behavior Disorders psychology, Child, Comorbidity, Conduct Disorder diagnosis, Conduct Disorder epidemiology, Conduct Disorder psychology, Humans, New York epidemiology, Obsessive-Compulsive Disorder diagnosis, Obsessive-Compulsive Disorder epidemiology, Obsessive-Compulsive Disorder psychology, Pilot Projects, Psychiatric Status Rating Scales, Severity of Illness Index, Tourette Syndrome epidemiology, Tourette Syndrome psychology, Rage, Tourette Syndrome diagnosis
Abstract

Background: Sudden, explosive episodes of rage occur in a significant number of clinically referred children with Tourette's disorder and cause considerable psychosocial morbidity. The etiology of these symptoms is unknown. We conducted a pilot study of 12 consecutive children with Tourette's disorder and rage attacks to determine whether comorbidity of Tourette's-associated disorders is related to these symptoms., Method: Twelve consecutive children with Tourette's disorder who presented with rage attacks were evaluated, including 2 females and 10 males. Tourette's disorder diagnosis, presence of comorbid disorders, and tic severity were assessed using DSM-IV diagnostic criteria and standardized rating scales., Results: All 12 children met diagnostic criteria for Tourette's disorder, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD). Two children were also diagnosed with comorbid oppositional defiant disorder, and 4 children were diagnosed with comorbid conduct disorder. None of the subjects met diagnostic criteria for a mood disorder. All subjects had only mild tic severity., Conclusion: The clinical phenomenon of rage attacks in children with Tourette's disorder resembles intermittent explosive disorder and may reflect specific underlying neurologic disturbances. This pilot study suggests that rage attacks in Tourette's disorder may be related to the presence of comorbid disorders.

Published
1998
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36. Paroxetine treatment of episodic rages associated with Tourette's disorder.

Author

Bruun RD and Budman CL

Subjects
Adolescent, Adult, Attention Deficit Disorder with Hyperactivity epidemiology, Attention Deficit Disorder with Hyperactivity psychology, Child, Comorbidity, Drug Administration Schedule, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Obsessive-Compulsive Disorder epidemiology, Obsessive-Compulsive Disorder psychology, Pilot Projects, Severity of Illness Index, Tic Disorders epidemiology, Tic Disorders psychology, Tourette Syndrome epidemiology, Tourette Syndrome psychology, Treatment Outcome, Paroxetine therapeutic use, Rage drug effects, Selective Serotonin Reuptake Inhibitors therapeutic use, Tourette Syndrome drug therapy
Abstract

Background: Episodic rages have been estimated to occur in as many as 30% of patients with Tourette's syndrome (Tourette's disorder), but their treatment has never been systematically investigated. We report on the results of an open-label pilot study using paroxetine for the treatment of Tourette's disorder-associated rage episodes., Method: Forty-five Tourette's/rage patients (DSM-IV) were treated with paroxetine, specifically to control their rages. Other symptoms such as tics, attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) were not targeted by this study. Treatment was deemed to be therapeutic when rage symptoms were diminished by 75% or more by patient report and were diminished in frequency by at least 1 point on a 4-point scale devised by the authors., Results: After 8 weeks on paroxetine treatment, 29 patients (76% of those who completed the study) reported that rages were significantly diminished or completely absent. Nine patients reported no significant change in rages. Seven patients did not complete the study (3 because of side effects and 4 whose rage frequency increased). The mean dose of paroxetine was 33 mg/day; minimum effective dose was 15 mg/day., Conclusion: We were unable to determine any factors that significantly altered the efficacy of paroxetine for treatment of Tourette's disorder-associated rage episodes. The great majority (87%) of the patients had both ADHD and OCD in addition to Tourette's disorder. The age, sex, and concomitant use of other medications revealed no significant differences in treatment outcome. The results suggest that paroxetine may have an important role in the clinical treatment of episodic rages in Tourette's disorder patients.

Published
1998
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37. Emergence of koro after abrupt cessation of olanzapine.

Author

Ramos RH and Budman CL

Subjects
Adult, Antipsychotic Agents therapeutic use, Benzodiazepines, Combined Modality Therapy, Depressive Disorder drug therapy, Depressive Disorder psychology, Depressive Disorder therapy, Electroconvulsive Therapy, Humans, Male, Olanzapine, Pirenzepine adverse effects, Pirenzepine therapeutic use, Antipsychotic Agents adverse effects, Koro chemically induced, Pirenzepine analogs & derivatives, Substance Withdrawal Syndrome etiology
Published
1998
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38. The course and prognosis of Tourette syndrome.

Author

Bruun RD and Budman CL

Subjects
Attention Deficit Disorder with Hyperactivity complications, Humans, Prognosis, Tourette Syndrome complications, Obsessive-Compulsive Disorder complications, Tourette Syndrome diagnosis
Abstract

The view of Tourette syndrome as a lifelong disorder, once held as a certainty, has changed considerably in the past two decades. It is now known that in the majority of cases, tics will ebb in severity and will no longer be problematic in the adult years. This discovery, however, has been accompanied by the realization that Tourette syndrome is a far more complex disorder than was originally discerned and that it has many unanswered questions.

Published
1997
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39. Viral infection and tic exacerbation.

Author

Budman CL, Kerjakovic M, and Bruun RD

Subjects
Child, Female, Humans, Stomatitis, Herpetic drug therapy, Tic Disorders virology, Tourette Syndrome complications, Tourette Syndrome virology, Acyclovir therapeutic use, Antiviral Agents therapeutic use, Stomatitis, Herpetic complications, Tic Disorders drug therapy
Published
1997
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40. Risperidone as a treatment for Tourette's syndrome.

Author

Bruun RD and Budman CL

Subjects
Adult, Child, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Patient Dropouts, Psychiatric Status Rating Scales, Risperidone administration & dosage, Risperidone adverse effects, Severity of Illness Index, Tourette Syndrome diagnosis, Tourette Syndrome psychology, Treatment Outcome, Risperidone therapeutic use, Tourette Syndrome drug therapy
Abstract

Background: An open-label trial was performed to assess the efficacy and safety of risperidone, a benzisoxazole derivative with potent D2 and 5-HT2 antagonism, for treatment of Tourette's syndrome., Method: Thirty-eight patients with Tourette's syndrome volunteered to take risperidone for treatment of their tics. All patients had failed to respond adequately to conventional treatments (with neuroleptics such as haloperidol and/or with the alpha 2-adrenergic agonist clonidine) or had suffered from intolerable side effects from such treatments. Patients were rated for tic severity by the Yale Global Tic Severity Scale (YGTSS) before treatment and after 1 month of treatment with risperidone. Patients were monitored carefully for side effects and clinical response., Results: Of the 38 patients, 8 discontinued risperidone treatment before the end of the trial because of intolerable side effects. At the end of the 4-week trial, 22 patients (58%) were improved, 7 patients (18%) had no appreciable change in their symptoms, and 1 patient (3%) had a documented worsening of tics. Doses of risperidone at the end of the trial ranged from 0.5 mg to 9 mg/day (mean = 2.7 mg/day)., Conclusion: This open clinical trial suggests that risperidone may be a promising alternative to conventional medications used for treating the symptoms of Tourette's syndrome.

Published
1996

41. Combined pharmacotherapy risk.

Author

Budman CL, Sherling M, and Bruun RD

Subjects
Child, Drug Therapy, Combination, Humans, Male, Selective Serotonin Reuptake Inhibitors adverse effects, Haloperidol adverse effects, Obsessive-Compulsive Disorder drug therapy, Paroxetine adverse effects, Tourette Syndrome drug therapy
Published
1995
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42. The cultural consultant in mental health care: the case of an Arab adolescent.

Author

Budman CL, Lipson JG, and Meleis AI

Subjects
Adolescent, Anxiety Disorders psychology, Combined Modality Therapy, Depressive Disorder psychology, Family Therapy, Humans, Iraq ethnology, Male, United States, Acculturation, Anxiety Disorders rehabilitation, Cultural Characteristics, Depressive Disorder rehabilitation, Emigration and Immigration, Ethnicity psychology, Patient Care Team
Abstract

Limited understanding by mental health providers of an immigrant's cultural background can lead to misdiagnosis and inappropriate treatment. A case involving the psychiatric hospitalization of an adolescent from Iraq is described, as are the role of a cultural consultant in clarifying cultural issues and the positive consequences for diagnosis and treatment. Implications for the training and function of cultural consultants in mental health care are discussed.

Published
1992
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44. Clonazepam treatment of acute mania in an AIDS patient.

Author

Budman CL and Vandersall TA

Subjects
Acquired Immunodeficiency Syndrome psychology, Acute Disease, Adult, Bipolar Disorder etiology, Bipolar Disorder psychology, Female, Humans, Acquired Immunodeficiency Syndrome complications, Bipolar Disorder drug therapy, Clonazepam therapeutic use
Published
1990

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