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1,338 results on '"Hoekstra, Pieter J."'

1. Effects of Positive Behaviour Support Delivered by Direct Staff on Challenging Behaviours and Quality of Life of Adults with Intellectual Disabilities: A Multicentre Cluster-Controlled Trial

Author

Bruinsma, Eke, van den Hoofdakker, Barbara J., Hoekstra, Pieter J., de Kuijper, Gerda M., and de Bildt, Annelies A.

Abstract

Background: Effects of staff provided positive behaviour support (PBS) for individuals with intellectual disabilities are unclear. Method: Using a multicentre non-randomised cluster controlled design, 26 teams of residential group homes, including 245 staff members of 167 individuals with intellectual disabilities, were allocated to a PBS or control group. Conducting multilevel analyses (n = 123) we examined individuals' changes in irritability, other challenging behaviours and quality of life. Results: Compared to controls, irritability did not significantly decrease more in the intervention group, but lethargic behaviours did. Personal development and self-determination significantly increased. Irritability of individuals in the PBS group with higher levels of irritability or lower levels of intellectual disability significantly reduced more compared to controls. Conclusions: PBS was effective in reducing irritability of individuals with severe levels of irritability or intellectual disabilities. Moreover, PBS decreased lethargic behaviours and improved several domains of quality of life.

Published
2024
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3. Short-term effects of an elimination diet and healthy diet in children with attention-deficit/hyperactivity disorder: a randomized-controlled trial

Author

Huberts-Bosch, Annick, Bierens, Margreet, Ly, Verena, van der Velde, Jessica, de Boer, Heleen, van Beek, Gerry, Appelman, Danielle, Visser, Sacha, Bos, Lisa H. P., Reijmers, Lisa, van der Meer, Jolanda, Kamphuis, Niki, Draaisma, Jos M. T., Donders, Rogier, van de Loo-Neus, Gigi H. H., Hoekstra, Pieter J., Bottelier, Marco, Arias-Vasquez, Alejandro, Klip, Helen, Buitelaar, Jan K., van den Berg, Saskia W., and Rommelse, Nanda N.

Published
2024
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8. Emotion recognition profiles in clusters of youth based on levels of callous-unemotional traits and reactive and proactive aggression

Author

Kleine Deters, Renee, Naaijen, Jilly, Holz, Nathalie E., Banaschewski, Tobias, Schulze, Ulrike M. E., Sethi, Arjun, Craig, Michael C., Sagar-Ouriaghli, Ilyas, Santosh, Paramala, Rosa, Mireia, Castro-Fornieles, Josefina, Penzol, María José, Arango, Celso, Brandeis, Daniel, Franke, Barbara, Glennon, Jeffrey C., Buitelaar, Jan K., Hoekstra, Pieter J., and Dietrich, Andrea

Published
2023
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9. Internalizing problems before and during the COVID-19 pandemic in independent samples of Dutch children and adolescents with and without pre-existing mental health problems

Author

Fischer, Karen, Tieskens, Jacintha M., Luijten, Michiel A. J., Zijlmans, Josjan, van Oers, Hedy A., de Groot, Rowdy, van der Doelen, Daniël, van Ewijk, Hanneke, Klip, Helen, van der Lans, Rikkert M., De Meyer, Ronald, van der Mheen, Malindi, van Muilekom, Maud M., Hyun Ruisch, I., Teela, Lorynn, van den Berg, Germie, Bruining, Hilgo, van der Rijken, Rachel, Buitelaar, Jan, Hoekstra, Pieter J., Lindauer, Ramón, Oostrom, Kim J., Staal, Wouter, Vermeiren, Robert, Cornet, Ronald, Haverman, Lotte, Bartels, Meike, Polderman, Tinca J. C., and Popma, Arne

Published
2023
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10. Preferred Outcome Measures in Treatments for Challenging Behaviour in Individuals with Intellectual Disabilities: Results of an Inclusive Delphi Method

Author

de Kuijper, Gerda M., Den Besten-van Ravenswaaij, Janneke J. C., Hoekstra, Pieter J., and de Bildt, Annelies

Abstract

Background: Interventions for challenging behaviours in individuals with intellectual disabilities benefit from outcome monitoring that takes clients' preferences into account. We determined clients' and representatives' preferred outcome domains and measures to secure their involvement in treatment decisions for challenging behaviours. Method: We used an inclusive Delphi method. A focus group of individuals with mild intellectual disabilities and representatives of those with moderate and severe intellectual disabilities prepared the first round by assisting us in collecting possible outcomes. Panels of individuals with intellectual disabilities and representatives were composed to achieve consensus on instruments for preferred outcome domains. Results: Preferred outcome domains were behaviour, side-effects of psychotropic drugs, quality of life, daily functioning, caregiver burden and family quality of life. Corresponding outcome measures included self-report, interview and proxy-scales, including spoken versions. Conclusion: Including the preferred domains on outcomes of interventions for challenging behaviours is recommended. Research on corresponding outcome measures is necessary.

Published
2023
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11. Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Author

Patel, Yash, Shin, Jean, Abé, Christoph, Agartz, Ingrid, Alloza, Clara, Alnæs, Dag, Ambrogi, Sonia, Antonucci, Linda A, Arango, Celso, Arolt, Volker, Auzias, Guillaume, Ayesa-Arriola, Rosa, Banaj, Nerisa, Banaschewski, Tobias, Bandeira, Cibele, Başgöze, Zeynep, Cupertino, Renata Basso, Bau, Claiton HD, Bauer, Jochen, Baumeister, Sarah, Bernardoni, Fabio, Bertolino, Alessandro, Bonnin, Caterina Del Mar, Brandeis, Daniel, Brem, Silvia, Bruggemann, Jason, Bülow, Robin, Bustillo, Juan R, Calderoni, Sara, Calvo, Rosa, Canales-Rodríguez, Erick J, Cannon, Dara M, Carmona, Susanna, Carr, Vaughan J, Catts, Stanley V, Chenji, Sneha, Chew, Qian Hui, Coghill, David, Connolly, Colm G, Conzelmann, Annette, Craven, Alexander R, Crespo-Facorro, Benedicto, Cullen, Kathryn, Dahl, Andreas, Dannlowski, Udo, Davey, Christopher G, Deruelle, Christine, Díaz-Caneja, Covadonga M, Dohm, Katharina, Ehrlich, Stefan, Epstein, Jeffery, Erwin-Grabner, Tracy, Eyler, Lisa T, Fedor, Jennifer, Fitzgerald, Jacqueline, Foran, William, Ford, Judith M, Fortea, Lydia, Fuentes-Claramonte, Paola, Fullerton, Janice, Furlong, Lisa, Gallagher, Louise, Gao, Bingchen, Gao, Si, Goikolea, Jose M, Gotlib, Ian, Goya-Maldonado, Roberto, Grabe, Hans J, Green, Melissa, Grevet, Eugenio H, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Haavik, Jan, Hahn, Tim, Harrison, Ben J, Heindel, Walter, Henskens, Frans, Heslenfeld, Dirk J, Hilland, Eva, Hoekstra, Pieter J, Hohmann, Sarah, Holz, Nathalie, Howells, Fleur M, Ipser, Jonathan C, Jahanshad, Neda, Jakobi, Babette, Jansen, Andreas, Janssen, Joost, Jonassen, Rune, Kaiser, Anna, Kaleda, Vasiliy, Karantonis, James, King, Joseph A, Kircher, Tilo, Kochunov, Peter, Koopowitz, Sheri-Michelle, Landén, Mikael, Landrø, Nils Inge, and Lawrie, Stephen

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Schizophrenia, Neurosciences, Brain Disorders, Biotechnology, Perinatal Period - Conditions Originating in Perinatal Period, Infant Mortality, Pediatric, Serious Mental Illness, Intellectual and Developmental Disabilities (IDD), Genetics, Mental Health, Preterm, Low Birth Weight and Health of the Newborn, 2.3 Psychological, social and economic factors, Aetiology, 2.1 Biological and endogenous factors, Neurological, Mental health, Reproductive health and childbirth, Good Health and Well Being, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Bipolar Disorder, Cerebral Cortex, Child, Depressive Disorder, Major, Female, Humans, Infant, Newborn, Magnetic Resonance Imaging, Pregnancy, Premature Birth, Cortical growth, Cortical surface area, Mental illness, Neurodevelopment, Neurogenesis, Psychiatric disorders, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences
Abstract

BackgroundMorphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life.MethodsInterregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed.ResultsAcross the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth.ConclusionsOur findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.

Published
2022

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

Author

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

Published
2024
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14. Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD

Author

Wang, Sheng, Wang, Belinda, Drury, Vanessa, Drake, Sam, Sun, Nawei, Alkhairo, Hasan, Arbelaez, Juan, Duhn, Clif, Bal, Vanessa H., Langley, Kate, Martin, Joanna, Hoekstra, Pieter J., Dietrich, Andrea, Xing, Jinchuan, Heiman, Gary A., Tischfield, Jay A., Fernandez, Thomas V., Owen, Michael J., O’Donovan, Michael C., Thapar, Anita, State, Matthew W., and Willsey, A. Jeremy

Published
2023
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15. Genomic patterns linked to gray matter alterations underlying working memory deficits in adults and adolescents with attention-deficit/hyperactivity disorder

Author

Duan, Kuaikuai, Chen, Jiayu, Calhoun, Vince D., Jiang, Wenhao, Rootes-Murdy, Kelly, Schoenmacker, Gido, Silva, Rogers F., Franke, Barbara, Buitelaar, Jan K., Hoogman, Martine, Oosterlaan, Jaap, Hoekstra, Pieter J., Heslenfeld, Dirk, Hartman, Catharina A., Sprooten, Emma, Arias-Vasquez, Alejandro, Turner, Jessica A., and Liu, Jingyu

Published
2023
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16. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Author

Jain, Pritesh, Miller-Fleming, Tyne, Topaloudi, Apostolia, Yu, Dongmei, Drineas, Petros, Georgitsi, Marianthi, Yang, Zhiyu, Rizzo, Renata, Müller-Vahl, Kirsten R., Tumer, Zeynep, Mol Debes, Nanette, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Mir, Pablo, Cath, Danielle C., Boomsma, Dorret I., Roessner, Veit, Wolanczyk, Tomasz, Janik, Piotr, Szejko, Natalia, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Benaroya-Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Morer, Astrid, Mueller, Norbert, Munchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Walitza, Susanne, Schrag, Anette, Martino, Davide, Dietrich, Andrea, Mathews, Carol A., Scharf, Jeremiah M., Hoekstra, Pieter J., Davis, Lea K., and Paschou, Peristera

Published
2023
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17. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Author

Dima, Danai, Modabbernia, Amirhossein, Papachristou, Efstathios, Doucet, Gaelle E, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn I, Andersson, Micael, Andreasen, Nancy C, Andreassen, Ole A, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Buckner, Randy L, Calhoun, Vincent, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Cervenka, Simon, Chaim-Avancini, Tiffany M, Ching, Christopher RK, Chubar, Victoria, Clark, Vincent P, Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A, Dannlowski, Udo, Dale, Anders M, Davey, Christopher, de Geus, Eco JC, de Haan, Lieuwe, de Zubicaray, Greig I, den Braber, Anouk, Dickie, Erin W, Di Giorgio, Annabella, Doan, Nhat Trung, Dørum, Erlend S, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fatouros-Bergman, Helena, Fisher, Simon E, Fouche, Jean-Paul, Franke, Barbara, Frodl, Thomas, Fuentes-Claramonte, Paola, Glahn, David C, Gotlib, Ian H, Grabe, Hans-Jörgen, Grimm, Oliver, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E, Gur, Ruben C, Hahn, Tim, Harrison, Ben J, Hartman, Catharine A, Hatton, Sean N, Heinz, Andreas, Heslenfeld, Dirk J, Hibar, Derrek P, Hickie, Ian B, Ho, Beng-Choon, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Hulshoff Pol, Hilleke E, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, Kahn, Rene, and Kalnin, Andrew

Subjects
Karolinska Schizophrenia Project, Amygdala, Hippocampus, Thalamus, Corpus Striatum, Humans, Human Development, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Child, Preschool, Female, Male, Young Adult, Neuroimaging, ENIGMA, brain morphometry, longitudinal trajectories, multisite, Neurosciences, Aging, Aetiology, 2.1 Biological and endogenous factors, Mental health, Cognitive Sciences, Experimental Psychology
Abstract

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.

Published
2022

18. Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3–90 years

Author

Frangou, Sophia, Modabbernia, Amirhossein, Williams, Steven CR, Papachristou, Efstathios, Doucet, Gaelle E, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes‐Eizagirre, Anton, Alnæs, Dag, Alpert, Kathryn I, Andersson, Micael, Andreasen, Nancy C, Andreassen, Ole A, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur‐Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Buckner, Randy L, Calhoun, Vincent, Canales‐Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Cervenka, Simon, Chaim‐Avancini, Tiffany M, Ching, Christopher RK, Chubar, Victoria, Clark, Vincent P, Conrod, Patricia, Conzelmann, Annette, Crespo‐Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A, Dale, Anders M, Dannlowski, Udo, Davey, Christopher, Geus, Eco JC, Haan, Lieuwe, Zubicaray, Greig I, Braber, Anouk, Dickie, Erin W, Di Giorgio, Annabella, Doan, Nhat Trung, Dørum, Erlend S, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fatouros‐Bergman, Helena, Fisher, Simon E, Fouche, Jean‐Paul, Franke, Barbara, Frodl, Thomas, Fuentes‐Claramonte, Paola, Glahn, David C, Gotlib, Ian H, Grabe, Hans‐Jörgen, Grimm, Oliver, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E, Gur, Ruben C, Hahn, Tim, Harrison, Ben J, Hartman, Catharine A, Hatton, Sean N, Heinz, Andreas, Heslenfeld, Dirk J, Hibar, Derrek P, Hickie, Ian B, Ho, Beng‐Choon, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Pol, Hilleke E Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, and Kahn, Rene

Subjects
Behavioral and Social Science, Neurosciences, Aging, Adolescent, Adult, Aged, Aged, 80 and over, Cerebral Cortex, Child, Child, Preschool, Cross-Sectional Studies, Female, Human Development, Humans, Male, Middle Aged, Neuroimaging, Young Adult, aging, cortical thickness, development, trajectories, Karolinska Schizophrenia Project, Cognitive Sciences, Experimental Psychology
Abstract

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.

Published
2022

19. Exploring the Association of Staff Characteristics with Staff Perceptions of Quality of Life of Individuals with Intellectual Disabilities and Challenging Behaviours

Author

Bruinsma, Eke, van den Hoofdakker, Barbara J., Hoekstra, Pieter J., de Kuijper, Gerda M., and de Bildt, Annelies A.

Abstract

Background: This study aimed to examine the associations between individual staff and staff team characteristics and quality of life of individuals with intellectual disabilities and challenging behaviours. Method: With multilevel analyses, we examined educational level, experience, attitudes and behaviours of 240 staff members, in relation to their perception of quality of life of 152 individuals with intellectual disabilities and challenging behaviours they cared for. Results: Two individual staff characteristics were related to better quality of life: higher educational and self-reflection levels. Of the team characteristics, higher educational level, higher self-efficacy and more friendly behaviour were associated with better quality of life. Unexpectedly, higher staff-individual ratio was related to lower quality of life. Conclusions: Both individual staff and staff team characteristics are associated with quality of life, indicating the need to take staff team characteristics into account when examining quality of life.

Published
2022
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21. Psychopharmacology in children and adolescents: unmet needs and opportunities

Author

Cortese, Samuele, Purper-Ouakil, Diane, Apter, Alan, Arango, Celso, Baeza, Inmaculada, Banaschewski, Tobias, Buitelaar, Jan, Castro-Fornieles, Josefina, Coghill, David, Cohen, David, Correll, Christoph U, Grünblatt, Edna, Hoekstra, Pieter J, James, Anthony, Jeppesen, Pia, Nagy, Péter, Pagsberg, Anne Katrine, Parellada, Mara, Persico, Antonio M, Roessner, Veit, Santosh, Paramala, Simonoff, Emily, Stevanovic, Dejan, Stringaris, Argyris, Vitiello, Benedetto, Walitza, Susanne, Weizman, Abraham, Wong, Ian C K, Zalsman, Gil, Zuddas, Alessandro, Carucci, Sara, Butlen-Ducuing, Florence, Tome, Maria, Bea, Myriam, Getin, Christine, Hovén, Nina, Konradsson-Geuken, Asa, Lamirell, Daphne, Olisa, Nigel, Nafria Escalera, Begonya, and Moreno, Carmen

Published
2024
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22. Investigation of gene-environment interactions in relation to tic severity.

Author

Abdulkadir, Mohamed, Yu, Dongmei, Osiecki, Lisa, King, Robert A, Fernandez, Thomas V, Brown, Lawrence W, Cheon, Keun-Ah, Coffey, Barbara J, Garcia-Delgar, Blanca, Gilbert, Donald L, Grice, Dorothy E, Hagstrøm, Julie, Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibanez-Gomez, Laura, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett, Madruga-Garrido, Marcos, Maras, Athanasios, Mir, Pablo, Morer, Astrid, Münchau, Alexander, Plessen, Kerstin J, Roessner, Veit, Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, Visscher, Frank, Zinner, Samuel H, Mathews, Carol A, Scharf, Jeremiah M, Tischfield, Jay A, Heiman, Gary A, Dietrich, Andrea, and Hoekstra, Pieter J

Subjects
Humans, Tourette Syndrome, Tics, Severity of Illness Index, Attention Deficit Disorder with Hyperactivity, Pregnancy, Female, Genome-Wide Association Study, Gene-Environment Interaction, Autism Spectrum Disorder, Gene–environment interaction, Pre- and perinatal complications, Tic severity, Tourette syndrome, Mental Health, Autism, Genetics, Pediatric, Neurosciences, Serious Mental Illness, Brain Disorders, Human Genome, Neurodegenerative, Intellectual and Developmental Disabilities (IDD), Aetiology, 2.1 Biological and endogenous factors, Mental health, Gene-environment interaction, Psychology, Neurology & Neurosurgery
Abstract

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies.

Published
2021

23. Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families

Author

Cao, Xiaolong, Zhang, Yeting, Abdulkadir, Mohamed, Deng, Li, Fernandez, Thomas V, Garcia-Delgar, Blanca, Hagstrøm, Julie, Hoekstra, Pieter J, King, Robert A, Koesterich, Justin, Kuperman, Samuel, Morer, Astrid, Nasello, Cara, Plessen, Kerstin J, Thackray, Joshua K, Zhou, Lisheng, Dietrich, Andrea, Tischfield, Jay A, Heiman, Gary A, and Xing, Jinchuan

Subjects
Human Genome, Brain Disorders, Genetics, Clinical Research, Biotechnology, Neurosciences, Genetic Testing, Aetiology, 2.1 Biological and endogenous factors, Cadherin Related Proteins, Family, Genetic Predisposition to Disease, Humans, Nerve Tissue Proteins, Pedigree, Serine Endopeptidases, Tourette Syndrome, Exome Sequencing, Tourette International Collaborative Genetics Study, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Tourette's Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein-protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.

Published
2021

24. Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets

Author

Postema, Merel C, Hoogman, Martine, Ambrosino, Sara, Asherson, Philip, Banaschewski, Tobias, Bandeira, Cibele E, Baranov, Alexandr, Bau, Claiton HD, Baumeister, Sarah, Baur‐Streubel, Ramona, Bellgrove, Mark A, Biederman, Joseph, Bralten, Janita, Brandeis, Daniel, Brem, Silvia, Buitelaar, Jan K, Busatto, Geraldo F, Castellanos, Francisco X, Cercignani, Mara, Chaim‐Avancini, Tiffany M, Chantiluke, Kaylita C, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Cupertino, Renata B, de Zeeuw, Patrick, Doyle, Alysa E, Durston, Sarah, Earl, Eric A, Epstein, Jeffery N, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas J, Faraone, Stephen V, Frodl, Thomas, Gabel, Matt C, Gogberashvili, Tinatin, Grevet, Eugenio H, Haavik, Jan, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hoekstra, Pieter J, Hohmann, Sarah, Høvik, Marie F, Jernigan, Terry L, Kardatzki, Bernd, Karkashadze, Georgii, Kelly, Clare, Kohls, Gregor, Konrad, Kerstin, Kuntsi, Jonna, Lazaro, Luisa, Lera‐Miguel, Sara, Lesch, Klaus‐Peter, Louza, Mario R, Lundervold, Astri J, Malpas, Charles B, Mattos, Paulo, McCarthy, Hazel, Namazova‐Baranova, Leyla, Nicolau, Rosa, Nigg, Joel T, Novotny, Stephanie E, Weiss, Eileen Oberwelland, Tuura, Ruth L O'Gorman, Oosterlaan, Jaap, Oranje, Bob, Paloyelis, Yannis, Pauli, Paul, Picon, Felipe A, Plessen, Kerstin J, Ramos‐Quiroga, J Antoni, Reif, Andreas, Reneman, Liesbeth, Rosa, Pedro GP, Rubia, Katya, Schrantee, Anouk, Schweren, Lizanne JS, Seitz, Jochen, Shaw, Philip, Silk, Tim J, Skokauskas, Norbert, Vila, Juan C Soliva, Stevens, Michael C, Sudre, Gustavo, Tamm, Leanne, Tovar‐Moll, Fernanda, van Erp, Theo GM, Vance, Alasdair, Vilarroya, Oscar, Vives‐Gilabert, Yolanda, von Polier, Georg G, Walitza, Susanne, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, Glahn, David C, and Jahanshad, Neda

Subjects
Biological Psychology, Psychology, Pediatric, Brain Disorders, Mental Health, Neurosciences, Attention Deficit Hyperactivity Disorder (ADHD), Pediatric Research Initiative, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Brain, Caudate Nucleus, Child, Humans, Magnetic Resonance Imaging, Attention&#8208, deficit, hyperactivity disorder, brain asymmetry, brain laterality, structural MRI, large&#8208, scale data, ENIGMA ADHD Working Group, Attention-deficit, large-scale data, Clinical Sciences, Cognitive Sciences, Developmental & Child Psychology, Clinical sciences, Applied and developmental psychology, Clinical and health psychology
Abstract

ObjectiveSome studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.MethodsWe analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.ResultsThere was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.ConclusionPrior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

Published
2021

25. Early-Life Environmental and Child Factors Associated with the Presence of Disruptive Behaviors in Seven-Year-Old Children with Autistic Traits in the Avon Longitudinal Study of Parents and Children

Author

Breider, Simone, Hoekstra, Pieter J., Wardenaar, Klaas J., van den Hoofdakker, Barbara J., Dietrich, Andrea, and de Bildt, Annelies

Abstract

We studied the association of early-life environmental and child factors with disruptive behaviors in children with autistic traits around age 7, in the Avon Longitudinal Study of Parents and Children (n = 6,401). Logistic regression with the least absolute shrinkage and selection operator indicated that disruptive behaviors were associated with prenatal smoking, no seafood-consumption during pregnancy, breech presentation at delivery, neonatal feeding problems, low social-economic situation, suboptimal preschool family environment, maternal depression, maternal antisocial behavior, male sex, and difficult child temperament. Compared to controls, male sex, maternal depression, and suboptimal preschool family environment were related to autistic traits without disruptive behaviors. Thus, there may be a difference in early-life factors related to autism spectrum disorder with and without disruptive behaviors.

Published
2022
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26. The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder

Author

Faraone, Stephen V, Banaschewski, Tobias, Coghill, David, Zheng, Yi, Biederman, Joseph, Bellgrove, Mark A, Newcorn, Jeffrey H, Gignac, Martin, Al Saud, Nouf M, Manor, Iris, Rohde, Luis Augusto, Yang, Li, Cortese, Samuele, Almagor, Doron, Stein, Mark A, Albatti, Turki H, Aljoudi, Haya F, Alqahtani, Mohammed MJ, Asherson, Philip, Atwoli, Lukoye, Bölte, Sven, Buitelaar, Jan K, Crunelle, Cleo L, Daley, David, Dalsgaard, Søren, Döpfner, Manfred, Espinet, Stacey, Fitzgerald, Michael, Franke, Barbara, Gerlach, Manfred, Haavik, Jan, Hartman, Catharina A, Hartung, Cynthia M, Hinshaw, Stephen P, Hoekstra, Pieter J, Hollis, Chris, Kollins, Scott H, Kooij, JJ Sandra, Kuntsi, Jonna, Larsson, Henrik, Li, Tingyu, Liu, Jing, Merzon, Eugene, Mattingly, Gregory, Mattos, Paulo, McCarthy, Suzanne, Mikami, Amori Yee, Molina, Brooke SG, Nigg, Joel T, Purper-Ouakil, Diane, Omigbodun, Olayinka O, Polanczyk, Guilherme V, Pollak, Yehuda, Poulton, Alison S, Rajkumar, Ravi Philip, Reding, Andrew, Reif, Andreas, Rubia, Katya, Rucklidge, Julia, Romanos, Marcel, Ramos-Quiroga, J Antoni, Schellekens, Arnt, Scheres, Anouk, Schoeman, Renata, Schweitzer, Julie B, Shah, Henal, Solanto, Mary V, Sonuga-Barke, Edmund, Soutullo, César, Steinhausen, Hans-Christoph, Swanson, James M, Thapar, Anita, Tripp, Gail, van de Glind, Geurt, van den Brink, Wim, Van der Oord, Saskia, Venter, Andre, Vitiello, Benedetto, Walitza, Susanne, and Wang, Yufeng

Subjects
Epidemiology, Health Sciences, Behavioral and Social Science, Mental Illness, Brain Disorders, Clinical Research, Attention Deficit Hyperactivity Disorder (ADHD), Mental Health, Comparative Effectiveness Research, Pediatric, Mental health, Attention Deficit Disorder with Hyperactivity, Humans, Network Meta-Analysis, Publication Bias, ADHD, Diagnosis, Treatment, Course, Outcome, Genetics, Brain, Medical and Health Sciences, Psychology and Cognitive Sciences, Behavioral Science & Comparative Psychology, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundMisconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base.MethodsWe reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder.ResultsWe generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents.ConclusionsMany findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.

Published
2021

27. Characterizing neuroanatomic heterogeneity in people with and without ADHD based on subcortical brain volumes

Author

Li, Ting, van Rooij, Daan, Mota, Nina Roth, Buitelaar, Jan K, Ambrosino, Sara, Banaschewski, Tobias, Bandeira, Cibele E, Bau, Claiton HD, Baumeister, Sarah, Baur‐Streubel, Ramona, Bellgrove, Mark A, Biederman, Joseph, Bralten, Janita, Bramati, Ivanei E, Brandeis, Daniel, Berm, Silvia, Busatto, Geraldo F, Calvo, Anna, Castellanos, Francisco X, Cercignani, Mara, Chantiluke, Kaylita C, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Cupertino, Renata B, de Zeeuw, Parick, Durston, Sarah, Earl, Eric A, Epstein, Jeffery N, Ethofer, Thomas, Fallgatter, Andreas J, Fair, Damien A, Faraone, Stephen V, Frodl, Thomas, Gabel, Matt C, Gogberashvili, Tinatin, Grevet, Eugenio H, Haavik, Jan, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hoekstra, Pieter J, Høvik, Marie F, Jahanshad, Neda, Kardatzki, Bernd, Karkashadze, Georgii, Kelly, Clare, Kohls, Gregor, Konrad, Kerstin, Kuntsi, Jonna, Lazaro, Luisa, Lera‐Miguel, Sara, Lesch, Klaus‐Peter, Louza, Mario R, Lundervold, Astri J, Malpas, Charles B, Mattos, Paulo, McCarthy, Hazel, Nicolau, Rosa, Nigg, Joel T, Tuura, Ruth L O'Gorman, Oosterlaan, Jaap, Oranje, Bob, Paloyelis, Yannis, Pauli, Paul, Picon, Felipe A, Plessen, Kerstin J, Ramos‐Quiroga, J Antoni, Reif, Andreas, Reneman, Liesbeth, Rosa, Pedro GP, Rubia, Katya, Schrantee, Anouk, Schweren, Lizanne JS, Seitz, Jochen, Shaw, Philip, Silk, Tim J, Skokauskas, Norbert, Vila, Juan Carlos Soliva, Soloveva, Anastasiia, Stevens, Michael C, Sudre, Gustavo, Tamm, Leanne, Thompson, Paul M, Tovar‐Moll, Fernanda, van Erp, Theo GM, Vance, Alasdair, Vilarroya, Oscar, Vives‐Gilabert, Yolanda, von Polier, Georg G, Walitza, Susanne, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, Anikin, Anatoly, Asherson, Philip, Baranov, Alexandr, Chaim‐Avanicini, Tiffany, and Dale, Anders M

Subjects
Biological Psychology, Psychology, Mental Health, Pediatric, Brain Disorders, Attention Deficit Hyperactivity Disorder (ADHD), Clinical Research, Neurosciences, Adult, Attention Deficit Disorder with Hyperactivity, Brain, Case-Control Studies, Female, Humans, Magnetic Resonance Imaging, Male, Thalamus, ADHD, subcortical volume, neuroanatomic heterogeneity, community detection, effect sizes, ENIGMA ADHD Working Group, Clinical Sciences, Cognitive Sciences, Developmental & Child Psychology, Clinical sciences, Applied and developmental psychology, Clinical and health psychology
Abstract

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Neuroanatomic heterogeneity limits our understanding of ADHD's etiology. This study aimed to parse heterogeneity of ADHD and to determine whether patient subgroups could be discerned based on subcortical brain volumes.MethodsUsing the large ENIGMA-ADHD Working Group dataset, four subsamples of 993 boys with and without ADHD and to subsamples of 653 adult men, 400 girls, and 447 women were included in analyses. We applied exploratory factor analysis (EFA) to seven subcortical volumes in order to constrain the complexity of the input variables and ensure more stable clustering results. Factor scores derived from the EFA were used to build networks. A community detection (CD) algorithm clustered participants into subgroups based on the networks.ResultsExploratory factor analysis revealed three factors (basal ganglia, limbic system, and thalamus) in boys and men with and without ADHD. Factor structures for girls and women differed from those in males. Given sample size considerations, we concentrated subsequent analyses on males. Male participants could be separated into four communities, of which one was absent in healthy men. Significant case-control differences of subcortical volumes were observed within communities in boys, often with stronger effect sizes compared to the entire sample. As in the entire sample, none were observed in men. Affected men in two of the communities presented comorbidities more frequently than those in other communities. There were no significant differences in ADHD symptom severity, IQ, and medication use between communities in either boys or men.ConclusionsOur results indicate that neuroanatomic heterogeneity in subcortical volumes exists, irrespective of ADHD diagnosis. Effect sizes of case-control differences appear more pronounced at least in some of the subgroups.

Published
2021

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

Author

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

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

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

Published
2021

33. Aripiprazole in Youth with Intellectual Disabilities: A Retrospective Chart Study

Author

Reurts, Eva Enneke, Troost, Pieter W., Dinnissen, Mariken, Reijnen, Sam, Hoekstra, Pieter J., and Popma, Arne

Abstract

A retrospective chart study of patients on open-label aripiprazole treatment was conducted in the Netherlands to add to the knowledge of aripiprazole in children and young adults with mild and borderline intellectual disabilities (IDs). Fifty-three youths, mean age 14.7 ± 3.4 years and mean IQ 64.5 ±13.8, were included. Treatment responders were defined as "much improved" or "very much improved" based on the Clinical Global Impression-Improvement scale. For 83% of the patients, disruptive behavior was the main target symptom. The overall response rate was 30% after 1-4 weeks and 69% after 5-8 weeks. The 5-8 weeks responders showed a response rate of 64% at 22-26 weeks. Mild adverse events were observed in 53% of the patients of which fatigue and weight gain were the most common. Seven patients (13.2%) discontinued because of adverse events. In 53 children and young adults with mild and borderline IDs, aripiprazole was effective in both the short and the long term. No serious adverse events were observed.

Published
2021
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34. The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications

Author

Cortese, Samuele, McGinn, Katherine, Højlund, Mikkel, Apter, Alan, Arango, Celso, Baeza, Immaculada, Banaschewski, Tobias, Buitelaar, Jan, Castro-Fornieles, Josefina, Coghill, David, Cohen, David, Grünblatt, Edna, Hoekstra, Pieter J., James, Anthony, Jeppesen, Pia, Nagy, Péter, Pagsberg, Anne Katrine, Parellada, Mara, Persico, Antonio M., Purper-Ouakil, Diane, Roessner, Veit, Santosh, Paramala, Simonoff, Emily, Stevanovic, Dejan, Stringaris, Argyris, Vitiello, Benedetto, Walitza, Susanne, Weizman, Abraham, Wohlfarth, Tamar, Wong, Ian C.K., Zalsman, Gil, Zuddas, Alessandro, Moreno, Carmen, Solmi, Marco, and Correll, Christoph U.

Published
2023
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35. Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups

Author

Boedhoe, Premika SW, van Rooij, Daan, Hoogman, Martine, Twisk, Jos WR, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anikin, Anatoly, Anticevic, Alan, Arango, Celso, Arnold, Paul D, Asherson, Philip, Assogna, Francesca, Auzias, Guillaume, Banaschewski, Tobias, Baranov, Alexander, Batistuzzo, Marcelo C, Baumeister, Sarah, Baur-Streubel, Ramona, Behrmann, Marlene, Bellgrove, Mark A, Benedetti, Francesco, Beucke, Jan C, Biederman, Joseph, Bollettini, Irene, Bose, Anushree, Bralten, Janita, Bramati, Ivanei E, Brandeis, Daniel, Brem, Silvia, Brennan, Brian P, Busatto, Geraldo F, Calderoni, Sara, Calvo, Anna, Calvo, Rosa, Castellanos, Francisco X, Cercignani, Mara, Chaim-Avancini, Tiffany M, Chantiluke, Kaylita C, Cheng, Yuqi, Cho, Kang Ik K, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Dale, Anders M, Dallaspezia, Sara, Daly, Eileen, Denys, Damiaan, Deruelle, Christine, Di Martino, Adriana, Dinstein, Ilan, Doyle, Alysa E, Durston, Sarah, Earl, Eric A, Ecker, Christine, Ehrlich, Stefan, Ely, Benjamin A, Epstein, Jeffrey N, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas J, Faraone, Stephen V, Fedor, Jennifer, Feng, Xin, Feusner, Jamie D, Fitzgerald, Jackie, Fitzgerald, Kate D, Fouche, Jean-Paul, Freitag, Christine M, Fridgeirsson, Egill A, Frodl, Thomas, Gabel, Matt C, Gallagher, Louise, Gogberashvili, Tinatin, Gori, Ilaria, Gruner, Patricia, Gürsel, Deniz A, Haar, Shlomi, Haavik, Jan, Hall, Geoffrey B, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hirano, Yoshiyuki, Hoekstra, Pieter J, Hoexter, Marcelo Q, Hohmann, Sarah, Høvik, Marie F, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, Jalbrzikowski, Maria, James, Anthony, Janssen, Joost, Jaspers-Fayer, Fern, Jernigan, Terry L, Kapilushniy, Dmitry, and Kardatzki, Bernd

Subjects
Attention Deficit Hyperactivity Disorder (ADHD), Behavioral and Social Science, Clinical Research, Mental Health, Neurosciences, Pediatric, Autism, Intellectual and Developmental Disabilities (IDD), Brain Disorders, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Neurological, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Cerebrum, Child, Female, Human Development, Humans, Male, Neuroimaging, Obsessive-Compulsive Disorder, Organ Size, Psychopathology, Research Report, Systems Analysis, ENIGMA ADHD working group, ENIGMA ASD working group, ENIGMA OCD working group, Attention Deficit Hyperactivity Disorder, ENIGMA, Structural MRI, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

ObjectiveAttention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.MethodsStructural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).ResultsNo shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.ConclusionsThe study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

Published
2020

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

Author

Consortium, Cross-Disorder Group of the Psychiatric Genomics, Lee, Phil H, Anttila, Verneri, Won, Hyejung, Feng, Yen-Chen A, Rosenthal, Jacob, Zhu, Zhaozhong, Tucker-Drob, Elliot M, Nivard, Michel G, Grotzinger, Andrew D, Posthuma, Danielle, Wang, Meg M-J, Yu, Dongmei, Stahl, Eli A, Walters, Raymond K, Anney, Richard JL, Duncan, Laramie E, Ge, Tian, Adolfsson, Rolf, Banaschewski, Tobias, Belangero, Sintia, Cook, Edwin H, Coppola, Giovanni, Derks, Eske M, Hoekstra, Pieter J, Kaprio, Jaakko, Keski-Rahkonen, Anna, Kirov, George, Kranzler, Henry R, Luykx, Jurjen J, Rohde, Luis A, Zai, Clement C, Agerbo, Esben, Arranz, MJ, Asherson, Philip, Bækvad-Hansen, Marie, Baldursson, Gísli, Bellgrove, Mark, Belliveau, Richard A, Buitelaar, Jan, Burton, Christie L, Bybjerg-Grauholm, Jonas, Casas, Miquel, Cerrato, Felecia, Chambert, Kimberly, Churchhouse, Claire, Cormand, Bru, Crosbie, Jennifer, Dalsgaard, Søren, Demontis, Ditte, Doyle, Alysa E, Dumont, Ashley, Elia, Josephine, Grove, Jakob, Gudmundsson, Olafur O, Haavik, Jan, Hakonarson, Hakon, Hansen, Christine S, Hartman, Catharina A, Hawi, Ziarih, Hervás, Amaia, Hougaard, David M, Howrigan, Daniel P, Huang, Hailiang, Kuntsi, Jonna, Langley, Kate, Lesch, Klaus-Peter, Leung, Patrick WL, Loo, Sandra K, Martin, Joanna, Martin, Alicia R, McGough, James J, Medland, Sarah E, Moran, Jennifer L, Mors, Ole, Mortensen, Preben B, Oades, Robert D, Palmer, Duncan S, Pedersen, Carsten B, Pedersen, Marianne G, Peters, Triinu, Poterba, Timothy, Poulsen, Jesper B, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Ribasés, Marta, Rothenberger, Aribert, Rovira, Paula, Sánchez-Mora, Cristina, Satterstrom, F Kyle, Schachar, Russell, Artigas, Maria Soler, Steinberg, Stacy, Stefansson, Hreinn, Turley, Patrick, Walters, G Bragi, Team, 23andMe Research, Werge, Thomas, Zayats, Tetyana, and Arking, Dan E

Subjects
Neurosciences, Serious Mental Illness, Human Genome, Schizophrenia, Intellectual and Developmental Disabilities (IDD), Brain Disorders, Genetics, Pediatric, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Mental health, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mental Disorders, Neurogenesis, Quantitative Trait Loci, Cross-Disorder Group of the Psychiatric Genomics Consortium. Electronic address: plee0@mgh.harvard.edu, Cross-Disorder Group of the Psychiatric Genomics Consortium, GWAS, Psychiatric genetics, cross-disorder genetics, functional genomics, gene expression, genetic architecture, genetic correlation, neurodevelopment, pleiotropy, psychiatric disorders, Biological Sciences, Medical and Health Sciences, Developmental Biology
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/hyperactivity 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

37. Common brain disorders are associated with heritable patterns of apparent aging of the brain

Author

Kaufmann, Tobias, van der Meer, Dennis, Doan, Nhat Trung, Schwarz, Emanuel, Lund, Martina J, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Bettella, Francesco, Beyer, Mona K, Bøen, Erlend, Borgwardt, Stefan, Brandt, Christine L, Buitelaar, Jan, Celius, Elisabeth G, Cervenka, Simon, Conzelmann, Annette, Córdova-Palomera, Aldo, Dale, Anders M, de Quervain, Dominique JF, Di Carlo, Pasquale, Djurovic, Srdjan, Dørum, Erlend S, Eisenacher, Sarah, Elvsåshagen, Torbjørn, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Haatveit, Beathe, Håberg, Asta K, Harbo, Hanne F, Hartman, Catharina A, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jernigan, Terry L, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Kolskår, Knut K, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Lovestone, Simon, Lundervold, Arvid, Lundervold, Astri J, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Norbom, Linn B, Nordvik, Jan Egil, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Richard, Geneviève, Rokicki, Jaroslav, Sanders, Anne-Marthe, Selbæk, Geir, Shadrin, Alexey A, Smeland, Olav B, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Ulrichsen, Kristine M, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, and Westlye, Lars T

Subjects
Biological Psychology, Psychology, Rare Diseases, Mental Health, Neurosciences, Brain Disorders, Biomedical Imaging, Aging, Aetiology, 2.3 Psychological, social and economic factors, 1.1 Normal biological development and functioning, Underpinning research, Mental health, Neurological, Adolescent, Adult, Aged, Aged, 80 and over, Algorithms, Brain, Brain Diseases, Child, Child, Preschool, Female, Genome-Wide Association Study, Humans, Infant, Magnetic Resonance Imaging, Male, Mental Disorders, Middle Aged, Neuropsychological Tests, Schizophrenia, Sex Characteristics, Young Adult, Karolinska Schizophrenia Project, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.

Published
2019

38. Different whole-brain functional connectivity correlates of reactive-proactive aggression and callous-unemotional traits in children and adolescents with disruptive behaviors

Author

Werhahn, Julia E., Smigielski, Lukasz, Sacu, Seda, Mohl, Susanna, Willinger, David, Naaijen, Jilly, Mulder, Leandra M., Glennon, Jeffrey C., Hoekstra, Pieter J., Dietrich, Andrea, Deters, Renee Kleine, Aggensteiner, Pascal M., Holz, Nathalie E., Baumeister, Sarah, Banaschewski, Tobias, Saam, Melanie C., Schulze, Ulrike M.E., Lythgoe, David J., Sethi, Arjun, Craig, Michael, Mastroianni, Mathilde, Sagar-Ouriaghli, Ilyas, Santosh, Paramala J., Rosa, Mireia, Bargallo, Nuria, Castro-Fornieles, Josefina, Arango, Celso, Penzol, Maria J., Zwiers, Marcel P., Franke, Barbara, Buitelaar, Jan K., Walitza, Susanne, and Brandeis, Daniel

Published
2023
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42. Application of Latent Class Analysis to Identify Subgroups of Children with Autism Spectrum Disorders Who Benefit from Social Skills Training

Author

Dekker, Vera, Nauta, Maaike H., Timmerman, Marieke E., Mulder, Erik J., Hoekstra, Pieter J., and de Bildt, Annelies

Abstract

With Latent Class Analysis applied on data of 98 children with autism spectrum disorder (ASD) (9-12 years; 17 girls) participating in social skills training (SST) in a randomized controlled trial (Dekker et al. 2019), four subgroups were detected, based on social-communicative skills before, and response patterns to training. Two subgroups improved after SST. Characterizing the subgroups based on participant and intervention characteristics showed that improvement was related to lower parent-reported perceived difficulty of social-communicative skills at start, higher verbal ability, younger age and milder symptoms of ASD and anxiety. The lowest performing non-improving subgroup participated more often in SST without parent/teacher involvement, compared to all other subgroups. Response to SST in ASD seems to vary depending on participant characteristics.

Published
2021
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43. Long-Term Effectiveness of Off-Label Risperidone Treatment in Children and Adolescents: A Randomized, Placebo-Controlled Discontinuation Study

Author

Dinnissen, Mariken, primary, Dietrich, Andrea, additional, Bierens, Margreet, additional, van der Molen, Judith H., additional, Verhallen, Anne M., additional, Overbeek, Wieske A., additional, van den Hoofdakker, Barbara J., additional, Roke, Yvette, additional, Troost, Pieter W., additional, Buitelaar, Jan K., additional, and Hoekstra, Pieter J., additional

Published
2024
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46. Genetic variants associated with longitudinal changes in brain structure across the lifespan

Author

Brouwer, Rachel M., Klein, Marieke, Grasby, Katrina L., Schnack, Hugo G., Jahanshad, Neda, Teeuw, Jalmar, Thomopoulos, Sophia I., Sprooten, Emma, Franz, Carol E., Gogtay, Nitin, Kremen, William S., Panizzon, Matthew S., Olde Loohuis, Loes M., Whelan, Christopher D., Aghajani, Moji, Alloza, Clara, Alnæs, Dag, Artiges, Eric, Ayesa-Arriola, Rosa, Barker, Gareth J., Bastin, Mark E., Blok, Elisabet, Bøen, Erlend, Breukelaar, Isabella A., Bright, Joanna K., Buimer, Elizabeth E. L., Bülow, Robin, Cannon, Dara M., Ciufolini, Simone, Crossley, Nicolas A., Damatac, Christienne G., Dazzan, Paola, de Mol, Casper L., de Zwarte, Sonja M. C., Desrivières, Sylvane, Díaz-Caneja, Covadonga M., Doan, Nhat Trung, Dohm, Katharina, Fröhner, Juliane H., Goltermann, Janik, Grigis, Antoine, Grotegerd, Dominik, Han, Laura K. M., Harris, Mathew A., Hartman, Catharina A., Heany, Sarah J., Heindel, Walter, Heslenfeld, Dirk J., Hohmann, Sarah, Ittermann, Bernd, Jansen, Philip R., Janssen, Joost, Jia, Tianye, Jiang, Jiyang, Jockwitz, Christiane, Karali, Temmuz, Keeser, Daniel, Koevoets, Martijn G. J. C., Lenroot, Rhoshel K., Malchow, Berend, Mandl, René C. W., Medel, Vicente, Meinert, Susanne, Morgan, Catherine A., Mühleisen, Thomas W., Nabulsi, Leila, Opel, Nils, de la Foz, Víctor Ortiz-García, Overs, Bronwyn J., Paillère Martinot, Marie-Laure, Redlich, Ronny, Marques, Tiago Reis, Repple, Jonathan, Roberts, Gloria, Roshchupkin, Gennady V., Setiaman, Nikita, Shumskaya, Elena, Stein, Frederike, Sudre, Gustavo, Takahashi, Shun, Thalamuthu, Anbupalam, Tordesillas-Gutiérrez, Diana, van der Lugt, Aad, van Haren, Neeltje E. M., Wardlaw, Joanna M., Wen, Wei, Westeneng, Henk-Jan, Wittfeld, Katharina, Zhu, Alyssa H., Zugman, Andre, Armstrong, Nicola J., Bonfiglio, Gaia, Bralten, Janita, Dalvie, Shareefa, Davies, Gail, Di Forti, Marta, Ding, Linda, Donohoe, Gary, Forstner, Andreas J., Gonzalez-Peñas, Javier, Guimaraes, Joao P. O. F. T., Homuth, Georg, Hottenga, Jouke-Jan, Knol, Maria J., Kwok, John B. J., Le Hellard, Stephanie, Mather, Karen A., Milaneschi, Yuri, Morris, Derek W., Nöthen, Markus M., Papiol, Sergi, Rietschel, Marcella, Santoro, Marcos L., Steen, Vidar M., Stein, Jason L., Streit, Fabian, Tankard, Rick M., Teumer, Alexander, van ‘t Ent, Dennis, van der Meer, Dennis, van Eijk, Kristel R., Vassos, Evangelos, Vázquez-Bourgon, Javier, Witt, Stephanie H., Adams, Hieab H. H., Agartz, Ingrid, Ames, David, Amunts, Katrin, Andreassen, Ole A., Arango, Celso, Banaschewski, Tobias, Baune, Bernhard T., Belangero, Sintia I., Bokde, Arun L. W., Boomsma, Dorret I., Bressan, Rodrigo A., Brodaty, Henry, Buitelaar, Jan K., Cahn, Wiepke, Caspers, Svenja, Cichon, Sven, Crespo-Facorro, Benedicto, Cox, Simon R., Dannlowski, Udo, Elvsåshagen, Torbjørn, Espeseth, Thomas, Falkai, Peter G., Fisher, Simon E., Flor, Herta, Fullerton, Janice M., Garavan, Hugh, Gowland, Penny A., Grabe, Hans J., Hahn, Tim, Heinz, Andreas, Hillegers, Manon, Hoare, Jacqueline, Hoekstra, Pieter J., Ikram, Mohammad A., Jackowski, Andrea P., Jansen, Andreas, Jönsson, Erik G., Kahn, Rene S., Kircher, Tilo, Korgaonkar, Mayuresh S., Krug, Axel, Lemaitre, Herve, Malt, Ulrik F., Martinot, Jean-Luc, McDonald, Colm, Mitchell, Philip B., Muetzel, Ryan L., Murray, Robin M., Nees, Frauke, Nenadić, Igor, Oosterlaan, Jaap, Ophoff, Roel A., Pan, Pedro M., Penninx, Brenda W. J. H., Poustka, Luise, Sachdev, Perminder S., Salum, Giovanni A., Schofield, Peter R., Schumann, Gunter, Shaw, Philip, Sim, Kang, Smolka, Michael N., Stein, Dan J., Trollor, Julian N., van den Berg, Leonard H., Veldink, Jan H., Walter, Henrik, Westlye, Lars T., Whelan, Robert, White, Tonya, Wright, Margaret J., Medland, Sarah E., Franke, Barbara, Thompson, Paul M., and Hulshoff Pol, Hilleke E.

Published
2022
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48. Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies

Author

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

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

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

Published
2019

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