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2. Rare coding variation provides insight into the genetic architecture and phenotypic context of autism

Author

Fu, Jack M, Satterstrom, F Kyle, Peng, Minshi, Brand, Harrison, Collins, Ryan L, Dong, Shan, Wamsley, Brie, Klei, Lambertus, Wang, Lily, Hao, Stephanie P, Stevens, Christine R, Cusick, Caroline, Babadi, Mehrtash, Banks, Eric, Collins, Brett, Dodge, Sheila, Gabriel, Stacey B, Gauthier, Laura, Lee, Samuel K, Liang, Lindsay, Ljungdahl, Alicia, Mahjani, Behrang, Sloofman, Laura, Smirnov, Andrey N, Barbosa, Mafalda, Betancur, Catalina, Brusco, Alfredo, Chung, Brian HY, Cook, Edwin H, Cuccaro, Michael L, Domenici, Enrico, Ferrero, Giovanni Battista, Gargus, J Jay, Herman, Gail E, Hertz-Picciotto, Irva, Maciel, Patricia, Manoach, Dara S, Passos-Bueno, Maria Rita, Persico, Antonio M, Renieri, Alessandra, Sutcliffe, James S, Tassone, Flora, Trabetti, Elisabetta, Campos, Gabriele, Cardaropoli, Simona, Carli, Diana, Chan, Marcus CY, Fallerini, Chiara, Giorgio, Elisa, Girardi, Ana Cristina, Hansen-Kiss, Emily, Lee, So Lun, Lintas, Carla, Ludena, Yunin, Nguyen, Rachel, Pavinato, Lisa, Pericak-Vance, Margaret, Pessah, Isaac N, Schmidt, Rebecca J, Smith, Moyra, Costa, Claudia IS, Trajkova, Slavica, Wang, Jaqueline YT, Yu, Mullin HC, Cutler, David J, De Rubeis, Silvia, Buxbaum, Joseph D, Daly, Mark J, Devlin, Bernie, Roeder, Kathryn, Sanders, Stephan J, and Talkowski, Michael E

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Autism, Brain Disorders, Pediatric, Biotechnology, Intellectual and Developmental Disabilities (IDD), Human Genome, Mental Health, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Mental health, Autism Spectrum Disorder, Autistic Disorder, DNA Copy Number Variations, Genetic Predisposition to Disease, Humans, Mutation, Autism Sequencing Consortium, Broad Institute Center for Common Disease Genomics, iPSYCH-BROAD Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR) ≤ 0.001 (185 at FDR ≤ 0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and 8.44% of association evidence, while CNVs conferred greatest relative risk. Meta-analysis with cohorts ascertained for developmental delay (DD) (n = 91,605) yielded 373 genes associated with ASD/DD at FDR ≤ 0.001 (664 at FDR ≤ 0.05), some of which differed in relative frequency of mutation between ASD and DD cohorts. The DD-associated genes were enriched in transcriptomes of progenitor and immature neuronal cells, whereas genes showing stronger evidence in ASD were more enriched in maturing neurons and overlapped with schizophrenia-associated genes, emphasizing that these neuropsychiatric disorders may share common pathways to risk.

Published
2022

4. A human leukocyte antigen imputation study uncovers possible genetic interplay between gut inflammatory processes and autism spectrum disorders

Author

Lombardi, Laura, Le Clerc, Sigrid, Wu, Ching-Lien, Bouassida, Jihène, Boukouaci, Wahid, Sugusabesan, Sobika, Richard, Jean-Romain, Lajnef, Mohamed, Tison, Maxime, Le Corvoisier, Philippe, Barau, Caroline, Banaschewski, Tobias, Holt, Rosemary, Durston, Sarah, Persico, Antonio M., Oakley, Bethany, Loth, Eva, Buitelaar, Jan, Murphy, Declan, Leboyer, Marion, Zagury, Jean-François, and Tamouza, Ryad

Published
2023
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6. Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism

Author

Pretzsch, Charlotte M., Floris, Dorothea L., Schäfer, Tim, Bletsch, Anke, Gurr, Caroline, Lombardo, Michael V., Chatham, Chris H., Tillmann, Julian, Charman, Tony, Arenella, Martina, Jones, Emily, Ambrosino, Sara, Bourgeron, Thomas, Dumas, Guillaume, Cliquet, Freddy, Leblond, Claire S., Loth, Eva, Oakley, Bethany, Buitelaar, Jan K., Baron-Cohen, Simon, Beckmann, Christian F., Persico, Antonio M., Banaschewski, Tobias, Durston, Sarah, Freitag, Christine M., Murphy, Declan G. M., and Ecker, Christine

Published
2023
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7. 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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8. Differences in Intrinsic Gray Matter Connectivity and Their Genomic Underpinnings in Autism Spectrum Disorder

Author

Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian F., Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Buitelaar, Jan K., Chakrabarti, Bhismadev, Charman, Tony, Cornelissen, Ineke, Crawley, Daisy, Dell’Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary, Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng-Chuan, D’ardhuy, Xavier Liogier, Lombardo, Michael V., Loth, Eva, Lythgoe, David J., Mandl, René, Marquand, Andre, Mason, Luke, Mennes, Maarten, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Bast, Nico, Murphy, Declan G.M., Oakley, Bethany, O’Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, San José Cáceres, Antonia, Simonoff, Emily, Spooren, Will, Tillmann, Julian, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, Zwiers, Marcel P., Leyhausen, Johanna, Schäfer, Tim, Gurr, Caroline, Berg, Lisa M., Seelemeyer, Hanna, Pretzsch, Charlotte M., Floris, Dorothea L., Chatham, Chris, and Murphy, Declan G.

Published
2024
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9. Autism Is Associated With Interindividual Variations of Gray and White Matter Morphology

Author

Buitelaar, Jan K., Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian F., Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Chakrabarti, Bhismadev, Charman, Tony, Cornelissen, Ineke, Crawley, Daisy, Dell’Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary, Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng-Chuan, Liogier d’Ardhuy, Xavier, Lombardo, Michael V., Loth, Eva, Lythgoe, David J., Mandl, René, Marquand, Andre, Mason, Luke, Mennes, Maarten, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, Murphy, Declan G.M., Oakley, Bethany, O’Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Rausch, Annika, Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, San José Cáceres, Antonia, Simonoff, Emily, Spooren, Will, Tillmann, Julian, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, Ilioska, Iva, Mei, Ting, Zwiers, Marcel P., Forde, Natalie J., Floris, Dorothea L., Stones, Richard, Holt, Rosemary J., and Llera, Alberto

Published
2023
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10. 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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11. Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

Author

Satterstrom, F Kyle, Kosmicki, Jack A, Wang, Jiebiao, Breen, Michael S, De Rubeis, Silvia, An, Joon-Yong, Peng, Minshi, Collins, Ryan, Grove, Jakob, Klei, Lambertus, Stevens, Christine, Reichert, Jennifer, Mulhern, Maureen S, Artomov, Mykyta, Gerges, Sherif, Sheppard, Brooke, Xu, Xinyi, Bhaduri, Aparna, Norman, Utku, Brand, Harrison, Schwartz, Grace, Nguyen, Rachel, Guerrero, Elizabeth E, Dias, Caroline, Consortium, Autism Sequencing, Aleksic, Branko, Anney, Richard, Barbosa, Mafalda, Bishop, Somer, Brusco, Alfredo, Bybjerg-Grauholm, Jonas, Carracedo, Angel, Chan, Marcus CY, Chiocchetti, Andreas G, Chung, Brian HY, Coon, Hilary, Cuccaro, Michael L, Curró, Aurora, Bernardina, Bernardo Dalla, Doan, Ryan, Domenici, Enrico, Dong, Shan, Fallerini, Chiara, Fernández-Prieto, Montserrat, Ferrero, Giovanni Battista, Freitag, Christine M, Fromer, Menachem, Gargus, J Jay, Geschwind, Daniel, Giorgio, Elisa, González-Peñas, Javier, Guter, Stephen, Halpern, Danielle, Hansen-Kiss, Emily, He, Xin, Herman, Gail E, Hertz-Picciotto, Irva, Hougaard, David M, Hultman, Christina M, Ionita-Laza, Iuliana, Jacob, Suma, Jamison, Jesslyn, Jugessur, Astanand, Kaartinen, Miia, Knudsen, Gun Peggy, Kolevzon, Alexander, Kushima, Itaru, Lee, So Lun, Lehtimäki, Terho, Lim, Elaine T, Lintas, Carla, Lipkin, W Ian, Lopergolo, Diego, Lopes, Fátima, Ludena, Yunin, Maciel, Patricia, Magnus, Per, Mahjani, Behrang, Maltman, Nell, Manoach, Dara S, Meiri, Gal, Menashe, Idan, Miller, Judith, Minshew, Nancy, Montenegro, Eduarda MS, Moreira, Danielle, Morrow, Eric M, Mors, Ole, Mortensen, Preben Bo, Mosconi, Matthew, Muglia, Pierandrea, Neale, Benjamin M, Nordentoft, Merete, Ozaki, Norio, Palotie, Aarno, Parellada, Mara, Passos-Bueno, Maria Rita, Pericak-Vance, Margaret, Persico, Antonio M, and Pessah, Isaac

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Brain Disorders, Mental Health, Pediatric, Human Genome, Clinical Research, Autism, Intellectual and Developmental Disabilities (IDD), Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Mental health, Neurological, Autistic Disorder, Case-Control Studies, Cell Lineage, Cerebral Cortex, Cohort Studies, Exome, Female, Gene Expression Regulation, Developmental, Gene Frequency, Genetic Predisposition to Disease, Humans, Male, Mutation, Missense, Neurobiology, Neurons, Phenotype, Sex Factors, Single-Cell Analysis, Exome Sequencing, Autism Sequencing Consortium, iPSYCH-Broad Consortium, autism spectrum disorder, cell type, cytoskeleton, excitatory neurons, excitatory-inhibitory balance, exome sequencing, genetics, inhibitory neurons, liability, neurodevelopment, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.

Published
2020

12. Autism Spectrum Disorder

Author

Bertelli, Marco O., Azeem, Muhammad Waqar, Underwood, Lisa, Scattoni, Maria Luisa, Persico, Antonio M., Ricciardello, Arianna, Sappok, Tanja, Bergmann, Thomas, Keller, Roberto, Bianco, Annamaria, Corti, Serafino, Miselli, Giovanni, Lassi, Stefano, Croce, Luigi, Bradley, Elspeth, Munir, Kerim, Bertelli, Marco O., editor, Deb, Shoumitro (Shoumi), editor, Munir, Kerim, editor, Hassiotis, Angela, editor, and Salvador-Carulla, Luis, editor

Published
2022
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13. Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis

Author

Garcés, Pilar, Baumeister, Sarah, Mason, Luke, Chatham, Christopher H., Holiga, Stefan, Dukart, Juergen, Jones, Emily J. H., Banaschewski, Tobias, Baron-Cohen, Simon, Bölte, Sven, Buitelaar, Jan K., Durston, Sarah, Oranje, Bob, Persico, Antonio M., Beckmann, Christian F., Bougeron, Thomas, Dell’Acqua, Flavio, Ecker, Christine, Moessnang, Carolin, Charman, Tony, Tillmann, Julian, Murphy, Declan G. M., Johnson, Mark, Loth, Eva, Brandeis, Daniel, and Hipp, Joerg F.

Published
2022
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14. In-depth characterization of neuroradiological findings in a large sample of individuals with autism spectrum disorder and controls

Author

Ambrosino, Sara, Elbendary, Hasnaa, Lequin, Maarten, Rijkelijkhuizen, Dominique, Banaschewski, Tobias, Baron-Cohen, Simon, Bast, Nico, Baumeister, Sarah, Buitelaar, Jan, Charman, Tony, Crawley, Daisy, Dell'Acqua, Flavio, Hayward, Hannah, Holt, Rosemary, Moessnang, Carolin, Persico, Antonio M., Sacco, Roberto, San José Cáceres, Antonia, Tillmann, Julian, Loth, Eva, Ecker, Christine, Oranje, Bob, Murphy, Declan, and Durston, Sarah

Published
2022
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16. Temporal Profiles of Social Attention Are Different Across Development in Autistic and Neurotypical People

Author

Ahmad, Jumana, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian F., Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Cornelissen, Ineke, Crawley, Daisy, Dell’Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hipp, Joerg, Holt, Rosemary, Lai, Meng-Chuan, D’Ardhuy, Xavier Liogier, Lombardo, Michael V., Lythgoe, David J., Mandl, René, Marquand, Andre, Mennes, Maarten, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, Murphy, Declan G.M., Oakley, Bethany, O’Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, San José Cáceres, Antonia, Simonoff, Emily, Spooren, Will, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, Zwiers, Marcel P., Del Bianco, Teresa, Mason, Luke, Charman, Tony, Tillman, Julian, Loth, Eva, Hayward, Hannah, Shic, Frederick, Buitelaar, Jan, Johnson, Mark H., and Jones, Emily J.H.

Published
2021
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17. Atypical Brain Asymmetry in Autism—A Candidate for Clinically Meaningful Stratification

Author

Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian F., Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Buitelaar, Jan K., Chakrabarti, Bhismadev, Charman, Tony, Cornelissen, Ineke, Crawley, Daisy, Dell’Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary, Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng-Chuan, Liogier d’Ardhuy, Xavier, Lombardo, Michael V., Loth, Eva, Lythgoe, David J., Mandl, René, Marquand, Andre, Mason, Luke, Mennes, Maarten, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, Murphy, Declan G.M., Oakley, Bethany, O’Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, San José Cáceres, Antonia, Simonoff, Emily, Spooren, Will, Tillmann, Julian, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, Zwiers, Marcel P., Floris, Dorothea L., Wolfers, Thomas, Zabihi, Mariam, and Holz, Nathalie E.

Published
2021
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18. 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, Moreno, Carmen, 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

Abstract

Psychopharmacological treatment is an important component of the multimodal intervention approach to treating mental health conditions in children and adolescents. Currently, there are many unmet needs but also opportunities, alongside possible risks to consider, regarding the pharmacological treatment of mental health conditions in children and adolescents. In this Position Paper, we highlight and address these unmet needs and opportunities, including the perspectives of clinicians and researchers from the European College of Neuropsychopharmacology–Child and Adolescent Network, alongside those of experts by lived experience from national and international associations, via a survey involving 644 participants from 13 countries, and of regulators, through representation from the European Medicines Agency. We present and discuss the evidence base for medications currently used for mental disorders in children and adolescents, medications in the pipeline, opportunities in the development of novel medications, crucial priorities for the conduct of future clinical studies, challenges and opportunities in terms of the regulatory and legislative framework, and innovations in the way research is conducted, reported, and promoted.

Published
2024

19. Cognitive, behavioral and socio-communication skills as predictors of response to Early Start Denver Model: a prospective study in 32 young children with Autism Spectrum Disorder.

Author

Asta, Lisa, Di Bella, Tiziana, La Fauci Belponer, Francesca, Bruschetta, Marianna, Martines, Silvia, Basile, Enrica, Boncoddo, Maria, Bellomo, Fabiana, Cucinotta, Francesca, Ricciardello, Arianna, Turriziani, Laura, Colombi, Costanza, Banchelli, Federico, Costantini, Riccardo Cuoghi, D'Amico, Roberto, and Persico, Antonio M.

Subjects
CHILDREN with autism spectrum disorders, AUTISTIC children, LONGITUDINAL method, END of treatment, EXPRESSIVE language
Abstract

Introduction: The effectiveness of early interventions in young autistic children is well established, but there is great interindividual variability in treatment response. Predictors of response to naturalistic developmental behavioral interventions (NDBI), like the Early Start Denver Model (ESDM), are needed. Methods: We conducted an exploratory study to prospectively seek predictors of response in 32 young children treated with ESDM after receiving an ASD diagnosis. All children were less than 39 months old (mean age: 29.7 mo), and received individualized ESDM for nine months. Tests were administered at the beginning, after 4 months, and at the end of treatment. Results: Four children (12.5%) were "strong responders", 8 children (25.0%) were "moderate responders", and 20 children (62.5%) were "poor responders". A more favorable response to ESDM was significantly predicted by higher PEP-3 Expressive Language, Receptive Language, Cognitive Verbal/Preverbal, Visuo-Motor Imitation scores, higher GMDS-ER Personal/Social, and VABS-II Communication scores, by lower ADI-R C restricted/stereotypic behaviors, and by joint attention level. Discussion: Most predictors showed a linear association with increasing response to ESDM, but GMDS-ER Personal-Social and joint attention level predicted strong response, while PEP-3 receptive language equally predicted moderate or strong response. Although larger samples will be necessary to reach definitive conclusions, in conjunction with prior reports our findings begin providing information able to assist clinicians in choosing the most appropriate treatment program for young autistic children. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Differences in Intrinsic Gray Matter Connectivity and Their Genomic Underpinnings in Autism Spectrum Disorder

Author

Leyhausen, Johanna, primary, Schäfer, Tim, additional, Gurr, Caroline, additional, Berg, Lisa M., additional, Seelemeyer, Hanna, additional, Pretzsch, Charlotte M., additional, Loth, Eva, additional, Oakley, Bethany, additional, Buitelaar, Jan K., additional, Beckmann, Christian F., additional, Floris, Dorothea L., additional, Charman, Tony, additional, Bourgeron, Thomas, additional, Banaschewski, Tobias, additional, Jones, Emily J.H., additional, Tillmann, Julian, additional, Chatham, Chris, additional, Murphy, Declan G., additional, Ecker, Christine, additional, Ahmad, Jumana, additional, Ambrosino, Sara, additional, Auyeung, Bonnie, additional, Baron-Cohen, Simon, additional, Baumeister, Sarah, additional, Bölte, Sven, additional, Bours, Carsten, additional, Brammer, Michael, additional, Brandeis, Daniel, additional, Brogna, Claudia, additional, de Bruijn, Yvette, additional, Chakrabarti, Bhismadev, additional, Cornelissen, Ineke, additional, Crawley, Daisy, additional, Dell’Acqua, Flavio, additional, Dumas, Guillaume, additional, Durston, Sarah, additional, Faulkner, Jessica, additional, Frouin, Vincent, additional, Garcés, Pilar, additional, Goyard, David, additional, Ham, Lindsay, additional, Hayward, Hannah, additional, Hipp, Joerg, additional, Holt, Rosemary, additional, Johnson, Mark H., additional, Kundu, Prantik, additional, Lai, Meng-Chuan, additional, D’ardhuy, Xavier Liogier, additional, Lombardo, Michael V., additional, Lythgoe, David J., additional, Mandl, René, additional, Marquand, Andre, additional, Mason, Luke, additional, Mennes, Maarten, additional, Meyer-Lindenberg, Andreas, additional, Moessnang, Carolin, additional, Bast, Nico, additional, Murphy, Declan G.M., additional, O’Dwyer, Laurence, additional, Oldehinkel, Marianne, additional, Oranje, Bob, additional, Pandina, Gahan, additional, Persico, Antonio M., additional, Ruggeri, Barbara, additional, Ruigrok, Amber, additional, Sabet, Jessica, additional, Sacco, Roberto, additional, San José Cáceres, Antonia, additional, Simonoff, Emily, additional, Spooren, Will, additional, Toro, Roberto, additional, Tost, Heike, additional, Waldman, Jack, additional, Williams, Steve C.R., additional, Wooldridge, Caroline, additional, and Zwiers, Marcel P., additional

Published
2024
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21. Psychopharmacology in children and adolescents: unmet needs and opportunities

Author

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

Published
2023
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23. Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-Site Sample of Individuals with Autism Spectrum Disorder

Author

Tillmann, J., Ashwood, K., Absoud, M., Bölte, S., Bonnet-Brilhault, F., Buitelaar, J. K., Calderoni, S., Calvo, R., Canal-Bedia, R., Canitano, R., De Bildt, A., Gomot, M., Hoekstra, P. J., Kaale, A., McConachie, H., Murphy, D. G., Narzisi, A., Oosterling, I., Pejovic-Milovancevic, M., Persico, A. M., Puig, O., Roeyers, H., Rommelse, N., Sacco, R., Scandurra, V., Stanfield, A. C., Zander, E., and Charman, T.

Abstract

Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology.

Published
2018
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24. Altered Connectivity Between Cerebellum, Visual, and Sensory-Motor Networks in Autism Spectrum Disorder: Results from the EU-AIMS Longitudinal European Autism Project

Author

Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian F., Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Buitelaar, Jan K., Chakrabarti, Bhismadev, Charman, Tony, Cornelissen, Ineke, Crawley, Daisy, Dell’Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary, Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng-Chuan, Liogier D’ardhuy, Xavier, Lombardo, Michael V., Loth, Eva, Lythgoe, David J., Mandl, René, Marquand, Andre, Mason, Luke, Mennes, Maarten, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, Murphy, Declan G.M., Oakley, Bethany, O’Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Spooren, Will, Tillmann, Julian, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, and Zwiers, Marcel P.

Published
2019
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26. Autisms

Author

Persico, Antonio M., primary, Cucinotta, Francesca, additional, Ricciardello, Arianna, additional, and Turriziani, Laura, additional

Published
2020
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27. Contributors

Author

Abyzov, Alexej, primary, Allan, Kevin Cameron, additional, Amiri, Anahita, additional, Brown, Heather M., additional, Calof, Anne L., additional, Chang, Qiang, additional, Christian, Kimberly M., additional, Clayton, Benjamin L.L., additional, Cucinotta, Francesca, additional, D'Gama, Alissa M., additional, Elitt, Mathew Sean, additional, Fernandez, L., additional, Fitch, R. Holly, additional, Golden, Jeffrey A., additional, Groves, Laura, additional, Hagerman, R.J., additional, Jaffe, Eric, additional, Johnson-Kerner, B.L., additional, Jourdon, Alexandre, additional, Lander, Arthur D., additional, Leigh, M.J., additional, Lim, Youngshin, additional, Mahnke, A.H., additional, Mariani, Jessica, additional, Ming, Guo-li, additional, Miranda, R.C., additional, Mooney, S.M., additional, Neul, Jeffrey L., additional, Nevin, Zachary Scott, additional, Niswander, Lee, additional, Oliver, Christopher, additional, Persico, Antonio M., additional, Pezoa, Sofia A., additional, Pyrgaki, Christina, additional, Reiter, Lawrence T., additional, Ricciardello, Arianna, additional, Rubenstein, Edward, additional, Sahin, Mustafa, additional, Santos, Rosaysela, additional, Scuderi, Soraya, additional, Sherr, E.H., additional, Song, Hongjun, additional, Srivastava, Siddharth, additional, Tesar, Paul J., additional, Turriziani, Laura, additional, Vaccarino, Flora M., additional, Walsh, Christopher A., additional, Wu, Feinan, additional, and Yuen, Eunice Y., additional

Published
2020
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28. Migraine Genetics

Author

Persico, Antonio M., Lamberti, Marco, Farkas, Viktor, Martelletti, Paolo, Series editor, Guidetti, Vincenzo, editor, Arruda, Marco A., editor, and Ozge, Aynur, editor

Published
2017
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31. Diagnostic yield and clinical impact of chromosomal microarray analysis in autism spectrum disorder

Author

Cucinotta, Francesca, primary, Lintas, Carla, additional, Tomaiuolo, Pasquale, additional, Baccarin, Marco, additional, Picinelli, Chiara, additional, Castronovo, Paola, additional, Sacco, Roberto, additional, Piras, Ignazio Stefano, additional, Turriziani, Laura, additional, Ricciardello, Arianna, additional, Scattoni, Maria Luisa, additional, and Persico, Antonio M., additional

Published
2023
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32. 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, Correll, Christoph U., 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.

Abstract

We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010–08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.

Published
2023

33. A human leukocyte antigen imputation study uncovers possible genetic interplay between gut inflammatory processes and autism spectrum disorders

Author

Onderwijscentrum, Brain, Ontwikkelingsstoornissen Ond., Lombardi, Laura, Le Clerc, Sigrid, Wu, Ching-Lien, Bouassida, Jihène, Boukouaci, Wahid, Sugusabesan, Sobika, Richard, Jean-Romain, Lajnef, Mohamed, Tison, Maxime, Le Corvoisier, Philippe, Barau, Caroline, Banaschewski, Tobias, Holt, Rosemary, Durston, Sarah, Persico, Antonio M, Oakley, Bethany, Loth, Eva, Buitelaar, Jan, Murphy, Declan, Leboyer, Marion, Zagury, Jean-François, Tamouza, Ryad, Onderwijscentrum, Brain, Ontwikkelingsstoornissen Ond., Lombardi, Laura, Le Clerc, Sigrid, Wu, Ching-Lien, Bouassida, Jihène, Boukouaci, Wahid, Sugusabesan, Sobika, Richard, Jean-Romain, Lajnef, Mohamed, Tison, Maxime, Le Corvoisier, Philippe, Barau, Caroline, Banaschewski, Tobias, Holt, Rosemary, Durston, Sarah, Persico, Antonio M, Oakley, Bethany, Loth, Eva, Buitelaar, Jan, Murphy, Declan, Leboyer, Marion, Zagury, Jean-François, and Tamouza, Ryad

Published
2023

34. Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism

Author

Pretzsch, Charlotte M; https://orcid.org/0000-0002-2761-6628, Floris, Dorothea L; https://orcid.org/0000-0001-5838-6821, Schäfer, Tim; https://orcid.org/0000-0002-3683-8070, Bletsch, Anke; https://orcid.org/0000-0002-6857-4065, Gurr, Caroline, Lombardo, Michael V, Chatham, Chris H; https://orcid.org/0000-0003-4427-8285, Tillmann, Julian, Charman, Tony; https://orcid.org/0000-0003-1993-6549, Arenella, Martina, Jones, Emily, Ambrosino, Sara, Bourgeron, Thomas; https://orcid.org/0000-0001-8164-9220, Dumas, Guillaume; https://orcid.org/0000-0002-2253-1844, Cliquet, Freddy; https://orcid.org/0000-0002-9989-0685, Leblond, Claire S, Loth, Eva; https://orcid.org/0000-0001-9458-9167, Oakley, Bethany, Buitelaar, Jan K; https://orcid.org/0000-0001-8288-7757, Baron-Cohen, Simon; https://orcid.org/0000-0001-9217-2544, Beckmann, Christian F, Persico, Antonio M, Banaschewski, Tobias; https://orcid.org/0000-0003-4595-1144, Durston, Sarah, Freitag, Christine M; https://orcid.org/0000-0001-9676-4782, Murphy, Declan G M; https://orcid.org/0000-0002-6664-7451, Ecker, Christine, Pretzsch, Charlotte M; https://orcid.org/0000-0002-2761-6628, Floris, Dorothea L; https://orcid.org/0000-0001-5838-6821, Schäfer, Tim; https://orcid.org/0000-0002-3683-8070, Bletsch, Anke; https://orcid.org/0000-0002-6857-4065, Gurr, Caroline, Lombardo, Michael V, Chatham, Chris H; https://orcid.org/0000-0003-4427-8285, Tillmann, Julian, Charman, Tony; https://orcid.org/0000-0003-1993-6549, Arenella, Martina, Jones, Emily, Ambrosino, Sara, Bourgeron, Thomas; https://orcid.org/0000-0001-8164-9220, Dumas, Guillaume; https://orcid.org/0000-0002-2253-1844, Cliquet, Freddy; https://orcid.org/0000-0002-9989-0685, Leblond, Claire S, Loth, Eva; https://orcid.org/0000-0001-9458-9167, Oakley, Bethany, Buitelaar, Jan K; https://orcid.org/0000-0001-8288-7757, Baron-Cohen, Simon; https://orcid.org/0000-0001-9217-2544, Beckmann, Christian F, Persico, Antonio M, Banaschewski, Tobias; https://orcid.org/0000-0003-4595-1144, Durston, Sarah, Freitag, Christine M; https://orcid.org/0000-0001-9676-4782, Murphy, Declan G M; https://orcid.org/0000-0002-6664-7451, and Ecker, Christine

Abstract

Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals’ adaptive skills naturally improve or remain stable, while others’ decrease. To pave the way for ‘precision-medicine’ approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6–30 years), with two assessment time points separated by ~12–24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful “Increasers”, “No-changers”, and “Decreasers” in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup’s neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences’ potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes.

Published
2023

35. 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; https://orcid.org/0000-0001-5877-8075, McGinn, Katherine, Højlund, Mikkel, Apter, Alan, Arango, Celso; https://orcid.org/0000-0003-3382-4754, Baeza, Immaculada, Banaschewski, Tobias, Buitelaar, Jan; https://orcid.org/0000-0001-8288-7757, Castro-Fornieles, Josefina; https://orcid.org/0000-0003-0632-2687, Coghill, David, Cohen, David, Grünblatt, Edna; https://orcid.org/0000-0001-8505-7265, Hoekstra, Pieter J; https://orcid.org/0000-0003-1018-9954, James, Anthony, Jeppesen, Pia, Nagy, Péter, Pagsberg, Anne Katrine, Parellada, Mara, Persico, Antonio M, Purper-Ouakil, Diane; https://orcid.org/0000-0003-0454-1579, Roessner, Veit; https://orcid.org/0000-0002-1873-7081, Santosh, Paramala, Simonoff, Emily; https://orcid.org/0000-0002-5450-0823, Stevanovic, Dejan, Stringaris, Argyris, Vitiello, Benedetto, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Weizman, Abraham, Wohlfarth, Tamar, Wong, Ian C K, Zalsman, Gil, Zuddas, Alessandro, Moreno, Carmen, Solmi, Marco, Correll, Christoph U; https://orcid.org/0000-0002-7254-5646, Cortese, Samuele; https://orcid.org/0000-0001-5877-8075, McGinn, Katherine, Højlund, Mikkel, Apter, Alan, Arango, Celso; https://orcid.org/0000-0003-3382-4754, Baeza, Immaculada, Banaschewski, Tobias, Buitelaar, Jan; https://orcid.org/0000-0001-8288-7757, Castro-Fornieles, Josefina; https://orcid.org/0000-0003-0632-2687, Coghill, David, Cohen, David, Grünblatt, Edna; https://orcid.org/0000-0001-8505-7265, Hoekstra, Pieter J; https://orcid.org/0000-0003-1018-9954, James, Anthony, Jeppesen, Pia, Nagy, Péter, Pagsberg, Anne Katrine, Parellada, Mara, Persico, Antonio M, Purper-Ouakil, Diane; https://orcid.org/0000-0003-0454-1579, Roessner, Veit; https://orcid.org/0000-0002-1873-7081, Santosh, Paramala, Simonoff, Emily; https://orcid.org/0000-0002-5450-0823, Stevanovic, Dejan, Stringaris, Argyris, Vitiello, Benedetto, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Weizman, Abraham, Wohlfarth, Tamar, Wong, Ian C K, Zalsman, Gil, Zuddas, Alessandro, Moreno, Carmen, Solmi, Marco, and Correll, Christoph U; https://orcid.org/0000-0002-7254-5646

Abstract

The pace of development and implementation of novel medications in child and adolescent psychiatry has remained slow. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010 to 08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia. We also included RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥1 primary outcome, 43 (19%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.

Published
2023

36. Processing of social and monetary rewards in autism spectrum disorders

Author

Baumeister, Sarah, Moessnang, Carolin, Bast, Nico, Hohmann, Sarah, Aggensteiner, Pascal, Kaiser, Anna, Tillmann, Julian, Goyard, David, Charman, Tony, Ambrosino, Sara, Baron-Cohen, Simon, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Rausch, Annika, Crawley, Daisy, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Floris, Dorothea L, Frouin, Vincent, Hayward, Hannah, Holt, Rosemary, Johnson, Mark H, Jones, Emily JH, Lai, Meng-Chuan, Lombardo, Michael V, Mason, Luke, Oakley, Bethany, Oldehinkel, Marianne, Persico, Antonio M, San José Cáceres, Antonia, Wolfers, Thomas, Loth, Eva, Murphy, Declan GM, Buitelaar, Jan K, Tost, Heike, Meyer-Lindenberg, Andreas, Banaschewski, Tobias, Brandeis, Daniel, EU-AIMS LEAP Group, Baumeister, Sarah [0000-0001-9005-0084], Aggensteiner, Pascal [0000-0002-1048-9044], Charman, Tony [0000-0003-1993-6549], Banaschewski, Tobias [0000-0003-4595-1144], and Apollo - University of Cambridge Repository

Subjects
Brain Mapping, Reward, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, fMRI, multisite, Humans, Brain, autism traits, Autistic Disorder, reward processing, ADHD symptoms, Magnetic Resonance Imaging
Abstract

BACKGROUND: Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD. AIMS: Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. METHOD: Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.6 years of age) and 181 typically developing participants (7.6-30.8 years of age). RESULTS: Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD. CONCLUSIONS: Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Published
2023
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38. Toe Walking in Children and Adolescents with Autism Spectrum Disorder Relationship with Sensory and Motor Functions, Language, Cognition, and Autism Severity

Author

Camia, Michela, primary, Sacco, Roberto, additional, Boncoddo, Maria, additional, Bellomo, Fabiana, additional, Cucinotta, Francesca, additional, Ricciardello, Arianna, additional, Turriziani, Laura, additional, Tomaiuolo, Pasquale, additional, Costantini, Riccardo Cuoghi, additional, D'Amico, Roberto, additional, and Persico, Antonio M., additional

Published
2023
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39. Coenzyme Q10, Vitamin E and Polyvitamin B: an exploratory double-blind randomized cross-over study in Phelan-McDermid Syndrome

Author

Persico, Antonio M., primary, Ricciardello, Arianna, additional, Cucinotta, Francesca, additional, Turriziani, Laura, additional, Calabrese, Giorgia, additional, Tomaiuolo, Pasquale, additional, Di Bella, Tiziana, additional, Bellomo, Fabiana, additional, Boncoddo, Maria, additional, Turturo, Giada, additional, Mirabelli, Silvestro, additional, Asta, Lisa, additional, Banchelli, Federico, additional, Costantini, Riccardo Cuoghi, additional, and D'Amico, Roberto, additional

Published
2023
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44. Autism Is Associated With Interindividual Variations of Gray and White Matter Morphology

Author

Mei, Ting, primary, Forde, Natalie J., additional, Floris, Dorothea L., additional, Dell’Acqua, Flavio, additional, Stones, Richard, additional, Ilioska, Iva, additional, Durston, Sarah, additional, Moessnang, Carolin, additional, Banaschewski, Tobias, additional, Holt, Rosemary J., additional, Baron-Cohen, Simon, additional, Rausch, Annika, additional, Loth, Eva, additional, Oakley, Bethany, additional, Charman, Tony, additional, Ecker, Christine, additional, Murphy, Declan G.M., additional, Beckmann, Christian F., additional, Llera, Alberto, additional, Buitelaar, Jan K., additional, Ahmad, Jumana, additional, Ambrosino, Sara, additional, Auyeung, Bonnie, additional, Baumeister, Sarah, additional, Bölte, Sven, additional, Bourgeron, Thomas, additional, Bours, Carsten, additional, Brammer, Michael, additional, Brandeis, Daniel, additional, Brogna, Claudia, additional, de Bruijn, Yvette, additional, Chakrabarti, Bhismadev, additional, Cornelissen, Ineke, additional, Crawley, Daisy, additional, Dumas, Guillaume, additional, Faulkner, Jessica, additional, Frouin, Vincent, additional, Garcés, Pilar, additional, Goyard, David, additional, Ham, Lindsay, additional, Hayward, Hannah, additional, Hipp, Joerg, additional, Holt, Rosemary, additional, Johnson, Mark H., additional, Jones, Emily J.H., additional, Kundu, Prantik, additional, Lai, Meng-Chuan, additional, Liogier d’Ardhuy, Xavier, additional, Lombardo, Michael V., additional, Lythgoe, David J., additional, Mandl, René, additional, Marquand, Andre, additional, Mason, Luke, additional, Mennes, Maarten, additional, Meyer-Lindenberg, Andreas, additional, Mueller, Nico, additional, O’Dwyer, Laurence, additional, Oldehinkel, Marianne, additional, Oranje, Bob, additional, Pandina, Gahan, additional, Persico, Antonio M., additional, Ruggeri, Barbara, additional, Ruigrok, Amber, additional, Sabet, Jessica, additional, Sacco, Roberto, additional, San José Cáceres, Antonia, additional, Simonoff, Emily, additional, Spooren, Will, additional, Tillmann, Julian, additional, Toro, Roberto, additional, Tost, Heike, additional, Waldman, Jack, additional, Williams, Steve C.R., additional, Wooldridge, Caroline, additional, Mei, Ting, additional, and Zwiers, Marcel P., additional

Published
2022
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