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2. Bright light therapy versus physical exercise to prevent co-occurring depression in adolescents and young adults with attention-deficit/hyperactivity disorder: a multicentre, three-arm, randomised controlled, pilot phase-IIa trial

Author

Mayer, Jutta S., Kohlhas, Laura, Stermann, Jacek, Medda, Juliane, Brandt, Geva A., Grimm, Oliver, Pawley, Adam D., Asherson, Philip, Sanchez, Judit Palacio, Richarte, Vanesa, Bergsma, Douwe, Koch, Elena D., Muntaner-Mas, Adrià, Ebner-Priemer, Ulrich W., Kieser, Meinhard, Retz, Wolfgang, Ortega, Francisco B., Colla, Michael, Buitelaar, Jan K., Kuntsi, Jonna, Ramos-Quiroga, Josep A., Reif, Andreas, and Freitag, Christine M.

Published
2024
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3. Emotion processing in maltreated boys and girls: Evidence for latent vulnerability

Author

Diaconu, Bianca, Kohls, Gregor, Rogers, Jack C., Pauli, Ruth, Cornwell, Harriet, Bernhard, Anka, Martinelli, Anne, Ackermann, Katharina, Fann, Nikola, Fernandez-Rivas, Aranzazu, Gonzalez-Torres, Miguel Angel, Gonzalez de Artaza-Lavesa, Maider, Hervas, Amaia, Stadler, Christina, Konrad, Kerstin, Freitag, Christine M., Fairchild, Graeme, Rotshtein, Pia, and De Brito, Stephane A.

Published
2023
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5. Intention Attribution in Children and Adolescents with Autism Spectrum Disorder: An EEG Study

Author

Schütz, Magdalena, Boxhoorn, Sara, Mühlherr, Andreas M., Mössinger, Hannah, Freitag, Christine M., and Luckhardt, Christina

Abstract

The ability to infer intentions from observed behavior and predict actions based on this inference, known as intention attribution (IA), has been hypothesized to be impaired in individuals with autism spectrum disorder (ASD). The underlying neural processes, however, have not been conclusively determined. The aim of this study was to examine the neural signature of IA in children and adolescents with ASD, and to elucidate potential links to contextual updating processes using electroencephalography. Results did not indicate that IA or early contextual updating was impaired in ASD. However, there was evidence of aberrant processing of expectation violations in ASD, particularly if the expectation was based on IA. Results are discussed within the context of impaired predictive coding in ASD.

Published
2023
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6. Action initiation and punishment learning differ from childhood to adolescence while reward learning remains stable

Author

Pauli, Ruth, Brazil, Inti A., Kohls, Gregor, Klein-Flügge, Miriam C., Rogers, Jack C., Dikeos, Dimitris, Dochnal, Roberta, Fairchild, Graeme, Fernández-Rivas, Aranzazu, Herpertz-Dahlmann, Beate, Hervas, Amaia, Konrad, Kerstin, Popma, Arne, Stadler, Christina, Freitag, Christine M., De Brito, Stephane A., and Lockwood, Patricia L.

Published
2023
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9. Intention Attribution in Children and Adolescents with Autism Spectrum Disorder: An EEG Study

Author

Schütz, Magdalena, Boxhoorn, Sara, Mühlherr, Andreas M., Mössinger, Hannah, Freitag, Christine M., and Luckhardt, Christina

Subjects
Pervasive developmental disorders -- Diagnosis -- Development and progression -- Demographic aspects, Intention -- Demographic aspects -- Evaluation, Health
Abstract

The ability to infer intentions from observed behavior and predict actions based on this inference, known as intention attribution (IA), has been hypothesized to be impaired in individuals with autism spectrum disorder (ASD). The underlying neural processes, however, have not been conclusively determined. The aim of this study was to examine the neural signature of IA in children and adolescents with ASD, and to elucidate potential links to contextual updating processes using electroencephalography. Results did not indicate that IA or early contextual updating was impaired in ASD. However, there was evidence of aberrant processing of expectation violations in ASD, particularly if the expectation was based on IA. Results are discussed within the context of impaired predictive coding in ASD., Author(s): Magdalena Schütz [sup.1] , Sara Boxhoorn [sup.1] , Andreas M. Mühlherr [sup.1] , Hannah Mössinger [sup.1] , Christine M. Freitag [sup.1] , Christina Luckhardt [sup.1] Author Affiliations: (1) grid.411088.4, [...]

Published
2023
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10. Autismus-Spektrum-Störungen

Author

Freitag, Christine M., Jarczok, Tomasz A., Gerlach, Manfred, editor, Mehler-Wex, Claudia, editor, Romanos, Marcel, editor, Walitza, Susanne, editor, and Wewetzer, Christoph, editor

Published
2023
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11. 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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12. Machine learning classification of conduct disorder with high versus low levels of callous-unemotional traits based on facial emotion recognition abilities

Author

Pauli, Ruth, Kohls, Gregor, Tino, Peter, Rogers, Jack C., Baumann, Sarah, Ackermann, Katharina, Bernhard, Anka, Martinelli, Anne, Jansen, Lucres, Oldenhof, Helena, Gonzalez-Madruga, Karen, Smaragdi, Areti, Gonzalez-Torres, Miguel Angel, Kerexeta-Lizeaga, Iñaki, Boonmann, Cyril, Kersten, Linda, Bigorra, Aitana, Hervas, Amaia, Stadler, Christina, Fernandez-Rivas, Aranzazu, Popma, Arne, Konrad, Kerstin, Herpertz-Dahlmann, Beate, Fairchild, Graeme, Freitag, Christine M., Rotshtein, Pia, and De Brito, Stephane A.

Published
2023
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14. Changes in the pattern of suicides and suicide attempt admissions in relation to the COVID-19 pandemic

Author

Reif-Leonhard, Christine, Lemke, Dorothea, Holz, Franziska, Ahrens, Kira F., Fehr, Christoph, Steffens, Markus, Grube, Michael, Freitag, Christine M., Kölzer, Sarah C., Schlitt, Sabine, Gebhardt, Rebekka, Gädeke, Theresa, Schmidt, Helga, Gerlach, Ferdinand M., Wolff, Kira, Stäblein, Michael, Hauschild, Nora, Beig, Inga, Wagner, Louisa, Müller, Juliane, Verhoff, Marcel A., Schlang, Christiane, and Reif, Andreas

Published
2023
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16. Effectiveness of a positive psychology and mindfulness-based app on mental health for parents of children with a neurodevelopmental disorder: study protocol of a pragmatic international randomized controlled trial

Author

Tönis, Kim J. M., Drossaert, Constance H. C., ten Klooster, Peter M., Schaer, Marie, Bourgeron, Thomas, Buitelaar, Jan K., Sadaka, Yair, Freitag, Christine M., Lapidus, Keren Mayer, Chiocchetti, Andreas G., Staal, Wouter G., and Bohlmeijer, Ernst T.

Published
2024
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18. Testing the Ecophenotype Model: Cortical Structure Alterations in Conduct Disorder With Versus Without Childhood Maltreatment

Author

Staginnus, Marlene, Cornwell, Harriet, Toschi, Nicola, Oosterling, Maaike, Paradysz, Michal, Smaragdi, Areti, González-Madruga, Karen, Pauli, Ruth, Rogers, Jack C., Bernhard, Anka, Martinelli, Anne, Kohls, Gregor, Raschle, Nora Maria, Konrad, Kerstin, Stadler, Christina, Freitag, Christine M., De Brito, Stephane A., and Fairchild, Graeme

Published
2023
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20. 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

21. Episignatures Stratifying Helsmoortel-Van Der Aa Syndrome Show Modest Correlation with Phenotype

Author

Breen, Michael S, Garg, Paras, Tang, Lara, Mendonca, Danielle, Levy, Tess, Barbosa, Mafalda, Arnett, Anne B, Kurtz-Nelson, Evangeline, Agolini, Emanuele, Battaglia, Agatino, Chiocchetti, Andreas G, Freitag, Christine M, Garcia-Alcon, Alicia, Grammatico, Paola, Hertz-Picciotto, Irva, Ludena-Rodriguez, Yunin, Moreno, Carmen, Novelli, Antonio, Parellada, Mara, Pascolini, Giulia, Tassone, Flora, Grice, Dorothy E, Di Marino, Daniele, Bernier, Raphael A, Kolevzon, Alexander, Sharp, Andrew J, Buxbaum, Joseph D, Siper, Paige M, and De Rubeis, Silvia

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Human Genome, Brain Disorders, Basic Behavioral and Social Science, Intellectual and Developmental Disabilities (IDD), Mental Health, Behavioral and Social Science, Autism, Neurosciences, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Neurological, Autism Spectrum Disorder, Child, DNA Methylation, Developmental Disabilities, Epigenesis, Genetic, Female, Homeodomain Proteins, Humans, Intellectual Disability, Male, Mutation, Nerve Tissue Proteins, Neurodevelopmental Disorders, Phenotype, Transcriptome, ADNP, DNA methylation, Helsmoortel-Van der Aa syndrome, autism spectrum disorder, biomarkers, epigenetic signature, episignature, genotype-phenotype correlations, intellectual disability, neurodevelopmental disorders, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Helsmoortel-Van der Aa syndrome (HVDAS) is a neurodevelopmental condition associated with intellectual disability/developmental delay, autism spectrum disorder, and multiple medical comorbidities. HVDAS is caused by mutations in activity-dependent neuroprotective protein (ADNP). A recent study identified genome-wide DNA methylation changes in 22 individuals with HVDAS, adding to the group of neurodevelopmental disorders with an epigenetic signature. This methylation signature segregated those with HVDAS into two groups based on the location of the mutations. Here, we conducted an independent study on 24 individuals with HVDAS and replicated the existence of the two mutation-dependent episignatures. To probe whether the two distinct episignatures correlate with clinical outcomes, we used deep behavioral and neurobiological data from two prospective cohorts of individuals with a genetic diagnosis of HVDAS. We found limited phenotypic differences between the two HVDAS-affected groups and no evidence that individuals with more widespread methylation changes are more severely affected. Moreover, in spite of the methylation changes, we observed no profound alterations in the blood transcriptome of individuals with HVDAS. Our data warrant caution in harnessing methylation signatures in HVDAS as a tool for clinical stratification, at least with regard to behavioral phenotypes.

Published
2020

22. Publisher Correction: Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

Author

Lim, Elaine T, Uddin, Mohammed, De Rubeis, Silvia, Chan, Yingleong, Kamumbu, Anne S, Zhang, Xiaochang, D’Gama, Alissa M, Kim, Sonia N, Hill, Robert Sean, Goldberg, Arthur P, Poultney, Christopher, Minshew, Nancy J, Kushima, Itaru, Aleksic, Branko, Ozaki, Norio, Parellada, Mara, Arango, Celso, Penzol, Maria J, Carracedo, Angel, Kolevzon, Alexander, Hultman, Christina M, Weiss, Lauren A, Fromer, Menachem, Chiocchetti, Andreas G, Freitag, Christine M, Church, George M, Scherer, Stephen W, Buxbaum, Joseph D, and Walsh, Christopher A

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Autism Sequencing Consortium, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

23. 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

26. Repetitive Behavior in Children and Adolescents: Psychometric Properties of the German Version of the Repetitive Behavior Scale-Revised

Author

Kästel, Isabella S., Vllasaliu, Leonora, Wellnitz, Sophia, Cholemkery, Hannah, Freitag, Christine M., and Bast, Nico

Abstract

Restricted repetitive behaviors (RRBs) are a core feature of autism spectrum disorders (ASD) and further occur in intellectual disability (ID), mental disorders (MD), and in typically developed people (TD). There is a need of a valid and reliable measure to record RRBs as transdiagnostic symptom, which captures RRBs heterogeneity and evaluates severity. The Repetitive Behavior Scale-Revised (RBS-R) is an established screening instrument for RRBs, but was predominantly limited to ASD samples. We examined the psychometric properties of the German version of the RBS-R in 948 participants with ASD, ID, MD and TD aged 4 to 17 years. The suitability was proofed delivering a four-factor solution, good internal consistency, external validity as well as group, age, and sex effects.

Published
2021
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27. Neuroanatomical predictors of transcranial direct current stimulation (tDCS)-induced modifications in neurocognitive task performance in typically developing individuals

Author

Gurr, Caroline, primary, Splittgerber, Maike, additional, Puonti, Oula, additional, Siemann, Julia, additional, Luckhardt, Christina, additional, Pereira, Helena C., additional, Amaral, Joana, additional, Crisóstomo, Joana, additional, Sayal, Alexandre, additional, Ribeiro, Mário, additional, Sousa, Daniela, additional, Dempfle, Astrid, additional, Krauel, Kerstin, additional, Borzikowsky, Christoph, additional, Brauer, Hannah, additional, Prehn-Kristensen, Alexander, additional, Breitling-Ziegler, Carolin, additional, Castelo-Branco, Miguel, additional, Salvador, Ricardo, additional, Damiani, Giada, additional, Ruffini, Giulio, additional, Siniatchkin, Michael, additional, Thielscher, Axel, additional, Freitag, Christine M., additional, Moliadze, Vera, additional, and Ecker, Christine, additional

Published
2024
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29. Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium

Author

Sha, Zhiqiang, van Rooij, Daan, Anagnostou, Evdokia, Arango, Celso, Auzias, Guillaume, Behrmann, Marlene, Bernhardt, Boris, Bolte, Sven, Busatto, Geraldo F., Calderoni, Sara, Calvo, Rosa, Daly, Eileen, Deruelle, Christine, Duan, Meiyu, Duran, Fabio Luis Souza, Durston, Sarah, Ecker, Christine, Ehrlich, Stefan, Fair, Damien, Fedor, Jennifer, Fitzgerald, Jacqueline, Floris, Dorothea L., Franke, Barbara, Freitag, Christine M., Gallagher, Louise, Glahn, David C., Haar, Shlomi, Hoekstra, Liesbeth, Jahanshad, Neda, Jalbrzikowski, Maria, Janssen, Joost, King, Joseph A., Lazaro, Luisa, Luna, Beatriz, McGrath, Jane, Medland, Sarah E., Muratori, Filippo, Murphy, Declan G. M., Neufeld, Janina, O’Hearn, Kirsten, Oranje, Bob, Parellada, Mara, Pariente, Jose C., Postema, Merel C., Remnelius, Karl Lundin, Retico, Alessandra, Rosa, Pedro Gomes Penteado, Rubia, Katya, Shook, Devon, Tammimies, Kristiina, Taylor, Margot J., Tosetti, Michela, Wallace, Gregory L., Zhou, Fengfeng, Thompson, Paul M., Fisher, Simon E., Buitelaar, Jan K., and Francks, Clyde

Published
2022
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33. The Lancet Commission on the future of care and clinical research in autism

Author

Lord, Catherine, Charman, Tony, Havdahl, Alexandra, Carbone, Paul, Anagnostou, Evdokia, Boyd, Brian, Carr, Themba, de Vries, Petrus J, Dissanayake, Cheryl, Divan, Gauri, Freitag, Christine M, Gotelli, Marina M, Kasari, Connie, Knapp, Martin, Mundy, Peter, Plank, Alex, Scahill, Lawrence, Servili, Chiara, Shattuck, Paul, Simonoff, Emily, Singer, Alison Tepper, Slonims, Vicky, Wang, Paul P, Ysrraelit, Maria Celica, Jellett, Rachel, Pickles, Andrew, Cusack, James, Howlin, Patricia, Szatmari, Peter, Holbrook, Alison, Toolan, Christina, and McCauley, James B

Published
2022
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34. Non-mental diseases associated with ADHD across the lifespan: Fidgety Philipp and Pippi Longstocking at risk of multimorbidity?

Author

Kittel-Schneider, Sarah, Arteaga-Henriquez, Gara, Vasquez, Alejandro Arias, Asherson, Phil, Banaschewski, Tobias, Brikell, Isabell, Buitelaar, Jan, Cormand, Bru, Faraone, Stephen V., Freitag, Christine M., Ginsberg, Ylva, Haavik, Jan, Hartman, Catharina A., Kuntsi, Jonna, Larsson, Henrik, Matura, Silke, McNeill, Rhiannon V., Ramos-Quiroga, J. Antoni, Ribases, Marta, Romanos, Marcel, Vainieri, Isabella, Franke, Barbara, and Reif, Andreas

Published
2022
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36. Dual Molecular Effects of Dominant RORA Mutations Cause Two Variants of Syndromic Intellectual Disability with Either Autism or Cerebellar Ataxia

Author

Guissart, Claire, Latypova, Xenia, Rollier, Paul, Khan, Tahir N, Stamberger, Hannah, McWalter, Kirsty, Cho, Megan T, Kjaergaard, Susanne, Weckhuysen, Sarah, Lesca, Gaetan, Besnard, Thomas, Õunap, Katrin, Schema, Lynn, Chiocchetti, Andreas G, McDonald, Marie, de Bellescize, Julitta, Vincent, Marie, Van Esch, Hilde, Sattler, Shannon, Forghani, Irman, Thiffault, Isabelle, Freitag, Christine M, Barbouth, Deborah Sara, Cadieux-Dion, Maxime, Willaert, Rebecca, Sacoto, Maria J Guillen, Safina, Nicole P, Dubourg, Christèle, Grote, Lauren, Carré, Wilfrid, Saunders, Carol, Pajusalu, Sander, Farrow, Emily, Boland, Anne, Karlowicz, Danielle Hays, Deleuze, Jean-François, Wojcik, Monica H, Pressman, Rena, Isidor, Bertrand, Vogels, Annick, Van Paesschen, Wim, Al-Gazali, Lihadh, Shamsi, Aisha Mohamed Al, Claustres, Mireille, Pujol, Aurora, Sanders, Stephan J, Rivier, François, Leboucq, Nicolas, Cogné, Benjamin, Sasorith, Souphatta, Sanlaville, Damien, Retterer, Kyle, Odent, Sylvie, Katsanis, Nicholas, Bézieau, Stéphane, Koenig, Michel, Davis, Erica E, Pasquier, Laurent, and Küry, Sébastien

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Intellectual and Developmental Disabilities (IDD), Neurodegenerative, Neurosciences, Pediatric, Rare Diseases, Brain Disorders, Autism, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adolescent, Adult, Aged, 80 and over, Alleles, Animals, Autistic Disorder, Brain, Cerebellar Ataxia, Child, Child, Preschool, DNA Copy Number Variations, Disease Models, Animal, Female, Genes, Dominant, Genetic Complementation Test, Humans, Intellectual Disability, Larva, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Missense, Nuclear Receptor Subfamily 1, Group F, Member 1, Purkinje Cells, Syndrome, Zebrafish, RORA, autistic features, cerebellar ataxia, dual molecular effects, epilepsy, intellectual disability, neurodevelopmental disorder, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

RORα, the RAR-related orphan nuclear receptor alpha, is essential for cerebellar development. The spontaneous mutant mouse staggerer, with an ataxic gait caused by neurodegeneration of cerebellar Purkinje cells, was discovered two decades ago to result from homozygous intragenic Rora deletions. However, RORA mutations were hitherto undocumented in humans. Through a multi-centric collaboration, we identified three copy-number variant deletions (two de novo and one dominantly inherited in three generations), one de novo disrupting duplication, and nine de novo point mutations (three truncating, one canonical splice site, and five missense mutations) involving RORA in 16 individuals from 13 families with variable neurodevelopmental delay and intellectual disability (ID)-associated autistic features, cerebellar ataxia, and epilepsy. Consistent with the human and mouse data, disruption of the D. rerio ortholog, roraa, causes significant reduction in the size of the developing cerebellum. Systematic in vivo complementation studies showed that, whereas wild-type human RORA mRNA could complement the cerebellar pathology, missense variants had two distinct pathogenic mechanisms of either haploinsufficiency or a dominant toxic effect according to their localization in the ligand-binding or DNA-binding domains, respectively. This dichotomous direction of effect is likely relevant to the phenotype in humans: individuals with loss-of-function variants leading to haploinsufficiency show ID with autistic features, while individuals with de novo dominant toxic variants present with ID, ataxia, and cerebellar atrophy. Our combined genetic and functional data highlight the complex mutational landscape at the human RORA locus and suggest that dual mutational effects likely determine phenotypic outcome.

Published
2018

37. Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

Author

Lim, Elaine T, Uddin, Mohammed, De Rubeis, Silvia, Chan, Yingleong, Kamumbu, Anne S, Zhang, Xiaochang, D'Gama, Alissa M, Kim, Sonia N, Hill, Robert Sean, Goldberg, Arthur P, Poultney, Christopher, Minshew, Nancy J, Kushima, Itaru, Aleksic, Branko, Ozaki, Norio, Parellada, Mara, Arango, Celso, Penzol, Maria J, Carracedo, Angel, Kolevzon, Alexander, Hultman, Christina M, Weiss, Lauren A, Fromer, Menachem, Chiocchetti, Andreas G, Freitag, Christine M, Church, George M, Scherer, Stephen W, Buxbaum, Joseph D, and Walsh, Christopher A

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Brain Disorders, Autism, Genetics, Pediatric, Mental Health, Intellectual and Developmental Disabilities (IDD), 2.1 Biological and endogenous factors, Aetiology, Mental health, Autism Spectrum Disorder, Databases, Genetic, Genetic Predisposition to Disease, Genetic Variation, Humans, Mosaicism, Mutation, Missense, Zygote, Autism Sequencing Consortium, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 × 10-6), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 × 10-3). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU and SMARCA4) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk.

Published
2017

38. Identifying Cortical Structure Markers of Resilience to Adversity in Young People using Surface-Based Morphometry

Author

Cornwell, Harriet, primary, Toschi, Nicola, additional, Hamilton-Giachritsis, Catherine, additional, Staginnus, Marlene, additional, Smaragdi, Areti, additional, Gonzalez-Madruga, Karen, additional, Mackes, Nuria, additional, Rogers, Jack, additional, Martinelli, Anne, additional, Kohls, Gregor, additional, Raschle, Nora Maria, additional, Konrad, Kerstin, additional, Stadler, Christina, additional, Freitag, Christine M, additional, De Brito, Stephane A, additional, and Fairchild, Graeme, additional

Published
2024
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41. Sex-specific associations of basal steroid hormones and neuropeptides with Conduct Disorder and neuroendocrine mediation of environmental risk

Author

Bernhard, Anka, Kirchner, Marietta, Martinelli, Anne, Ackermann, Katharina, Kohls, Gregor, Gonzalez-Madruga, Karen, Wells, Amy, Fernández-Rivas, Aranzazu, De Artaza-Lavesa, Maider Gonzalez, Raschle, Nora Maria, Konsta, Angeliki, Siklósi, Réka, Hervás, Amaia, Herpertz-Dahlmann, Beate, De Brito, Stephane A., Popma, Arne, Stadler, Christina, Konrad, Kerstin, Fairchild, Graeme, and Freitag, Christine M.

Published
2021
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42. Repetitive Behavior in Children and Adolescents: Psychometric Properties of the German Version of the Repetitive Behavior Scale-Revised

Author

Kästel, Isabella S., Vllasaliu, Leonora, Wellnitz, Sophia, Cholemkery, Hannah, Freitag, Christine M., and Bast, Nico

Subjects
Cognition -- Testing, Pervasive developmental disorders -- Complications and side effects -- Diagnosis, Children -- Behavior, Compulsive behavior -- Risk factors -- Diagnosis, Pediatric research, Health
Abstract

Restricted repetitive behaviors (RRBs) are a core feature of autism spectrum disorders (ASD) and further occur in intellectual disability (ID), mental disorders (MD), and in typically developed people (TD). There is a need of a valid and reliable measure to record RRBs as transdiagnostic symptom, which captures RRBs heterogeneity and evaluates severity. The Repetitive Behavior Scale-Revised (RBS-R) is an established screening instrument for RRBs, but was predominantly limited to ASD samples. We examined the psychometric properties of the German version of the RBS-R in 948 participants with ASD, ID, MD and TD aged 4 to 17 years. The suitability was proofed delivering a four-factor solution, good internal consistency, external validity as well as group, age, and sex effects., Author(s): Isabella S. Kästel [sup.1] , Leonora Vllasaliu [sup.1] , Sophia Wellnitz [sup.1] , Hannah Cholemkery [sup.1] , Christine M. Freitag [sup.1] , Nico Bast [sup.1] Author Affiliations: (1) grid.411088.4, [...]

Published
2021
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44. Cortical structure and subcortical volumes in conduct disorder: a coordinated analysis of 15 international cohorts from the ENIGMA-Antisocial Behavior Working Group

Author

Gao, Yidian, Staginnus, Marlene, Gao, Yidian, Staginnus, Marlene, Townend, Sophie, Arango, Celso, Bajaj, Sahil, Banaschewski, Tobias, Barker, Edward D., Benegal, Vivek, Berluti, Kathryn, Bernhard, Anka, Blair, Robert J.R., Boateng, Charlotte P.S., Bokde, Arun L.W., Brandeis, Daniel, Buitelaar, Jan K., Burt, S. Alexandra, Cardinale, Elise M., Castro-Fornieles, Josefina, Chen, Hui, Chen, Xianliang, Chester, Sally C., Colins, Olivier F., Cornwell, Harriet, Craig, Michael, Cubillo, Ana I., Desrivieres, Sylvane, Díaz, Dana E., Dietrich, Andrea, Dong, Daifeng, Dykstra, Anouk H., Franke, Barbara, Freitag, Christine M., Glennon, Jeffrey C., Gonzalez-Madruga, Karen, Hagan, Cindy C., Hoekstra, Pieter J., Holla, Bharath, Hyde, Luke W., Ibrahim, Karim, Jabeen, Nimrah, Jackson, Rebecca L., Jiang, Yali, Kohls, Gregor, Konrad, Kerstin, Kypta-Vivanco, Alexandra, Lamers, Kim, Ma, Ren, Marsh, Abigail A., Martinelli, Anne, Martinot, Jean-Luc, Michalska, Kalina J., Ming, Qingsen, Minosse, Silvia, Mitchell, Colter, Monk, Christopher S., Murphy, Declan, Mycue, Leah E., Naaijen, Jilly, Oosterling, Maaike, Passamonti, Luca, Pauli, Ruth, Penzol Alonso, Maria Jose, Phillips, Harriet, Ploe, Montana L., Raschle, Nora M., Roberts, Ruth, Rogers, Jack C., Rosa-Justicia, Mireia, Sagar-Ouriaghli, Ilyas, Schulze, Ulrike M.E., Schumann, Gunter, Sethi, Arjun, Smaragdi, Areti, Sonuga-Barke, Edmund J.S., Stadler, Christina, Stevens, Michael C., Sukhodolsky, Denis G., Sully, Kate, Sun, Xiaoqiang, Toschi, Nicola, Townsend, Christopher D., van der Wee, Nic J.A., Vermeiren, Robert, Viding, Essi, Wang, Xiaoping, Westerman, Heidi B., Wu, Qiong, Yao, Shuqiao, Zhang, Jibiao, Zhou, Jiansong, Zhou, Jiawei, Jahanshad, Neda, Thomopoulos, Sophia I., Ching, Christopher R.K., Kang, Melody J.Y., Thompson, Paul M., Klapwijk, Eduard T., Pine, Daniel S., Baskin-Sommers, Arielle, Cecil, Charlotte A.M., Aghajani, Moji, Walton, Esther, Fairchild, Graeme, and De Brito, Stephane A.

Abstract

Conduct disorder is associated with the highest burden of any mental disorder in childhood, yet its neurobiology remains unclear. Inconsistent findings limit our understanding of the role of brain structure alterations in conduct disorder. This study aims to identify the most robust and replicable brain structural correlates of conduct disorder.

Published
2024
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45. Sensitivity and Specificity of the ADOS-2 Algorithm in a Large German Sample

Author

Medda, Juliane E., Cholemkery, Hannah, and Freitag, Christine M.

Abstract

The aim of the present study was to establish diagnostic validity of the new algorithm of the Autism Diagnostic Observation Scale, the ADOS-2, to differentiate between ASD and other clinically relevant psychiatric and developmental disorders in a large German sample. Validity of ADOS and ADOS-2 diagnostic algorithms was established in 826 individuals (n = 455 autism, n = 216 autism spectrum, n = 155 non-ASD patients) by receiver operating curves. Confidence intervals overlapped largely for ADOS and ADOS-2 algorithms, confirming diagnostic validity of both algorithms. Adding information of the Social Communication Questionnaire and the Social Responsiveness Scale resulted in slightly improved classification rates for autism in Module 4. We thus replicated previous findings of the diagnostic validity of the ADOS-2 algorithms.

Published
2019
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47. START NOW: a cognitive behavioral skills training for adolescent girls with conduct or oppositional defiant disorder – a randomized clinical trial.

Author

Stadler, Christina, Freitag, Christine M., Popma, Arne, Nauta‐Jansen, Lucres, Konrad, Kerstin, Unternaehrer, Eva, Ackermann, Katharina, Bernhard, Anka, Martinelli, Anne, Oldenhof, Helena, Gundlach, Malou, Kohls, Gregor, Prätzlich, Martin, Kieser, Meinhard, Limprecht, Ronald, Raschle, Nora M., Vriends, Noortje, Trestman, Robert L., Kirchner, Marietta, and Kersten, Linda

Subjects
*RESEARCH, *CONFIDENCE intervals, *RESEARCH methodology, *PSYCHOSOCIAL functioning, *BEHAVIOR disorders, *PSYCHOLOGY of women, *OPPOSITIONAL defiant disorder in children, *AGGRESSION (Psychology), *COGNITIVE therapy, *MOTOR ability, *SOCIAL disabilities, *LONGITUDINAL method, *ADOLESCENCE
Abstract

Background: Conduct disorder (CD) and oppositional defiant disorder (ODD) both convey a high risk for maladjustment later in life and are understudied in girls. Here, we aimed at confirming the efficacy of START NOW, a cognitive‐behavioral, dialectical behavior therapy‐oriented skills training program aiming to enhance emotion regulation skills, interpersonal and psychosocial adjustment, adapted for female adolescents with CD or ODD. Methods: A total of 127 girls were included in this prospective, cluster randomized, multi‐center, parallel group, quasi‐randomized, controlled phase III trial, which tested the efficacy of START NOW (n = 72) compared with standard care (treatment as usual, TAU, n = 55). All female adolescents had a clinical diagnosis of CD or ODD, were 15.6 (±1.5) years on average (range: 12–20 years), and were institutionalized in youth welfare institutions. The two primary endpoints were the change in number of CD/ODD symptoms between (1) baseline (T1) and post‐treatment (T3), and (2) between T1 and 12‐week follow‐up (T4). Results: Both treatment groups showed reduced CD/ODD symptoms at T3 compared with T1 (95% CI: START NOW = −4.87, −2.49; TAU = −4.94, −2.30). There was no significant mean difference in CD/ODD symptom reduction from T1 to T3 between START NOW and TAU (−0.056; 95% CI = −1.860, 1.749; Hedge's g = −0.011). However, the START NOW group showed greater mean symptom reduction from T1 to T4 (−2.326; 95% CI = −4.274, −0.378; Hedge's g = −0.563). Additionally, secondary endpoint results revealed a reduction in staff reported aggression and parent‐reported irritability at post assessment. Conclusions: Although START NOW did not result in greater symptom reduction from baseline to post‐treatment compared with TAU, the START NOW group showed greater symptom reduction from baseline to follow‐up with a medium effect size, which indicates a clinically meaningful delayed treatment effect. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Phase-IIa randomized, double-blind, sham-controlled, parallel group trial on anodal transcranial direct current stimulation (tDCS) over the left and right tempo-parietal junction in autism spectrum disorder—StimAT: study protocol for a clinical trial

Author

Luckhardt, Christina, Schütz, Magdalena, Mühlherr, Andreas, Mössinger, Hannah, Boxhoorn, Sara, Dempfle, Astrid, Salvador, Ricardo, Ruffini, Giulio, Pereira, Helena C., Castelo-Branco, Miguel, Latinus, Marianne, Bonnet-Brilhault, Frédérique, Siemann, Julia, Siniatchkin, Michael, Ecker, Christine, and Freitag, Christine M.

Published
2021
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49. Author Correction: Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Author

Postema, Merel C., van Rooij, Daan, Anagnostou, Evdokia, Arango, Celso, Auzias, Guillaume, Behrmann, Marlene, Filho, Geraldo Busatto, Calderoni, Sara, Calvo, Rosa, Daly, Eileen, Deruelle, Christine, Di Martino, Adriana, Dinstein, Ilan, Duran, Fabio Luis S., Durston, Sarah, Ecker, Christine, Ehrlich, Stefan, Fair, Damien, Fedor, Jennifer, Feng, Xin, Fitzgerald, Jackie, Floris, Dorothea L., Freitag, Christine M., Gallagher, Louise, Glahn, David C., Gori, Ilaria, Haar, Shlomi, Hoekstra, Liesbeth, Jahanshad, Neda, Jalbrzikowski, Maria, Janssen, Joost, King, Joseph A., Kong, Xiang Zhen, Lazaro, Luisa, Lerch, Jason P., Luna, Beatriz, Martinho, Mauricio M., McGrath, Jane, Medland, Sarah E., Muratori, Filippo, Murphy, Clodagh M., Murphy, Declan G. M., O’Hearn, Kirsten, Oranje, Bob, Parellada, Mara, Puig, Olga, Retico, Alessandra, Rosa, Pedro, Rubia, Katya, Shook, Devon, Taylor, Margot J., Tosetti, Michela, Wallace, Gregory L., Zhou, Fengfeng, Thompson, Paul M., Fisher, Simon E., Buitelaar, Jan K., and Francks, Clyde

Published
2021
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50. Correction: SLC25A24 gene methylation and gray matter volume in females with and without conduct disorder: an exploratory epigenetic neuroimaging study

Author

Farrow, Elizabeth, Chiocchetti, Andreas G., Rogers, Jack C., Pauli, Ruth, Raschle, Nora M., Gonzalez-Madruga, Karen, Smaragdi, Areti, Martinelli, Anne, Kohls, Gregor, Stadler, Christina, Konrad, Kerstin, Fairchild, Graeme, Freitag, Christine M., Chechlacz, Magdalena, and De Brito, Stephane A.

Published
2021
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