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1. 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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4. 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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6. 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

7. 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

8. 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

9. 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. 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

13. 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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14. 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

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

Author

Stadler, Christina; https://orcid.org/0000-0003-2178-0635, Freitag, Christine M; https://orcid.org/0000-0001-9676-4782, Popma, Arne; https://orcid.org/0000-0003-2170-3023, Nauta‐Jansen, Lucres; https://orcid.org/0000-0001-8475-4050, Konrad, Kerstin; https://orcid.org/0000-0001-9039-2615, Unternaehrer, Eva, Ackermann, Katharina; https://orcid.org/0000-0001-6443-7680, Bernhard, Anka; https://orcid.org/0000-0001-8864-1360, Martinelli, Anne; https://orcid.org/0000-0002-7158-9778, Oldenhof, Helena; https://orcid.org/0000-0002-7210-1519, Gundlach, Malou, Kohls, Gregor; https://orcid.org/0000-0003-2408-2939, Prätzlich, Martin, Kieser, Meinhard, Limprecht, Ronald, Raschle, Nora Maria; https://orcid.org/0000-0002-3160-5999, Vriends, Noortje, Trestman, Robert L, Kirchner, Marietta, Kersten, Linda, Stadler, Christina; https://orcid.org/0000-0003-2178-0635, Freitag, Christine M; https://orcid.org/0000-0001-9676-4782, Popma, Arne; https://orcid.org/0000-0003-2170-3023, Nauta‐Jansen, Lucres; https://orcid.org/0000-0001-8475-4050, Konrad, Kerstin; https://orcid.org/0000-0001-9039-2615, Unternaehrer, Eva, Ackermann, Katharina; https://orcid.org/0000-0001-6443-7680, Bernhard, Anka; https://orcid.org/0000-0001-8864-1360, Martinelli, Anne; https://orcid.org/0000-0002-7158-9778, Oldenhof, Helena; https://orcid.org/0000-0002-7210-1519, Gundlach, Malou, Kohls, Gregor; https://orcid.org/0000-0003-2408-2939, Prätzlich, Martin, Kieser, Meinhard, Limprecht, Ronald, Raschle, Nora Maria; https://orcid.org/0000-0002-3160-5999, Vriends, Noortje, Trestman, Robert L, Kirchner, Marietta, and Kersten, Linda

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.

Published
2024

16. Verbal memory performance in adolescents and adults with ADHD

Author

Pawley, Adam D., Mayer, Jutta, Medda, Juliane, Brandt, Geva A., Agnew-Blais, Jessica C., Asherson, Philip, Rommel, Anna-Sophie, Ramos-Quiroga, J. Antoni, Palacio Sanchez, Judit, Bergsma, Douwe, Buitelaar, Jan K., Ortega, Francisco B., Muntaner-Mas, Adrià, Grimm, Oliver, Reif, Andreas, Freitag, Christine M., Kuntsi, Jonna, Pawley, Adam D., Mayer, Jutta, Medda, Juliane, Brandt, Geva A., Agnew-Blais, Jessica C., Asherson, Philip, Rommel, Anna-Sophie, Ramos-Quiroga, J. Antoni, Palacio Sanchez, Judit, Bergsma, Douwe, Buitelaar, Jan K., Ortega, Francisco B., Muntaner-Mas, Adrià, Grimm, Oliver, Reif, Andreas, Freitag, Christine M., and Kuntsi, Jonna

Abstract

Beyond well-established difficulties with working memory in individuals with attention deficit hyperactivity disorder (ADHD), evidence is emerging that other memory processes may also be affected. We investigated, first, which memory processes show differences in adults and adolescents with ADHD in comparison to control participants, focusing on working and short-term memory, initial learning, interference, delayed and recognition memory. Second, we investigated whether ADHD severity, co-occurring depressive symptoms, IQ and physical fitness are associated with the memory performance in the individuals with ADHD. We assessed 205 participants with ADHD (mean age 25.8 years, SD 7.99) and 50 control participants (mean age 21.1 years, SD 5.07) on cognitive tasks including the digit span forward (DSF) and backward (DSB), the Rey Auditory Verbal Learning Test (RAVLT), and the vocabulary and matrix reasoning subtests of the Wechsler Abbreviated Scale of Intelligence. Participants with ADHD were additionally assessed on ADHD severity, depression symptoms and cardiorespiratory fitness. A series of regressions were run, with sensitivity analyses performed when variables were skewed. ADHD-control comparisons were significant for DSF, DSB, delayed and recognition memory, with people with ADHD performing less well than the control participants. The result for recognition memory was no longer significant in sensitivity analysis. Memory performance was not associated with greater ADHD or depression symptoms severity. IQ was positively associated with all memory variables except DSF. Cardiorespiratory fitness was negatively associated with the majority of RAVLT variables. Individuals with ADHD showed difficulties with working memory, short-term memory and delayed memory, as well as a potential difficulty with recognition memory, despite preserved initial learning.

Published
2024

18. 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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19. 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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20. 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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21. 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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23. Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders

Author

Pinto, Dalila, Delaby, Elsa, Merico, Daniele, Barbosa, Mafalda, Merikangas, Alison, Klei, Lambertus, Thiruvahindrapuram, Bhooma, Xu, Xiao, Ziman, Robert, Wang, Zhuozhi, Vorstman, Jacob AS, Thompson, Ann, Regan, Regina, Pilorge, Marion, Pellecchia, Giovanna, Pagnamenta, Alistair T, Oliveira, Bárbara, Marshall, Christian R, Magalhaes, Tiago R, Lowe, Jennifer K, Howe, Jennifer L, Griswold, Anthony J, Gilbert, John, Duketis, Eftichia, Dombroski, Beth A, De Jonge, Maretha V, Cuccaro, Michael, Crawford, Emily L, Correia, Catarina T, Conroy, Judith, Conceição, Inês C, Chiocchetti, Andreas G, Casey, Jillian P, Cai, Guiqing, Cabrol, Christelle, Bolshakova, Nadia, Bacchelli, Elena, Anney, Richard, Gallinger, Steven, Cotterchio, Michelle, Casey, Graham, Zwaigenbaum, Lonnie, Wittemeyer, Kerstin, Wing, Kirsty, Wallace, Simon, van Engeland, Herman, Tryfon, Ana, Thomson, Susanne, Soorya, Latha, Rogé, Bernadette, Roberts, Wendy, Poustka, Fritz, Mouga, Susana, Minshew, Nancy, McInnes, L Alison, McGrew, Susan G, Lord, Catherine, Leboyer, Marion, Le Couteur, Ann S, Kolevzon, Alexander, González, Patricia Jiménez, Jacob, Suma, Holt, Richard, Guter, Stephen, Green, Jonathan, Green, Andrew, Gillberg, Christopher, Fernandez, Bridget A, Duque, Frederico, Delorme, Richard, Dawson, Geraldine, Chaste, Pauline, Café, Cátia, Brennan, Sean, Bourgeron, Thomas, Bolton, Patrick F, Bölte, Sven, Bernier, Raphael, Baird, Gillian, Bailey, Anthony J, Anagnostou, Evdokia, Almeida, Joana, Wijsman, Ellen M, Vieland, Veronica J, Vicente, Astrid M, Schellenberg, Gerard D, Pericak-Vance, Margaret, Paterson, Andrew D, Parr, Jeremy R, Oliveira, Guiomar, Nurnberger, John I, Monaco, Anthony P, Maestrini, Elena, Klauck, Sabine M, Hakonarson, Hakon, Haines, Jonathan L, Geschwind, Daniel H, Freitag, Christine M, Folstein, Susan E, and Ennis, Sean

Subjects
Genetics, Brain Disorders, Pediatric, Mental Health, Intellectual and Developmental Disabilities (IDD), Neurosciences, Autism, 2.1 Biological and endogenous factors, Aetiology, Child, Child Development Disorders, Pervasive, DNA Copy Number Variations, Female, Gene Regulatory Networks, Humans, Male, Metabolic Networks and Pathways, Multigene Family, Pedigree, Sequence Deletion, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.

Published
2014

24. The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses

Author

Buxbaum, Joseph D, Bolshakova, Nadia, Brownfeld, Jessica M, Anney, Richard JL, Bender, Patrick, Bernier, Raphael, Cook, Edwin H, Coon, Hilary, Cuccaro, Michael, Freitag, Christine M, Hallmayer, Joachim, Geschwind, Daniel, Klauck, Sabine M, Nurnberger, John I, Oliveira, Guiomar, Pinto, Dalila, Poustka, Fritz, Scherer, Stephen W, Shih, Andy, Sutcliffe, James S, Szatmari, Peter, Vicente, Astrid M, Vieland, Veronica, and Gallagher, Louise

Subjects
Intellectual and Developmental Disabilities (IDD), Clinical Research, Brain Disorders, Pediatric, Autism, Mental Health, Genetics, Behavioral and Social Science, Human Genome, Mental health, Good Health and Well Being, Clinical Sciences, Neurosciences
Abstract

BackgroundThere is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD.MethodsIn a unique public-private partnership, 13 sites with extensive experience in both the assessment and diagnosis of ASD embarked on an ambitious, 2-year program to collect samples for genetic and phenotypic research and begin analyses on these samples. The program was called The Autism Simplex Collection (TASC). TASC sample collection began in 2008 and was completed in 2010, and included nine sites from North America and four sites from Western Europe, as well as a centralized Data Coordinating Center.ResultsOver 1,700 trios are part of this collection, with DNA from transformed cells now available through the National Institute of Mental Health (NIMH). Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule-Generic (ADOS-G) measures are available for all probands, as are standardized IQ measures, Vineland Adaptive Behavioral Scales (VABS), the Social Responsiveness Scale (SRS), Peabody Picture Vocabulary Test (PPVT), and physical measures (height, weight, and head circumference). At almost every site, additional phenotypic measures were collected, including the Broad Autism Phenotype Questionnaire (BAPQ) and Repetitive Behavior Scale-Revised (RBS-R), as well as the non-word repetition scale, Communication Checklist (Children's or Adult), and Aberrant Behavior Checklist (ABC). Moreover, for nearly 1,000 trios, the Autism Genome Project Consortium (AGP) has carried out Illumina 1 M SNP genotyping and called copy number variation (CNV) in the samples, with data being made available through the National Institutes of Health (NIH). Whole exome sequencing (WES) has been carried out in over 500 probands, together with ancestry matched controls, and this data is also available through the NIH. Additional WES is being carried out by the Autism Sequencing Consortium (ASC), where the focus is on sequencing complete trios. ASC sequencing for the first 1,000 samples (all from whole-blood DNA) is complete and data will be released in 2014. Data is being made available through NIH databases (database of Genotypes and Phenotypes (dbGaP) and National Database for Autism Research (NDAR)) with DNA released in Dist 11.0. Primary funding for the collection, genotyping, sequencing and distribution of TASC samples was provided by Autism Speaks and the NIH, including the National Institute of Mental Health (NIMH) and the National Human Genetics Research Institute (NHGRI).ConclusionsTASC represents an important sample set that leverages expert sites. Similar approaches, leveraging expert sites and ongoing studies, represent an important path towards further enhancing available ASD samples.

Published
2014

26. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Author

Casey, Jillian P, Magalhaes, Tiago, Conroy, Judith M, Regan, Regina, Shah, Naisha, Anney, Richard, Shields, Denis C, Abrahams, Brett S, Almeida, Joana, Bacchelli, Elena, Bailey, Anthony J, Baird, Gillian, Battaglia, Agatino, Berney, Tom, Bolshakova, Nadia, Bolton, Patrick F, Bourgeron, Thomas, Brennan, Sean, Cali, Phil, Correia, Catarina, Corsello, Christina, Coutanche, Marc, Dawson, Geraldine, de Jonge, Maretha, Delorme, Richard, Duketis, Eftichia, Duque, Frederico, Estes, Annette, Farrar, Penny, Fernandez, Bridget A, Folstein, Susan E, Foley, Suzanne, Fombonne, Eric, Freitag, Christine M, Gilbert, John, Gillberg, Christopher, Glessner, Joseph T, Green, Jonathan, Guter, Stephen J, Hakonarson, Hakon, Holt, Richard, Hughes, Gillian, Hus, Vanessa, Igliozzi, Roberta, Kim, Cecilia, Klauck, Sabine M, Kolevzon, Alexander, Lamb, Janine A, Leboyer, Marion, Le Couteur, Ann, Leventhal, Bennett L, Lord, Catherine, Lund, Sabata C, Maestrini, Elena, Mantoulan, Carine, Marshall, Christian R, McConachie, Helen, McDougle, Christopher J, McGrath, Jane, McMahon, William M, Merikangas, Alison, Miller, Judith, Minopoli, Fiorella, Mirza, Ghazala K, Munson, Jeff, Nelson, Stanley F, Nygren, Gudrun, Oliveira, Guiomar, Pagnamenta, Alistair T, Papanikolaou, Katerina, Parr, Jeremy R, Parrini, Barbara, Pickles, Andrew, Pinto, Dalila, Piven, Joseph, Posey, David J, Poustka, Annemarie, Poustka, Fritz, Ragoussis, Jiannis, Roge, Bernadette, Rutter, Michael L, Sequeira, Ana F, Soorya, Latha, Sousa, Inês, Sykes, Nuala, Stoppioni, Vera, Tancredi, Raffaella, Tauber, Maïté, Thompson, Ann P, Thomson, Susanne, Tsiantis, John, Van Engeland, Herman, Vincent, John B, Volkmar, Fred, Vorstman, Jacob AS, Wallace, Simon, Wang, Kai, Wassink, Thomas H, White, Kathy, and Wing, Kirsty

Subjects
Autism, Genetics, Mental Health, Intellectual and Developmental Disabilities (IDD), Brain Disorders, Biotechnology, Pediatric, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adult, Child, Child Development Disorders, Pervasive, Cluster Analysis, Cohort Studies, DNA Copy Number Variations, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Haplotypes, Homozygote, Humans, Linkage Disequilibrium, Male, Middle Aged, Nuclear Family, Polymorphism, Single Nucleotide, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity
Abstract

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.

Published
2012

27. Genome-Wide Analysis of Copy Number Variants in Attention Deficit Hyperactivity Disorder: The Role of Rare Variants and Duplications at 15q13.3

Author

Williams, Nigel M, Franke, Barbara, Mick, Eric, Anney, Richard JL, Freitag, Christine M, Gill, Michael, Thapar, Anita, O'Donovan, Michael C, Owen, Michael J, Holmans, Peter, Kent, Lindsey, Middleton, Frank, Zhang-James, Yanli, Liu, Lu, Meyer, Jobst, Nguyen, Thuy Trang, Romanos, Jasmin, Romanos, Marcel, Seitz, Christiane, Renner, Tobias J, Walitza, Susanne, Warnke, Andreas, Palmason, Haukur, Buitelaar, Jan, Rommelse, Nanda, Vasquez, Alejandro Arias, Hawi, Ziarih, Langley, Kate, Sergeant, Joseph, Steinhausen, Hans-Christoph, Roeyers, Herbert, Biederman, Joseph, Zaharieva, Irina, Hakonarson, Hakon, Elia, Josephine, Lionel, Anath C, Crosbie, Jennifer, Marshall, Christian R, Schachar, Russell, Scherer, Stephen W, Todorov, Alexandre, Smalley, Susan L, Loo, Sandra, Nelson, Stanley, Shtir, Corina, Asherson, Philip, Reif, Andreas, Lesch, Klaus-Peter, and Faraone, Stephen V

Subjects
Human Genome, Clinical Research, Mental Health, Genetics, Pediatric, Attention Deficit Hyperactivity Disorder (ADHD), Brain Disorders, Serious Mental Illness, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Attention Deficit Disorder with Hyperactivity, Canada, Causality, Child, Child, Preschool, Female, Gene Dosage, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, In Situ Hybridization, Fluorescence, Inheritance Patterns, Polymorphism, Single Nucleotide, Receptors, Nicotinic, Segmental Duplications, Genomic, United Kingdom, United States, alpha7 Nicotinic Acetylcholine Receptor, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

ObjectiveAttention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology.MethodThe authors performed a genome-wide analysis of large, rare CNVs (100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder.ConclusionsThese findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5–3.6), this locus could be an important contributor to ADHD etiology.

Published
2012

29. The role of rare compound heterozygous events in autism spectrum disorder

Author

Lin, Bochao Danae, Colas, Fabrice, Nijman, Isaac J., Medic, Jelena, Brands, William, Parr, Jeremy R., van Eijk, Kristel R., Klauck, Sabine M., Chiocchetti, Andreas G., Freitag, Christine M., Maestrini, Elena, Bacchelli, Elena, Coon, Hilary, Vicente, Astrid, Oliveira, Guiomar, Pagnamenta, Alistair T., Gallagher, Louise, Ennis, Sean, Anney, Richard, Bourgeron, Thomas, Luykx, Jurjen J., and Vorstman, Jacob

Published
2020
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30. A genome-wide scan for common alleles affecting risk for autism

Author

Anney, Richard, Klei, Lambertus, Pinto, Dalila, Regan, Regina, Conroy, Judith, Magalhaes, Tiago R, Correia, Catarina, Abrahams, Brett S, Sykes, Nuala, Pagnamenta, Alistair T, Almeida, Joana, Bacchelli, Elena, Bailey, Anthony J, Baird, Gillian, Battaglia, Agatino, Berney, Tom, Bolshakova, Nadia, Bölte, Sven, Bolton, Patrick F, Bourgeron, Thomas, Brennan, Sean, Brian, Jessica, Carson, Andrew R, Casallo, Guillermo, Casey, Jillian, Chu, Su H, Cochrane, Lynne, Corsello, Christina, Crawford, Emily L, Crossett, Andrew, Dawson, Geraldine, de Jonge, Maretha, Delorme, Richard, Drmic, Irene, Duketis, Eftichia, Duque, Frederico, Estes, Annette, Farrar, Penny, Fernandez, Bridget A, Folstein, Susan E, Fombonne, Eric, Freitag, Christine M, Gilbert, John, Gillberg, Christopher, Glessner, Joseph T, Goldberg, Jeremy, Green, Jonathan, Guter, Stephen J, Hakonarson, Hakon, Heron, Elizabeth A, Hill, Matthew, Holt, Richard, Howe, Jennifer L, Hughes, Gillian, Hus, Vanessa, Igliozzi, Roberta, Kim, Cecilia, Klauck, Sabine M, Kolevzon, Alexander, Korvatska, Olena, Kustanovich, Vlad, Lajonchere, Clara M, Lamb, Janine A, Laskawiec, Magdalena, Leboyer, Marion, Le Couteur, Ann, Leventhal, Bennett L, Lionel, Anath C, Liu, Xiao-Qing, Lord, Catherine, Lotspeich, Linda, Lund, Sabata C, Maestrini, Elena, Mahoney, William, Mantoulan, Carine, Marshall, Christian R, McConachie, Helen, McDougle, Christopher J, McGrath, Jane, McMahon, William M, Melhem, Nadine M, Merikangas, Alison, Migita, Ohsuke, Minshew, Nancy J, Mirza, Ghazala K, Munson, Jeff, Nelson, Stanley F, Noakes, Carolyn, Noor, Abdul, Nygren, Gudrun, Oliveira, Guiomar, Papanikolaou, Katerina, Parr, Jeremy R, Parrini, Barbara, Paton, Tara, Pickles, Andrew, Piven, Joseph, Posey, David J, Poustka, Annemarie, and Poustka, Fritz

Subjects
Clinical Research, Human Genome, Mental Health, Genetics, Brain Disorders, Pediatric, Biotechnology, Intellectual and Developmental Disabilities (IDD), Autism, Prevention, Aetiology, 2.1 Biological and endogenous factors, Alleles, Autistic Disorder, DNA Copy Number Variations, Databases, Genetic, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Risk Factors, White People, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

Published
2010

31. The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder

Author

Rots, Dmitrijs, primary, Jakub, Taryn E., additional, Keung, Crystal, additional, Jackson, Adam, additional, Banka, Siddharth, additional, Pfundt, Rolph, additional, de Vries, Bert B.A., additional, van Jaarsveld, Richard H., additional, Hopman, Saskia M.J., additional, van Binsbergen, Ellen, additional, Valenzuela, Irene, additional, Hempel, Maja, additional, Bierhals, Tatjana, additional, Kortüm, Fanny, additional, Lecoquierre, Francois, additional, Goldenberg, Alice, additional, Hertz, Jens Michael, additional, Andersen, Charlotte Brasch, additional, Kibæk, Maria, additional, Prijoles, Eloise J., additional, Stevenson, Roger E., additional, Everman, David B., additional, Patterson, Wesley G., additional, Meng, Linyan, additional, Gijavanekar, Charul, additional, De Dios, Karl, additional, Lakhani, Shenela, additional, Levy, Tess, additional, Wagner, Matias, additional, Wieczorek, Dagmar, additional, Benke, Paul J., additional, Lopez Garcia, María Soledad, additional, Perrier, Renee, additional, Sousa, Sergio B., additional, Almeida, Pedro M., additional, Simões, Maria José, additional, Isidor, Bertrand, additional, Deb, Wallid, additional, Schmanski, Andrew A., additional, Abdul-Rahman, Omar, additional, Philippe, Christophe, additional, Bruel, Ange-Line, additional, Faivre, Laurence, additional, Vitobello, Antonio, additional, Thauvin, Christel, additional, Smits, Jeroen J., additional, Garavelli, Livia, additional, Caraffi, Stefano G., additional, Peluso, Francesca, additional, Davis-Keppen, Laura, additional, Platt, Dylan, additional, Royer, Erin, additional, Leeuwen, Lisette, additional, Sinnema, Margje, additional, Stegmann, Alexander P.A., additional, Stumpel, Constance T.R.M., additional, Tiller, George E., additional, Bosch, Daniëlle G.M., additional, Potgieter, Stephanus T., additional, Joss, Shelagh, additional, Splitt, Miranda, additional, Holden, Simon, additional, Prapa, Matina, additional, Foulds, Nicola, additional, Douzgou, Sofia, additional, Puura, Kaija, additional, Waltes, Regina, additional, Chiocchetti, Andreas G., additional, Freitag, Christine M., additional, Satterstrom, F. Kyle, additional, De Rubeis, Silvia, additional, Buxbaum, Joseph, additional, Gelb, Bruce D., additional, Branko, Aleksic, additional, Kushima, Itaru, additional, Howe, Jennifer, additional, Scherer, Stephen W., additional, Arado, Alessia, additional, Baldo, Chiara, additional, Patat, Olivier, additional, Bénédicte, Demeer, additional, Lopergolo, Diego, additional, Santorelli, Filippo M., additional, Haack, Tobias B., additional, Dufke, Andreas, additional, Bertrand, Miriam, additional, Falb, Ruth J., additional, Rieß, Angelika, additional, Krieg, Peter, additional, Spranger, Stephanie, additional, Bedeschi, Maria Francesca, additional, Iascone, Maria, additional, Josephi-Taylor, Sarah, additional, Roscioli, Tony, additional, Buckley, Michael F., additional, Liebelt, Jan, additional, Dagli, Aditi I., additional, Aten, Emmelien, additional, Hurst, Anna C.E., additional, Hicks, Alesha, additional, Suri, Mohnish, additional, Aliu, Ermal, additional, Naik, Sunil, additional, Sidlow, Richard, additional, Coursimault, Juliette, additional, Nicolas, Gaël, additional, Küpper, Hanna, additional, Petit, Florence, additional, Ibrahim, Veyan, additional, Top, Deniz, additional, Di Cara, Francesca, additional, Louie, Raymond J., additional, Stolerman, Elliot, additional, Brunner, Han G., additional, Vissers, Lisenka E.L.M., additional, Kramer, Jamie M., additional, and Kleefstra, Tjitske, additional

Published
2023
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32. Study protocol of the multi-centre, randomised controlled trial of the Frankfurt Early Intervention Programme A-FFIP versus early intervention as usual for toddlers and preschool children with Autism Spectrum Disorder (A-FFIP study)

Author

Kitzerow, Janina, Hackbusch, Matthes, Jensen, Katrin, Kieser, Meinhard, Noterdaeme, Michele, Fröhlich, Ulrike, Taurines, Regina, Geißler, Julia, Wolff, Nicole, Roessner, Veit, Bast, Nico, Teufel, Karoline, Kim, Ziyon, and Freitag, Christine M.

Published
2020
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33. 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
2019
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36. 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

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

Author

Staginnus, Marlene; https://orcid.org/0000-0002-4739-6271, Cornwell, Harriet, Toschi, Nicola, Oosterling, Maaike, Paradysz, Michal, Smaragdi, Areti, González-Madruga, Karen; https://orcid.org/0000-0002-7586-7536, Pauli, Ruth, Rogers, Jack C, Bernhard, Anka; https://orcid.org/0000-0001-8864-1360, Martinelli, Anne; https://orcid.org/0000-0002-7158-9778, Kohls, Gregor; https://orcid.org/0000-0003-2408-2939, Raschle, Nora Maria; https://orcid.org/0000-0002-3160-5999, Konrad, Kerstin; https://orcid.org/0000-0001-9039-2615, Stadler, Christina; https://orcid.org/0000-0003-2178-0635, Freitag, Christine M; https://orcid.org/0000-0001-9676-4782, De Brito, Stephane A; https://orcid.org/0000-0002-9082-6185, Fairchild, Graeme; https://orcid.org/0000-0001-7814-9938, Staginnus, Marlene; https://orcid.org/0000-0002-4739-6271, Cornwell, Harriet, Toschi, Nicola, Oosterling, Maaike, Paradysz, Michal, Smaragdi, Areti, González-Madruga, Karen; https://orcid.org/0000-0002-7586-7536, Pauli, Ruth, Rogers, Jack C, Bernhard, Anka; https://orcid.org/0000-0001-8864-1360, Martinelli, Anne; https://orcid.org/0000-0002-7158-9778, Kohls, Gregor; https://orcid.org/0000-0003-2408-2939, Raschle, Nora Maria; https://orcid.org/0000-0002-3160-5999, Konrad, Kerstin; https://orcid.org/0000-0001-9039-2615, Stadler, Christina; https://orcid.org/0000-0003-2178-0635, Freitag, Christine M; https://orcid.org/0000-0001-9676-4782, De Brito, Stephane A; https://orcid.org/0000-0002-9082-6185, and Fairchild, Graeme; https://orcid.org/0000-0001-7814-9938

Published
2023

39. Additional file 1 of Sensory salience processing moderates attenuated gazes on faces in autism spectrum disorder: a case–control study

Author

Bast, Nico, Mason, Luke, Ecker, Christine, Baumeister, Sarah, Banaschewski, Tobias, Jones, Emily J. H., Murphy, Declan G. M., Buitelaar, Jan K., Loth, Eva, Pandina, Gahan, and Freitag, Christine M.

Abstract

Additional file 1. Further information on duration of video scenes, pupil size comparisons between groups and video category, pupillary response components, stimuli characterization, comparison of model fits, model definitions, full linear mixed model results, Area-of-interest (AOI) definition criteria, applied R packages, and covariates in the statistical analyses.

Published
2023
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41. Bright light therapy versus physical exercise to prevent co-morbid depression and obesity in adolescents and young adults with attention-deficit / hyperactivity disorder: study protocol for a randomized controlled trial

Author

Mayer, Jutta S., Hees, Katharina, Medda, Juliane, Grimm, Oliver, Asherson, Philip, Bellina, Mariano, Colla, Michael, Ibáñez, Pol, Koch, Elena, Martinez-Nicolas, Antonio, Muntaner-Mas, Adrià, Rommel, Anna, Rommelse, Nanda, de Ruiter, Saskia, Ebner-Priemer, Ulrich W., Kieser, Meinhard, Ortega, Francisco B., Thome, Johannes, Buitelaar, Jan K., Kuntsi, Jonna, Ramos-Quiroga, J. Antoni, Reif, Andreas, and Freitag, Christine M.

Published
2018
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44. Depressive symptoms in youth with ADHD: the role of impairments in cognitive emotion regulation

Author

Mayer, Jutta, Brandt, Geva A., Medda, Juliane, Basten, Ulrike, Grimm, Oliver, Reif, Andreas, Freitag, Christine M., Mayer, Jutta, Brandt, Geva A., Medda, Juliane, Basten, Ulrike, Grimm, Oliver, Reif, Andreas, and Freitag, Christine M.

Abstract

Youth with attention-deficit/hyperactivity disorder (ADHD) are at increased risk to develop co-morbid depression. Identifying factors that contribute to depression risk may allow early intervention and prevention. Poor emotion regulation, which is common in adolescents, is a candidate risk factor. Impaired cognitive emotion regulation is a fundamental characteristic of depression and depression risk in the general population. However, little is known about cognitive emotion regulation in youth with ADHD and its link to depression and depression risk. Using explicit and implicit measures, this study assessed cognitive emotion regulation in youth with ADHD (N = 40) compared to demographically matched healthy controls (N = 40) and determined the association with depressive symptomatology. As explicit measure, we assessed the use of cognitive emotion regulation strategies via self-report. As implicit measure, performance in an ambiguous cue-conditioning task was assessed as indicator of affective bias in the processing of information. Compared to controls, patients reported more frequent use of maladaptive (i.e., self-blame, catastrophizing, and rumination) and less frequent use of adaptive (i.e., positive reappraisal) emotion regulation strategies. This pattern was associated with the severity of current depressive symptoms in patients. In the implicit measure of cognitive bias, there was no significant difference in response of patients and controls and no association with depression. Our findings point to depression-related alterations in the use of cognitive emotion regulation strategies in youth with ADHD. The study suggests those alterations as a candidate risk factor for ADHD-depression comorbidity that may be used for risk assessment and prevention strategies.

Published
2022

45. 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 Rita, Schmidt, Helga, Gerlach, Ferdinand M., Wolff, Kira, Stäblein, Michael, Hauschild, Nora, Beig, Inga, Wagner, Louisa, Müller, Juliane, Verhoff, Marcel A., Schlang, Christiane, Reif, Andreas, 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 Rita, 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

Abstract

The consequences of the current COVID-19 pandemic for mental health remain unclear, especially regarding the effects on suicidal behaviors. To assess changes in the pattern of suicide attempt (SA) admissions and completed suicides (CS) in association with the COVID-19 pandemic. As part of a longitudinal study, SA admissions and CS are systematically documented and analyzed in all psychiatric hospitals in Frankfurt/Main (765.000 inhabitants). Number, sociodemographic factors, diagnoses and methods of SA and CS were compared between the periods of March–December 2019 and March–December 2020. The number of CS did not change, while the number of SA significantly decreased. Age, sex, occupational status, and psychiatric diagnoses did not change in SA, whereas the percentage of patients living alone while attempting suicide increased. The rate and number of intoxications as a SA method increased and more people attempted suicide in their own home, which was not observed in CS. Such a shift from public places to home is supported by the weekday of SA, as the rate of SA on weekends was significantly lower during the pandemic, likely because of lockdown measures. Only admissions to psychiatric hospitals were recorded, but not to other institutions. As it seems unlikely that the number of SA decreased while the number of CS remained unchanged, it is conceivable that the number of unreported SA cases increased during the pandemic. Our data suggest that a higher number of SA remained unnoticed during the pandemic because of their location and the use of methods associated with lower lethality.

Published
2022

46. Mental health and illness in children and adolescents: Challenges for the two new German Research Centres DZKJ and DZPG

Author

Banaschewski, Tobias, Doepfner, Manfred, Fegert, Jorg M., Flechtner, Hans-Henning, Freitag, Christine M., Holtmann, Martin, Kamp-Becker, Inge, Konrad, Kerstin, Poustka, Luise, Renner, Tobias, Roessner, Veit, Romanos, Marcel, Schulte-Korne, Gerd, Thomasius, Rainer, Zepf, Florian, Koelch, Michael, Banaschewski, Tobias, Doepfner, Manfred, Fegert, Jorg M., Flechtner, Hans-Henning, Freitag, Christine M., Holtmann, Martin, Kamp-Becker, Inge, Konrad, Kerstin, Poustka, Luise, Renner, Tobias, Roessner, Veit, Romanos, Marcel, Schulte-Korne, Gerd, Thomasius, Rainer, Zepf, Florian, and Koelch, Michael

Published
2022

47. Developing gene-based personalised interventions in autism spectrum disorders

Author

Freitag, Christine M., Persico, Antonio M., Vorstman, Jacob A. S., Freitag, Christine M., Persico, Antonio M., and Vorstman, Jacob A. S.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with onset in early childhood. While highly heterogeneous, the core manifestations always include persistent difficulties in social interaction and communication, as well as a pattern of restricted interests, repetitive behaviours, and abnormal sensory processing [1]. In addition, psychiatric comorbidity is high [2], and there are genetic risk overlaps with some other mental and neurodevelopmental disorders. In the vast majority of cases, the condition persists into adulthood [3], albeit with various behavioural features and variable mental and somatic comorbidity over a given lifespan. ASD is associated with high societal, educational, and health care costs, and, in many cases, a dramatic impact on the quality of life of patients and their families. ASDs are highly heritable [4], and a multitude of genetic studies have been published. In addition, more recent reviews also emphasize the role of genetic and environmental factors in the pathophysiology of ASD [5,6], which are mediated by lasting epigenetic changes. The genetic architecture of ASD comprises common and rare variations as well as cytogenetic disturbances, such as copy number variations, translocations, inversions, and numerical chromosomal aberrations [7]. Based on the genes affected and the respective functional effects, the idea of personalised medicine is to eventually use that information for the development of targeted treatments or towards the ability to predict the response to a specific intervention, mainly pharmacological but also psychosocial, given the individual’s genetic and environmental risk constellation. The current Special Issue aims to highlight some core aspects regarding basic and applied science approaches in advancing this field of science. Currently, psychopharmacological treatment in ASD can improve many comorbid neurodevelopmental disorders, such as attention-deficit/hyperactivity disorder or aggressive behaviour, a

Published
2022

48. 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., Antoni Ramos-Quiroga, J., Ribases, Marta, Romanos, Marcel, Vainieri, Isabella, Franke, Barbara, Reif, Andreas, 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., Antoni Ramos-Quiroga, J., Ribases, Marta, Romanos, Marcel, Vainieri, Isabella, Franke, Barbara, and Reif, Andreas

Abstract

Several non-mental diseases seem to be associated with an increased risk of ADHD and ADHD seems to be associated with increased risk for non-mental diseases. The underlying trajectories leading to such brain-body co-occurrences are often unclear - are there direct causal relationships from one disorder to the other, or does the sharing of genetic and/or environmental risk factors lead to their occurring together more frequently or both? Our goal with this narrative review was to provide a conceptual synthesis of the associations between ADHD and non-mental disease across the lifespan. We discuss potential shared pathologic mechanisms and genetic background and treatments in co-occurring diseases. For those co-occurrences for which published studies with sufficient sample sizes exist, meta-analyses have been published by others and we discuss those in detail. We conclude that non-mental diseases are common in ADHD and vice versa and add to the disease burden of the patient across the lifespan. Insufficient attention to such co-occurring conditions may result in missed diagnoses and suboptimal treatment in the affected individuals., Funding agencies:Deutscher Akademischer Austausch Dienst (DAAD) European Commission 91690211 Lundbeck Foundation iPSYCH grant R102-A9118 R155-2014-1724 R248-2017-2003 Federal Ministry of Education & Research (BMBF)Spanish Government SAF2015-68341-R RTI2018-100968-B-I00 Agencia de Gestio D'Ajuts Universitaris de Recerca Agaur (AGAUR) Generalitat de Catalunya 2017-SGR-738 Innovative Medicine Initiative (IMI2)-Call 2 853966Instituto de Salud Carlos III CP09/ 00119 CPII15/00023 Instituto de Salud Carlos III PI17/00289Agencia de Gestio D'Ajuts Universitaris de Recerca Agaur (AGAUR)Generalitat de Catalunya General Electric 2017SGR1461Stiftelsen Kristian Gerhard Jebsen SKGJ MED-02Regional Health Authority of Western Norway F-10146

Published
2022
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49. Interindividual Differences in Cortical Thickness and Their Genomic Underpinnings in Autism Spectrum Disorder

Author

Ontwikkelingsstoornissen Ond., Brain, Ecker, Christine, Pretzsch, Charlotte M, Bletsch, Anke, Mann, Caroline, Schaefer, Tim, Ambrosino, Sara, Tillmann, Julian, Yousaf, Afsheen, Chiocchetti, Andreas, Lombardo, Michael V, Warrier, Varun, Bast, Nico, Moessnang, Carolin, Baumeister, Sarah, Dell'Acqua, Flavio, Floris, Dorothea L, Zabihi, Mariam, Marquand, Andre, Cliquet, Freddy, Leblond, Claire, Moreau, Clara, Puts, Nick, Banaschewski, Tobias, Jones, Emily J H, Mason, Luke, Bölte, Sven, Meyer-Lindenberg, Andreas, Persico, Antonio M, Durston, Sarah, Baron-Cohen, Simon, Spooren, Will, Loth, Eva, Freitag, Christine M, Charman, Tony, Dumas, Guillaume, Bourgeron, Thomas, Beckmann, Christian F, Buitelaar, Jan K, Murphy, Declan G M, Ontwikkelingsstoornissen Ond., Brain, Ecker, Christine, Pretzsch, Charlotte M, Bletsch, Anke, Mann, Caroline, Schaefer, Tim, Ambrosino, Sara, Tillmann, Julian, Yousaf, Afsheen, Chiocchetti, Andreas, Lombardo, Michael V, Warrier, Varun, Bast, Nico, Moessnang, Carolin, Baumeister, Sarah, Dell'Acqua, Flavio, Floris, Dorothea L, Zabihi, Mariam, Marquand, Andre, Cliquet, Freddy, Leblond, Claire, Moreau, Clara, Puts, Nick, Banaschewski, Tobias, Jones, Emily J H, Mason, Luke, Bölte, Sven, Meyer-Lindenberg, Andreas, Persico, Antonio M, Durston, Sarah, Baron-Cohen, Simon, Spooren, Will, Loth, Eva, Freitag, Christine M, Charman, Tony, Dumas, Guillaume, Bourgeron, Thomas, Beckmann, Christian F, Buitelaar, Jan K, and Murphy, Declan G M

Published
2022

50. The dynamical association between physical activity and affect in the daily life of individuals with ADHD

Author

Koch, Elena D., Freitag, Christine M., Mayer, Jutta, Medda, Juliane, Reif, Andreas, Grimm, Oliver, Ramos-Quiroga, Josep Antoni, Palacio Sanchez, Judit, Asherson, Philip, Kuntsi, Jonna, Pawley, Adam D., Buitelaar, Jan K., Bergsma, Douwe, Ortega, Francisco B., Muntaner-Mas, Adrià, Reinhard, Iris, Reichert, Markus, Giurgiu, Marco, Ebner-Priemer, Ulrich, Koch, Elena D., Freitag, Christine M., Mayer, Jutta, Medda, Juliane, Reif, Andreas, Grimm, Oliver, Ramos-Quiroga, Josep Antoni, Palacio Sanchez, Judit, Asherson, Philip, Kuntsi, Jonna, Pawley, Adam D., Buitelaar, Jan K., Bergsma, Douwe, Ortega, Francisco B., Muntaner-Mas, Adrià, Reinhard, Iris, Reichert, Markus, Giurgiu, Marco, and Ebner-Priemer, Ulrich

Abstract

Exercise interventions in mental disorders have evidenced a mood-enhancing effect. However, the association between physical activity and affect in everyday life has not been investigated in adult individuals with ADHD, despite being important features of this disorder. As physical activity and affect are dynamic processes in nature, assessing those in everyday life with e-diaries and wearables, has become the gold standard. Thus, we used an mHealth approach to prospectively assess physical activity and affect processes in individuals with ADHD and controls aged 14–45 years. Participants wore accelerometers across a four-day period and reported their affect via e-diaries twelve times daily. We used multilevel models to identify the within-subject effects of physical activity on positive and negative affect. We split our sample into three groups: 1. individuals with ADHD who were predominantly inattentive (n = 48), 2. individuals with ADHD having a combined presentation (i.e., being inattentive and hyperactive; n = 95), and 3. controls (n = 42). Our analyses revealed a significant cross-level interaction (F(2, 135.072)=5.733, p = 0.004) of physical activity and group on positive affect. In details, all groups showed a positive association between physical activity and positive affect. Individuals with a combined presentation significantly showed the steepest slope of physical activity on positive affect (slope_inattentive=0.005, p<0.001; slope_combined=0.009, p<0.001; slope_controls=0.004, p = 0.008). Our analyses on negative affect revealed a negative association only in the individuals with a combined presentation (slope=-0.003; p = 0.001). Whether this specifically pronounced association in individuals being more hyperactive might be a mechanism reinforcing hyperactivity needs to be empirically clarified in future studies.

Published
2022

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