Subcortical Brain Alterations in Carriers of Genomic Copy Number Variants
Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs), including autism (ASD) and schizophrenia. Little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structu...
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| Published in | The American journal of psychiatry Vol. 180; no. 9; pp. 685 - 698 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Psychiatric Association
01.09.2023
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0002-953X 1535-7228 1535-7228 |
| DOI | 10.1176/appi.ajp.20220304 |
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| Abstract | Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs), including autism (ASD) and schizophrenia. Little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs. To fill this gap, the authors investigated gross volume, vertex-level thickness, and surface maps of subcortical structures in 11 CNVs and six NPDs.
Subcortical structures were characterized using harmonized ENIGMA protocols in 675 CNV carriers (CNVs at 1q21.1, TAR, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2; age range, 6-80 years; 340 males) and 782 control subjects (age range, 6-80 years; 387 males) as well as ENIGMA summary statistics for ASD, schizophrenia, attention deficit hyperactivity disorder, obsessive-compulsive disorder, bipolar disorder, and major depression.
All CNVs showed alterations in at least one subcortical measure. Each structure was affected by at least two CNVs, and the hippocampus and amygdala were affected by five. Shape analyses detected subregional alterations that were averaged out in volume analyses. A common latent dimension was identified, characterized by opposing effects on the hippocampus/amygdala and putamen/pallidum, across CNVs and across NPDs. Effect sizes of CNVs on subcortical volume, thickness, and local surface area were correlated with their previously reported effect sizes on cognition and risk for ASD and schizophrenia.
The findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions, as well distinct effects, with some CNVs clustering with adult-onset conditions and others with ASD. These findings provide insight into the long-standing questions of why CNVs at different genomic loci increase the risk for the same NPD and why a single CNV increases the risk for a diverse set of NPDs. |
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| AbstractList | Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs), including autism (ASD) and schizophrenia. Little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs. To fill this gap, the authors investigated gross volume, vertex-level thickness, and surface maps of subcortical structures in 11 CNVs and six NPDs.
Subcortical structures were characterized using harmonized ENIGMA protocols in 675 CNV carriers (CNVs at 1q21.1, TAR, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2; age range, 6-80 years; 340 males) and 782 control subjects (age range, 6-80 years; 387 males) as well as ENIGMA summary statistics for ASD, schizophrenia, attention deficit hyperactivity disorder, obsessive-compulsive disorder, bipolar disorder, and major depression.
All CNVs showed alterations in at least one subcortical measure. Each structure was affected by at least two CNVs, and the hippocampus and amygdala were affected by five. Shape analyses detected subregional alterations that were averaged out in volume analyses. A common latent dimension was identified, characterized by opposing effects on the hippocampus/amygdala and putamen/pallidum, across CNVs and across NPDs. Effect sizes of CNVs on subcortical volume, thickness, and local surface area were correlated with their previously reported effect sizes on cognition and risk for ASD and schizophrenia.
The findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions, as well distinct effects, with some CNVs clustering with adult-onset conditions and others with ASD. These findings provide insight into the long-standing questions of why CNVs at different genomic loci increase the risk for the same NPD and why a single CNV increases the risk for a diverse set of NPDs. Objective: Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs), including autism (ASD) and schizophrenia. Little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs. To fill this gap, the authors investigated gross volume, vertex-level thickness, and surface maps of subcortical structures in 11 CNVs and six NPDs. Methods: Subcortical structures were characterized using harmonized ENIGMA protocols in 675 CNV carriers (CNVs at 1q21.1, TAR, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2; age range, 6–80 years; 340 males) and 782 control subjects (age range, 6–80 years; 387 males) as well as ENIGMA summary statistics for ASD, schizophrenia, attention deficit hyperactivity disorder, obsessive-compulsive disorder, bipolar disorder, and major depression. Results: All CNVs showed alterations in at least one subcortical measure. Each structure was affected by at least two CNVs, and the hippocampus and amygdala were affected by five. Shape analyses detected subregional alterations that were averaged out in volume analyses. A common latent dimension was identified, characterized by opposing effects on the hippocampus/amygdala and putamen/pallidum, across CNVs and across NPDs. Effect sizes of CNVs on subcortical volume, thickness, and local surface area were correlated with their previously reported effect sizes on cognition and risk for ASD and schizophrenia. Conclusions: The findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions, as well distinct effects, with some CNVs clustering with adult-onset conditions and others with ASD. These findings provide insight into the long-standing questions of why CNVs at different genomic loci increase the risk for the same NPD and why a single CNV increases the risk for a diverse set of NPDs. Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs), including autism (ASD) and schizophrenia. Little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs. To fill this gap, the authors investigated gross volume, vertex-level thickness, and surface maps of subcortical structures in 11 CNVs and six NPDs.OBJECTIVECopy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs), including autism (ASD) and schizophrenia. Little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs. To fill this gap, the authors investigated gross volume, vertex-level thickness, and surface maps of subcortical structures in 11 CNVs and six NPDs.Subcortical structures were characterized using harmonized ENIGMA protocols in 675 CNV carriers (CNVs at 1q21.1, TAR, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2; age range, 6-80 years; 340 males) and 782 control subjects (age range, 6-80 years; 387 males) as well as ENIGMA summary statistics for ASD, schizophrenia, attention deficit hyperactivity disorder, obsessive-compulsive disorder, bipolar disorder, and major depression.METHODSSubcortical structures were characterized using harmonized ENIGMA protocols in 675 CNV carriers (CNVs at 1q21.1, TAR, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2; age range, 6-80 years; 340 males) and 782 control subjects (age range, 6-80 years; 387 males) as well as ENIGMA summary statistics for ASD, schizophrenia, attention deficit hyperactivity disorder, obsessive-compulsive disorder, bipolar disorder, and major depression.All CNVs showed alterations in at least one subcortical measure. Each structure was affected by at least two CNVs, and the hippocampus and amygdala were affected by five. Shape analyses detected subregional alterations that were averaged out in volume analyses. A common latent dimension was identified, characterized by opposing effects on the hippocampus/amygdala and putamen/pallidum, across CNVs and across NPDs. Effect sizes of CNVs on subcortical volume, thickness, and local surface area were correlated with their previously reported effect sizes on cognition and risk for ASD and schizophrenia.RESULTSAll CNVs showed alterations in at least one subcortical measure. Each structure was affected by at least two CNVs, and the hippocampus and amygdala were affected by five. Shape analyses detected subregional alterations that were averaged out in volume analyses. A common latent dimension was identified, characterized by opposing effects on the hippocampus/amygdala and putamen/pallidum, across CNVs and across NPDs. Effect sizes of CNVs on subcortical volume, thickness, and local surface area were correlated with their previously reported effect sizes on cognition and risk for ASD and schizophrenia.The findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions, as well distinct effects, with some CNVs clustering with adult-onset conditions and others with ASD. These findings provide insight into the long-standing questions of why CNVs at different genomic loci increase the risk for the same NPD and why a single CNV increases the risk for a diverse set of NPDs.CONCLUSIONSThe findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions, as well distinct effects, with some CNVs clustering with adult-onset conditions and others with ASD. These findings provide insight into the long-standing questions of why CNVs at different genomic loci increase the risk for the same NPD and why a single CNV increases the risk for a diverse set of NPDs. |
| Author | Ragothaman, Anjani Glahn, David C. Moreau, Clara Ching, Christopher R.K. Bearden, Carrie E. Kushan, Leila Dumas, Guillaume Schultz, Laura M. Gutman, Boris A. Draganski, Bogdan Rodriguez-Herreros, Borja Linden, David E.J. Ho, Tiffany C. Harvey, Annabelle Isaev, Dmitry Thompson, Paul M. Douard, Elise Jacquemont, Sébastien van den Bree, Marianne B.M. Alpert, Kathryn Younis, Nadine Sønderby, Ida E. Pain, Aurélie Jean-Louis, Martineau Huguet, Guillaume Andreassen, Ole A. Tamer, Petra Martin-Brevet, Sandra Schmaal, Lianne Turner, Jessica A. Lippé, Sarah Maillard, Anne M. Almasy, Laura Hall, Jeremy Kumar, Kuldeep Wang, Lei Martin, Charles-Olivier Silva, Ana I. Owen, Michael J. Modenato, Claudia |
| AuthorAffiliation | Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila-Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l'Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Human Genetics and Cognitive Functions, Institut Pasteur, and Université de Paris, CNRS UMR 3571, Paris (Moreau); Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles (Kushan, Bearden); School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (Silva, Linden); Centre for Neuropsychiatric Genetics and Genomics (Silva, van den B |
| AuthorAffiliation_xml | – name: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila-Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l'Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Human Genetics and Cognitive Functions, Institut Pasteur, and Université de Paris, CNRS UMR 3571, Paris (Moreau); Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles (Kushan, Bearden); School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (Silva, Linden); Centre for Neuropsychiatric Genetics and Genomics (Silva, van den Bree, Owen, Hall), Division of Psychological Medicine and Clinical Neurosciences, School of Medicine (van den Bree, Owen, Hall), and Neuroscience and Mental Health Innovation Institute (van den Bree, Linden, Hall), Cardiff University, Cardiff, U.K.; Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Draganski); Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey (Ching, Moreau, Thompson); Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia (Schultz, Almasy); Lifespan Brain Institute, Children's Hospital of Philadelphia and Penn Medicine, Philadelphia (Schultz, Almasy); Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia (Almasy); Department of Psychiatry, Harvard Medical School, Boston, and Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston (Glahn); Department of Biomedical Engineering, Duke University, Durham, N.C. (Isaev); Department of Biomedical Engineering, Oregon Health and Science University, Portland (Ragothaman); Department of Psychology, Georgia State University, Atlanta (Turner); Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago (Alpert, Wang); Department of Psychiatry and Behavioral Health, Ohio State University Wexner Medical Center, Columbus (Wang); Department of Psychiatry and Behavioral Sciences and Department of Psychology, Stanford University, Stanford (Ho); Orygen, National Centre of Excellence in Youth Mental Health, Parkville, Australia, and Centre for Youth Mental Health, University of Melbourne, Melbourne (Schmaal); NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, and University of Oslo, Oslo (Sønderby, Andreassen); Department of Medical Genetics, Oslo University Hospital, Oslo (Sønderby); K.G. Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo (Sønderby, Andreassen); Department of Biomedical Engineering, Illinois Institute of Technology, Chicago (Gutman) – name: 27 Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia – name: 6 School for Mental Health and Neuroscience, Maastricht University, Netherlands – name: 28 Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia – name: 17 Department of Genetics, University of Pennsylvania, PA, USA – name: 20 Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA – name: 15 Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, PA, USA – name: 2 LREN - Department of clinical neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland – name: 13 Neurology Department, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany – name: 22 Psychology & Neuroscience, Georgia State University, Atlanta, Georgia, USA – name: 18 Harvard Medical School, Department of Psychiatry, 25 Shattuck St, Boston, MA 02115, USA – name: 4 Institut Pasteur, Université de Paris, CNRS UMR 3571, Human Genetics and Cognitive Functions, 25 rue du Dr. Roux, Paris, France – name: 25 Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA – name: 7 MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom – name: 8 Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom – name: 23 Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA – name: 1 Centre de recherche CHU Sainte-Justine and University of Montréal, Canada – name: 16 Lifespan Brain Institute of Children’s Hospital of Philadelphia and Penn Medicine, PA, USA – name: 31 KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway – name: 29 NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and University of Oslo, Oslo, Norway – name: 21 Department of biomedical engineering, Oregon Health and Science university, Portland, Oregon, USA – name: 24 Department of Psychiatry and Behavioral Health, Ohio State University Wexner Medical Center, Columbus, Ohio, USA – name: 5 Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles, USA – name: 30 Department of Medical Genetics, Oslo University Hospital, Oslo, Norway – name: 9 Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom – name: 32 Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois – name: 26 Department of Psychology, Stanford University, Stanford, CA USA – name: 3 Service des Troubles du Spectre de l’Autisme et apparentés, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland – name: 14 Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA – name: 19 Boston Children’s Hospital, Tommy Fuss Center for Neuropsychiatric Disease Research, 300 Longwood Avenue, Boston, MA 02115, USA |
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Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 20 givenname: Jessica A. surname: Turner fullname: Turner, Jessica A. organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 21 givenname: Lei surname: Wang fullname: Wang, Lei organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 22 givenname: Tiffany C. surname: Ho fullname: Ho, Tiffany C. organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 23 givenname: Lianne surname: Schmaal fullname: Schmaal, Lianne organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 24 givenname: Ana I. surname: Silva fullname: Silva, Ana I. organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 25 givenname: Marianne B.M. surname: van den Bree fullname: van den Bree, Marianne B.M. organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 26 givenname: David E.J. surname: Linden fullname: Linden, David E.J. organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 27 givenname: Michael J. surname: Owen fullname: Owen, Michael J. organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 28 givenname: Jeremy surname: Hall fullname: Hall, Jeremy organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 29 givenname: Sarah surname: Lippé fullname: Lippé, Sarah organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 30 givenname: Guillaume surname: Dumas fullname: Dumas, Guillaume organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 31 givenname: Bogdan surname: Draganski fullname: Draganski, Bogdan organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); 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Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 34 givenname: Ole A. surname: Andreassen fullname: Andreassen, Ole A. organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 35 givenname: Laura M. surname: Schultz fullname: Schultz, Laura M. organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 36 givenname: Laura surname: Almasy fullname: Almasy, Laura organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 37 givenname: David C. surname: Glahn fullname: Glahn, David C. organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 38 givenname: Carrie E. surname: Bearden fullname: Bearden, Carrie E. organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 39 givenname: Paul M. surname: Thompson fullname: Thompson, Paul M. organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and – sequence: 40 givenname: Sébastien surname: Jacquemont fullname: Jacquemont, Sébastien organization: Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila–Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l’Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/37434504$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright American Psychiatric Association Sep 2023 |
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| Keywords | Depressive Disorders Neuroimaging Genetics/Genomics Neurodevelopmental Disorders Schizophrenia Spectrum and Other Psychotic Disorders |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Data collection: C.Mod., A.M., B.R-H., A.P., S.R., and S.M-B. recruited and scanned participants in the 16p11.2 European Consortium. S.L., C.O.M., N.Y., P.T., E.D., F. T-D., V.C., A.R.C., F.D. recruited and scanned participants in the Brain Canada cohort. L.K., C.E.B collected and provided the data for the UCLA cohort. D.E.J.L., M.J.O., M.B.M. V.d.B., J.H. and A.I.S., provided the data for the Cardiff cohort. All authors provided feedback on the manuscript. Analyses: C.Mod. and C.C. performed all the preprocessing. K.K. and C.Mod. performed all the analyses of neuroimaging data. G.D. contributed to normative modeling. B.G. contributed to shape analysis. C.C, C.Mor., P.M.T., and C.E.B. contributed to result interpretation and in the editing of the manuscript. C.Mod., K.K., C.C, P.M.T., C.E.B., and S.J. designed the study, analyzed imaging data, and drafted the manuscript. These authors contributed equally Author contributions |
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| PublicationTitle | The American journal of psychiatry |
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| Snippet | Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs), including autism... Objective: Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs),... |
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| SubjectTerms | Adolescent Adult Aged Aged, 80 and over Amygdala Attention Deficit Disorder with Hyperactivity - genetics Attention deficit hyperactivity disorder Autism Brain - diagnostic imaging Child DNA Copy Number Variations - genetics Genomics Humans Male Mental disorders Middle Aged Risk factors Schizophrenia Schizophrenia - genetics Young Adult |
| Title | Subcortical Brain Alterations in Carriers of Genomic Copy Number Variants |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/37434504 https://www.proquest.com/docview/2860831758 https://www.proquest.com/docview/2836298900 https://pubmed.ncbi.nlm.nih.gov/PMC10885337 |
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