. 2024 Jan 15;95(2):147-160.

doi: 10.1016/j.biopsych.2023.08.018. Epub 2023 Sep 3.

Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

Rune Boen¹, Tobias Kaufmann², Dennis van der Meer³, Oleksandr Frei⁴, Ingrid Agartz⁵, David Ames⁶, Micael Andersson⁷, Nicola J Armstrong⁸, Eric Artiges⁹, Joshua R Atkins¹⁰, Jochen Bauer¹¹, Francesco Benedetti¹², Dorret I Boomsma¹³, Henry Brodaty¹⁴, Katharina Brosch¹⁵, Randy L Buckner¹⁶, Murray J Cairns¹⁷, Vince Calhoun¹⁸, Svenja Caspers¹⁹, Sven Cichon²⁰, Aiden P Corvin²¹, Benedicto Crespo-Facorro²², Udo Dannlowski²³, Friederike S David²⁴, Eco J C de Geus¹³, Greig I de Zubicaray²⁵, Sylvane Desrivières²⁶, Joanne L Doherty²⁷, Gary Donohoe²⁸, Stefan Ehrlich²⁹, Else Eising³⁰, Thomas Espeseth³¹, Simon E Fisher³², Andreas J Forstner³³, Lidia Fortaner-Uyà¹², Vincent Frouin³⁴, Masaki Fukunaga³⁵, Tian Ge³⁶, David C Glahn³⁷, Janik Goltermann²³, Hans J Grabe³⁸, Melissa J Green³⁹, Nynke A Groenewold⁴⁰, Dominik Grotegerd²³, Gøril Rolfseng Grøntvedt⁴¹, Tim Hahn²³, Ryota Hashimoto⁴², Jayne Y Hehir-Kwa⁴³, Frans A Henskens⁴⁴, Avram J Holmes⁴⁵, Asta K Håberg⁴⁶, Jan Haavik⁴⁷, Sebastien Jacquemont⁴⁸, Andreas Jansen⁴⁹, Christiane Jockwitz¹⁹, Erik G Jönsson⁵⁰, Masataka Kikuchi⁵¹, Tilo Kircher¹⁵, Kuldeep Kumar⁵², Stephanie Le Hellard⁵³, Costin Leu⁵⁴, David E Linden⁵⁵, Jingyu Liu⁵⁶, Robert Loughnan⁵⁷, Karen A Mather¹⁴, Katie L McMahon⁵⁸, Allan F McRae⁵⁹, Sarah E Medland⁶⁰, Susanne Meinert⁶¹, Clara A Moreau⁶², Derek W Morris⁶³, Bryan J Mowry⁶⁴, Thomas W Mühleisen⁶⁵, Igor Nenadić¹⁵, Markus M Nöthen²⁴, Lars Nyberg⁶⁶, Roel A Ophoff⁶⁷, Michael J Owen⁶⁸, Christos Pantelis⁶⁹, Marco Paolini¹², Tomas Paus⁷⁰, Zdenka Pausova⁷¹, Karin Persson⁷², Yann Quidé⁷³, Tiago Reis Marques⁷⁴, Perminder S Sachdev⁷⁵, Sigrid B Sando⁴¹, Ulrich Schall⁷⁶, Rodney J Scott⁷⁷, Geir Selbæk⁷⁸, Elena Shumskaya⁷⁹, Ana I Silva⁸⁰, Sanjay M Sisodiya⁸¹, Frederike Stein¹⁵, Dan J Stein⁸², Benjamin Straube¹⁵, Fabian Streit⁸³, Lachlan T Strike⁸⁴, Alexander Teumer⁸⁵, Lea Teutenberg¹⁵, Anbupalam Thalamuthu¹⁴, Paul A Tooney⁸⁶, Diana Tordesillas-Gutierrez⁸⁷, Julian N Trollor⁸⁸, Dennis van 't Ent¹³, Marianne B M van den Bree⁸⁹, Neeltje E M van Haren⁹⁰, Javier Vázquez-Bourgon⁹¹, Henry Völzke⁹², Wei Wen¹⁴, Katharina Wittfeld³⁸, Christopher R K Ching⁶², Lars T Westlye⁹³, Paul M Thompson⁶², Carrie E Bearden⁹⁴, Kaja K Selmer⁹⁵, Dag Alnæs⁹⁶, Ole A Andreassen⁹⁷, Ida E Sønderby⁹⁸; ENIGMA-CNV Working Group

Affiliations

¹ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: boenrune@gmail.com.
² Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry and Psychotherapy, Tübingen Center for Mental Health, University of Tübingen, Germany; German Center for Mental Health (DZPG), partner site Tübingen, Tübingen, Germany.
³ Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.
⁴ Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway.
⁵ Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Clinical Research, Diakonhjemmet Hospital, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden.
⁶ University of Melbourne Academic Unit for Psychiatry of Old Age, St George's Hospital, Kew, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia.
⁷ Department of Integrative Medical Biology and Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden.
⁸ Department of Mathematics and Statistics, Curtin University, Perth, Western Australia, Australia.
⁹ Institut National de la Santé et de la Recherche Médicale U1299, École Normale Supérieure Paris-Saclay, Université Paris Saclay, Gif-sur-Yvette, France; Établissement public de santé (EPS) Barthélemy Durand, Etampes, France.
¹⁰ School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia; Precision Medicine Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
¹¹ University Clinic for Radiology, University of Münster, Münster, Germany.
¹² Psychiatry and Clinical Psychobiology Unit, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy; Division of Neuroscience, Psychiatry and Clinical Psychobiology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.
¹³ Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹⁴ Centre for Healthy Brain Ageing, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
¹⁵ Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
¹⁶ Department of Psychology and Center for Brain Science, Harvard University, Cambridge, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts.
¹⁷ School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia; Precision Medicine Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
¹⁸ Tri-institutional Center for Translational Research in Neuroimaging and Data Science, Georgia State University/Georgia Institute of Technology/Emory University, Atlanta, Georgia.
¹⁹ Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
²⁰ Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; University Hospital Basel, Institute of Medical Genetics and Pathology, Basel, Switzerland.
²¹ Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
²² Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro superior de investigaciones científicas (CSIC), Sevilla, Spain; Centro de Investigación Biomédica en Red Salud Mental, Sevilla, Spain; Department of Psychiatry, University of Sevilla, Sevilla, Spain.
²³ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
²⁴ Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
²⁵ School of Psychology and Counselling, Queensland University of Technology, Brisbane, Queensland, Australia.
²⁶ Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
²⁷ Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, United Kingdom.
²⁸ School of Psychology and Center for Neuroimaging, Cognition and Genomics, University of Galway, Galway, Ireland.
²⁹ Translational Developmental Neuroscience Section, Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
³⁰ Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
³¹ Department of Psychology, University of Oslo, Oslo, Norway; Department of Psychology, Oslo New University College, Oslo, Norway.
³² Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.
³³ Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
³⁴ Neurospin, Commissariat a l'Energie Atomique (CEA), Université Paris-Saclay, Gif-sur-Yvette, France.
³⁵ Section of Brain Function Information, National Institute for Physiological Sciences, Okazaki, Japan.
³⁶ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
³⁷ Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
³⁸ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
³⁹ Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia; Neuroscience Research Australia, Sydney, New South Wales, Australia.
⁴⁰ Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁴¹ Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway.
⁴² Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
⁴³ Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
⁴⁴ School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Priority Research Centre for Health Behaviour, University of Newcastle, Newcastle, New South Wales, Australia.
⁴⁵ Department of Psychiatry, Rutgers University, New Brunswick, New Jersey; Brain Health Institute, Rutgers University, Piscataway, New Jersey.
⁴⁶ Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Radiology and Nuclear Medicine, St. Olav's Hospital, Trondheim, Norway.
⁴⁷ Department of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
⁴⁸ Sainte Justine Hospital Research Center, Montreal, Quebec, Canada; Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.
⁴⁹ Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany; Core-Facility Brainimaging and Department of Psychiatry, Faculty of Medicine, Philipps-University Marburg, Marburg, Germany.
⁵⁰ Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden.
⁵¹ Department of Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan.
⁵² Sainte Justine Hospital Research Center, Montreal, Quebec, Canada.
⁵³ Norwegian Centre for Mental Disorders Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
⁵⁴ Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; Department of Neurology, McGovern Medical School, UTHealth Houston, Houston, Texas.
⁵⁵ Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands.
⁵⁶ Department of Computer Science and Center for Translational Research in Neuroimaging and Data Science, Georgia State University, Atlanta, Georgia.
⁵⁷ Department of Cognitive Science and Population Neuroscience and Genetics Lab, University of California San Diego, La Jolla, California.
⁵⁸ School of Clinical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
⁵⁹ Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
⁶⁰ Psychiatric Genetics, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, Queensland, Australia; University of Queensland, Brisbane, Queensland, Australia; Queensland University of Technology, Brisbane, Queensland, Australia.
⁶¹ Institute for Translational Psychiatry, University of Münster, Münster, Germany; Institute for Translational Neuroscience, University of Münster, Münster, Germany.
⁶² Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, California.
⁶³ Centre for Neuroimaging, Cognition and Genomics, School of Biological and Chemical Sciences, University of Galway, Galway, Ireland.
⁶⁴ Queensland Brain Institute and Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, Australia.
⁶⁵ Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland.
⁶⁶ Departments of Radiation Sciences, Integrative Medical Biology and Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden.
⁶⁷ Department of Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands; Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, University of California Los Angeles, Los Angeles, California.
⁶⁸ Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom.
⁶⁹ Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Carlton South, Victoria, Australia; Western Centre for Health Research and Education, Sunshine Hospital, St Albans, Victoria, Australia.
⁷⁰ Departments of Psychiatry and Neuroscience, Faculty of Medicine and Sainte Justine Hospital Research Center, University of Montreal, Montreal, Quebec, Canada; Departments of Psychiatry and Psychology, University of Toronto, Toronto, Ontario, Canada.
⁷¹ The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
⁷² Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway; Norwegian National Centre for Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.
⁷³ Neuroscience Research Australia, Sydney, New South Wales, Australia; School of Psychology, University of New South Wales, Sydney, New South Wales, Australia.
⁷⁴ Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁷⁵ Centre for Healthy Brain Ageing, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, New South Wales, Australia.
⁷⁶ Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
⁷⁷ School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Division of Molecular Medicine, New South Wales Health Pathology, Newcastle, New South Wales, Australia.
⁷⁸ Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway; Norwegian National Centre for Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
⁷⁹ Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
⁸⁰ Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom.
⁸¹ Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; Chalfont Centre for Epilepsy, Chalfont St Peter, United Kingdom.
⁸² SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁸³ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
⁸⁴ Psychiatric Genetics, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Psychology and Counselling, Faculty of Health, Queensland University of Technology, Brisbane, Australia.
⁸⁵ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research, Greifswald, Germany.
⁸⁶ School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
⁸⁷ Instituto de Física de Cantabria UC-CSIC, Santander, Spain; Department of Radiology, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain.
⁸⁸ Department of Developmental Disability Neuropsychiatry and Centre for Healthy Brain Ageing, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁸⁹ Institute of Psychological Medicine and Clinical Neurosciences and Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; Institute for Translational Neuroscience, University of Münster, Münster, Germany.
⁹⁰ Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre, Rotterdam, the Netherlands; Department of Psychiatry, University Medical Centre Utrecht, Utrecht, the Netherlands.
⁹¹ Centro de Investigación Biomédica en Red Salud Mental, Sevilla, Spain; Department of Psychiatry, University Hospital Maqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain; Departamento de Medicina y Psiquiatría, Universidad de Cantabria, Santander, Spain.
⁹² German Centre for Cardiovascular Research, Greifswald, Germany; Greifswald University Hospital, Greifswald, Germany.
⁹³ Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
⁹⁴ Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, University of California Los Angeles, Los Angeles, California.
⁹⁵ Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital and the University of Oslo, Oslo, Norway.
⁹⁶ Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Kristiania University College, Oslo, Norway.
⁹⁷ Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
⁹⁸ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.

PMID: 37661008
PMCID: PMC7615370
DOI: 10.1016/j.biopsych.2023.08.018

Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

Rune Boen et al. Biol Psychiatry. 2024.

. 2024 Jan 15;95(2):147-160.

doi: 10.1016/j.biopsych.2023.08.018. Epub 2023 Sep 3.

Authors

Affiliations

¹ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: boenrune@gmail.com.
² Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry and Psychotherapy, Tübingen Center for Mental Health, University of Tübingen, Germany; German Center for Mental Health (DZPG), partner site Tübingen, Tübingen, Germany.
³ Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.
⁴ Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway.
⁵ Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Clinical Research, Diakonhjemmet Hospital, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden.
⁶ University of Melbourne Academic Unit for Psychiatry of Old Age, St George's Hospital, Kew, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia.
⁷ Department of Integrative Medical Biology and Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden.
⁸ Department of Mathematics and Statistics, Curtin University, Perth, Western Australia, Australia.
⁹ Institut National de la Santé et de la Recherche Médicale U1299, École Normale Supérieure Paris-Saclay, Université Paris Saclay, Gif-sur-Yvette, France; Établissement public de santé (EPS) Barthélemy Durand, Etampes, France.
¹⁰ School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia; Precision Medicine Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
¹¹ University Clinic for Radiology, University of Münster, Münster, Germany.
¹² Psychiatry and Clinical Psychobiology Unit, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy; Division of Neuroscience, Psychiatry and Clinical Psychobiology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.
¹³ Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹⁴ Centre for Healthy Brain Ageing, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
¹⁵ Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
¹⁶ Department of Psychology and Center for Brain Science, Harvard University, Cambridge, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts.
¹⁷ School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia; Precision Medicine Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
¹⁸ Tri-institutional Center for Translational Research in Neuroimaging and Data Science, Georgia State University/Georgia Institute of Technology/Emory University, Atlanta, Georgia.
¹⁹ Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
²⁰ Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; University Hospital Basel, Institute of Medical Genetics and Pathology, Basel, Switzerland.
²¹ Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
²² Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro superior de investigaciones científicas (CSIC), Sevilla, Spain; Centro de Investigación Biomédica en Red Salud Mental, Sevilla, Spain; Department of Psychiatry, University of Sevilla, Sevilla, Spain.
²³ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
²⁴ Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
²⁵ School of Psychology and Counselling, Queensland University of Technology, Brisbane, Queensland, Australia.
²⁶ Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
²⁷ Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, United Kingdom.
²⁸ School of Psychology and Center for Neuroimaging, Cognition and Genomics, University of Galway, Galway, Ireland.
²⁹ Translational Developmental Neuroscience Section, Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
³⁰ Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
³¹ Department of Psychology, University of Oslo, Oslo, Norway; Department of Psychology, Oslo New University College, Oslo, Norway.
³² Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.
³³ Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
³⁴ Neurospin, Commissariat a l'Energie Atomique (CEA), Université Paris-Saclay, Gif-sur-Yvette, France.
³⁵ Section of Brain Function Information, National Institute for Physiological Sciences, Okazaki, Japan.
³⁶ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
³⁷ Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
³⁸ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
³⁹ Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia; Neuroscience Research Australia, Sydney, New South Wales, Australia.
⁴⁰ Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁴¹ Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway.
⁴² Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
⁴³ Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
⁴⁴ School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Priority Research Centre for Health Behaviour, University of Newcastle, Newcastle, New South Wales, Australia.
⁴⁵ Department of Psychiatry, Rutgers University, New Brunswick, New Jersey; Brain Health Institute, Rutgers University, Piscataway, New Jersey.
⁴⁶ Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Radiology and Nuclear Medicine, St. Olav's Hospital, Trondheim, Norway.
⁴⁷ Department of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
⁴⁸ Sainte Justine Hospital Research Center, Montreal, Quebec, Canada; Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.
⁴⁹ Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany; Core-Facility Brainimaging and Department of Psychiatry, Faculty of Medicine, Philipps-University Marburg, Marburg, Germany.
⁵⁰ Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden.
⁵¹ Department of Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan.
⁵² Sainte Justine Hospital Research Center, Montreal, Quebec, Canada.
⁵³ Norwegian Centre for Mental Disorders Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
⁵⁴ Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; Department of Neurology, McGovern Medical School, UTHealth Houston, Houston, Texas.
⁵⁵ Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands.
⁵⁶ Department of Computer Science and Center for Translational Research in Neuroimaging and Data Science, Georgia State University, Atlanta, Georgia.
⁵⁷ Department of Cognitive Science and Population Neuroscience and Genetics Lab, University of California San Diego, La Jolla, California.
⁵⁸ School of Clinical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
⁵⁹ Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
⁶⁰ Psychiatric Genetics, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, Queensland, Australia; University of Queensland, Brisbane, Queensland, Australia; Queensland University of Technology, Brisbane, Queensland, Australia.
⁶¹ Institute for Translational Psychiatry, University of Münster, Münster, Germany; Institute for Translational Neuroscience, University of Münster, Münster, Germany.
⁶² Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, California.
⁶³ Centre for Neuroimaging, Cognition and Genomics, School of Biological and Chemical Sciences, University of Galway, Galway, Ireland.
⁶⁴ Queensland Brain Institute and Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, Australia.
⁶⁵ Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland.
⁶⁶ Departments of Radiation Sciences, Integrative Medical Biology and Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden.
⁶⁷ Department of Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands; Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, University of California Los Angeles, Los Angeles, California.
⁶⁸ Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom.
⁶⁹ Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Carlton South, Victoria, Australia; Western Centre for Health Research and Education, Sunshine Hospital, St Albans, Victoria, Australia.
⁷⁰ Departments of Psychiatry and Neuroscience, Faculty of Medicine and Sainte Justine Hospital Research Center, University of Montreal, Montreal, Quebec, Canada; Departments of Psychiatry and Psychology, University of Toronto, Toronto, Ontario, Canada.
⁷¹ The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
⁷² Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway; Norwegian National Centre for Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.
⁷³ Neuroscience Research Australia, Sydney, New South Wales, Australia; School of Psychology, University of New South Wales, Sydney, New South Wales, Australia.
⁷⁴ Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁷⁵ Centre for Healthy Brain Ageing, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, New South Wales, Australia.
⁷⁶ Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
⁷⁷ School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Division of Molecular Medicine, New South Wales Health Pathology, Newcastle, New South Wales, Australia.
⁷⁸ Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway; Norwegian National Centre for Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
⁷⁹ Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
⁸⁰ Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom.
⁸¹ Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; Chalfont Centre for Epilepsy, Chalfont St Peter, United Kingdom.
⁸² SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁸³ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
⁸⁴ Psychiatric Genetics, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Psychology and Counselling, Faculty of Health, Queensland University of Technology, Brisbane, Australia.
⁸⁵ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research, Greifswald, Germany.
⁸⁶ School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
⁸⁷ Instituto de Física de Cantabria UC-CSIC, Santander, Spain; Department of Radiology, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain.
⁸⁸ Department of Developmental Disability Neuropsychiatry and Centre for Healthy Brain Ageing, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁸⁹ Institute of Psychological Medicine and Clinical Neurosciences and Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; Institute for Translational Neuroscience, University of Münster, Münster, Germany.
⁹⁰ Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre, Rotterdam, the Netherlands; Department of Psychiatry, University Medical Centre Utrecht, Utrecht, the Netherlands.
⁹¹ Centro de Investigación Biomédica en Red Salud Mental, Sevilla, Spain; Department of Psychiatry, University Hospital Maqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain; Departamento de Medicina y Psiquiatría, Universidad de Cantabria, Santander, Spain.
⁹² German Centre for Cardiovascular Research, Greifswald, Germany; Greifswald University Hospital, Greifswald, Germany.
⁹³ Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
⁹⁴ Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, University of California Los Angeles, Los Angeles, California.
⁹⁵ Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital and the University of Oslo, Oslo, Norway.
⁹⁶ Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Kristiania University College, Oslo, Norway.
⁹⁷ Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
⁹⁸ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.

PMID: 37661008
PMCID: PMC7615370
DOI: 10.1016/j.biopsych.2023.08.018

Abstract

Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.

Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.

Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.

Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.

Keywords: 15q11.2 BP1-BP2; 1q21.1 distal; Brain structure; Copy number variants; Intraindividual variability; Magnetic resonance imaging.

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Conflict of interest statement

OAA has received speaker’s honorarium from Lundbeck, Janssen, and Sunovion and is a consultant to Coretechs.ai. TRM reports personal fees from Pfizer, Lundbeck, Astellas, Janssen, and Angelini outside the submitted work. He is an employee and shareholder of Pasithea Therapeutics. CRKC has received partial research support from Biogen for work unrelated to the topic of this article (principal investigator, PMT). PMT has received partial research support from Biogen for work unrelated to the topic of this article. MBMvdB and MJO report grants from Takeda Pharmaceuticals outside the submitted work. MJO reports a grant from Akrivia Health outside the submitted work. HJG has received travel grants and speaker’s honoraria from Fresenius Medical Care, Neuraxpharm, Servier, and Janssen as well as research funding from Fresenius Medical Care. GS has received honoraria for participating at advisory board meetings from Roche and Biogen regarding new Alzheimer’s disease drugs. KKS has received consultant and speaker’s honoraria from Roche and OrionPharma, reimbursement of travel and accommodation costs at a meeting from Kolpharma, and sponsorships for arranging conferences from Desitin and Eisai AB. IG has received speaker’s honorarium from Lundbeck. MMN has received fees for membership in an advisory board from HMG Systems Engineering GmbH, for membership in the Medical-Scientific Editorial Office of the Deutsches Ärzteblatt, and for serving as a consultant for Everis Belgium in a project of the European Commission (REFORM/SC2020/029). MMN also receives salary payments from Life & Brain GmbH and holds shares in Life & Brain GmbH. All these concerned activities outside the submitted work. CP received honoraria for talks from Lundbeck, Australia Pty Ltd. outside the submitted work. DJS has received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda and Vistagen. JH has received speaker’s honorarium from Medice and Takeda outside the submitted work. KP reports work with Novo Nordisk and Roche clinical trials outside the submitted work. All other authors report no biomedical financial interests or potential conflicts of interest.

Figures

**Figure 1. Cortical surface area comparison between 1q21.1 distal deletion carriers and non-carriers.**
A) Top panel shows z-scores - group differences in regional cortical surface area. Bottom panel shows RID-scores - group differences in regional cortical surface area that are scaled to the individual’s own global index. Non-carriers are represented by gray lines, and 1q21.1 distal deletion carriers are represented by black lines. Blue dots indicate significant differences. The insular cortex is included under frontal cortex for visualization purposes. B) Top panel displays the significant differences in Z-scores, and the bottom panel shows the significant differences in RID-scores. Blue-red diverging maps represent the effect size. C) Spatial distribution of all the mean differences in RID scores. Please note that all values are shown regardless of significance. Yellow-purple diverging maps represent the direction of the mean differences. Increased yellow intensity represents values that are less deviant than the overall global mean difference in cortical surface area, and increased purple intensity represents values that are more deviant than the overall global mean difference in cortical surface area. Z- and RID-scores are based on raw values adjusted for age, age², sex, and intracranial volume on site harmonized data.

**Figure 2. Cortical thickness comparison between 1q21.1 distal deletion carriers and non-carriers.**
A) Top panel shows z-scores - group differences in regional cortical thickness. Bottom panel shows RID-scores - group differences in regional cortical thickness that are scaled to the individual’s own global index. Non-carriers are represented by gray lines, and 1q21.1 distal deletion carriers are represented by black lines. Blue dots indicate significant differences. The insular cortex is included under frontal cortex for visualization purposes. B) Top panel displays the significant differences in Z-scores, and the bottom panel shows the significant differences in RID-scores. Blue-red diverging maps represent the effect size. C) Spatial distribution of all the mean differences in RID scores. Please note that all values are shown regardless of significance. Yellow-purple diverging maps represent the direction of the mean differences. Increased yellow intensity represents values that are less deviant than the overall global mean difference in cortical thickness, and increased purple intensity represents values that are more deviant than the overall global mean difference in cortical thickness. Z- and RID-scores are based on raw values adjusted for age, age², sex, and intracranial volume on site harmonized data.

**Figure 3. Cortical surface area comparison between 15q11.2 BP1-BP2 deletion carriers and non-carriers.**
A) Top panel shows z-scores - group differences in regional cortical surface area. Bottom panel shows RID-scores - group differences in regional cortical surface area that are scaled to the individual’s own global index. Non-carriers are represented by gray lines, and 15q11.2 BP1-BP2 deletion carriers are represented by black lines. Blue dots indicate significant differences. The insular cortex is included under frontal cortex for visualization purposes. B) Top panel displays the significant differences in Z-scores, and the bottom panel shows the significant differences in RID-scores. Blue-red diverging maps represent the effect size. C) Spatial distribution of all the mean differences in RID scores. Please note that all values are shown regardless of significance. Yellow-purple diverging maps represent the direction of the mean differences. Increased yellow intensity represents values that are less deviant than the overall global mean difference in cortical surface area, and increased purple intensity represents values that are more deviant than the overall global mean difference in cortical surface area. Z- and RID-scores are based on raw values adjusted for age, age², sex, and intracranial volume on site harmonized data.

**Figure 4. Cortical thickness comparison between 15q11.2 BP1-BP2 deletion carriers and non-carriers.**
A) Top panel shows z-scores - group differences in regional cortical thickness. Bottom panel shows RID-scores - group differences in regional cortical thickness that are scaled to the individual’s own global index. Non-carriers are represented by gray lines, and 15q11.2 BP1-BP2 deletion carriers are represented by black lines. Blue dots indicate significant differences. The insular cortex is included under frontal cortex for visualization purposes. B) Top panel displays the significant differences in Z-scores, and the bottom panel shows the significant differences in RID-scores. Blue-red diverging maps represent the effect size. C) Spatial distribution of all the mean differences in RID scores. Please note that all values are shown regardless of significance. Yellow-purple diverging maps represent the direction of the mean differences. Increased yellow intensity represents values that are less deviant than the overall global mean difference in cortical thickness, and increased purple intensity represents values that are more deviant than the overall global mean difference in cortical thickness. Z- and RID-scores are based on raw values adjusted for age, age², sex, and intracranial volume on site harmonized data.

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References

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Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

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Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

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