New Results
Dissociable Cellular and Genetic Mechanisms of Cortical Thinning at Different Life Stages
View ORCID ProfileAmirhossein Modabbernia, View ORCID ProfileDidac Vidal-Pineiro, View ORCID ProfileIngrid Agartz, View ORCID ProfileOle A Andreassen, View ORCID ProfileRosa Ayesa-Arriola, Alessandro Bertolino, View ORCID ProfileDorret I Boomsma, View ORCID ProfileJosiane Bourque, Alan Breier, Henry Brodaty, View ORCID ProfileRachel M Brouwer, View ORCID ProfileJan K Buitelaar, View ORCID ProfileErick J Canales-Rodríguez, View ORCID ProfileXavier Caseras, View ORCID ProfilePatricia J Conrod, View ORCID ProfileBenedicto Crespo-Facorro, View ORCID ProfileFabrice Crivello, View ORCID ProfileEveline A Crone, View ORCID ProfileGreig I de Zubicaray, View ORCID ProfileErin W Dickie, View ORCID ProfileDanai Dima, View ORCID ProfileStefan Frenzel, View ORCID ProfileSimon E Fisher, View ORCID ProfileBarbara Franke, View ORCID ProfileDavid C Glahn, View ORCID ProfileHans-Jörgen Grabe, View ORCID ProfileDominik Grotegerd, View ORCID ProfileOliver Gruber, View ORCID ProfileAmalia Guerrero-Pedraza, View ORCID ProfileRaquel E Gur, View ORCID ProfileRuben C Gur, View ORCID ProfileCatharina A Hartman, View ORCID ProfilePieter J Hoekstra, View ORCID ProfileHilleke E Hulshoff Pol, View ORCID ProfileNeda Jahanshad, View ORCID ProfileTerry L Jernigan, View ORCID ProfileJiyang Jiang, View ORCID ProfileAndrew J Kalnin, View ORCID ProfileNicole A Kochan, View ORCID ProfileBernard Mazoyer, View ORCID ProfileBrenna C McDonald, View ORCID ProfileKatie L McMahon, View ORCID ProfileLars Nyberg, View ORCID ProfileJaap Oosterlaan, View ORCID ProfileEdith Pomarol-Clotet, View ORCID ProfileJoaquim Radua, View ORCID ProfilePerminder S Sachdev, View ORCID ProfileTheodore D Satterthwaite, View ORCID ProfileRaymond Salvador, Salvador Sarro, View ORCID ProfileAndrew J Saykin, View ORCID ProfileGunter Schumann, View ORCID ProfileJordan W Smoller, View ORCID ProfileIris E Sommer, View ORCID ProfileThomas Espeseth, View ORCID ProfileSophia I Thomopoulos, View ORCID ProfileJulian N Trollor, View ORCID ProfileDennis van ‘t Ent, View ORCID ProfileAristotle Voineskos, View ORCID ProfileYang Wang, View ORCID ProfileBernd Weber, View ORCID ProfileLars T Westlye, View ORCID ProfileHeather C Whalley, View ORCID ProfileSteven CR Williams, View ORCID ProfileKatharina Wittfeld, View ORCID ProfileMargaret J Wright, View ORCID ProfilePaul M Thompson, Thomas Paus, View ORCID ProfileSophia Frangou
doi: https://doi.org/10.1101/2022.03.21.484899
Amirhossein Modabbernia
1Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA
Didac Vidal-Pineiro
2Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway
Ingrid Agartz
3Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway
4Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
5Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden
Ole A Andreassen
3Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway
6Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
Rosa Ayesa-Arriola
7Department of Psychiatry, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute (IDIVAL), Santander, Spain
Alessandro Bertolino
8Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy
Dorret I Boomsma
9Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Josiane Bourque
10Department of Psychiatry, University of Pennsylvania, Philadelphia, USA
Alan Breier
11Department of Psychiatry, Indiana University School of Medicine, Indiana, USA
Henry Brodaty
12Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, Australia
Rachel M Brouwer
13Department of Psychiatry, UMC Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
14Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Jan K Buitelaar
15Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, The Netherlands
Erick J Canales-Rodríguez
16FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
Xavier Caseras
17MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, Wales
Patricia J Conrod
18Department of Psychiatry and Addiction, Université de Montréal, CHU Ste Justine, Montréal, Québec, Canada
Benedicto Crespo-Facorro
19Mental Health Research Networking Center (CIBERSAM), Madrid, Spain
20University Hospital Virgen del Rocio, Seville, Spain; Department of Psychiatry, University of Seville, Institute of Biomedicine of Seville (IBIS), Seville, Spain
Fabrice Crivello
21Institut des maladies neurodégénératives, Université de Bordeaux, Bordeaux, France
Eveline A Crone
22Erasmus School of Social and Behavioral Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands
Greig I de Zubicaray
23School of Psychology & Counselling, Faculty of Health, Queensland University of Technology, Brisbane, Australia
Erin W Dickie
24Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
Danai Dima
25Department of Psychology, School of Arts and Social Sciences, City, University of London, London, UK
26Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
Stefan Frenzel
27Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany
Simon E Fisher
28Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands
29Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
Barbara Franke
29Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
30Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands
David C Glahn
31Department of Psychiatry, Tommy Fuss Center for Neuropsychiatric Disease Research Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Hans-Jörgen Grabe
27Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany
32German Center for Neurodegenerative Diseases (DZNE), Rostock, Greifswald, D-17475 Greifswald, Germany
Dominik Grotegerd
33Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany
Oliver Gruber
34Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany
Amalia Guerrero-Pedraza
35Benito Menni Complex Assistencial en Salut Mental, Barcelona, Spain
Raquel E Gur
10Department of Psychiatry, University of Pennsylvania, Philadelphia, USA
Ruben C Gur
10Department of Psychiatry, University of Pennsylvania, Philadelphia, USA
Catharina A Hartman
36University of Groningen, Groningen, The Netherlands; University Medical Center Groningen, Groningen, The Netherlands; Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Groningen, The Netherlands
Pieter J Hoekstra
37Department of Child and Psychiatry, Accare Child Study Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Hilleke E Hulshoff Pol
13Department of Psychiatry, UMC Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
38Department of Psychology, Utrecht University, Utrecht, The Netherlands
Neda Jahanshad
39Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA
Terry L Jernigan
40Center for Human Development, Departments of Cognitive Science, Psychiatry, and Radiology, University of California, San Diego, California, USA
Jiyang Jiang
12Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, Australia
Andrew J Kalnin
41Department of Radiology, The Ohio State University College of Medicine, Columbus, Ohio, USA
Nicole A Kochan
12Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, Australia
Bernard Mazoyer
21Institut des maladies neurodégénératives, Université de Bordeaux, Bordeaux, France
Brenna C McDonald
42Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA
Katie L McMahon
43School of Clinical Sciences, Centre for Biomedical Technologies, Queensland University of Technology, Brisbane, Queensland, Australia
Lars Nyberg
44Department of Radiation Sciences, Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden; Department of Integrative Medical Biology, Umeå University, Umeå, Sweden
Jaap Oosterlaan
45Clinical Neuropsychology Section, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Department of Pediatrics, Emma Children’s Hospital Amsterdam UMC Follow-Me program & Emma Neuroscience Group, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands
Edith Pomarol-Clotet
16FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
19Mental Health Research Networking Center (CIBERSAM), Madrid, Spain
Joaquim Radua
5Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden
19Mental Health Research Networking Center (CIBERSAM), Madrid, Spain
46August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
Perminder S Sachdev
12Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, Australia
Theodore D Satterthwaite
10Department of Psychiatry, University of Pennsylvania, Philadelphia, USA
Raymond Salvador
16FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
19Mental Health Research Networking Center (CIBERSAM), Madrid, Spain
Salvador Sarro
16FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
Andrew J Saykin
42Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA
Gunter Schumann
47Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology, and Neuroscience, Social, Genetic & Developmental Psychiatry Centre, King’s College London, London, UK; Institute for Science and Technology of Brain-inspired Intelligence, Fudan University, Shanghai, PR China; Centre for Population Neuroscience and Precision Medicine (PONS), Charite Mental Health, Department of Psychiatry and Psychotherapy, CCM, Charite Universitätsmedizin Berlin, Germany
Jordan W Smoller
48Center for Genomic Medicine, Massachusetts General Hospital, Massachusetts, USA
Iris E Sommer
49Department of Biomedical Sciences of Cells and Systems, Rijksuniversiteit Groningen, University Medical Center Groningen, Groningen, The Netherlands
Thomas Espeseth
50Department of Psychology, University of Oslo, Oslo, Norway
51Department of Psychology, Oslo New University College, Oslo, Norway
Sophia I Thomopoulos
52Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA
Julian N Trollor
12Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, Australia
53Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, Australia
Dennis van ‘t Ent
9Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Aristotle Voineskos
24Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
Yang Wang
54Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Bernd Weber
55Institute for Experimental Epileptology and Cognition Research, University of Bonn Germany, Bonn, Germany; University Hospital Bonn, Bonn, Germany
Lars T Westlye
50Department of Psychology, University of Oslo, Oslo, Norway
Heather C Whalley
56Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
Steven CR Williams
26Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
Katharina Wittfeld
27Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany
32German Center for Neurodegenerative Diseases (DZNE), Rostock, Greifswald, D-17475 Greifswald, Germany
Margaret J Wright
57Queensland Brain Institute, University of Queensland, Brisbane, Australia
Paul M Thompson
52Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA
Thomas Paus
58Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada; Department of Psychiatry and Neuroscience, University of Montreal, Montréal, Québec, Canada; Departments of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, Canada
Sophia Frangou
1Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA
59Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver British Columbia, Canada
Abstract
Mechanisms underpinning age-related variations in cortical thickness in the human brain remain poorly understood. We investigated whether inter-regional age-related variations in cortical thinning (in a multicohort neuroimaging dataset from the ENIGMA Lifespan Working Group totalling 14,248 individuals, aged 4-89 years) depended on cell-specific marker gene expression levels. We found differences amidst early-life (<20 years), mid-life (20-60 years), and late-life (>60 years) in the patterns of association between inter-regional profiles of cortical thickness and expression profiles of marker genes for CA1 and S1 pyramidal cells, astrocytes, and microglia. Gene ontology and enrichment analyses indicated that each of the three life-stages was associated with different biological processes and cellular components: synaptic modeling in early life, neurotransmission in mid-life, and neurodegeneration in late-life. These findings provide mechanistic insights into age-related cortical thinning during typical development and aging.
Competing Interest Statement
The authors have declared no competing interest.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Posted March 22, 2022.
Dissociable Cellular and Genetic Mechanisms of Cortical Thinning at Different Life Stages
Amirhossein Modabbernia, Didac Vidal-Pineiro, Ingrid Agartz, Ole A Andreassen, Rosa Ayesa-Arriola, Alessandro Bertolino, Dorret I Boomsma, Josiane Bourque, Alan Breier, Henry Brodaty, Rachel M Brouwer, Jan K Buitelaar, Erick J Canales-Rodríguez, Xavier Caseras, Patricia J Conrod, Benedicto Crespo-Facorro, Fabrice Crivello, Eveline A Crone, Greig I de Zubicaray, Erin W Dickie, Danai Dima, Stefan Frenzel, Simon E Fisher, Barbara Franke, David C Glahn, Hans-Jörgen Grabe, Dominik Grotegerd, Oliver Gruber, Amalia Guerrero-Pedraza, Raquel E Gur, Ruben C Gur, Catharina A Hartman, Pieter J Hoekstra, Hilleke E Hulshoff Pol, Neda Jahanshad, Terry L Jernigan, Jiyang Jiang, Andrew J Kalnin, Nicole A Kochan, Bernard Mazoyer, Brenna C McDonald, Katie L McMahon, Lars Nyberg, Jaap Oosterlaan, Edith Pomarol-Clotet, Joaquim Radua, Perminder S Sachdev, Theodore D Satterthwaite, Raymond Salvador, Salvador Sarro, Andrew J Saykin, Gunter Schumann, Jordan W Smoller, Iris E Sommer, Thomas Espeseth, Sophia I Thomopoulos, Julian N Trollor, Dennis van ‘t Ent, Aristotle Voineskos, Yang Wang, Bernd Weber, Lars T Westlye, Heather C Whalley, Steven CR Williams, Katharina Wittfeld, Margaret J Wright, Paul M Thompson, Thomas Paus, Sophia Frangou
bioRxiv 2022.03.21.484899; doi: https://doi.org/10.1101/2022.03.21.484899
Dissociable Cellular and Genetic Mechanisms of Cortical Thinning at Different Life Stages
Amirhossein Modabbernia, Didac Vidal-Pineiro, Ingrid Agartz, Ole A Andreassen, Rosa Ayesa-Arriola, Alessandro Bertolino, Dorret I Boomsma, Josiane Bourque, Alan Breier, Henry Brodaty, Rachel M Brouwer, Jan K Buitelaar, Erick J Canales-Rodríguez, Xavier Caseras, Patricia J Conrod, Benedicto Crespo-Facorro, Fabrice Crivello, Eveline A Crone, Greig I de Zubicaray, Erin W Dickie, Danai Dima, Stefan Frenzel, Simon E Fisher, Barbara Franke, David C Glahn, Hans-Jörgen Grabe, Dominik Grotegerd, Oliver Gruber, Amalia Guerrero-Pedraza, Raquel E Gur, Ruben C Gur, Catharina A Hartman, Pieter J Hoekstra, Hilleke E Hulshoff Pol, Neda Jahanshad, Terry L Jernigan, Jiyang Jiang, Andrew J Kalnin, Nicole A Kochan, Bernard Mazoyer, Brenna C McDonald, Katie L McMahon, Lars Nyberg, Jaap Oosterlaan, Edith Pomarol-Clotet, Joaquim Radua, Perminder S Sachdev, Theodore D Satterthwaite, Raymond Salvador, Salvador Sarro, Andrew J Saykin, Gunter Schumann, Jordan W Smoller, Iris E Sommer, Thomas Espeseth, Sophia I Thomopoulos, Julian N Trollor, Dennis van ‘t Ent, Aristotle Voineskos, Yang Wang, Bernd Weber, Lars T Westlye, Heather C Whalley, Steven CR Williams, Katharina Wittfeld, Margaret J Wright, Paul M Thompson, Thomas Paus, Sophia Frangou
bioRxiv 2022.03.21.484899; doi: https://doi.org/10.1101/2022.03.21.484899
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