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1. Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Author

Patel, Yash, Shin, Jean, Abé, Christoph, Agartz, Ingrid, Alloza, Clara, Alnæs, Dag, Ambrogi, Sonia, Antonucci, Linda A, Arango, Celso, Arolt, Volker, Auzias, Guillaume, Ayesa-Arriola, Rosa, Banaj, Nerisa, Banaschewski, Tobias, Bandeira, Cibele, Başgöze, Zeynep, Cupertino, Renata Basso, Bau, Claiton HD, Bauer, Jochen, Baumeister, Sarah, Bernardoni, Fabio, Bertolino, Alessandro, Bonnin, Caterina Del Mar, Brandeis, Daniel, Brem, Silvia, Bruggemann, Jason, Bülow, Robin, Bustillo, Juan R, Calderoni, Sara, Calvo, Rosa, Canales-Rodríguez, Erick J, Cannon, Dara M, Carmona, Susanna, Carr, Vaughan J, Catts, Stanley V, Chenji, Sneha, Chew, Qian Hui, Coghill, David, Connolly, Colm G, Conzelmann, Annette, Craven, Alexander R, Crespo-Facorro, Benedicto, Cullen, Kathryn, Dahl, Andreas, Dannlowski, Udo, Davey, Christopher G, Deruelle, Christine, Díaz-Caneja, Covadonga M, Dohm, Katharina, Ehrlich, Stefan, Epstein, Jeffery, Erwin-Grabner, Tracy, Eyler, Lisa T, Fedor, Jennifer, Fitzgerald, Jacqueline, Foran, William, Ford, Judith M, Fortea, Lydia, Fuentes-Claramonte, Paola, Fullerton, Janice, Furlong, Lisa, Gallagher, Louise, Gao, Bingchen, Gao, Si, Goikolea, Jose M, Gotlib, Ian, Goya-Maldonado, Roberto, Grabe, Hans J, Green, Melissa, Grevet, Eugenio H, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Haavik, Jan, Hahn, Tim, Harrison, Ben J, Heindel, Walter, Henskens, Frans, Heslenfeld, Dirk J, Hilland, Eva, Hoekstra, Pieter J, Hohmann, Sarah, Holz, Nathalie, Howells, Fleur M, Ipser, Jonathan C, Jahanshad, Neda, Jakobi, Babette, Jansen, Andreas, Janssen, Joost, Jonassen, Rune, Kaiser, Anna, Kaleda, Vasiliy, Karantonis, James, King, Joseph A, Kircher, Tilo, Kochunov, Peter, Koopowitz, Sheri-Michelle, Landén, Mikael, Landrø, Nils Inge, and Lawrie, Stephen

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Serious Mental Illness, Behavioral and Social Science, Genetics, Women's Health, Neurosciences, Schizophrenia, Brain Disorders, Preterm, Low Birth Weight and Health of the Newborn, Mental Health, Perinatal Period - Conditions Originating in Perinatal Period, Pregnancy, Pediatric, Mental Illness, Prevention, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Reproductive health and childbirth, Mental health, Neurological, Good Health and Well Being, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Bipolar Disorder, Cerebral Cortex, Child, Depressive Disorder, Major, Female, Humans, Infant, Newborn, Magnetic Resonance Imaging, Premature Birth, Cortical growth, Cortical surface area, Mental illness, Neurodevelopment, Neurogenesis, Psychiatric disorders, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences
Abstract

BackgroundMorphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life.MethodsInterregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed.ResultsAcross the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth.ConclusionsOur findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.

Published
2022

2. Genetic variants associated with longitudinal changes in brain structure across the lifespan

Author

Brouwer, Rachel M, Klein, Marieke, Grasby, Katrina L, Schnack, Hugo G, Jahanshad, Neda, Teeuw, Jalmar, Thomopoulos, Sophia I, Sprooten, Emma, Franz, Carol E, Gogtay, Nitin, Kremen, William S, Panizzon, Matthew S, Olde Loohuis, Loes M, Whelan, Christopher D, Aghajani, Moji, Alloza, Clara, Alnæs, Dag, Artiges, Eric, Ayesa-Arriola, Rosa, Barker, Gareth J, Bastin, Mark E, Blok, Elisabet, Bøen, Erlend, Breukelaar, Isabella A, Bright, Joanna K, Buimer, Elizabeth EL, Bülow, Robin, Cannon, Dara M, Ciufolini, Simone, Crossley, Nicolas A, Damatac, Christienne G, Dazzan, Paola, de Mol, Casper L, de Zwarte, Sonja MC, Desrivières, Sylvane, Díaz-Caneja, Covadonga M, Doan, Nhat Trung, Dohm, Katharina, Fröhner, Juliane H, Goltermann, Janik, Grigis, Antoine, Grotegerd, Dominik, Han, Laura KM, Harris, Mathew A, Hartman, Catharina A, Heany, Sarah J, Heindel, Walter, Heslenfeld, Dirk J, Hohmann, Sarah, Ittermann, Bernd, Jansen, Philip R, Janssen, Joost, Jia, Tianye, Jiang, Jiyang, Jockwitz, Christiane, Karali, Temmuz, Keeser, Daniel, Koevoets, Martijn GJC, Lenroot, Rhoshel K, Malchow, Berend, Mandl, René CW, Medel, Vicente, Meinert, Susanne, Morgan, Catherine A, Mühleisen, Thomas W, Nabulsi, Leila, Opel, Nils, de la Foz, Víctor Ortiz-García, Overs, Bronwyn J, Paillère Martinot, Marie-Laure, Redlich, Ronny, Marques, Tiago Reis, Repple, Jonathan, Roberts, Gloria, Roshchupkin, Gennady V, Setiaman, Nikita, Shumskaya, Elena, Stein, Frederike, Sudre, Gustavo, Takahashi, Shun, Thalamuthu, Anbupalam, Tordesillas-Gutiérrez, Diana, van der Lugt, Aad, van Haren, Neeltje EM, Wardlaw, Joanna M, Wen, Wei, Westeneng, Henk-Jan, Wittfeld, Katharina, Zhu, Alyssa H, Zugman, Andre, Armstrong, Nicola J, Bonfiglio, Gaia, Bralten, Janita, Dalvie, Shareefa, Davies, Gail, Di Forti, Marta, Ding, Linda, Donohoe, Gary, Forstner, Andreas J, and Gonzalez-Peñas, Javier

Subjects
Biological Psychology, Psychology, Neurosciences, Mental Illness, Human Genome, Genetics, Aging, Mental Health, Brain Disorders, 2.1 Biological and endogenous factors, Neurological, Mental health, Brain, Genome-Wide Association Study, Humans, Longevity, Magnetic Resonance Imaging, IMAGEN Consortium, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

Published
2022

3. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Author

Dima, Danai, Modabbernia, Amirhossein, Papachristou, Efstathios, Doucet, Gaelle E, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn I, Andersson, Micael, Andreasen, Nancy C, Andreassen, Ole A, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Buckner, Randy L, Calhoun, Vincent, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Cervenka, Simon, Chaim-Avancini, Tiffany M, Ching, Christopher RK, Chubar, Victoria, Clark, Vincent P, Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A, Dannlowski, Udo, Dale, Anders M, Davey, Christopher, de Geus, Eco JC, de Haan, Lieuwe, de Zubicaray, Greig I, den Braber, Anouk, Dickie, Erin W, Di Giorgio, Annabella, Doan, Nhat Trung, Dørum, Erlend S, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fatouros-Bergman, Helena, Fisher, Simon E, Fouche, Jean-Paul, Franke, Barbara, Frodl, Thomas, Fuentes-Claramonte, Paola, Glahn, David C, Gotlib, Ian H, Grabe, Hans-Jörgen, Grimm, Oliver, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E, Gur, Ruben C, Hahn, Tim, Harrison, Ben J, Hartman, Catharine A, Hatton, Sean N, Heinz, Andreas, Heslenfeld, Dirk J, Hibar, Derrek P, Hickie, Ian B, Ho, Beng-Choon, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Hulshoff Pol, Hilleke E, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, Kahn, Rene, and Kalnin, Andrew

Subjects
Karolinska Schizophrenia Project, Amygdala, Hippocampus, Thalamus, Corpus Striatum, Humans, Human Development, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Child, Preschool, Female, Male, Young Adult, Neuroimaging, ENIGMA, brain morphometry, longitudinal trajectories, multisite, Neurosciences, Aging, Aetiology, 2.1 Biological and endogenous factors, Mental health, Cognitive Sciences, Experimental Psychology
Abstract

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.

Published
2022

4. Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3–90 years

Author

Frangou, Sophia, Modabbernia, Amirhossein, Williams, Steven CR, Papachristou, Efstathios, Doucet, Gaelle E, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes‐Eizagirre, Anton, Alnæs, Dag, Alpert, Kathryn I, Andersson, Micael, Andreasen, Nancy C, Andreassen, Ole A, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur‐Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Buckner, Randy L, Calhoun, Vincent, Canales‐Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Cervenka, Simon, Chaim‐Avancini, Tiffany M, Ching, Christopher RK, Chubar, Victoria, Clark, Vincent P, Conrod, Patricia, Conzelmann, Annette, Crespo‐Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A, Dale, Anders M, Dannlowski, Udo, Davey, Christopher, Geus, Eco JC, Haan, Lieuwe, Zubicaray, Greig I, Braber, Anouk, Dickie, Erin W, Di Giorgio, Annabella, Doan, Nhat Trung, Dørum, Erlend S, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fatouros‐Bergman, Helena, Fisher, Simon E, Fouche, Jean‐Paul, Franke, Barbara, Frodl, Thomas, Fuentes‐Claramonte, Paola, Glahn, David C, Gotlib, Ian H, Grabe, Hans‐Jörgen, Grimm, Oliver, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E, Gur, Ruben C, Hahn, Tim, Harrison, Ben J, Hartman, Catharine A, Hatton, Sean N, Heinz, Andreas, Heslenfeld, Dirk J, Hibar, Derrek P, Hickie, Ian B, Ho, Beng‐Choon, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Pol, Hilleke E Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, and Kahn, Rene

Subjects
Behavioral and Social Science, Neurosciences, Aging, Adolescent, Adult, Aged, Aged, 80 and over, Cerebral Cortex, Child, Child, Preschool, Cross-Sectional Studies, Female, Human Development, Humans, Male, Middle Aged, Neuroimaging, Young Adult, aging, cortical thickness, development, trajectories, Karolinska Schizophrenia Project, Cognitive Sciences, Experimental Psychology
Abstract

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.

Published
2022

5. Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets

Author

Postema, Merel C, Hoogman, Martine, Ambrosino, Sara, Asherson, Philip, Banaschewski, Tobias, Bandeira, Cibele E, Baranov, Alexandr, Bau, Claiton HD, Baumeister, Sarah, Baur‐Streubel, Ramona, Bellgrove, Mark A, Biederman, Joseph, Bralten, Janita, Brandeis, Daniel, Brem, Silvia, Buitelaar, Jan K, Busatto, Geraldo F, Castellanos, Francisco X, Cercignani, Mara, Chaim‐Avancini, Tiffany M, Chantiluke, Kaylita C, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Cupertino, Renata B, de Zeeuw, Patrick, Doyle, Alysa E, Durston, Sarah, Earl, Eric A, Epstein, Jeffery N, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas J, Faraone, Stephen V, Frodl, Thomas, Gabel, Matt C, Gogberashvili, Tinatin, Grevet, Eugenio H, Haavik, Jan, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hoekstra, Pieter J, Hohmann, Sarah, Høvik, Marie F, Jernigan, Terry L, Kardatzki, Bernd, Karkashadze, Georgii, Kelly, Clare, Kohls, Gregor, Konrad, Kerstin, Kuntsi, Jonna, Lazaro, Luisa, Lera‐Miguel, Sara, Lesch, Klaus‐Peter, Louza, Mario R, Lundervold, Astri J, Malpas, Charles B, Mattos, Paulo, McCarthy, Hazel, Namazova‐Baranova, Leyla, Nicolau, Rosa, Nigg, Joel T, Novotny, Stephanie E, Weiss, Eileen Oberwelland, Tuura, Ruth L O'Gorman, Oosterlaan, Jaap, Oranje, Bob, Paloyelis, Yannis, Pauli, Paul, Picon, Felipe A, Plessen, Kerstin J, Ramos‐Quiroga, J Antoni, Reif, Andreas, Reneman, Liesbeth, Rosa, Pedro GP, Rubia, Katya, Schrantee, Anouk, Schweren, Lizanne JS, Seitz, Jochen, Shaw, Philip, Silk, Tim J, Skokauskas, Norbert, Vila, Juan C Soliva, Stevens, Michael C, Sudre, Gustavo, Tamm, Leanne, Tovar‐Moll, Fernanda, van Erp, Theo GM, Vance, Alasdair, Vilarroya, Oscar, Vives‐Gilabert, Yolanda, von Polier, Georg G, Walitza, Susanne, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, Glahn, David C, and Jahanshad, Neda

Subjects
Biological Psychology, Psychology, Brain Disorders, Mental Illness, Mental Health, Pediatric, Clinical Research, Attention Deficit Hyperactivity Disorder (ADHD), Behavioral and Social Science, Neurosciences, 2.1 Biological and endogenous factors, Mental health, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Brain, Caudate Nucleus, Child, Humans, Magnetic Resonance Imaging, Attention&#8208, deficit, hyperactivity disorder, brain asymmetry, brain laterality, structural MRI, large&#8208, scale data, ENIGMA ADHD Working Group, Attention-deficit, large-scale data, Clinical Sciences, Cognitive Sciences, Developmental & Child Psychology, Clinical sciences, Applied and developmental psychology, Clinical and health psychology
Abstract

ObjectiveSome studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.MethodsWe analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.ResultsThere was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.ConclusionPrior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

Published
2021

6. Characterizing neuroanatomic heterogeneity in people with and without ADHD based on subcortical brain volumes

Author

Li, Ting, van Rooij, Daan, Mota, Nina Roth, Buitelaar, Jan K, Ambrosino, Sara, Banaschewski, Tobias, Bandeira, Cibele E, Bau, Claiton HD, Baumeister, Sarah, Baur‐Streubel, Ramona, Bellgrove, Mark A, Biederman, Joseph, Bralten, Janita, Bramati, Ivanei E, Brandeis, Daniel, Berm, Silvia, Busatto, Geraldo F, Calvo, Anna, Castellanos, Francisco X, Cercignani, Mara, Chantiluke, Kaylita C, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Cupertino, Renata B, de Zeeuw, Parick, Durston, Sarah, Earl, Eric A, Epstein, Jeffery N, Ethofer, Thomas, Fallgatter, Andreas J, Fair, Damien A, Faraone, Stephen V, Frodl, Thomas, Gabel, Matt C, Gogberashvili, Tinatin, Grevet, Eugenio H, Haavik, Jan, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hoekstra, Pieter J, Høvik, Marie F, Jahanshad, Neda, Kardatzki, Bernd, Karkashadze, Georgii, Kelly, Clare, Kohls, Gregor, Konrad, Kerstin, Kuntsi, Jonna, Lazaro, Luisa, Lera‐Miguel, Sara, Lesch, Klaus‐Peter, Louza, Mario R, Lundervold, Astri J, Malpas, Charles B, Mattos, Paulo, McCarthy, Hazel, Nicolau, Rosa, Nigg, Joel T, Tuura, Ruth L O'Gorman, Oosterlaan, Jaap, Oranje, Bob, Paloyelis, Yannis, Pauli, Paul, Picon, Felipe A, Plessen, Kerstin J, Ramos‐Quiroga, J Antoni, Reif, Andreas, Reneman, Liesbeth, Rosa, Pedro GP, Rubia, Katya, Schrantee, Anouk, Schweren, Lizanne JS, Seitz, Jochen, Shaw, Philip, Silk, Tim J, Skokauskas, Norbert, Vila, Juan Carlos Soliva, Soloveva, Anastasiia, Stevens, Michael C, Sudre, Gustavo, Tamm, Leanne, Thompson, Paul M, Tovar‐Moll, Fernanda, van Erp, Theo GM, Vance, Alasdair, Vilarroya, Oscar, Vives‐Gilabert, Yolanda, von Polier, Georg G, Walitza, Susanne, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, Anikin, Anatoly, Asherson, Philip, Baranov, Alexandr, Chaim‐Avanicini, Tiffany, and Dale, Anders M

Subjects
Biological Psychology, Psychology, Mental Health, Pediatric, Brain Disorders, Attention Deficit Hyperactivity Disorder (ADHD), Clinical Research, Neurosciences, Adult, Attention Deficit Disorder with Hyperactivity, Brain, Case-Control Studies, Female, Humans, Magnetic Resonance Imaging, Male, Thalamus, ADHD, subcortical volume, neuroanatomic heterogeneity, community detection, effect sizes, ENIGMA ADHD Working Group, Clinical Sciences, Cognitive Sciences, Developmental & Child Psychology, Clinical sciences, Applied and developmental psychology, Clinical and health psychology
Abstract

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Neuroanatomic heterogeneity limits our understanding of ADHD's etiology. This study aimed to parse heterogeneity of ADHD and to determine whether patient subgroups could be discerned based on subcortical brain volumes.MethodsUsing the large ENIGMA-ADHD Working Group dataset, four subsamples of 993 boys with and without ADHD and to subsamples of 653 adult men, 400 girls, and 447 women were included in analyses. We applied exploratory factor analysis (EFA) to seven subcortical volumes in order to constrain the complexity of the input variables and ensure more stable clustering results. Factor scores derived from the EFA were used to build networks. A community detection (CD) algorithm clustered participants into subgroups based on the networks.ResultsExploratory factor analysis revealed three factors (basal ganglia, limbic system, and thalamus) in boys and men with and without ADHD. Factor structures for girls and women differed from those in males. Given sample size considerations, we concentrated subsequent analyses on males. Male participants could be separated into four communities, of which one was absent in healthy men. Significant case-control differences of subcortical volumes were observed within communities in boys, often with stronger effect sizes compared to the entire sample. As in the entire sample, none were observed in men. Affected men in two of the communities presented comorbidities more frequently than those in other communities. There were no significant differences in ADHD symptom severity, IQ, and medication use between communities in either boys or men.ConclusionsOur results indicate that neuroanatomic heterogeneity in subcortical volumes exists, irrespective of ADHD diagnosis. Effect sizes of case-control differences appear more pronounced at least in some of the subgroups.

Published
2021

7. Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups

Author

Boedhoe, Premika SW, van Rooij, Daan, Hoogman, Martine, Twisk, Jos WR, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anikin, Anatoly, Anticevic, Alan, Arango, Celso, Arnold, Paul D, Asherson, Philip, Assogna, Francesca, Auzias, Guillaume, Banaschewski, Tobias, Baranov, Alexander, Batistuzzo, Marcelo C, Baumeister, Sarah, Baur-Streubel, Ramona, Behrmann, Marlene, Bellgrove, Mark A, Benedetti, Francesco, Beucke, Jan C, Biederman, Joseph, Bollettini, Irene, Bose, Anushree, Bralten, Janita, Bramati, Ivanei E, Brandeis, Daniel, Brem, Silvia, Brennan, Brian P, Busatto, Geraldo F, Calderoni, Sara, Calvo, Anna, Calvo, Rosa, Castellanos, Francisco X, Cercignani, Mara, Chaim-Avancini, Tiffany M, Chantiluke, Kaylita C, Cheng, Yuqi, Cho, Kang Ik K, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Dale, Anders M, Dallaspezia, Sara, Daly, Eileen, Denys, Damiaan, Deruelle, Christine, Di Martino, Adriana, Dinstein, Ilan, Doyle, Alysa E, Durston, Sarah, Earl, Eric A, Ecker, Christine, Ehrlich, Stefan, Ely, Benjamin A, Epstein, Jeffrey N, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas J, Faraone, Stephen V, Fedor, Jennifer, Feng, Xin, Feusner, Jamie D, Fitzgerald, Jackie, Fitzgerald, Kate D, Fouche, Jean-Paul, Freitag, Christine M, Fridgeirsson, Egill A, Frodl, Thomas, Gabel, Matt C, Gallagher, Louise, Gogberashvili, Tinatin, Gori, Ilaria, Gruner, Patricia, Gürsel, Deniz A, Haar, Shlomi, Haavik, Jan, Hall, Geoffrey B, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hirano, Yoshiyuki, Hoekstra, Pieter J, Hoexter, Marcelo Q, Hohmann, Sarah, Høvik, Marie F, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, Jalbrzikowski, Maria, James, Anthony, Janssen, Joost, Jaspers-Fayer, Fern, Jernigan, Terry L, Kapilushniy, Dmitry, and Kardatzki, Bernd

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Biomedical Imaging, Intellectual and Developmental Disabilities (IDD), Pediatric, Brain Disorders, Attention Deficit Hyperactivity Disorder (ADHD), Mental Health, Neurosciences, Autism, Clinical Research, Mental Illness, Behavioral and Social Science, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Mental health, Neurological, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Cerebrum, Child, Female, Human Development, Humans, Male, Neuroimaging, Obsessive-Compulsive Disorder, Organ Size, Psychopathology, Research Report, Systems Analysis, ENIGMA ADHD working group, ENIGMA ASD working group, ENIGMA OCD working group, Attention Deficit Hyperactivity Disorder, ENIGMA, Structural MRI, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract

ObjectiveAttention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.MethodsStructural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).ResultsNo shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.ConclusionsThe study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

Published
2020

8. The genetic architecture of the human cerebral cortex

Author

Grasby, Katrina L, Jahanshad, Neda, Painter, Jodie N, Colodro-Conde, Lucía, Bralten, Janita, Hibar, Derrek P, Lind, Penelope A, Pizzagalli, Fabrizio, Ching, Christopher RK, McMahon, Mary Agnes B, Shatokhina, Natalia, Zsembik, Leo CP, Thomopoulos, Sophia I, Zhu, Alyssa H, Strike, Lachlan T, Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio AA, Alnæs, Dag, Amlien, Inge K, Andersson, Micael, Ard, Tyler, Armstrong, Nicola J, Ashley-Koch, Allison, Atkins, Joshua R, Bernard, Manon, Brouwer, Rachel M, Buimer, Elizabeth EL, Bülow, Robin, Bürger, Christian, Cannon, Dara M, Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W, Couvy-Duchesne, Baptiste, Dale, Anders M, Dalvie, Shareefa, de Araujo, Tânia K, de Zubicaray, Greig I, de Zwarte, Sonja MC, Braber, Anouk den, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah-Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O, Foley, Sonya F, Ford, Judith M, Fukunaga, Masaki, Garrett, Melanie E, Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L, Green, Melissa J, Groenewold, Nynke A, Grotegerd, Dominik, Gurholt, Tiril P, Gutman, Boris A, Hansell, Narelle K, Harris, Mathew A, Harrison, Marc B, Haswell, Courtney C, Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J, Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke-Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E, Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R, Krämer, Bernd, Lam, Max, Lancaster, Thomas M, Lee, Phil H, Lett, Tristram A, Lewis, Lindsay B, Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F, Mathias, Samuel R, Melzer, Tracy R, and Milaneschi, Yuri

Subjects
Biological Sciences, Genetics, Brain Disorders, Mental Health, Stem Cell Research, Neurosciences, Human Genome, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Cerebral Cortex, Cognition, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Organ Size, Parkinson Disease, Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN Consortium, IMAGEN Consortium, SYS Consortium, Parkinson’s Progression Markers Initiative, Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group, General Science & Technology
Abstract

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Published
2020

10. Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples

Author

Hoogman, Martine, Muetzel, Ryan, Guimaraes, Joao P, Shumskaya, Elena, Mennes, Maarten, Zwiers, Marcel P, Jahanshad, Neda, Sudre, Gustavo, Wolfers, Thomas, Earl, Eric A, Soliva Vila, Juan Carlos, Vives-Gilabert, Yolanda, Khadka, Sabin, Novotny, Stephanie E, Hartman, Catharina A, Heslenfeld, Dirk J, Schweren, Lizanne JS, Ambrosino, Sara, Oranje, Bob, de Zeeuw, Patrick, Chaim-Avancini, Tiffany M, Rosa, Pedro GP, Zanetti, Marcus V, Malpas, Charles B, Kohls, Gregor, von Polier, Georg G, Seitz, Jochen, Biederman, Joseph, Doyle, Alysa E, Dale, Anders M, van Erp, Theo GM, Epstein, Jeffery N, Jernigan, Terry L, Baur-Streubel, Ramona, Ziegler, Georg C, Zierhut, Kathrin C, Schrantee, Anouk, Høvik, Marie F, Lundervold, Astri J, Kelly, Clare, McCarthy, Hazel, Skokauskas, Norbert, O’Gorman Tuura, Ruth L, Calvo, Anna, Lera-Miguel, Sara, Nicolau, Rosa, Chantiluke, Kaylita C, Christakou, Anastasia, Vance, Alasdair, Cercignani, Mara, Gabel, Matt C, Asherson, Philip, Baumeister, Sarah, Brandeis, Daniel, Hohmann, Sarah, Bramati, Ivanei E, Tovar-Moll, Fernanda, Fallgatter, Andreas J, Kardatzki, Bernd, Schwarz, Lena, Anikin, Anatoly, Baranov, Alexandr, Gogberashvili, Tinatin, Kapilushniy, Dmitry, Solovieva, Anastasia, El Marroun, Hanan, White, Tonya, Karkashadze, Georgii, Namazova-Baranova, Leyla, Ethofer, Thomas, Mattos, Paulo, Banaschewski, Tobias, Coghill, David, Plessen, Kerstin J, Kuntsi, Jonna, Mehta, Mitul A, Paloyelis, Yannis, Harrison, Neil A, Bellgrove, Mark A, Silk, Tim J, Cubillo, Ana I, Rubia, Katya, Lazaro, Luisa, Brem, Silvia, Walitza, Susanne, Frodl, Thomas, Zentis, Mariam, Castellanos, Francisco X, Yoncheva, Yuliya N, Haavik, Jan, Reneman, Liesbeth, Conzelmann, Annette, Lesch, Klaus-Peter, Pauli, Paul, Reif, Andreas, Tamm, Leanne, Konrad, Kerstin, Oberwelland Weiss, Eileen, Busatto, Geraldo F, and Louza, Mario R

Subjects
Biological Psychology, Psychology, Biomedical Imaging, Mental Illness, Neurosciences, Behavioral and Social Science, Mental Health, Brain Disorders, Attention Deficit Hyperactivity Disorder (ADHD), Pediatric, Clinical Research, 2.1 Biological and endogenous factors, Mental health, Adolescent, Adult, Age Factors, Attention Deficit Disorder with Hyperactivity, Case-Control Studies, Cerebral Cortex, Child, Child, Preschool, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Psychiatric Status Rating Scales, Sex Factors, Young Adult, Attention Deficit Hyperactivity Disorder, Cortical Surface Area, Cortical Thickness, Imaging, Meta-Analysis, Neuroanatomy, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract

ObjectiveNeuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies.MethodsCortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707).ResultsIn the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample.ConclusionsSubtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

Published
2019

11. Hearing Impairment: Reduced Pupil Dilation Response and Frontal Activation During Degraded Speech Perception.

Author

Zekveld, Adriana A., Kramer, Sophia E., Heslenfeld, Dirk J., Versfeld, Niek J., and Vriende, Chris

Subjects
PEARSON correlation (Statistics), RESEARCH funding, INSULAR cortex, DATA analysis, T-test (Statistics), REFLEXES, SENSORINEURAL hearing loss, HEARING aids, MAGNETIC resonance imaging, INTELLIGIBILITY of speech, AUDIOMETRY, MANN Whitney U Test, DESCRIPTIVE statistics, TEMPORAL lobe, FRONTAL lobe, SPEECH audiometry, STATISTICS, ANALYSIS of variance, HEARING disorders, SPEECH perception, HEARING, ACOUSTIC stimulation, COMPARATIVE studies, DATA analysis software
Abstract

Purpose: A relevant aspect of listening is the effort required during speech processing, which can be assessed by pupillometry. Here, we assessed the pupil dilation response of normal-hearing (NH) and hard of hearing (HH) individuals during listening to clear sentences and masked or degraded sentences. We combined this assessment with functional magnetic resonance imaging (fMRI) to investigate the neural correlates of the pupil dilation response. Method: Seventeen NH participants (Mage = 46 years) were compared to 17 HH participants (Mage = 45 years) who were individually matched in age and educational level. Participants repeated sentences that were presented clearly, that were distorted, or that were masked. The sentence intelligibility level of masked and distorted sentences was 50% correct. Silent baseline trials were presented as well. Performance measures, pupil dilation responses, and fMRI data were acquired. Results: HH individuals had overall poorer speech reception than the NH participants, but not for noise-vocoded speech. In addition, an interaction effect was observed with smaller pupil dilation responses in HH than in NH listeners for the degraded speech conditions. Hearing impairment was associated with higher activation across conditions in the left superior temporal gyrus, as compared to the silent baseline. However, the region of interest analysis indicated lower activation during degraded speech relative to clear speech in bilateral frontal regions and the insular cortex, for HH compared to NH listeners. Hearing impairment was also associated with a weaker relation between the pupil response and activation in the right inferior frontal gyrus. Overall, degraded speech evoked higher frontal activation than clear speech. Conclusion: Brain areas associated with attentional and cognitive-control processes may be increasingly recruited when speech is degraded and are related to the pupil dilation response, but this relationship is weaker in HH listeners. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis

Author

Hoogman, Martine, Bralten, Janita, Hibar, Derrek P, Mennes, Maarten, Zwiers, Marcel P, Schweren, Lizanne SJ, van Hulzen, Kimm JE, Medland, Sarah E, Shumskaya, Elena, Jahanshad, Neda, de Zeeuw, Patrick, Szekely, Eszter, Sudre, Gustavo, Wolfers, Thomas, Onnink, Alberdingk MH, Dammers, Janneke T, Mostert, Jeanette C, Vives-Gilabert, Yolanda, Kohls, Gregor, Oberwelland, Eileen, Seitz, Jochen, Schulte-Rüther, Martin, Ambrosino, Sara, Doyle, Alysa E, Høvik, Marie F, Dramsdahl, Margaretha, Tamm, Leanne, van Erp, Theo GM, Dale, Anders, Schork, Andrew, Conzelmann, Annette, Zierhut, Kathrin, Baur, Ramona, McCarthy, Hazel, Yoncheva, Yuliya N, Cubillo, Ana, Chantiluke, Kaylita, Mehta, Mitul A, Paloyelis, Yannis, Hohmann, Sarah, Baumeister, Sarah, Bramati, Ivanei, Mattos, Paulo, Tovar-Moll, Fernanda, Douglas, Pamela, Banaschewski, Tobias, Brandeis, Daniel, Kuntsi, Jonna, Asherson, Philip, Rubia, Katya, Kelly, Clare, Di Martino, Adriana, Milham, Michael P, Castellanos, Francisco X, Frodl, Thomas, Zentis, Mariam, Lesch, Klaus-Peter, Reif, Andreas, Pauli, Paul, Jernigan, Terry L, Haavik, Jan, Plessen, Kerstin J, Lundervold, Astri J, Hugdahl, Kenneth, Seidman, Larry J, Biederman, Joseph, Rommelse, Nanda, Heslenfeld, Dirk J, Hartman, Catharina A, Hoekstra, Pieter J, Oosterlaan, Jaap, von Polier, Georg, Konrad, Kerstin, Vilarroya, Oscar, Ramos-Quiroga, Josep Antoni, Soliva, Joan Carles, Durston, Sarah, Buitelaar, Jan K, Faraone, Stephen V, Shaw, Philip, Thompson, Paul M, and Franke, Barbara

Subjects
Brain Disorders, Neurosciences, Attention Deficit Hyperactivity Disorder (ADHD), Clinical Research, Mental Health, Pediatric, Biomedical Imaging, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Brain, Case-Control Studies, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Linear Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Young Adult, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

BackgroundNeuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis.MethodsIn this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156.FindingsOur sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (21 years): in the accumbens (Cohen's d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5).InterpretationWith the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes.FundingNational Institutes of Health.

Published
2017

15. Genetic architecture of subcortical brain structures in 38,851 individuals

Author

Satizabal, Claudia L., Adams, Hieab H. H., Hibar, Derrek P., White, Charles C., Knol, Maria J., Stein, Jason L., Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V., Smith, Albert V., Bis, Joshua C., Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J., Yang, Jingyun, Yanek, Lisa R., Lee, Tom V., Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D., Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentería, Miguel E., Kim, Sungeun, Hoehn, David, Armstrong, Nicola J., Chen, Qiang, Holmes, Avram J., den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santiañez, Roberto, Kraemer, Bernd, Håberg, Asta K., Jones, Hannah J., Pike, G. Bruce, Stein, Dan J., Stevens, Allison, Bralten, Janita, Vernooij, Meike W., Harris, Tamara B., Filippi, Irina, Witte, A. Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H., Becker, James T., Doan, Nhat Trung, Hagenaars, Saskia P., Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M., Ames, David, Goldman, Aaron L., Lee, Phil H., Boomsma, Dorret I., Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M., Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M., Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E., Shin, Jean, Ipser, Jonathan C., Vinke, Louis N., Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K., Aribisala, Benjamin S., Schmidt, Helena, Strike, Lachlan T., Cheng, Ching-Yu, Risacher, Shannon L., Pütz, Benno, Fleischman, Debra A., Assareh, Amelia A., Mattay, Venkata S., Buckner, Randy L., Mecocci, Patrizia, Dale, Anders M., Cichon, Sven, Boks, Marco P., Matarin, Mar, Penninx, Brenda W. J. H., Calhoun, Vince D., Chakravarty, M. Mallar, Marquand, Andre F., Macare, Christine, Kharabian Masouleh, Shahrzad, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome I., Schork, Andrew J., Liewald, David C. M., de Zubicaray, Greig I., Wong, Tien Yin, Shen, Li, Sämann, Philipp G., Brodaty, Henry, Roffman, Joshua L., de Geus, Eco J. C., Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R., Cavalleri, Gianpiero L., van der Wee, Nic J. A., McIntosh, Andrew M., Gollub, Randy L., Bulayeva, Kazima B., Bernard, Manon, Richards, Jennifer S., Himali, Jayandra J., Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T., Valdés Hernández, Maria C., Hansell, Narelle K., van Erp, Theo G. M., Wolf, Christiane, Kwok, John B. J., Vellas, Bruno, Heinz, Andreas, Olde Loohuis, Loes M., Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R. K., Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M., Bastin, Mark E., Montgomery, Grant W., Foroud, Tatiana M., Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D., van Donkelaar, Marjolein M. J., Yang, Qiong, Hosten, Norbert, Green, Robert C, Thalamuthu, Anbupalam, Mohnke, Sebastian, Hulshoff Pol, Hilleke E., Lin, Honghuang, Jack, Jr, Clifford R., Schofield, Peter R., Mühleisen, Thomas W., Maillard, Pauline, Potkin, Steven G., Wen, Wei, Fletcher, Evan, Toga, Arthur W., Gruber, Oliver, Huentelman, Matthew, Davey Smith, George, Launer, Lenore J., Nyberg, Lars, Jönsson, Erik G., Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N., Uitterlinden, André G., Weinberger, Daniel R., Steen, Vidar M., Fedko, Iryna O., Groenewold, Nynke A., Niessen, Wiro J., Toro, Roberto, Tzourio, Christophe, Longstreth, Jr, William T., Ikram, M. Kamran, Smoller, Jordan W., van Tol, Marie-Jose, Sussmann, Jessika E., Paus, Tomas, Lemaître, Hervé, Schroeter, Matthias L., Mazoyer, Bernard, Andreassen, Ole A., Holsboer, Florian, Depondt, Chantal, Veltman, Dick J., Turner, Jessica A., Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J., McMahon, Katie L., Müller-Myhsok, Bertram, Brouwer, Rachel M., Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H., Cheung, Joshua W., Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P., Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G., Kanai, Ryota, Westman, Eric, Kahn, René S., Sisodiya, Sanjay M., White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G., Völzke, Henry, Wright, Margaret J., van ‘t Ent, Dennis, Nöthen, Markus M., Ophoff, Roel A., Buitelaar, Jan K., Fernández, Guillén, Sachdev, Perminder S., Rietschel, Marcella, van Haren, Neeltje E. M., Fisher, Simon E., Beiser, Alexa S., Francks, Clyde, Saykin, Andrew J., Mather, Karen A., Romanczuk-Seiferth, Nina, Hartman, Catharina A., DeStefano, Anita L., Heslenfeld, Dirk J., Weiner, Michael W., Walter, Henrik, Hoekstra, Pieter J., Nyquist, Paul A., Franke, Barbara, Bennett, David A., Grabe, Hans J., Johnson, Andrew D., Chen, Christopher, van Duijn, Cornelia M., Lopez, Oscar L., Fornage, Myriam, Wardlaw, Joanna M., Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L., Villringer, Arno, Debette, Stéphanie, Gudnason, Vilmundur, Medland, Sarah E., Shulman, Joshua M., Thompson, Paul M., Seshadri, Sudha, and Ikram, M. Arfan

Published
2019
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24. Increased Neural Responses to Reward in Adolescents and Young Adults With Attention-Deficit/Hyperactivity Disorder and Their Unaffected Siblings

Author

von Rhein, Daniel, Cools, Roshan, Zwiers, Marcel P., van der Schaaf, Marieke, Franke, Barbara, Luman, Marjolein, Oosterlaan, Jaap, Heslenfeld, Dirk J., Hoekstra, Pieter J., Hartman, Catharina A., Faraone, Stephen V., van Rooij, Daan, van Dongen, Eelco V., Lojowska, Maria, Mennes, Maarten, and Buitelaar, Jan

Published
2015
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25. Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition

Author

van der Meer, Dennis, Hartman, Catharina A., van Rooij, Daan, Franke, Barbara, Heslenfeld, Dirk J., Oosterlaan, Jaap, Faraone, Stephen V., Buitelaar, Jan K., and Hoekstra, Pieter J.

Subjects
Neural circuitry -- Genetic aspects -- Health aspects, Inhibition (Neurophysiology) -- Genetic aspects, Attention deficit hyperactivity disorder -- Genetic aspects, Dopaminergic mechanisms -- Genetic aspects -- Health aspects, Health, Psychology and mental health
Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that individuals carrying the ADHD risk alleles of the dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) genes may be especially sensitive to their effects. Methods: Functional MRI data, information on prenatal adversities and genetic data were available for 239 adolescents and young adults participating in the multicentre ADHD cohort study NeuroIMAGE (average age 17.3 yr). We analyzed the effects of DRD4 and DAT1, prenatal exposure to alcohol and smoking and their interactions on ADHD severity, response inhibition and neural activity. Results: We found no significant gene x environment interaction effects. We did find that the DRD4 7-repeat allele was associated with less superior frontal and parietal brain activity and with greater activity in the frontal pole and occipital cortex. Prenatal exposure to smoking was also associated with lower superior frontal activity, but with greater activity in the parietal lobe. Further, those exposed to alcohol had more activity in the lateral orbitofrontal cortex, and the DAT1 risk variant was associated with lower cerebellar activity. Limitations: Retrospective reports of maternal substance use and the cross-sectional study design restrict causal inference. Conclusion: While we found no evidence of gene x environment interactions, the risk factors under investigation influenced activity of brain regions associated with response inhibition, suggesting they may add to problems with inhibiting behaviour., Introduction Many individuals with attention-deficit/hyperactivity disorder (ADHD) have impaired response inhibition (i.e., a compromised ability to suppress inappropriate responses). (1) Functional neuroimaging studies of response inhibition have typically implicated 2 [...]

Published
2017
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31. Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder

Author

Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T, Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J, Di Carlo, Pasquale, Gurholt, Tiril P, Harms, Robbert L, Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A, Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K, Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J, Kirsch, Peter, McIntosh, Andrew M, Nöthen, Markus M, Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H, Zink, Mathias, Meyer-Lindenberg, Andreas, and The IMAGEMEND Consortium, Karolinska Schizophrenia Project (KaSP) Consortium

Published
2019
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32. A 6-year follow-up of a large European cohort of children with attention-deficit/hyperactivity disorder-combined subtype: outcomes in late adolescence and young adulthood

Author

van Lieshout, Marloes, Luman, Marjolein, Twisk, Jos W. R., van Ewijk, Hanneke, Groenman, Annabeth P., Thissen, Andrieke J. A. M., Faraone, Stephen V., Heslenfeld, Dirk J., Hartman, Catharina A., Hoekstra, Pieter J., Franke, Barbara, Buitelaar, Jan K., Rommelse, Nanda N. J., and Oosterlaan, Jaap

Published
2016
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35. ERPs Associated with Monitoring and Evaluation of Monetary Reward and Punishment in Children with ADHD

Author

van Meel, Catharina S., Heslenfeld, Dirk J., and Oosterlaan, Jaap

Abstract

Background: Several models of attention-deficit hyperactivity disorder (ADHD) propose abnormalities in the response to behavioural contingencies. Using event-related potentials (ERPs), the present study investigated the monitoring and subsequent evaluation of performance feedback resulting in either reward or punishment in children with ADHD (N = 18) and normal controls (N = 18) aged 8 to 12 years. Methods: Children performed a time production task, in which visual performance feedback was given after each response. To manipulate its motivational salience, feedback was coupled with monetary gains, losses or no incentives. Results: Performance feedback signalling omitted gains as well as omitted losses evoked a feedback-related negativity (FRN) in control children. The FRN, however, was entirely absent in children with ADHD in all conditions. Moreover, while losses elicited enhanced amplitudes of the late positive potential (LPP) in controls, omitted rewards had this effect in ADHD. Conclusions: The lack of modulation of the FRN by contingencies in ADHD suggests deficient detection of environmental cues as a function of their motivational significance. LPP findings suggest diminished response to punishment, but oversensitivity to the loss of desired rewards. These findings suggest that children with ADHD have problems assigning relative motivational significance to outcomes of their actions.

Published
2011
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36. Spatial Working Memory Effects in Early Visual Cortex

Author

Munneke, Jaap, Heslenfeld, Dirk J., and Theeuwes, Jan

Abstract

The present study investigated how spatial working memory recruits early visual cortex. Participants were required to maintain a location in working memory while changes in blood oxygen level dependent (BOLD) signals were measured during the retention interval in which no visual stimulation was present. We show working memory effects during the retention period in early visual cortex which were retinotopically organized in the sense that evoked BOLD responses were specific to the position of the remembered location on an imaginary clock. We demonstrate that this activity is similar to activity observed in conditions in which participants have to direct spatial attention to the same location. We suggest that during the retention interval modulation of neurons coding the remembered location evoke a baseline shift, providing converging evidence for the notion that spatial working memory may use spatial attention as a rehearsal mechanism. (Contains 4 figures.)

Published
2010
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38. Motivational Effects on Motor Timing in Attention-Deficit/hyperactivity Disorder.

Author

Van Meel, Catharina S., Oosterlaan, Jaap, and Heslenfeld, Dirk J.

Abstract

Objective: This study was designed to clarify whether poor performance of children with attention-deficit/hyperactivity disorder (ADHD) on motor timing tasks reflects a true deficit in the temporal organization of motor output or is due to a lack of intrinsic motivation. Method: Eighteen children with ADHD (age 8-12) were compared with 18 age- and gender-matched normal controls with respect to timing precision, timing variability, and the frequency of extreme under- and overestimations during a 1-second interval production task. Monetary reward, response cost, and no reward were implemented to manipulate motivation. Results: Children with ADHD produced significantly more inaccurate and more variable time intervals and exhibited a larger number of extreme over- and underestimations than control children. Although all children performed significantly better when monetary incentives were applied, group differences were not eliminated. Conclusions: In this study, no evidence was found for a motivational deficit as an explanation for impaired performance on a time production task in ADHD. Rather, results provide clear support for a generic motor timing deficit, probably due to a dysfunctional frontostriatocerebellar network involved in temporal aspects of motor preparation. J. Am. Acad. Child Adolesc. Psychiatry, 2005;44(5):451-460. Key Words: attention-deficit/hyperactivity disorder, motor timing, response variability, motivation, reward.

Published
2005

39. Intentional and Unintentional Contributions to Nonspecific Preparation: Electrophysiological Evidence

Author

Los, Sander A. and Heslenfeld, Dirk J.

Abstract

The authors hypothesized that there are distinct intentional and unintentional influences on nonspecific preparation for a future event. In 2 experiments, participants responded to an imperative stimulus (S-sub-2) that was presented equiprobably either 400 ms or 1,200 ms after the offset of a warning stimulus (S-sub-1). During the S-sub-1-S-sub-2 interval, the authors measured the contingent negative variation (CNV), an event-related brain potential reflecting nonspecific preparation. S-sub-1 provided either no information or reliable information about the duration of the impending S-sub-1-S-sub-2 interval, thereby allowing an intentional influence on the state of preparation. The effect of S-sub-1 information on the CNV was approximately additive to the effect of the S-sub-1-S-sub-2 interval that was used on the preceding trial. This supports the view that the preceding S-sub-1-S-sub-2 interval contributes unintentionally to the state of nonspecific preparation guided by a process of trace conditioning.

Published
2005

43. Optimal Measurement Conditions for Spatiotemporal EEG/MEG Source Analysis.

Author

Huizenga, Hilde M., Heslenfeld, Dirk J., and Molenaar, Peter C. M.

Abstract

Developed a method to determine the required number and position of sensors for human brain electromagnetic source analysis. Studied the method through a simulation study and an empirical study on visual evoked potentials in one adult male. Results indicate the method is fast and reliable and improves source precision. (SLD)

Published
2002

44. Greater male than female variability in regional brain structure across the lifespan

Author

Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, Tamnes, Christian K., Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, and Tamnes, Christian K.

Abstract

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Published
2022
Full Text
View/download PDF

45. Greater male than female variability in regional brain structure across the lifespan

Author

Wierenga, Lara M, Doucet, Gaelle E, Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn I, Andreassen, Ole A, Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Calhoun, Vince D, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Chaim-Avancini, Tiffany M, Ching, Christopher Rk, Clark, Vincent P, Conrod, Patricia J, Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G, Dickie, Erin W, Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E, Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco Jc, Giorgio, Annabella Di, Glahn, David C, Gotlib, Ian H, Grabe, Hans J, Gruber, Oliver, Gruner, Patricia, Gur, Raquel E, Gur, Ruben C, Gurholt, Tiril P, de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J, Hartman, Catharina A, Hatton, Sean N, Heslenfeld, Dirk J, van den Heuvel, Odile A, Hickie, Ian B, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Hulshoff Pol, Hilleke E, Huyser, Chaim, Jahanshad, Neda, James, Anthony C, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, Kalnin, Andrew J, Klein, Marieke, Koenders, Laura, Kolskår, Knut K, Krämer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S, Lee, Phil H, Lochner, Christine, Machielsen, Marise Wj, Maingault, Sophie, Martin, Nicholas G, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C, McDonald, Colm, McIntosh, Andrew M, McMahon, Katie L, McPhilemy, Genevieve, van der Meer, Dennis, Menchón, José M, Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J, Radua, Joaquim, Reif, Andreas, Richard, Geneviève, Roffman, Joshua L, Rosa, Pedro Gp, Sacchet, Matthew D, Sachdev, Perminder S, Salvador, Raymond, Sarró, Salvador, Satterthwaite, Theodore D, Saykin, Andrew J, Serpa, Mauricio H, Sim, Kang, Simmons, Andrew, Smoller, Jordan W, Sommer, Iris E, Soriano-Mas, Carles, Stein, Dan J, Strike, Lachlan T, Szeszko, Philip R, Temmingh, Henk S, Thomopoulos, Sophia I, Tomyshev, Alexander S, Trollor, Julian N, Uhlmann, Anne, Veer, Ilya M, Veltman, Dick J, Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D, Westlye, Lars T, Whalley, Heather C, Williams, Steven Cr, Wittfeld, Katharina, Wolf, Daniel H, Wright, Margaret J, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, de Zubicaray, Greig I, Thompson, Paul M., Crone, Eveline A, Frangou, Sophia, Tamnes, Christian K, Wierenga, Lara M, Doucet, Gaelle E, Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn I, Andreassen, Ole A, Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Calhoun, Vince D, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Chaim-Avancini, Tiffany M, Ching, Christopher Rk, Clark, Vincent P, Conrod, Patricia J, Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G, Dickie, Erin W, Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E, Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco Jc, Giorgio, Annabella Di, Glahn, David C, Gotlib, Ian H, Grabe, Hans J, Gruber, Oliver, Gruner, Patricia, Gur, Raquel E, Gur, Ruben C, Gurholt, Tiril P, de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J, Hartman, Catharina A, Hatton, Sean N, Heslenfeld, Dirk J, van den Heuvel, Odile A, Hickie, Ian B, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Hulshoff Pol, Hilleke E, Huyser, Chaim, Jahanshad, Neda, James, Anthony C, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, Kalnin, Andrew J, Klein, Marieke, Koenders, Laura, Kolskår, Knut K, Krämer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S, Lee, Phil H, Lochner, Christine, Machielsen, Marise Wj, Maingault, Sophie, Martin, Nicholas G, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C, McDonald, Colm, McIntosh, Andrew M, McMahon, Katie L, McPhilemy, Genevieve, van der Meer, Dennis, Menchón, José M, Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J, Radua, Joaquim, Reif, Andreas, Richard, Geneviève, Roffman, Joshua L, Rosa, Pedro Gp, Sacchet, Matthew D, Sachdev, Perminder S, Salvador, Raymond, Sarró, Salvador, Satterthwaite, Theodore D, Saykin, Andrew J, Serpa, Mauricio H, Sim, Kang, Simmons, Andrew, Smoller, Jordan W, Sommer, Iris E, Soriano-Mas, Carles, Stein, Dan J, Strike, Lachlan T, Szeszko, Philip R, Temmingh, Henk S, Thomopoulos, Sophia I, Tomyshev, Alexander S, Trollor, Julian N, Uhlmann, Anne, Veer, Ilya M, Veltman, Dick J, Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D, Westlye, Lars T, Whalley, Heather C, Williams, Steven Cr, Wittfeld, Katharina, Wolf, Daniel H, Wright, Margaret J, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, de Zubicaray, Greig I, Thompson, Paul M., Crone, Eveline A, Frangou, Sophia, and Tamnes, Christian K

Abstract

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Published
2022

46. Virtual ontogeny of cortical growth preceding mental illness

Author

German Research Foundation, University of Münster, National Health and Medical Research Council (Australia), University of Cape Town, National Research Foundation (South Africa), Swinburne University of Technology, Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L. Cooper Medical Research Foundation, Society for Mental Health Research (Australia), Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Brain Foundation, Health Research Board (Ireland), Russian Foundation for Basic Research, University of Zurich, Pratt Foundation, Ramsay Health Care, Viertel Charitable Foundation, Schizophrenia Research Institute (Australia), European Commission, Australian Research Council, Instituto de Salud Carlos III, National Institute for Health and Care Research (US), National Institute for Health Research (UK), Ministry of Health of the Czech Republic, Bill & Melinda Gates Foundation, South African Medical Research Council, Carnegie Corporation of New York, Wellcome Trust, Medical Research Council (UK), Medical Research Scotland, Netherlands Organization for Scientific Research, Ambrogi, Sonia [0000-0002-2897-358X], Banaschewski, Tobias [0000-0003-4595-1144], Bandeira, Cibele Edom [0000-0003-0681-1309], Cupertino, Renata [0000-0002-3452-0632], Calderoni, Sara [0000-0002-6250-5739], Cannon, Dara [0000-0001-7378-3411], Carr, Vaughan [0000-0002-8907-5804], Chew, Qian Hui [0000-0003-0969-7994], Coghill, David [0000-0003-3017-9737], Cullen, Kathryn [0000-0001-9631-3770], Dahl, Andreas [0000-0002-8097-2082], Epstein, Jeffery [0000-0003-3464-5256], Foran, William [0000-0001-7491-9798], Fortea, Lydia [0000-0001-6778-2316], Fuentes-Claramonte, Paola [0000-0002-1428-7976], Fullerton, Janice M. [0000-0003-4014-4490], Furlong, Lisa [0000-0001-6196-4565], Gallagher, Louise [0000-0001-9462-2836], Gao, Si [0000-0002-4473-1142], Gotlib, Ian [0000-0002-3622-3199], Haavik, Jan [0000-0001-7865-2808], Henskens, Frans [0000-0003-2358-5630], Hilland, Eva [0000-0002-7102-8372], Hoekstra, Pieter J [0000-0001-7260-4119], Howells, Fleur M [0000-0001-9759-2556], Ipser, Jonathan [0000-0003-1272-0032], Jørgensen, Jes Kristian [0000-0001-9133-1670], Karantonis, James A. [0000-0003-2281-0912], Lawrie, Stephen [0000-0002-2444-5675], Patel, Yash, Shin, Jean, Abé, Christoph, Agartz, Ingrid, Alloza, Clara, Alnæs, Dag, Ambrogi, Sonia, Antonucci, Linda A., Arango, Celso, Arolt, Volker, Auzias, Guillaume, Gruber, Oliver, Haavik, Jan, McDonald, Colm, Hahn, Tim, Harrison, Ben J., Heindel, Walter, Henskens, Frans, Heslenfeld, Dirk J., Hilland, Eva, King, Joseph A., Vernooij, Meike W., Hoekstra, Pieter J., Hohmann, Sarah, Holz, Nathalie, Howells, Fleur M., McIntosh, Andrew, Ipser, Jonathan C., Meinert, Susanne, Hoogman, Martine, Kircher, Tilo, Kochunov, Peter, Vieta, Eduard, Koopowitz, Sheri-Michelle, Landén, Mikael, Landrø, Nils Inge, Lawrie, Stephen, Michie, Patricia T., Ayesa Arriola, Rosa, Mitchell, Philip, Moreno-Alcázar, Ana, Franke, Barbara, Mowry, Bryan, Bau, Claiton H. D., Muratori, Filippo, Nabulsi, Leila, Nenadić, Igor, O'Gorman Tuura, Ruth, Oosterlaan, Jaap, Overs, Bronwyn, Pantelis, Christos, Banaj, Nerisa, Parellada, Mara, van Rooij, Daan, Vilarroya, Oscar, Pariente, Jose C., Pauli, Paul, Pergola, Giulio, Piarulli, Francesco Maria, Picon, Felipe, Piras, Fabrizio, Pomarol-Clotet, Edith, Pretus, Clara, Quidé, Yann, Banaschewski, Tobias, Weickert, Cynthia, Buitelaar, Jan, Radua, Joaquim, Ramos-Quiroga, J. Antoni, Rasser, Paul E., Reif, Andreas, Retico, Alessandra, Roberts, Gloria, Rossell, Susan, Rovaris, Diego Luiz, Rubia, Katya, Weickert, Thomas, Sacchet, Matthew, Ching, Christopher R. K., Bandeira, Cibele, Salavert, Josep, Salvador, Raymond, Sarró, Salvador, Sawa, Akira, Schall, Ulrich, Scott, Rodney, Selvaggi, Pierluigi, Westlye, Lars T., Silk, Tim, Sim, Kang, Andreassen, Ole A., Skoch, Antonin, Başgöze, Zeynep, Spalletta, Gianfranco, Spaniel, Filip, Stein, Dan J., Steinsträter, Olaf, Stolicyn, Aleks, Whalley, Heather, Takayanagi, Yoichiro, Tamm, Leanne, Tavares, Maria, Pozzi, Elena, Teumer, Alexander, Thiel, Katharina, Cupertino, Renata Basso, Thomopoulos, Sophia I., Tomecek, David, Tomyshev, Alexander S., Willinger, David, Tordesillas-Gutiérrez, Diana, Tosetti, Michela, Uhlmann, Anne, Van Rheenen, Tamsyn, Veltman, Dick, Vázquez-Bourgon, Javier, Schmaal, Lianne, Jahanshad, Neda, Winter, Alexandra, Wittfeld, Katharina, Yang, Tony T., Yoncheva, Yuliya, Bauer, Jochen, Zijlmans, Jendé L., Baumeister, Sarah, Lebedeva, Irina, van Erp, Theo G. M., Turner, Jessica, Jakobi, Babette, Castellanos, F. Xavier, Pausova, Zdenka, Thompson, Paul, Paus, Tomas, Bernardoni, Fabio, Bertolino, Alessandro, Bonnin, Caterina Del Mar, Brandeis, Daniel, Luna, Beatriz, Brem, Silvia, Jansen, Andreas, Bruggemann, Jason, Bülow, Robin, Bustillo, Juan R., Calderoni, Sara, Calvo, Rosa, Canales-Rodríguez, Erick J., Cannon, Dara M., Carmona, Susanna, Carr, Vaughan J., Lundervold, Astri J., Janssen, Joost, Catts, Stanley V., Chenji, Sneha, Chew, Qian Hui, Coghill, David, Connolly, Colm G., Conzelmann, Annette, Craven, Alexander R., Crespo-Facorro, Benedicto, Cullen, Kathryn, Dahl, Andreas, Jonassen, Rune, MacMaster, Frank P., Dannlowski, Udo, Davey, Christopher G., Deruelle, Christine, Díaz-Caneja, Covadonga M., Dohm, Katharina, Ehrlich, Stefan, Epstein, Jeffery, Erwin-Grabner, Tracy, Eyler, Lisa T., Kaiser, Anna, Fedor, Jennifer, Maglanoc, Luigi A., Fitzgerald, Jacqueline, Foran, William, Ford, Judith M., Fortea, Lydia, Fuentes-Claramonte, Paola, Fullerton, Janice, Furlong, Lisa, Gallagher, Louise, Kaleda, Vasiliy, Gao, Bingchen, Gao, Si, Mathalon, Daniel H., Goikolea, Jose M., Gotlib, Ian, Goya-Maldonado, Roberto, Grabe, Hans J., Green, Melissa, Grevet, Eugenio H., Groenewold, Nynke A., Karantonis, James, Grotegerd, Dominik., German Research Foundation, University of Münster, National Health and Medical Research Council (Australia), University of Cape Town, National Research Foundation (South Africa), Swinburne University of Technology, Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L. Cooper Medical Research Foundation, Society for Mental Health Research (Australia), Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Brain Foundation, Health Research Board (Ireland), Russian Foundation for Basic Research, University of Zurich, Pratt Foundation, Ramsay Health Care, Viertel Charitable Foundation, Schizophrenia Research Institute (Australia), European Commission, Australian Research Council, Instituto de Salud Carlos III, National Institute for Health and Care Research (US), National Institute for Health Research (UK), Ministry of Health of the Czech Republic, Bill & Melinda Gates Foundation, South African Medical Research Council, Carnegie Corporation of New York, Wellcome Trust, Medical Research Council (UK), Medical Research Scotland, Netherlands Organization for Scientific Research, Ambrogi, Sonia [0000-0002-2897-358X], Banaschewski, Tobias [0000-0003-4595-1144], Bandeira, Cibele Edom [0000-0003-0681-1309], Cupertino, Renata [0000-0002-3452-0632], Calderoni, Sara [0000-0002-6250-5739], Cannon, Dara [0000-0001-7378-3411], Carr, Vaughan [0000-0002-8907-5804], Chew, Qian Hui [0000-0003-0969-7994], Coghill, David [0000-0003-3017-9737], Cullen, Kathryn [0000-0001-9631-3770], Dahl, Andreas [0000-0002-8097-2082], Epstein, Jeffery [0000-0003-3464-5256], Foran, William [0000-0001-7491-9798], Fortea, Lydia [0000-0001-6778-2316], Fuentes-Claramonte, Paola [0000-0002-1428-7976], Fullerton, Janice M. [0000-0003-4014-4490], Furlong, Lisa [0000-0001-6196-4565], Gallagher, Louise [0000-0001-9462-2836], Gao, Si [0000-0002-4473-1142], Gotlib, Ian [0000-0002-3622-3199], Haavik, Jan [0000-0001-7865-2808], Henskens, Frans [0000-0003-2358-5630], Hilland, Eva [0000-0002-7102-8372], Hoekstra, Pieter J [0000-0001-7260-4119], Howells, Fleur M [0000-0001-9759-2556], Ipser, Jonathan [0000-0003-1272-0032], Jørgensen, Jes Kristian [0000-0001-9133-1670], Karantonis, James A. [0000-0003-2281-0912], Lawrie, Stephen [0000-0002-2444-5675], Patel, Yash, Shin, Jean, Abé, Christoph, Agartz, Ingrid, Alloza, Clara, Alnæs, Dag, Ambrogi, Sonia, Antonucci, Linda A., Arango, Celso, Arolt, Volker, Auzias, Guillaume, Gruber, Oliver, Haavik, Jan, McDonald, Colm, Hahn, Tim, Harrison, Ben J., Heindel, Walter, Henskens, Frans, Heslenfeld, Dirk J., Hilland, Eva, King, Joseph A., Vernooij, Meike W., Hoekstra, Pieter J., Hohmann, Sarah, Holz, Nathalie, Howells, Fleur M., McIntosh, Andrew, Ipser, Jonathan C., Meinert, Susanne, Hoogman, Martine, Kircher, Tilo, Kochunov, Peter, Vieta, Eduard, Koopowitz, Sheri-Michelle, Landén, Mikael, Landrø, Nils Inge, Lawrie, Stephen, Michie, Patricia T., Ayesa Arriola, Rosa, Mitchell, Philip, Moreno-Alcázar, Ana, Franke, Barbara, Mowry, Bryan, Bau, Claiton H. D., Muratori, Filippo, Nabulsi, Leila, Nenadić, Igor, O'Gorman Tuura, Ruth, Oosterlaan, Jaap, Overs, Bronwyn, Pantelis, Christos, Banaj, Nerisa, Parellada, Mara, van Rooij, Daan, Vilarroya, Oscar, Pariente, Jose C., Pauli, Paul, Pergola, Giulio, Piarulli, Francesco Maria, Picon, Felipe, Piras, Fabrizio, Pomarol-Clotet, Edith, Pretus, Clara, Quidé, Yann, Banaschewski, Tobias, Weickert, Cynthia, Buitelaar, Jan, Radua, Joaquim, Ramos-Quiroga, J. Antoni, Rasser, Paul E., Reif, Andreas, Retico, Alessandra, Roberts, Gloria, Rossell, Susan, Rovaris, Diego Luiz, Rubia, Katya, Weickert, Thomas, Sacchet, Matthew, Ching, Christopher R. K., Bandeira, Cibele, Salavert, Josep, Salvador, Raymond, Sarró, Salvador, Sawa, Akira, Schall, Ulrich, Scott, Rodney, Selvaggi, Pierluigi, Westlye, Lars T., Silk, Tim, Sim, Kang, Andreassen, Ole A., Skoch, Antonin, Başgöze, Zeynep, Spalletta, Gianfranco, Spaniel, Filip, Stein, Dan J., Steinsträter, Olaf, Stolicyn, Aleks, Whalley, Heather, Takayanagi, Yoichiro, Tamm, Leanne, Tavares, Maria, Pozzi, Elena, Teumer, Alexander, Thiel, Katharina, Cupertino, Renata Basso, Thomopoulos, Sophia I., Tomecek, David, Tomyshev, Alexander S., Willinger, David, Tordesillas-Gutiérrez, Diana, Tosetti, Michela, Uhlmann, Anne, Van Rheenen, Tamsyn, Veltman, Dick, Vázquez-Bourgon, Javier, Schmaal, Lianne, Jahanshad, Neda, Winter, Alexandra, Wittfeld, Katharina, Yang, Tony T., Yoncheva, Yuliya, Bauer, Jochen, Zijlmans, Jendé L., Baumeister, Sarah, Lebedeva, Irina, van Erp, Theo G. M., Turner, Jessica, Jakobi, Babette, Castellanos, F. Xavier, Pausova, Zdenka, Thompson, Paul, Paus, Tomas, Bernardoni, Fabio, Bertolino, Alessandro, Bonnin, Caterina Del Mar, Brandeis, Daniel, Luna, Beatriz, Brem, Silvia, Jansen, Andreas, Bruggemann, Jason, Bülow, Robin, Bustillo, Juan R., Calderoni, Sara, Calvo, Rosa, Canales-Rodríguez, Erick J., Cannon, Dara M., Carmona, Susanna, Carr, Vaughan J., Lundervold, Astri J., Janssen, Joost, Catts, Stanley V., Chenji, Sneha, Chew, Qian Hui, Coghill, David, Connolly, Colm G., Conzelmann, Annette, Craven, Alexander R., Crespo-Facorro, Benedicto, Cullen, Kathryn, Dahl, Andreas, Jonassen, Rune, MacMaster, Frank P., Dannlowski, Udo, Davey, Christopher G., Deruelle, Christine, Díaz-Caneja, Covadonga M., Dohm, Katharina, Ehrlich, Stefan, Epstein, Jeffery, Erwin-Grabner, Tracy, Eyler, Lisa T., Kaiser, Anna, Fedor, Jennifer, Maglanoc, Luigi A., Fitzgerald, Jacqueline, Foran, William, Ford, Judith M., Fortea, Lydia, Fuentes-Claramonte, Paola, Fullerton, Janice, Furlong, Lisa, Gallagher, Louise, Kaleda, Vasiliy, Gao, Bingchen, Gao, Si, Mathalon, Daniel H., Goikolea, Jose M., Gotlib, Ian, Goya-Maldonado, Roberto, Grabe, Hans J., Green, Melissa, Grevet, Eugenio H., Groenewold, Nynke A., Karantonis, James, and Grotegerd, Dominik.

Abstract

[Background]: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life., [Methods]: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed., [Results]: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth., [Conclusions]: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.

Published
2022

47. Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years

Author

European Commission, National Institute of Child Health and Human Development (US), QIMR Berghofer Medical Research Institute (Australia), University of Queensland, National Cancer Institute (US), Dutch Research Council, Netherlands Organisation for Health Research and Development, National Institute of Mental Health (US), European Research Council, National Center for Advancing Translational Sciences (US), Medical Research Council (UK), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, South-Eastern Norway Regional Health Authority, Research Council of Norway, Icahn School of Medicine at Mount Sinai, South London and Maudsley NHS Foundation Trust, NHS Foundation Trust, National Institute for Health Research (UK), Frangou, Sophia, Modabbernia, Amirhossein, Williams, Steven C. R., Papachristou, Efstathios, Doucet, Gaelle E., Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Antón, Alnæs, Dag, Alpert, Kathryn I., Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Walton, Esther, Wang, Lei, Wang, Yang, Wassink, Thomas H., Weber, Bernd, Bertolino, Alessandro, Wen, Wei, Kalnin, Andrew, West, John D., Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Wittfeld, Katharina, Wolf, Daniel H., Worker, Amanda, Wright, Margaret J., Yang, Kun, Bonvino, Aurora, Kanai, Ryota, Yoncheva, Yulyia, Zanetti, Marcus V., Ziegler, Georg C., Karolinska Schizophrenia Project, Thompson, Paul M., Dima, Danai, Boomsma, Dorret I., Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Klein, Marieke, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Buckner, Randy L., Calhoun, Vincent, Canales-Rodríguez, Erick J., Cannon, Dara M., Caseras, Xavier, Klyushnik, Tatyana P., Castellanos, Francisco X., Cervenka, Simon, Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Chubar, Victoria, Clark, Vincent P., Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Koenders, Laura, Crone, Eveline A., Dale, Anders M., Dannlowski, Udo, Davey, Christopher, Geus, Eco J. C. de, Haan, Lieuwe de, Zubicaray, Greig I. de, den Braber, Anouk, Dickie, Erin W., Di Giorgio, Annabella, Koops, Sanne, Doan, Nhat Trung, Dørum, Erlend S., Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fatouros-Bergman, Helena, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Frodl, Thomas, Krämer, Bernd, Fuentes-Claramonte, Paola, Glahn, David C., Gotlib, Ian H., Grabe, Hans-Jörgen, Grimm, Oliver, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E., Kuntsi, Jonna, Gur, Ruben C., Hahn, Tim, Harrison, Ben J., Hartman, Catharine A., Hatton, Sean N., Heinz, Andreas, Heslenfeld, Dirk J., Hibar, Derrek P., Hickie, Ian B., Ho, Beng-Choon, Lagopoulos, Jim, Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Hulshoff Pol, Hilleke E., Huyser, Chaim, Jahanshad, Neda, James, Anthony, Lázaro, Luisa, Jernigan, Terry L., Jiang, Jiyang, Jönsson, Erik G., Joska, John A., Kahn, René S., Andersson, Micael, Lebedeva, Irina, Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, Andreasen, Nancy C., McDonald, Colm, McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, Meinert, Susanne, Menchón, José M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Andreassen, Ole A., Najt, Pablo, Nakao, Tomohiro, Nordvik, Jan E., Nyberg, Lars, Oosterlaan, Jaap, Ortiz-Garcia de la Foz, Victor, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Asherson, Philip, Portella, Maria J., Potkin, Steven G., Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Banaschewski, Tobias, Sánchez-Juan, Pascual, Sarró, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Smoller, Jordan W., Bargalló, Núria, Sommer, Iris, Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Swagerman, Suzanne C., Tamnes, Christian K., Temmingh, Henk S., Thomopoulos, Sophia I., Tomyshev, Alexander S., Baumeister, Sarah, Tordesillas-Gutiérrez, Diana, Trollor, Julian N., Turner, Jessica A., Uhlmann, Anne, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van 't Ent, Dennis, van Erp, Theo G. M., Baur-Streubel, Ramona, Veer, Ilya M., Veltman, Dick J., European Commission, National Institute of Child Health and Human Development (US), QIMR Berghofer Medical Research Institute (Australia), University of Queensland, National Cancer Institute (US), Dutch Research Council, Netherlands Organisation for Health Research and Development, National Institute of Mental Health (US), European Research Council, National Center for Advancing Translational Sciences (US), Medical Research Council (UK), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, South-Eastern Norway Regional Health Authority, Research Council of Norway, Icahn School of Medicine at Mount Sinai, South London and Maudsley NHS Foundation Trust, NHS Foundation Trust, National Institute for Health Research (UK), Frangou, Sophia, Modabbernia, Amirhossein, Williams, Steven C. R., Papachristou, Efstathios, Doucet, Gaelle E., Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Antón, Alnæs, Dag, Alpert, Kathryn I., Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Walton, Esther, Wang, Lei, Wang, Yang, Wassink, Thomas H., Weber, Bernd, Bertolino, Alessandro, Wen, Wei, Kalnin, Andrew, West, John D., Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Wittfeld, Katharina, Wolf, Daniel H., Worker, Amanda, Wright, Margaret J., Yang, Kun, Bonvino, Aurora, Kanai, Ryota, Yoncheva, Yulyia, Zanetti, Marcus V., Ziegler, Georg C., Karolinska Schizophrenia Project, Thompson, Paul M., Dima, Danai, Boomsma, Dorret I., Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Klein, Marieke, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Buckner, Randy L., Calhoun, Vincent, Canales-Rodríguez, Erick J., Cannon, Dara M., Caseras, Xavier, Klyushnik, Tatyana P., Castellanos, Francisco X., Cervenka, Simon, Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Chubar, Victoria, Clark, Vincent P., Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Koenders, Laura, Crone, Eveline A., Dale, Anders M., Dannlowski, Udo, Davey, Christopher, Geus, Eco J. C. de, Haan, Lieuwe de, Zubicaray, Greig I. de, den Braber, Anouk, Dickie, Erin W., Di Giorgio, Annabella, Koops, Sanne, Doan, Nhat Trung, Dørum, Erlend S., Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fatouros-Bergman, Helena, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Frodl, Thomas, Krämer, Bernd, Fuentes-Claramonte, Paola, Glahn, David C., Gotlib, Ian H., Grabe, Hans-Jörgen, Grimm, Oliver, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E., Kuntsi, Jonna, Gur, Ruben C., Hahn, Tim, Harrison, Ben J., Hartman, Catharine A., Hatton, Sean N., Heinz, Andreas, Heslenfeld, Dirk J., Hibar, Derrek P., Hickie, Ian B., Ho, Beng-Choon, Lagopoulos, Jim, Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Hulshoff Pol, Hilleke E., Huyser, Chaim, Jahanshad, Neda, James, Anthony, Lázaro, Luisa, Jernigan, Terry L., Jiang, Jiyang, Jönsson, Erik G., Joska, John A., Kahn, René S., Andersson, Micael, Lebedeva, Irina, Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, Andreasen, Nancy C., McDonald, Colm, McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, Meinert, Susanne, Menchón, José M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Andreassen, Ole A., Najt, Pablo, Nakao, Tomohiro, Nordvik, Jan E., Nyberg, Lars, Oosterlaan, Jaap, Ortiz-Garcia de la Foz, Victor, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Asherson, Philip, Portella, Maria J., Potkin, Steven G., Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Banaschewski, Tobias, Sánchez-Juan, Pascual, Sarró, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Smoller, Jordan W., Bargalló, Núria, Sommer, Iris, Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Swagerman, Suzanne C., Tamnes, Christian K., Temmingh, Henk S., Thomopoulos, Sophia I., Tomyshev, Alexander S., Baumeister, Sarah, Tordesillas-Gutiérrez, Diana, Trollor, Julian N., Turner, Jessica A., Uhlmann, Anne, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van 't Ent, Dennis, van Erp, Theo G. M., Baur-Streubel, Ramona, Veer, Ilya M., and Veltman, Dick J.

Abstract

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.

Published
2022

48. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years

Author

National Institute of Mental Health (US), Karolinska Institute, Stockholm County Council, South-Eastern Norway Regional Health Authority, German Centre for Cardiovascular Research, Siemens Healthcare, University of Queensland, Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), National Health and Medical Research Council (Australia), National Institute on Drug Abuse (US), Indiana State Department of Health, Parents of children with epilepsy, Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures, Epilepsy Foundation, American Epilepsy Society, Knut and Alice Wallenberg Foundation, European Commission, Dutch Research Council, Netherlands Organization for Scientific Research, Netherlands Brain Foundation, Utrecht University, European Research Council, National Center for Advancing Translational Sciences (US), National Institutes of Health (US), National Center for Research Resources (US), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, Kings College London, South London and Maudsley NHS Foundation Trust, NIHR Biomedical Research Centre (UK), National Institute for Health Research (UK), Dima, Danai, Modabbernia, Amirhossein, Papachristou, Efstathios, Doucet, Gaelle E., Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Antón, Alnæs, Dag, Alpert, Kathryn I., Andersson, Micael, Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sánchez-Juan, Pascual, Tordesillas-Gutiérrez, Diana, Ehrlich, Stefan, Bargalló, Núria, Weber, Bernd, Sarró, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Erk, Susanne, West, John D., Smoller, Jordan W., Sommer, Iris, Wen, Wei, Baumeister, Sarah, Hartman, Catharine A., Trollor, Julian N., Baur-Streubel, Ramona, Turner, Jessica A., Uhlmann, Anne, Espeseth, Thomas, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van't Ent, Dennis, van Erp, Theo G. M., Hatton, Sean N., Bonvino, Aurora, Veer, Ilya M., Veltman, Dick J., Fatouros-Bergman, Helena, Bertolino, Alessandro, Voineskos, Aristotle, Kanai, Ryota, Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Williams, Steven C. R., Heinz, Andreas, Wittfeld, Katharina, Wolf, Daniel H., Fisher, Simon E., Worker, Amanda, Wright, Margaret J., Yang, Kun, Yoncheva, Yulyia, Klein, Marieke, Boomsma, Dorret I., Zanetti, Marcus V., Ziegler, Georg C., Heslenfeld, Dirk J., Thompson, Paul M., Fouche, Jean-Paul, Frangou, Sophia, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Klyushnik, Tatyana P., Brouwer, Rachel M., Buitelaar, Jan K., Hibar, Derrek P., Franke, Barbara, Busatto, Geraldo F., Buckner, Randy L., Calhoun, Vincent, Canales-Rodríguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Cervenka, Simon, Koenders, Laura, Chaim-Avancini, Tiffany M., Frodl, Thomas, Hickie, Ian B., Ching, Christopher R. K., Chubar, Victoria, Clark, Vincent P., Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A., Dannlowski, Udo, Fuentes-Claramonte, Paola, Koops, Sanne, Ho, Beng-Choon, Dale, Anders M., Davey, Christopher, Geus, Eco J. C. de, de Haan, Lieuwe, Zubicaray, Greig I. de, den Braber, Anouk, Dickie, Erin W., Di Giorgio, Annabella, Hohmann, Sarah, Doan, Nhat Trung, Dørum, Erlend S., Hoekstra, Pieter J., Krämer, Bernd, Soriano-Mas, Carles, Glahn, David C., Kuntsi, Jonna, Gotlib, Ian H., Grabe, Hans-Jörgen, Grimm, Oliver, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E., Stein, Dan J., Lázaro, Luisa, Gur, Ruben C., Hahn, Tim, Lagopoulos, Jim, Harrison, Ben J., Völzke, Henry, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Strike, Lachlan T., Hulshoff Pol, Hilleke E., Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L., Jiang, Jiyang, Walter, Henrik, Lebedeva, Irina, Jönsson, Erik G., Joska, John A., Swagerman, Suzanne C., Kahn, René S., Kalnin, Andrew, Andreasen, Nancy C., Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Walton, Esther, Maingault, Sophie, Martin, Nicholas G., Tamnes, Christian K., Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Colm, Andreassen, Ole A., McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., Wang, Lei, McPhilemy, Genevieve, Temmingh, Henk S., Meinert, Susanne, Menchón, José M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Najt, Pablo, Asherson, Philip, Nakao, Tomohiro, Nordvik, Jan E., Wang, Yang, Thomopoulos, Sophia I., Nyberg, Lars, Oosterlaan, Jaap, Ortiz-Garcia de la Foz, Victor, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Banaschewski, Tobias, Potkin, Steven G., Tomyshev, Alexander S., Wassink, Thomas H., National Institute of Mental Health (US), Karolinska Institute, Stockholm County Council, South-Eastern Norway Regional Health Authority, German Centre for Cardiovascular Research, Siemens Healthcare, University of Queensland, Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), National Health and Medical Research Council (Australia), National Institute on Drug Abuse (US), Indiana State Department of Health, Parents of children with epilepsy, Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures, Epilepsy Foundation, American Epilepsy Society, Knut and Alice Wallenberg Foundation, European Commission, Dutch Research Council, Netherlands Organization for Scientific Research, Netherlands Brain Foundation, Utrecht University, European Research Council, National Center for Advancing Translational Sciences (US), National Institutes of Health (US), National Center for Research Resources (US), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, Kings College London, South London and Maudsley NHS Foundation Trust, NIHR Biomedical Research Centre (UK), National Institute for Health Research (UK), Dima, Danai, Modabbernia, Amirhossein, Papachristou, Efstathios, Doucet, Gaelle E., Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Antón, Alnæs, Dag, Alpert, Kathryn I., Andersson, Micael, Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sánchez-Juan, Pascual, Tordesillas-Gutiérrez, Diana, Ehrlich, Stefan, Bargalló, Núria, Weber, Bernd, Sarró, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Erk, Susanne, West, John D., Smoller, Jordan W., Sommer, Iris, Wen, Wei, Baumeister, Sarah, Hartman, Catharine A., Trollor, Julian N., Baur-Streubel, Ramona, Turner, Jessica A., Uhlmann, Anne, Espeseth, Thomas, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van't Ent, Dennis, van Erp, Theo G. M., Hatton, Sean N., Bonvino, Aurora, Veer, Ilya M., Veltman, Dick J., Fatouros-Bergman, Helena, Bertolino, Alessandro, Voineskos, Aristotle, Kanai, Ryota, Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Williams, Steven C. R., Heinz, Andreas, Wittfeld, Katharina, Wolf, Daniel H., Fisher, Simon E., Worker, Amanda, Wright, Margaret J., Yang, Kun, Yoncheva, Yulyia, Klein, Marieke, Boomsma, Dorret I., Zanetti, Marcus V., Ziegler, Georg C., Heslenfeld, Dirk J., Thompson, Paul M., Fouche, Jean-Paul, Frangou, Sophia, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Klyushnik, Tatyana P., Brouwer, Rachel M., Buitelaar, Jan K., Hibar, Derrek P., Franke, Barbara, Busatto, Geraldo F., Buckner, Randy L., Calhoun, Vincent, Canales-Rodríguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Cervenka, Simon, Koenders, Laura, Chaim-Avancini, Tiffany M., Frodl, Thomas, Hickie, Ian B., Ching, Christopher R. K., Chubar, Victoria, Clark, Vincent P., Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A., Dannlowski, Udo, Fuentes-Claramonte, Paola, Koops, Sanne, Ho, Beng-Choon, Dale, Anders M., Davey, Christopher, Geus, Eco J. C. de, de Haan, Lieuwe, Zubicaray, Greig I. de, den Braber, Anouk, Dickie, Erin W., Di Giorgio, Annabella, Hohmann, Sarah, Doan, Nhat Trung, Dørum, Erlend S., Hoekstra, Pieter J., Krämer, Bernd, Soriano-Mas, Carles, Glahn, David C., Kuntsi, Jonna, Gotlib, Ian H., Grabe, Hans-Jörgen, Grimm, Oliver, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E., Stein, Dan J., Lázaro, Luisa, Gur, Ruben C., Hahn, Tim, Lagopoulos, Jim, Harrison, Ben J., Völzke, Henry, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Strike, Lachlan T., Hulshoff Pol, Hilleke E., Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L., Jiang, Jiyang, Walter, Henrik, Lebedeva, Irina, Jönsson, Erik G., Joska, John A., Swagerman, Suzanne C., Kahn, René S., Kalnin, Andrew, Andreasen, Nancy C., Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Walton, Esther, Maingault, Sophie, Martin, Nicholas G., Tamnes, Christian K., Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Colm, Andreassen, Ole A., McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., Wang, Lei, McPhilemy, Genevieve, Temmingh, Henk S., Meinert, Susanne, Menchón, José M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Najt, Pablo, Asherson, Philip, Nakao, Tomohiro, Nordvik, Jan E., Wang, Yang, Thomopoulos, Sophia I., Nyberg, Lars, Oosterlaan, Jaap, Ortiz-Garcia de la Foz, Victor, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Banaschewski, Tobias, Potkin, Steven G., Tomyshev, Alexander S., and Wassink, Thomas H.

Abstract

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.

Published
2022

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