Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3–90 years
Human Brain Mapping. 2021-02-17; 43(1): 431-451
DOI: 10.1002/hbm.25364
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Frangou S(#)(1)(2), Modabbernia A(#)(1), Williams SCR(3), Papachristou E(4),
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N(21)(22), Baumeister S(20), Baur-Streubel R(23), Bertolino A(24), Bonvino
A(25), Boomsma DI(25), Borgwardt S(26), Bourque J(27), Brandeis D(20), Breier
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Buckner RL(35)(36), Calhoun V(37), Canales-Rodríguez EJ(13)(14), Cannon DM(12),
Caseras X(38), Castellanos FX(39), Cervenka S(8)(40), Chaim-Avancini TM(34),
Ching CRK(41), Chubar V(42), Clark VP(43)(44), Conrod P(45), Conzelmann A(46),
Crespo-Facorro B(14)(47), Crivello F(48), Crone EA(49)(50), Dale AM(51)(52),
Dannlowski U(53), Davey C(54), de Geus EJC(25), de Haan L(55), de Zubicaray
GI(56), den Braber A(25), Dickie EW(57)(58), Di Giorgio A(59), Doan NT(6), Dørum
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Fatouros-Bergman H(8)(40), Fisher SE(33)(66), Fouche JP(67), Franke
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Gruber O(77), Gruner P(78)(79), Gur RE(27)(80)(81), Gur RC(27)(80)(81), Hahn
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DJ(85), Hibar DP(86), Hickie IB(84), Ho BC(18), Hoekstra PJ(87), Hohmann S(20),
Holmes AJ(88), Hoogman M(33)(68), Hosten N(89), Howells FM(67)(76), Hulshoff Pol
HE(30), Huyser C(90), Jahanshad N(42), James A(91), Jernigan TL(92), Jiang
J(29), Jönsson EG(6), Joska JA(67), Kahn R(1), Kalnin A(93), Kanai R(94), Klein
M(33)(68)(95), Klyushnik TP(96), Koenders L(55), Koops S(30), Krämer B(77),
Kuntsi J(19), Lagopoulos J(97), Lázaro L(14)(98), Lebedeva I(96), Lee WH(1),
Lesch KP(99), Lochner C(100), Machielsen MWJ(55), Maingault S(48), Martin
NG(101), Martínez-Zalacaín I(14)(102), Mataix-Cols D(8)(40), Mazoyer B(48),
McDonald C(12), McDonald BC(28), McIntosh AM(103), McMahon KL(104), McPhilemy
G(12), Meinert S(53), Menchón JM(14)(102), Medland SE(101), Meyer-Lindenberg
A(105), Naaijen J(32)(33), Najt P(12), Nakao T(106), Nordvik JE(107), Nyberg
L(17)(108), Oosterlaan J(109), de la Foz VO(14)(110)(111), Paloyelis Y(3), Pauli
P(23)(112), Pergola G(24), Pomarol-Clotet E(13)(14), Portella MJ(13)(113),
Potkin SG(114), Radua J(8)(22)(115), Reif A(75), Rinker DA(6), Roffman JL(36),
Rosa PGP(34), Sacchet MD(116), Sachdev PS(29), Salvador R(13), Sánchez-Juan
P(110)(117), Sarró S(13), Satterthwaite TD(27), Saykin AJ(28), Serpa MH(34),
Schmaal L(118)(119), Schnell K(120), Schumann G(19)(121), Sim K(122), Smoller
JW(123), Sommer I(124), Soriano-Mas C(14)(102), Stein DJ(100), Strike LT(125),
Swagerman SC(25), Tamnes CK(6)(7)(126), Temmingh HS(67), Thomopoulos SI(41),
Tomyshev AS(96), Tordesillas-Gutiérrez D(13)(127), Trollor JN(29), Turner
JA(128), Uhlmann A(67), van den Heuvel OA(9), van den Meer D(6)(15)(129), van
der Wee NJA(130)(131), van Haren NEM(132), van ‘t Ent D(25), van Erp
TGM(114)(133)(134), Veer IM(64), Veltman DJ(9), Voineskos A(57)(58), Völzke
H(134)(135)(136), Walter H(64), Walton E(137), Wang L(138), Wang Y(139), Wassink
TH(18), Weber B(140), Wen W(29), West JD(28), Westlye LT(60), Whalley H(103),
Wierenga LM(141), Wittfeld K(73)(74), Wolf DH(27), Worker A(2), Wright MJ(125),
Yang K(142), Yoncheva Y(143), Zanetti MV(34)(144), Ziegler GC(145); Karolinska
Schizophrenia Project (KaSP); Thompson PM(41), Dima D(3)(146).
Author information:
(1)Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York
City, New York, USA.
(2)Department of Psychiatry, Djavad Mowafaghian Centre for Brain Health,
University of British Columbia, Vancouver, Canada.
(3)Department of Neuroimaging, Institute of Psychiatry, Psychology and
Neuroscience, King’s College London, London, United Kingdom.
(4)Psychology and Human Development, Institute of Education, University College
London, London, United Kingdom.
(5)Institute for Human Neuroscience, Boys Town National Research Hospital,
Omaha, Nebraska, USA.
(6)Norwegian Centre for Mental Disorders Research (NORMENT), Institute of
Clinical Medicine, University of Oslo, Oslo, Norway.
(7)Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
(8)Centre for Psychiatric Research, Department of Clinical Neuroscience,
Karolinska Institutet, Solna, Sweden.
(9)Department of Psychiatry, Amsterdam University Medical Centre, Vrije
Universiteit, Amsterdam, Netherlands.
(10)Section Forensic Family & Youth Care, Institute of Education & Child
Studies, Leiden University, Netherlands.
(11)Institute of Medical Imaging and Visualisation, Department of Medical
Science and Public Health, Faculty of Health and Social Sciences, Bournemouth
University, Poole, United Kingdom.
(12)Clinical Neuroimaging Laboratory, Centre for Neuroimaging and Cognitive
Genomics and NCBES Galway Neuroscience Centre, National University of Ireland,
Galway, Ireland.
(13)FIDMAG Germanes Hospitalàries, Barcelona, Spain.
(14)Mental Health Research Networking Center (CIBERSAM), Madrid, Spain.
(15)Division of Mental Health and Addiction, Institute of Clinical Medicine,
University of Oslo, Oslo, Norway.
(16)Radiologics, Inc, Saint Louis, Missouri, USA.
(17)Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
(18)Department of Psychiatry, Carver College of Medicine, The University of
Iowa, Iowa City, Iowa, USA.
(19)Social, Genetic and Developmental Psychiatry Centre, Institute of
Psychiatry, Psychology and Neuroscience, King’s College London, London, United
Kingdom.
(20)Department of Child and Adolescent Psychiatry and Psychotherapy, Central
Institute of Mental Health, Heidelberg University, Heidelberg, Germany.
(21)Imaging Diagnostic Centre, Hospital Clinic, Barcelona University Clinic,
Barcelona, Spain.
(22)August Pi i Sunyer Biomedical Research Institut (IDIBAPS), Barcelona, Spain.
(23)Department of Psychology, Biological Psychology, Clinical Psychology and
Psychotherapy, University of Würzburg, Würzburg, Germany.
(24)Department of Basic Medical Science, Neuroscience and Sense Organs,
University of Bari Aldo Moro, Bari, Italy.
(25)Department of Biological Psychology, Vrije Universiteit, Amsterdam,
Netherlands.
(26)Department of Psychiatry & Psychotherapy, University of Lübeck, Lübeck,
Germany.
(27)Department of Psychiatry, University of Pennsylvania, Philadelphia,
Pennsylvania, USA.
(28)Department of Radiology and Imaging Sciences, Indiana University School of
Medicine, Indianapolis, Indiana, USA.
(29)Centre for Healthy Brain Ageing, School of Psychiatry, University of New
South Wales, Kensington, New South Wales, Australia.
(30)Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht,
Utrecht, Netherlands.
(31)Donders Center of Medical Neurosciences, Radboud University, Nijmegen,
Netherlands.
(32)Donders Centre for Cognitive Neuroimaging, Radboud University, Nijmegen,
Netherlands.
(33)Donders Institute for Brain, Cognition and Behaviour, Radboud University,
Nijmegen, Netherlands.
(34)Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de
Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade
de São Paulo, São Paulo, Brazil.
(35)Department of Psychology, Center for Brain Science, Harvard University,
Cambridge, Massachusetts, USA.
(36)Department of Psychiatry, Massachusetts General Hospital, Boston,
Massachusetts, USA.
(37)Tri-Institutional Center for Translational Research in Neuroimaging and Data
Science (TReNDS), Georgia State University, Georgia Institute of Technology,
Emory University, USA Neurology, Radiology, Psychiatry and Biomedical
Engineering, Emory University, Atlanta, Georgia, USA.
(38)MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University,
Cardiff, United Kingdom.
(39)Department of Child and Adolescent Psychiatry, New York University, New
York, New York, USA.
(40)Stockholm Health Care Services, Stockholm, Sweden.
(41)Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics
Institute, Keck School of Medicine, University of Southern California, Marina
del Rey, California, USA.
(42)Mind-Body Research Group, Department of Neuroscience, KU Leuven, Leuven,
Belgium.
(43)Department of Psychology, University of New Mexico, Albuquerque, New Mexico,
USA.
(44)Mind Research Network, Albuquerque, New Mexico, USA.
(45)Department of Psychiatry, Université de Montréal, Montreal, Canada.
(46)Department of Child and Adolescent Psychiatry, Psychosomatics and
Psychotherapy, University of Tübingen, Tübingen, Germany.
(47)HU Virgen del Rocio, IBiS, University of Sevilla, Sevilla, Spain.
(48)Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies
Neurodégénératives, UMR5293, Université de Bordeaux, Bordeaux, France.
(49)Erasmus School of Social and Behavioural Sciences, Erasmus University
Rotterdam, Rotterdam, Netherlands.
(50)Faculteit der Sociale Wetenschappen, Instituut Psychologie, Universiteit
Leiden, Leiden, Netherlands.
(51)Center for Multimodal Imaging and Genetics, Department of Neuroscience,
University of California-San Diego, San Diego, California, USA.
(52)Department of Radiology, University of California-San Diego, San Diego,
California, USA.
(53)Department of Psychiatry and Psychotherapy, University of Münster, Germany.
(54)Department of Psychiatry, University of Melbourne, Melbourne, Australia.
(55)Academisch Medisch Centrum, Universiteit van Amsterdam, Amsterdam,
Netherlands.
(56)Faculty of Health, Institute of Health and Biomedical Innovation, Queensland
University of Technology, Queensland, Australia.
(57)Kimel Family Translational Imaging Genetics Laboratory, Campbell Family
Mental Health Research Institute, CAMH, Campbell, Canada.
(58)Department of Psychiatry, University of Toronto, Toronto, Canada.
(59)Biological Psychiatry Lab, Fondazione IRCCS Casa Sollievo della Sofferenza,
San Giovanni Rotondo (FG), Italy.
(60)Department of Psychology, University of Oslo, Oslo, Norway.
(61)Sunnaas Rehabilitation Hospital HT, Nesodden, Norway.
(62)Division of Psychological and Social Medicine and Developmental
Neurosciences, Technische Universität Dresden, Dresden, Germany.
(63)Faculty of Medicine, Universitätsklinikum Carl Gustav Carus an der TU
Dresden, Dresden, Germany.
(64)Division of Mind and Brain Research, Department of Psychiatry and
Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
(65)Bjørknes College, Oslo, Norway.
(66)Language and Genetics Department, Max Planck Institute for
Psycholinguistics, Nijmegen, Netherlands.
(67)Department of Psychiatry and Mental Health, University of Cape Town, Cape
Town, South Africa.
(68)Department of Human Genetics, Radboud University Medical Center, Nijmegen,
Netherlands.
(69)Department of Psychiatry, Radboud University Medical Center, Nijmegen,
Netherlands.
(70)Department of Psychiatry and Psychotherapy, Otto von Guericke University
Magdeburg, Magdeburg, Germany.
(71)Department of Psychiatry, Tommy Fuss Center for Neuropsychiatric Disease
Research Boston Children’s Hospital, Harvard Medical School, Boston,
Massachusetts, USA.
(72)Department of Psychology, Stanford University, Stanford, California, USA.
(73)Department of Psychiatry and Psychotherapy, University Medicine Greifswald,
University of Greifswald, Greifswald, Germany.
(74)German Center for Neurodegenerative Diseases (DZNE), Site
Rostock/Greifswald, Greifswald, Germany.
(75)Department for Psychiatry, Psychosomatics and Psychotherapy,
Universitätsklinikum Frankfurt, Goethe Universitat, Frankfurt, Germany.
(76)Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
(77)Section for Experimental Psychopathology and Neuroimaging, Department of
General Psychiatry, Heidelberg University, Heidelberg, Germany.
(78)Department of Psychiatry, Yale University, New Haven, Connecticut, USA.
(79)Learning Based Recovery Center, VA Connecticut Health System, West Haven,
Connecticut, USA.
(80)Lifespan Brain Institute, Perelman School of Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania, USA.
(81)Children’s Hospital of Philadelphia, University of Pennsylvania,
Philadelphia, Pennsylvania, USA.
(82)Melbourne Neuropsychiatry Center, University of Melbourne, Melbourne,
Australia.
(83)Interdisciplinary Center Psychopathology and Emotion regulation, University
Medical Center Groningen, University of Groningen, Groningen, Netherlands.
(84)Brain and Mind Centre, University of Sydney, Sydney, Australia.
(85)Departments of Experimental and Clinical Psychology, Vrije Universiteit
Amsterdam, Amsterdam, Netherlands.
(86)Personalized Healthcare, Genentech, Inc., South San Francisco, California,
USA.
(87)Department of Psychiatry, University Medical Center Groningen, University of
Groningen, Groningen, Netherlands.
(88)Department of Psychology, Yale University, New Haven, Connecticut, USA.
(89)Norbert Institute of Diagnostic Radiology and Neuroradiology, University
Medicine Greifswald, University of Greifswald, Greifswald, Germany.
(90)De Bascule, Academic Centre for Children and Adolescent Psychiatry,
Amsterdam, Netherlands.
(91)Department of Psychiatry, Oxford University, Oxford, United Kingdom.
(92)Center for Human Development, Departments of Cognitive Science, Psychiatry,
and Radiology, University of California, San Diego, California, USA.
(93)Department of Radiology, Ohio State University College of Medicine,
Columbus, Ohio, USA.
(94)Department of Neuroinformatics, Araya, Inc., Tokyo, Japan.
(95)Department of Psychiatry, University of California San Diego, San Diego,
California, USA.
(96)Mental Health Research Center, Russian Academy of Medical Sciences, Moscow,
Russia.
(97)Sunshine Coast Mind and Neuroscience, Thompson Institute, University of the
Sunshine Coast, Queensland, Australia.
(98)Department of Child and Adolescent Psychiatry and Psychology, Hospital
Clinic, University of Barcelona, Barcelona, Spain.
(99)Department of Psychiatry, Psychosomatics and Psychotherapy,
Julius-Maximilians Universität Würzburg, Würzburg, Germany.
(100)SA MRC Unit on Risk and Resilience in Mental Disorders, Department of
Psychiatry, Stellenbosch University, Stellenbosch, South Africa.
(101)Queensland Institute of Medical Research, Berghofer Medical Research
Institute, Queensland, Australia.
(102)Department of Psychiatry, Bellvitge University Hospital-IDIBELL, University
of Barcelona, Barcelona, Spain.
(103)Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
(104)School of Clinical Sciences, Institute of Health and Biomedical Innovation,
Queensland University of Technology, Queensland, Australia.
(105)Department of Psychiatry and Psychotherapy, Central Institute of Mental
Health, Heidelberg University, Heidelberg, Germany.
(106)Department of Clinical Medicine, Kyushu University, Fukuoka, Japan.
(107)CatoSenteret Rehabilitation Hospital, Son, Norway.
(108)Department of Radiation Sciences, Umeå Center for Functional Brain Imaging,
Umeå University, Umeå, Sweden.
(109)Department of Clinical Neuropsychology, Amsterdam University Medical
Centre, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
(110)Department of Psychiatry, University Hospital “Marques de Valdecilla”,
Instituto de Investigación Valdecilla (IDIVAL), Santander, Spain.
(111)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM),
Instituto de Salud Carlos III, Madrid, Spain.
(112)Centre of Mental Health, University of Würzburg, Würzburg, Germany.
(113)Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Institut
d’Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Barcelona,
Spain.
(114)Department of Psychiatry, University of California at Irvine, Irvine,
California, USA.
(115)Department of Psychosis Studies, Institute of Psychiatry, Psychology &
Neuroscience, King’s College London, London, United Kingdom.
(116)Center for Depression, Anxiety, and Stress Research, McLean Hospital,
Harvard Medical School, Boston, Massachusetts, USA.
(117)Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas
(CIBERNED), Valderrebollo, Spain.
(118)Orygen, The National Centre of Excellence in Youth Mental Health,
Melbourne, Australia.
(119)Centre for Youth Mental Health, The University of Melbourne, Melbourne,
Australia.
(120)Department of Psychiatry and Psychotherapy, University Medical Center
Göttingen, Göttingen, Germany.
(121)Centre for Population Neuroscience and Precision Medicine, Institute of
Psychiatry, Psychology & Neuroscience, King’s College London, London, United
Kingdom.
(122)Department of General Psychiatry, Institute of Mental Health, Singapore,
Singapore.
(123)Center for Genomic Medicine, Massachusetts General Hospital, Boston,
Massachusetts, USA.
(124)Department of Biomedical Sciences of Cells and Systems, Rijksuniversiteit
Groningen, University Medical Center Groningen, Groningen, Netherlands.
(125)Queensland Brain Institute, University of Queensland, Queensland,
Australia.
(126)PROMENTA Research Center, Department of Psychology, University of Oslo,
Oslo, Norway.
(127)Neuroimaging Unit, Technological Facilities, Valdecilla Biomedical Research
Institute IDIVAL, Cantabria, Spain.
(128)College of Arts and Sciences, Georgia State University, Atlanta, Georgia,
USA.
(129)School of Mental Health and Neuroscience, Faculty of Health, Medicine and
Life Sciences, Maastricht University, Maastricht, Netherlands.
(130)Department of Psychiatry, Leiden University Medical Center, Leiden,
Netherlands.
(131)Leiden Institute for Brain and Cognition, Leiden University Medical Center,
Leiden, Netherlands.
(132)Department of Child and Adolescent Psychiatry/Psychology, Erasmus
University Medical Center, Sophia Children’s Hospital, Rotterdam, The
Netherlands.
(133)Center for the Neurobiology of Learning and Memory, University of
California Irvine, Irvine, California, USA.
(134)Institute of Community Medicine, University Medicine, Greifswald,
University of Greifswald, Greifswald, Germany.
(135)German Centre for Cardiovascular Research (DZHK), partner site Greifswald,
Greifswald, Germany.
(136)German Center for Diabetes Research (DZD), partner site Greifswald,
Greifswald, Germany.
(137)Department of Psychology, University of Bath, Bath, United Kingdom.
(138)Department of Psychiatry and Behavioral Sciences, Feinberg School of
Medicine, Northwestern University, Evanston, Illinois, USA.
(139)Department of Radiology, Medical College of Wisconsin, Milwaukee,
Wisconsin, USA.
(140)Institute for Experimental Epileptology and Cognition Research, University
of Bonn, Bonn, Germany.
(141)Developmental and Educational Psychology Unit, Institute of Psychology,
Leiden University, Leiden, Netherlands.
(142)National High Magnetic Field Laboratory, Florida State University,
Tallahassee, Florida, USA.
(143)Department of Child and Adolescent Psychiatry, Child Study Center, NYU
Langone Health, New York City, New York, USA.
(144)Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês, São Paulo, Brazil.
(145)Division of Molecular Psychiatry, Center of Mental Health, University of
Würzburg, Würzburg, Germany.
(146)Department of Psychology, School of Arts and Social Sciences, City
University of London, London, United Kingdom.
(#)Contributed equally
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.
© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.
DOI: 10.1002/hbm.25364
PMCID: PMC8675431
PMID: 33595143 [Indexed for MEDLINE]
Conflict of interest statement: Hans Jörgen Grabe: Travel grants and speaker
honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag;
reseach funding from Fresenius Medical Care. Ole A Andreasen: Consultant to
HealthLytix, speaker honorarium from Lundbeck. Anders M Dale: Founder and member
of the Scientific Advisory Board CorTechs Labs, Inc where he holds equity;
member of the Scientific Advisory of Human Longevity Inc; research grants with
General Electric Healthcare.