Greater male than female variability in regional brain structure across the lifespan
Human Brain Mapping. 2020-10-12; 43(1): 470-499
DOI: 10.1002/hbm.25204
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Wierenga LM(1)(2), Doucet GE(3)(4), Dima D(5)(6), Agartz I(7)(8)(9), Aghajani
M(10)(11)(12), Akudjedu TN(13)(14), Albajes-Eizagirre A(15)(16)(17), Alnaes
D(7)(18), Alpert KI(19), Andreassen OA(7)(18), Anticevic A(20), Asherson P(21),
Banaschewski T(22), Bargallo N(23)(24), Baumeister S(22), Baur-Streubel R(25),
Bertolino A(26), Bonvino A(26), Boomsma DI(27), Borgwardt S(28)(29), Bourque
J(30)(31), den Braber A(27)(32), Brandeis D(22)(33)(34)(35), Breier A(36),
Brodaty H(37)(38), Brouwer RM(39), Buitelaar JK(40)(41), Busatto GF(42), Calhoun
VD(43), Canales-Rodríguez EJ(15)(16), Cannon DM(13), Caseras X(44), Castellanos
FX(45)(46), Chaim-Avancini TM(42), Ching CR(47), Clark VP(48)(49), Conrod
PJ(31)(50), Conzelmann A(51)(52), Crivello F(53), Davey CG(54)(55), Dickie
EW(56)(57), Ehrlich S(58), Van’t Ent D(27), Fisher SE(59)(60), Fouche JP(61),
Franke B(60)(62)(63), Fuentes-Claramonte P(15)(16), de Geus EJ(27), Di Giorgio
A(64), Glahn DC(65)(66), Gotlib IH(67), Grabe HJ(68)(69), Gruber O(70), Gruner
P(20), Gur RE(30)(71), Gur RC(30), Gurholt TP(7)(18), de Haan L(72), Haatveit
B(7)(18), Harrison BJ(73), Hartman CA(74), Hatton SN(75)(76), Heslenfeld DJ(77),
van den Heuvel OA(10)(78), Hickie IB(75), Hoekstra PJ(79), Hohmann S(22), Holmes
AJ(20)(80)(81), Hoogman M(60)(62), Hosten N(82), Howells FM(83)(84), Hulshoff
Pol HE(39), Huyser C(85)(86), Jahanshad N(47), James AC(87)(88), Jiang J(37),
Jönsson EG(7)(9), Joska JA(84), Kalnin AJ(89); Karolinska Schizophrenia Project
(KaSP) Consortium; Klein M(39)(60)(62), Koenders L(72), Kolskår KK(18)(90)(91),
Krämer B(70), Kuntsi J(21), Lagopoulos J(92)(93), Lazaro L(16)(94)(95)(96),
Lebedeva IS(97), Lee PH(81)(98), Lochner C(99), Machielsen MW(100), Maingault
S(101), Martin NG(102), Martínez-Zalacaín I(103)(104), Mataix-Cols D(9), Mazoyer
B(105)(106), McDonald BC(107), McDonald C(13), McIntosh AM(108), McMahon
KL(109)(110), McPhilemy G(13), van der Meer D(7)(18)(111), Menchón
JM(16)(103)(104), Naaijen J(40), Nyberg L(112)(113), Oosterlaan J(114)(115),
Paloyelis Y(6), Pauli P(116)(117), Pergola G(26)(118), Pomarol-Clotet E(15)(16),
Portella MJ(16)(119), Radua J(9)(15)(16)(17)(120), Reif A(121), Richard
G(7)(18), Roffman JL(122), Rosa PG(42), Sacchet MD(123), Sachdev PS(37)(124),
Salvador R(15)(16), Sarró S(15)(16), Satterthwaite TD(30), Saykin AJ(107)(125),
Serpa MH(42), Sim K(126)(127), Simmons A(128), Smoller JW(81)(129), Sommer
IE(130), Soriano-Mas C(16)(103)(131), Stein DJ(132), Strike LT(133), Szeszko
PR(3)(134), Temmingh HS(84), Thomopoulos SI(47), Tomyshev AS(97), Trollor
JN(37), Uhlmann A(84)(135), Veer IM(136), Veltman DJ(137), Voineskos A(56),
Völzke H(138)(139)(140), Walter H(136), Wang L(19), Wang Y(141), Weber B(142),
Wen W(37), West JD(107), Westlye LT(7)(18)(90), Whalley HC(108)(143), Williams
SC(144), Wittfeld K(68)(69), Wolf DH(30), Wright MJ(133)(145), Yoncheva YN(146),
Zanetti MV(42)(147), Ziegler GC(148), de Zubicaray GI(110), Thompson PM(47),
Crone EA(1)(2)(149), Frangou S(3)(150), Tamnes CK(7)(8)(151).
Author information:
(1)Institute of Psychology, Leiden University, Leiden, The Netherlands.
(2)Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
(3)Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York,
New York, USA.
(4)Boys Town National Research Hospital, Omaha, Nebraska, USA.
(5)Department of Psychology, School of Arts and Social Sciences, City,
University of London, London, UK.
(6)Department of Neuroimaging, Institute of Psychiatry, Psychology and
Neuroscience, King’s College London, London, UK.
(7)Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental
Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo,
Norway.
(8)Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
(9)Centre for Psychiatry Research, Department of Clinical Neuroscience,
Karolinska Institutet, & Stockholm Health Care Services, Stockholm County
Council, Stockholm, Sweden.
(10)Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, Vrije
Universiteit, Amsterdam, The Netherlands.
(11)Department of Research & Innovation, GGZ inGeest, Amsterdam, The
Netherlands.
(12)Institute of Education and Child Studies, Forensic Family and Youth Care,
Leiden University, Leiden, The Netherlands.
(13)Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging
Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and
Health Sciences, National University of Ireland Galway, Galway, Ireland.
(14)Institute of Medical Imaging & Visualisation, Faculty of Health & Social
Sciences, Bournemouth University, Bournemouth, UK.
(15)FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
(16)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid,
Spain.
(17)Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS),
Barcelona, Spain.
(18)Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental
Health and Addiction, Oslo University Hospital, Oslo, Norway.
(19)Department of Psychiatry and Behavioral Sciences, Northwestern University
Feinberg School of Medicine, Chicago, Illinois, USA.
(20)Department of Psychiatry, Yale University, New Haven, Connecticut, USA.
(21)Social, Genetic and Developmental Psychiatry Centre, Institute of
Psychiatry, Psychology and Neuroscience, King’s College London, London, UK.
(22)Department of Child and Adolescent Psychiatry and Psychotherapy, Central
Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim,
Mannheim, Germany.
(23)Imaging Diagnostic Center, Hospital Clínic, Barcelona, Spain.
(24)Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain.
(25)Department for Clinical Psychology, Würzburg University, Margetshöchheim,
Germany.
(26)Department of Basic Medical Science, Neuroscience and Sense Organs,
University of Bari Aldo Moro, Bari, Italy.
(27)Department of Biological Psychology, VU University Amsterdam, Amsterdam, The
Netherlands.
(28)Department of Psychiatry, University of Basel, Basel, Switzerland.
(29)Department of Psychiatry, University of Lübeck, Lübeck, Germany.
(30)Department of Psychiatry, University of Pennsylvania, Philadelphia,
Pennsylvania, USA.
(31)CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
(32)Alzheimer Center, Amsterdam UMC, Location VUMC, Amsterdam, The Netherlands.
(33)Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric
Hospital, University of Zurich, Zurich, Switzerland.
(34)Zurich Center for Integrative Human Physiology, University of Zurich,
Zurich, Switzerland.
(35)Neuroscience Centre Zurich, University and ETH Zurich, Zurich, Switzerland.
(36)Department of Psychiatry, Indiana University School of Medicine,
Indianapolis, Indiana, USA.
(37)Centre for Healthy Brain Ageing, School of Psychiatry, University of New
South Wales, Sydney, New South Wales, Australia.
(38)Dementia Centre for Research Collaboration, School of Psychiatry, University
of New South Wales, Sydney, New South Wales, Australia.
(39)Department of Psychiatry, University Medical Center Utrecht Brain Center,
Utrecht University, Utrecht, The Netherlands.
(40)Department of Cognitive Neuroscience, Radboud University Medical Centre,
Nijmegen, The Netherlands.
(41)Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The
Netherlands.
(42)Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de
Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade
de São Paulo, São Paulo, Brazil.
(43)Tri-institutional Center for Translational Research in Neuroimaging and Data
Science (TReNDS), Georgia State, Georgia Tech, Atlanta, Georgia, USA.
(44)MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University,
Cardiff, UK.
(45)Department of Child and Adolescent Psychiatry, NYU Grossman School of
Medicine, New York, New York, USA.
(46)Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, USA.
(47)Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics
Institute, Keck School of Medicine, University of Southern California, Los
Angeles, California, USA.
(48)Psychology Clinical Neuroscience Center, Department of Psychology,
University of New Mexico, Albuquerque, New Mexico, USA.
(49)Mind Research Network, Albuquerque, New Mexico, USA.
(50)Department of Psychiatry, University of Montreal, Montreal, Canada.
(51)Department of Child and Adolescent Psychiatry, Psychosomatics and
Psychotherapy, University of Tübingen, Tübingen, Germany.
(52)Department of Psychology (Clinical Psychology II), PFH – Private University
of Applied Sciences, Göttingen, Germany.
(53)Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies
Neurodégénératives, Bordeaux, France.
(54)Centre for Youth Mental Health, University of Melbourne, Parkville,
Victoria, Australia.
(55)Orygen, Parkville, Victoria, Australia.
(56)Campbell Family Mental Health Institute, Centre for Addiction and Mental
Health, Department of Psychiatry, University of Toronto, Toronto, Canada.
(57)Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
(58)Division of Psychological & Social Medicine and Developmental Neurosciences;
Technische Universität Dresden, Faculty of Medicine, University Hospital C.G.
Carus, Dresden, Germany.
(59)Language and Genetics Department, Max Planck Institute for
Psycholinguistics, Nijmegen, The Netherlands.
(60)Donders Institute for Brain, Cognition and Behaviour, Radboud University,
Nijmegen, The Netherlands.
(61)Department of Psychiatry and Neuroscience Institute, University of Cape
Town, Cape Town, Western Cape, South Africa.
(62)Department of Human Genetics, Radboud University Medical Center, Nijmegen,
The Netherlands.
(63)Department of Psychiatry, Radboud University Medical Center, Nijmegen, The
Netherlands.
(64)IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
(65)Tommy Fuss Center for Neuropsychiatric Disease Research, Department of
Psychiatry, Boston Children’s Hospital and Harvard Medical School, Boston,
Massachusetts, USA.
(66)Olin Center for Neuropsychiatric Research, Institute of Living, Hartford
Hospital, Hartford, Connecticut, USA.
(67)Department of Psychology, Stanford University, Stanford, California, USA.
(68)Department of Psychiatry and Psychotherapy, University Medicine Greifswald,
Greifswald, Germany.
(69)German Center for Neurodegenerative Diseases (DZNE), Site
Rostock/Greifswald, Greifswald, Germany.
(70)Section for Experimental Psychopathology and Neuroimaging, Department of
General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
(71)Lifespan Brain Institute, Children’s Hospital of Philadelphia, Philadelphia,
Pennsylvania, USA.
(72)Department of Early Psychosis, Amsterdam UMC, Amsterdam, The Netherlands.
(73)Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University
of Melbourne & Melbourne Health, Melbourne, Australia.
(74)Interdisciplinary Center Psychopathology and Emotion regulation, University
of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
(75)Brain and Mind Centre, University of Sydney, Sydney, New South Wales,
Australia.
(76)Department of Neurosciences, University of California San Diego, La Jolla,
California, USA.
(77)Departments of Experimental and Clinical Psychology, Vrije Universiteit
Amsterdam, Amsterdam, The Netherlands.
(78)Department of Anatomy & Neurosciences, Amsterdam Neuroscience, Amsterdam
UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
(79)Department of Psychiatry, University of Groningen, University Medical Center
Groningen, Groningen, The Netherlands.
(80)Department of Psychology, Yale University, New Haven, Connecticut, USA.
(81)Department of Psychiatry, Massachusetts General Hospital, Boston,
Massachusetts, USA.
(82)Institute of Diagnostic Radiology and Neuroradiology, University Medicine
Greifswald, Greifswald, Germany.
(83)Neuroscience Institute, University of Cape Town, Cape Town, Western Cape,
South Africa.
(84)Department of Psychiatry and Mental Health, University of Cape Town, Cape
Town, Western Cape, South Africa.
(85)De Bascule, Academic center child and adolescent psychiatry, Duivendrecht,
The Netherlands.
(86)Amsterdam UMC Department of Child and Adolescent Psychiatry, Amsterdam, The
Netherlands.
(87)Department of Psychiatry, Warneford Hospital, Oxford, UK.
(88)Highfield Unit, Warneford Hospital, Oxford, UK.
(89)Department of Radiology, The Ohio State University College of Medicine,
Columbus, Ohio, USA.
(90)Department of Psychology, University of Oslo, Oslo, Norway.
(91)Sunnaas Rehabilitation Hospital HT, Nesodden, Norway.
(92)Sunshine Coast Mind and Neuroscience Thompson Institute, Birtinya,
Queensland, Australia.
(93)University of the Sunshine Coast, Sunshine Coast, Queensland, Australia.
(94)Department of Child and Adolescent Psychiatry and Psychology, Hospital
Clínic, Barcelona, Spain.
(95)August Pi i Sunyer Biomedical Research Institut (IDIBAPS), Barcelona, Spain.
(96)Department of Medicine, University of Barcelona, Barcelona, Spain.
(97)Laboratory of Neuroimaging and Multimodal Analysis, Mental Health Research
Center, Moscow, Russia.
(98)Department of Psychiatry, Harvard Medical School, Boston, Massachusetts,
USA.
(99)SA MRC Unit on Risk and Resilience in Mental Disorders, Department of
Psychiatry, Stellenbosch University, Cape Town, Western Cape, South Africa.
(100)Department of Psychiatry, Academic Medical Center, Amsterdam, The
Netherlands.
(101)Institut des maladies neurodégénératives, Université de Bordeaux, Bordeaux,
France.
(102)Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane,
Queensland, Australia.
(103)Department of Psychiatry, Bellvitge University Hospital, Bellvitge
Biomedical Research Institute-IDIBELL, Barcelona, Spain.
(104)Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
(105)University of Bordeaux, Bordeaux, France.
(106)Bordeaux University Hospital, Bordeaux, France.
(107)Department of Radiology and Imaging Sciences, Indiana University School of
Medicine, Indianapolis, Indiana, USA.
(108)Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
(109)Herston Imaging Research Facility and School of Clinical Sciences,
Queensland University of Technology (QUT), Brisbane, Queensland, Australia.
(110)Faculty of Health, Institute of Health and Biomedical Innovation,
Queensland University of Technology (QUT), Brisbane, Queensland, Australia.
(111)School of Mental Health and Neuroscience, Faculty of Health, Medicine and
Life Sciences, Maastricht University, Maastricht, The Netherlands.
(112)Department of Radiation Sciences, Umeå University, Umeå, Sweden.
(113)Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
(114)Emma Children’s Hospital, Amsterdam UMC University of Amsterdam and Vrije
Universiteit Amsterdam, Emma Neuroscience Group, Department of Pediatrics,
Amsterdam Reproduction & Development, Amsterdam, The Netherlands.
(115)Clinical Neuropsychology Section, Vrije Universiteit Amsterdam, Amsterdam,
The Netherlands.
(116)Department of Psychology, University of Würzburg, Würzburg, Germany.
(117)Centre of Mental Health, Medical Faculty, University of Würzburg, Würzburg,
Germany.
(118)Lieber Institute for Brain Development, Johns Hopkins Medical Campus,
Baltimore, Mary Land, USA.
(119)Department of Psychiatry, Institut d’Investigació Biomèdica Sant Pau,
Barcelona, Spain.
(120)Early Psychosis: Interventions and Clinical-detection (EPIC) lab,
Department of Psychosis Studies, Institute of Psychiatry, Psychology and
Neuroscience, King’s College London, London, UK.
(121)Department of Psychiatry, Psychosomatic Medicine and Psychotherapy,
University Hospital Frankfurt, Frankfur am Maint, Germany.
(122)Department of Psychiatry, Massachusetts General Hospital and Harvard
Medical School, Charlestown, Massachusetts, USA.
(123)Center for Depression, Anxiety, and Stress Research, McLean Hospital,
Harvard Medical School, Belmont, Massachusetts, USA.
(124)Neuropsychiatric Institute, The Prince of Wales Hospital, Randwick, New
South Wales, Australia.
(125)Indiana Alzheimer Disease Center, Indianapolis, Indiana, USA.
(126)West Region, Institute of Mental Health, Singapore, Singapore.
(127)Yong Loo Lin School of Medicine, National University of Singapore,
Singapore.
(128)Department of Neuroimaging, Institute of Psychiatry, Psychology and
Neurology, King’s College London, London, UK.
(129)Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic
Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
(130)Department of Biomedical Sciences of Cells and Systems, Rijksuniversiteit
Groningen, University Medical Center Groningen, Groningen, The Netherlands.
(131)Department of Psychobiology and Methodology in Health Sciences, Universitat
Autònoma de Barcelona, Barcelona, Spain.
(132)SAMRC Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry &
Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South
Africa.
(133)Queensland Brain Institute, University of Queensland, Brisbane, Queensland,
Australia.
(134)Mental Illness Research, Education and Clinical Center (MIRECC), James J.
Peters VA Medical Center, New York, New York, USA.
(135)Department of Child and Adolescent Psychiatry and Psychotherapy, Faculty of
Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany.
(136)Department of Psychiatry and Psychotherapy CCM, Charité –
Universitätsmedizin Berlin, corporate member of Freie Universität Berlin,
Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
(137)Department of Psychiatry & Amsterdam Neuroscience, Amsterdam UMC, location
VUMC, Amsterdam, The Netherlands.
(138)Institute for Community Medicine, University Medicine Greifswald,
Greifswald, Germany.
(139)DZHK (German Centre for Cardiovascular Research), partner site Greifswald,
Greifswald, Germany.
(140)DZD (German Center for Diabetes Research), partner site Greifswald,
Greifswald, Germany.
(141)Department of Radiology, Medical College of Wisconsin, Milwaukee,
Wisconsin, USA.
(142)Institute for Experimental Epileptology and Cognition Research, University
Hospital Bonn, Bonn, Germany.
(143)Division of Psychiatry, Royal Edinburgh Hospital, Edinburgh, UK.
(144)Department of Neuroimaging, King’s College London, London, UK.
(145)Centre for Advanced Imaging, University of Queensland, Brisbane,
Queensland, Australia.
(146)Department of Child and Adolescent Psychiatry, NYU Child Study Center,
Hassenfeld Children’s Hospital at NYU Langone, New York, New York, USA.
(147)Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês, São Paulo, Brazil.
(148)Division of Molecular Psychiatry, Center of Mental Health, University of
Würzburg, Würzburg, Germany.
(149)Department of Psychology, Education and Child Studies (DPECS), Erasmus
School of Social and Behavioral Sciences, Erasmus University Rotterdam, The
Netherlands.
(150)Centre for Brain Health, University of British Columbia, Vancouver, British
Columbia, Canada.
(151)PROMENTA Research Center, Department of Psychology, University of Oslo,
Oslo, Norway.
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.
© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.
DOI: 10.1002/hbm.25204
PMCID: PMC8675415
PMID: 33044802 [Indexed for MEDLINE]
Conflict of interest statement: The authors declare the following competing
interests: OAA: Speaker’s honorarium from Lundbeck, Consultant of HealthLyti;
PA: Received payments for consultancy to Shire/Takeda, Medic,
educational/research awards from Shire/Takeda, GW Pharma, Janssen‐Cila, speaker
at sponsored events for Shire, Flynn Pharma, Medic; TB: advisory or consultancy
role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and
Infectopharm, conference support or speaker’s fee by Lilly, Medice, and Shire,
received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University
Press ‐ the present work is unrelated to the above grants and relationship; DB:
serves as an unpaid scientific consultant for an EU‐funded neurofeedback trial
that is unrelated to the present work; HB: Advisory Board, Nutricia Australi;
CRKC: received partial research support from Biogen, Inc. (Boston, USA) for work
unrelated to the topic of this manuscript; BF: received educational speaking
fees from Medice; HJG: received travel grants and speakers honoraria from
Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as
research funding from Fresenius Medical Care; NJ and PMT: MPI of a research
related grant from Biogen, Inc., for research unrelated to the contents of this
manuscript; JK: given talks at educational events sponsored by Medic; all funds
are received by King’s College London and used for studies of ADHD; DM‐C:
receives fees from UpToDate, Inc and Elsevier, all unrelated to the current
work; AMM: received research support from Eli Lilly, Janssen, and the Sackler
Foundation, and speaker fees from Illumina and Janssen; DJS: received research
grants and/or honoraria from Lundbeck and Sun. The remaining authors declare no
competing interests.