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Longitudinally mapping the influence of sex and androgen signaling on the dynamics of human cortical maturation in adolescence
Open accessAbstract
Humans have systematic sex differences in brain-related behavior, cognition, and pattern of mental illness risk. Many of these differences emerge during adolescence, a developmental period of intense neurostructural and endocrine change. Here, by creating "movies" of sexually dimorphic brain development using longitudinal in vivo structural neuroimaging, we show regionally specific sex differences in development of the cerebral cortex during adolescence. Within cortical subsystems known to underpin domains of cognitive behavioral sex difference, structural change is faster in the sex that tends to perform less well within the domain in question. By stratifying participants through molecular analysis of the androgen receptor gene, we show that possession of an allele conferring more efficient functioning of this sex steroid receptor is associated with "masculinization" of adolescent cortical maturation. Our findings extend models first established in rodents, and suggest that in humans too, sex and sex steroids shape brain development in a spatiotemporally specific manner, within neural systems known to underpin sexually dimorphic behaviors.
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Cites
Mixed-Effects Models in Sand S-PLUS
Pinheiro, J. C., & Bates, D. M. (2000) · Statistics and Computing · doi:10.1007/978-1-4419-0318-1 · Cited by 11,187
Dynamic mapping of human cortical development during childhood through early adulthood
Gogtay, N., Giedd, J. N., Lusk, L., Hayashi, K. M., Greenstein, D., Vaituzis, A. C., Nugent, T. F., Herman, D. H., Clasen, L. S., Toga, A. W., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402680101 · Cited by 5,604 · cited 2×
“The cerebral cortex is of particular interest in this regard as it undergoes its most dynamic structural change in adolescence (17) when many cognitive behavioral sex differences in humans emerge, shows sexually dimorphic structuralmaturation at the gross lobar scale (18), and is known to subserve several sexually dim…”
BackgroundBrain development during childhood and adolescence: a longitudinal MRI study
Giedd, J. N., Blumenthal, J., Jeffries, N. O., Castellanos, F. X., Liu, H., Zijdenbos, A., Paus, T., Evans, A. C., & Rapoport, J. L. (1999) · Nature Neuroscience · doi:10.1038/13158 · Cited by 5,552
Four Factor Index of Social Status [1975]
Hollingshead, A. B. (1975) · Cited by 5,151
Gene Action in the X-chromosome of the Mouse (Mus musculus L.)
LYON, M. F. (1961) · Nature · doi:10.1038/190372a0 · Cited by 3,978
Cognitive and affective development in adolescence
Steinberg, L. (2005) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2004.12.005 · Cited by 2,978
Voyer, D., Voyer, S., & Bryden, M. P. (1995) · Psychological Bulletin · doi:10.1037/0033-2909.117.2.250 · Cited by 2,868
Sex Differences in Cognitive Abilities
Halpern, D. F. (2000) · Psychology Press eBooks · doi:10.4324/9781410605290 · Cited by 1,989
Neurodevelopmental Trajectories of the Human Cerebral Cortex
Shaw, P., Kabani, N. J., Lerch, J. P., Eckstrand, K., Lenroot, R., Gogtay, N., Greenstein, D., Clasen, L., Evans, A., Rapoport, J. L., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5309-07.2008 · Cited by 1,644
Intellectual ability and cortical development in children and adolescents
Shaw, P., Greenstein, D., Lerch, J., Clasen, L., Lenroot, R., Gogtay, N., Evans, A., Rapoport, J., & Giedd, J. (2006) · Nature · doi:10.1038/nature04513 · Cited by 1,543
Self-citationSexual dimorphism of brain developmental trajectories during childhood and adolescence
Lenroot, R. K., Gogtay, N., Greenstein, D. K., Wells, E. M., Wallace, G. L., Clasen, L. S., Blumenthal, J. D., Lerch, J., Zijdenbos, A. P., Evans, A. C., et al. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.03.053 · Cited by 1,309
Galvan, A., Hare, T. A., Parra, C. E., Penn, J., Voss, H., Glover, G., & Casey, B. J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1062-06.2006 · Cited by 1,282
Mental Health of Children and Young People in Great Britain, 2004: (557702010-001)
Green, H., McGinnity, A., Meltzer, H., Ford, T., & Goodman, R. (2005) · PsycEXTRA Dataset · doi:10.1037/e557702010-001 · Cited by 1,216
Chamberlain, N. L., Driver, E. D., & Miesfeld, R. L. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.15.3181 · Cited by 1,149
Yang, Y., & Raine, A. (2009) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2009.03.012 · Cited by 888
Automated 3-D Extraction of Inner and Outer Surfaces of Cerebral Cortex from MRI
MacDonald, D. J., Kabani, N. J., Avis, D., & Evans, A. C. (2000) · NeuroImage · doi:10.1006/nimg.1999.0534 · Cited by 850
Neuroimaging Studies of Mental Rotation: A Meta-analysis and Review
Zacks, J. M. (2007) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2008.20013 · Cited by 796
Automatic "pipeline" analysis of 3-D MRI data for clinical trials: application to multiple sclerosis
Zijdenbos, A. P., Forghani, R., & Evans, A. C. (2002) · IEEE Transactions on Medical Imaging · doi:10.1109/tmi.2002.806283 · Cited by 755
Cortical thickness analysis examined through power analysis and a population simulation
Lerch, J. P., & Evans, A. C. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.07.045 · Cited by 715
Sexual differentiation of the vertebrate nervous system
Morris, J. A., Jordan, C. L., & Breedlove, S. M. (2004) · Nature Neuroscience · doi:10.1038/nn1325 · Cited by 627
Sex differences in the adolescent brain
Lenroot, R., & Giedd, J. N. (2009) · Brain and Cognition · doi:10.1016/j.bandc.2009.10.008 · Cited by 608
Tut, T. G., Ghadessy, F. J., Trifiro, M. A., Pinsky, L., & Yong, E. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.11.4385 · Cited by 520
Kazemi‐Esfarjani, P., Trifiro, M. A., & Pinsky, L. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.4.523 · Cited by 447
Brain Size and Cortical Structure in the Adult Human Brain
Im, K., Lee, J., Lyttelton, O. C., Kim, S. H., Evans, A. C., & Kim, S. I. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhm244 · Cited by 439
Sex Differences and the Impact of Steroid Hormones on the Developing Human Brain
Neufang, S., Specht, K., Hausmann, M., Güntürkün, O., Herpertz‐Dahlmann, B., Fink, G. R., & Konrad, K. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhn100 · Cited by 435
Tut, T. G. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.82.11.3777 · Cited by 365
Complete Androgen Insensitivity Syndrome: Long-Term Medical, Surgical, and Psychosexual Outcome
Wisniewski, A. B., Migeon, C. J., Meyer‐Bahlburg, H. F. L., Gearhart, J. P., Berkovitz, G. D., Brown, T. R., & Money, J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.8.6742 · Cited by 344
Growth of white matter in the adolescent brain: role of testosterone and androgen receptor
Perrin, J. S., Hervé, P.-Y., Leonard, G., Perron, M., Pike, G. B., Pitiot, A., Richer, L., Veillette, S., Pausova, Z., & Paus, T. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1212-08.2008 · Cited by 331
Hormonal influences on sexually differentiated behavior in nonhuman primates.
Wallen, K. (2005) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2005.02.001 · Cited by 305
Sex steroids and brain structure in pubertal boys and girls
Peper, J. S., Brouwer, R. M., Schnack, H. G., van Baal, G. C. M., van Leeuwen, M., van den Berg, S. M., de Waal, H. A. D., Boomsma, D. I., Kahn, R. S., & Pol, H. E. H. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.09.012 · Cited by 290
Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length
Irvine, R. A. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.2.267 · Cited by 263
Zuloaga, D. G., Puts, D. A., Jordan, C. L., & Breedlove, S. M. (2008) · Hormones and Behavior · doi:10.1016/j.yhbeh.2008.01.013 · Cited by 236 · cited 3×
“Second, as far as we are aware, no one has ever longitudinally tested the hypothesis that nonhuman vertebrate models of androgen receptor–dependent structural masculinization of sexually dimorphic brain regions subserving sexually dimorphic behavior (12) also apply to humans.”
BackgroundStructural and functional consequences of glutamine tract variation in the androgen receptor
Buchanan, G. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh181 · Cited by 225
Testosterone reduces amygdala–orbitofrontal cortex coupling
van Wingen, G. A., Mattern, C., Verkes, R. J., Buitelaar, J. K., & Fernández, G. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.09.007 · Cited by 215
Global Sex Differences in Test Score Variability
Machin, S. J., & Tuomas Pekkarinen, Y. (2008) · Science · doi:10.1126/science.1162573 · Cited by 211
Brambilla, D. J., O'Donnell, A. B., Matsumoto, A. M., & McKinlay, J. B. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02976.x · Cited by 207
Witte, A. V., Savli, M., Holik, A., Kasper, S. F., & Lanzenberger, R. R. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.09.046 · Cited by 158
Androgen Binding and Metabolism in the Cerebral Cortex of the Developing Rhesus Monkey*
Clark, A. S., MacLusky, N. J., & Goldman‐Rakic, P. S. (1988) · Endocrinology · doi:10.1210/endo-123-2-932 · Cited by 155
Christakou, A., Halari, R., Smith, A. B., Ifkovits, E., Brammer, M., & Rubia, K. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.06.070 · Cited by 140
Paus, T., Nawaz-Khan, I., Leonard, G. T., Perron, M., Pike, G. B., Pitiot, A., Richer, L., Susman, E. J., Veillette, S., & Pausová, Z. (2009) · Hormones and Behavior · doi:10.1016/j.yhbeh.2009.08.004 · Cited by 140
Complete Androgen Insensitivity Syndrome: Long-Term Medical, Surgical, and Psychosexual Outcome
Wisniewski, A. B., Migeon, C. J., Meyer‐Bahlburg, H. F. L., Gearhart, J. P., Berkovitz, G. D., Brown, T. R., & Money, J. (2001) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-200101000-00018 · Cited by 140
Male Gender Identity in Complete Androgen Insensitivity Syndrome
T'Sjoen, G. G., Cuypere, G. D., Monstrey, S., Hoebeke, P. B., Freedman, F. K., Appari, M., Holterhus, P., Borsel, J. V., & Cools, M. (2010) · Archives of Sexual Behavior · doi:10.1007/s10508-010-9624-1 · Cited by 92
Imperato‐McGlnley, J., Plchardo, M., Gautier, T., Voyer, D., & Bryden, M. P. (1991) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1991.tb00303.x · Cited by 89
Factors that influence vocabulary development in two‐year‐old children
Stokes, S. F., & Klee, T. M. (2008) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2008.01991.x · Cited by 87
Albertelli, M. A., Scheller, A., Brogley, M. A., & Robins, D. M. (2006) · Molecular Endocrinology · doi:10.1210/me.2006-0021 · Cited by 82
Early androgen influences on human neural and behavioural development
Hines, M. (2008) · Early Human Development · doi:10.1016/j.earlhumdev.2008.09.006 · Cited by 75
The Role of the CAG Repeat Androgen Receptor Polymorphism in Andrology
Zitzmann, M. (2008) · Frontiers of hormone research · doi:10.1159/000175843 · Cited by 74
Sex steroid–related candidate genes in psychiatric disorders
Westberg, L., & Eriksson, E. (2008) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0830 · Cited by 72
Garagorri, J. M., Rodrı́guez, G., Elboj, A. L., Olivares, J. L., Lario-Muñoz, Á., & Orden, I. (2007) · European Journal of Pediatrics · doi:10.1007/s00431-007-0565-1 · Cited by 58
Androgen receptor gene (CAG)n polymorphism in patients with polycystic ovary syndrome
Ferk, P., Perme, M. P., Teran, N., & Geršak, K. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2007.07.1291 · Cited by 39
Nieuwerburgh, F. V., Stoop, D., Cabri, P., Dhont, M. A., Deforce, D. L. D., & Sutter, P. D. (2008) · Gynecological Endocrinology · doi:10.1080/09513590802342841 · Cited by 39
Garcés, C., de Oya, I., López-Simón, L., Cano, B., Schoppen, S., Gil, A., & de Oya, M. (2008) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2008.01.003 · Cited by 15
Male Gender Identity in Complete Androgen Insensitivity Syndrome.
T'Sjoen, G. G., Cuypere, G. D., Monstrey, S., Hoebeke, P. B., Freedman, F. K., Borsel, J. V., & Cools, M. (2010) · The Endocrine Society's 92nd Annual Meeting, June 19–22, 2010 - San Diego · doi:10.1210/endo-meetings.2010.part2.p9.p2-434 · Cited by 6
Research works printed but not linked: 2
- America's Children: Key National Indicators of Well-Being (US Government Printing Office, Washington, DC, 2009).
- Aristotle History of Animals trans Cresswell R (Henry G Bohn, London, 1862).
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Metadata
- Authors
- Raznahan, A., Lee, Y., Stidd, R., Long, R., Greenstein, D., Clasen, L., Addington, A., Gogtay, N., Rapoport, J. L., & Giedd, J. N.
- Affiliations
- King's College London (GB)
- National Institute of Mental Health (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-09-14
- Volume
- 107
- Issue
- 39
- Pages
- 16988-16993
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2947865
- OpenAlex
- W2097394514
- Cited by
- 278
- References
- 55
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 9 · 2023: 17 · 2022: 14 · 2021: 14 · 2020: 22 · 2019: 16 · 2018: 16 · 2017: 26 · 2016: 23 · 2015: 20 · 2014: 20 · 2013: 21 · 2012: 23
- FWCI
- 8.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- sex differences, androgen signaling, androgen receptor gene, cortical maturation, adolescence, cortical development, sex steroids, masculinization, sex differences in cognition, neuroendocrine development
- MeSH terms
- Adolescent, Adolescent Behavior, Androgens, Animals, Brain Mapping, Cerebral Cortex, Female, Humans, Male, Receptors, Androgen, Sex Characteristics, Sex Factors, Genetic Variation, Signal Transduction, Adolescent Development
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