Abstract
Many traits of the brain and body show marked sex differences, but the distributions of their values overlap substantially between the two sexes. To investigate variations associated with biological sex, beyond binary differences, we create continuous sex scores capturing the inter-individual variability in phenotypes. In an adolescent cohort (n = 1,029; 533 females), we have generated three sex scores based on brain–body traits: ‘overall’ (48 traits), ‘pubertal’ (26 traits) and ‘non-pubertal’ (22 traits). We then conducted sex-stratified multiple linear regressions (adjusting for age) using sex scores to test associations with sex hormones, personality traits and internalizing–externalizing behaviour. Higher sex scores (that is, greater ‘femaleness’) were associated with lower testosterone in males only, as well as lower extraversion, higher internalizing and lower externalizing in both sexes. The associations with testosterone, internalizing and externalizing were driven by pubertal sex scores, underscoring the importance of adolescence in shaping within-sex individual variability.
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Data availability
The data are available upon request, addressed to T.P. (tpausresearch@gmail.com) or Z.P. (zdenka.pausova@sickkids.ca).
Code availability
The R code used to compute the sex scores is provided as a supplementary attachment.
References
Speijer, D., Lukeš, J. & Eliáš, M. Sex is a ubiquitous, ancient, and inherent attribute of eukaryotic life. Proc. Natl Acad. Sci. USA 112, 8827–8834 (2015).
Servedio, M. R. & Boughman, J. W. The role of sexual selection in local adaptation and speciation. Annu. Rev. Ecol. Evol. Syst. 48, 85–109 (2017).
Mesnick, S. & Ralls, K. Sexual dimorphism. in Encyclopedia of Marine Mammals 3rd edn (eds Würsig, B., Thewissen, J.G.M. & Kovacs, K. M.) 848–853 (Academic Press, 2018).
Sztkely, T., Reynolds, J. D. & Figuerola, J. Sexual size dimorphism in shorebirds, gulls, and alcids: the influence of sexual and natural selection. Society 54, 1404–1413 (2009).
Paus, T., Wong, A. P. Y., Syme, C. & Pausova, Z. Sex differences in the adolescent brain and body: findings from the saguenay youth study. J. Neurosci. Res. 95, 362–370 (2017).
Clayton, J. A. & Tannenbaum, C. Reporting sex, gender, or both in clinical research? JAMA 316, 1863–1864 (2016).
Schulz, K. M., Molenda-Figueira, H. A. & Sisk, C. L. Back to the future: the organizational–activational hypothesis adapted to puberty and adolescence. Horm. Behav. 55, 597–604 (2009).
Perrin, J. S. et al. Growth of white matter in the adolescent brain: role of testosterone and androgen receptor. J. Neurosci. 28, 9519–9524 (2008).
Pangelinan, M. M. et al. Puberty and testosterone shape the corticospinal tract during male adolescence. Brain Struct. Funct. 221, 1083–1094 (2016).
Nguyen, T. V. et al. Testosterone-related cortical maturation across childhood and adolescence. Cereb. Cortex 23, 1424–1432 (2013).
Agirbasli, M. et al. Sex hormones and metabolic syndrome in children and adolescents. Metabolism 58, 1256–1262 (2009).
Markova, D. et al. Age-and sex-related variations in vocal-tract morphology and voice acoustics during adolescence. Horm. Behav. 81, 84–96 (2016).
Arnold, A. P. A general theory of sexual differentiation. J. Neurosci. Res. 95, 291–300 (2017).
Verweij, K. J. H., Mosing, M. A., Ullén, F. & Madison, G. Individual differences in personality masculinity–femininity: examining the effects of genes, environment, and prenatal hormone transfer. Twin Res. Hum. Genet. 19, 87–96 (2016).
Kajonius, P. J. & Johnson, J. Sex differences in 30 facets of the five factor model of personality in the large public (N = 320,128). Pers. Individ. Dif. 129, 126–130 (2018).
McCarthy, M. M. Multifaceted origins of sex differences in the brain. Philos. Trans. R. Soc. B 371, 20150106 (2016).
Martel, M. M. Sexual selection and sex differences in the prevalence of childhood externalizing and adolescent internalizing disorders. Psychol. Bull. 139, 1221–1259 (2013).
Demmer, D. H., Hooley, M., Sheen, J., McGillivray, J. A. & Lum, J. A. G. Sex differences in the prevalence of oppositional defiant disorder during middle childhood: a meta-analysis. J. Abnorm. Child Psychol. 45, 313–325 (2017).
Eme, R. & Kavanaugh, L. Sex differences in conduct disorder. J. Clin. Child Psychol. 24, 406–426 (1995).
Altemus, M., Sarvaiya, N. & Neill Epperson, C. Sex differences in anxiety and depression clinical perspectives. Front. Neuroendocrinol. 35, 320–330 (2014).
Sudlow, C. et al. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 12, 1–10 (2015).
Boyd, A. et al. Cohort profile: the’Children of the 90s’—The index offspring of the Avon Longitudinal Study of Parents and Children. Int. J. Epidemiol. 42, 111–127 (2013).
Garavan, H. et al. Recruiting the ABCD sample: design considerations and procedures. Dev. Cogn. Neurosci. 32, 16–22 (2018).
Wong, A. P. Y. et al. Estimating volumes of the pituitary gland from T1-weighted magnetic-resonance images: effects of age, puberty, testosterone, and estradiol. Neuroimage 94, 216–221 (2014).
Lehre, A. C., Lehre, K. P., Laake, P. & Danbolt, N. C. Greater intrasex phenotype variability in males than in females is a fundamental aspect of the gender differences in humans. Dev. Psychobiol. 51, 198–206 (2009).
Wierenga, L. M. et al. Greater male than female variability in regional brain structure across the lifespan. Preprint at bioRxiv https://doi.org/10.1101/2020.02.17.952010 (2020).
Reinhold, K. & Engqvist, L. The variability is in the sex chromosomes. Evolution (N. Y.) 67, 3662–3668 (2013).
Migeon, B. R. Why females are mosaics, x-chromosome inactivation, and sex differences in disease. Gend. Med. 4, 97–105 (2007).
Van Anders, S. M., Goldey, K. L. & Kuo, P. X. The steroid/peptide theory of social bonds: integrating testosterone and peptide responses for classifying social behavioral contexts. Psychoneuroendocrinology 36, 1265–1275 (2011).
Bancroft, J. Sexual effects of androgens in women: some theoretical considerations. Fertil. Steril. 77, 55–59 (2002).
Geniole, S. N. et al. Is testosterone linked to human aggression? A meta-analytic examination of the relationship between baseline, dynamic, and manipulated testosterone on human aggression. Horm. Behav. 123, 104644 (2020).
Perel, E. & Killinger, D. W. The interconversion and aromatization of androgens by human adipose tissue. J. Steroid Biochem. 10, 623–627 (1979).
Berenbaum, S. A. & Beltz, A. M. Sexual differentiation of human behavior: effects of prenatal and pubertal organizational hormones. Front. Neuroendocrinol. 32, 183–200 (2011).
Sisk, C. L. & Zehr, J. L. Pubertal hormones organize the adolescent brain and behavior. Front. Neuroendocrinol. 26, 163–174 (2005).
Schulz, K. M. & Sisk, C. L. The organizing actions of adolescent gonadal steroid hormones on brain and behavioral development. Neurosci. Biobehav. Rev. 70, 148–158 (2016).
Alloy, L. B., Hamilton, J. L., Hamlat, E. J. & Abramson, L. Y. Pubertal development, emotion regulatory styles, and the emergence of sex differences in internalizing disorders and symptoms in adolescence. Clin. Psychol. Sci. 4, 867–881 (2016).
Van Anders, S. M., Steiger, J. & Goldey, K. L. Effects of gendered behavior on testosterone in women and men. Proc. Natl Acad. Sci. USA 112, 13805–13810 (2015).
Suderman, M. et al. Sex-associated autosomal DNA methylation differences are wide-spread and stable throughout childhood. bioRxiv 44, 118265 (2017).
Ainsworth, C. Sex redefined. Nature 518, 288–291 (2015).
Joel, D. et al. Sex beyond the genitalia: the human brain mosaic. Proc. Natl Acad. Sci. USA 112, 15468–15473 (2015).
Joel, D. et al. Analysis of human brain structure reveals that the brain “types” typical of males are also typical of females, and vice versa. Front. Hum. Neurosci. 12, 1–18 (2018).
Pausova, Z. et al. Cohort profile: the Saguenay Youth Study (SYS). Int. J. Epidemiol. 46, e19 (2017).
van Buuren, S. & Groothuis-Oudshoorn, K. mice: multivariate imputation by chained equations in R. J. Stat. Softw. 45, 1–68 (2011).
Costa Jr, P. T. & McCrae, R. R. The Revised NEO Personality Inventory (NEO-PI-R). in The SAGE Handbook of Personality Theory and Assessment, Vol. 2. Personality Measurement and Testing (eds Boyle, G. J., Matthews, G. & Saklofske, D. H.) 179–198 (Sage, 2008).
Lucas, C. P. et al. The DISC predictive scales (DPS): efficiently screening for diagnoses. J. Am. Acad. Child Adolesc. Psychiatry 40, 443–449 (2001).
Caspi, A., Houts, R. M., Belsky, D. W. & Goldman-mellor, S. J. The p factor: one general psychopathology factor in the structure of psychiatric disorders? Clin. Psychol. Sci. 2, 119–137 (2015).
Grömping, U. Relative importance for linear regression in R: the package relaimpo. J. Stat. Softw. 17, 1–27 (2006).
R Core Team. R: a language and environment for statistical computing (R Foundation for Statistical Computing, 2019).
Acknowledgements
The Canadian Institutes of Health Research (Z.P., T.P.), Heart and Stroke Foundation of Quebec (Z.P.) and the Canadian Foundation for Innovation (Z.P.) support the Saguenay Youth Study. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors acknowledge J. Shin for her statistical advice.
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D.E.V. contributed to the project conception, manuscript writing, analyses and figures. C.S. contributed to the participant recruitment and testing, analyses and manuscript editing. N.P. contributed to the analyses and manuscript editing. L.R. and Z.P. contributed to the SYS study design, participant recruitment and testing, and manuscript editing. T.P. contributed to the project conception, SYS study design, participant recruitment and testing, and manuscript writing.
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Supplementary Information
Supplementary Figs. 1–3 and Supplementary Tables 1–4.
Supplementary Software
R script used to compute sex scores.
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Vosberg, D.E., Syme, C., Parker, N. et al. Sex continuum in the brain and body during adolescence and psychological traits. Nat Hum Behav 5, 265–272 (2021). https://doi.org/10.1038/s41562-020-00968-8
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DOI: https://doi.org/10.1038/s41562-020-00968-8
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