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Neurobiology of Pediatric Gender Identity

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Pediatric Gender Identity

Abstract

Our understanding of the neurobiological basis of gender diversity is limited. Even though more and more neuroimaging studies in adults hint towards sex-atypical and less pronounced sexual differentiation, the picture is far from clear and relatively little is known about the neurobiological correlates of gender incongruence in childhood and youth. In addition, recent studies in adults challenge atypical sexual differentiation of the brain as a sole neurobiological explanation of the condition, also suggesting alterations in brain regions processing self- and body-awareness. Furthermore, the interplay between neurobiological and psychosocial factors in the development of diverse gender identities is poorly understood. In this chapter, we review the literature investigating mechanisms that may underlie gender diversity from a neurobiological perspective. In the first section, we focus on genetic factors that may contribute to gender diverse behaviour and gender identity development. Based on heritability studies, a hypothesis is formulated that there is not one single gene that accounts for the development of gender identity, but many genes are asserted to contribute in addition to other factors that are non-genetic. Next, principles of the prominent sexual differentiation hypothesis of gender incongruence will be discussed. We will summarize the evidence for sex-atypical differentiation of brain function and structure among transgender and gender diverse youth. Moreover, findings with regard to the effects of gender-affirming hormonal treatment on the brain will be presented. We will close the chapter with future directions for research into the neurobiology of gender diversity.

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References

  1. World Health Organization. International classification of diseases. 11th ed. Geneva: Author; 2018.

    Google Scholar 

  2. Heylens G, De Cuypere G, Zucker KJ, Schelfaut C, Elaut E, Vanden Bossche H, De Baere E, T’Sjoen G. Gender identity disorder in twins: a review of the case report literature. J Sex Med. 2012;9:751–7.

    Article  PubMed  Google Scholar 

  3. Fernández R, Esteva I, Gómez-Gil E, Rumbo T, Almaraz MC, Roda E, Haro-Mora J-J, Guillamón A, Pásaro E. The (CA)n polymorphism of ERβ gene is associated with FtM transsexualism. J Sex Med. 2014;11:720–8.

    Article  CAS  PubMed  Google Scholar 

  4. Ujike H, Otani K, Nakatsuka M, et al. Association study of gender identity disorder and sex hormone-related genes. Prog Neuro-Psychopharmacol Biol Psychiatry. 2009;33:1241–4.

    Article  CAS  Google Scholar 

  5. Hare L, Bernard P, Sánchez FJ, Baird PN, Vilain E, Kennedy T, Harley VR. Androgen receptor repeat length polymorphism associated with male-to-female transsexualism. Biol Psychiatry. 2009;65:93–6.

    Article  CAS  PubMed  Google Scholar 

  6. Fernández R, Esteva I, Gómez-Gil E, Rumbo T, Almaraz MC, Roda E, Haro-Mora J-J, Guillamón A, Pásaro E. Association study of ERβ, AR, and CYP19A1 genes and MtF transsexualism. J Sex Med. 2014;11:2986–94.

    Article  CAS  PubMed  Google Scholar 

  7. Henningsson S, Westberg L, Nilsson S, et al. Sex steroid-related genes and male-to-female transsexualism. Psychoneuroendocrinology. 2005;30:657–64.

    Article  CAS  PubMed  Google Scholar 

  8. Fernández R, Guillamon A, Cortés-Cortés J, Gómez-Gil E, Jácome A, Esteva I, Almaraz M, Mora M, Aranda G, Pásaro E. Molecular basis of gender dysphoria: androgen and estrogen receptor interaction. Psychoneuroendocrinology. 2018;98:161–7.

    Article  CAS  PubMed  Google Scholar 

  9. Polderman TJC, Kreukels BPC, Irwig MS, et al. The biological contributions to gender identity and gender diversity: bringing data to the table. Behav Genet. 2018;48:95–108.

    Article  PubMed  Google Scholar 

  10. Iervolino AC, Hines M, Golombok SE, Rust J, Plomin R. Genetic and environmental influences on sex-typed behavior during the preschool years. Child Dev. 2005;76:826–40.

    Article  PubMed  Google Scholar 

  11. Knafo A, Iervolino AC, Plomin R. Masculine girls and feminine boys: genetic and environmental contributions to atypical gender development in early childhood. J Pers Soc Psychol. 2005;88:400–12.

    Article  PubMed  Google Scholar 

  12. van Beijsterveldt CEM, Hudziak JJ, Boomsma DI. Genetic and environmental influences on cross-gender behavior and relation to behavior problems: a study of Dutch twins at ages 7 and 10 years. Arch Sex Behav. 2006;35:647–58.

    Article  PubMed  Google Scholar 

  13. Coolidge FL, Thede LL, Young SE. The heritability of gender identity disorder in a child and adolescent twin sample. Behav Genet. 2002;32:251–7.

    Article  PubMed  Google Scholar 

  14. Association AP. Diagnostic and statistical manual of mental disorders. 4th ed., text rev. Washington, DC: Author; 2000.

    Google Scholar 

  15. Sasaki S, Ozaki K, Yamagata S, Takahashi Y, Shikishima C, Kornacki T, Nonaka K, Ando J. Genetic and environmental influences on traits of gender identity disorder: a study of Japanese twins across developmental stages. Arch Sex Behav. 2016;45:1681–95.

    Article  PubMed  Google Scholar 

  16. Association AP. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Publishing; 2013.

    Book  Google Scholar 

  17. Phoenix CH, Goy RW, Gerall AA, Young WC. Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology. 1959;65:369–82.

    Article  CAS  PubMed  Google Scholar 

  18. Kreukels BPC, Guillamon A. Neuroimaging studies in people with gender incongruence. Int Rev Psychiatry. 2016;28:120–8.

    Article  PubMed  Google Scholar 

  19. Bakker J. Sex differentiation: organizing effects of sex hormones. Gend Dysphoria Disord Sex Dev. 2014; https://doi.org/10.1007/978-1-4614-7441-8.

  20. Hines M. Prenatal endocrine influences on sexual orientation and on sexually differentiated childhood behavior. Front Neuroendocrinol. 2011;32:170–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. de Vries ALC, Doreleijers TAH, Cohen-Kettenis PT. Disorders of sex development and gender identity outcome in adolescence and adulthood: understanding gender identity development and its clinical implications. Pediatr Endocrinol Rev. 2007;4:343–51.

    PubMed  Google Scholar 

  22. Jordan-Young RM. Hormones, context, and ‘brain gender’: a review of evidence from congenital adrenal hyperplasia. Soc Sci Med. 2012;74:1738–44.

    Article  PubMed  Google Scholar 

  23. Bakker J. The sexual differentiation of the human brain: role of sex hormones versus sex chromosomes. Curr Top Behav Neurosci. 2019; https://doi.org/10.1007/7854_2018_70.

  24. Zhou J-NN, Hofman MA, Gooren LJG, Swaab DF. A sex difference in the human brain and its relation to transsexuality. Nature. 1995;378:68–70.

    Article  CAS  PubMed  Google Scholar 

  25. Kruijver FPM, Zhou JN, Pool CW, Hofman MA, Gooren LJ, Swaab DF. Male-to-female transsexuals have female neuron numbers in a limbic nucleus. J Clin Endocrinol Metab. 2000;85:2034–41.

    Article  CAS  PubMed  Google Scholar 

  26. Garcia-Falgueras A, Swaab DF. A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity. Brain. 2008;131:3132–46.

    Article  PubMed  Google Scholar 

  27. Taziaux M, Swaab DF, Bakker J. Sex differences in the neurokinin B system in the human infundibular nucleus. J Clin Endocrinol Metab. 2012;97:E2210–20.

    Article  CAS  PubMed  Google Scholar 

  28. Dörner G. Neuroendocrine response to estrogen and brain differentiation in heterosexuals, homosexuals, and transsexuals. Arch Sex Behav. 1988;17:57–75.

    Article  PubMed  Google Scholar 

  29. Swaab DF, Hofman MA. Sexual differentiation of the human hypothalamus in relation to gender and sexual orientation. Trends Neurosci. 1995;18:264–70.

    Article  CAS  PubMed  Google Scholar 

  30. Swaab DF, Garcia-Falgueras A. Sexual differentiation of the human brain in relation to gender identity and sexual orientation. Funct Neurol. 2009;24:17–28.

    PubMed  Google Scholar 

  31. Steensma TD, Kreukels BPC, de Vries ALC, Cohen-Kettenis PT. Gender identity development in adolescence. Horm Behav. 2013;64:288–97.

    Article  PubMed  Google Scholar 

  32. Sisk C, Doncarlos L. Puberty and brain sexual differentiation: getting organized. 2011. https://www.fasebj.org/doi/abs/10.1096/fasebj.25.1_supplement.187.4

  33. McCarthy MM, Arnold AP. Reframing sexual differentiation of the brain. Nat Neurosci. 2011;14:677–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ahmed EI, Zehr JL, Schulz KM, Lorenz BH, DonCarlos LL, Sisk CL. Pubertal hormones modulate the addition of new cells to sexually dimorphic brain regions. Nat Neurosci. 2008;11:995–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Schulz KM, Sisk CL. The organizing actions of adolescent gonadal steroid hormones on brain and behavioral development. Neurosci Biobehav Rev. 2016;70:148–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Vijayakumar N, Allen NB, Youssef G, Dennison M, Yücel M, Simmons JG, Whittle S. Brain development during adolescence: a mixed-longitudinal investigation of cortical thickness, surface area, and volume. Hum Brain Mapp. 2016;37:2027–38.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Wierenga LM, Bos MGN, Schreuders E, Vd Kamp F, Peper JS, Tamnes CK, Crone EA. Unraveling age, puberty and testosterone effects on subcortical brain development across adolescence. Psychoneuroendocrinology. 2018;91:105–14.

    Article  CAS  PubMed  Google Scholar 

  38. Giedd JN, Raznahan A, Mills K, Lenroot RK. Review: magnetic resonance imaging of male/female differences in human adolescent brain anatomy. Biol Sex Differ. 2012;3:19.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Pfeifer JH, Peake SJ. Self-development: integrating cognitive, socioemotional, and neuroimaging perspectives. Dev Cogn Neurosci. 2012;2:55–69.

    Article  PubMed  Google Scholar 

  40. Mills KL, Lalonde F, Clasen LS, Giedd JN, Blakemore SJ. Developmental changes in the structure of the social brain in late childhood and adolescence. Soc Cogn Affect Neurosci. 2014;9:123–31.

    Article  PubMed  Google Scholar 

  41. Blakemore S-J. The social brain in adolescence. Nat Rev Neurosci. 2008;9:267–77.

    Article  CAS  PubMed  Google Scholar 

  42. Choudhury S, Blakemore S-J, Charman T. Social cognitive development during adolescence. Soc Cogn Affect Neurosci. 2006;1:165–74.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Selman RL. The growth of interpersonal understanding: developmental and clinical analyses. New York: Academic Press; 1980.

    Google Scholar 

  44. Harter S. The construction of the self: a developmental perspective. New York: Guilford Press; 1999.

    Google Scholar 

  45. Steensma TD, McGuire JK, Kreukels BPC, Beekman AJ, Cohen-Kettenis PT. Factors associated with desistence and persistence of childhood gender dysphoria: a quantitative follow-up study. J Am Acad Child Adolesc Psychiatry. 2013;52:582–90.

    Article  PubMed  Google Scholar 

  46. Steensma TD, Biemond R, de Boer F, Cohen-Kettenis PT. Desisting and persisting gender dysphoria after childhood: a qualitative follow-up study. Clin Child Psychol Psychiatry. 2011;16:499–516.

    Article  PubMed  Google Scholar 

  47. de Graaf NM, Cohen-Kettenis PT, Carmichael P, de Vries ALC, Dhondt K, Laridaen J, Pauli D, Ball J, Steensma TD. Psychological functioning in adolescents referred to specialist gender identity clinics across Europe: a clinical comparison study between four clinics. Eur Child Adolesc Psychiatry. 2018;27:909–19.

    Article  PubMed  Google Scholar 

  48. Kaltiala-Heino R, Sumia M, Työläjärvi M, Lindberg N. Two years of gender identity service for minors: overrepresentation of natal girls with severe problems in adolescent development. Child Adolesc Psychiatry Ment Health. 2015;9:9.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Olson J, Schrager SM, Belzer M, Simons LK, Clark LF. Baseline physiologic and psychosocial characteristics of transgender youth seeking care for gender dysphoria. J Adolesc Health. 2015;57:374–80.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Temple Newhook J, Pyne J, Winters K, Feder S, Holmes C, Tosh J, Sinnott M-L, Jamieson A, Pickett S. A critical commentary on follow-up studies and ‘desistance’ theories about transgender and gender-nonconforming children. Int J Transgend. 2018;19:212–24.

    Article  Google Scholar 

  51. Zucker KJ. The myth of persistence: response to ‘a critical commentary on follow-up studies and ‘desistance’ theories about transgender and gender non-conforming children’ by Temple Newhook et al. (2018). Int J Transgend. 2018;19:231–45.

    Article  Google Scholar 

  52. Steensma TD, Cohen-Kettenis PT. A critical commentary on ‘a critical commentary on follow-up studies and ‘desistence’ theories about transgender and gender non-conforming children’. Int J Transgend. 2018;19:225–30.

    Article  Google Scholar 

  53. Kreukels BPC, Cohen-Kettenis PT. Puberty suppression in gender identity disorder: the Amsterdam experience. Nat Rev Endocrinol. 2011;7:466–72.

    Article  CAS  PubMed  Google Scholar 

  54. Smith KP, Madison CM, Milne NM. Gonadal suppressive and cross-sex hormone therapy for gender dysphoria in adolescents and adults. Pharmacotherapy. 2014;34:1282–97.

    Article  CAS  PubMed  Google Scholar 

  55. Dhejne C, Van Vlerken R, Heylens G, Arcelus J. Mental health and gender dysphoria: a review of the literature. Int Rev Psychiatry. 2016;28:44–57.

    Article  PubMed  Google Scholar 

  56. Gómez-Gil E, Zubiaurre-Elorza L, Esteva I, Guillamon A, Godás T, Cruz Almaraz M, Halperin I, Salamero M. Hormone-treated transsexuals report less social distress, anxiety and depression. Psychoneuroendocrinology. 2012;37:662–70.

    Article  CAS  PubMed  Google Scholar 

  57. Rametti G, Carrillo B, Gomez-Gil E, Junque C, Segovia S, Gomez A, Guillamon A. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. J Psychiatr Res. 2011;45:199–204.

    Article  PubMed  Google Scholar 

  58. Rametti G, Carrillo B, Gómez-Gil E, Junque C, Zubiarre-Elorza L, Segovia S, Gomez Á, Guillamon A. The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study. J Psychiatr Res. 2011;45:949–54.

    Article  PubMed  Google Scholar 

  59. Hahn A, Kranz GS, Küblböck M, et al. Structural connectivity networks of transgender people. Cereb Cortex. 2015;25:3527–34.

    Article  PubMed  Google Scholar 

  60. Zubiaurre-Elorza L, Junque C, Gómez-Gil E, Guillamon A. Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals. J Sex Med. 2014;11:1248–61.

    Google Scholar 

  61. Zubiaurre-Elorza L, Junque C, Gómez-Gil E, Segovia S, Carrillo B, Rametti G, Guillamon A. Cortical thickness in untreated transsexuals. Cereb Cortex. 2013;23:2855–62.

    Article  PubMed  Google Scholar 

  62. Simon L, Kozák LR, Simon V, Czobor P, Unoka Z, Szabó A, Csukly G. Regional grey matter structure differences between transsexuals and healthy controls-a voxel based morphometry study. PLoS One. 2013;8:e83947.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Luders E, Sánchez FJ, Gaser C, Toga AW, Narr KL, Hamilton LS, Vilain E. Regional gray matter variation in male-to-female transsexualism. NeuroImage. 2009;46:904–7.

    Article  PubMed  Google Scholar 

  64. Savic I, Arver S. Sex dimorphism of the brain in male-to-female transsexuals. Cereb Cortex. 2011;21:2525–33.

    Article  PubMed  Google Scholar 

  65. Spizzirri G, Duran FLS, Chaim-Avancini TM, et al. Grey and white matter volumes either in treatment-naïve or hormone-treated transgender women: a voxel-based morphometry study. Sci Rep. 2018;8:736.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kim T-H, Kim S-K, Jeong G-W. Cerebral gray matter volume variation in female-to-male transsexuals: a voxel-based morphometric study. Neuroreport. 2015;26:1119–25.

    Article  PubMed  Google Scholar 

  67. Hoekzema E, Schagen SEE, Kreukels BPC, Veltman DJ, Cohen-Kettenis PT, Delemarre-van de Waal H, Bakker J. Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain. Psychoneuroendocrinology. 2015;55:59–71.

    Article  PubMed  Google Scholar 

  68. Manzouri A, Kosidou K, Savic I. Anatomical and functional findings in female-to-male transsexuals: testing a new hypothesis. Cereb Cortex. 2015;27(2):998–1010.

    Google Scholar 

  69. Soleman RS, Schagen SEE, Veltman DJ, Kreukels BPC, Cohen-Kettenis PT, Lambalk CB, Wouters F, Delemarre-van de Waal HA. Sex differences in verbal fluency during adolescence: a functional magnetic resonance imaging study in gender dysphoric and control boys and girls. J Sex Med. 2013;10:1969–77.

    Article  PubMed  Google Scholar 

  70. Bolla KI, Lindgren KN, Bonaccorsy C, Bleecker ML. Predictors of verbal fluency (FAS) in the healthy elderly. J Clin Psychol. 1990;46:623–8.

    Article  CAS  PubMed  Google Scholar 

  71. Zarnhofer S, Braunstein V, Ebner F, Koschutnig K, Neuper C, Reishofer G, Ischebeck A. The influence of verbalization on the pattern of cortical activation during mental arithmetic. Behav Brain Funct. 2012;8:13.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Burke SM, Cohen-Kettenis PT, Veltman DJ, Klink DT, Bakker J. Hypothalamic response to the chemo-signal androstadienone in gender dysphoric children and adolescents. Front Endocrinol (Lausanne). 2014;5:60.

    Article  Google Scholar 

  73. Berglund H, Lindström P, Dhejne-Helmy C, Savic I. Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids. Cereb Cortex. 2008;18:1900–8.

    Article  CAS  PubMed  Google Scholar 

  74. Nota NM, Kreukels BPC, den Heijer M, Veltman DJ, Cohen-Kettenis PT, Burke SM, Bakker J. Brain functional connectivity patterns in children and adolescents with gender dysphoria: sex-atypical or not? Psychoneuroendocrinology. 2017;86:187–95.

    Article  PubMed  Google Scholar 

  75. Cole MW, Bassett DS, Power JD, Braver TS, Petersen SE. Intrinsic and task-evoked network architectures of the human brain. Neuron. 2014;83:238–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Fair DA, Cohen AL, Dosenbach NUF, Church JA, Miezin FM, Barch DM, Raichle ME, Petersen SE, Schlaggar BL. The maturing architecture of the brain’s default network. Proc Natl Acad Sci U S A. 2008;105:4028–32.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Whitfield-Gabrieli S, Moran JM, Nieto-Castañón A, Triantafyllou C, Saxe R, Gabrieli JDE. Associations and dissociations between default and self-reference networks in the human brain. NeuroImage. 2011;55:225–32.

    Article  PubMed  Google Scholar 

  78. Northoff G, Bermpohl F. Cortical midline structures and the self. Trends Cogn Sci. 2004;8:102–7.

    Article  PubMed  Google Scholar 

  79. Feusner JD, Dervisic J, Kosidou K, Dhejne C, Bookheimer S, Savic I. Female-to-male transsexual individuals demonstrate different own body identification. Arch Sex Behav. 2016;45:525–36.

    Article  PubMed  Google Scholar 

  80. Feusner JD, Lidström A, Moody TD, Dhejne C, Bookheimer SY, Savic I. Intrinsic network connectivity and own body perception in gender dysphoria. Brain Imaging Behav. 2016;11:964. https://doi.org/10.1007/s11682-016-9578-6.

    Article  Google Scholar 

  81. Burke SM, Manzouri AH, Dhejne C, Bergström K, Arver S, Feusner JD, Savic-Berglund I. Testosterone effects on the brain in transgender men. Cereb Cortex. 2018;28:1582–96.

    Article  PubMed  Google Scholar 

  82. Hjelmervik H, Hausmann M, Osnes B, Westerhausen R, Specht K. Resting states are resting traits–an FMRI study of sex differences and menstrual cycle effects in resting state cognitive control networks. PLoS One. 2014;9:e103492.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Scheinost D, Finn ES, Tokoglu F, Shen X, Papademetris X, Hampson M, Constable RT. Sex differences in normal age trajectories of functional brain networks. Hum Brain Mapp. 2015;36:1524–35.

    Article  PubMed  Google Scholar 

  84. Berenbaum SA, Beltz AM. Sexual differentiation of human behavior: effects of prenatal and pubertal organizational hormones. Front Neuroendocrinol. 2011;32:183–200.

    Article  CAS  PubMed  Google Scholar 

  85. Staphorsius AS, Kreukels BPC, Cohen-Kettenis PT, Veltman DJ, Burke SM, Schagen SEE, Wouters FM, Delemarre-van de Waal HA, Bakker J. Puberty suppression and executive functioning: an fMRI-study in adolescents with gender dysphoria. Psychoneuroendocrinology. 2015;56:190–9.

    Article  PubMed  Google Scholar 

  86. Wiepjes CM, Nota NM, de Blok CJM, et al. The Amsterdam cohort of gender dysphoria study (1972–2015): trends in prevalence, treatment, and regrets. J Sex Med. 2018;15:582–90.

    Article  PubMed  Google Scholar 

  87. Wallien MSC, Cohen-Kettenis PT. Psychosexual outcome of gender-dysphoric children. J Am Acad Child Adolesc Psychiatry. 2008;47:1413–23.

    Article  PubMed  Google Scholar 

  88. Ristori J, Steensma TD. Gender dysphoria in childhood. Int Rev Psychiatry. 2016;28:13–20.

    Article  PubMed  Google Scholar 

  89. Juraska JM, Willing J. Pubertal onset as a critical transition for neural development and cognition. Brain Res. 2017;1654:87–94.

    Article  CAS  PubMed  Google Scholar 

  90. Wojniusz S, Vögele C, Ropstad E, et al. Prepubertal gonadotropin-releasing hormone analog leads to exaggerated behavioral and emotional sex differences in sheep. Horm Behav. 2011;59:22–7.

    Article  CAS  PubMed  Google Scholar 

  91. Schneider MA, Spritzer PM, Soll BMB, et al. Brain maturation, cognition and voice pattern in a gender dysphoria case under pubertal suppression. Front Hum Neurosci. 2017;11:528.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Hulshoff Pol EH, Cohen-Kettenis PT, Van Haren NEM, Peper JS, Brans RGH, Cahn W, Schnack HG, Gooren LJG, Kahn RS. Changing your sex changes your brain: influences of testosterone and estrogen on adult human brain structure. Eur J Endocrinol. 2006;155:S107–14.

    Article  CAS  Google Scholar 

  93. Burke SM, Kreukels BPC, Cohen-Kettenis PT, Veltman DJ, Klink DT, Bakker J. Male-typical visuospatial functioning in gynephilic girls with gender dysphoria — organizational and activational effects of testosterone. J Psychiatry Neurosci. 2016;41:395–404.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Linn MC, Petersen AC. Emergence and characterization of sex differences in spatial ability: a meta-analysis. Child Dev. 1985;56:1479–98.

    Article  CAS  PubMed  Google Scholar 

  95. Voyer D, Voyer S, Bryden MP. Magnitude of sex differences in spatial abilities: a meta-analysis and consideration of critical variables. Psychol Bull. 1995;117:250–70.

    Article  CAS  PubMed  Google Scholar 

  96. Jordan K, Wüstenberg T, Heinze HJ, Peters M, Jäncke L. Women and men exhibit different cortical activation patterns during mental rotation tasks. Neuropsychologia. 2002;40:2397–408.

    Article  PubMed  Google Scholar 

  97. Hugdahl K, Thomsen T, Ersland L. Sex differences in visuo-spatial processing: an fMRI study of mental rotation. Neuropsychologia. 2006;44:1575–83.

    Article  PubMed  Google Scholar 

  98. Sommer IEC, Cohen-Kettenis PT, van Raalten T, Vd Veer AJ, Ramsey LE, Gooren LJG, Kahn RS, Ramsey NF. Effects of cross-sex hormones on cerebral activation during language and mental rotation: an fMRI study in transsexuals. Eur Neuropsychopharmacol. 2008;18:215–21.

    Article  CAS  PubMed  Google Scholar 

  99. Burke SM, Menks WM, Cohen-Kettenis PT, Klink DT, Bakker J. Click-evoked otoacoustic emissions in children and adolescents with gender identity disorder. Arch Sex Behav. 2014;43:1515–23.

    Article  PubMed  Google Scholar 

  100. Burke SM, Manzouri AH, Savic I. Structural connections in the brain in relation to gender identity and sexual orientation. Sci Rep. 2017;7:17954.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Manzouri A, Savic I. Possible neurobiological underpinnings of homosexuality and gender dysphoria. Cereb Cortex. 2019;29(5):2084–101.

    Article  CAS  PubMed  Google Scholar 

  102. Cohen-Kettenis PT, Schagen SEE, Steensma TD, de Vries ALC, Delemarre-van de Waal HA. Puberty suppression in a gender-dysphoric adolescent: a 22-year follow-up. Arch Sex Behav. 2011;40:843–7.

    Article  PubMed  PubMed Central  Google Scholar 

  103. de Vries ALC, McGuire JK, Steensma TD, Wagenaar ECF, Doreleijers T a H, Cohen-Kettenis PT. Young adult psychological outcome after puberty suppression and gender reassignment. Pediatrics. 2014;134:696–704.

    Article  PubMed  Google Scholar 

  104. Mul D, Versluis-den Bieman H, Slijper F, Oostdijk W, Waelkens J, Drop S. Psychological assessments before and after treatment of early puberty in adopted children. Acta Paediatr. 2007;90:965–71.

    Article  Google Scholar 

  105. Hayes P. Commentary: cognitive, emotional, and psychosocial functioning of girls treated with pharmacological puberty blockage for idiopathic central precocious puberty. Front Psychol. 2017;8:44.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Stenbæk DS, Fisher PM, Budtz-Jørgensen E, Pinborg A, Hjordt LV, Jensen PS, Knudsen GM, Frokjaer VG. Sex hormone manipulation slows reaction time and increases labile mood in healthy women. Psychoneuroendocrinology. 2016;68:39–46.

    Article  CAS  PubMed  Google Scholar 

  107. Wojniusz S, Callens N, Sütterlin S, et al. Cognitive, emotional, and psychosocial functioning of girls treated with pharmacological puberty blockage for idiopathic central precocious puberty. Front Psychol. 2016;7:1053.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Macoveanu J, Henningsson S, Pinborg A, Jensen P, Knudsen GM, Frokjaer VG, Siebner HR. Sex-steroid hormone manipulation reduces brain response to reward. Neuropsychopharmacology. 2016;41:1057–65.

    Article  CAS  PubMed  Google Scholar 

  109. Hough D, Bellingham M, Haraldsen IR, McLaughlin M, Robinson JE, Solbakk AK, Evans NP. A reduction in long-term spatial memory persists after discontinuation of peripubertal GnRH agonist treatment in sheep. Psychoneuroendocrinology. 2017;77:1–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Hough D, Bellingham M, Haraldsen IRH, McLaughlin M, Rennie M, Robinson JE, Solbakk AK, Evans NP. Spatial memory is impaired by peripubertal GnRH agonist treatment and testosterone replacement in sheep. Psychoneuroendocrinology. 2017;75:173–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Nuruddin S, Bruchhage M, Ropstad E, Krogenæs A, Evans NP, Robinson JE, Endestad T, Westlye LT, Madison C, Haraldsen IRH. Effects of peripubertal gonadotropin-releasing hormone agonist on brain development in sheep–a magnetic resonance imaging study. Psychoneuroendocrinology. 2013;38:1994–2002.

    Article  CAS  PubMed  Google Scholar 

  112. Nuruddin S, Krogenæs A, Brynildsrud OB, Verhaegen S, Evans NP, Robinson JE, Haraldsen IRH, Ropstad E. Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex biased gene expression of amygdala in sheep. Psychoneuroendocrinology. 2013;38:3115–27.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Center of Expertise on Gender Dysphoria, Department of Medical Psychology, Amsterdam University Medical Centers, Amsterdam, The Netherlands

    Baudewijntje P. C. Kreukels

  2. Brain and Development Research Centre, Department of Developmental & Educational Psychology, Institute of Psychology, Leiden University, Leiden, The Netherlands

    Sarah M. Burke

Authors
  1. Baudewijntje P. C. Kreukels
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  2. Sarah M. Burke
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Correspondence to Baudewijntje P. C. Kreukels .

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Editors and Affiliations

  1. Department of Pediatrics, Brown University, Providence, RI, USA

    Michelle Forcier

  2. Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA

    Gerrit Van Schalkwyk

  3. Division of Child & Adolescent Psychiatry, Massachusetts General Hospital, Boston, MA, USA

    Jack L. Turban

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Kreukels, B.P.C., Burke, S.M. (2020). Neurobiology of Pediatric Gender Identity. In: Forcier, M., Van Schalkwyk, G., Turban, J. (eds) Pediatric Gender Identity. Springer, Cham. https://doi.org/10.1007/978-3-030-38909-3_4

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  • DOI: https://doi.org/10.1007/978-3-030-38909-3_4

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