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Sexual Differentiation of the Human Brain in Relation to Gender-Identity, Sexual Orientation, and Neuropsychiatric Disorders

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Neuroscience in the 21st Century

Abstract

Gender identity (an individual’s perception of being male or female) and sexual orientation (heterosexuality, homosexuality, or bisexuality) are programmed into our brain during early development. During the intrauterine period in the second half of pregnancy, a testosterone surge masculinizes the fetal male brain. If such a testosterone surge does not occur, this will result in a feminine brain. As sexual differentiation of the brain takes place at a much later stage in development than sexual differentiation of the genitals, these two processes can be influenced independently of each other and can result in gender dysphoria. Nature produces a great variability for all aspects of sexual differentiation of the brain. Mechanisms involved in sexual differentiation of the brain include hormones, genetics, epigenetics, endocrine disruptors, immune response, and self-organization. Furthermore, structural and functional differences in the hypothalamus relating to gender dysphoria and sexual orientation are described in this review. All the genetic, postmortem, and in vivo scanning observations support the neurobiological theory about the origin of gender dysphoria, i.e., it is the sizes of brain structures, the neuron numbers, the molecular composition, functions, and connectivity of brain structures that determine our gender identity or sexual orientation. There is no evidence that one’s postnatal social environment plays a crucial role in the development of gender identity or sexual orientation.

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Abbreviations

AR :

Androgen receptor

BSTc :

Central nucleus of the human bed nucleus of the stria terminalis

CAH :

Congenital adrenal hyperplasia

CAIS :

Complete androgen insensitivity syndrome

DES :

Diethylstilbestrol

ER :

Estrogen receptor

FtM :

Female-to-male transsexual person

INAH :

Interstitial nucleus of the anterior hypothalamus

InM :

Intermediate nucleus

MtF :

Male-to-female transsexual person

PTSD :

Posttraumatic stress disorder

SCN :

Suprachiasmatic nucleus

SDN-POA :

Sexually dimorphic nucleus of the preoptic area = intermediate nucleus

SON :

Supraoptic nucleus

NA :

Noradrenaline

GR :

Glucocorticoid receptor

MR :

Mineralocorticoid receptor

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Authors and Affiliations

  1. Netherlands Institute for Neuroscience, Amsterdam, The Netherlands

    Dick Swaab & Samantha E. C. Wolff

  2. Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Ai-Min Bao

  3. NHC and CAMS key laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, China

    Ai-Min Bao

Authors
  1. Dick Swaab
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  2. Samantha E. C. Wolff
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  3. Ai-Min Bao
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Corresponding author

Correspondence to Dick Swaab .

Editor information

Editors and Affiliations

  1. Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY, USA

    Donald W. Pfaff

  2. National Institute on Drug Abuse, Rockville, MD, USA

    Nora D. Volkow

  3. Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA

    John L. Rubenstein

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Swaab, D., Wolff, S.E.C., Bao, AM. (2022). Sexual Differentiation of the Human Brain in Relation to Gender-Identity, Sexual Orientation, and Neuropsychiatric Disorders. In: Pfaff, D.W., Volkow, N.D., Rubenstein, J.L. (eds) Neuroscience in the 21st Century. Springer, Cham. https://doi.org/10.1007/978-3-030-88832-9_115

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