Gender Dysphoria: A Review Investigating the Relationship Between Genetic Influences and Brain Development

Abstract

Gender dysphoria (GD) is a facet of modern human biology which is believed to be derived from the sexual differentiation of the brain. GD "involves a conflict between a person's physical or assigned gender and the gender with which he/she/they identify", as defined in the DSM-5. Individuals report feeling uncomfortable and faced with prejudice from those around them, affecting their mental health. Elucidating the relationship between genetic influences on gonadal and brain development could give an insight into understanding this clinical condition. To explore this issue, a review of the literature database was carried out. Evidence suggests that abnormal biological processes, including mutations in certain genes, can lead to abnormal gonadal development, causing some fetuses to present with indifferent gonads and to be reassigned at birth to the default female sex. This disparity in genetic influences relates to an increased likelihood of a diagnosis of GD. An investigation into complete androgen insensitivity syndrome, involving androgen receptor (AR) gene mutation, suggests that such individuals also experience GD. It is known that the brains of males and females are different. Evidence further suggests that brain anatomy and neuronal signaling pathways are more closely aligned with a person's perceived gender identity. Individuals who present with discordant gonadal and brain developments experience psychological challenges that may contribute to a state of unease or generalized dissatisfaction with their biological sex. These point to a possible biological and genetic underpinning of GD as stemming from a discordance between gonadal and brain development. However, not enough evidence has associated these differences with GD. Further research is required to elucidate the true mechanisms and possible inheritance pattern of GD for a better education and greater understanding by clinicians and the general public on perceptions regarding GD.

Keywords: brain development; gender; gender dysphoria; gonadal development; sex.

Figure 1

Influence of the SRY gene on indifferent gonads. Influence of the SRY gene on indifferent gonads. A summary figure highlighting the importance of the SRY gene, whereby its presence dictates the outcome of differentiation of the gonads. In individuals who have this gene, normally located on the Y chromosome, testes development will occur. In the gene’s absence, ovaries will form.

Figure 2

Sexual differentiation of the gonads following activation of SRY gene on tissues. A summary of the hormones produced, and which tissue develop following their effect on the sex organs.