ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Sci Rep. 2017 Dec 20;7(1):17954

[Comments on 6.1 and 6.2] Gender dysphoria (GD) is still an enigma when it comes to the biological background and pathophysiology. Many different theories have been put forward but none is yet prevailing due to a poor evidence base. Earlier anatomical studies searching for gender specific brain structures that could be associated with gender identity (GI) have indicated the presence of such loci but more modern brain imaging methods as used in the paper by Burke et al. (6.2) described here have failed to support these observations. Findings of monozygous twins who are discordant to GI disorder excludes simplistic genetic causes. Currently there is no “objective” diagnostic method available for GD and it is presently not possible to diagnose experimental animals or human infants with GD as it requires a critical component of verbal expression. Analysis of reproductive behavior in animals does not distinguish sexual orientation from GI. The importance of psychosocial factors for the expression of GD is generally agreed.

The first paper (6.1) by Polderman et al. from the International Gender Diversity Genomics Consortium defines the important concepts and reviews the evidence that GI is influenced at least in part by innate factors including genes. They hypothesize that GI is a multifactorial complex trait with a heritable polygenic component. The authors argue that increasing the awareness of the biological diversity underlying GI development is relevant to all domains of social, medical, and brain research.

Secondly, Burke et al. (6.2) used advanced neuroimaging technology (fractional anisotropy) which is a measure of brain white matter connections that have shown consistent sex differences. Transgender males and females were investigated and compared with homosexual and hetersosexual male and female cis-gender controls. Although the interpretation was complex the results suggested that brain areas involved in the processing of the perception of self and body ownership were affected in GD but not in homosexual subjects. Taken together, these two papers support a complex biological and genetic background to GI which seems to involve white matter trajectories rather than distinct brain loci. Much more is expected from the research areas discussed here.