The molecular mechanisms of sexual orientation and gender identity

Highlights

• The sexual dimorphic brain is the anatomical substrate of psychosexual development.

• Sexual orientation is defined by the target of sexual arousal.

• Gender identity refers to the inner sense of being male, female or something else.

• Sexual orientation and gender identity are the most sexually differentiated traits.

Abstract

Differences between males and females are widely represented in nature. There are gender differences in phenotypes, personality traits, behaviors and interests, cognitive performance, and proneness to specific diseases. The most marked difference in humans is represented by sexual orientation and core gender identity, the origins of which are still controversial and far from being understood. Debates continue on whether sexual behavior and gender identity are a result of biological (nature) or cultural (nurture) factors, with biology possibly playing a major role. The main goal of this review is to summarize the studies available to date on the biological factors involved in the development of both sexual orientation and gender identity. A systematic search of published evidence was performed using Medline (from January 1948 to June 2017). Review of the relevant literature was based on authors’ expertise. Indeed, different studies have documented the possible role and interaction of neuroanatomic, hormonal and genetic factors. The sexual dimorphic brain is considered the anatomical substrate of psychosexual development, on which genes and gonadal hormones may have a shaping effect. In particular, growing evidence shows that prenatal and pubertal sex hormones permanently affect human behavior. In addition, heritability studies have demonstrated a role of genetic components. However, a convincing candidate gene has not been identified. Future studies (e.i. genome wide studies) are needed to better clarify the complex interaction between genes, anatomy and hormonal influences on psychosexual development.

Introduction

Differences between the two sexes are widely represented in nature. Even among humans, males and females differ in many aspects: biological phenotypes (Luders et al., 2009, Ngun et al., 2011), personality traits (Luders et al., 2009, Ngun et al., 2011, Collazzoni et al., 2017), behaviors and interests, cognitive performance and proneness to specific diseases (Berenbaum and Beltz, 2011). In the last few decades, science has focused on understanding the origins of such differences, in particular the specific influence and shaping role of genes, hormones, environment and/or socialization (Berenbaum and Beltz, 2011). Moreover, more than 50 years of empirical research have documented the sexual differentiation of the brain quite extensively, given that the existence of behavioral sex differences implies the existence of neural sex differences. However, various considerations have led to the challenging of the idea that sexual differences in behavior may depend on sexual differences within the brain. Indeed, there are some inconsistencies in literature regarding the sexual dimorphic brain areas. In addition, it is difficult to find a linear relationship between anatomy and behavior. Furthermore, sex differences in the brain may depend on life experiences (Hines, 2011a, Juraska, 1998, Maguire et al., 2006, Ming and Song, 2005). Finally, the popular view that there is a female and a male brain, mirroring the behavioral differences in the two sexes, does not have a solid scientific foundation. On the contrary, although consistent differences have been identified - including the size of the brain and of specific brain regions, the constellation of neurons, neurotransmitter content, number of receptors, etc (Cahill, 2006, Lenroot and Giedd, 2010, McCarthy et al., 2009, Sakuma, 2009). - the male and female brain are very similar. In addition, men and women present with a great variability in behavioral and psychological differences (Berenbaum and Beltz, 2016). In general, using the term “sexual dimorphic” is correct only regarding a few brain characteristics, while most do not overlap or have a minimal overlap between the two sexes (Cosgrove et al., 2007, Joel, 2011, Juraska, 1991, Koscik et al., 2009, Koscik et al., 2009, Lenroot and Giedd, 2010, McCarthy and Konkle, 2005). Moreover, the size of the brain differences is usually small (Feingold, 1994, Halpern, 1997, Hyde, 2005). Indeed, the traits that markedly differ between the two sexes are essentially two: sexual orientation and core gender identity.