The classifier performed at 90.2% accuracy (AUC = 0.97) when assessed in the training sample and at 88.3% accuracy (AUC = 0.97) when assessed in our 48 cisgender brains. These measures indicate a suitable classification performance and a reliable distinction between the sexes based on brain anatomy. The estimated Brain Sex index was significantly different between the three groups (F(2,69) = 40.07, p < 0.001), with a mean of 1.00 ± 0.41 in cisgender men and of 0.00 ± 0.41 in cisgender women. The Brain Sex of transgender women was estimated as 0.75 ± 0.39, thus hovering between cisgender men and cisgender women, albeit closer to cisgender men (see also Figure 1). The follow-up post hoc tests revealed that transgender women were significantly more female than cisgender men (Cohen’s d = 0.64, t(46) = 2.20, p = 0.016), but significantly less female than cisgender women (Cohen’s d = 1.87, t(46) = 6.48, p < 0.001).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955456/
Transgender people report discomfort with their birth sex and a strong identification with the opposite sex. The current study was designed to shed further light on the question of whether the brains of transgender people resemble their birth sex or their gender identity. For this purpose, we analyzed a sample of 24 cisgender men, 24 cisgender women, and 24 transgender women before gender-affirming hormone therapy. We employed a recently developed multivariate classifier that yields a continuous probabilistic (rather than a binary) estimate for brains to be male or female. The brains of transgender women ranged between cisgender men and cisgender women (albeit still closer to cisgender men), and the differences to both cisgender men and to cisgender women were significant (p = 0.016 and p < 0.001, respectively).
These findings add support to the notion that the underlying brain anatomy in transgender people is shifted away from their biological sex towards their gender identity.
The observed shift away from a male-typical brain anatomy towards a female-typical one in people who identify as transgender women suggests a possible underlying neuroanatomical correlate for a female gender identity. That is, all transgender women included in this study were confirmed to be genetic males who had not undergone any gender-affirming hormone therapy. Thus, these transgender women have been subject to the influence of androgens and grown up (at least up until a certain age) in an environment that presumably treated them as males. The combination of male genes, androgens, and (to some degree) male upbringing should ordinarily be expected to result in a male-typical brain [39,40,41,42,43,44,45], making a female-typical brain anatomy extremely unlikely. Yet, the brain anatomy in the current sample of transgender women is shifted towards their gender identity—an observation that is at least partly in agreement with previous reports, as discussed in the following.
=====
More recently, Foreman et al. [116] conducted a study on a large sample of transwomen and control males, evaluating several candidate genes. The authors found a significant association between gender dysphoria and oestrogen receptor alpha (ERα), SRD5A2 and STS alleles, as well as ERα and SULT2A1 genotypes. These genetic variants could be functional, influencing oestrogen signalling. In fact, in SULT2A1, the genotype associated with gender dysphoria leads to elevated levels of sex hormone binding globulin, inducing a decreased effect of circulating hormones during intrauterine period. In the same way, the SRD5A2 allele evaluated in this study may lead to a reduction of DHT levels, thus determining a reduction of this potent androgen among transwomen. The authors identified several allele combinations overrepresented in transwomen, mostly involving AR, which may lead to long CAG repeats of the AR.
In conclusion, the evidence from these studies support the idea that brain sexual differentiation and the development of gender identity have a polygenic basis, involving interactions among multiple genes and polymorphism. However, results are in most cases conflicting and the number of genetic studies remains limited.
The aforementioned studies, although very heterogeneous, provide data supporting the biological bases of the psychosexual development. In particular, post-mortem and in vivo neuroimaging studies strongly suggest the existence of a sexual dimorphic brain, i.e., slight differences in brain anatomy and functioning between the two sexes. It is less clear how such brain structures become the substrate of sex differences in cognition and behaviour. This matter has been mainly investigated through the examination of specific populations, such as subjects with gender incongruence and intersex individuals: gender identity is one of the most sex-specific human trait, and many studies show how brain sexually dimorphic structures are often in line with gender identity rather than with sex assigned at birth. Research on this field has reported a possible organizational-activational role of sex hormones: in fact, studies on people with intersexual conditions highlight the role of prenatal and pubertal sex hormones in the determination of gender identity and other sex-specific cognitive traits. This evidence is also supported by the data from studies on hormonal treatment of transgender persons: indeed, a little but promising group of longitudinal studies also demonstrated the brain plasticity in response to cross-sex hormonal treatment in adult life. Anyway, to provide reliable conclusions, more data are needed. In fact, it is important to note that the size of the brain sex differences is really small, and that life experiences could have a deep impact on brain development. Additionally, little is known about the specific biological activity of sex hormones on brain structures: in particular, further studies should examine the role of androgens and oestrogens brain receptors.
Besides sex hormones, genetic factors are supposed to be the main determinants of brain sexual differentiation: again, the study on allele variations in transsexual individuals allowed to identify several candidate genes, mostly involving sex hormones receptors or steroidogenic enzymes, as possible determinants of sexual differentiation. The results were contrasting, but they may suggest the hypothesis of a polygenic basis of gender identity; in any case, the complex interaction between these genetic factors is far from understood, and that should be the matter of further studies.
Go to:
3. Conclusions
Prenatal and pubertal sex hormones seem to permanently affect human behaviour and, in addition, heritability studies have demonstrated a role of genetic components. However, a convincing candidate gene has not been identified. Future studies (i.e., genome wide studies) are needed to better clarify the complex interaction between genes, anatomy and hormonal influences on psychosexual development.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139786/
00000000000000000000000000
===========================
Is There Something Unique about the Transgender Brain?
By Francine Russo on January 1, 2016
Some children insist, from the moment they can speak, that they are not the gender indicated by their biological sex. So where does this knowledge reside? And is it possible to discern a genetic or anatomical basis for transgender identity? Exploration of these questions is relatively new, but there is a bit of evidence for a genetic basis. Identical twins are somewhat more likely than fraternal twins to both be trans.
Male and female brains are, on average, slightly different in structure, although there is tremendous individual variability. Several studies have looked for signs that transgender people have brains more similar to their experienced gender. Spanish investigators—led by psychobiologist Antonio Guillamon of the National Distance Education University in Madrid and neuropsychologist Carme Junqué Plaja of the University of Barcelona—used MRI to examine the brains of 24 female-to-males and 18 male-to-females—both before and after treatment with cross-sex hormones.
Their results, published in 2013, showed that even before treatment the brain structures of the trans people were more similar in some respects to the brains of their experienced gender than those of their natal gender. For example, the female-to-male subjects had relatively thin subcortical areas (these areas tend to be thinner in men than in women). Male-to-female subjects tended to have thinner cortical regions in the right hemisphere, which is characteristic of a female brain. (Such differences became more pronounced after treatment.)
“Trans people have brains that are different from males and females, a unique kind of brain,” Guillamon says. “It is simplistic to say that a female-to-male transgender person is a female trapped in a male body. It's not because they have a male brain but a transsexual brain.” Of course, behavior and experience shape brain anatomy, so it is impossible to say if these subtle differences are inborn.
Other investigators have looked at sex differences through brain functioning. In a study published in 2014, psychologist Sarah M. Burke of VU University Medical Center in Amsterdam and biologist Julie Bakker of the Netherlands Institute for Neuroscience used functional MRI to examine how 39 prepubertal and 41 adolescent boys and girls with gender dysphoria responded to androstadienone, an odorous steroid with pheromonelike properties that is known to cause a different response in the hypothalamus of men versus women. They found that the adolescent boys and girls with gender dysphoria responded much like peers of their experienced gender. The results were less clear with the prepubertal children.
https://www.scientificamerican.com/arti ... der-brain/
I think there's more evidence for a biological link to transgenderism then homosexuality.