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GID studies


The conceptualization of GID as a form of DSD limited to the central nervous system (Swaab and Garcia-Falgueras, 2009) is referred to as the sexual differentiation hypothesis. To test this hypothesis, post mortem studies were conducted. They showed that male-to-female (MtF) transsexuals had a bed nucleus of the stria terminalis (central portion, BSTc) and interstitial nucleus of the anterior hypothalamus 3 (INAH3) of female volume and neuron number, that was smaller than those of men (Swaab and Garcia-Falgueras, 2009). Recent work shows that the volume and neuron number of another hypothalamic nucleus, the intermediate nucleus, of MtF transsexuals has intermediate values compared to those of men and women (Garcia-Falgueras et al., 2011). These post-mortem studies suggest a sex reversal in certain nuclei in the brains of transsexuals and were significant for the formulation of the sexual differentiation hypothesis. A methodological problem, how- ever is that possible influences of the cross-sex hormone treatment on the findings of these studies can never be completely ruled out. Studies into the effects of sex hormones on the sexual differentiation of the brain should be done before, rather than after the start of cross-sex hor- mone treatment.
Support for the sexual differentiation hypothesis came also from two neuropsychological studies in transsexuals before administration of cross-sex hormones. It was found that untreated transsexuals performed in the direction of their desired gender on sex-specific tasks (Cohen-Kettenis et al., 1998; van Goozen et al., 2002). In contrast,

a Norwegian study failed to replicate these findings (Haraldsen et al., 2003).
The first of a series of structural and functional imaging studies ex- amined anatomic variations of the corpus callosum and revealed no differences between the sexes, nor between transsexuals and controls (Emory et al., 1991). However, the majority of the participants in this study were already on hormonal treatment. More recent studies, using participants before the start of treatment, did find similarities between transsexuals and controls with the same gender identity in white mat- ter microstructure (FtM transsexuals, Rametti et al., 2011a), hypotha- lamic activation while smelling odourous steroids (MtF's, Berglund et al., 2008), brain activation patterns while viewing erotic videos (MtF's, Gizewski et al., 2009), and sources in EEG frequencies (MtF's, Flor-Henry, 2010). In addition, untreated transsexuals differed from controls of their natal sex in regional cerebral blood flow in the left an- terior cingulate cortex and right insula (FtM's, Nawata et al., 2010) and brain activation during mental rotation (Schöning et al., 2010).
Other imaging studies give reason to believe that there are less straightforward gender-atypical patterns of brain structure in individuals with GID. For instance, before hormonal intervention, MtFs appeared to have a white matter microstructure pattern that differs from male as well as from female controls (androphilic, sexually attracted to natal males, MtFs, Rametti et al., 2011b), and similar volumes of gray matter
compared to control men, except for the putamen, in which MtFs showed greater similarity with the female volume (androphilic and non- androphilic MtFs, Luders et al., 2009). In contrast, Savic and Arver (2011) found the putamen volume to be smaller in non-androphilic MtFs compared to men and women. In addition, they found smaller volumes in the thalamus and higher volumes in gray matter in the temporoparietal junction and the insular and inferofrontal cortex in MtFs compared to controls. The authors state that their findings argue against a sex-atypical dimorphism in MtFs, but that the differences between MtFs and male and female controls may be associated with gen- der dysphoria (Savic and Arver, 2011). Recently, Zubiaurre-Elorza et al. (2012) found evidence for subcortical masculinization in FtMs and corti- cal thickness feminization in MtFs.
As mentioned before, transsexuals (especially MtFs), form a hetero- geneous group with regard to the age of onset and sexual orientation. Although the brains of the various subtypes may differ from control men, only those of androphilic/homosexual MtFs are thought to have developed in the direction of the female sex, according to Blanchard (see Cantor, 2011). Not all imaging studies provide information on onset age and sexual orientation, but some do (see for a summary Table 1). In MtFs two studies in particular were noted for their support of Blanchard's typology (Cantor, 2011): Savic and Arver (2011) only studied non-androphilic/non-homosexual MtFs and did not find any

Table 1
Imaging studies before the start of hormonal treatment in transsexuals. (Adapted from Kreukels, 2011).
Study Technique Measure Subjects (N, sexual orientation and onset age)
FtM MtF Control men Control women