Neuroscience in transgender people : an update

Transgender persons identify with a gender different from the one they were assigned at birth. Although describing oneself as transgender is not a new phenomenon, media attention has lately been increasing exponentially, thanks to progressive changes in laws and change in societal attitudes. These changes also allow more people nowadays to (openly) identify as transgender and/or seek gender-affirming treatment. However, simultaneously, not much is presently understood about the underlying neurobiology, and specifically the brain structure and brain function of transgender persons. One major question in neuroimaging and neuroscience has been to determine whether, at the brain level, transgender people resemble more their gender identity, their sex assigned at birth, or have a unique neural profile. Although the evidence is presently inconsistent, it suggests that while the brain structure, at least before hormonal treatment, is more similar to sex assigned at birth, it may shift with hormonal treatment. By contrast, on “sex-stereotypical tasks,” brain function may already be more similar to gender identity in transgender persons, also before receiving gender-affirming hormone treatment. However, studies continue to be limited by small sample sizes and new initiatives are needed to further elucidate the neurobiology of a ‘brain gender’ (sex-dimorphic change according to one’s gender).Transgender-Personen identifizieren sich mit einem anderen Geschlecht als dem bei der Geburt zugewiesenen. Obwohl Menschen, die sich mit einem anderen Geschlecht identifizieren, kein neues Phänomen sind, so ist die mediale Aufmerksamkeit in den letzten Jahren diesbezüglich exponentiell gestiegen. Dies ist auch den gesetzlichen Verbesserungen und einer Veränderung in der gesellschaftlichen Einstellung zu dem Thema zu verdanken. Zur gleichen Zeit aber weiß man noch nicht viel über die Gehirnstruktur und Gehirnfunktion bei transgender Menschen. Eine Hauptfrage in den Neurowissenschaften ist es, ob die Gehirne von Transgender-Personen jenen ähneln des Geschlechtes, dem sie bei der Geburt zugewiesen wurden, des Geschlechtes mit dem sie sich identifizieren, oder ob sie ein unabhängiges neuronales Profil aufzeigen. Obwohl die Befunde derzeit widersprüchlich sind, zeigen sie in die Richtung, dass sich die Gehirnstruktur vor der hormonellen Behandlung nur unwesentlich verändert. Auf der anderen Seite gleicht die neuronale Aktivität bei “geschlechtstypischen Aufgaben” von Transgender-Personen der neuronalen Aktivität ihres identifizierten Geschlechts (auch schon vor der Hormonbehandlung). Trotzdem sind Studien weiterhin limitiert, da sie oft mit kleinen Stichproben auskommen müssen und neue Initiativen zur Bestätigung der ersten Befunde nötig sind

Reward prospect improves inhibitory control in female university students with a history of childhood sexual and physical abuse

Background and objectives: Childhood abuse and neglect increase the risk for psychiatric disorders (e.g., depression and anxiety) during adulthood and have been associated with deficits in cognitive control. The specific mechanisms underlying these cognitive control deficits are still unknown. Methods: This study examined the expectation for reward to improve inhibitory control in young women (ages 18-35 years) with a history of childhood sexual and/or physical abuse (AG, N = 28), childhood emotional and/or physical neglect (NG, N = 30), or unaffected comparison women (HC, N = 40). They completed a previously validated rewarded (color-word) Stroop task and filled out questionnaires on depression, anxiety, and resilience. Results: Surprisingly, a significant group by reward interaction revealed larger performance benefits under reward prospect (relative to no-reward) for the AG group relative to both the NG and HC groups. Limitations: A small sample size limiting generalizability. Conclusions: These results demonstrate sensitivity of abused subjects to reward in modulating cognitive control and might aid in discussing whether using reward schedules during therapeutic interventions could be effective

Epigenetics Is Implicated in the Basis of Gender Incongruence: An Epigenome-Wide Association Analysis

[Abstract] Introduction: The main objective was to carry out a global DNA methylation analysis in a population with gender incongruence before gender-affirming hormone treatment (GAHT), in comparison to a cisgender population. Methods: A global CpG (cytosine-phosphate-guanine) methylation analysis was performed on blood from 16 transgender people before GAHT vs. 16 cisgender people using the Illumina© Infinium Human Methylation 850k BeadChip, after bisulfite conversion. Changes in the DNA methylome in cisgender vs. transgender populations were analyzed with the Partek® Genomics Suite program by a 2-way ANOVA test comparing populations by group and their sex assigned at birth. Results: The principal components analysis (PCA) showed that both populations (cis and trans) differ in the degree of global CpG methylation prior to GAHT. The 2-way ANOVA test showed 71,515 CpGs that passed the criterion FDR p < 0.05. Subsequently, in male assigned at birth population we found 87 CpGs that passed both criteria (FDR p < 0.05; fold change ≥ ± 2) of which 22 were located in islands. The most significant CpGs were related to genes: WDR45B, SLC6A20, NHLH1, PLEKHA5, UBALD1, SLC37A1, ARL6IP1, GRASP, and NCOA6. Regarding the female assigned at birth populations, we found 2 CpGs that passed both criteria (FDR p < 0.05; fold change ≥ ± 2), but none were located in islands. One of these CpGs, related to the MPPED2 gene, is shared by both, trans men and trans women. The enrichment analysis showed that these genes are involved in functions such as negative regulation of gene expression (GO:0010629), central nervous system development (GO:0007417), brain development (GO:0007420), ribonucleotide binding (GO:0032553), and RNA binding (GO:0003723), among others. Strengths and Limitations: It is the first time that a global CpG methylation analysis has been carried out in a population with gender incongruence before GAHT. A prospective study before/during GAHT would provide a better understanding of the influence of epigenetics in this process. Conclusion: The main finding of this study is that the cis and trans populations have different global CpG methylation profiles prior to GAHT. Therefore, our results suggest that epigenetics may be involved in the etiology of gender incongruence.Xunta de Galicia; ED431 B 019/02 (EP) Ministerio de Ciencia, Innovación y Universidades; PGC2018-094919-B-C21 (AG) e PGC2018-094919-B-C22 (RF and EP) Ghent University.; BOF interdisciplinary project (IOP003-18

Understanding the brains of transgender people: Are we there yet?

Over the last 25 years, scientists have become more and more keen on understanding the contribution of the brain in how transgender people feel about themselves. Although studies are increasing, neuroscientists are still trying to answer the question whether the brains of transgender people resemble those of their self-identified gender, their sex assigned at birth, or whether they have a totally different brain profile

Does reward improve cognitive control? A comparison between formerly abused vs. neglected (vs. comparison) groups during the rewarded Stroop task

Background: Early-life stress (ELS) such as abuse and neglect have a detrimental effect on cognitive control. In parallel, studies in maltreated samples have documented deficits in reward processing. Yet, surprisingly, few studies have examined whether reward can still improve cognitive control in ELS samples as it does in healthy populations. Objective: To test the extent to which reward may improve cognitive control in different types of maltreated samples. Method: Ninety-eight female university students, age 18–27 years, participated and were split into three groups: those with prior sexual abuse experience (SA, N = 28), those with emotional neglect experience (EN, N = 30) and unaffected comparison women (HC, N = 40). To assess the main objective, participants performed a previously validated version of the rewarded Stroop task. Results: The results suggested that women from the SA group had a larger reward effect (faster performance) than women from the other two groups during rewarded relative to nonrewarded Stroop trials. This was still present when the response mapping was incongruent. Conclusions: Although the data are contrary to expectation, they are consistent with some prior published work. This may suggest that the precise factors (internal motivation, ingratiating behaviour) surrounding reward processing after maltreatment remain to be determine

Characterization of the H-1-MRS metabolite spectra in transgender men with gender dysphoria and cisgender people

Much research has been conducted on sexual differences of the human brain to determine whether and to what extent a brain gender exists. Consequently, a variety of studies using different neuroimaging techniques attempted to identify the existence of a brain phenotype in people with gender dysphoria (GD). However, to date, brain sexual differences at the metabolite level using magnetic resonance spectroscopy (H-1-MRS) have not been explored in transgender people. In this study, 28 cisgender men (CM) and 34 cisgender women (CW) and 29 transgender men with GD (TMGD) underwent H-1-MRS at 3 Tesla MRI to characterize common brain metabolites. Specifically, levels of N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), glutamate and glutamine (Glx), and myo-inositol + glycine (mI + Gly) were assessed in two brain regions, the amygdala-anterior hippocampus and the lateral parietal cortex. The results indicated a sex-assigned at birth pattern for Cho/Cr in the amygdala of TMGD. In the parietal cortex, a sex-assigned at birth and an intermediate pattern were found. Though assessed post-hoc, exploration of the age of onset of GD in TMGD demonstrated within-group differences in absolute NAA and relative Cho/Cr levels, suggestive for a possible developmental trend. While brain metabolite levels in TMGD resembled those of CW, some interesting findings, such as modulation of metabolite concentrations by age of onset of GD, warrant future inquiry

Gender-affirming hormonal treatment changes neural processing of emotions in trans men: An fMRI study

Background: Some transgender people desire a transition through gender-affirming hormone treatment (GAHT). To date, it is unknown how GAHT changes emotion perception in transgender people.Methods: Thirty transgender men (TM), 30 cisgender men (CM), and 35 cisgender women (CW) underwent 3 Tesla functional magnetic resonance imaging (fMRI) while passively viewing emotional faces (happy, angry, surprised faces) at two timepoints (T0 and T1). At T0 all participants were hormone-naive, while TM immedi-ately commenced testosterone supplementation at T0. The second scanning session (T1) occurred after 6-10 months of GAHT in TM. All 3 groups completed both T0 and T1Results: GAHT in TM shifted the neural profile whilst processing emotions from a sex-assigned at birth pattern at T0 (similar to CW) to a consistent with gender identity pattern at T1 (similar to CM). Overall, the brain patterns stayed the same for the cis people at T0 and T1.Conclusions: These findings document the impact of hormone treatment, and testosterone supplementation specifically, on emotion perception in TM