Brain network interactions in transgender individuals with gender incongruence

Uribe, Carme; Junqué, Carme; Gómez‐Gil, Esther; Abós, Alexandra; Mueller, Sven C.; Guillamón, Antonio

doi:10.1016/j.neuroimage.2020.116613

Cited by 51 publications

(85 citation statements)

References 53 publications

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“…20 The origin of gender incongruence seems to be multifactorial. It might be related to neurodevelopmental processes of the brain 19,21 probably as a consequence of a genetic vulnerability 22e32 that implicates variations in the nuclear receptor's sensitivity to their ligand. In our previous studies, 31 we first proposed a hypothetic genetic model based on ERa, ERb, and AR allele combinations.…”

Section: Introductionmentioning

confidence: 99%

Gender-Affirming Hormone Therapy Modifies the CpG Methylation Pattern of the ESR1 Gene Promoter After Six Months of Treatment in Transmen

Fernández

Ramírez

Gómez‐Gil

et al. 2020

The Journal of Sexual Medicine

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Background: Brain sexual differentiation is a process that results from the effects of sex steroids on the developing brain. Evidence shows that epigenetics plays a main role in the formation of enduring brain sex differences and that the estrogen receptor a (ESR1) is one of the implicated genes. Aim: To analyze whether the methylation of region III (RIII) of the ESR1 promoter is involved in the biological basis of gender dysphoria. Methods: We carried out a prospective study of the CpG methylation profile of RIII (À1,188 to À790 bp) of the ESR1 promoter using bisulfite genomic sequencing in a cisgender population (10 men and 10 women) and in a transgender population (10 trans men and 10 trans women), before and after 6 months of gender-affirming hormone treatment. Cisgender and transgender populations were matched by geographical origin, age, and sex. DNAs were treated with bisulfite, amplified, cloned, and sequenced. At least 10 clones per individual from independent polymerase chain reactions were sequenced. The analysis of 671 bisulfite sequences was carried out with the QUMA (QUantification tool for Methylation Analysis) program. Outcomes: The main outcome of this study was RIII analysis using bisulfite genomic sequencing. Results: We found sex differences in RIII methylation profiles in cisgender and transgender populations. Cismen showed a higher methylation degree than ciswomen at CpG sites 297, 306, 509, and at the total fragment (P .003, P .026, P .001, P .006). Transmen showed a lower methylation level than trans women at sites 306, 372, and at the total fragment (P .0001, P .018, P .0107). Before the hormone treatment, transmen showed the lowest methylation level with respect to cisgender and transgender populations, whereas transwomen reached an intermediate methylation level between both the cisgender groups. After the hormone treatment, transmen showed a statistically significant methylation increase, whereas transwomen showed a non-significant methylation decrease. After the hormone treatment, the RIII methylation differences between transmen and transwomen disappeared, and both transgender groups reached an intermediate methylation level between both the cisgender groups. Clinical Implications: Clinical implications in the hormonal treatment of trans people. Strengths & Limitations: Increasing the number of regions analyzed in the ESR1 promoter and increasing the number of tissues analyzed would provide a better understanding of the variation in the methylation pattern. Conclusions: Our data showed sex differences in RIII methylation patterns in cisgender and transgender populations before the hormone treatment. Furthermore, before the hormone treatment, transwomen and

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Section: Introductionmentioning

confidence: 99%

Gender-Affirming Hormone Therapy Modifies the CpG Methylation Pattern of the ESR1 Gene Promoter After Six Months of Treatment in Transmen

Fernández

Ramírez

Gómez‐Gil

et al. 2020

The Journal of Sexual Medicine

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“…Further studies have focused on functional MRI connectivity evaluating differences between transgender and cisgender persons in cerebral networks involved in own body perception, given its importance in GD [ 14 , 15 , 24 , 25 , 26 , 27 ]. Several authors hypothesized that GD could be based on the disconnection of fronto-parietal networks involved in the processing of own body image.…”

Section: Introductionmentioning

confidence: 99%

Neural Correlates of Gender Face Perception in Transgender People

Fisher

Ristori

Castellini

et al. 2020

JCM

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To date, MRI studies focused on brain sexual dimorphism have not explored the presence of specific neural patterns in gender dysphoria (GD) using gender discrimination tasks. Considering the central role of body image in GD, the present study aims to evaluate brain activation patterns with 3T-scanner functional MRI (fMRI) during gender face discrimination task in a sample of 20 hormone-naïve transgender and 20 cisgender individuals. Additionally, participants were asked to complete psychometric measures. The between-group analysis of average blood oxygenation level dependent (BOLD) activations of female vs. male face contrast showed a significant positive cluster in the bilateral precuneus in transmen when compared to the ciswomen. In addition, the transwomen group compared to the cismen showed higher activations also in the precuneus, as well as in the posterior cingulate gyrus, the angular gyrus and the lateral occipital cortices. Moreover, the activation of precuneus, angular gyrus, lateral occipital cortices and posterior cingulate gyrus was significantly associated with higher levels of body uneasiness. These results show for the first time the existence of a possible specific GD-neural pattern. However, it remains unclear if the differences in brain phenotype of transgender people may be the result of a sex-atypical neural development or of a lifelong experience of gender non-conformity.

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“…Frontal-subcortical circuits constitute a closed-loop of anatomically segregated neurons, while their functional connectivity incorporates open-loop elements (Bonelli & Cummings, 2007). Regions of the CNS that relate to the development of body perception are incorporated in the frontoparietal cortex, amygdala, hypothalamus (Uribe et al, 2020;Manzouri, Kosidou, & Savic, 2017;Savic & Arver, 2011;Northoff et al, 2006).…”

Section: Prefrontal Cortexmentioning

confidence: 99%

“…The perception of one's body and one's self (Samuels, 1986) "heavily involves cerebral midline structures incorporating a parieto-occipital 'body detection"'network" (Manzouri, Kosidou, & Savic, 2017, p. 1005. Studies suggest own body recognition or perception as connectivity phenotypes (Uribe et al, 2020) may be mediated by the communication architecture or interacting brain networks (Feusner et al, 2017). The frontoparietal region related to the own body perception shows sex differences (Uribe et al, 2020;Ritchie et al 2018).…”

Section: Connectivity / Connectomementioning

confidence: 99%

Sex vs Gender: A Biological Location for Gender, not Sex.

Woodhill¹,

Samuels

2021

Preprint

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The origins of bodily sex are well understood but consensus on origins for gender are missing. While gonadal sex and sexual orientation are accepted as emanating from genetic and hormonal templates, gender’s existence, when it is acknowledged, currently has so far emanated from either social origins or a nebulous ‘somewhere’ in the brain. Although the characteristics of sex-related behavior relative to the physicality of reproduction are clearly dimorphic, other cognitive behaviors relative to reproduction have not been explicitly identified and presented. This article synthesizes important research to present a biological location of gender as opposed to sex. These cognitive behaviors can be differentially linked with reproduction throughout the lifespan. A physiological location for gender in the human phenotype may help advance this research further.

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Brain network interactions in transgender individuals with gender incongruence

Cited by 51 publications

References 53 publications

Gender-Affirming Hormone Therapy Modifies the CpG Methylation Pattern of the ESR1 Gene Promoter After Six Months of Treatment in Transmen

Gender-Affirming Hormone Therapy Modifies the CpG Methylation Pattern of the ESR1 Gene Promoter After Six Months of Treatment in Transmen

Neural Correlates of Gender Face Perception in Transgender People

Sex vs Gender: A Biological Location for Gender, not Sex.

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