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Possible Neurobiological Underpinnings of Homosexuality and Gender Dysphoria
Abstract
Although frequently discussed in terms of sex dimorphism, the neurobiology of sexual orientation and identity is unknown. We report multimodal magnetic resonance imaging data, including cortical thickness (Cth), subcortical volumes, and resting state functional magnetic resonance imaging, from 27 transgender women (TrW), 40 transgender men (TrM), and 80 heterosexual (40 men) and 60 homosexual cisgender controls (30 men). These data show that whereas homosexuality is linked to cerebral sex dimorphism, gender dysphoria primarily involves cerebral networks mediating self-body perception. Among the homosexual cisgender controls, weaker sex dimorphism was found in white matter connections and a partly reversed sex dimorphism in Cth. Similar patterns were detected in transgender persons compared with heterosexual cisgender controls, but the significant clusters disappeared when adding homosexual controls, and correcting for sexual orientation. Instead, both TrW and TrM displayed singular features, showing greater Cth as well as weaker structural and functional connections in the anterior cingulate-precuneus and right occipito-parietal cortex, regions known to process own body perception in the context of self.
... Transgender groups presented thicker clusters at the temporal and parietal cortex compared to heterosexual controls of their experienced gender, but these results were no longer observed when compared against homosexual controls. (Manzouri & Savic, 2019). ...
... Some authors refer to an early programming of gender and sexual inclination driven by sexual differentiation in the brain, proposing that the latter influences the development of the brain areas modulating body perception (i.e., related to gender identity) or sexual arousal (i.e., related to sexual orientation) Manzouri & Savic, 2019). Others underline the interaction between brain, culture and behavior, arguing that structural and functional brain changes in transgender individuals may be consequence of culture and behavior (Mohammadi & Khalegi, 2018). ...
... Gender identity and sexual orientation are conceptually different, i.e., both cisgender and transgender people are either heterosexual or homosexual Moser, 2010), and there are more gender identities other than cis-/transgender(ism) (such as genderqueer or non-binary) and other sexual orientations other than hetero-/homosexual(ism) (such as bi-, pan-, and asexual). Sexual orientation could be associated with brain structural specific features regardless and independently from gender identity as some recent studies suggest (Baldinger-Melich et al., 2020;Manzouri & Savic, 2019). Thus, meaning that the structural, functional, and metabolic variations found in homosexual transgenders with respect to heterosexual cisgenders may be related to their sexual orientation rather than to their gender identity (Blanchard et al., 1987). ...
This review systematically explored structural, functional, and metabolic features of the cisgender brain compared with the transgender brain before hormonal treatment and the heterosexual brain compared to the homosexual brain from the analysis of the neuroimaging literature up to 2018, and identified and discussed subsequent studies published up to March 2021. Our main aim was to help identifying neuroradiological brain features that have been related to human sexuality to contribute to the understanding of the biological elements involved in gender identity and sexual orientation. We analyzed 39 studies on gender identity and 24 on sexual orientation. Our results suggest that some neuroanatomical, neurophysiological, and neurometabolic features in transgender individuals resemble those of their experienced gender despite the majority resembling those from their natal sex. In homosexual individuals the majority resemble those of their same-sex heterosexual population rather than their opposite-sex heterosexual population. However, it is always difficult to interpret findings with noninvasive neuroimaging. Given the gross nature of these measures, it is possible that more differences too subtle to measure with available tools yet contributing to gender identity and sexual orientation could be found. Conflicting results contributed to the difficulty of identifying specific brain features which consistently differ between cisgender and transgender or between heterosexual and homosexual groups. The small number of studies, the small-to-moderate sample size of each study, and the heterogeneity of the investigations made it impossible to meta-analyze all the data extracted. Further studies are necessary to increase the understanding of the neurological substrates of human sexuality.
... Transgender groups presented thicker clusters at the temporal and parietal cortex compared to heterosexual controls of their experienced gender, but these results were no longer observed when compared against homosexual controls. (Manzouri & Savic, 2019). ...
... Some authors refer to an early programming of gender and sexual inclination driven by sexual differentiation in the brain, proposing that the latter influences the development of the brain areas modulating body perception (i.e., related to gender identity) or sexual arousal (i.e., related to sexual orientation) (Burke, Manzouri & Savic, 2017;Manzouri & Savic, 2019). Others underline the interaction between brain, culture and behavior, arguing that structural and functional brain changes in transgender individuals may be consequence of culture and behavior (Mohammadi & Khalegi, 2018). ...
... Gender identity and sexual orientation are conceptually different, i.e., both cisgender and transgender people are either heterosexual or homosexual (Burke et al., 2017;Moser, 2010), and there are more gender identities other than cis-/transgender(ism) (such as genderqueer or non-binary) and other sexual orientations other than hetero-/homosexual(ism) (such as bi-, pan-, and asexual). Sexual orientation could be associated with brain structural specific features regardless and independently from gender identity as some recent studies suggest (Baldinger-Melich et al., 2020;Manzouri & Savic, 2019). Thus, meaning that the structural, functional, and metabolic variations found in homosexual transgenders with respect to heterosexual cisgenders may be related to their sexual orientation rather than to their gender identity (Blanchard et al., 1987). ...
This review systematically explored structural, functional, and metabolic features of the cisgender brain compared with the transgender brain before hormonal treatment and the heterosexual brain compared to the homosexual brain from the analysis of the neuroimaging literature up to 2018, and identified and discussed subsequent studies published up to March 2021. Our main aim was to help identifying neuroradiological brain features that have been related to human sexuality to contribute to the understanding of the biological elements involved in gender identity and sexual orientation. We analyze 39 studies on gender identity and 24 on sexual orientation. Our results suggest that some neuroanatomical, neurophysiological, and neurometabolic features in transgender individuals resemble those of their experienced gender despite the majority resembling those from their natal sex. In homosexual individuals the majority resemble those of their same sex heterosexual population rather than their opposite sex heterosexual population. However, it is always difficult to interpret findings with non-invasive neuroimaging. Given the gross nature of these measures, it is possible that more differences too subtle to measure with available tools yet contributing to gender identity and sexual orientation could be found. Conflicting results contributed to the difficulty of identifying specific brain features which consistently differ between cisgender and transgender or between heterosexual and homosexual groups. The small number of studies, the small-to-moderate sample size of each study, and the heterogeneity of the investigations made it impossible to meta-analyze all the data extracted. Further studies are necessary to increase the understanding of the neurological substrates of human sexuality.
... Studies examining children and studies only comparing total brain volumes or cortical thickness were excluded. This search process yielded 11 studies [9][10][11]15,17,[31][32][33][34][35][36]. ...
... The gender identity effect in the putamen in the present findings corroborates six of the seven previous studies reporting GMV differences in this region. Except for Savic and colleagues [10], six previous studies [9,[32][33][34][35][36] and the present study found larger GMV for trans-as compared to cisgender participants. It is beyond the scope of the present study to investigate the reasons for this discrepancy between Savic and colleagues [10] and the remaining studies. ...
... However, what makes the putamen especially relevant for transgender and GI? In accordance with previous studies [10,33], we suggest that the specific role for the putamen in GI is most likely related to the general function of this brain region in processing body representations and the own body image. Such an explanation seems reasonable, considering that the strong feeling of being trapped in the wrong body and persistent discomfort with one's physical appearance represent key features of GI. ...
The brain structural changes related to gender incongruence (GI) are still poorly understood. Previous studies comparing gray matter volumes (GMV) between cisgender and transgender individuals with GI revealed conflicting results. Leveraging a comprehensive sample of transmen (n = 33), transwomen (n = 33), cismen (n = 24), and ciswomen (n = 25), we employ a region-of-interest (ROI) approach to examine the most frequently reported brain regions showing GMV differences between trans- and cisgender individuals. The primary aim is to replicate previous findings and identify anatomical regions which differ between transgender individuals with GI and cisgender individuals. On the basis of a comprehensive literature search, we selected a set of ROIs (thalamus, putamen, cerebellum, angular gyrus, precentral gyrus) for which differences between cis- and transgender groups have been previously observed. The putamen was the only region showing significant GMV differences between cis- and transgender, across previous studies and the present study. We observed increased GMV in the putamen for transwomen compared to both transmen and ciswomen and for all transgender participants compared to all cisgender participants. Such a pattern of neuroanatomical differences corroborates the large majority of previous studies. This potential replication of previous findings and the known involvement of the putamen in cognitive processes related to body representations and the creation of the own body image indicate the relevance of this region for GI and its potential as a structural biomarker for GI.
... This theory, however, has not been substantiated in brain imaging and behavioral studies of trans women (TrW), (persons who are assigned as males at birth, but identify as women) (Rametti, Carrillo, Gómez-Gil, Junque, Segovia, et al. 2011a;Luders et al. 2012;Zubiaurre-Elorza et al. 2014) or trans men (TrM), (persons who are assigned as females at birth, but identify as men) (Rametti, Carrillo, Gómez-Gil, Junque, Zubiarre-Elorza, et al. 2011b;Simon et al. 2013;Zubiaurre-Elorza et al. 2013;Manzouri et al. 2017;Burke et al. 2018). This also applies for studies combining TrW and TrM (Savic et al. 2010;Kranz et al. 2014;Hahn et al. 2015;Guillamon et al. 2016;Kreukels and Guillamon 2016;Burke et al. 2017;Feusner et al. 2017;Majid et al. 2020;Manzouri and Savic 2019). One reason for the described inability to find consistent features among transgender study groups might be that the aforementioned studies did not focus on the incongruence between perception of self (for a detailed definition, please see Northoff and Panksepp (2008)) and perception of one's own body, in reference to self. ...
... Firstly functional connections between the two major nodes of this network (the inferior parietal cortex, and EBA, mediating own body perception) and the (pAC-C/mPFC, mediating perception of self) were less pronounced among transgender groups (Burke et al. 2017;Feusner et al. 2017;Majid et al. 2020). Secondly, the functional connections were associated with a lower degree of perception of own body as self (Burke et al. 2017;Manzouri et al. 2017;Manzouri and Savic 2019). Third, the thickness of mPFC, pACC, the precuneus, and the temporo-occipito-parietal cortex was greater among trans-compared with cisgender persons Manzouri and Savic 2019). ...
... Secondly, the functional connections were associated with a lower degree of perception of own body as self (Burke et al. 2017;Manzouri et al. 2017;Manzouri and Savic 2019). Third, the thickness of mPFC, pACC, the precuneus, and the temporo-occipito-parietal cortex was greater among trans-compared with cisgender persons Manzouri and Savic 2019). No specific sex-atypical traits were found. ...
Gender incongruence (GI) is characterized by a feeling of estrangement from the own body in the context of self. GI is often described in people who identify as transgender. The underlying mechanisms are unknown. Data from MRI measurements and tests of own body perception triggered us to pose a model that GI in transgender persons (TGI) could be associated with a disconnection within the brain circuits mediating the perception of own body as self. This is a departure from a previous model of sex atypical cerebral dimorphism, introducing a concept that better accords with a core feature of TGI. The present MRI study of 54 hormone naive transmen (TrM), 38 transwomen (TrW), 44 cismen and 41 ciswomen show that cortical gyrification, a metric that reflects early maturation of cerebral cortex, is significantly lower in transgender compared with cisgender participants. This reduction is limited to the occipito-parietal cortex and the sensory motor cortex, regions encoding own body image and body ownership. Moreover, the cortical gyrification correlated inversely with own body-self incongruence in these regions. These novel data suggest that GI in TGI may originate in the neurodevelopment of body image encoding regions. The results add potentially to understanding neurobiological contributors to gender identity.
... We expected to detect pre-to post-treatment changes in cerebral connectivity in the DMN. We chose to study DMN because it is shown to be robust with high test-retest reproducibility, and because it has in several previous studies (including our own) shown to overlap with the brain areas involved in the perception of own body in the context of self (e.g., see 25,28,30,41 ). We assumed that tentative between-scan changes in functional connectivity changes would be associated with the altered degree of own body-self-perception (as measured by the 0% morph ratings). ...
... For a detailed description of the methods please see our previous publications [21][22][23] . Forty TrM with GD (Mean age = 22.93 ± 5.28 age range = 18-40 years old; education 13.38 ± 1.95, range 9-17.5 years), 25 TrW with GD (Mean age = 27.96 ± 7.12; age range = 20-50 years old; education 14.6 ± 2.46, range 8-19 years), 5 cis gender women (Mean age = 30.6 ± 8.849; age range = 20−44 years old; education 15.3 ± 2.11, range 13-18.5 years) and 10 cis gender men (Mean age = 30.30 ...
... Data acquisition. This acquisition of MRI data has been detailed elsewhere 25 and will be reviewed here too. The images were acquired on a 3-T MRI scanner (Discovery 3 T GE-MR750, General Electric) equipped Table 1. ...
Referrals for gender dysphoria (GD), characterized by a distressful incongruence between gender identity and at-birth assigned sex, are steadily increasing. The underlying neurobiology, and the mechanisms of the often-beneficial cross-sex hormone treatment are unknown. Here, we test hypothesis that own body perception networks (incorporated in the default mode network—DMN, and partly in the salience network—SN), are different in trans-compared with cis-gender persons. We also investigate whether these networks change with cross-sex hormone treatment. Forty transmen (TrM) and 25 transwomen (TrW) were scanned before and after cross-sex hormone institution. We used our own developed Body Morph test (BM), to assess the perception of own body as self. Fifteen cisgender persons were controls. Within and between-group differences in functional connectivity were calculated using independent components analysis within the DMN, SN, and motor network (a control network). Pretreatment, TrM and TrW scored lower “self” on the BM test than controls. Their functional connections were weaker in the anterior cingulate-, mesial prefrontal-cortex (mPFC), precuneus, the left angular gyrus, and superior parietal cortex of the DMN, and ACC in the SN “Self” identification and connectivity in the mPFC in both TrM and TrW increased from scan 1 to 2, and at scan 2 no group differences remained. The neurobiological underpinnings of GD seem subserved by cerebral structures composing major parts of the DMN.
... A growing domain in the neuroimaging literature has examined brain features related to variations in human sexual orientation and gender identity [1,2]. Aspects of cortical structure-most notably, cortical volume, thickness, and surface area-have often been the focus of these studies [3][4][5][6][7]. A recent multi-modal neuroimaging study of 12-to 17-year-olds by Skorska et al. [8] examined cortical thickness, surface area, and T1 relaxation time-the latter measure being a previously unconsidered metric that provides information pertaining to the relative presence vs. absence of macromolecules or the free-water content within brain tissue [9]. ...
... Structural brain metrics that can be examined in existing data sets of sexually and/or gender-diverse participants would be particularly useful as they would offer a more immediate avenue for further examining variations in neural tissue density. Diffusion-weighted imaging (DWI), which has been more commonly acquired in the neuroimaging literature on sexual orientation and gender identity to investigate white matter and to examine sex or gender differences [6,[10][11][12][13][14][15][16], might provide a viable alternative. ...
Recent research found that the combination of masculine gender identity and gynephilia was associated with cortical T1 relaxation time, which is considered to reflect gray matter density. We hypothesized that mean diffusivity (MD), a diffusion tensor imaging metric that reflects the degree to which water movement is free versus constrained, in combination with T1 relaxation time would provide further insight regarding cortical tissue characteristics. MD and T1 relaxation time were measured in 76 cortical regions in 15 adolescents assigned female at birth who experience gender dysphoria (GD AFAB) and were not receiving hormone therapy, 17 cisgender girls, and 14 cisgender boys (ages 12–17 years). Sexual orientation was represented by the degree of androphilia–gynephilia and the strength of sexual attraction. In multivariate analyses, cortical T1 relaxation time showed a weak but statistically significant positive association with MD across the cortex, suggesting that macromolecule-rich cortical tissue also tends to show water movement that is somewhat more constrained. In further multivariate analyses, in several left frontal, parietal, and temporal regions, the combination of shorter T1 relaxation time and faster MD was associated with older age and greater gynephilia in GD AFAB individuals and cisgender boys and with stronger attractions in cisgender boys only. Thus, for these cortical regions in these groups, older age, gynephilia, and stronger attractions (cisgender boys only) were associated with macromolecule-rich tissue in which water movement was freer—a pattern that some prior research suggests is associated with greater cell density and size. Overall, this study indicates that investigating T1 relaxation time and MD together can further inform how cortical gray matter tissue characteristics relate to age and psychosexuality.
... 4 There is also evidence of neuroanatomical differences among transgender individuals. [5][6][7] A diagnosis of gender dysphoria can be made if a patient is experiencing gender incongruence that causes significant distress. Individuals typically present with gender dysphoria during adolescence, but it is not uncommon for patients to present in early childhood or after the age of 18. 8,9 Patients with gender dysphoria who receive treatment report happier lives. ...
... Studies in this field are mainly neuroimaging studies that find increased cortical thickness, and weaker connections in regions of the brain known for processing one's own body perception. [5][6][7] More recently, brain connectivity studies find that brain connectivity dynamics are similar among transgender individuals and the gender they identify with than with the gender they were assigned at birth. 19 While more studies need to be done to further elucidate the neuroanatomy and neurophysiology, the current research suggests that brain architecture and function play an important role in gender identity and gender dysphoria. ...
Gender dysphoria is defined by severe or persistent distress associated with an incongruence between one’s gender identity and biological sex. It is estimated that 1.4 million Americans and 25 million people worldwide identify as transgender and that 0.6% of Americans experience gender dysphoria. The pathophysiology of gender dysphoria is multifactorial and incompletely understood. Genetics, androgen exposure, neuroanatomy, brain connectivity, history of trauma, parents with psychological disorders, and being raised by less than two parents are associated with gender dysphoria. Gender dysphoria most frequently presents in early teenage years but can present earlier or later. Anxiety and depression are the two most common comorbid diagnoses and may be the reason for presentation to medical care. Diagnosis is established through history and or validated questionnaires. Treatment includes psychosocial therapy, pharmacotherapy for underlying depression and/or anxiety, hormonal therapy, non-genital and/or genital feminization or masculinization operations. The frequency and severity of treatment related morbidity increases progressively as treatments go from conservative to more invasive. Gender dysphoria and its treatment is individualized and not completely understood.
... To date, most of the LGBT neuroimaging literature focuses on the etiology of identities (20). Studies generally compare cisgender and transgender groups or cisgender heterosexual and cisgender gay or lesbian people (16,(21)(22)(23)(24)(25). This approach underscores a framework that assumes cisgender heterosexuality as the default, and variation in sexual orientation or gender identity as aberrant. ...
... However, all people have sexual orientations and gender identities, including those who do not identify as LGBT. Other studies use erotic stimuli to argue that the pattern of activation to samesex erotic stimuli in gay men and women is similar to the pattern of activation to opposite-sex stimuli in heterosexuals (24)(25)(26)(27)(28)(29). The preponderance of studies focused on erotic stimuli overall suggests an unnecessary preoccupation with the identification of biological markers of arousal to validate the experiences of LGBT people. ...
There are opportunities to improve neuroscience that includes lesbian, gay, bisexual, and transgender (LGBT) people. In this commentary, we briefly describe how the history of LGBT people in psychiatry has influenced neuroimaging approaches, how these attitudes have shifted over time, and what we can do to ensure that our future work is rigorous, ethical, and in service of the LGBT community. We suggest ways to refine neuroimaging methodologies to improve our understanding of marginalization and stigma while shifting away from research that focuses solely on the ‘etiology’ or origins of LGBT identities. We also offer suggestions for conducting representative research that is LGBT-inclusive, regardless of the population of interest.
... On the other hand, it involves 3 In order to establish a dialogue between different disciplines and approaches, I chose a pragmatic approach to the use of terminology. The terms "transgender"/"trans" and "cisgender"/"cis" are extracted from the field, following the vocabulary of recent neuroscientific papers (see Burke et al., 2017;Nota et al., 2017;Manzouri and Savic, 2018 for example) that seemed the most compatible with terms as used in gender and trans studies. The same applies to the use of "gender identity", taken from the field. ...
... ,Rametti et al. (2011a,b), andKranz et al. (2014). The sample of the recent studies was based on publication date, inclusion of different approaches, relevance of the findings, and availability of researchers for the interview:Guillamón et al. (2016),Burke et al. (2017), Feusner et al. (2017,Manzouri et al. (2017),Nota et al. (2017), andManzouri and Savic (2018). ...
This study undertakes an analysis of the conceptualization of gender identity in neuroscientific studies of (trans)gender identity that contrast the brains of cisgender and transgender participants. The analysis focuses on instances of epistemic injustice that combine scientific deficiencies and the exclusion of relevant bodies of knowledge. The results of a content analysis show how the ignoring of biosocial, developmental, mosaicist, contextualist, and depathologizing approaches leads to internal conceptual inconsistencies, hermeneutical deficiencies and the upholding of questionable paradigms in the research field. Interviews with researchers involved in these brain studies reveal targeted and diffuse forms of testimonial injustice against alternative approaches, promoted by the hierarchical arrangements of research teams in combination with the careerist and economic logic of research. The analysis points to the exclusion of critical epistemologies of science and the historical oppression of trans people as epistemic agents as the underlying hermeneutical deficiencies.
... The neurohormonal hypothesis has also been invoked to explain the development of sexual orientation [22][23][24][25], but sexual orientation has seldom been investigated in brain studies of GD ( [6]; but see [26] for a study in adults). For example, Hoekzema et al. [5] did not examine associations with sexual orientation, likely because all GD AFAB were gynephilic (i.e., attracted to girls/women) and the GD AMAB were mostly androphilic (i.e., attracted to boys/men). ...
... Furthermore, our results cannot generalize to ages beyond 12-to 17-years-old. Studies on adults have examined cortical structure related to GD [9,26,[102][103][104][105][106][107][108], but we know of no studies examining cortical structure of GD children. Lastly, we examined three cortical structural brain features; other aspects of adolescent GD brain structure (e.g., white matter microstructure) await investigation. ...
Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Sex-differentiated brain regions are hypothesized to reflect the experienced gender in GD and may play a role in sexual orientation development. Magnetic resonance brain images were acquired from 16 GD adolescents assigned female at birth (AFAB) not receiving hormone therapy, 17 cisgender girls, and 14 cisgender boys (ages 12–17 years) to examine three morphological and microstructural gray matter features in 76 brain regions: surface area (SA), cortical thickness (CT), and T1 relaxation time. Sexual orientation was represented by degree of androphilia-gynephilia and sexual attraction strength. Multivariate analyses found that cisgender boys had larger SA than cisgender girls and GD AFAB. Shorter T1, reflecting denser, macromolecule-rich tissue, correlated with older age and stronger gynephilia in cisgender boys and GD AFAB, and with stronger attractions in cisgender boys. Thus, cortical morphometry (mainly SA) was related to sex assigned at birth, but not experienced gender. Effects of experienced gender were found as similarities in correlation patterns in GD AFAB and cisgender boys in age and sexual orientation (mainly T1), indicating the need to consider developmental trajectories and sexual orientation in brain studies of GD.
... We additionally included the (v) dorsal and (vi) ventral attention networks because they include the temporal parietal junction and surrounding cortices important in own body perception (Blanke et al., 2005). Finally, we included the (vii) memory retrieval network, as it includes midline portions of the posterior cingulate shown to be important for self-perception and which in our earlier studies showed greater cortical thickness compared to (Manzouri et al., 2017;Manzouri and Savic, 2019). All network-defined regions of interest (ROIs) were derived using a brain parcellation from Power (Power et al., 2011) who partitioned the brain into functional networks based on resting-state connectivity data. ...
... These findings have implications for identifying those who will benefit more or less from hormone therapy. Furthermore, these results support our previous finding using anatomical metrics (Kilpatrick et al., 2019;Manzouri and Savic, 2019), and contribute to identifying the specific brain networks in GI, prior to therapy, whose connectivity patterns are critical with respect to hormone therapy effects. ...
Individuals with gender incongruence (GI) experience serious distress due to incongruence between their gender identity and birth-assigned sex. Sociological, cultural, interpersonal, and biological factors are likely contributory, and for some individuals medical treatment such as cross-sex hormone therapy and gender-affirming surgery can be helpful. Cross-sex hormone therapy can be effective for reducing body incongruence, but responses vary, and there is no reliable way to predict therapeutic outcomes. We used clinical and MRI data before cross-sex hormone therapy as features to train a machine learning model to predict individuals’ post-therapy body congruence (the degree to which photos of their bodies match their self-identities). Twenty-five trans women and trans men with gender incongruence participated. The model significantly predicted post-therapy body congruence, with the highest predictive features coming from the cingulo-opercular (R² = 0.41) and fronto-parietal (R² = 0.30) networks. This study provides evidence that hormone therapy efficacy can be predicted from information collected before therapy, and that patterns of functional brain connectivity may provide insights into body-brain effects of hormones, affecting one's sense of body congruence. Results could help identify the need for personalized therapies in individuals predicted to have low body-self congruence after standard therapy.
... Among transgender individuals a higher prevalence of a bi-or homosexual orientation (i.e., feeling sexually attracted to individuals of the same birth-assigned sex, or to both sexes), compared to heterosexual orientation (i.e., feeling sexually attracted to individuals of the opposite birth-assigned sex), has repeatedly been reported (Blanchard et al., 1987;Cerwenka et al., 2014). In addition, both cisgender homosexual (gay men lesbian women) and transgender (of both sexes and with mixed sexual orientations) groups have been found to show less pronounced sexual differentiation of brain structures (Burke et al., 2017; SEX EFFECTS IN ADOLESCENT BRAIN DEVELOPMENT Manzouri and Savic, 2018;Manzouri and Savic, 2019). Importantly, when in these studies individual differences in sexual orientation were statistically accounted for, the transgender groups, compared to both hetero-and homosexual cisgender males and females, showed singular features of thicker cortex and less functional and structural connectivity in regions implicated in self-and own body perception (Burke et al., 2017;Manzouri and Savic, 2019). ...
... In addition, both cisgender homosexual (gay men lesbian women) and transgender (of both sexes and with mixed sexual orientations) groups have been found to show less pronounced sexual differentiation of brain structures (Burke et al., 2017; SEX EFFECTS IN ADOLESCENT BRAIN DEVELOPMENT Manzouri and Savic, 2018;Manzouri and Savic, 2019). Importantly, when in these studies individual differences in sexual orientation were statistically accounted for, the transgender groups, compared to both hetero-and homosexual cisgender males and females, showed singular features of thicker cortex and less functional and structural connectivity in regions implicated in self-and own body perception (Burke et al., 2017;Manzouri and Savic, 2019). A different perception of the own body, paralleled by altered specific neural networks, may thus be the distinguishing feature differentiating between transgender and cisgender persons, while differences in cerebral sexual differentiation seem to pertain more to diversity in sexual orientations. ...
Sex differences in behavior, and whether these behavioral differences are related to sex differences in brain development, has been a longstanding topic of debate. Presumably, sex differences can provide critically important leads for explaining the etiology of various illnesses that show (i) large sex differences in prevalence and (ii) have an origin before or during adolescence. The general aim of this chapter is to provide an overview of scientific studies on sex differences in normative brain and behavioral development across puberty and adolescence, including the (sex) hormone-driven transition phase of puberty. Moreover, we describe the literature on brain and behavioral development in gender dysphoria, a severe and persistent incongruence between the self-identified gender and the assigned sex at birth. From the literature it becomes clear there is evidence for a specific link between pubertal maturation and developmental changes in arousal, motivation, and emotion. However, this link is rather similar between boys and girls. Moreover, although there is substantial evidence for sex differences in mean brain structure, these have not always been linked to sex differences in behavior, cognition, or psychopathology. Furthermore, there is little evidence for sex differences in brain development and thus, studies so far have been unable to explain sex differences in cognition. Suggestions for future research and methodologic considerations are provided.
... Moreover, among individuals whose gender identity matches their sex assigned at birth, mastectomy and androgen deprivation cancer therapies, which both involve changes to one's feminine or masculine bodily characteristics, are often related to a gender identity crisis 13,14 . There are also data suggesting that the mental representation of one's own body is altered in transgender individuals 15 and that the brain regions involved in this representation are anatomically and functionally different in this group compared to controls [16][17][18][19][20][21][22][23] . However, the link between own body perception and gender identity remains poorly understood from a behavioral experimental perspective, and we do not know whether, and if so how, the perceived sex of own body influences the sense of own gender in nontransgender individuals. ...
... Multisensory representations in the posterior parietal cortex may be particularly important in this respect, as this region is sensitive to the perceived size and shape of one's own body 33,72 , including waist size 72 , which is likely to be important for the identification of the body's sex based on secondary sex characteristics. Notably, the pattern of resting-state connectivity in the posterior parietal cortex is different in transgender individuals compared to age-matched controls 21 , and a recent study reported that individuals with gender dysphoria display greater cortical thickness of the anterior cingulate cortex and lateral occipital cortex than controls 23 . Interestingly, the lateral occipital cortex, which includes the extrastriate body area-a higher-order visual area that is involved in the processing of images of human body parts 73 -shows increased activation during body ownership illusions 33,38,70,71 . ...
Gender identity is a collection of thoughts and feelings about one’s own gender, which may or may not correspond to the sex assigned at birth. How this sense is linked to the perception of one’s own masculine or feminine body remains unclear. Here, in a series of three behavioral experiments conducted on a large group of control volunteers (N = 140), we show that a perceptual illusion of having the opposite-sex body is associated with a shift toward a more balanced identification with both genders and less gender-stereotypical beliefs about own personality characteristics, as indicated by subjective reports and implicit behavioral measures. These findings demonstrate that the ongoing perception of one’s own body affects the sense of one’s own gender in a dynamic, robust, and automatic manner.
... Mounting research efforts over the past two decades have been trying to determine whether transgender persons bear more neuroanatomical resemblance to their gender identity or their sex assigned at birth (Guillamon, Junque, & Gomez-Gil, 2016;Mueller, De Cuypere, & T'Sjoen, 2017;Smith, Junger, Derntl, & Habel, 2015). Yet, neuroanatomical findings in transgender persons remain highly discrepant possibly due to a variety of factors including sexual orientation (Burke, Manzouri, & Savic, 2017;Manzouri & Savic, 2019), genetics (Heylens et al., 2012), hormonal factors (Wallien, Zucker, Steensma, & Cohen-Kettenis, 2008), as well as small size of the cohorts (Arcelus et al., 2015). In addition, cultural factors have remained unexplored to date as the majority of transgender neuroimaging has been conducted in Western populations (Mueller, De Cuypere, et al., 2017). ...
... Of note, sexual orientation may also contribute to prior discrepancy. Guillamon et al. (2016) and Savic and colleagues (Manzouri & Savic, 2019) hypothesized that sexual orientation may significantly contribute to the discrepant findings as it was not well-controlled for in previous work (e.g., Luders et al., 2009;Mueller, Landre, et al., 2017) or, instead, the sample size was very small (Simon et al., 2013). One strength of the present study was that both trans- The second objective aimed to examine how divergence in anatomical findings can be further reduced, especially when dealing with populations with small prevalence rates. ...
Although the neuroanatomy of transgender persons is slowly being charted, findings are presently discrepant. Moreover, the major body of work has focused on Western populations. One important factor is the issue of power and low signal‐to‐noise (SNR) ratio in neuroimaging studies of rare study populations including endocrine or neurological patient groups. The present study focused on the structural neuroanatomy of a Non‐Western (Iranian) sample of 40 transgender men (TM), 40 transgender women (TW), 30 cisgender men (CM), and 30 cisgender women (CW), while assessing whether the reliability of findings across structural anatomical measures including gray matter volume (GMV), cortical surface area (CSA), and cortical thickness (CTh) could be increased by using two back‐to‐back within‐session structural MRI scans. Overall, findings in transgender persons were more consistent with sex assigned at birth in GMV and CSA, while no group differences emerged for CTh. Repeated measures analysis also indicated that having a second scan increased SNR in all regions of interest, most notably bilateral frontal poles, pre‐ and postcentral gyri and putamina. The results suggest that a simple time and cost‐effective measure to improve SNR in rare clinical populations with low prevalence rates is a second anatomical scan when structural MRI is of interest. This study assesses the reproducibility of previous neuroanatomical findings in Western transgender persons in a Non‐Western population. It then shows that repeating an anatomical MRI sequence can increase data reliability especially in brain regions that have previously been implicated to differ between transgender and cisgender persons. This scan–rescan method might enhance the power of studies with small samples due to low prevalence of target population.
... 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. ...
... For this reason, we measured the differential activation deriving by the contrast female vs. male faces and not the absolute activations induced by the perception of male or female faces. Since other investigations conducted with different tasks have shown that sexual attraction can affect brain activations [25,66,67], we cannot exclude the contribution of sexual orientation in our results. However, we believe that the sexual orientation may marginally if ever have influenced our results. ...
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.
... Od rodovo kongruentných jedincov sa líšia napríklad v neuronálnych sieťach, ktoré sprostredkovávajú cerebrálnu reprezentáciu vlastnej telesnej schémy. Rozdiely možno nájsť v pregenuálnom anteriórnom kortexe cingula, v temporo-parietálnej junkcii a v area fusiformis, respektíve sa ukazuje, že transrodové osoby majú nižšiu štrukturálnu a funkčnú konektivitu medzi anteriórnym cingulom a precuneom a v pravej okcipitoparietálnej kôre (23). Keďže neuroanatomické diferencie transrodových jedincov presahujú neuronálne okruhy relevantné pre sexuálne alebo endokrinné funkcie, možno konštatovať, že transrodovosť je podmienená aj neuronálnymi sieťami dôležitými pre vnímanie seba samého (24). ...
Izáková Ľ, Bartl I, Jamborová O, Kalafutová I, Krištúfková A, Máthé R, Patarák M, Štefániková J, Vašečková B. Štandardný postup pre diagnostiku a komplexný manažment zdravotnej starostlivosti o dospelú osobu s transsexualizmom (F64.0). Sexuológia, 2023; 23(2): 15-34.
... Functional connections from the right insular cortex to the left angular gyrus are increased in MTF transgenders treated with hormonal therapy (antiandrogen and estrogen administration) compared to cisgender men, and the alexithymia tendency is also altered by hormonal therapy (68). Furthermore, functional and structural differences have been suggested between transgender and cisgender individuals in the brain regions that process bodily sensations (69). Regarding bodily sensations, individuals with higher concentrations of salivary oxytocin may experience a stronger sense of body possession during the rubber hand illusion (70). ...
Introduction: The extreme male brain (EMB) theory, a major causal hypothesis of autism (ASD: autism spectrum disorder), attributes excess androgens during early development as one of the causes. While studies have generally followed the EMB theory in females at birth, the co-occurrence of ASD in males at birth has been observed in conditions that are assumed to be associated with reduced androgen action during early development, including Klinefelter syndrome (KS) and sexual minorities. ASD is also associated with atypical sensory sensitivity, synesthesia, and savant syndrome.
Methods: In the present study, we examined adult KS individuals (n = 22), sexual minorities assigned male at birth (n = 66), and control males matched for age and educational background to those with KS [Exploratory analysis (control 1st): n = 36; Reanalysis (control 2nd): n = 583]. Participants completed a self-report questionnaire assessing sensory hypersensitivity/hyposensitivity, savant tendency (developed for the present study), synesthesia, and sexual aspects, including gender identity and sexual orientation.
Results: The results of the exploratory analysis suggested that individuals with KS exhibited a higher tendency toward sensory hypersensitivity/hyposensitivity than the tendency exhibited by the controls. In the Reanalysis, sexual minorities were more likely to be synesthetes, and in both analyses sexual minorities exhibited a higher savant tendency and sensory hypersensitivity/hyposensitivity than the controls. Moreover, the gender dysphoric state was associated with phenotypes observed in individuals with ASD, such as synesthesia, savant tendency, and sensory hypersensitivity/hyposensitivity.
Discussion: These results suggest a common physiological background among gender dysphoria, synesthesia, savant tendency, and atypical sensory sensitivity. Thus, androgynous features (reduced effects of sex steroids during early development) in males at birth may be partially related to the phenotype commonly observed in individuals with ASD. Based on the present results, we propose that the reduction of sex steroids during early development may lead to atypical neurodevelopment and be involved in the atypicality of external and internal sensory perception, and thus in the atypicality of self-concept integration, through the disruption of oxytocin and the gamma-aminobutyric acid system modulating the neural excitation/inhibition balance.
... Interestingly, trans individuals showed peculiarities in structural and functional patterns implicated in body perception [10], such as the insula [6], the cingulate cortex, precuneus cortex, mesial prefrontal cortex, the left angular gyrus, and the superior parietal cortex [21][22][23][24][25][26]. Clemens and colleagues [27] examined the effect of hormonal treatment on resting state functional connectivity (rs-FC) of subjects with GD, finding a stronger FC in the thalamus of hormone-naïve trans women compared with treated ones and cis women; however, after receiving hormone therapy, their rs-FC shifted more toward their aspired gender. ...
Introduction: Several studies have investigated the specific neural correlates of trans people, highlighting mixed results. This study aimed to compare the presence of specific functional connectivity and differences in cognitive profile and hormone levels in trans men diagnosed with gender dysphoria (GD), and a homogeneous group of cisgender men and cisgender women. Methods: A total of 42 participants (19 trans men, 11 cisgender men, and 12 cisgender women) underwent a resting state fMRI and were measured for blood levels of testosterone, estradiol, and progesterone. A neuropsychological battery evaluated executive functions, attention, visual-perceptual ability, verbal fluency, manual preference, and general intelligence. Results: Trans men showed weaker functional connectivity in the precentral gyrus, subcallosal cortex, paracingulate gyrus, temporal pole, and cingulate gyrus than cisgender men (p < 0.01). Trans men performed worse than cisgender men in verbal and visuospatial working memory but similarly to cisgender women (p < 0.05). In trans men, functional connectivity of the precentral gyrus correlated positively with testosterone (r = 0.459, p = 0.064) and negatively with estradiol (r = −0.654, p = 0.004) and progesterone blood levels (r = −0.475, p = 0.054). The cluster involving the subcallosal cortex showed a positive correlation with testosterone (r = 0.718, p = 0.001), and a negative correlation with estradiol (r = −0.602, p = 0.011). The functional connectivity from a cluster involving the paracingulate gyrus showed a positive correlation with testosterone (r = 0.592, p = 0.012). Conclusions: This study highlights the importance of overpassing the binary model by underlining the presence of neural pathways that could represent the peculiarity of the neural profile of people with GD.
... Kilpatrick et al., (2019, pp. 3276-3277) and Manzouri and Savic (2019, pp. 2096-2097 insist on the reasons to believe that their findings reflect underlying factors rather than the effects of gender dysphoria, pointing that the neuroanatomical differences found in transgender people could be due to changes or differences in cortical development, and thus linked to its cause. ...
This paper critically analyses three main neurobiological hypotheses on trans* identities: the neurobiological theory about the origin of gender dysphoria, the neurodevelopmental cortical hypothesis, and the alternative hypothesis of self-referential thinking and body perception. In this study I focus then the attention on three elements: the issue of (de)pathologisation, the idea of the trans brain, and the aetiology of trans* identities. While the neurobiological theory about the origin of gender dysphoria and the neurodevelopmental cortical hypothesis claim the existence of the trans brain, each offering its own neurobiological depiction, the hypothesis of self-referential thinking and body perception doesn’t postulate a distinctive neurobiological trait for all trans* people. I problematize both portrayals of the trans brain departing from the findings and conceptualizations of the paradigm shifting brain mosaicism. Unlike the hypothesis of self-referential thinking and body perception that keeps the question of causation open, both the neurobiological theory about the origin of gender dysphoria and the neurodevelopmental cortical hypothesis situate the origin of trans* identities in the neurobiological domain. I challenge the biological deterministic framework in which this aetiology is inscribed from a dynamic processual entanglement perspective. Finally, concerning the issue of (de)pathologisation of trans* identities, an evolution can be seen in each of the hypothesis and among them, from the least to the most depathologising. However, I question their complete departure from a pathologising framework.
... This finding discloses a difference in the two groups in areas that are necessary for controlling the perception of one's own body and for recognizing faces [60]. In a study conducted in 2018, it was shown that transgender people had an increased cortical thickness in the prefrontal mesial region and the left area of the occipitotemporal cortex [61]. Furthermore, a study conducted in 2015 found a reduced hemispheric connection between the subcortical and limbic areas in transgender subjects compared to those studied [62]. ...
Gender dysphoria is a clinical condition characterized by significant distress due to the discordance between biological sex and gender identity. Currently, gender dysphoria is also found more frequently in children and adolescents, thanks to greater social sensibleness and new therapeutic possibilities. In fact, it is estimated that the prevalence of gender dysphoria in pediatric age is between 0.5% and 2% based on the statistics of the various countries. Therefore, the pediatrician cannot fail to update himself on these issues and above all should be the reference figure in the management of these patients. Even if the patient must be directed to a referral center and be followed up by a multidisciplinary team, the treating pediatrician will care to coordinate the clinical and therapeutic framework. The aim of the present report is therefore to integrate literature data with our clinical experience to propose a new clinical approach in which the pediatrician should be the reference in the care of these patients, directing them towards the best therapeutic approach and staying in contact with the specialists of the referral center.
Supplementary Information
The online version contains supplementary material available at 10.1186/s13052-023-01466-z.
... Zaobserwowany został istotny spadek przeciętnego poziomu samooceny wśród osób z mniejszości seksualnych w porównaniu do badania opisującego sytuację społeczną osób LGBTQ+ w Polsce w latach 2015-2016 [9]. Oznacza to, że na przestrzeni czterech lat średnio opinia wszystkich osób społeczności LGBTQIA+ na swój temat uległa znacznemu pogorszeniu -co potwierdzają inne badania naukowe [10][11][12][13][14][15][16]. Sytuacja ta dotyczy również dzieci i młodzieży, którzy utożsamiają się z mniejszością seksualną. ...
SPOŁECZNOŚĆ OSÓB LGBTQIA+, JAKOŚĆ ŻYCIA I SAMOOCENA
... In a study of brain white matter tracts in which heterosexual sex differences in tissue microstructure were observed, homosexual participants showed little-to-no difference from same-sex heterosexuals; however, differences were more pronounced when heterosexual men and women were compared with transgender women (androphilic males) and men (gynephilic females), respectively (Burke et al., 2017). In another study, Manzouri and Savic (2019) examined both brain structure and resting-state functional connectivity. Among their cisgender and transgender participants, attraction to the same birth-assigned sex was associated with cortical thickness that was intermediate relative to other-sex attracted cisgender controls, but transgender participants were unique in that they showed a different pattern of functional connectivity within a brain network thought to be involved in body representation. ...
Sexual orientation is a core aspect of human experience and understanding its development is fundamental to psychology as a scientific discipline. Biological perspectives have played an important role in uncovering the processes that contribute to sexual orientation development. Research in this field has relied on a variety of populations, including community, clinical, and cross-cultural samples, and has commonly focused on female gynephilia (i.e., female sexual attraction to adult females) and male androphilia (i.e., male sexual attraction to adult males). Genetic, hormonal, and immunological processes all appear to influence sexual orientation. Consistent with biological perspectives, there are sexual orientation differences in brain development and evidence indicates that similar biological influences apply across cultures. An outstanding question in the field is whether the hypothesized biological influences are all part of the same process or represent different developmental pathways leading to same-sex sexual orientation. Some studies indicate that same-sex sexually oriented people can be divided into subgroups who likely experienced different biological influences. Consideration of gender expression in addition to sexual orientation might help delineate such subgroups. Thus, future research on the possible existence of such subgroups could prove to be valuable for uncovering the biological development of sexual orientation. Recommendations for such future research are discussed.
... In the right posterior cingulate gyrus, a component of the posterior default mode network, cisgender boys showed stronger functional connectivity to the rest of this network than all other groups. The authors interpreted the results as generally supporting two theoretical perspectives on brain characteristics in GD, which have also been supported by studies in GD adults (e.g., [15][16][17][18]. ...
Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Brain functional connectivity in adolescents who experience GD may be associated with experienced gender (vs. assigned sex) and/or brain networks implicated in own-body perception. Furthermore, sexual orientation may be related to brain functional organization given commonalities in developmental mechanisms proposed to underpin GD and same-sex attractions. Here, we applied group independent component analysis to resting-state functional magnetic resonance imaging (rs-fMRI) BOLD timeseries data to estimate inter-network (i.e., between independent components) timeseries correlations, representing functional connectivity, in 17 GD adolescents assigned female at birth (AFAB) not receiving gender-affirming hormone therapy, 17 cisgender girls, and 15 cisgender boys (ages 12-17 years). Sexual orientation was represented by degree of androphilia-gynephilia and sexual attractions strength. Multivariate partial least squares analyses found that functional connectivity differed among cisgender boys, cisgender girls, and GD AFAB, with the largest difference between cisgender boys and GD AFAB. Regarding sexual orientation and age, the brain’s intrinsic functional organization of GD AFAB was both similar to and different from cisgender girls, and both differed from cisgender boys. The pattern of group differences and the networks involved aligned with the hypothesis that brain functional organization is different among GD AFAB (vs. cisgender) adolescents, and certain aspects of this organization relate to brain areas implicated in own-body perception and self-referential thinking. Overall, brain functional organization of GD AFAB was generally more similar to that of cisgender girls than cisgender boys.
... Instead, most brains comprise unique 'mosaics' of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males (Joel et al. 2015). However, recent studies comparing transgender and cisgender persons show differences in the cerebral networks involved in own body perception in the context of self (Manzouri and Savic 2019;Nota et al. 2017), and in the patterns of brain connectivity that might affect one's sense of body congruence (Moody et al. 2021). If proven, a biological aetiology would destigmatize transgender behaviour. ...
This article is a historical review of the medical and psychiatric diagnoses associated with transgender people across epochs. Ancient Greek and Roman writings already mention gender change. Before a diagnosis even existed, historical documents described the lives of numerous people whom we would consider transgender today. The development of medical classifications took off in the nineteenth century, driven by the blooming of natural sciences. In the nineteenth century, most authors conflated questions of sexual orientation and gender. For example, the psychiatrist Krafft-Ebing reported cases of transgender people but understood them as paranoia, or as the extreme degree of severity in a dimension of sexual inversion. In the early 1900s, doctors such as Magnus Hirschfeld first distinguished homosexual and transgender behaviour. The usual term for transgender people was transvestite, before Harry Benjamin generalised the term transsexual in the mid-20th century. The term transgender became common in the 1970s. This article details the evolution of diagnoses for transgender people from DSM-III and ICD-10 to DSM-5 and ICD-11.
... A prominent hypothesis on the etiology of gender incongruence proposes that divergent early sexual differentiation mediates sex-atypical organization of the brain, and thereby the development of a gender identity not aligning with one's sex (Dörner, 1988;Zhou, Hofman, Gooren, & Swaab, 1995). Partial support for the sexual differentiation hypothesis, which was recently refined (Guillamon, Junque, & Gómez-Gil, 2016;Uribe et al., 2020), has since been provided by several magnetic resonance imaging (MRI) studies (Manzouri & Savic, 2019; also see reviews by Kreukels & Guillamon, 2016;Nguyen et al., 2019). One of these MRI measures, used to characterize white-matter microstructure by means of Diffusion Tensor Imaging (DTI), is fractional anisotropy (FA). ...
Background
Increasing numbers of adolescents seek help for gender-identity questions. Consequently, requests for medical treatments, such as puberty suppression, are growing. However, studies investigating the neurobiological substrate of gender incongruence (when birth-assigned sex and gender identity do not align) are scarce, and knowledge about the effects of puberty suppression on the developing brain of transgender youth is limited.
Methods
Here we cross-sectionally investigated sex and gender differences in regional fractional anisotropy (FA) as measured by diffusion MR imaging, and the impact of puberty on alterations in the white-matter organization of 35 treatment-naive prepubertal children and 41 adolescents with gender incongruence, receiving puberty suppression. The transgender groups were compared with 79 age-matched, treatment-naive cisgender (when sex and gender align) peers.
Results
We found that transgender adolescents had lower FA in the bilateral inferior fronto-occipital fasciculus (IFOF), forceps major and corpus callosum than cisgender peers. In addition, average FA values of the right IFOF correlated negatively with adolescents' cumulative dosage of puberty suppressants received. Of note, prepubertal children also showed significant FA group differences in, again, the right IFOF and left cortico-spinal tract, but with the reverse pattern (transgender > cisgender) than was seen in adolescents.
Conclusions
Importantly, our results of lower FA (indexing less longitudinal organization, fiber coherence, and myelination) in the IFOF of gender-incongruent adolescents replicate prior findings in transgender adults, suggesting a salient neural correlate of gender incongruence. Findings highlight the complexity with which (pubertal) sex hormones impact white-matter development and add important insight into the neurobiological substrate associated with gender incongruence.
... Taken together, current MRI work in trans people before initiation of GAHT has shown many inconsistencies regarding (dis)similarities between the brain characteristics of trans persons and cis persons. Research has found the trans brain to resemble the sex assigned at birth [16][17][18], the gender identity [11,[19][20][21], or even suggesting an intermediate phenotype situated between that of their sex assigned at birth and their gender identity, or showcasing a different pattern altogether [22][23][24][25][26]. Surprisingly lacking from current neuroimaging research in this cohort is the opportunity to utilize MRI to assess metabolite distribution in the brain. ...
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 (1H-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 1H-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.
... Transrodoví jedinci sa odlišujú od rodovo kongruentných cis jedincov napríklad v neuronálnych sieťach, ktoré sprostredkovávajú cerebrálnu reprezentáciu vlastnej telesnej schémy. Rozdiely možno nájsť v pregenuálnom anteriórnom kortexe cingula (pACC), v temporo-parietálnej junkcii a v area fusiformis, respektíve transrodové osoby majú väčšiu kortikálnu hrúbku a nižšiu štrukturálnu a funkčnú konektivitu medzi anteriórnym cingulom a precuneom a v pravej okcipito--parietálnej kôre (15). Keďže neuroanatomické diferencie transrodových jedincov presahujú neuronálne okruhy relevantné pre sexuálne alebo endokrinné funkcie, možno konštatovať, že transrodovosť je podmienená aj neuronálnymi sieťami dôležitými pre vnímanie seba samého (16). ...
Gender Incongruence of Adolescence and Adulthood is characterised by a marked and persistent incongruence between an individual´s experienced gender and the assigned sex, which often leads to a desire to transition, in order to live and be accepted as a person of the experienced gender. The article presents the essential differences between the concepts of gender incongruence, gender dysphoria and transsexualism, as well as a basic medical overview of the issue.
... Some authors refer to an early programming of gender and sexual inclination driven by sexual differentiation in the brain, proposing that the latter influences the development of the brain areas modulating body perception (i.e., related to gender identity) or sexual arousal (i.e., related to sexual orientation) (Burke, Manzouri & Savic, 2017;Manzouri & Savic, 2019). Others underline the interaction between brain, culture and behavior, arguing that structural and functional brain changes in transgender individuals may be consequence of culture and behavior (Mohammadi & Khalegi, 2018). ...
This systematic review explored structural, functional, and metabolic features of the cisgender brain compared with the transgender brain before hormonal treatment and the heterosexual brain compared to the homosexual brain from the analysis of the neuroimaging literature up to 2018. Our main aim was to help identifying neuroradiological brain features that have been related to human sexuality to contribute to the understanding of the biological elements involved in gender identity and sexual orientation. We analyze 30 studies on gender identity and 21 on sexual orientation. Our results suggest that some neuroanatomical, neurophysiological, and neurometabolic features in transgender individuals resemble those of their experienced gender despite the majority resembling those from their natal sex. In homosexual individuals the majority resemble those of their same sex heterosexual population rather than their opposite sex heterosexual population. However, it is always difficult to interpret findings with non-invasive neuroimaging. Given the gross nature of these measures, it is possible that more differences too subtle to measure with available tools yet contributing to gender identity and sexual orientation could be found. Conflicting results contributed to the difficulty of identifying specific brain features which consistently differ between cisgender and transgender or between heterosexual and homosexual groups. The small number of studies, the small sample size of each study, and the heterogeneity of the investigations made it impossible to meta-analyze all the data extracted. Further studies are necessary to increase the understanding of the neurological substrates of human sexuality.
... These findings have implications for identifying those who will benefit more or less from hormone therapy. Furthermore, these results support our previous finding using anatomical metrics (Kilpatrick et al., 2019;Manzouri and Savic, 2019), and contribute to identifying the specific brain networks in GD, prior to therapy, whose connectivity patterns are critical with respect to hormone therapy effects. ...
Individuals with gender dysphoria experience life-threatening distress due to incongruence between their gender identity and birth-assigned sex. Hormone therapy can be effective for reducing body incongruence, but responses vary, and there is no reliable way to predict therapeutic outcomes. We use clinical and MRI data before cross-sex hormone therapy as features to train a machine learning model to predict individuals’ post-therapy body congruence (the degree to which photos of their bodies match their self-identities). Twenty-five transwomen and transmen with gender dysphoria participated. The model significantly predicted post-therapy body congruence. This study provides evidence that hormone therapy efficacy can be predicted from information collected before therapy and that patterns of connectivity within fronto-parietal and cingulo-opercular networks may provide insights into body-brain effects of hormones, affecting one’s sense of body congruence. Results could help identify the need for personalized therapies in individuals predicted to have low body-self congruence after standard therapy.
Impact Statement
Outcomes of cross-sex hormone therapy in gender dysphoria can be predicted on an individual level prior to initiating therapy. Multivariate neuroimaging features provided superior prediction performance over clinical data alone.
... Studies have revealed an intermediate white matter microstructure in transgender men and women relative to that of cisgender men and women. For example, the white matter tracts between the frontal lobe and the parietal lobe are less strongly connected in transgender persons relative to cisgender persons (Manzouri and Savic, 2018). Furthermore, trans people have been found to differ in their axonal organization of the white matter (Rametti et al., 2011a, b) and their rate of diffusion of molecules and water in the brain (Kranz et al., 2014) taking in-between positions between cisgender men and women. ...
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).
Keywords: cross-sex hormones; gender; magnetic resonance imaging; neurobiology; trans
... Second, the association between homosexuality and gender nonconformity appears to hold cross-culturally (VanderLaan, Ren, & Vasey, 2013;Vasey & Bartlett, 2007). Third, a range of physiological and neuroimaging data suggest that male homosexuality is associated with weaker sex dimorphism or sex-reversed dimorphism in the brain (Burke, Manzouri, & Savic, 2017;LeVay, 1991;Manzouri & Savic, 2018a, 2018b. Differentiation of the relevant brain regions is known to occur prenatally (or, in some cases, very early postnatally). ...
Recent literature has described the phenomenon of “straight-acting” gay men: gay men who identify with traditional heteronormative masculinity. The current study examined predictors of “straight-acting” identification in gay men and how identifying as straight-acting relates to well-being. A sample of Australian gay men (N = 966) provided self-report data on two potential predictors of straight-acting identity: self-perceived masculinity and internalized homophobia. A path analysis assessed how these variables related to straight-acting identification. While masculine self-presentation positively predicted well-being and internalized homophobia negatively predicted well-being, straight-acting identification, which positively correlated with both, did not independently predict either psychological distress or physical well-being. Analyses further suggested that internalized homophobia had particularly deleterious effects among gay men who were more feminine. Implications for clinical and public health interventions among gay men are discussed.
Gender Dysphoria (GD) is a common condition seen in clinical practice. The current chapter provides the clinician with an overview of the disorders and looks at various facets of the causation, evaluation, and management of GD. Various terminology related to GD and related terms are defined. The epidemiology and clinical presentation of the disorder are discussed. The chapter provides a glance at various causative theories that have been implicated in the causation of GD. A team-based approach to the management of GD is discussed and the role of the psychiatrist and psychologist are defined. Difficulties in the management are also discussed. The chapter provides good insight for clinicians who deal with GD in their psychiatric clinics on a day-to-day basis.
Gender dysphoria and autism spectrum disorder (ASD) co-occur at high rates. Yet, it is unknown whether gender dysphoria and ASD are associated with common or distinct neurobiological correlates or how they relate to experiences of gender-related body incongruence. Using the Social Responsiveness Scale, we assessed autistic traits in 99 transgender and 99 cisgender individuals and investigated their associations with gender-related body incongruence, measured via a visually based “Body Morph” test, and with cortical thickness in the brain. Autistic traits were significantly higher among transgender individuals, and those with higher autistic traits had higher body incongruence scoring. Among transgender individuals, higher autistic traits were linked with a thinner cortex bilaterally in the temporal pole and the superior and inferior temporal gyri. Autistic traits were only partly associated with cortical morphology patterns previously reported in transgender individuals; instead, they were primarily linked to temporal lobe areas mediating social cognition. While replicating the previous literature on the increased prevalence of autistic traits among transgender individuals, this study reports specific regions in the brains of transgender individuals where cortical thickness is associated with autistic traits.
RESUMEN En las últimas décadas se ha recolectado numerosa información que ayuda a entender algunas bases biológicas de las orientaciones sexuales e identidad de género. El objetivo de la presente investigación fue caracterizar los conocimientos biológicos de la homosexualidad y transexualidad en estudiantes de primer año de Pedagogía en Educación Física. La muestra estuvo constituida por 91 estudiantes de una Universidad de la ciudad de Santiago de Chile. Se aplicó una encuesta sociodemográfica y el cuestionario de conocimientos biológicos de la homosexualidad y transexualidad (CBHT). Los resultados revelan bajos niveles de conocimiento sobre estas temáticas, situación que ocurre tanto en mujeres y hombres. Sólo las creencias religiosas marcan una diferencia, siendo los agnósticos/as o ateos/as los/as que presentan mayores niveles de conocimiento. Se recomienda replicar esta investigación con muestras de estudiantes de Educación Física de otros cursos y otras universidades. PALABRAS CLAVE: Homosexualidad, bisexualidad, transexualidad, biología, educación física.
Introduction:
There has been a drastic increase in the reported number of people seeking help for gender dysphoria in many countries over the last two decades. Yet, our knowledge of gender dysphoria and related outcomes is restricted due to the lack of high-quality studies employing comprehensive approaches. This longitudinal study aims to enhance our knowledge of gender dysphoria; different aspects will be scrutinised, focusing primarily on the psychosocial and mental health outcomes, prognostic markers and, secondarily, on the underlying mechanisms for its origin.
Methods and analysis:
The Swedish Gender Dysphoria Study is an ongoing multicentre longitudinal cohort study with 501 registered participants with gender dysphoria who are 15 years old or older. Participants at different phases of their clinical evaluation process can enter the study, and the expected follow-up duration is three years. The study also includes a comparison group of 458 age- and county-matched individuals without gender dysphoria. Data on the core outcomes of the study, which are gender incongruence and experienced gender dysphoria, body satisfaction and satisfaction with gender-affirming treatments, as well as other relevant outcomes, including mental health, social functioning and life satisfaction, are collected via web surveys. Two different research visits, before and after starting on gender-affirming hormonal treatment (if applicable), are planned to collect respective biological and cognitive measures. Data analysis will be performed using appropriate biostatistical methods. A power analysis showed that the current sample size is big enough to analyse continuous and categorical outcomes, and participant recruitment will continue until December 2022.
Ethics and dissemination:
The ethical permission for this study was obtained from the Local Ethical Review Board in Uppsala, Sweden. Results of the study will be presented at national and international conferences and published in peer-reviewed journals. Dissemination will also be implemented through the Swedish Gender Dysphoria Study network in Sweden.
The chapter discusses twice-exceptionality of the homosexual/lesbian-bisexual/queer gifted child and adolescent from neuropsychological point of view. Non-cisgender gifted have come into the center of giftedness research only around the last decade of the twentieth century, a long time after other sub-subjects of giftedness, such as gender, twice-exceptionality, emotional- and psychiatric problems of the gifted have been already a main part of both theory and practice in the field of giftedness. Thus, the intersection of gay studies and giftedness is still in its infancy, and its study from the neuroscientific point of view is even more limited.
Introduction: There is increasing public and research interest in transgender people and communities. Coupled with this interest is a renewed pursuit of research into the possible biological origins of transgender identity. In this review, we critically examine the biological literature which explores the etiology of transgender identity, including endocrinological, behavioral, genetic, and neuroimaging studies, with the goal of identifying key trends in this literature, limitations, critical gaps, and future directions. Methods: We searched the Pubmed database for peer reviewed original experimental research conducted since 1990, using a combination of six transgender identity-related search terms and 18 topic search terms. Results: A total of 102 articles across the disciplines of endocrinology, genetics, cognitive function, and neuroanatomy met our review criteria. Most studies were conducted at gender identity clinics. Several approaches yielded compelling results, but where replication has been attempted, results have varied. We identified several issues in experimental design and/or interpretation that might account for this inconsistency. Conclusion: A number of research studies have investigated biological factors that could potentially contribute to transgender identity, but results often contradict each other. Interpretation of etiological studies of transgender identity can be misunderstood and/or misused by media, politicians, and care providers, placing transgender people at risk. We question the utility of etiological studies in clinical care, given that transgender identity is not pathological. When etiological studies are undertaken, we recommend new, inclusive designs for a rigorous and compassionate approach to scientific practice in the service of transgender communities and the providers who serve them.
Several studies investigated the specific neural correlates of trans people, highlighting mixed results. This study aimed to investigate the presence of specific functional connectivity in trans men, compared to a homogeneous group of cisgender men and cisgender women. 42 participants (19 trans men, 11 cisgender men, and 12 cisgender women) underwent a resting state fMRI; a blood sample was collected in order to evaluate the hormonal status of testosterone, estradiol, and progesterone. Screening measures were administered for evaluating the intellectual ability and manual preference. Moreover, all participants underwent a neuropsychological evaluation of executive functions, attention, visual-perceptual ability, and verbal fluency. Trans men showed a weaker functional connectivity in the precentral gyrus, subcallosal cortex, paracingulate gyrus, temporal pole, and cingulate gyrus in contrast to cisgender men. Furthermore, trans men showed a worse performance than cisgender men and similar to that of cis women in verbal and visuospatial working-memory. In trans men, functional connectivity of precentral gyrus was positively correlated with blood testosterone and negatively correlated with estradiol and progesterone; the cluster involving the subcallosal cortex showed a positive correlation with testosterone and negative with estradiol, and the functional connectivity from a cluster involving the paracingulate gyrus showed a positive correlation with testosterone.
This study sheds light to the importance of overpassing the binary-model, by highlighting the presence of neural pathways that could represent the peculiarity of the neural profile of people with gender dysphoria.
Background:
Sexual orientation in humans represents a multilevel construct that is grounded in both neurobiological and environmental factors.
Objective:
Here, we bring to bear a machine learning approach to predict sexual orientation from gray matter volumes (GMVs) or resting-state functional connectivity (RSFC) in a cohort of 45 heterosexual and 41 homosexual participants.
Methods:
In both brain assessments, we used penalized logistic regression models and nonparametric permutation.
Results:
We found an average accuracy of 62% (±6.72) for predicting sexual orientation based on GMV and an average predictive accuracy of 92% (±9.89) using RSFC. Regions in the precentral gyrus, precuneus and the prefrontal cortex were significantly informative for distinguishing heterosexual from homosexual participants in both the GMV and RSFC settings.
Conclusions:
These results indicate that, aside from self-reports, RSFC offers neurobiological information valuable for highly accurate prediction of sexual orientation. We demonstrate for the first time that sexual orientation is reflected in specific patterns of RSFC, which enable personalized, brain-based predictions of this highly complex human trait. While these results are preliminary, our neurobiologically based prediction framework illustrates the great value and potential of RSFC for revealing biologically meaningful and generalizable predictive patterns in the human brain.
Sexual orientation is a core aspect of human experience and understanding its development is fundamental to psychology as a scientific discipline. Biological perspectives have played an important role in helping to uncover the processes that contribute to sexual orientation development. Research in this field has relied on a variety of populations, including community, clinical, and cross-cultural samples, and has commonly focused on female gynephilia (i.e., female sexual attraction to adult females) and male androphilia (i.e., male sexual attraction to adult males). Genetic, hormonal, and immunological processes all appear to influence sexual orientation. Consistent with biological perspectives, there are sexual orientation differences in brain development and evidence indicates that similar biological influences apply across cultures. An outstanding question in the field is whether the hypothesized biological influences are all part of the same process or represent different developmental pathways leading to same-sex sexual orientation. Some studies indicate that same-sex sexually oriented people can be divided into subgroups who likely experienced different biological influences. Consideration of gender expression in addition to sexual orientation might help delineate such subgroups. Thus, future research on the possible existence of such subgroups could prove to be valuable for uncovering the biological development of sexual orientation. Recommendations for such future research are discussed.KeywordsSexual orientationDevelopmentGeneticsSex hormonesMaternal immune hypothesisGender expression
Introducción:
La orientación sexual y la identidad de género poseen algunas bases biológicas que radican en genes, hormonas perinatales y dimorfismos cerebrales que han sido estudiados en las últimas décadas. Los objetivos del presente estudio son conocer las propiedades psicométricas de un cuestionario que evalúa conocimientos biológicos de la homosexualidad y transexualidad e indagar dichos conocimientos en una muestra chilena.
Metodología:
Se encuestaron a 144 personas de tres regiones de Chile. Se aplicó una encuesta sociodemográfica y el Cuestionario de Conocimientos Biológicos de la Homosexualidad y Transexualidad (CBHT).
Resultados:
Muestran que el instrumento es válido y confiable para la muestra utilizada. También se observa que el 75,7% de los encuestados obtuvieron entre 1 y 6 respuestas correctas de un máximo de 18. De las variables sociodemográficas sólo las creencias religiosas y el haber tratado temas de homosexualidad y transexualidad en sus clases de educación sexual son predictores de los puntajes del cuestionario CBHT.
Conclusiones y recomendaciones:
el CBTH es válido y confiable para ser aplicado en muestras de población chilena. La muestra evaluada posee bajos niveles de conocimientos sobre las bases biológicas de la homosexualidad y transexualidad. Se recomienda replicar esta investigación en muestras de mayor tamaño, en otras regiones de Chile y en otros países latinoamericanos.
Resumen. Estudios realizados durante las últimas tres décadas han revelado fuertes bases biológicas de la homosexualidad y transexualidad. Los objetivos de la presente investigación fueron validar el cuestionario de Conocimientos Biológicos de la Homosexualidad y Transexualidad (CBHT) en una muestra de estudiantes del área de la actividad física de México y describir estos conocimientos en la muestra evaluada. Para ello se encuestaron a 324 estudiantes de México aplicando una encuesta sociodemográfica y el cuestionario CBHT. Los resultados revelan índices adecuados de validez y confiabilidad del cuestionario CBHT en la muestra, que los niveles de conocimientos biológicos sobre estos temas son bajos y que las variables sociodemográficas que inciden en dichos resultados son el sexo y el tener un amigo/a o conocido/a homosexual o bisexual. Se recomienda continuar con la evaluación de muestras de estudiantes de otras carreras de pedagogía y de diferentes regiones de México.
Abstract. Studies conducted over the past three decades have revealed strong biological bases for homosexuality and transsexuality. The objectives of this research were to validate the Biological Knowledge of Homosexuality and Transsexuality (BKHT) questionnaire in a sample of students from the area of physical activity in Mexico and describe this knowledge in the sample evaluated. To this end, 324 students from Mexico were surveyed using a sociodemographic survey and the BKHT questionnaire. The results reveal adequate indices of validity and reliability of the BKHT questionnaire in the sample, that the levels of biological knowledge on these topics are low and that the sociodemographic variables that affect these results are sex and having a friend/a known/a homosexual or bisexual. It is recommended to continue with the evaluation of samples of students from other pedagogy careers and from different regions of Mexico.
Research related to the lives of transgender and gender diverse (TGD) people has grown substantially in recent years. One area of such growth has been research on TGD people’s sexuality. Sexuality can include sexual behaviors, sexual attraction, and sexual identity, among other domains. Historically, sexuality of TGD people was often policed by providers with expectations of heterosexuality or the conflation of sexuality and gender experiences. This resulted in a lag in understanding the lived experiences of TGD people in relation to sexuality. In this review, we examine research that has been conducted over the past 5 years with any measurement of sexuality with TGD participants. The initial search revealed 11,891 articles. After removing duplicates, there were 6,538 articles in the abstract review stage, with 1,669 retained for full text review and 179 retained for extraction. Most studies included majority white samples, and about half were conducted solely in the United States. Most studies measured a single dimension of sexuality, specifically sexual identity, whereas only 2.2% asked about all three dimensions of identity, behavior, and attraction. Of those that inquired about sexual identity, most samples were majority sexual minorities. Many studies had issues related to inclusivity, such as the language used in response options or questions. These findings are placed within the context of the revised 2021 guidelines for practice with sexual minorities and emphasize the importance of diversifying our field’s understandings and assessments of sexuality for TGD people.
Resumen. Introducción: la homosexualidad y la transexualidad están mediadas por mecanismos biológicos de tipo genético, accionar temprano de hormonas y por mecanismos ambientales, lo que repercute en cambios estructurales y funcionales de diversas regiones cerebrales. El objetivo de la presente investigación es describir los conocimientos biológicos de la homosexualidad y transexualidad de estudiantes de Educación Física. Método: se construyó y valido un cuestionario diseñado ad hoc a 305 estudiantes de Pedagogía en Educación Física de tres universidades de Chile. Resultados: el cuestionario quedó constituido por 18 ítems, además presenta seis factores que explican el 58.378% de la varianza y un alfa de Cronbach de .763. El ítem que presentó mayor cantidad de respuestas acertadas fue Existe un «gen gay» que determina la homosexualidad y el lesbianismo y el que presento menor cantidad de aciertos fue Cuando una mujer es lesbiana existen más probabilidad que su hermana también sea lesbiana. Conclusión: los análisis demuestran que el instrumento es válido y confiable para evaluar el conocimiento biológico de la homosexualidad y transexualidad en estudiantes de Pedagogía en Educación Física. En 14 ítems más del 50% de la muestra contesto no sé y el 78.6% de la muestra obtuvo sólo entre una y seis respuestas correctas. Palabras claves: biología, cerebro, homosexualidad, transexualidad, educación física. Abstract. Introduction: homosexuality and transsexuality are mediated by biological mechanisms of genetic type, early action of hormones and by environmental mechanisms, affecting structural and functional changes in various brain regions. The aim of this research is describe the biological knowledge of homosexuality and transsexuality for students of Physical Education. Method: an ad hoc questionnaire was built and applied to 305 students of Pedagogy in Physical Education from three universities in Chile. Results: the questionnaire was constituted by 18 items, in addition it presents six factors that explain the 58.378% of variance and a Cronbach alpha of .763. The item that presented the most successful answers was There is a «gay gene» that determines homosexuality and lesbianism and the one that presents the least number of successful was When a woman is a lesbian there is more chance that her sister is also a lesbian. Conclusion: Analyses show that the instrument is valid and reliable for assessing the biological knowledge of homosexuality and transsexuality in students of Physical Education Pedagogy. In 14 items more than 50% of the sample answered I do not know and 78.6% of the sample obtained only between one and six correct answers.
El presente trabajo es una revisión de los estudios científicos que se han desarrollado en los últimos años para tratar de comprender que es el amor, cuáles son las bases de la monogamia y fidelidad, porque surge el deseo sexual y cuáles son las bases biológicas de la homosexualidad y la identidad de género. El desarrollo de la neurociencia ha generado la posibilidad de explicar fenómenos que hasta hace un siglo parecían misterios sin solución. Entre ellos, el amor y el sexo ocupan un lugar importante entre las modernas investigaciones de la conducta.
Este libro es una invitación para conocer un poco más sobre estos fenómenos tan importantes y que son parte de las vivencias de casi todas las personas. Una visión seria basada en los más recientes descubrimientos logrados por la biología, para tratar de aclarar porque nos enamoramos de una pareja, donde surge el amor materno, porque muchas personas son infieles, porque hay personas que le atraen personas de su mismo sexo y porque hay personas que se sienten del sexo opuesto
Introduction
Recent research found gender‐related differences in resting‐state functional connectivity (rs‐FC) measured by functional magnetic resonance imaging (fMRI). To the best of our knowledge, there are no studies examining the differences in rs‐FC between men, women, and individuals who report a discrepancy between their anatomical sex and their gender identity, i.e. gender dysphoria (GD).
Methods
To address this important issue, we present the first fMRI study systematically investigating the differences in typical resting‐state networks (RSNs) and hormonal treatment effects in 26 male‐to‐female GD individuals (MtFs) compared with 19 men and 20 women.
Results
Differences between male and female control groups were found only in the auditory RSN, whereas differences between both control groups and MtFs were found in the auditory and fronto‐parietal RSNs, including both primary sensory areas (e.g. calcarine gyrus) and higher order cognitive areas such as the middle and posterior cingulate and dorsomedial prefrontal cortex. Overall, differences in MtFs compared with men and women were more pronounced before cross‐sex hormonal treatment. Interestingly, rs‐FC between MtFs and women did not differ significantly after treatment. When comparing hormonally untreated and treated MtFs, we found differences in connectivity of the calcarine gyrus and thalamus in the context of the auditory network, as well as the inferior frontal gyrus in context of the fronto‐parietal network.
Conclusion
Our results provide first evidence that MtFs exhibit patterns of rs‐FC which are different from both their assigned and their aspired gender, indicating an intermediate position between the two sexes. We suggest that the present study constitutes a starting point for future research designed to clarify whether the brains of individuals with GD are more similar to their assigned or their aspired gender.
The World Health Organization (WHO) is revising the tenth version of the International Classification of Diseases and Related Health Problems (ICD-10). This includes a reconceptualization of the definition and positioning of Gender Incongruence of Childhood (GIC). This study aimed to: 1) collect the views of transgender individuals and professionals regarding the retention of the diagnosis; 2) see if the proposed GIC criteria were acceptable to transgender individuals and health care providers; 3) compare results between two countries with two different healthcare systems to see if these differences influence opinions regarding the GIC diagnosis; and 4) determine whether healthcare providers from high-income countries feel that the proposed criteria are clinically useful and easy to use. A total of 628 participants were included in the study: 284 from the Netherlands (NL; 45.2%), 8 from Flanders (Belgium; 1.3%), and 336 (53.5%) from the United Kingdom (UK). Most participants were transgender people (or their partners/relatives; TG) (n = 522), 89 participants were healthcare providers (HCPs) and 17 were both HCP and TG individuals. Participants completed an online survey developed for this study. Overall, the majority response from transgender participants (42.9%) was that if the diagnosis would be removed from the mental health chapter it should also be removed from the ICD-11 completely, while 33.6% thought it should remain in the ICD-11. Participants were generally satisfied with other aspects of the proposed ICD-11 GIC diagnosis: most TG participants (58.4%) thought the term Gender Identity Disorder should change, and most thought Gender Incongruence was an improvement (63.0%). Furthermore, most participants (76.1%) did not consider GIC to be a psychiatric disorder and placement in a separate chapter dealing with Gender and Sexual Health (the majority response in the NL and selected by 37.5% of the TG participants overall) or as a Z-code (the majority response in the UK and selected by 26.7% of the TG participants overall) would be preferable. In the UK, the majority response (35.8%) was that narrowing the GIC diagnosis was an improvement, while the NL majority response (49.5%) was that this was not an improvement. Although generally the results from HCPs were in line with the results from TG participants some differences were found. This study suggests that, although in an ideal world a diagnosis is not welcomed, several participants felt the diagnosis should not be removed. This is likely due to concerns about restricting access to reimbursed healthcare. The choice for positioning of a diagnosis of GIC within the ICD-11 was as a separate chapter dealing with symptoms and/or disorders regarding sexual and gender health. This was the overall first choice for NL participants and second choice for UK participants, after the use of a Z-code. The difference reflects that in the UK, Z-codes carry no negative implications for reimbursement of treatment costs. These findings highlight the challenges faced by the WHO in their attempt to integrate research findings from different countries, with different cultures and healthcare systems in their quest to create a manual that is globally applicable.
Background
Anorexia nervosa (AN) is a severe mental illness, with an unknown etiology. Magnetic resonance imaging studies show reduced brain volumes and cortical thickness in patients compared to healthy controls. However, findings are inconsistent, especially concerning the anatomical location and extent of the differences. The purpose of this study was to estimate and compare brain volumes and regional cortical thickness in young females with AN and healthy controls. Methods
Magnetic resonance imaging data was acquired from young females with anorexia nervosa (n = 23) and healthy controls (n = 28). Two different scanner sites were used. BMI varied from 13.5 to 20.7 within the patient group, and 11 patients had a BMI > 17.5. FreeSurfer was used to estimate brain volumes and regional cortical thickness. ResultsThere were no differences between groups in total cerebral cortex volume, white matter volume, or lateral ventricle volume. There were also no volume differences in subcortical grey matter structures. However the results showed reduced cortical thickness bilaterally in the superior parietal gyrus, and in the right inferior parietal and superior frontal gyri. Conclusions
The functional significance of the findings is undetermined as the majority of the included patients was already partially weight-restored. We discuss whether these regions could be related to predisposing factors of the illness, or whether they are regions that are more vulnerable to starvation, malnutrition or associated processes in AN.
While most people take identification with their body for granted, conditions such as phantom limb pain, alien hand syndrome, and xenomelia suggest that the feeling of bodily congruence is constructed and susceptible to alteration. Individuals with xenomelia typically experience one of their limbs as over-present and aversive, leading to a desire to amputate the limb. Similarly, many transgender individuals describe their untreated sexed body parts as incongruent and aversive, and many experience phantom body parts of the sex they identify with (Ramachandran, 2008). This experience may relate to differences in brain representation of the sexed body part, as suggested in xenomelia (McGeoch et al., 2011). We utilized magnetoencephalography imaging to record brain activity during somatosensory stimulation of the breast—a body part that feels incongruent to most presurgical female-to-male (FtM)-identified transgender individuals—and the hand, a body part that feels congruent. We measured the sensory evoked response in right hemisphere somatosensory and body-related brain areas and found significantly reduced activation in the supramarginal gyrus and secondary somatosensory cortex, but increased activation at the temporal pole for chest sensation in the FtM group (N = 8) relative to non-transgender females (N = 8). In addition, we found increased white matter coherence in the supramarginal gyrus and temporal pole and decreased white matter diffusivity in the anterior insula and temporal pole in the FtM group. These findings suggest that dysphoria related to gender-incongruent body parts in FtM individuals may be tied to differences in neural representation of the body and altered white matter connectivity.
Gender dysphoria (GD) is characterized by incongruence between one’s identity and gender assigned at birth. The biological mechanisms of GD are unclear. We investigated brain network connectivity patterns involved in own body perception in the context of self in GD. Twenty-seven female-to-male (FtM) individuals with GD, 27 male controls, and 27 female controls underwent resting state fMRI. We compared functional connections within intrinsic connectivity networks involved in self-referential processes and own body perception –default mode network (DMN) and salience network – and visual networks, using independent components analyses. Behavioral correlates of network connectivity were also tested using self-perception ratings while viewing own body images morphed to their sex assigned at birth, and to the sex of their gender identity. FtM exhibited decreased connectivity of anterior and posterior cingulate and precuneus within the DMN compared with controls. In FtM, higher “self” ratings for bodies morphed towards the sex of their gender identity were associated with greater connectivity of the anterior cingulate within the DMN, during long viewing times. In controls, higher ratings for bodies morphed towards their gender assigned at birth were associated with right insula connectivity within the salience network, during short viewing times. Within visual networks FtM showed weaker connectivity in occipital and temporal regions. Results suggest disconnectivity within networks involved in own body perception in the context of self in GD. Moreover, perception of bodies in relation to self may be reflective rather than reflexive, as a function of mesial prefrontal processes. These may represent neurobiological correlates to the subjective disconnection between perception of body and self-identification.
The present review focuses on the brain structure of male-to-female (MtF) and female-to-male (FtM) homosexual transsexuals before and after cross-sex hormone treatment as shown by in vivo neuroimaging techniques. Cortical thickness and diffusion tensor imaging studies suggest that the brain of MtFs presents complex mixtures of masculine, feminine, and demasculinized regions, while FtMs show feminine, masculine, and defeminized regions. Consequently, the specific brain phenotypes proposed for MtFs and FtMs differ from those of both heterosexual males and females. These phenotypes have theoretical implications for brain intersexuality, asymmetry, and body perception in transsexuals as well as for Blanchard's hypothesis on sexual orientation in homosexual MtFs. Falling within the aegis of the neurohormonal theory of sex differences, we hypothesize that cortical differences between homosexual MtFs and FtMs and male and female controls are due to differently timed cortical thinning in different regions for each group. Cross-sex hormone studies have reported marked effects of the treatment on MtF and FtM brains. Their results are used to discuss the early postmortem histological studies of the MtF brain.
The current review gives an overview of brain studies in transgender people. First, we describe studies into the aetiology of feelings of gender incongruence, primarily addressing the sexual differentiation hypothesis: does the brain of transgender individuals resemble that of their natal sex, or that of their experienced gender? Findings from neuroimaging studies focusing on brain structure suggest that the brain phenotypes of trans women (MtF) and trans men (FtM) differ in various ways from control men and women with feminine, masculine, demasculinized and defeminized features. The brain phenotypes of people with feelings of gender incongruence may help us to figure out whether sex differentiation of the brain is atypical in these individuals, and shed light on gender identity development. Task-related imaging studies may show whether brain activation and task performance in transgender people is sex-atypical. Second, we review studies that evaluate the effects of cross-sex hormone treatment on the brain. This type of research provides knowledge on how changes in sex hormone levels may affect brain structure and function.
Gender dysphoria (GD) is characterized by incongruence between onés gender assigned at birth and the gender that one identifies
with. The biological mechanisms of GD are unclear, especially in female-to-male transsexuals (FtM-TR). Here, we investigate
whether distinct structural and functional patterns along cerebral midline networks processing own-body perception may constitute
a biological correlate. Method: MRI of functional connectivity, cortical thickness, surface area, and gray matter volume was
carried out in 28 female-to-male transsexuals (FtM-TR) and 68 cis-sexual controls (34 male). FtM-TR displayed thicker mid-frontal, precuneal-parietal, and lingual cortex than both male and
female controls, whereas, in regions with reported anatomical sex differences among the controls, FtM-TR followed patterns
of the gender assigned at their birth. FtM-TR also displayed weaker functional connections from the pregenual anterior cingulate
to the insular cortex, and the temporo parietal junction compared with both control groups. Distinct structural and functional
pattern in the own-body image network may represent biological markers for the dysphoric own-body perception in transgender
individuals.
Transsexualism is characterized by feelings of incongruity between one's natal sex and one's gender identity. It is unclear whether transsexual individuals have a body image that is more congruent with their gender identity than their sex assigned at birth (natal sex) and, if so, whether there are contributions from perceptual dysfunctions. We compared 16 pre-hormone treatment female-to-male transsexual (FtM) individuals to 20 heterosexual female and 20 heterosexual male controls on a visual identification task. Participants viewed photographs of their own body that were morphed by different degrees to bodies of other females or males, and were instructed to rate "To what degree is this picture you?" We also tested global vs. local visual processing using the inverted faces task. FtM differed from both control groups in demonstrating higher self-identification ratings for bodies morphed to the sex congruent with their gender identity, and across a broad range of morph percentages. This difference was more pronounced for longer viewing durations. FtM showed reduced accuracy for upright faces compared with female controls for short duration stimuli, but no advantage for inverted faces. These results suggest different own body identification in FtM, consisting of a relatively diffuse identification with body images congruent with their gender identity. This is more likely accounted for by conscious, cognitive factors than perceptual differences.
Sex hormones have been shown to contribute to the organization and function of the brain during puberty and adolescence. Moreover, it has been suggested that distinct hormone changes in girls versus boys may contribute to the emergence of sex differences in internalizing and externalizing behavior during adolescence. In the current longitudinal study, the influence of within-subject changes in puberty (physical and hormonal) on cortical thickness and surface area was examined across a 2-year span, while controlling for age. Greater increases in Tanner Stage predicted less superior frontal thinning and decreases in precuneus surface area in both sexes. Significant Tanner Stage and sex interactions were also seen, with less right superior temporal thinning in girls but not boys, as well as greater decreases in the right bank of the superior temporal sulcus surface area in boys compared to girls. In addition, within-subject changes in testosterone over the 2-year follow-up period were found to relate to decreases in middle superior frontal surface area in boys, but increases in surface area in girls. Lastly, larger increases in estradiol in girls predicted greater middle temporal lobe thinning. These results show that within-subject physical and hormonal markers of puberty relate to region and sex-specific changes in cortical development across adolescence.
Previous neuroimaging studies demonstrated sex and also sexual orientation related structural and functional differences in the human brain. Genetic information and effects of sex hormones are assumed to contribute to the male/female differentiation of the brain, and similar effects could play a role in processes influencing human's sexual orientation. However, questions about the origin and development of a person's sexual orientation remain unanswered, and research on sexual orientation related neurobiological characteristics is still very limited. To contribute to a better understanding of the neurobiology of sexual orientation, we used magnetic resonance imaging (MRI) in order to compare regional cortical thickness (Cth) and subcortical volumes of homosexual men (hoM), heterosexual men (heM) and heterosexual women (heW). hoM (and heW) had thinner cortices primarily in visual areas and smaller thalamus volumes than heM, in which hoM and heW did not differ. Our results support previous studies, which suggest cerebral differences between hoM and heM in regions, where sex differences have been reported, which are frequently proposed to underlie biological mechanisms. Thus, our results contribute to a better understanding of the neurobiology of sexual orientation.
Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects' sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development.
Gender dysphoria (also known as "transsexualism") is characterized as a discrepancy between anatomical sex and gender identity. Research points towards neurobiological influences. Due to the sexually dimorphic characteristics of the human voice, voice gender perception provides a biologically relevant function, e.g. in the context of mating selection. There is evidence for a better recognition of voices of the opposite sex and a differentiation of the sexes in its underlying functional cerebral correlates, namely the prefrontal and middle temporal areas. This fMRI study investigated the neural correlates of voice gender perception in 32 male-to-female gender dysphoric individuals (MtFs) compared to 20 non-gender dysphoric men and 19 non-gender dysphoric women. Participants indicated the sex of 240 voice stimuli modified in semitone steps in the direction to the other gender. Compared to men and women, MtFs showed differences in a neural network including the medial prefrontal gyrus, the insula, and the precuneus when responding to male vs. female voices. With increased voice morphing men recruited more prefrontal areas compared to women and MtFs, while MtFs revealed a pattern more similar to women. On a behavioral and neuronal level, our results support the feeling of MtFs reporting they cannot identify with their assigned sex.
Although previous investigations of transsexual people have focused on regional brain alterations, evaluations on a network level, especially those structural in nature, are largely missing. Therefore, we investigated the structural connectome of 23 female-to-male (FtM) and 21 male-to-female (MtF) transgender patients before hormone therapy as compared with 25 female and 25 male healthy controls. Graph theoretical analysis of whole-brain probabilistic tractography networks (adjusted for differences in intracranial volume) showed decreased hemispheric connectivity ratios of subcortical/limbic areas for both transgender groups. Subsequent analysis revealed that this finding was driven by increased interhemispheric lobar connectivity weights (LCWs) in MtF transsexuals and decreased intrahemispheric LCWs in FtM patients. This was further reflected on a regional level, where the MtF group showed mostly increased local efficiencies and FtM patients decreased values. Importantly, these parameters separated each patient group from the remaining subjects for the majority of significant findings. This work complements previously established regional alterations with important findings of structural connectivity. Specifically, our data suggest that network parameters may reflect unique characteristics of transgender patients, whereas local physiological aspects have been shown to represent the transition from the biological sex to the actual gender identity.
Background:
The etiology of anorexia nervosa is still unknown. Multiple and distributed brain regions have been implicated in its pathophysiology, implying a dysfunction of connected neural circuits. Despite these findings, the role of white matter in anorexia nervosa has been rarely assessed. In this study, we used diffusion tensor imaging (DTI) to characterize alterations of white matter microstructure in a clinically homogeneous sample of patients with anorexia nervosa.
Methods:
Women with anorexia nervosa (restricting subtype) and healthy controls underwent brain DTI. We used tract-based spatial statistics to compare fractional anisotropy (FA) and mean diffusivity (MD) maps between the groups. Furthermore, axial (AD) and radial diffusivity (RD) measures were extracted from regions showing group differences in either FA or MD.
Results:
We enrolled 19 women with anorexia nervosa and 19 healthy controls in our study. Patients with anorexia nervosa showed significant FA decreases in the parietal part of the left superior longitudinal fasciculus (SLF; p(FWE) < 0.05), with increased MD and RD but no differences in AD. Patients with anorexia nervosa also showed significantly increased MD in the fornix (p(FWE) < 0.05), accompanied by decreased FA and increased RD and AD.
Limitations:
Limitations include our modest sample size and cross-sectional design.
Conclusion:
Our findings support the presence of white matter pathology in patients with anorexia nervosa. Alterations in the SLF and fornix might be relevant to key symptoms of anorexia nervosa, such as body image distortion or impairments in body-energy-balance and reward processes. The differences found in both areas replicate those found in previous DTI studies and support a role for white matter pathology of specific neural circuits in individuals with anorexia nervosa.
Untreated transsexuals have a brain cortical phenotype. Cross-sex hormone treatments are used to masculinize or feminize the bodies of female-to-male (FtMs) or male-to-female (MtFs) transsexuals, respectively.
A longitudinal design was conducted to investigate the effects of treatments on brain cortical thickness (CTh) of FtMs and MtFs.
This study investigated 15 female-to-male (FtMs) and 14 male-to-female (MtFs) transsexuals prior and during at least six months of cross-sex hormone therapy treatment. Brain MRI imaging was performed in a 3-Tesla TIM-TRIO Siemens scanner. T1-weighted images were analyzed with FreeSurfer software to obtain CTh as well as subcortical volumetric values.
Changes in brain CTh thickness and volumetry associated to changes in hormonal levels due to cross-sex hormone therapy.
After testosterone treatment, FtMs showed increases of CTh bilaterally in the postcentral gyrus and unilaterally in the inferior parietal, lingual, pericalcarine, and supramarginal areas of the left hemisphere and the rostral middle frontal and the cuneus region of the right hemisphere. There was a significant positive correlation between the serum testosterone and free testosterone index changes and CTh changes in parieto-temporo-occipital regions. In contrast, MtFs, after estrogens and antiandrogens treatment, showed a general decrease in CTh and subcortical volumetric measures and an increase in the volume of the ventricles.
Testosterone therapy increases CTh in FtMs. Thickening in cortical regions is associated to changes in testosterone levels. Estrogens and antiandrogens therapy in MtFs is associated to a decrease in the CTh that consequently induces an enlargement of the ventricular system. Zubiaurre-Elorza L, Junque C, Gómez-Gil E, and Guillamon A. Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals. J Sex Med **;**:**-**.
Sexual dimorphism in human brain structure is well recognised, but less is known about gender differences in white matter microstructure. We used diffusion tensor imaging to explore gender differences in fractional anisotropy (FA), an index of microstructural integrity. We previously found increased FA in the corpus callosum in women, and increased FA in the cerebellum and left superior longitudinal fasciculus (SLF) in men, using a whole-brain voxel-based analysis.
A whole-brain tract-based spatial statistics analysis of 120 matched subjects from the previous analysis, and 134 new subjects (147 men and 107 women in total) using a 1.5T scanner, with division into tract-based regions of interest.
Men had higher FA in the superior cerebellar peduncles and women had higher FA in corpus callosum in both the first and second samples. The higher SLF FA in men was not found in either sample.
We confirmed our previous, controversial finding of increased FA in the corpus callosum in women, and increased cerebellar FA in men. The corpus callosum FA difference offers some explanation for the otherwise puzzling advantage in inter-callosal transfer time shown in women; the cerebellar FA difference may be associated with the developmental motor advantage shown in men.
In the last decade, diffusion MRI (dMRI) studies of the human and animal brain have been used to investigate a multitude of pathologies and drug-related effects in neuroscience research. Study after study identifies white matter (WM) degeneration as a crucial biomarker for all these diseases. The tool of choice for studying WM is dMRI. However, dMRI has inherently low signal-to-noise ratio and its acquisition requires a relatively long scan time; in fact, the high loads required occasionally stress scanner hardware past the point of physical failure. As a result, many types of artifacts implicate the quality of diffusion imagery. Using these complex scans containing artifacts without quality control (QC) can result in considerable error and bias in the subsequent analysis, negatively affecting the results of research studies using them. However, dMRI QC remains an under-recognized issue in the dMRI community as there are no user-friendly tools commonly available to comprehensively address the issue of dMRI QC. As a result, current dMRI studies often perform a poor job at dMRI QC. Thorough QC of dMRI will reduce measurement noise and improve reproducibility, and sensitivity in neuroimaging studies; this will allow researchers to more fully exploit the power of the dMRI technique and will ultimately advance neuroscience. Therefore, in this manuscript, we present our open-source software, DTIPrep, as a unified, user friendly platform for thorough QC of dMRI data. These include artifacts caused by eddy-currents, head motion, bed vibration and pulsation, venetian blind artifacts, as well as slice-wise and gradient-wise intensity inconsistencies. This paper summarizes a basic set of features of DTIPrep described earlier and focuses on newly added capabilities related to directional artifacts and bias analysis.
Puberty reflects a period of hormonal changes, physical maturation and structural brain reorganization. However, little attention has been paid to what extent sex steroids and pituitary hormones are associated with the refinement of brain maturation across adolescent development. Here we used high-resolution structural MRI scans from 215 typically developing individuals between ages 8-25, to examine the association between cortical thickness, surface area and (sub)cortical brain volumes with luteinizing hormone, testosterone and estradiol, and pubertal stage based on self-reports. Our results indicate sex-specific differences in testosterone related influences on gray matter volumes of the anterior cingulate cortex after controlling for age effects. No significant associations between subcortical structures and sex hormones were found. Pubertal stage was not a stronger predictor than chronological age for brain anatomical differences. Our findings indicate that sex steroids are associated with cerebral gray matter morphology in a sex specific manner. These hormonal and morphological differences may explain in part differences in brain development between boys and girls.
Gender identity disorder (GID) refers to transsexual individuals who feel that their assigned biological gender is incongruent with their gender identity and this cannot be explained by any physical intersex condition. There is growing scientific interest in the last decades in studying the neuroanatomy and brain functions of transsexual individuals to better understand both the neuroanatomical features of transsexualism and the background of gender identity. So far, results are inconclusive but in general, transsexualism has been associated with a distinct neuroanatomical pattern. Studies mainly focused on male to female (MTF) transsexuals and there is scarcity of data acquired on female to male (FTM) transsexuals. Thus, our aim was to analyze structural MRI data with voxel based morphometry (VBM) obtained from both FTM and MTF transsexuals (n = 17) and compare them to the data of 18 age matched healthy control subjects (both males and females). We found differences in the regional grey matter (GM) structure of transsexual compared with control subjects, independent from their biological gender, in the cerebellum, the left angular gyrus and in the left inferior parietal lobule. Additionally, our findings showed that in several brain areas, regarding their GM volume, transsexual subjects did not differ significantly from controls sharing their gender identity but were different from those sharing their biological gender (areas in the left and right precentral gyri, the left postcentral gyrus, the left posterior cingulate, precuneus and calcarinus, the right cuneus, the right fusiform, lingual, middle and inferior occipital, and inferior temporal gyri). These results support the notion that structural brain differences exist between transsexual and healthy control subjects and that majority of these structural differences are dependent on the biological gender.
The degree to which one identifies as male or female has a profound impact on one's life. Yet, there is a limited understanding of what contributes to this important characteristic termed gender identity. In order to reveal factors influencing gender identity, studies have focused on people who report strong feelings of being the opposite sex, such as male-to-female (MTF) transsexuals.
To investigate potential neuroanatomical variations associated with transsexualism, we compared the regional thickness of the cerebral cortex between 24 MTF transsexuals who had not yet been treated with cross-sex hormones and 24 age-matched control males.
Results revealed thicker cortices in MTF transsexuals, both within regions of the left hemisphere (i.e., frontal and orbito-frontal cortex, central sulcus, perisylvian regions, paracentral gyrus) and right hemisphere (i.e., pre-/post-central gyrus, parietal cortex, temporal cortex, precuneus, fusiform, lingual, and orbito-frontal gyrus).
These findings provide further evidence that brain anatomy is associated with gender identity, where measures in MTF transsexuals appear to be shifted away from gender-congruent men.
Recent imaging studies have shown that brain morphology and neural activity during sexual arousal differ between homosexual and heterosexual men. However, functional differences in neural networks at the resting state is unknown. The study is to characterize the association of homosexual preference with measures of regional homogeneity and functional connectivity in the resting state. Participants were 26 healthy homosexual men and 26 age-matched healthy heterosexual men in whom we collected echo planar magnetic resonance imaging data in the resting state. The sexual orientation was evaluated using the Kinsey Scale. We first assessed group differences in regional homogeneity and then, taking the identified differences as seed regions, we compared groups in measures of functional connectivity from those seeds. The behavioral significances of the differences in regional homogeneity and functional connectivity were assessed by examining their associations with Kinsey Scores. Homosexual participants showed significantly reduced regional homogeneity in the left inferior occipital gyrus, right middle occipital gyrus, right superior occipital gyrus, left cuneus, right precuneus, and increased regional homogeneity in rectal gyrus, bilateral midbrain, and left temporal lobe. Regional homogeneity correlated positively with Kinsey scores in the left inferior occipital gyrus. The homosexual group also showed reduced functional connectivity between left middle temporal gyrus, left supra-marginal gyrus, right cuneus and the seed region, i.e. left inferior occipital gyrus. Additionly, the connection between the left inferior occipital gyrus and right thalamus correlated positively with Kinsey scores. These differences in regional homogeneity and functional connectivity may contribute to a better understanding of the neural basis of male sexual orientation.
Diffusion magnetic resonance imaging is a quantitative imaging technique that measures the underlying molecular diffusion of protons. Diffusion-weighted imaging (DWI) quantifies the apparent diffusion coefficient (ADC) which was first used to detect early ischemic stroke. However this does not take account of the directional dependence of diffusion seen in biological systems (anisotropy).Diffusion tensor imaging (DTI) provides a mathematical model of diffusion anisotropy and is widely used. Parameters, including fractional anisotropy (FA), mean diffusivity (MD), parallel and perpendicular diffusivity can be derived to provide sensitive, but non-specific, measures of altered tissue structure. They are typically assessed in clinical studies by voxel-based or region-of-interest based analyses.The increasing recognition of the limitations of the diffusion tensor model has led to more complex multi-compartment models such as CHARMED, AxCaliber or NODDI being developed to estimate microstructural parameters including axonal diameter, axonal density and fiber orientations. However these are not yet in routine clinical use due to lengthy acquisition times.In this review, I discuss how molecular diffusion may be measured using diffusion MRI, the biological and physical bases for the parameters derived from DWI and DTI, how these are used in clinical studies and the prospect of more complex tissue models providing helpful micro-structural information.
Female-to-male (FTM) transgender persons are often assumed to have been lesbian in sexual orientation prior to transition and to have maintained a primary attraction for women after transition. However, limited research and anecdotal information from clinicians who work with FTM have indicated that many identify as gay men post-transition. This article described the results of a qualitative study that employed interviews with 17 FTM in order to understand their experience of transition and sexual orientation. Of the 17 participants, seven identified as lesbian prior to transition, three as heterosexual, and seven as bisexual or queer. After transition, 10 identified as gay men and the remaining seven identified as bisexual or queer. Four patterns of sexual behavior emerged from the data and were described and discussed. These patterns were named steadfast, aligned, shifted, and fluid. These findings bring additional options to the belief that there are two distinct types of transgender: a homosexual subtype and a nonhomosexual subtype.
Sex differences in cortical thickness (CTh) have been extensively investigated but as yet there are no reports on CTh in transsexuals.
Our aim was to determine whether the CTh pattern in transsexuals before hormonal treatment follows their biological sex or
their gender identity. We performed brain magnetic resonance imaging on 94 subjects: 24 untreated female-to-male transsexuals
(FtMs), 18 untreated male-to-female transsexuals (MtFs), and 29 male and 23 female controls in a 3-T TIM-TRIO Siemens scanner.
T1-weighted images were analyzed to obtain CTh and volumetric subcortical measurements with FreeSurfer software. CTh maps showed
control females have thicker cortex than control males in the frontal and parietal regions. In contrast, males have greater
right putamen volume. FtMs had a similar CTh to control females and greater CTh than males in the parietal and temporal cortices.
FtMs had larger right putamen than females but did not differ from males. MtFs did not differ in CTh from female controls
but had greater CTh than control males in the orbitofrontal, insular, and medial occipital regions. In conclusion, FtMs showed
evidence of subcortical gray matter masculinization, while MtFs showed evidence of CTh feminization. In both types of transsexuals,
the differences with respect to their biological sex are located in the right hemisphere.
Neuroendocrine theories of brain development hold testosterone as the predominant factor mediating sex-specific cortical growth and the ensuing lateralization of hemispheric function. However, studies to date have focussed on prenatal testosterone rather than pubertal changes in testosterone. Yet, animal studies have shown a high density of androgen-sensitive receptors in multiple key cortical areas, and puberty is known to coincide with both a significant rise in testosterone and the emergence of behavioral sex differences, suggesting peripubertal influences of testosterone on brain development. Here, we used linear mixed models to examine sex-specific cortical maturation associated with changes in testosterone levels in a longitudinal sample of developmentally healthy children and adolescents. A significant "sex by age by testosterone" interaction on cortical thickness (CTh) involving widespread areas of the developing brain was found. Testosterone levels were associated with CTh changes in regions of the left hemisphere in males and of the right hemisphere in females. In both sexes, the relationship between testosterone and CTh varied across the age span. These findings show the association between testosterone and CTh to be complex, highly dynamic, and to vary, depending on sex and age; they also suggest sex-related hemispheric lateralization effects of testosterone in humans.
Age-related changes in cortical thickness have been observed during adolescence, including thinning in frontal and parietal cortices, and thickening in the lateral temporal lobes. Studies have shown sex differences in hormone-related brain maturation when boys and girls are age-matched, however, because girls mature 1-2 years earlier than boys, these sex differences could be confounded by pubertal maturation. To address puberty effects directly, this study assessed sex differences in testosterone-related cortical maturation by studying 85 boys and girls in a narrow age range and matched on sexual maturity. We expected that testosterone-by-sex interactions on cortical thickness would be observed in brain regions known from the animal literature to be high in androgen receptors. We found sex differences in associations between circulating testosterone and thickness in left inferior parietal lobule, middle temporal gyrus, calcarine sulcus, and right lingual gyrus, all regions known to be high in androgen receptors. Visual areas increased with testosterone in boys, but decreased in girls. All other regions were more impacted by testosterone levels in girls than boys. The regional pattern of sex-by-testosterone interactions may have implications for understanding sex differences in behavior and adolescent-onset neuropsychiatric disorders.
Body integrity identity disorder (BIID) is characterised by profound experience of incongruity between the biological and desired body structure. The condition manifests in "non-belonging" of body parts, and the subsequent desire to amputate, paralyse or disable a limb. Little is known about BIID; however, a neuropsychological model implicating right fronto-parietal and insular networks is emerging, with potential disruption to body representation. We argue that, as there is scant systematic research on BIID published to date and much of the research is methodologically weak, it is premature to assume that the only process underlying bodily experience that is compromised is body representation. The present review systematically investigates which aspects of neurological processing of the body, and sense of self, may be compromised in BIID. We argue that the disorder most likely reflects dysregulation in multiple levels of body processing. That is, the disunity between self and the body could arguably come about through congenital and/or developmental disruption of body representations, which, together with altered multisensory integration, may preclude the experience of self-attribution and embodiment of affected body parts. Ulimately, there is a need for official diagnostic criteria to facilitate epidemiological characterisation of BIID, and for further research to systematically investigate which aspects of body representation and processing are truly compromised in the disorder.
Many people believe that sexual orientation (homosexuality vs. heterosexuality) is determined by education and social constraints. There are, however, a large number of studies indicating that prenatal factors have an important influence on this critical feature of human sexuality. Sexual orientation is a sexually differentiated trait (over 90% of men are attracted to women and vice versa). In animals and men, many sexually differentiated characteristics are organized during early life by sex steroids, and one can wonder whether the same mechanism also affects human sexual orientation. Two types of evidence support this notion. First, multiple sexually differentiated behavioral, physiological, or even morphological traits are significantly different in homosexual and heterosexual populations. Because some of these traits are known to be organized by prenatal steroids, including testosterone, these differences suggest that homosexual subjects were, on average, exposed to atypical endocrine conditions during development. Second, clinical conditions associated with significant endocrine changes during embryonic life often result in an increased incidence of homosexuality. It seems therefore that the prenatal endocrine environment has a significant influence on human sexual orientation but a large fraction of the variance in this behavioral characteristic remains unexplained to date. Genetic differences affecting behavior either in a direct manner or by changing embryonic hormone secretion or action may also be involved. How these biological prenatal factors interact with postnatal social factors to determine life-long sexual orientation remains to be determined.
The neurobiology of sexual orientation is frequently discussed in terms of cerebral sex dimorphism (defining both functional and structural sex differences). Yet, the information about possible cerebral differences between sex-matched homo and heterosexual persons is limited, particularly among women. In this multimodal MRI study, we addressed these issues by investigating possible cerebral differences between homo and heterosexual persons, and by asking whether there is any sex difference in this aspect. Measurements of cortical thickness (Cth), subcortical volumes, and functional and structural resting-state connections among 40 heterosexual males (HeM) and 40 heterosexual females (HeF) were compared with those of 30 homosexual males (HoM) and 30 homosexual females (HoF). Congruent with previous reports, sex differences were detected in heterosexual controls with regard to fractional anisotropy (FA), Cth, and several subcortical volumes. Homosexual groups did not display any sex differences in FA values. Furthermore, their functional connectivity was significantly less pronounced in the mesial prefrontal and precuneus regions. In these two particular regions, HoM also displayed thicker cerebral cortex than other groups, whereas HoF did not differ from HeF. In addition, in HoM the parietal Cth showed “sex-reversed” values, not observed in HoF. Homosexual orientation seems associated with a less pronounced sexual differentiation of white matter tracts and a less pronounced functional connectivity of the self-referential networks compared to heterosexual orientation. Analyses of Cth suggest that male and female homosexuality are not simple analogues of each other and that differences from heterosexual controls are more pronounced in HoM.
Transgender individuals experience incongruence between their gender identity and birth-assigned sex. The resulting gender dysphoria (GD), which some gender-incongruent individuals experience, is theorized to be a consequence of atypical cerebral sexual differentiation, but support for this assertion is inconsistent. We recently found that GD is associated with disconnected networks involved in self-referential thinking and own body perception. Here, we investigate how these networks in trans men (assigned female at birth with male gender identity) are affected by testosterone. In 22 trans men, we obtained T1-weighted, diffusion-weighted, and resting-state functional magnetic resonance imaging scans before and after testosterone treatment, measuring cortical thickness (Cth), subcortical volumes, fractional anisotropy (FA), and functional connectivity. Nineteen cisgender controls (male and female) were also scanned twice. The medial prefrontal cortex (mPFC) was thicker in trans men than controls pretreatment, and remained unchanged posttreatment. Testosterone treatment resulted in increased Cth in the insular cortex, changes in cortico-cortical thickness covariation between mPFC and occipital cortex, increased FA in the fronto-occipital tract connecting these regions, and increased functional connectivity between mPFC and temporo-parietal junction, compared with controls. Concluding, in trans men testosterone treatment resulted in functional and structural changes in self-referential and own body perception areas.
Previous research suggests that the sexual identities, attractions, and behaviors of sexual-minority (i.e., nonheterosexual) women change over time, yet there have been few longitudinal studies addressing this question, and no longitudinal studies of sexual-minority youths. The results of 2-year follow-up interviews with 80 lesbian, bisexual, and "unlabeled" women who were first interviewed at 16-23 years of age are reported. Half of the participants changed sexual-minority identities more than once, and one third changed identities since the first interview. Changes in sexual attractions were generally small but were larger among bisexuals and unlabeled women. Most women pursued sexual behavior consistent with their attractions, but one fourth of lesbians had sexual contact with men between the two interviews. These findings suggest that there is more fluidity in women's sexual identities and behaviors than in their attractions. This fluidity may stem from the prevalence of nonexclusive attractions among sexual-minority women.
The volumetric quantification of brain structures is of great interest in pediatric populations because it allows the investigation of different factors influencing neurodevelopment. FreeSurfer and FSL both provide frequently used packages for automatic segmentation of brain structures. In this study, we examined the accuracy and consistency of those two automated protocols relative to manual segmentation, commonly considered as the “gold standard” technique, for estimating hippocampus and amygdala volumes in a sample of preadolescent children aged between 6 to 11 years. The volumes obtained with FreeSurfer and FSL-FIRST were evaluated and compared with manual segmentations with respect to volume difference, spatial agreement and between- and within-method correlations.
Results highlighted a tendency for both automated techniques to overestimate hippocampus and amygdala volumes, in comparison to manual segmentation. This was more pronounced when using FreeSurfer than FSL-FIRST and, for both techniques, the overestimation was more marked for the amygdala than the hippocampus. Pearson correlations support moderate associations between manual tracing and FreeSurfer for hippocampus (right r = 0.69, p < 0.001; left r = 0.77, p < 0.001) and amygdala (right r = 0.61, p < 0.001; left r = 0.67, p < 0.001) volumes. Correlation coefficients between manual segmentation and FSL-FIRST were statistically significant (right hippocampus r = 0.59, p < 0.001; left hippocampus r = 0.51, p < 0.001; right amygdala r = 0.35, p < 0.001; left amygdala r = 0.31, p < 0.001) but were significantly weaker, for all investigated structures. When computing intraclass correlation coefficients between manual tracing and automatic segmentation, all comparisons, except for left hippocampus volume estimated with FreeSurfer, failed to reach 0.70. When looking at each method separately, correlations between left and right hemispheric volumes showed strong associations between bilateral hippocampus and bilateral amygdala volumes when assessed using manual segmentation or FreeSurfer. These correlations were significantly weaker when volumes were assessed with FSL-FIRST. Finally, Bland–Altman plots suggest that the difference between manual and automatic segmentation might be influenced by the volume of the structure, because smaller volumes were associated with larger volume differences between techniques.
These results demonstrate that, at least in a pediatric population, the agreement between amygdala and hippocampus volumes obtained with automated FSL-FIRST and FreeSurfer protocols and those obtained with manual segmentation is not strong. Visual inspection by an informed individual and, if necessary, manual correction of automated segmentation outputs are important to ensure validity of volumetric results and interpretation of related findings.
Head motion during functional MRI (fMRI) scanning can induce spurious findings and/or harm detection of true effects. Solutions have been proposed, including deleting ('scrubbing') or regressing out ('spike regression') motion volumes from fMRI time-series. These strategies remove motion-induced signal variations at the cost of destroying the autocorrelation structure of the fMRI time-series and reducing temporal degrees of freedom. ICA-based fMRI denoising strategies overcome these drawbacks but typically require re-training of a classifier, needing manual labeling of derived components (e.g. ICA-FIX; [42]). Here, we propose an ICA-based strategy for Automatic Removal Of Motion Artifacts (ICA-AROMA) that uses a small (n=4), but robust set of theoretically motivated temporal and spatial features. Our strategy does not require classifier re-training, retains the data's autocorrelation structure and largely preserves temporal degrees of freedom. We describe ICA-AROMA, its implementation, and initial validation. ICA-AROMA identified motion components with high accuracy and robustness as illustrated by leave-N-out cross-validation. We additionally validated ICA-AROMA in resting-state (100 participants) and task-based fMRI data (118 participants). Our approach removed (motion-related) spurious noise from both rfMRI and task-based fMRI data to larger extent than regression using 24 motion parameters or spike regression. Furthermore, ICA-AROMA increased sensitivity to group-level activation. Our results show that ICA-AROMA effectively reduces motion-induced signal variations in fMRI data, is applicable across datasets without requiring classifier re-training, and preserves the temporal characteristics of the fMRI data.
Copyright © 2015. Published by Elsevier Inc.
The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine whether there are signs of a sex-atypical brain development in GD, we quantified regional neural gray matter (GM) volumes in 55 female-to-male and 38 male-to-female adolescents, 44 boys and 52 girls without GD and applied both univariate and multivariate analyses. In girls, more GM volume was observed in the left superior medial frontal cortex, while boys had more volume in the bilateral superior posterior hemispheres of the cerebellum and the hypothalamus. Regarding the GD groups, at whole-brain level they differed only from individuals sharing their gender identity but not from their natal sex. Accordingly, using multivariate pattern recognition analyses, the GD groups could more accurately be automatically discriminated from individuals sharing their gender identity than those sharing their natal sex based on spatially distributed GM patterns. However, region of interest analyses indicated less GM volume in the right cerebellum and more volume in the medial frontal cortex in female-to-males in comparison to girls without GD, while male-to-females had less volume in the bilateral cerebellum and hypothalamus than natal boys. Deviations from the natal sex within sexually dimorphic structures were also observed in the untreated subsamples. Our findings thus indicate that GM distribution and regional volumes in GD adolescents are largely in accordance with their respective natal sex. However, there are subtle deviations from the natal sex in sexually dimorphic structures, which can represent signs of a partial sex-atypical differentiation of the brain.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Fluidity in attractions and behaviors among same-sex attracted women has been well-documented, suggesting the appropriateness of dynamical systems modeling of these phenomena over time. As dynamical systems modeling offer an approach to explaining the patterns of complex phenomena, it may be apt for explaining variability in female same-sex sexuality. The present research is the first application of this analytical approach to such data. Dynamical systems modeling, and specifically generalized local linear approximation modeling, was used to fit daily diary data on same-sex attractions and behaviors over a 21 day period among a group of 33 sexual minority women characterized as lesbian, bisexual or "fluid" based on their identity histories. Daily measures of women's reported same-sex attractions were fit using a linear oscillator model and its parameters estimated the cyclicity in these attractions. Results supported the existence of a "core sexual orientation" for women in this sample, regardless of how they identified and despite a high degree of variability in daily same-sex attractions. Thus, modeling individual differences in the variability of attractions and behaviors of sexual minority women may be critical to furthering our understanding of female same-sex sexuality and human sexual orientation more broadly.
IntroductionNeuroimaging studies have reported differences in brain structure and function between homosexual and heterosexual men. The neural basis for homosexual orientation, however, is still unknown.AimThis study characterized the association of homosexual preference with measures of fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) in the resting state.Methods
We collected echo planar magnetic resonance imaging data in 26 healthy homosexual men and 26 age-matched heterosexual men in the resting state.Main Outcome MeasuresSexual orientation was evaluated using the Kinsey scale. We assessed group differences in fALFF and then, taking the identified group differences as seed regions, we compared groups on measures of FC from those seeds. The behavioral significance of the group differences in fALFF and FC was assessed by examining their associations with the Kinsey scores.ResultsCompared with heterosexual participants, homosexual men showed significantly increased fALFF in the right middle frontal gyrus and right anterior cerebellum, and decreased fALFF in the left postcentral gyrus, left lingual gyrus, right pallidum, right postcentral gyrus, left interior parietal gyrus, right superior temporal gyrus, left cuneus, and left inferior frontal gyrus. Additionally, fALFF in the left postcentral gyrus and left cuneus correlated positively with Kinsey scores in the homosexual participants. When the seeds in the left cuneus, left cuneus, and left superior parietal gyrus also had reduced FC in homosexual participants, FC correlated positively with the Kinsey scores.Conclusions
Differences in fALFF and FC suggest male sexual preference may influence the pattern activity in the default mode network. Hu S, Xu D, Peterson BS, Wang Q, Lai J, Hu J, Wei N, Zhang M, and Xu Y. Differing default mode network activities in men with homosexual or heterosexual preferences. J Sex Med **;**:**–**.
Although it has been shown that cortical thickness (Cth) differs between sexes, the underlying mechanisms are unknown. Seeing
as XXY males have 1 extra X chromosome, we investigated the possible effects of X- and sex-chromosome dosage on Cth by comparing
data from 31 XXY males with 39 XY and 47 XX controls. Plasma testosterone and estrogen were also measured in an effort to
differentiate between possible sex-hormone and sex-chromosome gene effects. Cth was calculated with FreeSurfer software. Parietal
and occipital Cth was greater in XX females than XY males. In these regions Cth was inversely correlated with z-normalized testosterone. In the motor strip, the cortex was thinner in XY males compared with both XX females and XXY males,
indicating the possibility of an X-chromosome gene-dosage effect. XXY males had thinner right superior temporal and left middle
temporal cortex, and a thicker right orbitofrontal cortex and lingual cortex than both control groups. Based on these data
and previous reports from women with XO monosomy, it is hypothesized that programming of the motor cortex is influenced by
processes linked to X-escapee genes, which do not have Y-chromosome homologs, and that programming of the superior temporal
cortex is mediated by X-chromosome escapee genes with Y-homologs.
Background:
Several neuroimaging studies have investigated brain grey matter in people with body dysmorphic disorder (BDD), showing possible abnormalities in the limbic system, orbitofrontal cortex, caudate nuclei and temporal lobes. This study takes these findings forward by investigating white matter properties in BDD compared with controls using diffusion tensor imaging. It was hypothesized that the BDD sample would have widespread significantly reduced white matter connectivity as characterized by fractional anisotropy (FA).
Method:
A total of 20 participants with BDD and 20 healthy controls matched on age, gender and handedness underwent diffusion tensor imaging. FA, a measure of water diffusion within a voxel, was compared between groups on a voxel-by-voxel basis across the brain using tract-based spatial statistics within the FSL package.
Results:
Results showed that, compared with healthy controls, BDD patients demonstrated significantly lower FA (p < 0.05) in most major white matter tracts throughout the brain, including in the superior longitudinal fasciculus, inferior fronto-occipital fasciculus and corpus callosum. Lower FA levels could be accounted for by increased radial diffusivity as characterized by eigenvalues 2 and 3. No area of higher FA was found in BDD.
Conclusions:
This study provided the first evidence of compromised white matter integrity within BDD patients. This suggests that there are inefficient connections between different brain areas, which may explain the cognitive and emotion regulation deficits within BDD patients.
Purpose:
To investigate age-related differences, gender differences, and age-by-gender interactions on the volumes of 18 neuroanatomical structures, with a large sample at a single institution.
Materials and methods:
A total of 861 normal subjects (mean age = 56.1 ± 9.8 years, age range = 24.0-84.8 years) were included in this study. All subjects were scanned at 3.0 T. Measurement of the 18 neuroanatomical volumes was performed with FreeSurfer v. 4.5. Differences in volumes of neuroanatomical structures were tested using analysis of covariance with intracranial volume-normalized volume as the dependent variable, and independent variables of age, sex, age × sex, age × age, age × age × sex, and scanner. Nonsignificant higher-order terms were removed sequentially from the model. A P value of < 0.0028 (=0.5/18) was considered to indicate a statistically significant difference.
Results:
All neuroanatomical volumes, except for the caudate nucleus, pallidum, and 4th ventricle, were significantly related to age (linearly or quadratically). Significant gender differences were found in all neuroanatomical volumes, except for cerebral white matter, cerebellar cortex, caudate nucleus, and amygdala. No neuroanatomical volume showed a significant interaction between age (age × age) and gender.
Conclusion:
Our results showed age and gender effects on neuroanatomical volumes, and indicate no gender difference in the aging process of neuroanatomical volumes.
While there has been increasing support for the existence of cerebral sex differences, the mechanisms underlying these differences are unclear. Based on animal data, it has long been believed that sexual differentiation of the brain is primarily linked to organizational effects of fetal testosterone. This view is, however, in question as more recent data show the presence of sex differences before the onset of testosterone production. The present study focuses on the impact that sex chromosomes might have on these differences. Utilizing the inherent differences in sex and X-chromosome dosage among XXY males, XY males, and XX females, comparative voxel-based morphometry was conducted using sex hormones and sex chromosomes as covariates. Sex differences in the cerebellar and precentral gray matter volumes (GMV) were found to be related to X-chromosome dosage, whereas sex differences in the amygdala, the parahippocamus, and the occipital cortex were linked to testosterone levels. An increased number of sex chromosomes was associated with reduced GMV in the amygdala, caudate, and the temporal and insular cortices, with increased parietal GMV and reduced frontotemporal white matter volume. No selective, testosterone independent, effect of the Y-chromosome was detected. Based on these observations, it was hypothesized that programming of the motor cortex and parts of cerebellum is mediated by processes linked to X-escapee genes, which do not have Y-chromosome homologs, and that programming of certain limbic structures involves testosterone and X-chromosome escapee genes with Y-homologs.
Previous studies suggest organizing effects of sex hormones on brain structure during early life and puberty, yet little is known about the adult period. The aim of the present study was to elucidate the role of 17β-estradiol, progesterone, and testosterone on cortical sex differences in grey matter volume (GM) of the adult human brain. To assess sexual dimorphism, voxel-based morphometry (VBM) was applied on structural magnetic resonance images of 34 healthy, young adult humans (17 women, 17 men, 26.6 ± 5 years) using analyses of covariance. Subsequently, circulating levels of sex hormones were associated with regional GM using linear regression analyses. After adjustment for sex and total GM, significant associations of regional GM and 17β-estradiol were observed in the left inferior frontal gyrus (β = 0.39, p = 0.02). Regional GM was inversely associated with testosterone in the left inferior frontal gyrus (β = −0.16, p = 0.04), and with progesterone in the right temporal pole (β = −0.39, p = 0.008). Our findings indicate that even in young adulthood, sex hormones exert organizing effects on regional GM. This might help to shed further light on the underlying mechanisms of both functional diversities and congruence between female and male brains.
The question of how we experience ownership of an entire body distinct from the external world is a fundamental problem in psychology and neuroscience [1-6]. Earlier studies suggest that integration of visual, tactile, and proprioceptive information in multisensory areas [7-11] mediates self-attribution of single limbs. However, it is still unknown how ownership of individual body parts translates into the unitary experience of owning a whole body. Here, we used a "body-swap" illusion [12], in which people experienced an artificial body to be their own, in combination with functional magnetic resonance imaging to reveal a coupling between the experience of full-body ownership and neural responses in bilateral ventral premotor and left intraparietal cortices, and left putamen. Importantly, activity in the ventral premotor cortex reflected the construction of ownership of a whole body from the parts, because it was stronger when the stimulated body part was attached to a body, was present irrespective of whether the illusion was triggered by stimulation of the hand or the abdomen, and displayed multivoxel patterns carrying information about full-body ownership. These findings suggest that the unitary experience of owning an entire body is produced by neuronal populations that integrate multisensory information across body segments.
Gender dysphoria is suggested to be a consequence of sex atypical cerebral differentiation. We tested this hypothesis in a magnetic resonance study of voxel-based morphometry and structural volumetry in 48 heterosexual men (HeM) and women (HeW) and 24 gynephillic male to female transsexuals (MtF-TR). Specific interest was paid to gray matter (GM) and white matter (WM) fraction, hemispheric asymmetry, and volumes of the hippocampus, thalamus, caudate, and putamen. Like HeM, MtF-TR displayed larger GM volumes than HeW in the cerebellum and lingual gyrus and smaller GM and WM volumes in the precentral gyrus. Both male groups had smaller hippocampal volumes than HeW. As in HeM, but not HeW, the right cerebral hemisphere and thalamus volume was in MtF-TR lager than the left. None of these measures differed between HeM and MtF-TR. MtF-TR displayed also singular features and differed from both control groups by having reduced thalamus and putamen volumes and elevated GM volumes in the right insular and inferior frontal cortex and an area covering the right angular gyrus.The present data do not support the notion that brains of MtF-TR are feminized. The observed changes in MtF-TR bring attention to the networks inferred in processing of body perception.
Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests. In addition, growing evidence shows that testosterone exposure contributes similarly to the development of other human behaviors that show sex differences, including sexual orientation, core gender identity, and some, though not all, sex-related cognitive and personality characteristics. In addition to these prenatal hormonal influences, early infancy and puberty may provide additional critical periods when hormones influence human neurobehavioral organization. Sex-linked genes could also contribute to human gender development, and most sex-related characteristics are influenced by socialization and other aspects of postnatal experience, as well. Neural mechanisms underlying the influences of gonadal hormones on human behavior are beginning to be identified. Although the neural mechanisms underlying experiential influences remain largely uninvestigated, they could involve the same neural circuitry as that affected by hormones.
Diffusion tensor imaging (DTI) has been shown to be sensitive in detecting white matter differences between sexes. Before cross-sex hormone treatment female to male transsexuals (FtM) differ from females but not from males in several brain fibers. The purpose of this paper is to investigate whether white matter patterns in male to female (MtF) transsexuals before commencing cross-sex hormone treatment are also more similar to those of their biological sex or whether they are more similar to those of their gender identity.
DTI was performed in 18 MtF transsexuals and 19 male and 19 female controls scanned with a 3 T Trio Tim Magneton. Fractional anisotropy (FA) was performed on white matter of the whole brain, which was spatially analyzed using Tract-Based Spatial Statistics.
MtF transsexuals differed from both male and female controls bilaterally in the superior longitudinal fasciculus, the right anterior cingulum, the right forceps minor, and the right corticospinal tract.
Our results show that the white matter microstructure pattern in untreated MtF transsexuals falls halfway between the pattern of male and female controls. The nature of these differences suggests that some fasciculi do not complete the masculinization process in MtF transsexuals during brain development.