Papers by Antonio Guillamon q
The Journal of Sexual Medicine
Background Gender minority individuals, on average, experience higher rates of mental health prob... more Background Gender minority individuals, on average, experience higher rates of mental health problems. Mounting work suggests that gender minority stress (GMS) contributes to mental health outcomes in transgender/gender-nonconforming individuals. Aim We assessed whether GMS decreased in transgender people after initiating gender-affirming hormone therapy (GAHT), and we identified social predictors and hormonal associations for GMS at 2 time points. Methods GMS was surveyed through self-report questionnaires tapping into proximal and distal stressors and coping constructs following the minority stress framework. Eighty-five transgender persons wishing to undertake hormonal interventions were assessed prospectively at start of GAHT and after 7.7 ± 3.5 months (mean ± SD). Sixty-five cisgender persons served as a control group. Outcomes (1) Proximal stressors were surveyed by the Beck Depression Inventory II, State-Trait Anxiety Inventory, Scale for Suicide Ideation, Suicidal Thoughts/A...
Large-scale brain network interactions have been described between trans- and cis-gender identiti... more Large-scale brain network interactions have been described between trans- and cis-gender identities. However, a temporal perspective of the brain spontaneous fluctuations is missing. We investigated the functional connectivity dynamics in transmen with gender incongruence and its relationship with interoceptive awareness. We describe four states in native and meta-state spaces: i) one state highly prevalent with sparse overall connections; ii) a second with strong couplings mainly involving components of the salience, default and executive control networks. Two states with global sparse connectivity but positive couplings iii) within the sensorimotor network, and iv) between salience network regions. Transmen had more dynamical fluidity than cismen, while cismen presented less meta-state fluidity and range dynamism than transmen and ciswomen. A positive association between attention regulation and fluidity, and meta-state range dynamism was found in transmen. There exist gender diff...
International Journal of Neuropsychopharmacology, 2021
Background Minority stress via discrimination, stigmatization, and exposure to violence can lead ... more Background Minority stress via discrimination, stigmatization, and exposure to violence can lead to development of mood and anxiety disorders and underlying neurobiochemical changes. To date, the neural and neurochemical correlates of emotion processing in transgender people (and their interaction) are unknown. Methods This study combined functional magnetic resonance imaging and magnetic resonance spectroscopy to uncover the effects of anxiety and perceived stress on the neural and neurochemical substrates, specifically choline, on emotion processing in transgender men. Thirty transgender men (TM), 30 cisgender men, and 35 cisgender women passively viewed angry, neutral, happy, and surprised faces in the functional magnetic resonance imaging scanner, underwent a magnetic resonance spectroscopy scan, and filled out mood- and anxiety-related questionnaires. Results As predicted, choline levels modulated the relationship between anxiety and stress symptoms and the neural response to a...
AbstractWe investigated the presence of nitric oxide in the bed nucleus of the accessory olfactor... more AbstractWe investigated the presence of nitric oxide in the bed nucleus of the accessory olfactory tract (BAOT) in males, diestrous females andestrous females using NADPH-diaphorase. Our results demonstrate a significant increase in the density of the medium-stained cells in theestrous female rats suggesting that during estrous a specific subpopulation of nitrinergic cells are activated in the BAOT. This might berelated to the physiological and behavioral changes that occurs in estrous. 2003 Elsevier B.V. All rights reserved. Theme: Neurotransmitters, modulators, transporters and receptorsTopic: Regional localization of receptors and transmittersKeywords:Accessory olfactory pathway; Estrous cycle; Nitric oxide; Nicotinamide adenine dinucleotide phosphate-diaphorase; Rat 1. Introduction correlation between high levels of estradiol and an incre-ment in the nNOS or NADPH activities in ventromedialNitric oxide (NO) is synthesized from arginine by the (VMN) and medial preoptic nuclei [5,2...
Frontiers in Neuroscience, 2021
IntroductionThe main objective was to carry out a global DNA methylation analysis in a population... more IntroductionThe main objective was to carry out a global DNA methylation analysis in a population with gender incongruence before gender-affirming hormone treatment (GAHT), in comparison to a cisgender population.MethodsA global CpG (cytosine-phosphate-guanine) methylation analysis was performed on blood from 16 transgender people before GAHT vs. 16 cisgender people using the Illumina© Infinium Human Methylation 850k BeadChip, after bisulfite conversion. Changes in the DNA methylome in cisgender vs. transgender populations were analyzed with the Partek® Genomics Suite program by a 2-way ANOVA test comparing populations by group and their sex assigned at birth.ResultsThe principal components analysis (PCA) showed that both populations (cis and trans) differ in the degree of global CpG methylation prior to GAHT. The 2-way ANOVA test showed 71,515 CpGs that passed the criterion FDR p < 0.05. Subsequently, in male assigned at birth population we found 87 CpGs that passed both criteri...
How the brain constructs gender identity is largely unknown, but some neural differences have rec... more How the brain constructs gender identity is largely unknown, but some neural differences have recently been discovered. Here, we used an intrinsic-ignition framework to investigate if gender identity changes the propagation of the neural activity across the whole-brain network and within resting-state networks. Studying 29 transmen and 17 transwomen with gender incongruence, 22 ciswomen, and 19 cismen, we computed the capability of a given brain area in space to propagate activity to other areas (mean-ignition) and its variability across time (node-metastability). We found that both measures differentiated all four groups across the whole-brain network. Furthermore, at the network level, we found that compared to the other groups, cismen showed higher mean-ignition of the dorsal attention network and node-metastability of the dorsal and ventral attention, executive control, and temporal parietal networks. We also found mean-ignition differences between cismen and ciswomen within the...
Cerebral Cortex, 2017
Androgenization in adult natal women, as in transsexual men (TM), affects brain cortical thicknes... more Androgenization in adult natal women, as in transsexual men (TM), affects brain cortical thickness and the volume of subcortical structures. In order to understand the mechanism underlying these changes we have developed an adult female rat model of androgenization. Magnetic resonance imaging and spectroscopy were used to monitor brain volume changes, white matter microstructure and ex vivo metabolic profiles over 32 days in androgenized and control subjects. Supraphysiological doses of testosterone prevents aging decrease of fractional anisotropy values, decreased general cortical volume and the relative concentrations of glutamine (Gln) and myo-Inositol (mI). An increase in the N-acetylaspartate (NAA)/mI ratio was detected d. Since mI and Gln are astrocyte markers and osmolytes, we suspect that the anabolic effects of testosterone change astrocyte osmolarity so as to extrude Mi and Gln from these cells in order to maintain osmotic homeostasis. This mechanism could explain the brain changes observed in TM and other individuals receiving androgenic anabolic steroids.
Archives of Sexual Behavior, 2016
The present review focuses on the brain structure of male-to-female (MtF) and female-to-male (FtM... more 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 wellas 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.
Quality of Life Research, 2013
To evaluate the self-reported perceived quality of life (QoL) in transsexuals attending a Spanish... more To evaluate the self-reported perceived quality of life (QoL) in transsexuals attending a Spanish gender identity unit before genital sex reassignment surgery, and to identify possible determinants that likely contribute to their QoL. A sample of 119 male-to-female (MF) and 74 female-to-male (FM) transsexuals were included in the study. The WHOQOL-BREF scale was used to evaluate self-reported QoL. Possible determinants included age, sex, education, employment, partnership status, undergoing cross-sex hormonal therapy, receiving at least one non-genital sex reassignment surgery, and family support (assessed with the family APGAR questionnaire). Mean scores of all QoL domains ranged from 55.44 to 63.51. Linear regression analyses revealed that undergoing cross-sex hormonal treatment, having family support, and having an occupation were associated with a better QoL for all transsexuals. FM transsexuals have higher social domain QoL scores than MF transsexuals. The model accounts for 20.6 % of the variance in the physical, 32.5 % in the psychological, 21.9 % in the social, and 20.1 % in the environment domains, and 22.9 % in the global QoL factor. Cross-sex hormonal treatment, family support, and working or studying are linked to a better self-reported QoL in transsexuals. Healthcare providers should consider these factors when planning interventions to promote the health-related QoL of transsexuals.
Psychoneuroendocrinology, 2012
Please cite this article in press as: Rametti, G., et al., Effects of androgenization on the whit... more Please cite this article in press as: Rametti, G., et al., Effects of androgenization on the white matter microstructure of female-to-male transsexuals. A diffusion tensor imaging study. Psychoneuroendocrinology (2012),
Psychoneuroendocrinology, 2012
Introduction: The aim of the present study was to evaluate the presence of symptoms of current so... more Introduction: The aim of the present study was to evaluate the presence of symptoms of current social distress, anxiety and depression in transsexuals. Methods: We investigated a group of 187 transsexual patients attending a gender identity unit; 120 had undergone hormonal sex-reassignment (SR) treatment and 67 had not. We used the Social Anxiety and Distress Scale (SADS) for assessing social anxiety and the Hospital Anxiety and Depression Scale (HADS) for evaluating current depression and anxiety. Results: The mean SADS and HADS scores were in the normal range except for the HAD-Anxiety subscale (HAD-A) on the non-treated transsexual group. SADS, HAD-A, and HAD-Depression (HAD-D) mean scores were significantly higher among patients who had not begun cross-sex hormonal treatment compared with patients in hormonal treatment (F = 4.362, p = .038; F = 14.589, p = .001; F = 9.523, p = .002 respectively). Similarly, current symptoms of anxiety and depression were present in a significantly higher percentage of untreated patients than in treated patients (61% vs. 33% and 31% vs. 8% respectively). Conclusions: The results suggest that most transsexual patients attending a gender identity unit reported subclinical levels of social distress, anxiety, and depression. Moreover, patients under cross-sex hormonal treatment displayed a lower prevalence of these symptoms than patients who
Psychoneuroendocrinology, 2010
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright
The Journal of Sexual Medicine, 2014
Introduction. Untreated transsexuals have a brain cortical phenotype. Cross-sex hormone treatment... more Introduction. 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. Aim. A longitudinal design was conducted to investigate the effects of treatments on brain cortical thickness (CTh) of FtMs and MtFs. Methods. 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. Main Outcome Measures. Changes in brain CTh thickness and volumetry associated to changes in hormonal levels due to cross-sex hormone therapy. Results. 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. Conclusions. 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 **;**:**-**.
Cerebral Cortex, 2012
Sex differences in cortical thickness (CTh) have been extensively investigated but as yet there a... more 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. T 1-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.
Brain Research, 2005
Central nervous system sex differences have two morphological patterns. In one pattern, males sho... more Central nervous system sex differences have two morphological patterns. In one pattern, males show larger measurements (volume, number of neurons) than females (male > female; m > f) and, in the other, the opposite is true (female > male; f > m). The bed nucleus of the stria terminalis (BST) is a unique model for the study of sex differences because it has dimorphic and isomorphic subdivisions, with the former showing the two sexually differentiated morphological patterns. Meanwhile, other CNS structures, like the locus coeruleus (LC), present the f > m pattern. The philogenetic maintenance of the two patterns of sexual differentiation can help to disentangle the functional meaning of sex differences. Laboratory rat strains, whether albino or pigmented, descend from the Wistar strain through artificial selection. The present work compares the BST and LC of Wistar and Long-Evans rats. The medial posterior subdivision of the BST (BSTMP) is sexually dimorphic (m > f pattern) in the original (Wistar) and derived (Long-Evans) strains, while the lateral anterior and medial anterior subdivisions of the BST and the LC only present sex differences (f > m pattern) in the ancestor Wistar strain. Isomorphic BST regions are the same in both strains. The fact that the BSTMP, which is implicated in male copulatory behavior, is sexually dimorphic in both strains, as well as in other species, including humans, indicates the relevance of this structure in male sexual behavior in mammals.
Brain Research, 2006
Studies have shown that the vomeronasal system (VNS), an olfactory neural network that participat... more Studies have shown that the vomeronasal system (VNS), an olfactory neural network that participates in the control of reproductive physiology and behavior, is sexually dimorphic in the rat. These works have also shown two main characteristics of brain sexual dimorphism: (a) dimorphism appears in neural networks related to reproduction and (b) it can present two morphological patterns: one in which males present greater morphological measures than females (male > female) and another in which the opposite is true (female > male). The present work extends the hypothesis to the rabbit, as a representative species of Lagomorpha. In addition, the locus coeruleus (LC), which is known to send rich noradrenergic projections to VNS structures, was also studied. Sex differences were found in: (a) the number of mitral, and dark and light granule cells (female > male) of the accessory olfactory bulb (AOB); (b) the medial amygdala (Me) and its dorsal (Med) and ventral (Mev) subdivisions, males showing greater values than females in volume and number of neurons, while in the posteromedial cortical amygdala (PMCo or C 3), females show greater density of neurons than males and (c) the posteromedial division of the bed nucleus of the stria terminalis (BSTMP) in which males have more neurons than females. No sex differences were seen in the bed nucleus of the accessory olfactory tract (BAOT) and the LC. These results evidence that, as it was observed in rodents, sex differences are also seen in the VNS of Lagomorpha and that these sex differences present the two morphological patterns seen in Rodentia. Differences between orders are discussed with respect to the species-specific physiological and behavioral peculiarities.
Behavioural Brain Research, 2009
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit:
Archives of Sexual Behavior, 2009
Familial studies and reports of co-occurrence of gender identity disorder (GID) within a family m... more Familial studies and reports of co-occurrence of gender identity disorder (GID) within a family may help to clarify the question of whether transsexualism is a familial phenomenon. In a sample of 995 consecutive transsexual probands (677 male-to-female [MF] and 318 female-to-male [FM]), we report 12 pairs of transsexual non-twin siblings (nine pairs of MF siblings, two pairs of MF-FM siblings, and one pair of FM siblings). The present study doubles the number of case reports of co-occurrence of transsexualism in nontwin siblings available in the literature. According to our data, the probability that a sibling of a transsexual will also be transsexual was 4.48 times higher for siblings of MF than for siblings of FM transsexual probands, and 3.88 times higher for the brothers than for the sisters of transsexual probands. Moreover, the prevalence of transsexualism in siblings of transsexuals (1/211 siblings) was much higher than the range expected according to the prevalence data of transsexualism in Spain. The study suggests that siblings of transsexuals may have a higher risk of being transsexual than the general population, and that the risk is higher for brothers than sisters of transsexuals, and for siblings of MF than FM transsexuals. Nevertheless, the risk is low.
Hormones and Behavior, 2020
The Journal of Sexual Medicine, 2020
Background Brain sexual differentiation is a process that results from the effects of sex steroid... more Background Brain sexual differentiation is a process that results from the effects of sex steroids on the developing brain. Evidence shows that epigenetics plays a main role in the formation of enduring brain sex differences and that the estrogen receptor α (ESR1) is one of the implicated genes. Aim To analyze whether the methylation of region III (RIII) of the ESR1 promoter is involved in the biological basis of gender dysphoria. Methods We carried out a prospective study of the CpG methylation profile of RIII (−1,188 to −790 bp) of the ESR1 promoter using bisulfite genomic sequencing in a cisgender population (10 men and 10 women) and in a transgender population (10 trans men and 10 trans women), before and after 6 months of gender-affirming hormone treatment. Cisgender and transgender populations were matched by geographical origin, age, and sex. DNAs were treated with bisulfite, amplified, cloned, and sequenced. At least 10 clones per individual from independent polymerase chain...
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Papers by Antonio Guillamon q