Gender Incongruence and Autistic Traits: Cerebral and Behavioral Underpinnings.

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.

Occupational stress is associated with sex and subregion specific modifications of the amygdala volumes.

Background: Despite the rapid increase in reports of exhaustion syndrome (ES) due to daily occupational stress, the mechanisms underlying ES are unknown. In the present study, we investigated whether occupational ES is associated with specific modifications of the subfields of the amygdala and hippocampus resembling those described in other chronic stress conditions. Special focus was paid to possible sex differences.Methods: As a follow up to our previous studies of occupational ES, we carried out MRI-based subfield segmentation of the hippocampus and amygdala volumes in 58 patients with occupational ES (22 males) and 65 age-matched controls (27 males) (age range 30-46 years).Results: There was a significant and bilateral enlargement of the lateral, basal and central nucleus of the amygdala in patients with ES (corrected for the total intracranial volume (ICV)). These differences were detected only in females. Higher values in the right central and right basal amygdala remained when the whole amygdala volume was used as reference, instead of the ICV. Notably, in female patients the volumes of these specific nuclei were positively correlated with the degree of perceived stress. No changes in the hippocampus subfields were detected in female or male patients.Conclusions: The findings underline that ES is a chronic stress condition, suggesting that not only extreme forms of stress, but also the everyday stress is associated with localized differences from controls in the amygdala. The absence of significant alterations among men with ES despite a similar degree of perceived stress supports the notion that women seem more susceptible to stress-related cerebral changes, and may explain the higher prevalence of ES among women.

Amygdala subfield and prefrontal cortex abnormalities in patients with functional seizures.

BACKGROUND: Functional seizures (FS) are paroxysmal episodes, resembling epileptic seizures, but without underlying epileptic abnormality. The aetiology and neuroanatomic associations are incompletely understood. Recent brain imaging data indicate cerebral changes, however, without clarifying possible pathophysiology. In the present study, we specifically investigated the neuroanatomic changes in subregions of the amygdala and hippocampus in FS. METHODS: T1 MRI scans of 37 female patients with FS and 37 age-matched female seizure naïve controls (SNC) were analyzed retrospectively in FreeSurfer version 7.1. Seizure naïve controls included patients with depression and anxiety disorders. The analysis included whole-brain cortical thickness, subcortical volumes, and subfields of the amygdala and hippocampus. Group comparisons were carried out using multivariable linear models. RESULTS: The FS and SNC groups did not differ in the whole hippocampus and amygdala volumes. However, patients had a significant reduction of the right lateral amygdala volume (p = 0.00041), an increase of the right central amygdala, (p = 0.037), and thinning of the left superior frontal gyrus (p = 0.024). Additional findings in patients were increased volumes of the right medial amygdala (p = 0.031), left anterior amygdala (p = 0.017), and left dentate gyrus of the hippocampus (p = 0.035). CONCLUSIONS: The observations from the amygdala and hippocampus segmentation affirm that there are neuroanatomic associations of FS. The pattern of these changes aligned with some of the cerebral changes described in chronic stress conditions and depression. The pattern of detected changes further study, and may, after validation, provide biomarkers for diagnosis and treatment.

Clinical MRI morphological analysis of functional seizures compared to seizure-naïve and psychiatric controls.

PURPOSE: Functional seizures (FS), also known as psychogenic nonepileptic seizures (PNES), are physical manifestations of acute or chronic psychological distress. Functional and structural neuroimaging have identified objective signs of this disorder. We evaluated whether magnetic resonance imaging (MRI) morphometry differed between patients with FS and clinically relevant comparison populations. METHODS: Quality-screened clinical-grade MRIs were acquired from 666 patients from 2006 to 2020. Morphometric features were quantified with FreeSurfer v6. Mixed-effects linear regression compared the volume, thickness, and surface area within 201 regions-of-interest for 90 patients with FS, compared to seizure-naïve patients with depression (n = 243), anxiety (n = 68), and obsessive-compulsive disorder (OCD, n = 41), respectively, and to other seizure-naïve controls with similar quality MRIs, accounting for the influence of multiple confounds including depression and anxiety based on chart review. These comparison populations were obtained through review of clinical records plus research studies obtained on similar scanners. RESULTS: After Bonferroni-Holm correction, patients with FS compared with seizure-naïve controls exhibited thinner bilateral superior temporal cortex (left 0.053 mm, p = 0.014; right 0.071 mm, p = 0.00006), thicker left lateral occipital cortex (0.052 mm, p = 0.0035), and greater left cerebellar white-matter volume (1085 mm3, p = 0.0065). These findings were not accounted for by lower MRI quality in patients with FS. CONCLUSIONS: These results reinforce prior indications of structural neuroimaging correlates of FS and, in particular, distinguish brain morphology in FS from that in depression, anxiety, and OCD. Future work may entail comparisons with other psychiatric disorders including bipolar and schizophrenia, as well as exploration of brain structural heterogeneity within FS.

A minority of patients with functional seizures have abnormalities on neuroimaging.

OBJECTIVE: Functional seizures often are managed incorrectly as a diagnosis of exclusion. However, a significant minority of patients with functional seizures may have abnormalities on neuroimaging that typically are associated with epilepsy, leading to diagnostic confusion. We evaluated the rate of epilepsy-associated findings on MRI, FDG-PET, and CT in patients with functional seizures. METHODS: We studied radiologists' reports from neuroimages at our comprehensive epilepsy center from a consecutive series of patients diagnosed with functional seizures without comorbid epilepsy from 2006 to 2019. We summarized the MRI, FDG-PET, and CT results as follows: within normal limits, incidental findings, unrelated findings, non-specific abnormalities, post-operative study, epilepsy risk factors (ERF), borderline epilepsy-associated findings (EAF), and definitive EAF. RESULTS: Of the 256 MRIs, 23% demonstrated ERF (5%), borderline EAF (8%), or definitive EAF (10%). The most common EAF was hippocampal sclerosis, with the majority of borderline EAF comprising hippocampal atrophy without T2 hyperintensity or vice versa. Of the 87 FDG-PETs, 26% demonstrated borderline EAF (17%) or definitive EAF (8%). Epilepsy-associated findings primarily included focal hypometabolism, especially of the temporal lobes, with borderline findings including subtle or questionable hypometabolism. Of the 51 CTs, only 2% had definitive EAF. SIGNIFICANCE: This large case series provides further evidence that, while uncommon, EAF are seen in patients with functional seizures. A significant portion of these abnormal findings are borderline. The moderately high rate of these abnormalities may represent framing bias from the indication of the study being "seizures," the relative subtlety of EAF, or effects of antiseizure medications.

Cortical Gyrification in Transgender Individuals.

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.

Cross-sex hormone treatment and own-body perception: behavioral and brain connectivity profiles.

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.

Predicting outcomes of cross-sex hormone therapy in transgender individuals with gender incongruence based on pre-therapy resting-state brain connectivity.

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.

MRS Shows Regionally Increased Glutamate Levels among Patients with Exhaustion Syndrome Due to Occupational Stress.

Despite the rapid increase of reports of exhaustion syndrome (ES) due to daily occupational stress, the mechanisms underlying ES are unknown. We used voxel-based 1H-MR spectroscopy to examine the potential role of glutamate in this condition. The levels of glutamate were found to be elevated among ES patients (n = 30, 16 females) compared with controls (n = 31, 15 females). Notably, this increase was detected only in the anterior cingulate and mesial prefrontal cortex (ACC/mPFC), and the glutamate levels were linearly correlated with the degree of perceived stress. Furthermore, there was a sex by group interaction, as the glutamate elevation was present only in female patients. Female but not male ES patients also showed an increase in N-acetyl aspartate (NAA) levels in the amygdala. No group differences were detected in glutamine concentration (also measured). These data show the key role of glutamate in stress-related neuronal signaling and the specific roles of the amygdala and ACC/mPFC. The data extend previous reports about the neurochemical basis of stress and identify a potential neural marker and mediator of ES due to occupational stress. The observation of specific sex differences provides a tentative explanation to the well-known female predominance in stress-related psychopathology.

Neural Systems for Own-body Processing Align with Gender Identity Rather Than Birth-assigned Sex.

Gender identity is a core aspect of self-identity and is usually congruent with birth-assigned sex and own body sex-perception. The neuronal circuits underlying gender identity are unknown, but greater awareness of transgenderism has sparked interest in studying these circuits. We did this by comparing brain activation and connectivity in transgender individuals (for whom gender identity and birth-assigned sex are incongruent) with that in cisgender controls (for whom they are congruent) when performing a body self-identification task during functional magnetic resonance imaging. Thirty transgender and 30 cisgender participants viewed images of their own bodies and bodies morphed in sex toward or opposite to birth-assigned sex, rating each image to the degree they identified with it. While controls identified with images of themselves, transgender individuals identified with images morphed "opposite" to their birth-assigned sex. After covarying out the effect of self-similarity ratings, both groups activated similar self- and body-processing systems when viewing bodies that aligned with their gender identity rather than birth-assigned sex. Additionally, transgender participants had greater limbic involvement when viewing ambiguous, androgynous images of themselves morphed toward their gender identity. These results shed light on underlying self-processing networks specific to gender identity and uncover additional involvement of emotional processing in transgender individuals.

Reduced left amygdala volume in patients with dissociative seizures (psychogenic nonepileptic seizures).

PURPOSE: This study specifically investigated differences of amygdalar and hippocampal volumes between patients with dissociative seizures (DS), mesial temporal lobe sclerosis (MTS), and normal controls (NC). METHODS: Between 2003 and 2018, 127 patients diagnosed with DS and 278 with MTS were recruited. An additional 52 NC subjects were recruited between 2015 and 2018. We retrospectively selected 29 patients with DS (male:female, 6:23) with absence of structural confounding factors and obtained sex- and age-matched MTS and NC. We used Neuroreader to assess the volume of the amygdala and hippocampus as a percentage of total intracranial volume based on thin-slice (0.9-1.2 mm) T1-weighted images. Statistical analyses controlled for psychiatric comorbidity and logistic regression were used to evaluate efficacy of these values for individual-level diagnosis. RESULTS: The left amygdala and right hippocampus were significantly smaller in DS compared to NC (both p = 0.04), which was not explained by differences in psychiatric comorbidity. When controlling for ipsilateral hippocampal or amygdala volume, which was seen equally in all groups (Spearman, p < 0.02), these differences were no longer significant (amygdala, p = 0.16, hippocampus, p = 0.18), suggesting that amygdalar and hippocampal atrophy may reflect network or regional changes rather than focal abnormalities. The three-way accuracy for differentiating DS, MTS, and NC using these data was 64 % (95 % confidence interval: 54-74 %). CONCLUSION: Volumetric analysis demonstrates smaller left amygdalar and right hippocampal volumes in patients with DS compared to NC, which may mirror abnormalities in functional networks seen in conversion disorders and post-traumatic stress disorder.

Cortical structure abnormalities in females with conduct disorder prior to age 15.

Among females, conduct disorder (CD) before age 15 is associated with multiple adverse outcomes in adulthood. The few existing structural neuroimaging studies of females with CD report abnormalities of gray matter volumes. The present study compared cortical thickness and surface area of young women with childhood/adolescent CD and healthy women to determine whether cortical abnormalities were present in adulthood and whether they were related to prior CD. Structural brain images from 31 women with CD and 25 healthy women were analyzed using FreeSurfer. Group differences between cortical thickness and surface area were assessed using cluster-wise corrections with Monte Carlo simulations. Women with prior CD, relative to healthy women, showed: (1) reduced cortical thickness in left fusiform gyrus extending up to entorhinal cortex and lingual gyrus; (2) reduced surface area in right superior parietal cortex; (3) increased surface area in left superior temporal gyrus, and right precentral gyrus. These differences remained significant after adjusting for past comorbid disorders, current symptoms of anxiety and depression, current substance use as well as maltreatment. The study suggests that among females, CD prior to age 15 is associated with cortical structure abnormalities in brain regions involved in emotion processing and social interaction.

Cross sex hormone treatment is linked with a reversal of cerebral patterns associated with gender dysphoria to the baseline of cisgender controls.

Transgender persons experience incongruence between their gender identity and birth-assigned sex. The resulting gender dysphoria (GD), is frequently treated with cross-sex hormones. However, very little is known about how this treatment affects the brain of individuals with GD, nor do we know the neurobiology of GD. We recently suggested that disconnection of fronto-parietal networks involved in own-body self-referential processing could be a plausible mechanism, and that the anatomical correlate could be a thickening of the mesial prefrontal and precuneus cortex, which is unrelated to sex. Here, we investigate how cross-sex hormone treatment affects cerebral tissue in persons with GD, and how potential changes are related to self-body perception. Longitudinal MRI measurements of cortical thickness (Cth) were carried out in 40 transgender men (TrM), 24 transgender women (TrW) and 19 controls. Cth increased in the mesial temporal and insular cortices with testosterone treatment in TrM, whereas anti-androgen and oestrogen treatment in TrW caused widespread cortical thinning. However, after correction for treatment-related changes in total grey and white matter volumes (increase with testosterone; decrease with anti-androgen and oestrogen), significant Cth decreases were observed in the mesial prefrontal and parietal cortices, in both TrM and TrW (vs. controls) - regions showing greater pre-treatment Cth than in controls. The own body - self congruence ratings increased with treatment, and correlated with a left parietal cortical thinning. These data confirm our hypothesis that GD may be associated with specific anatomical features in own-body/self-processing circuits that reverse to the pattern of cisgender controls after cross-sex hormone treatment.

Sex differences in own and other body perception.

Own body perception, and differentiating and comparing one's body to another person's body, are common cognitive functions that have relevance for self-identity and social interactions. In several psychiatric conditions, including anorexia nervosa, body dysmorphic disorder, gender dysphoria, and autism spectrum disorder, self and own body perception, as well as aspects of social communication are disturbed. Despite most of these conditions having skewed prevalence sex ratios, little is known about whether the neural basis of own body perception differs between the sexes. We addressed this question by investigating brain activation using functional magnetic resonance imaging during a Body Perception task in 15 male and 15 female healthy participants. Participants viewed their own body, bodies of same-sex, or opposite-sex other people, and rated the degree that they appeared like themselves. We found that men and women did not differ in the pattern of brain activation during own body perception compared to a scrambled control image. However, when viewing images of other bodies of same-sex or opposite-sex, men showed significantly stronger activations in attention-related and reward-related brain regions, whereas women engaged stronger activations in striatal, medial-prefrontal, and insular cortices, when viewing the own body compared to other images of the opposite sex. It is possible that other body images, particularly of the opposite sex, may be of greater salience for men, whereas images of own bodies may be more salient for women. These observations provide tentative neurobiological correlates to why women may be more vulnerable than men to conditions involving own body perception.

Multimodal MRI suggests that male homosexuality may be linked to cerebral midline structures.

The neurobiology of sexual preference is often discussed in terms of cerebral sex dimorphism. Yet, our knowledge about possible cerebral differences between homosexual men (HoM), heterosexual men (HeM) and heterosexual women (HeW) are extremely limited. In the present MRI study, we addressed this issue investigating measures of cerebral anatomy and function, which were previously reported to show sex difference. Specifically, we asked whether there were any signs of sex atypical cerebral dimorphism among HoM, if these were widely distributed (providing substrate for more general 'female' behavioral characteristics among HoM), or restricted to networks involved in self-referential sexual arousal. Cortical thickness (Cth), surface area (SA), subcortical structural volumes, and resting state functional connectivity were compared between 30 (HoM), 35 (HeM) and 38 (HeW). HoM displayed a significantly thicker anterior cingulate cortex (ACC), precuneus, and the left occipito-temporal cortex compared to both control groups. These differences seemed coordinated, since HoM also displayed stronger cortico-cortical covariations between these regions. Furthermore, functional connections within the default mode network, which mediates self- referential processing, and includes the ACC and precuneus were significantly weaker in HoM than HeM and HeW, whereas their functional connectivity between the thalamus and hypothalamus (important nodes for sexual behavior) was stronger. In addition to these singular features, HoM displayed 'female' characteristics, with a similar Cth in the left superior parietal and cuneus cortices as HeW, but different from HeM. These data suggest both singular and sex atypical features and motivate further investigations of cerebral midline structures in relation to male homosexuality.

Associations of Psychopathic Traits With Local and Global Brain Network Topology in Young Adult Women.

BACKGROUND: Psychopathic traits vary dimensionally in the population and are associated with multiple negative outcomes. The impaired integration theory (IIT) proposes that psychopathic traits are associated with abnormal neural network topology, such that disturbed integration of neural networks results in a self-perpetuating impairment in rapid integration and learning from multiple components of information. The IIT is based on findings from male offenders presenting high scores on all psychopathic traits. The present study investigated whether IIT predictions of topology abnormalities were associated with psychopathic traits, measured dimensionally, in young adult women with subsyndromal scores. METHODS: Seventy-three women, with an average age of 25 years, were assessed using the Psychopathy Checklist-Revised and completed resting-state magnetic resonance imaging. Preprocessed time series from 90 anatomical regions were extracted to form connectivity matrices and used to calculate network topology based on graph theory. Correlations between total psychopathy and factor scores with both the raw connectivity matrix and global and local graph theory measures were computed. RESULTS: Total psychopathy scores and behavioral factor scores were related to connectivity between several pairs of regions, primarily limbic/paralimbic. Psychopathic traits were not associated with global topology measures. Topology abnormalities, robust across network formation thresholds, were found in nodes of the default mode network and in hubs connecting several resting-state networks. CONCLUSIONS: IIT predictions of abnormal topology of hubs and default mode network nodes with dimensionally measured psychopathic traits were confirmed in a sample of young women. Regional abnormalities, accompanied by preserved global topology, may underlie context-specific abnormal information processing and integration.

Candida bloodstream infections in Serbia: First multicentre report of a national prospective observational survey in intensive care units.

Candida bloodstream infections (BSI) are a significant cause of mortality in intensive care units (ICU), hereof the prospective 12-months (2014-2015) hospital- and laboratory-based survey was performed at the Serbian National Reference Medical Mycology Laboratory (NRMML). Candida identification was done by a matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry and a susceptibility test, according to the Clinical and Laboratory Standards Institute methodology. Among nine centres (265 beds; 10 820 patient admissions), four neonatal/paediatric (NICU/PICUs) and five adult centres (ICUs) participated, representing 89 beds and 3446 patient admissions, 166 beds and 7347 patient admissions respectively. The NRMML received 43 isolates, 17 from NICU/PICUs and 26 from adult ICUs. C. albicans dominated highly in NICU/PICUs (~71%), whereas C. albicans and C. parapsilosis were equally distributed within adults (46%, each), both accounting for ~90% of received isolates. The resistance to itraconazole and flucytosine were 25% and 2.4% respectively. In addition, the 2 C. albicans were azole cross-resistant (4.6%). The overall incidence of CandidaBSI was ~3.97 cases/1000 patient admissions (4.93 in NICU/PICU and 3.53 in adult ICU). The 30-day mortality was ~37%, most associated with C. tropicalis and C. glabrataBSI. Data from this national survey may contribute to improving the Balkan and Mediterranean region epidemiology of CandidaBSI within ICUs.

Cerebral sex dimorphism and sexual orientation.

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.

Structural connections in the brain in relation to gender identity and sexual orientation.

Both transgenderism and homosexuality are facets of human biology, believed to derive from different sexual differentiation of the brain. The two phenomena are, however, fundamentally unalike, despite an increased prevalence of homosexuality among transgender populations. Transgenderism is associated with strong feelings of incongruence between one's physical sex and experienced gender, not reported in homosexual persons. The present study searches to find neural correlates for the respective conditions, using fractional anisotropy (FA) as a measure of white matter connections that has consistently shown sex differences. We compared FA in 40 transgender men (female birth-assigned sex) and 27 transgender women (male birth-assigned sex), with both homosexual (29 male, 30 female) and heterosexual (40 male, 40 female) cisgender controls. Previously reported sex differences in FA were reproduced in cis-heterosexual groups, but were not found among the cis-homosexual groups. After controlling for sexual orientation, the transgender groups showed sex-typical FA-values. The only exception was the right inferior fronto-occipital tract, connecting parietal and frontal brain areas that mediate own body perception. Our findings suggest that the neuroanatomical signature of transgenderism is related to brain areas processing the perception of self and body ownership, whereas homosexuality seems to be associated with less cerebral sexual differentiation.