The organization of functional neurocognitive networks in focal epilepsy correlates with domain-specific cognitive performance.

Understanding and diagnosing cognitive impairment in epilepsy remains a prominent challenge. New etiological models suggest that cognitive difficulties might not be directly linked to seizure activity, but are rather a manifestation of a broader brain pathology. Consequently, treating seizures is not sufficient to alleviate cognitive symptoms, highlighting the need for novel diagnostic tools. Here, we investigated whether the organization of three intrinsic, resting-state functional connectivity networks was correlated with domain-specific cognitive test performance. Using individualized EEG source reconstruction and graph theory, we examined the association between network small worldness and cognitive test performance in 23 patients with focal epilepsy and 17 healthy controls, who underwent a series of standardized pencil-and-paper and digital cognitive tests. We observed that the specific networks robustly correlated with test performance in distinct cognitive domains. Specifically, correlations were evident between the default mode network and memory in patients, the central-executive network and executive functioning in controls, and the salience network and social cognition in both groups. Interestingly, the correlations were evident in both groups, but in different domains, suggesting an alteration in these functional neurocognitive networks in focal epilepsy. The present findings highlight the potential clinical relevance of functional brain network dysfunction in cognitive impairment.

The Predictive Value of Depression in the Years After Heart Transplantation for Mortality During Long-Term Follow-Up.

OBJECTIVE: Current understanding of the prognostic impact of depression on mortality after heart transplantation (HTx) is limited. We examined whether depression after HTx is a predictor of mortality during extended follow-up. Subsequently, we explored whether different symptom dimensions of depression could be identified and whether they were differentially associated with mortality. METHODS: Survival analyses were performed in a sample of 141 HTx recipients assessed for depression, measured by self-report of depressive symptoms (Beck Depression Inventory - version 1A [BDI-1A]), at median 5.0 years after HTx, and followed thereafter for survival status for up to 18.6 years. We used uni- and multivariate Cox proportional hazard models to examine the association of clinically significant depression (BDI-1A total score ≥10), as well as the cognitive-affective and the somatic subscales of the BDI-1A (resulting from principal component analysis) with mortality. In the multivariate analyses, we adjusted for relevant sociodemographic and clinical variables. RESULTS: Clinically significant depression was a significant predictor of mortality (hazard ratio = 2.088; 95% confidence interval = 1.366-3.192; p = .001). Clinically significant depression also was an independent predictor of mortality in the multivariate analysis (hazard ratio = 1.982; 95% confidence interval = 1.220-3.217; p = .006). The somatic subscale, but not the cognitive-affective subscale, was significantly associated with increased mortality in univariate analyses, whereas neither of the two subscales was an independent predictor of mortality in the multivariate analysis. CONCLUSIONS: Depression measured by self-report after HTx is associated with increased mortality during extended follow-up. Clinical utility and predictive validity of specific depression components require further study.

Cognitive function after heart transplantation: Comparing everolimus-based and calcineurin inhibitor-based regimens.

BACKGROUND: Studies have shown conflicting results concerning the occurrence of cognitive impairment after successful heart transplantation (HTx). Another unresolved issue is the possible differential impact of immunosuppressants on cognitive function. In this study, we describe cognitive function in a cohort of HTx recipients and subsequently compare cognitive function between subjects on either everolimus- or calcineurin inhibitor (CNI)-based immunosuppression. METHODS: Cognitive function, covering attention, processing speed, executive functions, memory, and language functions, was assessed with a neuropsychological test battery. Thirty-seven subjects were included (everolimus group: n=20; CNI group: n=17). The extent of cerebrovascular pathology was assessed with magnetic resonance imaging. RESULTS: About 40% of subjects had cognitive impairment, defined as performance at least 1.5 standard deviations below normative mean in one or several cognitive domains. Cerebrovascular pathology was present in 33.3%. There were no statistically significant differences between treatment groups across cognitive domains. CONCLUSIONS: Given the high prevalence of cognitive impairment in the sample, plus the known negative impact of cognitive impairment on clinical outcome, our results indicate that cognitive assessment should be an integrated part of routine clinical follow-up after HTx. However, everolimus- and CNI-based immunosuppressive regimens did not show differential impacts on cognitive function.

Cognitive function among long-term survivors of heart transplantation.

BACKGROUND: Cognitive impairment is documented early after heart transplantation (HTx), but we lack data on cognitive function beyond the fourth year post-transplant. Against the background of good long-term survival, this knowledge is necessary to improve clinical care throughout the entire post-transplant period. METHODS: We assessed cognitive function with a neuropsychological test battery in a sample of HTx recipients ≥16 years post-transplant. To improve clinical utility, we also applied adapted consensus criteria for Mild Cognitive Impairment (MCI). Furthermore, we explored sociodemographic and clinical characteristics possibly related to cognitive function. RESULTS: Thirty-seven subjects were included 20.3 (±3.8) years after HTx. Mean age was 57.5 (±14.2) years, and 18.9% were women. Up to 38.9% exhibited impaired test performance (ie, performance at least 1.5 standard deviations below the normative mean) on several individual cognitive measures, especially on measures of processing speed, executive functions, memory, and language functions. One subject was diagnosed with dementia, and 30.1% qualified for MCI. Those with MCI had lower hemoglobin than those without. CONCLUSIONS: A substantial proportion of long-term survivors of HTx might be cognitively impaired. The level of impairment appears comparable to what is defined as MCI in the literature. Modifiable factors related to cognitive impairment might exist.

Recent Development of Non-Peptide GnRH Antagonists.

The decapeptide gonadotropin-releasing hormone, also referred to as luteinizing hormone-releasing hormone with the sequence (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) plays an important role in regulating the reproductive system. It stimulates differential release of the gonadotropins FSH and LH from pituitary tissue. To date, treatment of hormone-dependent diseases targeting the GnRH receptor, including peptide GnRH agonist and antagonists are now available on the market. The inherited issues associate with peptide agonists and antagonists have however, led to significant interest in developing orally active, small molecule, non-peptide antagonists. In this review, we will summarize all developed small molecule GnRH antagonists along with the most recent clinical data and therapeutic applications.

Measuring Gender Dysphoria: A Multicenter Examination and Comparison of the Utrecht Gender Dysphoria Scale and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults.

This study examined two instruments measuring gender dysphoria within the multicenter study of the European Network for the Investigation of Gender Incongruence (ENIGI). The Utrecht Gender Dysphoria Scale (UGDS) and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA) were examined for their definitions of gender dysphoria and their psychometric properties, and evaluated for their congruence in assessing the construct. The sample of 318 participants consisted of 178 male-to-females (MtF) and 140 female-to-males (FtM) who were recruited from the four ENIGI gender clinics. Both instruments were significantly correlated in the group of MtFs. For the FtM group, there was a trend in the same direction but smaller. Gender dysphoria was found to be defined differently in the two instruments, which led to slightly different findings regarding the subgroups. The UGDS detected a difference between the subgroups of early and late onset of gender identity disorder in the group of MtFs, whereas the GIDYQ-AA did not. For the FtM group, no significant effect of age of onset was found. Therefore, both instruments seem to capture not only similar but also different aspects of gender dysphoria. The UGDS focusses on bodily aspects, gender identity, and gender role, while the GIDYQ-AA addresses subjective, somatic, social, and sociolegal aspects. For future research, consistency in theory and definition of gender dysphoria is needed and should be in line with the DSM-5 diagnosis of gender dysphoria in adolescents and adults.

Body Image in Young Gender Dysphoric Adults: A European Multi-Center Study.

The alteration of sex-specific body features and the establishment of a satisfactory body image are known to be particularly relevant for individuals with Gender Dysphoria (GD). The aim of the study was to first develop new scales and examine the psychometric properties of the Hamburg Body Drawing Scale (Appelt & Strauß 1988). For the second part of this study, the satisfaction with different body features in young GD adults before cross-sex treatment were compared to female and male controls. Data collection took place within the context of the European Network for the Investigation of Gender Incongruence (ENIGI) including 135 female-to-male (FtMs) and 115 male-to-female (MtFs) young GD adults and 235 female and 379 male age-adjusted controls. The five female and six male body feature subscales revealed good internal consistency. The ENIGI sample reported less satisfaction with overall appearance (d = 0.30) and with all of their body features than controls, but no subgroup differences for sexual orientation (FtM and MtF) and Age of Onset (FtM) were found. Body dissatisfaction was higher with regard to sex-specific body features (largest effect sizes of d = 3.21 for Genitalia in FtMs and d = 2.85 for Androgen-responsive features and genitalia in MtFs) than with those that appeared less related to the natal sex (d = 0.64 for Facial features in FtMs and d = 0.59 for Body shape in MtFs). Not only medical body modifying interventions, but also psychosocial guidance with regard to body image might be helpful for GD individuals before transitioning.

Body Satisfaction and Physical Appearance in Gender Dysphoria.

Gender dysphoria (GD) is often accompanied by dissatisfaction with physical appearance and body image problems. The aim of this study was to compare body satisfaction with perceived appearance by others in various GD subgroups. Data collection was part of the European Network for the Investigation of Gender Incongruence. Between 2007 and 2012, 660 adults who fulfilled the criteria of the DSM-IV gender identity disorder diagnosis (1.31:1 male-to-female [MtF]:female-to-male [FtM] ratio) were included into the study. Data were collected before the start of clinical gender-confirming interventions. Sexual orientation was measured via a semi-structured interview whereas onset age was based on clinician report. Body satisfaction was assessed using the Body Image Scale. Congruence of appearance with the experienced gender was measured by means of a clinician rating. Overall, FtMs had a more positive body image than MtFs. Besides genital dissatisfaction, problem areas for MtFs included posture, face, and hair, whereas FtMs were mainly dissatisfied with hip and chest regions. Clinicians evaluated the physical appearance to be more congruent with the experienced gender in FtMs than in MtFs. Within the MtF group, those with early onset GD and an androphilic sexual orientation had appearances more in line with their gender identity. In conclusion, body image problems in GD go beyond sex characteristics only. An incongruent physical appearance may result in more difficult psychological adaptation and in more exposure to discrimination and stigmatization.

Psychiatric characteristics in transsexual individuals: multicentre study in four European countries.

BACKGROUND: Research into the relationship between gender identity disorder and psychiatric problems has shown contradictory results. AIMS: To investigate psychiatric problems in adults fulfilling DSM-IV-TR criteria for a diagnosis of gender identity disorder. METHOD: Data were collected within the European Network for the Investigation of Gender Incongruence using the Mini International Neuropsychiatric Interview - Plus and the Structured Clinical Interview for DSM-IV Axis II Disorders (n = 305). RESULTS: In 38% of the individuals with gender identity disorder a current DSM-IV-TR Axis I diagnosis was found, mainly affective disorders and anxiety disorders. Furthermore, almost 70% had a current and lifetime diagnosis. All four countries showed a similar prevalence, except for affective and anxiety disorders, and no difference was found between individuals with early-onset and late-onset disorder. An Axis II diagnosis was found in 15% of all individuals with gender identity disorder, which is comparable to the general population. CONCLUSIONS: People with gender identity disorder show more psychiatric problems than the general population; mostly affective and anxiety problems are found.

Cross-sex hormone therapy in trans persons is safe and effective at short-time follow-up: results from the European network for the investigation of gender incongruence.

INTRODUCTION: Data on the effects of cross-sex hormone therapy (CHT) are limited due to the low prevalence of gender dysphoria, small number of subjects treated at each center, lack of prospective studies, and wide variations in treatment modalities. AIM: The aim of this study is to report the short-term effects of CHT on hormonal and clinical changes, side effects, and adverse events in trans men (female-to-male gender dysphoric persons) and trans women (male-to-female gender dysphoric persons). METHODS: This was a multicenter 1-year prospective study in 53 trans men and 53 trans women. Trans men received injections of testosterone undecanoate every 3 months. Trans women younger than 45 years received 50 mg cyproterone acetate (CA) and 4 mg estradiol valerate daily, whereas those older than 45 years received 50 mg CA daily together with 100 µg/24 hours transdermal 17-ß estradiol. MAIN OUTCOME MEASURES: Sex steroids, prolactin, liver enzymes, lipids, hematocrit, blood pressure, anthropometrics, Ferriman and Gallwey score, and global acne grading scale were measured. Side effects, adverse events, and desired clinical changes were examined. RESULTS: No deaths or severe adverse events were observed. Two trans men developed erythrocytosis, and two had transient elevation of the liver enzymes. Trans men reported an increase in sexual desire, voice instability, and clitoral pain (all P ≤ 0.01). Testosterone therapy increased acne scores, facial and body hair, and prevalence of androgenetic alopecia. Waist-hip ratio, muscle mass, triglycerides, total cholesterol (C), and LDL-C increased, whereas total body fat mass and HDL-C decreased. Three trans women experienced transient elevation of liver enzymes. A significant increase in breast tenderness, hot flashes, emotionality, and low sex drive was observed (all P ≤ 0.02). Fasting insulin, total body fat mass, and prolactin levels increased, and waist-hip ratio, lean mass, total C, and LDL-C decreased. CONCLUSIONS: Current treatment modalities were effective and carried a low risk for side effects and adverse events at short-time follow-up.

Synthesis and in vitro evaluation of small-molecule [18F] labeled gonadotropin-releasing hormone (GnRH) receptor antagonists as potential PET imaging agents for GnRH receptor expression.

Two novel small molecule gonadotropin-releasing hormone (GnRH) receptor antagonists (12 and 13) of the furamide-class were synthesized and evaluated in vitro for their receptor binding affinities for the rat GnRH receptor. Radiolabeling with no carrier added fluorine-18 of the appropriate precursors was investigated in a one-step reaction. LogP (Octanol/PBS pH 7.4) and serum stability of the compounds were investigated. The antagonists showed low nM affinity for the rat GnRH receptor. (18)F-radiolabled compounds were obtained in high radiochemical purity (>95%) and specific activity (>75 GBq/µmol). These findings suggest this class of compounds holds promise as potential probes for PET targeting of GnRH-receptor expression.

Sexual behavior of gender-dysphoric individuals before gender-confirming interventions: a European multicenter study.

A transsexual course of development that starts before puberty (early onset) or during or after puberty, respectively (late onset), may lead to diverse challenges in coping with sexual activity. The authors explored the sexual behavior of 380 adult male-to-female and female-to-male individuals diagnosed according to DSM-IV-TR criteria who had not yet undergone gender-confirming interventions. Data originated from the European Network for the Investigation of Gender Incongruence Initiative, conducted in Belgium, Germany, The Netherlands, and Norway. Information on outcome variables was collected using self-administered questionnaires at first clinical presentation. Compared with late-onset male-to-females, early-onset individuals tended to show sexual attraction toward males more frequently (50.5%), involve genitals less frequently in partner-related sexual activity, and consider penile sensations and orgasm as more negative. Early-onset female-to-males predominantly reported sexual attraction toward females (84.0%), whereas those with a late-onset more frequently showed other sexual attractions (41.7%). The study (a) shows that early- and late-onset male-to-females differ considerably with regard to coping strategies involving their body during sexual relations and (b) reveals initial insights into developmental pathways of late-onset female-to-males.

Artificial intelligence in neurology: opportunities, challenges, and policy implications.

Neurological conditions are the leading cause of disability and mortality combined, demanding innovative, scalable, and sustainable solutions. Brain health has become a global priority with adoption of the World Health Organization's Intersectoral Global Action Plan in 2022. Simultaneously, rapid advancements in artificial intelligence (AI) are revolutionizing neurological research and practice. This scoping review of 66 original articles explores the value of AI in neurology and brain health, systematizing the landscape for emergent clinical opportunities and future trends across the care trajectory: prevention, risk stratification, early detection, diagnosis, management, and rehabilitation. AI's potential to advance personalized precision neurology and global brain health directives hinges on resolving core challenges across four pillars-models, data, feasibility/equity, and regulation/innovation-through concerted pursuit of targeted recommendations. Paramount actions include swift, ethical, equity-focused integration of novel technologies into clinical workflows, mitigating data-related issues, counteracting digital inequity gaps, and establishing robust governance frameworks balancing safety and innovation.

Psychiatric outcome after severe cardio-respiratory failure treated with extracorporeal membrane oxygenation: a case-series.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used to save patients with severe cardiopulmonary failure at high risk of dying, but the long-term psychiatric outcome of the treatment has not been studied. METHODS: Twenty-eight adults who survived ECMO were subjected to psychiatric assessment 5 years after ECMO by means of interviews (MINI-Neuropsychiatric Interview and Montgomery-Åsberg Depression Rating Scale) and psychometrics [Neuroticism and social conformity (EPQ-N+L); General Health Questionnaire (GHQ), Hospital Anxiety Depression Scale; Aggression Questionnaire, Toronto Alexithymia Scale, and Giessener somatic symptom checklist (GBB)]. RESULTS: Fifteen patients (54%) suffered lifetime psychiatric disorders prior to ECMO. After ECMO, 11 subjects (39%) developed new psychiatric disorders, mostly organic mental (18%), obsessive-compulsive disorders (OCD) 15%, and/or post-traumatic stress disorders (PTSD) 11%. These 11 patients reported higher scores on Montgomery-Åsberg Depression Rating Scale (MADRS), GHQ, EPQ-N, and GBB. Disregarding the presence of psychiatric disorders at follow-up, ECMO patients reported high levels of distress, physical aggression, anger, and alexithymic traits. CONCLUSIONS: Severe life-threatening cardiovascular or pulmonary failure with subsequent ECMO is associated with an increased prevalence of long-term psychiatric disorders and distress. Studies addressing the etiology and prevalence of psychiatric consequences after ECMO are needed.

Reliable evaluation of functional connectivity and graph theory measures in source-level EEG: How many electrodes are enough?

OBJECTIVE: Using EEG to characterise functional brain networks through graph theory has gained significant interest in clinical and basic research. However, the minimal requirements for reliable measures remain largely unaddressed. Here, we examined functional connectivity estimates and graph theory metrics obtained from EEG with varying electrode densities. METHODS: EEG was recorded with 128 electrodes in 33 participants. The high-density EEG data were subsequently subsampled into three sparser montages (64, 32, and 19 electrodes). Four inverse solutions, four measures of functional connectivity, and five graph theory metrics were tested. RESULTS: The correlation between the results obtained with 128-electrode and the subsampled montages decreased as a function of the number of electrodes. As a result of decreased electrode density, the network metrics became skewed: mean network strength and clustering coefficient were overestimated, while characteristic path length was underestimated. CONCLUSIONS: Several graph theory metrics were altered when electrode density was reduced. Our results suggest that, for optimal balance between resource demand and result precision, a minimum of 64 electrodes should be utilised when graph theory metrics are used to characterise functional brain networks in source-reconstructed EEG data. SIGNIFICANCE: Characterisation of functional brain networks derived from low-density EEG warrants careful consideration.

Introducing Region Based Pooling for handling a varied number of EEG channels for deep learning models.

Introduction: A challenge when applying an artificial intelligence (AI) deep learning (DL) approach to novel electroencephalography (EEG) data, is the DL architecture's lack of adaptability to changing numbers of EEG channels. That is, the number of channels cannot vary neither in the training data, nor upon deployment. Such highly specific hardware constraints put major limitations on the clinical usability and scalability of the DL models. Methods: In this work, we propose a technique for handling such varied numbers of EEG channels by splitting the EEG montages into distinct regions and merge the channels within the same region to a region representation. The solution is termed Region Based Pooling (RBP). The procedure of splitting the montage into regions is performed repeatedly with different region configurations, to minimize potential loss of information. As RBP maps a varied number of EEG channels to a fixed number of region representations, both current and future DL architectures may apply RBP with ease. To demonstrate and evaluate the adequacy of RBP to handle a varied number of EEG channels, sex classification based solely on EEG was used as a test example. The DL models were trained on 129 channels, and tested on 32, 65, and 129-channels versions of the data using the same channel positions scheme. The baselines for comparison were zero-filling the missing channels and applying spherical spline interpolation. The performances were estimated using 5-fold cross validation. Results: For the 32-channel system version, the mean AUC values across the folds were: RBP (93.34%), spherical spline interpolation (93.36%), and zero-filling (76.82%). Similarly, on the 65-channel system version, the performances were: RBP (93.66%), spherical spline interpolation (93.50%), and zero-filling (85.58%). Finally, the 129-channel system version produced the following results: RBP (94.68%), spherical spline interpolation (93.86%), and zero-filling (91.92%). Conclusion: In conclusion, RBP obtained similar results to spherical spline interpolation, and superior results to zero-filling. We encourage further research and development of DL models in the cross-dataset setting, including the use of methods such as RBP and spherical spline interpolation to handle a varied number of EEG channels.

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

Prepubertal gonadotropin-releasing hormone analog leads to exaggerated behavioral and emotional sex differences in sheep.

In mammals, sex specialization is reflected by differences in brain anatomy and function. Measurable differences are documented in reproductive behavior, cognition, and emotion. We hypothesized that gonadotropin-releasing hormone (GnRH) plays a crucial role in controlling the extent of the brain's sex specificity and that changes in GnRH action during critical periods of brain development, such as puberty, will result in altered sex-specific behavioral and physiological patterns. We blocked puberty in half of the 48 same-sex Scottish mule Texel cross sheep twins with GnRH analog (GnRHa) goserelin acetate every 3 weeks, beginning just before puberty. To determine the effects of GnRHa treatment on sex-specific behavior and emotion regulation in different social contexts, we employed the food acquisition task (FAT) and measurement of heart rate variability (HRV). ANOVA revealed significant sex and sex×treatment interaction effects, suggesting that treated males were more likely to leave their companions to acquire food than untreated, while the opposite effect was observed in females. Concordant results were seen in HRV; treated males displayed higher HRV than untreated, while the reverse pattern was found in females, as shown by significant sex and sex×treatment interaction effects. We conclude that long-term prepubertal GnRHa treatment significantly affected sex-specific brain development, which impacted emotion and behavior regulation in sheep. These results suggest that GnRH is a modulator of cognitive function in the developing brain and that the sexes are differentially affected by GnRH modulation.

Assessing the utility of diagnostic criteria: a multisite study on gender identity disorder.

INTRODUCTION: Studies involving patients with gender identity disorder (GID) are inconsistent with regard to outcomes and often difficult to compare because of the vague descriptions of the diagnostic process. A multisite study is needed to scrutinize the utility and generality of different aspects of the diagnostic criteria for GID. AIM: To investigate the way in which the diagnosis-specific Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria for GID were used to reach a psychiatric diagnosis in four European countries: the Netherlands (Amsterdam), Norway (Oslo), Germany (Hamburg), and Belgium (Ghent). The main goal was to compare item (symptom) characteristics across countries. METHODS: The current study included all new applicants to the four GID clinics who were seen between January 2007 and March 2009, were at least 16 years of age at their first visit, and had completed the diagnostic assessment (N = 214, mean age = 32 ± 12.2 years). Mokken scale analysis, a form of Nonparametric Item Response Theory (NIRT) was performed. MAIN OUTCOME MEASURES: Operationalization and quantification of the core criteria A and B resulted in a 23-item score sheet that was filled out by the participating clinicians after they had made a diagnosis. RESULTS: We found that, when ordering the 23 items according to their means for each country separately, the rank ordering was similar among the four countries for 21 of the items. Furthermore, only one scale emerged, which combined criteria A and B when all data were analyzed together. CONCLUSIONS: Our results indicate that patients' symptoms were interpreted in a similar fashion in all four countries. However, we did not find support for the treatment of A and B as two separate criteria. We recommend the use of NIRT in future studies, especially in studies with small sample sizes and/or with data that show a poor fit to parametric IRT models.

Age of onset and sexual orientation in transsexual males and females.

INTRODUCTION: With regard to transsexual developments, onset age (OA) appears to be the starting point of different psychosexual pathways. AIM: To explore differences between transsexual adults with an early vs. late OA. METHODS: Data were collected within the European Network for the Investigation of Gender Incongruence using the Dutch Biographic Questionnaire on Transsexualism (Biografische Vragenlijst voor Transseksuelen) and a self-constructed score sheet according to the DSM-IV-TR (Diagnostic and Statistical Manual, Fourth Edition, Text Revision) criteria of Gender Identity Disorder (GID) and Gender Identity Disorder in Childhood (GIDC). One hundred seventy participants were included in the analyses. MAIN OUTCOME MEASURES: Transsexual adults who, in addition to their GID diagnosis, also fulfilled criteria A and B of GIDC ("a strong cross-gender identification,""persistent discomfort about her or his assigned sex") retrospectively were considered as having an early onset (EO). Those who fulfilled neither criteria A nor B of GIDC were considered as having a late onset (LO). Participants who only fulfilled criterion A or B of GIDC were considered a residual (RES) group. RESULTS: The majority of female to males (FtMs) appeared to have an early OA (EO = 60 [77.9%] compared to LO = 10 [13%] and to RES = 7 [9.1%]). Within male to females (MtFs), percentages of EO and LO developments were more similar (EO = 36 [38.7%], LO = 45 [48.4%], RES = 12 [12.9%]). FtMs presented to gender clinics at an earlier age than MtFs (28.04 to 36.75). The number of EO vs. LO transsexual adults differed from country to country (Belgium, Germany, the Netherlands, Norway). CONCLUSION: OA has a discriminative value for transsexual developments and it would appear that retrospective diagnosis of GIDC criteria is a valid method of assessment. Differences in OA and sex ratio exist between European countries.