Introduction Long-term effects and side effects of cross-sex hormone treatment in transsexual persons are not well known. Aim The aim of this study is to describe the effects and side effects of cross-sex hormone therapy in both transsexual men and women. Main Outcome Measures Hormone levels were measured by immunoassays. Physical health was assessed by physical examination and questionnaires on general health and specific side effects, areal bone parameters by dual energy X-ray absorptiometry. Methods Single center cross-sectional study in 100 transsexual persons post-sex reassignment surgery and on average 10 years on cross-sex hormone therapy. Results Transsexual men did not experience important side effects such as cardiovascular events, hormone-related cancers, or osteoporosis. In contrast, a quarter of the transsexual women had osteoporosis at the lumbar spine and radius. Moreover, 6% of transsexual women experienced a thromboembolic event and another 6% experienced other cardiovascular problems after on average 11.3 hormone treatment years. None of the transsexual women experienced a hormone-related cancer during treatment. Conclusion Cross-sex hormone treatment appears to be safe in transsexual men. On the other hand, a substantial number of transsexual women suffered from osteoporosis at the lumbar spine and distal arm. Twelve percent of transsexual women experienced thromboembolic and/or other cardiovascular events during hormone treatment, possibly related to older age, estrogen treatment, and lifestyle factors. In order to decrease cardiovascular morbidity, more attention should be paid to decrease cardiovascular risk factors during hormone therapy management.

Early-life stress (ES) has been associated with diverse forms of psychopathology. Some investigators suggest that these associations reflect the effects of stress on the neural circuits that support cognitive control. However, very few prior studies have examined the associations between ES, cognitive control, and underlying neural architecture. The present study compares adolescents with a documented history of ES to typical adolescents on a cognitive control task using functional magnetic resonance imaging (fMRI). Twelve ES adolescents who were adopted because of early caregiver deprivation (9 females, age = 13 years ± 2.58) and 21 healthy control adolescents without a history of ES (10 females, age = 13 years ± 1.96) who resided with their biological parents performed the change task (Nelson et al., 2007) -a variant of the stop taskduring fMRI. Behaviourally, ES adolescents took longer to switch from a prepotent response ("go") to an alternative response ("change") than control adolescents. During correct "change" responses vs. correct "go" responses, this behavioural group difference was accompanied by higher activation in ES subjects than controls. These differences were noted in regions involved in primary sensorimotor processes (pre-and postcentral gyri), conflict monitoring (dorsal anterior cingulate gyrus), inhibitory and response control (inferior prefrontal cortex and striatum), and somatic representations (posterior insula). Furthermore, correct "change" responses vs. incorrect "change" responses recruited the inferior prefrontal cortex (BA 44/46) more strongly in ES subjects than controls. These data suggest impaired cognitive control in youth who experienced ES.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attentiondeficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1,400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive and psychosocial factors.

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Tourette's syndrome (TS) is a neurodevelopmental disorder characterized by the presence of chronic vocal and motor tics. Tics are sudden, highly stereotyped, movements that can be simple or complex in appearance. Since patients with TS have difficulties preventing unwanted movements, one might expect that their ability to voluntarily control goal-directed movements would be similarly poor. Indeed, it has been suggested that TS sufferers are impaired at inhibiting reflexively triggered movements and in rapidly selecting or switching between different motor sets. This idea is consistent with current views on the neurological basis of TS that posit a dysfunction of the neural circuits linking the frontal lobes and the striatum. These circuits are known to be involved in the voluntary control of action. By using an oculomotor switching task, we show for the first time that young people with TS exhibit paradoxically greater levels of cognitive control over their movements than their age-matched controls. This finding is consistent with an increased need to monitor and control movements and may indicate a subcortical locus for the triggering of tics. It also suggests that the constant need to suppress tics could have resulted in an enhancement of the executive processes involved in inhibitory control.

Tourette Syndrome (TS) is a developmental neurological condition that is characterised by the presence of multiple motor and one or more vocal tics. Tics are highly stereotyped repetitive behaviours that fluctuate in type, complexity and severity. TS has been linked to impaired cognitive control processes, however, a recent study (Mueller et al. in Curr Biol 16:570-573, 2006) demonstrated that young people with TS, although exhibiting chronic motor and vocal tics, nevertheless performed significantly better than a group of age-matched controls on a task that required extremely high levels of cognitive control (i.e., predictably shifting between executing pro-saccade and anti-saccade responses to a visual stimulus). As predictable task sequences allow task-related cognitive processes to commence prior to the presentation of target stimuli we examined whether the superior performance of the TS group could be replicated when task sequences were varied unpredictably. Our results confirmed that both the TS group and an age-matched control group benefited, by the same extent, when the saccade task (pro-saccade vs. anti-saccade) was pre-cued. In contrast, while the control group showed a significant decrease in performance on task switch trials relative to task repetition trials-the TS group exhibited no significant 'costs' of switching task. While task performance was modulated by response and target location shifts in the control group, these factors had less impact on the TS group's performance on task switch trials. These results confirm and extend the previous demonstration that individuals with TS exhibit paradoxically greater levels of cognitive control than healthy controls.