Sex-sensitive cognitive performance in untreated patients with early onset gender identity disorder

BACKGROUND: We explored whether the cognitive performance of gender identity disorder patients (GID) was comparable to that of their biological sex or skewed towards that of their gender identity. METHOD: We tested four potentially sex-sensitive cognitive factors (rotation, visualization, perception, and verbalization) as well as two neutral factors (logic and arithmetic) in GID patients from Norway (GID-N, n = 33) or the USA (GID-US, n = 19) and in a control group (C, n = 29). The testing was undertaken prior to cross sex hormone treatment. Four-way ANOVA was applied in the final analysis of the cognitive performance and its dependency on different predictors (age, biological sex, education, group). RESULTS: In both GID groups as well as in the control group (C) males excelled in visualization and rotation, also when controlling for potential confounders (biological sex, group, age and education). No female advantage was detected. Furthermore, no interaction between biological sex and group assignment was revealed in the samples. CONCLUSION: In this study the cognitive pattern of GID patients is consistent with that of their biological sex and not that of their gender identity.     

Activating effects of cross-sex hormones on cognitive functioning: a study of short-term and long-term hormone effects in transsexuals.

In an earlier study we demonstrated that 3 months of cross-sex hormone treatment clearly influenced cognitive functioning in transsexuals. The aims of the present study were to examine: (a) whether we could replicate these findings in a new group of transsexuals; (b) whether a similar pattern of change could be found for novel tasks, i.e. tasks, not used in the previous study, that measured closely related cognitive abilities; (c) whether the cognitive changes following cross-sex hormone treatment had stabilized after 3 months or continued to develop over a period of 1 year; and finally, (d) whether the effects were quickly reversible when the hormone treatment was temporarily stopped. Again a pronounced effect of androgen treatment was found on spatial ability in female-to-male transsexuals (FMs) over a period of one and a half years. As expected, untreated male-to-female transsexuals (MFs) had higher scores on visuo-spatial tasks than untreated FMs; after 3 months of cross-sex hormone treatment, the group difference had disappeared, while after about 10 months of hormone treatment, the sex difference was reversed. These effects did not disappear after termination of cross-sex hormone therapy for a period of 5 weeks, but continued to change slightly in the same direction. Earlier findings of an opposite effect of cross-sex hormones on verbal fluency (i.e. MFs improved and FMs deteriorated after 3 months of cross-sex hormone treatment) were not replicated in this study, nor did we find an hormonal influence on other cognitive functions. This study shows that testosterone had an enhancing, and not quickly reversible effect, on spatial ability performance, but no deteriorating effect on verbal fluency in adult women (FMs). In contrast, anti-androgen treatment in combination with estrogen therapy had no declining effect on spatial ability, nor an enhancing effect on verbal fluency in adult men (MFs).     

Adolescents with gender identity disorder: reconsideration of the age limits for endocrine treatment and surgery

The third versions of the guideline for treatment of people with gender identity disorder (GID) of the Japanese Society of Psychiatry and Neurology does not include puberty-delaying hormone therapy. It is recommended that feminizing/masculinizing hormone therapy and genital surgery should not be carried out until 18 year old and 20 year old, respectively. On the other hand, the sixth (2001) and the seventh (2011) versions of the standards of care for the health of transsexual, transgender, and gender nonconforming people of World Professional Association for Transgender Health (WPATH) recommend that transsexual adolescents (Tanner stage 2, [mainly 12-13 years of age]) are treated by the endocrinologists to suppress puberty with gonadotropin-releasing hormone (GnRH) agonists until age 16 years old, after which cross-sex hormones may be given. A questionnairing on 181 people with GID diagnosed in the Okayama University Hospital (Japan) showed that female to male (FTM) transsexuals hoped to begin masculinizing hormone therapy at age of 15.6 +/- 4.0 (mean +/- S.D.) whereas male to female (MTF) transsexuals hoped to begin feminizing hormone therapy as early as age 12.5 +/- 4.0, before presenting secondary sex characters. After confirmation of strong and persistent cross-gender identification, adolescents with GID should be treated with cross-gender hormone or puberty-delaying hormone to prevent developing undesired sex characters. These treatments may prevent transsexual adolescents from attempting suicide, being depressive, and refusing to attend school. Subsequent early breast and genital surgery may help being employed in desired sexuality.     

Suicidal ideation among patients with gender identity disorder

In this study, we tried to clarify the prevalence of suicidal ideation and self-mutilation including suicide attempts among patients with gender identity disorder (GID) and the relationship of those behaviors to demographic characteristics. A total of 500 consecutive Japanese GID patients without any other psychiatric comorbidity were evaluated at the outpatient GID Clinic of Okayama University Hospital. The lifetime rate of suicidal ideation was 72.0% of the total sample. There were no significant differences in the prevalence of suicidal ideation among groups divided by sex, age, age at onset or education. The lifetime prevalence of self-mutilation including suicide attempts was 31.8% of the total sample. Low level of education was significantly related to self-mutilation among both male-to-female and female-to-male GID patients. Younger age at onset was a significant factor affecting self-mutilation only among MTF GID patients. A lack of strategies to cope with severe distress among persons with lower education might induce a high frequency of self-mutilation including suicidal attempt. GID patients with a low level education might be at high risk of self-mutilation and should be watched with special attention to self-mutilation.     

At issue: Sex and gender in schizophrenia

Using data collected in a study of sex differences in schizophrenia, I undertook this study to show the utility of distinguishing between sex and gender in the study of schizophrenia. Schizophrenia and schizoaffective disorder were combined to yield 213 patients (141 men, 72 women). There were 98 healthy controls (41 men, 57 women). The relative contributions of sex and gender to the prediction of age of first hospitalization and neuropsychological functioning were examined in linear regression analyses. Sex, but not gender, was a significant predictor of age at first hospitalization, even when controlling for illness severity. Among patients, sex and gender significantly contributed to the prediction of neuropsychological performance, beyond the contributions of education, age, and illness severity. Comparable results were found among healthy controls, although gender was significant only for women. For both healthy subjects and patients, more frequent endorsement of female typical social roles predicted better neuropsychological functioning. Being female also predicted higher neuropsychological scores in patients. The findings suggest that some aspects of schizophrenia study, such as the disorder's onset, may be best pursued from a more biological (sex difference) perspective, while a sociocultural (gender difference) perspective may best serve other aspects of study, such as neuropsychological functioning.     

Cognitive impairment but preservation of sexual dimorphism in cognitive abilities in chronic schizophrenia

Neurocognitive impairment in schizophrenia is well established, though sex differences on cognitive tasks have produced equivocal findings. The present study was designed to examine performance of schizophrenia patients on a sexually dimorphic cognitive battery. The cognitive battery comprising tests of spatial (mental rotation, computerized version of the Benton Judgment of Line Orientation) and verbal abilities (phonological and semantic fluency) was administered to men (n = 22) and women (n = 21) with schizophrenia and healthy controls (n = 21 men and 21 women). A series of multivariate analyses showed that the patient group performed worse than controls on all the cognitive tasks. Cognitive sexual dimorphism on all spatial tasks favoring men and verbal tasks favoring women remained. Within the patient sample, correlational data demonstrated that earlier age at onset of illness related to poorer spatial performance. It is concluded that normal sexual dimorphism is undisturbed on both spatial and verbal tasks by the schizophrenia disease process.     

Cognitive profiles and clinical factors in type III spinal muscular atrophy: a preliminary study

Cognitive abilities are often affected in progressive neurodegenerative disorders, but there is a lack of understanding about whether spinal muscular atrophy (SMA) patients experience cognitive deficits and, if so, whether they are associated with clinical factors. A sample of 22 type III SMA patients and 22 healthy controls completed a comprehensive neuropsychological battery, including tests in memory, executive function, language, visuospatial, and global cognitive functioning. Clinical severity was assessed using the Hammersmith Functional Motor Scale, the Revised Upper Limb Module and the Six Minute Walk Test. SMA patients showed poorer performance in visuospatial abilities, executive functions and language as compared to healthy controls. In the SMA sample, patients with greater motor difficulties had lower performance in attention, but higher performance in measures of language, verbal fluency, and memory. In men, but not women, cognitive test performance was associated with motor functioning. Our findings showing cognitive changes in SMA type III may reflect the presence of intrinsic brain pathology and cognitive adaptation mechanisms following physical dysfunction, which may be mediated by other factors, such as sex.     

Comorbidity of Asperger syndrome and gender identity disorder

Abstract The case of a 35-yearold biological woman with Asperger syndrome (AS) and gender identity disorder (GID) fulfilling DSM-IV criteria is reported. Against the background of recently emerging theories of cognitive male pattern underlying autism we present additional psychological assessments in order to discuss any possible interaction or discrimination between AS and GID. Whilst we explain GID as a secondary feature of AS, we examine the assumption of the necessity of treating GID in AS as a primary GID in accordance with international standards. We consider the treatment of GID as compelling, particularly because curative therapy for AS is lacking and with GID treatment in this vein, the patient gains psychosocial improvement.     

Interactive effects of sex hormones and gender stereotypes on cognitive sex differences--a psychobiosocial approach

Biological and social factors have been shown to affect cognitive sex differences. For example, several studies have found that sex hormones have activating effects on sex-sensitive tasks. On the other hand, it has been shown that gender stereotypes can influence the cognitive performance of (gender-) stereotyped individuals. However, few studies have investigated the combined effects of both factors. The present study investigated the interaction between sex hormones and gender stereotypes within a psychobiosocial approach. One hundred and fourteen participants (59 women) performed a battery of sex-sensitive cognitive tasks, including mental rotation, verbal fluency, and perceptual speed. Saliva samples were taken immediately after cognitive testing. Levels of testosterone (T) were analysed using chemiluminescence immunoassay (LIA). To activate gender stereotypes, a questionnaire was applied to the experimental group that referred to the cognitive tasks used. The control group received an identical questionnaire but with a gender-neutral content. As expected, significant sex differences favouring males and females appeared for mental rotation and verbal fluency tasks, respectively. The results revealed no sex difference in perceptual speed. The male superiority in the Revised Vandenberg and Kuse Mental Rotations Tests (MRT-3D) was mainly driven by the stereotype-active group. No significant sex difference in MRT-3D appeared in the control group. The MRT-3D was also the task in which a strong gender-stereotype favouring males was present for both males and females. Interestingly, T levels of the stereotype-activated group were 60% higher than that of male controls. The results suggest that sex hormones mediate the effects of gender stereotypes on specific cognitive abilities.     

Gender differences in cognitive function of patients with chronic schizophrenia

Schizophrenic patients have cognitive impairments, but gender differences in these cognitive deficits have had limited study. This study assessed cognitive functioning in 471 subjects including 122 male and 78 female schizophrenic patients and 141 male and 130 female healthy controls. We found that immediate memory, language, delayed memory and total RBANS scores were significantly decreased in schizophrenia compared with healthy controls for both genders. Male patients had significant lower immediate memory, delayed memory and total RBANS scores than female patients, and healthy controls showed a similar gender difference. The RBANS showed modest correlations with PANSS scores, duration of illness and antipsychotic dose (chlorpromazine equivalents). Almost all RBANS scores in the schizophrenics and healthy controls showed significant positive correlations with education. Thus, patients of both sexes with schizophrenia experienced more deteriorated performance than healthy controls on cognitive domains of immediate memory, language and delayed memory. Furthermore, male schizophrenic patients had more serious cognitive deficits than female patients in immediate and delayed memory, but not in language, visuospatial and attention indices.     

Clinical characteristics of patients with gender identity disorder at a Japanese gender identity disorder clinic

The aim of this study was to examine the clinical characteristics of patients with gender identity disorder (GID) at a GID clinic in Japan. A total of 603 consecutive patients were evaluated at the GID clinic using clinical information and results of physical and neurological examinations. Using DSM-IV criteria, 579 patients (96.0%) were diagnosed with GID. Four patients were excluded for transvestic fetishism, eight for homosexuality, five for schizophrenia, three for personality disorders, and four for other psychiatric disorders. Among the GID patients, 349 (60.3%) were the female-to-male (FTM) type, and 230 (39.7%) were the male-to-female (MTF) type. Almost all FTM-type GID patients started to feel discomfort with their sex before puberty and were sexually attracted to females. The proportion of FTM patients who had experienced marriage as a female was very low, and very few had children. Therefore, FTM-type GID patients seem to be highly homogeneous. On the other hand, various patterns of age at onset and sexual attraction existed among MTF patients. Among the MTF-type GID patients, 28.3% had married as males and 18.7% had sired children. Thus, MTF-type GID patients seem to be more heterogeneous.     

Patients with epilepsy: Cognitively compromised before the start of antiepileptic drug treatment?

Purpose:   To compare the cognitive profile of newly diagnosed untreated epilepsy patients with healthy volunteers using a comprehensive neuropsychological test battery.
Methods:   A total of 155 untreated patients with newly diagnosed epilepsy, and no known brain pathology, were assessed before the start of treatment with antiepileptic medication. Their scores across the neuropsychological measures were compared with 87 healthy volunteers from the general population equated for age and sex.
Results:   After adjusting for age, sex, and education, patients with epilepsy performed significantly worse than healthy volunteers on 6 of 14 cognitive measures, particularly in the domains of memory and psychomotor speed. Cognitive performance was not related to the number of seizures, type of epilepsy, or mood. When an impairment index was calculated, 53.5% patients had a least one abnormal score [>2 standard deviations (SD) below the control mean] on the test battery compared with 20.7% of healthy volunteers.
Discussion:   Newly diagnosed untreated patients with epilepsy are cognitively compromised before the start of antiepileptic drug medication. The domains most affected are memory and psychomotor speed. More than one-half of the patients had at least one abnormal test score across the test battery. There were no differences in epilepsy-related or mood variables between those who demonstrated dysfunction and those that did not.     

Neuropsychological profile of DYT1 dystonia.

The common belief that primary dystonia is a purely motor disorder has recently been challenged. We examined separately the cognitive profiles of symptomatic (SYM) and nonsymptomatic (N-SYM) groups of carriers of DYT1 mutation using a comprehensive neuropsychological test battery. Self-report inventories of anxiety, depression, and pain levels were also administered, as well as manual motor dexterity assessment. Each group was matched with healthy controls by age, sex, mother tongue, and education. No significant differences between the SYM group to its control group were found on cognitive tests evaluating verbal and nonverbal abstract abilities, attention, information processing speed, and spatial organization. However, the SYM group showed increased verbal memory retroactive interference. Interestingly, the patients also showed higher semantic fluency performance. No significant differences between the N-SYM group to controls were found. It was concluded that symptomatic DYT1 mutation carriers do not suffer the distinctive cognitive decline that is seen in other primary degenerative extrapyramidal disorders.     

Neuroimaging studies in people with gender incongruence

Abstract

The current review gives an overview of brain studies in transgender people. First, we describe studies into the aetiology of feelings of gender incongruence, primarily addressing the sexual differentiation hypothesis: does the brain of transgender individuals resemble that of their natal sex, or that of their experienced gender? Findings from neuroimaging studies focusing on brain structure suggest that the brain phenotypes of trans women (MtF) and trans men (FtM) differ in various ways from control men and women with feminine, masculine, demasculinized and defeminized features. The brain phenotypes of people with feelings of gender incongruence may help us to figure out whether sex differentiation of the brain is atypical in these individuals, and shed light on gender identity development. Task-related imaging studies may show whether brain activation and task performance in transgender people is sex-atypical. Second, we review studies that evaluate the effects of cross-sex hormone treatment on the brain. This type of research provides knowledge on how changes in sex hormone levels may affect brain structure and function.     

Improvement of therapeutic environment--effort to establish the medical center for GID in a general hospital

Treatment for gender identity disorder (GID) should be done in cooperation with psychologist, gynecologist, urologist, plastic surgeon and extramural scholars as a team treatment. And if possible, it should be a comprehensive treatment with supports of a social worker, a coordinator and an expert nurse. The ethical committee for individual GID patient treatment has already dissolved according to the third edition of the guideline. We call the therapeutic team Okayama University Hospital Gender Center. It treats not only GID patients, but also gender associated diseases such as disorders of sex development (DSD). Unfortunately, there are not so many institutions which meet our conditions throughout the country. In the present circumstances we can't go along with their needs. So many GID patients go abroad and have Sex reassignment surgery (SRS). To solve this problem national insurance for SRS should be approved as soon as possible and many institutes should start GID treatment.     

1-year follow-up study of cognitive function in first-episode non-affective psychosis

The longitudinal course of primary cognitive dysfunction seen in schizophrenia has yet to be fully clarified. Whereas some studies in chronic patients have revealed a progressive decline in cognitive abilities, those studies with first-episode patients have indicated that initial cognitive deficits might remain stable over time. The aim of this study was to examine the longitudinal course of cognitive functioning in patients with a first episode of schizophrenia. 112 patients with a first episode of schizophrenia-spectrum disorders and 22 healthy controls completed clinical and cognitive evaluations at baseline and again after 1 year. An extensive neuropsychological battery that comprised seven cognitive domains was used. Patients and controls improved their cognitive performance in virtually all the cognitive domains after one year. However, patients continued to show marked cognitive deficits after one year, unlike healthy volunteers. The longitudinal cognitive changes were similar in patients and controls in all domains except Verbal Memory (F = 11.67; df = 1; P = 0.001). The increase in cognitive scores found during early phases of the illness seems to be associated to practice-related changes and would not reflect a real cognitive enhancement but rather stability of deficit. Patients' deficits remained stable over time in all cognitive domains except Verbal Memory, in which less performance improvement was found. Further investigations are warranted to discern the variability in patterns of specific cognitive deficits over time.     

Meta-analysis of Cognitive Deficits in Ultra-high Risk to Psychosis and First-Episode Psychosis: Do the Cognitive Deficits Progress Over,or After,the Onset of Psychosis?

Cognitive dysfunction is a well-established feature of schizophrenia, and there is evidence suggesting that cognitive deficits are secondary to abnormal neurodevelopment leading to problems in acquiring such abilities. However, it is not clear whether there is also a decline in cognitive performance over, or after, the onset of psychosis. Our objective was to quantitatively examine the longitudinal changes in cognitive function in patients who presented with first-episode psychosis (FEP), ultra-high risk (UHR) for psychosis, and controls. Electronic databases were searched for the studies published between January 1987 and February 2013. All studies reporting longitudinal cognitive data in FEP and UHR subjects were retrieved. We conducted meta-analyses of 25 studies including 905 patients with FEP, 560 patients at UHR, and 405 healthy controls. The cognitive performances of FEP, UHR, and healthy controls all significantly improved over time. There was no publication bias, and distributions of effect sizes were very homogenous. In FEP, the degree of improvement in verbal working memory and executive functions was significantly associated with reduction in negative symptoms. There was no evidence of cognitive decline in patients with UHR and FEP. In contrast, the cognitive performances of both groups improved at follow-up. These findings suggest that cognitive deficits are already established before the prodromal phases of psychosis. These data support the neurodevelopmental model rather than neurodegenerative and related staging models of schizophrenia.Key words: schizophrenia, psychosis, cognition, neuropsychology, longitudinal     

The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study

Background

Diffusion tensor imaging (DTI) has been shown to be sensitive in detecting white matter differences between sexes. Before cross-sex hormone treatment female to male transsexuals (FtM) differ from females but not from males in several brain fibers. The purpose of this paper is to investigate whether white matter patterns in male to female (MtF) transsexuals before commencing cross-sex hormone treatment are also more similar to those of their biological sex or whether they are more similar to those of their gender identity.

Method

DTI was performed in 18 MtF transsexuals and 19 male and 19 female controls scanned with a 3 T Trio Tim Magneton. Fractional anisotropy (FA) was performed on white matter of the whole brain, which was spatially analyzed using Tract-Based Spatial Statistics.

Results

MtF transsexuals differed from both male and female controls bilaterally in the superior longitudinal fasciculus, the right anterior cingulum, the right forceps minor, and the right corticospinal tract.

Conclusions

Our results show that the white matter microstructure pattern in untreated MtF transsexuals falls halfway between the pattern of male and female controls. The nature of these differences suggests that some fasciculi do not complete the masculinization process in MtF transsexuals during brain development.     

Neuropsychological correlates of P50 sensory gating in patients with schizophrenia

Impaired inhibition of P50 cerebral evoked response is one of the best validated endophenotypes in schizophrenia. There are controversial data on the relationship between P50 evoked potential deficit and measures of cognitive function in schizophrenia. A comprehensive clinical and neurocognitive assessment plus an evaluation of P50 sensory gating was performed in 160 schizophrenia patients and 64 controls. Neurocognitive scores from each cognitive domain were converted to demographically-adjusted T-scores (age, gender, and years of education) for all study participants. The relationship between P50 and neurocognitive variables was assessed via parametric and nonparametric correlations and categorical strategies: we compared neuropsychological test scores in patients and controls in the lowest P50 quartile vs. the highest. Controls had better performance than schizophrenia patients in all cognitive domains. Schizophrenia patients had significantly higher P50 ratios than controls, and no significant correlation was found between P50 gating measures and neuropsychological test scores in schizophrenia patients or healthy controls. Moreover, no differences in neurocognitive performance were found between subjects in the lowest P50 ratio quartile vs. the highest in healthy controls or patients with schizophrenia. We concluded that there is no evidence of an association between P50 ratio and cognitive measures in schizophrenia patients, and this seems to be also the case in healthy controls.     

Disease- and treatment-related effects on the pituitary–gonadal functional axis: a study in men with epilepsy

The consideration of the patient’s gender has become an established practice in the choice of antiepileptic drugs (AEDs) for the treatment of epilepsy. This study was undertaken to confirm that temporal lobe epilepsy and the use of hepatic enzyme-inducing AEDs, have a negative effect on sex hormones in men. We calculated the testosterone (T)/luteinizing hormone (LH) ratio to reflect the effects of epilepsy or its treatment on the most important androgen and its pituitary control hormone. Of 324 men with focal epilepsy identified (untreated or on AED monotherapy), 201 were eligible for inclusion (mean age 37.5 years¸ mean duration of epilepsy 14.7 years). A total of 105 men served as healthy controls (mean age 33.9 years). Patients with temporal lobe epilepsy were more likely to show abnormal T/LH ratios than patients with extratemporal epilepsy (p < 0.01). Patients receiving AEDs with marked hepatic enzyme-inducing effects were more likely to have low T/LH ratios than patients taking nonenzyme-inducing AEDs or healthy controls (p < 0.01). Focus localization and AED choice affect male sex hormones. Findings raise some concerns about the effect of enzyme-inducing AEDs on sexual endocrine functions.