Triple-x research in adults

47,XXX (Triple X syndrome) is a sex chromosome aneuploidy characterized by the presence of a supernumerary X chromosome in affected females, and has been associated with a variable cognitive, behavioral, and psychiatric phenotype. Alterations in brain gray matter structure and function have been reported, but less is known about white matter (WM) organization in 47,XXX. Therefore, we conducted 7 T diffusion tensor imaging and characterized fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of 22 adult women with 47,XXX and 22 age-matched typically developing females using tract-based spatial statistics. Relationships between phenotypic traits and WM organization characteristics in 47,XXX were also investigated. Adults with 47,XXX showed lower axial diffusivity in the body of the corpus callosum and the right superior longitudinal fasciculus. WM organization variability was not associated with IQ and social cognition and social functioning deficits in 47,XXX. Our findings indicate an effect of a supernumerary X chromosome in adult women on axonal integrity of the body of the corpus callosum and the right superior longitudinal fasciculus. These findings provide additional insight into the role of the X chromosome on WM organization. Future research is warranted to explore the clinical significant impact of altered WM organization in 47,XXX.

47,XXX (Triple X syndrome) is a sex chromosome aneuploidy characterized by the presence of a supernumerary X chromosome in affected females and is associated with a variable cognitive, behavioral, and psychiatric phenotype. The effect of a supernumerary X chromosome in affected females on intracortical microstructure is currently unknown. Therefore, we conducted 7 Tesla structural MRI and compared T1 (ms), as a proxy for intracortical myelin (ICM), across laminae of 21 adult women with 47,XXX and 22 age-matched typically developing females using laminar analyses. Relationships between phenotypic traits and T1 values in 47,XXX were also investigated. Adults with 47,XXX showed higher bilateral T1 across supragranular laminae in the banks of the superior temporal sulcus, and in the right inferior temporal gyrus, suggesting decreases of ICM primarily within the temporal cortex in 47,XXX. Higher social functioning in 47,XXX was related to larger inferior temporal gyrus ICM content. Our findings indicate an effect of a supernumerary X chromosome in adult-aged women on ICM across supragranular laminae within the temporal cortex. These findings provide insight into the role of X chromosome dosage on ICM across laminae. Future research is warranted to further explore the functional significance of altered ICM across laminae in 47,XXX.

Background Women with Triple X syndrome (TXS) have an extra X chromosome. TXS appeared to be associated with psychiatric disorders in biased or underpowered studies. Aims This study aims to describe the prevalence of psychiatric disorders in adults with TXS in a relatively large and less biased group of participants. Method In this cross-sectional study, data were collected from 34 women with TXS (mean age = 32.9; s.d. = 13.1) and 31 controls (mean age = 34.9; s.d. = 13.7). Psychiatric disorders were assessed using the MINI International Neuropsychiatric Interview and the Adult Behaviour Checklist (ABCL). Trait and state anxiety were assessed using the State-Trait Anxiety Inventory (STAI). Results In the TXS group, MINI results showed a higher prevalence of major depressive episodes (43.3%), psychotic disorders (29.4%), and suicidality (23.5%). Only fifty per cent of the TXS group earned a normal score for the total syndrome score using the ABCL. In addition, levels of trait anxiety were higher in the TXS group. Only three women in each group received psychotropic medication. Impaired social functioning appeared to represent a major risk factor in TXS as regards psychotic, affective disorders, trait anxiety and low self-esteem. Conclusions Women with TXS are vulnerable to developing psychiatric disorders, and women with both TXS and impaired social functioning are even more vulnerable.

Background Triple X syndrome (47,XXX) is a relatively common sex chromosomal aneuploidy characterized by the presence of a supernumerary X chromosome in females and has been associated with a variable cognitive, behavioural and psychiatric phenotype. 47,XXX may serve as a suitable model for studying the effect of genetic architecture on brain morphology. Previous studies have shown alterations in brain structure in 47,XXX particularly in childhood and adolescence. In this study, we examined subcortical and cortical brain morphology in adult women with 47,XXX using ultra-high field 7T MRI. Given previous evidence of impaired social functioning and emotion recognition in adults with 47,XXX, we also investigated the relationship of these functions with brain morphology. Methods Twenty-one adult women with 47,XXX and 22 age- and sex-matched healthy controls were included. Structural T1-weighted images were acquired using a 7-Tesla magnetic resonance scanner. Measures of subcortical brain volumes, cortical surface area and thickness, and cortical folding were obtained and compared between the groups using general linear models. Additionally, we examined potential relationships between brain outcome measures and social functioning and social cognition in 47,XXX using correlation analyses. Results Adults with 47,XXX showed lower volumes of the thalamus, caudate, putamen, hippocampus, nucleus accumbens and pallidum, and larger lateral ventricle volumes. Lower surface area was found in the superior frontal gyrus and superior temporal gyrus in 47,XXX participants compared to healthy controls. Altered cortical thickness and cortical folding were not present in 47,XXX. Cortical thickness was associated with social cognition in 47,XXX. Conclusions Results suggest that a supernumerary X chromosome in females affects subcortical and lateral ventricle volumes, and cortical surface area in adulthood. 47,XXX may serve as a suitable model for studying genetic influences on structural brain morphology across developmental stages in order to understand neurobiological mechanisms underlying cognitive and behavioural impairments.

Triple X syndrome is a sex chromosomal aneuploidy characterized by the presence of a supernumerary X chromosome, resulting in a karyotype of 47,XXX in affected females. It has been associated with a variable cognitive, behavioral, and psychiatric phenotype, but little is known about its effects on brain function. We therefore conducted 7 T resting-state functional magnetic resonance imaging and compared data of 19 adult individuals with 47,XXX and 21 age-matched healthy control women using independent component analysis and dual regression. Additionally, we examined potential relationships between social cognition and social functioning scores, and IQ, and mean functional connectivity values. The 47,XXX group showed significantly increased functional connectivity of the fronto-parietal resting-state network with the right postcentral gyrus. Resting-state functional connectivity (rsFC) variability was not associated with IQ and social cognition and social functioning deficits in the participants with 47,XXX. We thus observed an effect of a supernumerary X chromosome in adult women on fronto-parietal rsFC. These findings provide additional insight into the role of the X chromosome on functional connectivity of the brain. Further research is needed to understand the clinical implications of altered rsFC in 47,XXX.

Background Triple X syndrome (TXS) is caused by aneuploidy of the X chromosome and is associated with impaired social functioning in children; however, its effect on social functioning and emotion recognition in adults is poorly understood. Aims The aim of this study was to investigate social functioning and emotion recognition in adults with TXS. Method This cross-sectional cohort study was designed to compare social functioning and emotion recognition between adults with TXS ( n = 34) and an age-matched control group ( n = 31). Social functioning was assessed with the Adult Behavior Checklist and Social Responsiveness Scale for Adults. Emotion recognition was assessed with the Emotion Recognition Task in the Cambridge Neuropsychological Test Automated Battery. Differences were analysed by Mann-Whitney U -test. Results Compared with controls, women with TXS scored higher on the Adult Behavior Checklist, including the Withdrawn scale ( P < 0.001, effect size 0.4) and Thought Problems scale ( P < 0.001, effect size 0.4); and higher on the Social Responsiveness Scale for Adults, indicating impaired social functioning ( P < 0.001, effect size 0.5). In addition, women with TXS performed worse on the Emotion Recognition Task, particularly with respect to recognising sadness ( P < 0.005, effect size 0.4), fear ( P < 0.01, effect size 0.4) and disgust ( P < 0.02, effect size 0.3). Conclusions Our findings indicate that adults with TXS have a higher prevalence of impaired social functioning and emotion recognition. These results highlight the relevance of sex chromosome aneuploidy as a potential model for studying disorders characterised by social impairments such as autism spectrum disorder, particularly among women.

‘Wat voegt klinisch-genetische diagnostiek toe aan de (psychologische) behandeling van de patiënt?’ Die vraag willen we in dit hoofdstuk proberen te beantwoorden door te illustreren dat klinisch-genetische diagnostiek client-centered benaderd kan worden: om het welzijn van de cliënt te bevorderen.

Background: Triple X syndrome (47,XXX or trisomy X) is a relatively frequent cytogenetic condition with a large variety of physical and behavioural phenotypes.

Method: Two adult patients with a triple X karyotype are described.

Results: Their karyotype was unknown until some years ago. What these patients have in common is that they were diagnosed with a broader autism phenotype, they were sexually abused, they suffer from psychotic illness and they show challenging behaviour, suicidality and a decline in occupational capacity.

Discussion: These gene–environment interactions are discussed. Gene–environment interactions may explain the variety of behavioural and psychiatric phenotypes in triple X syndrome. Ongoing atypical development in adults is hypothesized.

Conclusions: Gene–environment interactions and ongoing atypical development in adults should be taken into account in research concerning the psychiatric phenotype of developmental disorders, especially those involving triple X syndrome.

The developmental and clinical aspects in the literature on triple X syndrome are reviewed. Prenatal diagnosis depends on karyotyping. The incidence is 1 of 1000 females. At birth, 47,XXX girls have a lower mean birth weight and a smaller head circumference. Triple X diagnosis was not suspected at birth. The maternal age seems to be increased. Toddlers with triple X syndrome show delayed language development. The youngest girls show accelerated growth until puberty. EEG abnormalities seem to be rather common. Many girls show motor-coordination problems and auditory-processing disorders are not rare. Scoliosis is probably more common in adolescent cases. The IQ levels are 20 points below that of controls, and verbal IQ is lowest. The girls struggle with low self-esteem and they need psychological, behavioural and educational support. They perform best in stable families. After leaving school they seem to feel better. In adults, premature ovarian failure seems to be more prevalent than in controls. MRIs of the brain seem to show decreased brain volumes. The 47,XXX women most often find jobs that reflect their performance abilities. Psychotic illness seems to be more prevalent in triple X adult women than in controls. Psychotic disorders respond well to psychotropic drugs. Triple X adults suffer more frequently from cyclothymic and labile personality traits. Research on triple X syndrome may yield more insight into brain and behaviour relations, developmental psychopathology, auditory-processing disorders, EEG disorders, personality and psychotic disorders, etc.

The phenotype of triple X syndrome comprises a variety of physical, psychiatric, and cognitive features. Recent evidence suggests that patients are prone to severe language impairments. However, it remains unclear whether verbal impairments are pervasive at all levels of language, or whether one domain is relatively more spared than others. Here we document the language profile of one patient with triple X, using standardized language tests and reports. Results concur in showing that impairments are noticeable both in expressive and receptive language skills, and in vocabulary as well as in structural components of language. Although receptive ability in some tests appears relatively spared, even here A’s performance is clearly below average. This single case study further underscores that language and communication at all levels can be severely compromised in patients with triple X. Practitioners should be aware of the limited language abilities that possibly exist in patients with triple X.