Resting-state functional connectivity in adults with 47,XXX: a 7 Tesla MRI study.

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.

Altered subcortical and cortical brain morphology in adult women with 47,XXX: a 7-Tesla magnetic resonance imaging study.

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.