The neurosocial phenotype of the Triple X Syndrome

Triple X syndrome (47,XXX) occurs with a frequency of 1:800 to 1:1000 in girls, although it is possible that the syndrome is not diagnosed due to the often inconspicuous symptomatology. Although there are some anecdotal reports of abnormalities in social interaction (e.g., in the regulation of closeness and distance and the decoding of social signals), and affected individuals and their relatives report problems in everyday social life, no systematic studies regarding socio-cognitive and socio-affective characteristics are available to date. Therefore, the present study aims at the cognitive, affective and behavioral characterization of women with 47,XXX in the context of social interactions. Another goal is to explore neural structural correlates of the presumed socio-cognitive features using functional and structural MRI. In addition to morphometric investigations, the focus will also be on investigations of structural connectivity.

Duration: 01/21 - 11/23
Funding: Internal
Contact: Jobst Meyer, Marie-Anne Croyé, Gregor Domes
in collaboration with  Prof. med. Winfried Willinek (BKT)

Publication

Croyé, M.-A., Freilinger, P., Jürgenlimke, H., Domes, G., & Meyer, J. (2025). Elevated autistic traits and social anxiety, and reduced empathy in adult women with triple X syndrome. Journal of Neurodevelopmental Disorders, 17(1). https://doi.org/10.1186/s11689-025-09631-7

Domes, G., Croyé, M.-A., Freilinger, P., Bohlscheid, A., Willinek, W., & Meyer, J. (2025). Brain structure in triple x syndrome: Regional gray matter volume and cortical  thickness in adult women with 47,XXX. Journal of Neurodevelopmental Disorders, 17, 18. https://doi.org/10.1186/s11689-025-09608-6

MRI Triple X
Fig. 1 Results of voxel-based morphometry (VBM). Statistical parametric maps (SPM) are projected on coronal slices of the MNI152 template illustrating regions with reduced GM volume in women with a 47,XXX karyotype. (a) Extended clusters showing gray matter volume reduction comprising hippocampus, amygdala, putamen, insula. (b) Extended clusters in the cerebellum. Results were FWE-corrected with a voxel threshold of T > 6.14; p < .05
MRI
Fig. 3 Point-wise cortical thickness analysis showing significant clusters of altered cortical thickness in women with 47,XXX compared to controls. Blue clusters indicate increased vs. red areas indicate reduced cortical thickness in 47,XXX. Results are presented uncorrected at p < .05 for illustrative purpose