Sex chromosome aneuploidy alters the relationship between neuroanatomy and cognition.

Sex chromosome aneuploidy (SCA) increases the risk for cognitive deficits, and confers changes in regional cortical thickness (CT) and surface area (SA). Neuroanatomical correlates of inter-individual variation in cognitive ability have been described in health, but are not well-characterized in SCA. Here, we modeled relationships between general cognitive ability (estimated using full-scale IQ [FSIQ] from Wechsler scales) and regional estimates of SA and CT (from structural MRI scans) in both aneuploid (28 XXX, 55 XXY, 22 XYY, 19 XXYY) and typically-developing euploid (79 XX, 85 XY) individuals. Results indicated widespread decoupling of normative anatomical-cognitive relationships in SCA: we found five regions where SCA significantly altered SA-FSIQ relationships, and five regions where SCA significantly altered CT-FSIQ relationships. The majority of areas were characterized by the presence of positive anatomy-IQ relationships in health, but no or slightly negative anatomy-IQ relationships in SCA. Disrupted anatomical-cognitive relationships generalized from the full cohort to karyotypically defined subcohorts (i.e., XX-XXX; XY-XYY; XY-XXY), demonstrating continuity across multiple supernumerary SCA conditions. As the first direct evidence of altered regional neuroanatomical-cognitive relationships in supernumerary SCA, our findings shed light on potential genetic and structural correlates of the cognitive phenotype in SCA, and may have implications for other neurogenetic disorders.