Patterns of psychopathology and cognition in sex chromosome aneuploidy

Abstract

Background Sex chromosome aneuploidies (SCAs) are a collectively common family of genetic disorders that increase the risk for neuropsychiatric and cognitive impairment. Beyond being important medical disorders in their own right, SCAs also offer a unique naturally occurring model for studying X- and Y-chromosome influences on the human brain. However, it remains unclear if (i) different SCAs are associated with different profiles of psychopathology and (ii) the notable interindividual variation in psychopathology is related to co-occurring variation in cognitive ability. Methods We examined scores for 11 dimensions of psychopathology [Child/Adult Behavior Checklist (CBCL)] and general cognitive ability [full-scale IQ (FSIQ) from Wechsler tests] in 110 youth with varying SCAs (XXY = 41, XYY = 22, XXX = 27, XXYY = 20) and 131 typically developing controls (XX = 59, XY = 72). Results All SCAs were associated with elevated CBCL scores across several dimensions of psychopathology (two-sample t tests comparing the euploidic and aneuploidic groups [all |T| > 9, and p < 0.001]). Social and attentional functioning were particularly sensitive to the carriage of a supernumerary Y-chromosome. In particular, the XYY group evidenced significantly more social problems than both extra-X groups (Cohen’s d effect size > 0.5, Bonferroni corrected p < .05). There was marked variability in CBCL scores within each SCA group, which generally correlated negatively with IQ, but most strongly so for social and attentional difficulties (standardized β, − 0.3). These correlations showed subtle differences as a function of the SCA group and CBCL scale. Conclusions There is domain-specific variation in psychopathology across SCA groups and domain-specific correlation between psychopathology and IQ within SCAs. These findings (i) help to tailor clinical assessment of this common and impactful family of genetic disorders and (ii) suggest that dosage abnormalities of X- and Y-linked genes impart somewhat distinct profiles of neuropsychiatric risk.

Influences of sex chromosome aneuploidy on height, weight, and body mass index in human childhood and adolescence

“…| INTRODUCTIONSex chromosome aneuploidies (SCAs) are a set of neurogenetic conditions defined by carriage of a sex chromosome dosage other than the typical XX or XY complements. These conditions are collectively common (affecting $1:400 newborns[Nielsen & Wohlert, 1991]) and can impact multiple body systems(Gravholt et al, 2017;Hong & Reiss, 2014;Rau et al, 2021;Skuse et al, 2018;Zitzmann et al, 2021). Many SCAs are associated with changes in diverse aspects of biological structure and function like metabolism, endocrine function, cardiac function, and brain anatomy(Chen et al, 2013;Salzano et al, 2016;Tartaglia et al, 2020;Warling et al, 2020).…”