Effect of sex chromosome number variation on attention-deficit/hyperactivity disorder symptoms, executive function, and processing speed

Dev Med Child Neurol. 2022 Mar;64(3):331-339. doi: 10.1111/dmcn.15020. Epub 2021 Aug 24.

Abstract

Aim: To study sex differences in attention-deficit/hyperactivity disorder (ADHD) symptoms, we explored whether X chromosome absence or excess is independently associated with deficits in attention and hyperactivity, executive function, and processing speed.

Method: We assessed 116 children (ages 3y 10mo-11y 11mo, mean 8y 5mo, SD 1y 11mo) with a variable number of sex chromosomes: 36 females with Turner syndrome (45, X0), 20 males with Klinefelter syndrome (47, XXY), 37 typically developing females (XX), and 23 typically developing males (XY).

Results: X chromosome absence was associated with increased attention problems, hyperactivity, and deficits in inhibitory control, compared with female children with XX (all p<0.003). Conversely, X chromosome excess was associated with weakness in working memory (p=0.018) and approached significance for attention problems (p=0.071) but not with hyperactivity, or weakness in inhibitory control relative to male children with XY. Using non-parametric effect size to quantify the clinical effect revealed that X chromosome absence affected attention, hyperactivity, executive function, and processing speed (all r>0.4), while X excess affected in-laboratory as well as parent-reported working memory (all r>0.4).

Interpretation: Our observations provide compelling evidence that the absence or excess of an X chromosome distinctly affects cognition and behaviors associated with ADHD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Child
  • Child, Preschool
  • Chromosomes, Human, X / genetics*
  • Executive Function / physiology*
  • Female
  • Humans
  • Inhibition, Psychological*
  • Klinefelter Syndrome / genetics
  • Klinefelter Syndrome / physiopathology
  • Male
  • Memory, Short-Term / physiology*
  • Psychomotor Performance / physiology*
  • Sex Characteristics*
  • Turner Syndrome / genetics
  • Turner Syndrome / physiopathology