ADHD and ASD symptoms in young males with fragile X syndrome: associations with early trajectories of inhibitory control

ABSTRACT

Inhibitory control (IC), the ability to suppress inappropriate responses, emerges late in the first year of life and improves across typical development, concurrent with brain maturation. The development of IC is critical to various social-emotional and behavioral functions, with IC difficulties being linked to numerous neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Fragile X syndrome (FXS) is a single-gene disorder characterized by IC difficulties, and elevated rates of ADHD and ASD, making it a useful model for understanding the early development and consequences of IC. In this longitudinal study, we characterized IC trajectories across multiple time points between 16 and 71 months of age in young males with FXS (n = 79) relative to neurotypical (NT) controls (n=49). To explore the association between behavioral outcomes and IC, we identified a subsample of 50 children with longitudinal IC data and an outcome assessment for ADHD and ASD symptoms at age 5 (FXS: n = 26, NT: n = 24). Results indicated that, compared to their NT peers, young males with FXS exhibit differences in IC as early as 24 months, with group differences increasing through age 5. Additionally, we determined that lower IC levels at 24 months were associated with later ADHD symptoms and a decreasing slope in IC over time was associated with later ASD symptoms in male children with FXS. These findings help refine early developmental phenotypes of FXS and highlight IC as a potential target for early detection and intervention of ASD and ADHD symptoms in male children with FXS.

KEYWORDS:

• Inhibitory control
• Fragile X syndrome
• attention-deficit/hyperactivity disorder
• autism spectrum disorder
• developmental trajectories

Acknowledgments

The authors would like to thank the families who participated in this research.

Disclosure statement

The authors report no biomedical financial interests or potential conflicts of interest.

Additional information

Funding

This work was supported by the National Institute of Child Health and Human Development [1K99HD105980-01]; National Institute of General Medical Sciences [T32-GM081740]; National Institute of Mental Health [R01HD003110,R01MH107573]; Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIGMS or NIH. The funders had no role in the study design, data analysis, data interpretation, or writing of this article.