UC Davis

Fragile X syndrome (FXS) and Down syndrome (DS) are genetic syndromes associated with intellectual disability and other cognitive, behavioral, and emotional impairments, which have extensive impacts on daily life. These syndromes, particularly FXS, are increasingly being targeted in clinical trials, yet much is still unknown about the cognitive strengths and weaknesses of each phenotype. Executive function challenges are common in FXS and DS, though findings are mixed regarding specific aspects of executive function, and measures and control groups vary widely. The aim of better characterizing executive function trajectories in these groups can inform research on cognitive phenotypes of these syndromes as well as potential targets in treatment trials. The present studies evaluated inhibitory control, an executive function component reflecting the ability to override prepotent responses, in individuals ages 6 to 25 with FXS, DS, or intellectual disability of other or unknown cause (OID) as a comparison group. Latent difference score modeling was used to measure inhibitory control at baseline and after two years to characterize developmental growth of inhibitory control in the FXS and DS phenotypes.Heart rate variability (HRV) is an index of the functioning of the autonomic nervous system and is thought to reflect self-regulatory behavior governed by the prefrontal cortex. Research in FXS and DS has shown unique HRV activity in these groups compared to typical developing individuals, though findings are mixed. Here we evaluated baseline HRV in FXS, DS, and OID to characterize their parasympathetic activity and potential group differences. We also evaluated whether initial HRV predicted concurrent inhibitory control or developmental growth of inhibitory control. Results showed some group differences on inhibitory control, with findings varying based on score type. Generally, DS had poorer inhibitory control than the OID and FXS groups, which did not differ significantly from each other. HRV results showed significantly worse parasympathetic control in FXS than DS and in OID than DS. Regarding longitudinal results, utilizing a total prorated score, all groups displayed significant growth in inhibitory control over two years around age 10. Importantly, in DS, significant two-year growth of inhibitory control continued to be detected in early adulthood. Impact of initial HRV on inhibitory control growth also varied by group; in OID, initial HRV was positively associated with inhibitory control change. In FXS and DS, there was an unexpected negative effect of baseline HRV on inhibitory control change. Challenges with Flanker scoring metrics and may have obscured some results, and future research is needed to replicate these findings. Overall, the present studies provide meaningful insight into developmental patterns of inhibitory control development in individuals with FXS and DS. The potential for HRV to serve as an index of executive function remains unclear in these groups. Differing HRV and inhibitory control patterns between groups suggest that further research is warranted.