Authors: Jessica Klusek, Jinkuk Hong, Audra Sterling, Elizabeth Berry-Kravis, and Marsha Mailick
Drs. Jessica Klusek, Marsha Mailick, and colleagues investigated how a dimension of executive function, inhibition, is affected by age and FMR1 CGG repeats among mothers of children with Fragile X syndrome. Inhibition is the ability to suppress an action, such as not eating that piece of chocolate even though you really want it. Difficulties with inhibition can affect relationships and are linked to mental health problems. This study looked at relationships between inhibition, measured in two different ways, and individual factors, such as age and the FMR1 gene, among female premutation carriers.
This study included 134 premutation carriers who were mothers of children with Fragile X syndrome. Participants completed a test over the phone called the Hayling Sentence Completion Test, which directly measures verbal inhibition (i.e., how quickly and accurately a participant completes a sentence). Separately, participants answered questions about daily tasks associated with inhibition, such as waiting your turn. FMR1 CGG repeat length was also measured.
On the Hayling test, greater difficulties with inhibition were associated with older age. Additionally, individuals who had CGG repeats between 80 and 90 had greater difficulties with inhibition compared to individuals with who had 90–115 CGG repeats. On the questionnaire, participants with 90–110 CGG repeats reported the greatest difficulties with daily activities of inhibition.
Why This Matters
This study highlighted that older mothers of children with Fragile X syndrome (over 70 years) who have “mid-range” CGG repeats (~80–100) may be at increased risk for difficulties with inhibition. The mid-range has been previously associated with risks for mental health problems and FXPOI, as well as increased vulnerability to stress, suggesting important implications for these individuals’ health and well-being.
Researchers would like to better understand how age-related differences in inhibition may be associated with changes in the brain. Such information may provide insight into FXTAS and the role of the FMR1 gene in aging.
Funding: This work was supported by the National Institutes of Health under grant numbers R01HD082110, P30 HD003100-S1, U54 HD090256, R21DC017804, R03HD098291.
more research results
A Human Forebrain Organoid Model of Fragile X Syndrome Exhibits Altered Neurogenesis
While there is promise for future treatments, utilizing this iPSC brain organoid model for future treatment development could prove to be successful.
Trajectories of Change in the Behavioral and Health Phenotype of Adolescents and Adults with Fragile X Syndrome and Intellectual Disability: Longitudinal Trends Over a Decade
This study shines a light on the need for better long-term support and care planning for individuals with Fragile X syndrome.
Raising Knowledge and Awareness of Fragile X Syndrome in Serbia, Georgia, and Colombia: A Model for Other Developing Countries?
Raising knowledge and awareness of Fragile X syndrome to medical professionals leads to direct benefits for families and individuals.
Parent Clinical Trial Priorities for Fragile X Syndrome: A Best-Worst Scaling
The aim of this study was to determine parents’ main priorities for clinical trials, at a time when the clinical trial opportunities are on the rise.
AI–Assisted Phenotype Discovery of Fragile X Syndrome in a Population-Based Sample
This study is important for later-diagnosed individuals as it creates successful predictive models that can identify cases five years earlier than clinical diagnosis.
Emergence of Developmental Delay in Infants and Toddlers With an FMR1 Mutation
Data from 8 unique studies speaks to the necessity of early identification of FXS, which leads to earlier, effective medical and non-medical interventions.