4.1. Summary of Findings
Although the presence of RRBs are core to the diagnosis of ASD, they are also quite common in typically developing children and have been found in a variety of other clinical and neurodevelopmental disorders, including FXS. At the global level, individuals with FXS are known for exhibiting RRBs, with a unique RRB profile being observed across the preschool years through adolescence [2
], with developmental stability across time [30
] and age [2
]. To date, there has been little work examining the FXS RRB profile across the lifespan through adulthood, with limited information about the female RRB profile [4
]. Further, the FXS RRB profile is suggested to resemble idiopathic ASD across several sublevels of RRBs (e.g., stereotypy, sameness, and SIB); however, rates of Compulsive, Sensory-Motor, and Ritualistic behaviors may also be specific to the FXS profile [2
]. The present study aimed to build on the fields current understanding of the FXS RRB phenotypic profile up through adulthood, while teasing apart differences between males and females with FXS and expanding on the impact of a comorbid ASD diagnosis on RRB severity. This study is one of the first to provide detailed findings about differences in RRB profiles at the item and subtype level based on gender.
Overall, the present study builds on the premise that higher ratings of RRBs are associated with poorer outcomes in FXS [12
]. Specifically, lower IQ, lower adaptive behavior skills, and higher rates of problem behavior and ASD symptomology were related to higher rates of RRBs. Although age was not significantly correlated with the majority of the RBS-R subscales, severity of problems reported by caregivers suggest the FXS RRB profile differs based on age. Specifically, severity of more complex forms of RRBs (Restricted Interests, Compulsive, and Ritualistic/Sameness behaviors) appear to peak between 7 and 12 years of age before declining and becoming stable across adolescence and adulthood. Sensory-Motor behaviors appear to peak even earlier in childhood between 2 and 6 years, remain stable across age 12, and then decline and become stable across adolescence and adulthood. Similar to Oakes et al. [2
], SIBs were rated least problematic with these findings extending beyond middle childhood with the severity of SIBs remaining stable throughout the lifespan. Overall, RRB’s appear to decline across age in severity across all of the RRB subscales, which is inconsistent with previous literature suggesting stability up through adolescence [2
]. These inconsistent findings could be due to the observed peak in severity across several of the RBS-R subscales for children between 7 and 12 years of age. Otherwise, the severity of RRBs outside of 7 to 12 years of age as rated by their caregivers aligns with previous literature suggesting stability across the lifespan with the exception of Sensory Motor behaviors.
Consistent with previous literature [2
], the present study found certain sublevels of RRBs to be more problematic in FXS, building on the premise of a distinct RRB in profile. However, in contrast to Wolff et al. [3
] and Oakes et al. [2
], our findings revealed Restricted Interest behaviors to be most problematic for FXS caregivers, proceeded by Sensory-Motor and Ritualistic/Sameness behaviors; however, they did align with findings reported by Moskowitz et al. [4
]. Given a different profile emerged in the present study, this suggests age may play a factor in these profiles given our age range extended beyond adolescence. Further, the present study also found Self-injurious behaviors to be least problematic [2
]. When considering gender at the subscale level, some differences emerged as hypothesized but also some commonalities. Specifically, Restricted Interest behaviors were rated as most problematic in both males and females with FXS, with Ritualistic behaviors also being rated as third most problematic. However, males with FXS were rated as having more Sensory-Motor behaviors, whereas females with FXS were rated as having more Compulsive behaviors. Further, Sensory-Motor behaviors were the only area where both genders significantly differed in their severity ratings, suggesting males with FXS are more likely to engage in Sensory-Motor behaviors in comparison to females. Not only may there be a specific FXS RRB profile that potentially shifts with age, but there are also differences in profiles based on gender which helps lay important groundwork for targeted treatment development.
When considering the impact of ASD diagnosis on the RRB profile of FXS, the same core problems were reported in individuals with FXS and ASD (e.g., Restricted Interests, Sensory-Motor, and Ritualistic/Sameness behaviors being most problematic) as the overall sample; however, the severity of these problems almost doubles in comparison to individuals with FXS only, with significant differences emerging across all of the RBS-R subscales. These findings build on the premise that although these problems may be core to the FXS behavioral phenotype, the added diagnosis of ASD increases the risk for more problem behaviors in FXS including increased RRBs [12
]. These findings suggest the RBS-R may be a valid measure for differentiating individuals with FXS who have ASD in comparison to those without ASD based on severity of ratings.
At the item level, some common problems emerged in FXS within the Sensory-Motor, Restricted Interests, and Ritualistic/Sameness subscales. Within the entire sample, FXS caregivers rated resisting changes in activities/difficulty with transitions and hand/finger mannerisms as the most problematic followed by fascination with one subject or activity, strongly attached to one specific object, and sensory repetitive behaviors. Interestingly, difficulty with transitions were most problematic for both males and females, supporting that this is core to the FXS behavioral phenotype. As hypothesized, some differences were identified based on gender. In comparison to males with FXS, caregivers of females with FXS endorsed becoming upset if interrupted in what he/she is doing and hoarding/saving items. Aligning with the subscale finding, hand/finger mannerisms and sensory behaviors appear to be specific problems in males with FXS. Overall, significant differences at the item level were found across several of the items on the RBS-R based on gender (Table 3
), but not to the degree that was hypothesized. Females were primarily rated with less severe RRBs in comparison to males with FXS, which aligns with the fields current understanding about males with FXS being more severely impacted than females, but may not be to the same degree as other problem behaviors commonly found in FXS [6
Similar to the subscale findings based on ASD diagnosis, the top-rated problems in those with FXS and diagnosis of ASD closely aligned to those with FXS only. Within the top five items endorsed based on ASD diagnosis, differences emerged where individuals with FXS and ASD were reported to have higher ratings of being strongly attached to one specific object, whereas individuals with FXS only were reported to have higher ratings of being upset if interrupted in what he/she is doing. Not only at the subscale level may the RBS-R be able to differentiate ASD diagnosis in FXS, but also the item level. Overall, individuals with FXS and ASD were rated as significantly higher for a large portion of items on the RBS-R; however, not to the degree that was hypothesized. It appears there are specific items within the RBS-R subscales that are driving the subscale differences that were found. These findings are important for understanding the utility of the RBS-R in FXS. Specifically, the RBS-R subscales may not be best interpreted at face value in FXS given item level analyses provide more nuanced details into understanding how ASD impacts specific RRBs found in FXS.
Given the controversy of IQ possibly driving the ASD symptoms seen in FXS and other genetic syndromes at high risk for ASD [18
], the present study aimed to examine these differences further by assessing if these differences remain when controlling for IQ and age. The current study’s findings suggest that only Sensory-Motor behaviors remain as problematic in males with FXS and a diagnosis of ASD when considering IQ and age. These findings map onto those reported by Wolff et al. [3
] and suggest that high rates of Sensory-Motor problems in FXS are most likely driven by ASD itself, rather than IQ. Further, ASD is most likely driving the increased rates of Restricted Interests seen in individuals with FXS and ASD regardless of gender.