Dataset Information

Adaptive, behavioral, and cognitive outcomes in individuals with fragile X syndrome with varying autism severity.

ABSTRACT: This study aimed to determine the association between severity of autism spectrum disorder (ASD) and cognitive, behavioral, and molecular measures in individuals with fragile X syndrome (FXS). Study inclusion criteria included individuals with FXS and (1) age 6-40 years, (2) full-scale IQ < 84, and (3) language ≥3-word phrases. ASD symptom severity was determined by Autism Diagnostic Observation Schedule-2 (ADOS-2). Other measures identified non-verbal IQ, adaptive skills, and aberrant behaviors. Molecular measures included blood FMR1 and CYFIP1 mRNA levels, FMRP and MMP9 levels. Analysis of variance (ANOVA) and Spearman's correlations were used to compare ASD severity groups. Data from 54 individuals was included with no/mild (N = 7), moderate (N = 18), and severe (N = 29) ASD. Individuals with high ASD severity had lower adaptive behavior scores (47.48 ± 17.49) than the no/mild group (69.00 ± 20.45, p = 0.0366); they also had more challenging behaviors, lethargy, and stereotypic behaviors. CYFIP1 mRNA expression levels positively correlated with the ADOS-2 comparison score(r² = 0.33, p = 0.0349), with no significant correlations with other molecular markers. In conclusion, autism symptom severity is associated with more adverse cognitive and adaptive skills and specific behaviors in FXS, whereas CYFIP1 mRNA expression levels may be a potential biomarker for severity of ASD in FXS.

SUBMITTER: Aishworiya R

PROVIDER: S-EPMC10868665 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Adaptive, behavioral, and cognitive outcomes in individuals with fragile X syndrome with varying autism severity.

Aishworiya Ramkumar R Tak Ye Eun YE Ponzini Matthew Dominic MD Biag Hazel Maridith Barlahan HMB Salcedo-Arellano Maria Jimena MJ Kim Kyoungmi K Tassone Flora F Schneider Andrea A Thurman Angela John AJ Abbeduto Leonard L Hessl David D Randol Jamie Leah JL Bolduc Francois V FV Lippe Sarah S Hagerman Paul P Hagerman Randi R

International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 20230919 8

This study aimed to determine the association between severity of autism spectrum disorder (ASD) and cognitive, behavioral, and molecular measures in individuals with fragile X syndrome (FXS). Study inclusion criteria included individuals with FXS and (1) age 6-40 years, (2) full-scale IQ < 84, and (3) language ≥3-word phrases. ASD symptom severity was determined by Autism Diagnostic Observation Schedule-2 (ADOS-2). Other measures identified non-verbal IQ, adaptive skills, and aberrant behaviors ...[more]

PMID: 37724826

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Project description:Approximately one-fourth of autism spectrum disorder (ASD) cases are associated with a disruptive genetic variant. Many of these ASD genotypes have been described previously, and are characterized by unique constellations of medical, psychiatric, developmental, and behavioral features. Development of precision medicine care for affected individuals has been challenging due to the phenotypic heterogeneity that exists even within each genetic subtype. In the present study, we identify developmental milestones that predict cognitive and adaptive outcomes for five of the most common ASD genotypes. Sixty-five youth with a known pathogenic variant involving ADNP, CHD8, DYRK1A, GRIN2B, or SCN2A genes participated in cognitive and adaptive testing. Exploratory linear regressions were used to identify developmental milestones that predicted cognitive and adaptive outcomes within each gene group. We hypothesized that the earliest and most predictive milestones would vary across gene groups, but would be consistent across outcomes within each genetic subtype. Within the ADNP group, age of walking predicted cognitive outcomes, while age of first words predicted adaptive behaviors. Age of phrases predicted adaptive functioning in the CHD8 group, but cognitive outcomes were not clearly associated with early developmental milestones. Verbal milestones were the strongest predictors of cognitive and adaptive outcomes for individuals with mutations to DYRK1A, GRIN2B, or SCN2A. These trends inform decisions about treatment planning and long-term expectations for affected individuals, and they add to the growing body of research linking molecular genetic function to brain development and phenotypic outcomes. LAY SUMMARY: Researchers have found many genetic causes of autism including mutations to ADNP, CHD8, DYRK1A, GRIN2B, and SCN2A genes. We found that each genetic cause had different early developmental milestones that explained the overall functioning of the children when they were older. Depending on the genetic cause, the age that a child first starts walking and/or talking may help to better understand and support a child's development who has a mutation to one of the above genes. Autism Res 2020, 13: 1659-1669. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

Project description:Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the abnormal expansion of CGG repeats in the fragile X mental retardation 1 (FMR1) gene. Many FXS patients experience sleep disruptions, and we sought to explore these symptoms along with the possible benefits of a scheduled feeding intervention using the Fmr1 knockout (KO) mouse model. These mutants displayed clear evidence for sleep and circadian disturbances including delay in the onset of sleep and fragmented activity rhythms with increases in cycle-to-cycle variability. Importantly, the Fmr1 KO mice exhibited deficits in their circadian behavioral response to light with reduced masking, longer time to resetting to shifts in the Light-Dark cycle, altered synchronization to a skeleton photoperiod and lower magnitude light-induced phase shifts of activity rhythms. Investigation of the retinal input to the surprachiasmatic nucleus (SCN) with the neurotracer cholera toxin (β subunit) and quantification of the light-evoked cFos expression in the SCN revealed an abnormal retinal innervation of the SCN in the Fmr1 KO, providing a possible mechanistic explanation for the observed behavioral deficits. Interestingly, disruptions in social and repetitive behaviors correlated with sleep duration and fragmentation. Understanding the nature of the deficits, we decided to apply a scheduled feeding regimen (6-hr/18-hr feed/fast cycle) as a circadian-based strategy to boast circadian rhythms independently of light. This intervention significantly improved the activity rhythms and sleep in the mutants. Strikingly, the scheduled feeding ameliorated social interactions and reduced repetitive behaviors as well as the levels of Interferon-gamma and Interleukin-12 in the Fmr1 KO mutants, suggesting that timed eating may be an effective way to lessen inflammation. Collectively, this work adds support to efforts to develop circadian based interventions to help with symptoms of neurodevelopmental disorders.

Dataset Information

Adaptive, behavioral, and cognitive outcomes in individuals with fragile X syndrome with varying autism severity.

Publications

Adaptive, behavioral, and cognitive outcomes in individuals with fragile X syndrome with varying autism severity.

Similar Datasets

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