Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndrome
Abstract Background Fragile X syndrome (FXS) is caused by a mutation in the FMR1 gene on the X chromosome, leading to decreased levels of FMR1 protein (FMRP), which causes the array of neuropsychological impairments that define FXS. Because FXS is an X-linked condition, fewer females display FXS and...
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doaj-4e80aa411fb946d9a2af917011986a9a2020-11-25T02:34:01ZengBMCJournal of Neurodevelopmental Disorders1866-19471866-19552018-06-0110111110.1186/s11689-018-9240-2Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndromeLaura del Hoyo Soriano0Angela John Thurman1Danielle Jenine Harvey2W. Ted Brown3Leonard Abbeduto4MIND Institute, University of California DavisMIND Institute, University of California DavisDivision of Biostatistics, Department of Public Health Sciences, University of CaliforniaNY Institute for Basic Research on Developmental DisabilitiesMIND Institute, University of California DavisAbstract Background Fragile X syndrome (FXS) is caused by a mutation in the FMR1 gene on the X chromosome, leading to decreased levels of FMR1 protein (FMRP), which causes the array of neuropsychological impairments that define FXS. Because FXS is an X-linked condition, fewer females display FXS and females with FXS are more mildly affected than males, on average. However, there is a considerable variability in terms of severity of affectedness among females with FXS. The current study was designed to investigate potential genetic (FMRP level and ratio of affected to total chromosomes) and environmental factors (maternal psychological distress and closeness in the mother–child relationship) influencing the cognitive (fluid and crystallized intelligence) and behavioral (anxiety and withdrawal) phenotype of females with FXS. Methods We conducted a prospective 3-year longitudinal study of 16 females with FXS (with up to four assessments, each separated by a year) using an accelerated longitudinal design so that we had coverage of the age range of 10–15 years at study start and 13–18 at study end. We focused on both the level of functioning related to chronological age expectations (standard scores) and absolute change in skill (raw scores) over the 3-year period. Results At a cross-sectional level, fluid intelligence and crystallized intelligence were both predicted by a closer mother–child relationship and lower maternal psychological distress. However, only fluid intelligence was predicted by a lower ratio of affected to total chromosomes. Anxiety and withdrawal were predicted by a higher ratio of affected to total chromosomes. Withdrawal was also predicted by lower closeness in the mother–child relationship and higher maternal distress. In terms of longitudinal change, gains were observed in fluid and crystallized intelligence, whereas anxious and withdrawn behaviors remained stable over visits. Gains in fluid intelligence were solely predicted by FXS biomarkers (higher FMRP level and lower ratio of affected to total chromosomes), while gains in crystallized intelligence were not predicted by any of the biological and environmental variables. Conclusions Our results show that FXS biomarkers and maternal variables contribute differentially to the cognitive and behavioral features of the adolescent female with FXS. These findings can help in the design of treatment studies aimed at enhancing cognitive and behavioral abilities in the FXS population.http://link.springer.com/article/10.1186/s11689-018-9240-2Females with FXSRatio of affected to total chromosomesFMRPMaternal psychological distressCloseness in the mother–child relationshipFluid intelligence |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laura del Hoyo Soriano Angela John Thurman Danielle Jenine Harvey W. Ted Brown Leonard Abbeduto |
spellingShingle |
Laura del Hoyo Soriano Angela John Thurman Danielle Jenine Harvey W. Ted Brown Leonard Abbeduto Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndrome Journal of Neurodevelopmental Disorders Females with FXS Ratio of affected to total chromosomes FMRP Maternal psychological distress Closeness in the mother–child relationship Fluid intelligence |
author_facet |
Laura del Hoyo Soriano Angela John Thurman Danielle Jenine Harvey W. Ted Brown Leonard Abbeduto |
author_sort |
Laura del Hoyo Soriano |
title |
Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndrome |
title_short |
Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndrome |
title_full |
Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndrome |
title_fullStr |
Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndrome |
title_full_unstemmed |
Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndrome |
title_sort |
genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile x syndrome |
publisher |
BMC |
series |
Journal of Neurodevelopmental Disorders |
issn |
1866-1947 1866-1955 |
publishDate |
2018-06-01 |
description |
Abstract Background Fragile X syndrome (FXS) is caused by a mutation in the FMR1 gene on the X chromosome, leading to decreased levels of FMR1 protein (FMRP), which causes the array of neuropsychological impairments that define FXS. Because FXS is an X-linked condition, fewer females display FXS and females with FXS are more mildly affected than males, on average. However, there is a considerable variability in terms of severity of affectedness among females with FXS. The current study was designed to investigate potential genetic (FMRP level and ratio of affected to total chromosomes) and environmental factors (maternal psychological distress and closeness in the mother–child relationship) influencing the cognitive (fluid and crystallized intelligence) and behavioral (anxiety and withdrawal) phenotype of females with FXS. Methods We conducted a prospective 3-year longitudinal study of 16 females with FXS (with up to four assessments, each separated by a year) using an accelerated longitudinal design so that we had coverage of the age range of 10–15 years at study start and 13–18 at study end. We focused on both the level of functioning related to chronological age expectations (standard scores) and absolute change in skill (raw scores) over the 3-year period. Results At a cross-sectional level, fluid intelligence and crystallized intelligence were both predicted by a closer mother–child relationship and lower maternal psychological distress. However, only fluid intelligence was predicted by a lower ratio of affected to total chromosomes. Anxiety and withdrawal were predicted by a higher ratio of affected to total chromosomes. Withdrawal was also predicted by lower closeness in the mother–child relationship and higher maternal distress. In terms of longitudinal change, gains were observed in fluid and crystallized intelligence, whereas anxious and withdrawn behaviors remained stable over visits. Gains in fluid intelligence were solely predicted by FXS biomarkers (higher FMRP level and lower ratio of affected to total chromosomes), while gains in crystallized intelligence were not predicted by any of the biological and environmental variables. Conclusions Our results show that FXS biomarkers and maternal variables contribute differentially to the cognitive and behavioral features of the adolescent female with FXS. These findings can help in the design of treatment studies aimed at enhancing cognitive and behavioral abilities in the FXS population. |
topic |
Females with FXS Ratio of affected to total chromosomes FMRP Maternal psychological distress Closeness in the mother–child relationship Fluid intelligence |
url |
http://link.springer.com/article/10.1186/s11689-018-9240-2 |
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