Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndrome

Laura Del Hoyo Soriano, Angela John Thurman, Danielle J Harvey, W. Ted Brown, Leonard J Abbeduto

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 In terms of longitudinal change, gains were observed in fluid and crystallized intelligence, whereas anxious and withdrawn behaviors remained stable over visits.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.

Original languageEnglish (US)
Article number22
JournalJournal of Neurodevelopmental Disorders
Volume10
Issue number1
DOIs
StatePublished - Jun 20 2018

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Fragile X Syndrome
Mothers
Intelligence
Mother-Child Relations
Chromosomes
Anxiety
Biomarkers
Psychology
X-Linked Genes
Proteins
Aptitude
Longitudinal Studies

Keywords

  • Anxiety
  • Closeness in the mother-child relationship
  • Crystallized intelligence
  • Females with FXS
  • Fluid intelligence
  • FMRP
  • Longitudinal
  • Maternal psychological distress
  • Ratio of affected to total chromosomes
  • Withdrawal

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cognitive Neuroscience

Cite this

Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndrome. / Del Hoyo Soriano, Laura; Thurman, Angela John; Harvey, Danielle J; Ted Brown, W.; Abbeduto, Leonard J.

In: Journal of Neurodevelopmental Disorders, Vol. 10, No. 1, 22, 20.06.2018.

Research output: Contribution to journalArticle

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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.",
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AU - Del Hoyo Soriano, Laura

AU - Thurman, Angela John

AU - Harvey, Danielle J

AU - Ted Brown, W.

AU - Abbeduto, Leonard J

PY - 2018/6/20

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