Developmental trajectories and correlates of sensory processing in young boys with fragile X syndrome.

Division of Occupational Science, Department of Allied Health Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Physical & Occupational Therapy in Pediatrics (Impact Factor: 1.42). 02/2008; 28(1):79-98. DOI: 10.1300/J006v28n01_06
Source: PubMed

ABSTRACT No longitudinal study on sensory processing in children with fragile X syndrome (FXS) exists. This study examined developmental trajectories and correlates of sensory processing from infancy through preschool years in 13 boys with FXS.
Participants were assessed using observational and parent-report measures 2-6 times between 9 and 54 months of age.
Over time, an increasing proportion of boys displayed sensory processing that differed significantly from test norms. Observational measures were more sensitive than parent-reports early in infancy. Age and developmental quotient significantly predicted levels of hyporesponsiveness; there was a trend for hyperresponsiveness to increase with age. Baseline physiological and biological measures were not predictive.
Sensory processing problems are observable early and grow increasingly problematic from infancy through the preschool ages. Early identification and intervention may attenuate long-term difficulties for children with FXS.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fragile X syndrome is a developmental disorder that affects sensory systems. A null mutation of the Fragile X Mental Retardation protein 1 (Fmr1) gene in mice has varied effects on developmental plasticity in different sensory systems, including normal barrel cortical plasticity, altered ocular dominance plasticity and grossly impaired auditory frequency map plasticity. The mutation also has different effects on long-term synaptic plasticity in somatosensory and visual cortical neurons, providing insights on how it may differentially affect the sensory systems. Here we present evidence that long-term potentiation (LTP) is impaired in the developing auditory cortex of the Fmr1 knockout (KO) mice. This impairment of synaptic plasticity is consistent with impaired frequency map plasticity in the Fmr1 KO mouse. Together, these results suggest a potential role of LTP in sensory map plasticity during early sensory development.
    PLoS ONE 08/2014; 9(8):e104691. DOI:10.1371/journal.pone.0104691 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cognitive deficits in fragile X syndrome (FXS) are attributed to molecular abnormalities of the brain's vast and heterogeneous synapse populations. Unfortunately, the density of synapses coupled with their molecular heterogeneity presents formidable challenges in understanding the specific contribution of synapse changes in FXS. We demonstrate powerful new methods for the large-scale molecular analysis of individual synapses that allow quantification of numerous specific changes in synapse populations present in the cortex of a mouse model of FXS. Analysis of nearly a million individual synapses reveals distinct, quantitative changes in synaptic proteins distributed across over 6,000 pairwise metrics. Some, but not all, of these synaptic alterations are reversed by treatment with the candidate therapeutic fenobam, an mGluR5 antagonist. These patterns of widespread, but diverse synaptic protein changes in response to global perturbation suggest that FXS and its treatment must be understood as a networked system at the synapse level. Copyright © 2014 Elsevier Inc. All rights reserved.
    Neuron 12/2014; 84(6):1273-86. DOI:10.1016/j.neuron.2014.11.016 · 15.98 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite the significance of efforts to understand the biological basis of autism, progress in this area has been hindered, in part, by the considerable heterogeneity in the disorder. Fragile X syndrome (FXS), a monogenic condition associated with high risk for autism, may pave the way for the dissection of biological heterogeneity within idiopathic autism. This article adopts a cross-syndrome biomarker approach to evaluate potentially overlapping profiles of cardiac arousal dysregulation (and broader autonomic dysfunction) in autism and FXS. Approaches such as this, aimed at delineating shared mechanisms across genetic syndromes, hold great potential for improving diagnostic precision, promoting earlier identification, and uncovering key systems that can be targeted in pharmaceutical/behavioral interventions. Biomarker approaches may be vital to deconstructing complex psychiatric disorders and are currently promoted as such by major research initiatives such as the NIMH Research Domain Criteria (RDoC). Evidence reviewed here supports physiological dysregulation in a subset of individuals with autism, as evidenced by patterns of hyperarousal and dampened parasympathetic vagal tone that overlap with the well-documented physiological profile of FXS. Moreover, there is growing support for a link between aberrant cardiac activity and core deficits associated with autism, such as communication and social impairment. The delineation of physiological mechanisms common to autism and FXS could lend insight into relationships between genetic etiology and behavioral endstates, highlighting FMR1 as a potential candidate gene. Research gaps and potential pitfalls are discussed to inform timely, well-controlled biomarker research that will ultimately promote better diagnosis and treatment of autism and associated conditions. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Psychological Bulletin 11/2014; 141(1). DOI:10.1037/a0038237 · 14.39 Impact Factor