Developmental trajectories of executive functions in young males with fragile X syndrome.

BACKGROUND: Executive functions (EF) have been identified as impaired in FXS, but few studies have examined their developmental trajectories. AIMS: The primary aim of this longitudinal study was to examine the development of EF in young males with FXS compared to Mental Age (MA)-matched controls. METHODS AND PROCEDURES: The sample comprised 56 boys with FXS (ages 7-13 years), and 48 MA-matched typical boys (ages 4-8 years). EF tasks included measures of inhibitory control, working memory, cognitive flexibility/set-shifting, problem solving/planning, and processing speed. Tasks were administered at three time points over five-years. OUTCOMES AND RESULTS: The MA-Matched Typical boys significantly outperformed the FXS boys on all EF tasks, with the FXS Group showing a pattern of slow, but positive growth on most EF tasks. For working memory tasks, significant interactions were noted between MA and autism symptom severity, and MA and medication status. The probability of task completion increased with higher MA. CONCLUSIONS AND IMPLICATIONS: These findings contribute to our understanding of the development of EF in this population. They also lay the foundation for use of EF tasks in treatment efforts, particularly with respect to documenting improvements and practice effects, and in understanding associations with targeted developmental outcomes.

The Emergence of Effortful Control in Young Boys With Fragile X Syndrome.

Effortful control, or the ability to suppress a dominant response to perform a subdominant response, is an early-emerging temperament trait that is linked with positive social-emotional development. Fragile X syndrome (FXS) is a single-gene disorder characterized by hallmark regulatory impairments, suggesting diminished effortful control. This study compared the development of effortful control in preschool boys with FXS ( n = 97) and typical development ( n = 32). Unlike their typical peers, the boys with FXS did not exhibit growth in effortful control over time, which could not be accounted for by adaptive impairments, FMR1 molecular measures, or autism symptoms. These results contribute to our understanding of the childhood phenotype of FXS that may be linked to the poor social-emotional outcomes seen in this group.

Stranger Fear and Early Risk for Social Anxiety in Preschoolers with Fragile X Syndrome Contrasted to Autism Spectrum Disorder.

This study investigated behavioral indicators of social fear in preschool boys with fragile X syndrome (FXS) with a low degree of autism spectrum disorder (ASD) symptoms (FXS-Low; n = 29), FXS with elevated ASD symptoms (FXS-High; n = 25), idiopathic ASD (iASD; n = 11), and typical development (TD; n = 36). Gaze avoidance, escape behaviors, and facial fear during a stranger approach were coded. Boys with elevated ASD symptoms displayed more avoidant gaze, looking less at the stranger and parent than those with low ASD symptoms across etiologies. The iASD group displayed more facial fear than the other groups. Results suggest etiologically distinct behavioral patterns of social fear in preschoolers with elevated ASD symptoms.

HPA axis function predicts development of working memory in boys with FXS.

The present study examines verbal working memory over time in boys with fragile X syndrome (FXS) compared to nonverbal mental-age (NVMA) matched, typically developing (TD) boys. Concomitantly, the relationship between cortisol-a physiological marker for stress-and verbal working memory performance over time is examined to understand the role of physiological mechanisms in cognitive development in FXS. Participants were assessed between one and three times over a 2-year time frame using two verbal working memory tests that differ in complexity: memory for words and auditory working memory with salivary cortisol collected at the beginning and end of each assessment. Multilevel modeling results indicate specific deficits over time on the memory for words task in boys with FXS compared to TD controls that is exacerbated by elevated baseline cortisol. Similar increasing rates of growth over time were observed for boys with FXS and TD controls on the more complex auditory working memory task, but only boys with FXS displayed an association of increased baseline cortisol and lower performance. This study highlights the benefit of investigations of how dynamic biological and cognitive factors interact and influence cognitive development over time.

Language development in infants and toddlers with fragile X syndrome: change over time and the role of attention.

Fragile X syndrome (FXS) is associated with significant language and communication delays, as well as problems with attention. This study investigated early language abilities in infants and toddlers with FXS (n  =  13) and considered visual attention as a predictor of those skills. We found that language abilities increased over the study period of 9 to 24 months, with moderate correlations among language assessments. In comparison to typically developing infants (n  =  11), language skills were delayed beyond chronological age and developmental-level expectations. Aspects of early visual attention predicted later language ability. Atypical visual attention is an important aspect of the FXS phenotype with implications for early language development, particularly in the domain of vocabulary.

Developmental trajectories of attentional control in preschool males with fragile X syndrome.

Attention problems are among the most impairing features associated with fragile X syndrome (FXS). However, few studies have examined behavioral development of inhibitory control in very young children with FXS. We examined attentional control in 3-6 year boys with FXS using both an experimental inhibitory control paradigm and parent-report of attention problems. Study 1 examined attentional control in FXS compared to comparison groups matched on chronological and mental age. To determine the stability of impairments over time in FXS, Study 2 examined patterns of developmental change in an expanded longitudinal sample. Across studies, males with FXS demonstrated persistent impairments in inhibitory control and parent-reported attention problems. Inhibitory control was related to, but not solely driven by, lower mental age. Although parent-rated attention problems remained stable across ages, inhibitory control improved with time. Children with more severe attention problems often displayed initially poorer inhibitory control. However, these trajectories also improved more rapidly with age. Our findings indicate that despite persistent deficits in attentional control in young children with FXS, multi-method assessment can be used to capture developmental growth that should be further supported through early, targeted intervention.

Reading and phonological skills in boys with fragile X syndrome.

Although reading skills are critical for the success of individuals with intellectual disabilities, literacy has received little attention in fragile X syndrome (FXS). This study examined the literacy profile of FXS. Boys with FXS (n = 51; mean age 10.2 years) and mental age-matched boys with typical development (n = 35) participated in standardized assessments of reading and phonological skills. Phonological skills were impaired in FXS, while reading was on-par with that of controls. Phonological awareness predicted reading ability and ASD severity predicted poorer phonological abilities in FXS. Boys with FXS are capable of attaining reading skills that are commensurate with developmental level and phonological awareness skills may play a critical role in reading achievement in FXS.

Temperament factor structure in fragile X syndrome: the children's behavior questionnaire.

Early patterns of temperament lay the foundation for a variety of developmental constructs such as self-regulation, psychopathology, and resilience. Children with fragile X syndrome (FXS) display unique patterns of temperament compared to age-matched clinical and non-clinical samples, and early patterns of temperament have been associated with later anxiety in this population. Despite these unique patterns in FXS and recent reports of atypical factor structure of temperament questionnaires in Williams Syndrome (Leyfer, John, Woodruff-Borden, & Mervis, 2012), no studies have examined the latent factor structure of temperament scales in FXS to ensure measurement validity in this sample. The present study used confirmatory factor analysis to examine the factor structure of a well-validated parent-reported temperament questionnaire, the Children's Behavior Questionnaire (Rothbart, Ahadi, Hershey, & Fisher, 2001), in a sample of 90 males with FXS ages 3-9 years. Our data produced a similar, but not identical, three-factor model that retained the original CBQ factors of negative affectivity, effortful control, and extraversion/surgency. In particular, our FXS sample demonstrated stronger factor loadings for fear and shyness than previously reported loadings in non-clinical samples, consistent with reports of poor social approach and elevated anxiety in this population. Although the original factor structure of the Children's Behavior Questionnaire is largely retained in children with FXS, differences in factor loading magnitudes may reflect phenotypic characteristics of the syndrome. These findings may inform future developmental and translational research efforts.

Early negative affect predicts anxiety, not autism, in preschool boys with fragile X syndrome.

Children with fragile X syndrome (FXS) face high risk for anxiety disorders, yet no studies have explored FXS as a high-risk sample for investigating early manifestations of anxiety outcomes. Negative affect is one of the most salient predictors of problem behaviors and has been associated with both anxiety and autistic outcomes in clinical and non-clinical pediatric samples. In light of the high comorbidity between autism and anxiety within FXS, the present study investigates the relationship between longitudinal trajectories of negative affect (between 8 and 71 months) and severity of anxiety and autistic outcomes in young males with FXS (n = 25). Multilevel models indicated associations between elevated anxiety and higher fear and sadness, lower soothability, and steeper longitudinal increases in approach. Autistic outcomes were unrelated to negative affect. These findings suggest early negative affect differentially predicts anxiety, not autistic symptoms, within FXS. Future research is warranted to determine the specificity of the relationship between negative affect and anxiety, as well as to explore potential moderators. Characterizing the relationship between early negative affect and anxiety within FXS may inform etiology and treatment considerations specific to children with FXS, as well as lend insight into precursors of anxiety disorders in other clinical groups and community samples.

Biobehavioral indicators of social fear in young children with fragile X syndrome.

Anxiety is among the most impairing conditions associated with Fragile X syndrome (FXS) and is putatively linked to atypical physiological arousal. However, few studies have examined this association in young children with FXS. The authors examined whether patterns of arousal and behavior during an experimental stranger approach paradigm differ between a cross-sectional sample of 21 young children with FXS and 19 controls (12-58 months old). Groups did not differ in mean levels of behavioral fear. Unlike the control group, however, the FXS group demonstrated increased facial fear at older ages, as well as age-dependent changes in associations between heart activity and distress vocalizations. These findings may inform theoretical models of anxiety etiology in FXS and early detection efforts.

Visual attention and autistic behavior in infants with fragile X syndrome.

Aberrant attention is a core feature of fragile X syndrome (FXS), however, little is known regarding the developmental trajectory and underlying physiological processes of attention deficits in FXS. Atypical visual attention is an early emerging and robust indictor of autism in idiopathic (non-FXS) autism. Using a biobehavioral approach with gaze direction and heart activity, we examined visual attention in infants with FXS at 9, 12, and 18 months of age with a cross-sectional comparison to 12-month-old typically developing infants. Analyses revealed lower HR variability, shallower HR decelerations, and prolonged look durations in 12-month old infants with FXS compared to typical controls. Look duration and increased latency to disengage attention were correlated with severity of autistic behavior but not mental age.

Treatment effects of stimulant medication in young boys with fragile X syndrome.

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and is caused by a CGG repeat expansion at Xq27.3 on the FMR1 gene. The majority of young boys with FXS display poor attention and hyperactivity that is disproportionate to their cognitive disability, and approximately 70% meet diagnostic criteria for attention-deficit/hyperactivity disorder. Psychopharmacology is employed with 82% of young males 5-17 years of age, with stimulant medication as the most common medication prescribed. This study evaluated the effects of stimulant medication on the academic performance, attention, motor activity, and psychophysiological arousal of boys with FXS, as well as the concordance of effects within individuals. Participants in this study included 12 boys with FXS who were treated with stimulants. Participants completed videotaped academic testing on two consecutive days and were randomly assigned to be off stimulants for 1 day and on stimulants the other day. On each day, multiple measures including academic performance, behavior regulation, and psychophysiological arousal were collected. Approximately 75% of participants performed better on attention and academic measures, and 70% showed improved physiological regulation while on stimulant medication. A high degree of concordance among measures was found. Lower intelligence quotient (IQ), but not age, correlated with greater improvements in in-seat behavior. IQ and age did not relate to on-task behaviors. The frequency and magnitude of response to stimulant medication in boys with FXS is higher than those reported for most children with non-specific intellectual disabilities and autism spectrum disorder.

Developmental trajectories of young girls with fragile x syndrome.

To describe the early phenotype of girls with full mutation fragile X, we used 54 observations of 15 girls between the ages of 6 months and 9 years to examine developmental trajectories as measured by the Battelle Development Inventory. In this sample, autistic behavior was associated with poorer developmental outcomes, primarily due to interactions of age with autistic behavior, even though autistic behavior, measured continuously, was relatively mild. Although this small sample, ascertained primarily through male relatives with fragile X syndrome, limits generalizability, considerable variability in developmental outcome in young girls was documented. In addition, findings support previous research suggesting that even mild autistic behaviors in girls can be associated with developmental outcomes.

Trajectories and predictors of the development of very young boys with fragile X syndrome.

OBJECTIVE: To describe the development of young boys with fragile X syndrome (FXS). METHODS: Fifty-five boys (aged 8-48 months at study entry) with the full mutation FXS received multiple developmental assessments. RESULTS: As expected, the boys' rate of development was significantly lower than chronological age expectations. No evidence of slowing in the rate of development was found. Autistic behavior was negatively associated with development, but maternal IQ was not. Developmental delays were evident in some domains as early as 9 months; however, initial detection of delays is complicated by measures and criteria used. Developmental age scores at 31 months of age were related to scores obtained at 61 months of age only in the global composite and visual reception domain. CONCLUSIONS: Developmental delays are evident in some infants with FXS as young as 9 months of age. Pediatric psychologists need to be informed about the developmental profiles in young children with FXS to accurately diagnose, treat, and support these children and their families.

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

BACKGROUND AND PURPOSE: 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. METHOD: Participants were assessed using observational and parent-report measures 2-6 times between 9 and 54 months of age. RESULTS: 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. CONCLUSIONS: 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.

Child and genetic variables associated with maternal adaptation to fragile X syndrome: a multidimensional analysis.

One hundred eight carrier mothers (95 premutation, 13 full mutation) of children with the full mutation fragile X syndrome completed seven scales to assess maternal stress, depressive symptoms, anger, anxiety, quality of life, hope, and optimism. A wide range of responses was found on each measure, with most mothers scoring in the non-clinical range on any individual measure. However, nearly half of the mothers scored in the clinically significant range on at least one measure and 25% on two or more measures. High stress and low quality of life were the most common domains of concern. Mothers with the full mutation generally did not differ from mothers with the premutation. CGG repeat length was not associated with responses on any of the measures completed by mothers with the premutation. Severity of the child's delay was not associated with any of the outcome measures, but child behavior problems accounted for significant variance in stress, depressive symptoms, anxiety, anger, and quality of life. Maternal adaptation appears to be a multidimensional phenomenon experienced in unique ways by each mother. Most mothers experienced positive adaptation, but a subset appear to be more vulnerable, especially those with children who have significant behavior problems. Future research needs to identify family, child, and support factors associated with maternal vulnerability and how adaptation changes over time in response to these factors.

Executive functions in young males with fragile X syndrome in comparison to mental age-matched controls: baseline findings from a longitudinal study.

The performance of 54 boys with fragile X syndrome (FXS), ages 7 to 13 years, was compared to that of a group of typically developing boys who were matched on mental age (MA) and ethnicity across multiple measures of executive function (EF). Boys with FXS varied in their ability to complete EF measures, with only 25.9% being able to complete a set-shifting task and 94.4% being able to complete a memory for word span task. When compared to the control group, and controlling for MA and maternal education, boys with FXS showed significant deficits in inhibition, working memory, cognitive flexibility/set-shifting, and planning. No group differences were observed in processing speed. Mental age significantly impacted performance on working memory, set-shifting, planning, and processing speed tasks for both groups. In boys with FXS, MA significantly predicted performance on working memory and set-shifting tasks. Our findings suggest that deficits in EF in boys with FXS are not solely attributable to developmental delays but, rather, present as a true array of neurocognitive deficits.

Memory skills of boys with fragile X syndrome.

Multiple aspects of memory were examined in 42 boys with fragile X syndrome and a comparison group of 42 typically developing boys matched on MA. Working memory, incidental memory, and deliberate memory were assessed with a battery that included both free-recall and recognition tasks. Findings indicated that boys with fragile X syndrome performed more poorly than their matches on most measures. The exception was free recall, in which their accuracy was equal to that of the control participants. Results from analyses of a subset of boys with fragile X syndrome who exhibit characteristics of autism and their MA matches, though preliminary, support the conclusion that memory deficits are especially marked in boys who have fragile X syndrome and evidence autistic behaviors.

Babies Count: the national registry for children with visual impairments, birth to 3 years.

INTRODUCTION: Information about the prevalence of visual impairment in children is not collected systematically. Further, little information is available about children under age 6. Babies Count is a national registry of children with visual impairment in the United States, aged birth to 3 years. METHODS: Data were collected on 2,155 children at the point of entry into specialized early intervention programs. Data include patient diagnosis, functional vision, age, gender, ethnicity, and family characteristics. Concurrent visual pathology and systemic disabilities were also documented. RESULTS: Of the sample of 2,155 children, 1,167 (54%) were boys; approximately 40% of the children were legally blind, and 68% had disabilities in addition to visual impairment. Cortical visual impairment, retinopathy of prematurity (ROP), and optic nerve hypoplasia (ONH) were the three most prevalent visual conditions. In children with these three conditions, those with ROP were diagnosed the earliest (mean, 3.4 months), and those with cortical visual impairment were diagnosed latest (mean, 7.6 months). There was on average a 4.5 month mean lag between the diagnosis of children's visual impairment and referral for services. ONH carried a poorer visual outcome when compared with other diagnoses, including CVI, ROP, and albinism. CONCLUSIONS: Prevalent visual conditions in children in the United States differ from those found in developing countries and in adults with visual impairment. Babies Count is a comprehensive set of data that may affect our understanding of the epidemiology of visual impairment in the United States. In an era of preventive and outcome-based medicine, and with competition for health care and research funding, these data provide a valuable means for understanding the impact of these disorders on society.

Correlates of maternal behaviours in mothers of children with fragile X syndrome.

BACKGROUND: The behaviours of 24 mothers of children with fragile X syndrome (FXS) with their affected children were examined during planned observations in their homes. The goal of this study was to describe concurrent maternal interactive behaviour and the factors that influence the type and frequency of these behaviours within this group. METHODS: The frequency of maintaining, directive and scaffolding behaviours and the extent to which the mothers displayed warm sensitivity and restrictions were examined within a 60-min naturalistic observation and a 10-min toy play observation. Rating scales and parent questionnaires were used to assess selected maternal mental health factors, including depression, anxiety, stress and social support. The cognitive status of mothers and developmental and behavioural abilities of children were also examined. RESULTS: The women in this study used primarily maintaining behaviours in interactions with their children. Maintaining behaviours and warm sensitivity were consistent across structured and unstructured settings, while directive, scaffolding and restricting were not correlated across the two settings. Child receptive language skills were related to higher rates of maintaining and scaffolding behaviours. The women reported clinically significant levels of stress, depression and anxiety at a prevalence rate higher than that of the general public. Child behaviour problems contributed to maternal stress, and mothers with higher stress engaged in fewer interactions with their children. CONCLUSIONS: The relations between maternal stress, child problem behaviour and number of interactive behaviours exhibited by the mothers in this study provide information that can inform interventions and provide direction for future research exploring environmental influences on the development of children with fragile X syndrome.