Angela John Thurman

The fragile X syndrome-autism comorbidity: what do we really know?

Autism spectrum disorder (ASD) is a common comorbid condition in people with fragile X syndrome (FXS). It has been assumed that ASD symptoms reflect the same underlying psychological and neurobiological impairments in both FXS and non-syndromic ASD, which has led to the claim that targeted pharmaceutical treatments that are efficacious for core symptoms of FXS are likely to be beneficial for non-syndromic ASD as well. In contrast, we present evidence from a variety of sources suggesting that there are important differences in ASD symptoms, behavioral and psychiatric correlates, and developmental trajectories between individuals with comorbid FXS and ASD and those with non-syndromic ASD. We also present evidence suggesting that social impairments may not distinguish individuals with FXS with and without ASD. Finally, we present data that demonstrate that the neurobiological substrates of the behavioral impairments, including those reflecting core ASD symptoms, are different in FXS and non-syndromic ASD. Together, these data suggest that there are clinically important differences between FXS and non-syndromic ASD that are masked by reliance on the categorical diagnosis of ASD. We argue for use of a symptom-based approach in future research, including studies designed to evaluate treatment efficacy.

Symptoms of Autism in Males with Fragile X Syndrome: A Comparison to Nonsyndromic ASD Using Current ADI-R Scores.

Symptoms of autism are frequent in males with fragile X syndrome (FXS), but it is not clear whether symptom profiles differ from those of nonsyndromic ASD. Using individual item scores from the Autism Diagnostic Inventory-Revised, we examined which current symptoms of autism differed in boys with FXS relative to same-aged boys diagnosed with nonsyndromic ASD. In addition, different subsamples of participants were matched on autism diagnostic status and severity of autism symptoms. Between-group comparisons revealed that boys with FXS showed significantly less impairment in Social Smiling than did age-, diagnostic-, and severity-matched boys with nonsyndromic ASD. Severity-matched boys with FXS showed more impairment in complex mannerisms than did boys with nonsyndromic ASD. Behavioral differences between FXS and nonsyndromic ASD may be of theoretical importance in understanding the causes and correlates of ASD in FXS and in developing and implementing appropriate treatments.

Psychiatric symptoms in boys with fragile X syndrome: A comparison with nonsyndromic autism spectrum disorder

In the present study, we examined the profile of psychiatric symptoms in boys with fragile X syndrome (FXS) using a parent report instrument. In addition, by comparing boys with FXS to boys with nonsyndromic autism spectrum disorder (ASD) utilizing multiple matching strategies, we examined between-group differences in the types of psychiatric symptoms observed and in the strength of their concurrent associations. Across all matching strategies, symptoms of manic/hyperactive behaviors and general anxiety were more frequently reported for boys with FXS than for boys with nonsyndromic ASD. Results also indicated a positive association between social avoidance and general anxiety in FXS that was stronger than that observed in nonsyndromic ASD across all matching strategies. Theoretical and treatment implications are discussed.

Autism Symptomatology in Boys with Fragile X Syndrome: A Cross Sectional Developmental Trajectories Comparison with Nonsyndromic Autism Spectrum Disorder

Although males with fragile X syndrome (FXS) are frequently described as demonstrating autism symptomatology, there is much debate regarding whether the behavioral symptoms representing the core domains of autism are the result of the same or different underlying neurological/psychological mechanisms. The present study used a cross-sectional developmental trajectories approach to compare the profiles of autism symptomatology relative to chronological age (CA), nonverbal IQ, and expressive vocabulary ability between individuals with FXS and individuals with nonsyndromic ASD. Results suggest that the onset of autism symptoms and their developmental trajectories in males with FXS differ in important ways as a function of CA, nonverbal cognitive ability, and expressive vocabulary relative to males with nonsyndromic ASD. Theoretical and clinical implications are discussed.

Characterising repetitive behaviours in young boys with fragile X syndrome

BACKGROUND Repetitive behaviours are frequently observed in individuals with intellectual disability (ID). The present study examined the profile, inter-correlations and predictive correlates of repetitive behaviours in boys with fragile X syndrome (FXS), the leading inherited cause of ID. Specific child characteristics examined as predictors included anxiety, nonverbal cognition and autism social-affective symptomatology. METHOD Participants were 39 boys with FXS (aged 6-10 years). Repetitive behaviours were measured using the Repetitive Behavior Scale - Revised (RBS-R) - a 43-item caregiver-report measure normed on individuals with ID. RESULTS Restricted Interests and Sensory Motor behaviours were reported as most problematic for this sample of boys, whereas Self-injurious behaviours were less problematic. All subscales of the RBS-R were significantly inter-correlated. Nonverbal IQ was negatively related, whereas anxiety and social affective symptoms of autism spectrum disorder were positively related, to scores for Restricted Interests. Anxiety was also positively related to scores for Compulsive behaviours and Ritualistic Sameness behaviours. CONCLUSIONS This study provides a preliminary description of repetitive behaviours in boys with FXS, which may form the groundwork for future research.

Examining the operant function of challenging behavior in young males with fragile X syndrome: A summary of 12 cases

This study used experimental functional analyses to examine the operant function of challenging behaviors exhibited by 12 males (ages 27-51 months) with fragile X syndrome (FXS). Eight children met criteria for negatively reinforced challenging behavior in the form of escape from demands and/or escape from social interactions. Nine children met criteria for positively reinforced challenging behavior in the form of obtaining access to highly preferred items. Attention was identified as a maintaining consequence for three children. The functional analysis was inconclusive for one child. Results suggest that, for young males with FXS, challenging behaviors may more likely be tangibly and escape maintained than attention maintained. Our findings affirm past research suggesting a unique behavioral phenotype for this population.

Use of Emotional Cues for Lexical Learning: A Comparison of Autism Spectrum Disorder and Fragile X Syndrome

Abstract The present study evaluated the ability of males with fragile X syndrome (FXS), nonsyndromic autism spectrum disorder (ASD), or typical development to learn new words by using as a cue to the intended referent an emotional reaction indicating a successful (excitement) or unsuccessful (disappointment) search for a novel object. Performance for all groups exceeded chance-levels in both search conditions. In the Successful Search condition, participants with nonsyndromic ASD performed similarly to participants with FXS after controlling for severity of ASD. In the Unsuccessful Search condition, participants with FXS performed significantly worse than participants with nonsyndromic ASD, after controlling for severity of ASD. Predictors of performance in both search conditions differed between the three groups. Theoretical and clinical implications are discussed.

Effect of Speaker Gaze on Word Learning in Fragile X Syndrome: A Comparison With Nonsyndromic Autism Spectrum Disorder

PURPOSE This study examined use of a speakers direction of gaze during word learning by boys with fragile X syndrome (FXS), boys with nonsyndromic autism spectrum disorder (ASD), and typically developing (TD) boys. METHOD A fast-mapping task with follow-in and discrepant labeling conditions was administered. We expected that the use of speaker gaze would lead to participants selecting as the referent of the novel label the object to which they attended in follow-in trials and the object to which the examiner attended in the discrepant labeling trials. Participants were school-aged boys with FXS (n=18) or ASD (n=18) matched on age, intelligence quotient, and nonverbal cognition and younger TD boys (n=18) matched on nonverbal cognition. RESULTS All groups performed above chance in both conditions, although the TD boys performed closest to the expected pattern. Boys with FXS performed better during follow-in than in discrepant label trials, whereas TD boys and boys with ASD did equally well in both trial types. The type of trial administered first influenced subsequent responding. Error patterns also distinguished the groups. CONCLUSION The ability to utilize a speakers gaze during word learning is not as well developed in boys with FXS or nonsyndromic ASD as in TD boys of the same developmental level.

Language disorders in children with intellectual disability of genetic origin

Part 1. Typology of Child Language Disorders. R.G. Schwartz, Specific Language Impairment. A. McDuffie, L. Abbeduto, Language Disorders in Children with Mental Retardation of Genetic Origin: Down Syndrome, Fragile X Syndrome, and Williams Syndrome. J. Gerenser, Language Disorders in Children with Autism. M. Cleary, Language Disorders in Children with Hearing Impairment. S.E. Shaywitz, J.R. Gruen, M. Mody, B.A. Shaywitz, Dyslexia. Part 2. Bases of Child Language Disorders. I. Botwinik-Rotem, N. Friedmann, Linguistic Bases of Child Language Disorders. B. Tropper, R.G. Schwartz, Neurobiology of Child Language Disorders. R.B. Gillam, J.W. Montgomery, S.L. Gillam, Attention and Memory in Child Language Disorders. J. Edwards, B. Munson, Speech Perception and Production in Child Language Disorders. J.B. Tomblin, Genetics of Child Language Disorders. M.F. Joanisse, Model-Based Approaches to Child Language Disorders. Part 3. Language Contexts of Child Language Disorders. E.D. Pena, L.M. Bedore, Bilingualism in Child Language Disorders. L.B. Leonard, Cross-Linguistic Studies of Child Language Disorders. J.A. Washington, Language Variation in Child Language Disorders. Part 4. Deficits, Assessment, and Intervention in Child Language Disorders. J.B. Oetting, P.A. Hadley, Morphosyntax in Child Language Disorders. K.K. McGregor, Semantics in Child Language Disorders. P. Fletcher, Syntax in Child Language Disorders. M. Fujiki, B. Brinton, Pragmatics and Social Communication in Child Language Disorders. P.E. Hook, C.W. Haynes, Reading and Writing in Child Language Disorders. J. Windsor, K. Kohnert, Processing Speed, Attention, and Perception in Child Language Disorders. Part 5: Research Methods in Child Language Disorders. L. Seiger-Gardner, Language Production Approaches to Child Language Disorders. P. Deevy, Language Comprehension Approaches to Child Language Disorders. M.E. Fey, L.H. Finestack, Research and Development in Child Language Intervention: A Five-Phase Model. V.L. Shafer, N.D. Maxfield, Neuroscience Approaches to Child Language Disorders.

Language Skills of Males with Fragile X Syndrome or Nonsyndromic Autism Spectrum Disorder

Despite the similarities observed between the fragile X syndrome (FXS) and autism spectrum disorder (ASD) phenotypes, few studies have compared their behavioral profiles outside of ASD symptomatology. In the present study, we sought to compare lexical and grammatical abilities in these two conditions. Comparisons of language abilities in both of these conditions are particularly interesting because both conditions are characterized by difficulties navigating social interactions. Results suggest that although both FXS and ASD are associated with language difficulties, there are important differences between the two conditions in terms of the language profiles observed and the factors influencing language when considering children of similar developmental levels. Theoretical implications are discussed.