Social Communication and Theory of Mind in Boys with Autism and Fragile X Syndrome

Impairments in the social use of language, or pragmatics, constitute a core characteristic of autism. Problems with pragmatic language have also been documented in fragile X syndrome (FXS), a monogenic condition that is the most common known genetic cause of autism. Evidence suggests that social cognitive ability, or theory of mind, may also be impaired in both conditions, and in autism, may importantly relate to pragmatic language ability. Given the substantial overlap observed in autism and FXS, this study aimed to better define those social-communicative phenotypes that overlap in these two conditions by comparing pragmatic language ability and theory of mind in children with idiopathic autism and children with FXS, with and without autism, as well as children with Down syndrome and typically developing controls. We further examined correlations between these cognitive-behavioral phenotypes and molecular genetic variation related to the Fragile X Mental Retardation-1 gene (FMR1) in the FXS group. Results indicated that children with idiopathic autism and those with FXS and autism performed comparably on directassessment measures of pragmatic language and theory of mind, whereas those with FXS only did not differ from controls. Theory of mind was related to pragmatic language ability in all groups. Pragmatic language and theory of mind also correlated with genetic variation at the FMR1 locus (Cytosine-Guanine-Guanine repeats and percent methylation). These results point toward substantial overlap in the social and language phenotypes in autism and FXS and suggest a molecular genetic basis to these phenotypic profiles

COMPARISON OF SPEECH AND PRACTICED NONSPEECH INTRAORAL PRESSURE WAVEFORM CHARACTERISTICS

Intraoral pressure waveforms of a learned volitional nonspeech task were compared to that of a parallel speech task in order to drawl inferences regarding a possible shared sensorimotor control mechanism. Similarities between the dependent variables at question (the percents of the increase and decrease interval involved in the total duration and the slopes of the increase and decrease interval) may provide preliminary evidence of a shared generalized motor program. The nonspeech task (which was devised as part of a larger study by Shaiman et al., 2004; 2006) reflected the goal and complexity of speech, by the incorporation of intraoral pressure targets and practiced, co-articulated gestures. Six subjects participated in the study. Subjects practiced the nonspeech task over two sessions, totaling to over 600 repetitions of the task, with KR regarding accuracy of reaching the pressure target provided for 65% of trials. Nonspeech retention data was gathered at the end of both practicing sessions. Parallel speech task data were then taken. The measures of the dependent variables were calculated by the division of the pressure waveform into three distinct intervals: the increase, plateau, and decrease interval. These intervals were automatically detected using a pressure waveform analysis program, which used the first derivative of the pressure signal to mark parts of the waveform. The means for the nonspeech retention data and the speech data were taken for each dependent variable. Univariate analysis revealed no significant difference between the speech and nonspeech condition for any of the four dependent variables (p<0.05). The finding of no significant difference for any of the four dependent variables may provide preliminary evidence for a shared generalized motor program for speech and nonspeech gestures. However, future research with data from additional subjects would assess this finding. Also, descriptive observations of waveform shape during the plateau interval indicate the need for further analysis of additional waveform measurements not analyzed in the current study, and also the need to control rate and precision of production in the future

Pragmatic language in autism and fragile X syndrome: links with physiological arousal and anxiety

This dissertation is comprised of three manuscripts focused on delineating pragmatic language profiles in children with autism and fragile X syndrome, and on understanding the potential impact of physiological dysregulation on these profiles. The first manuscript presents a review of the existing literature on physiological arousal in autism and fragile X syndrome, with a focus on the relationship between arousal modulation and social competence. The second two manuscripts present original research: the first consists of a cross-population comparison of pragmatic language in autism and fragile X syndrome; the second extends upon this line of research by examining cardiac arousal as a mechanism that may play a role of social-communicative impairment in these disorders. These three manuscripts address the extent to which pragmatic language deficits overlap in autism and fragile X syndrome, and whether such deficits are linked with dysfunction of the autonomic nervous system. This work has implications for developing syndrome-specific interventions and ultimately may inform biological pathways that may be common to autism and fragile X syndrome.Doctor of Philosoph

Sex differences and within-family associations in the broad autism phenotype

While there is a strong sex bias in the presentation of autism, it is unknown whether this bias is also present in subclinical manifestations of autism among relatives, or the broad autism phenotype. This study examined this question and investigated patterns of co-occurrence of broad autism phenotype traits within families of individuals with autism. Pragmatic language and personality features of the broad autism phenotype were studied in 42 fathers and 50 mothers of individuals with autism using direct assessment tools used in prior family studies of the broad autism phenotype. Higher rates of aloof personality style were detected among fathers, while no sex differences were detected for other broad autism phenotype traits. Within individuals, pragmatic language features were associated with the social personality styles of the broad autism phenotype in mothers but not in fathers. A number of broad autism phenotype features were correlated within spousal pairs. Finally, the associations were detected between paternal broad autism phenotype characteristics and the severity of children’s autism symptoms in all three domains (social, communication, and repetitive behaviors). Mother–child correlations were detected for aspects of communication only. Together, the findings suggest that most features of the broad autism phenotype express comparably in males and females and raise some specific questions about how such features might inform studies of the genetic basis of autism. </jats:p

Language Characteristics of Individuals with Down Syndrome

On average, language and communication characteristics of individuals with Down syndrome (the most common genetic cause of intellectual disability) follow a consistent profile. Despite considerable individual variability, receptive language is typically stronger than expressive language, with particular challenges in phonology and syntax. We review the literature on language and literacy skills of individuals with Down syndrome, with emphasis on the areas of phonology, vocabulary, syntax, and pragmatics. We begin by describing the hearing, oral-motor, cognitive, social, and prelinguistic and early nonverbal communication characteristics of individuals with Down syndrome. We conclude with a discussion of clinical implications and research directions

Pragmatic Language Features of Mothers with the FMR1 Premutation are Associated with the Language Outcomes of Adolescents and Young Adults with Fragile X Syndrome

PURPOSE: Pragmatic language difficulties have been documented as part of the FMR1 premutation phenotype, yet the interplay between these features in mothers and the language outcomes of their children with fragile X syndrome is unknown. This study aimed to determine whether pragmatic language difficulties in mothers with the FMR1 premutation are related to the language development of their children. METHOD: Twenty-seven mothers with the FMR1 premutation and their adolescent/young adult sons with fragile X syndrome participated. Maternal pragmatic language violations were rated from conversational samples using the Pragmatic Rating Scale (Landa et al., 1992). Children completed standardized assessments of vocabulary, syntax, and reading. RESULTS: Maternal pragmatic language difficulties were significantly associated with poorer child receptive vocabulary and expressive syntax skills, with medium effect sizes. CONCLUSIONS: This work contributes to knowledge of the FMR1 premutation phenotype and its consequences at the family level, with the goal of identifying modifiable aspects of the child's language-learning environment that may promote the selection of treatments targeting the specific needs of families affected by fragile X. Findings contribute to our understanding of the multifaceted environment in which children with fragile X syndrome learn language and highlight the importance of family-centered intervention practices for this group

Physiological Arousal in Autism and Fragile X Syndrome: Group Comparisons and Links With Pragmatic Language

This study tested the hypothesis that pragmatic (i.e., social) language impairment is linked to arousal dysregulation in autism spectrum disorder (ASD) and fragile X syndrome (FXS). Forty boys with ASD, 39 with FXS, and 28 with typical development (TD), aged 4–15 years, participated. Boys with FXS were hyperaroused compared to boys with TD but did not differ from boys with ASD. Dampened vagal tone predicted pragmatic impairment in ASD, and associations emerged between cardiac activity and receptive/expressive vocabulary across groups. Findings support autonomic dysfunction as a mechanism underlying pragmatic impairment in ASD and suggest that biophysiological profiles are shared in ASD and FXS, which has implications for understanding the role of fragile X mental retardation-1 (FMR1, the FXS gene) in the pathophysiology of ASD

Sex differences and within-family associations in the broad autism phenotype

While there is a strong sex bias in the presentation of autism, it is unknown whether this bias is also present in subclinical manifestations of autism among relatives, or the broad autism phenotype (BAP). This study examined this question, and investigated patterns of co-occurrence of BAP traits within families of individuals with autism. Pragmatic language and personality features of the BAP were studied in 42 fathers and 50 mothers of individuals with autism using direct assessment tools used in prior family studies of the BAP. Higher rates of aloof personality style were detected among fathers, while no sex differences were detected for other BAP traits. Within individuals, pragmatic language features were associated with the social personality styles of the BAP in mothers but not fathers. A number of BAP features were correlated within spousal pairs. Finally, associations were detected between paternal BAP characteristics and the severity of children’s autism symptoms in all three domains (social, communication, and repetitive behaviors). Mother-child correlations were detected for aspects of communication only. Together, findings suggest that most features of the BAP express comparably in males and females, and raise some specific questions about how such features might inform studies of the genetic basis of autism

A Comparison of Pragmatic Language in Boys With Autism and Fragile X Syndrome

Impaired pragmatic language (i.e., language use for social interaction) is a hallmark feature of both autism spectrum disorder (ASD) and fragile X syndrome (FXS), the most common known monogenic disorder associated with ASD. However, few cross-population comparisons of ASD and FXS have been conducted, and it is unclear whether pragmatic language profiles in these conditions overlap

Maternal Pragmatic Language Difficulties in the \u3ci\u3eFMR1\u3c/i\u3e Premutation and the Broad Autism Phenotype: Associations with Individual and Family Outcomes

Broader phenotypes associated with genetic liability, including mild difficulties with pragmatic language skills, have been documented in mothers of children with autism spectrum disorder (ASD) and mothers of children with fragile X syndrome (FXS). This study investigated the relationship between pragmatic difficulties and indicators of maternal well-being and family functioning. Pragmatic difficulty was associated with loneliness in mothers of children with ASD or FXS, and with depression, decreased life satisfaction, and poorer family relationship quality but only in mothers of children with FXS. Results suggest that subtle maternal pragmatic language difficulties are a risk factor that that may contribute to reduced health and well-being, informing tailored support services to better meet the unique needs of families of children with ASD or FXS