Overlap Between ASD and SLI
Autism and SLI are two developmental disorders that share language as a deficit. In both disorders, concerns are typically raised during the toddler years [Dahlgren & Gillberg, 1989; Tager-Flusberg & Cooper, 1999]. Autism and SLI are both considered as spectrum disorders [Bishop, 1989; Gillberg & Coleman, 2000; Resnick & Rapin, 1991], and this is supported by the considerable heterogeneity in language abilities observed in affected individuals [Tager-Flusberg, Paul, & Lord, 2005; Tomblin & Zhang, 1999]. There is also evidence that genes play a significant role in these disorders. Several studies have supported this hypothesis in autism [for reviews, see Bespalova & Buxbaum, 2003; Folstein & Rosen-Sheidley, 2001], and a strong genetic basis of SLI is supported by significant differences in the concordance rates for monozygotic vs. dizygotic twins [Bishop, North, & Donlan, 1995; Lewis & Thompson, 1992; Tomblin & Buckwalter, 1998]. Segregation analyses provide strong evidence of familial transmission of SLI [Lewis, Cox, & Byard, 1993; Tomblin & Zhang, 1999], and several studies have described an increased prevalence of language delay and language-based learning deficits in the parents and siblings of autistic individuals [Bailey, Palferman, Heavey, & Le Couteur, 1998; Bolton et al., 1994; Fombonne, Bolton, Prior, Jordan, & Rutter, 1997; Piven, Palmer, Jacobi, Childress, & Arndt, 1997]. This relationship may be bi-directional, and siblings of children with SLI may also be at a higher risk of developing autism. A study by Tomblin, Hafeman, and O'Brien  found that although there were no significant group differences in autism risk to siblings when SLI and control groups were defined categorically, when language was treated as a continuous variable, siblings of children who had poor spoken language skills in kindergarten were at higher risk for autism. Similarly, although Rapin [1996a] described higher rates of autism in siblings of high- and low-functioning children with autism, the rate of autism in siblings of SLI children was higher than that in siblings of non-autistic children with low IQs. Finally, some genetic studies have described overlap in genetic loci implicated in autism and SLI [for an ASD review, see Abrahams & Geschwind, 2008; Alarcon et al., 2008; Arking et al., 2008; Bakkaloglu et al., 2008; O'Brien, Zhang, Nishimura, Tomblin, & Murray, 2003; Vernes et al., 2008; Warburton et al., 2000]. Of particular interest is the recent study by Vernes et al.  that identified a candidate gene for SLI showing significant associations with non-word repetition performance. This gene, CNTNAP2, has also been implicated in ASD [Alarcon et al., 2008; Arking et al., 2008; Bakkaloglu et al., 2008], especially in individuals who experienced language delay [Alarcon et al., 2008]. These findings support the view that there is at least one gene contributing to the common language phenotype observed in these disorders.
Despite these similarities, there are differences between autism and SLI. Autism is defined by qualitative impairments in three realms by the age of three: social interaction, communication, and a restricted repertoire of activities and interests [American Psychiatric Association, 1994]. SLI is characterized by delayed onset and slowed acquisition of language as compared to other areas of development [Tager-Flusberg & Cooper, 1999], but according to Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition [American Psychiatric Association, 1994], individuals cannot meet criteria for autism and receive a diagnosis of SLI. There are also differences in the types of language difficulties observed in these disorders. In autism, some individuals express a developmental regression, especially in language, with one study citing rates as high as 33% [Goldberg et al., 2003], while this trajectory is absent in individuals with SLI [Rapin, 1996b]. Furthermore, individuals with autism may exhibit other language characteristics, such as echolalia and pronoun reversal, that are not often described in SLI [e.g., Bartak, Rutter, & Cox, 1975, 1977].
There have been several studies investigating overlap between language phenotypes in autism and SLI. Bartak et al. [1975, 1977] completed the first studies to directly investigate this relationship. The authors found that although autistic children scored significantly lower on measures of language comprehension, the groups exhibited similar deficits in expressive language and language production. In another study by Kjelgaard and Tager-Flusberg , a large group of children with autism was tested on a variety of standardized language measures, including the Clinical Evaluation of Language Fundamentals—Third Edition (CELF-III) and a non-word repetition test. The authors found that, as a group, children with autism performed one standard deviation or more below the mean in total language ability as measured by the CELF-III and on non-word repetition. However, when the group was subdivided based on total language ability on the CELF-III into normal, borderline, or impaired language ability, only the borderline and impaired groups (about 75% of the total sample) scored significantly below the mean on non-word repetition. These children exhibited language profiles of grammar, vocabulary, and phonological processing similar to children with SLI. A follow-up study found that children with autism and language impairment made grammatical tense marking errors that were similar to those of children with SLI [Roberts, Rice, & Tager-Flusberg, 2004], further supporting the hypothesis of overlap between these groups. Finally, a recent study by Whitehouse, Barry, and Bishop  was the first to directly compare children with autism and SLI on non-word repetition performance. The authors found that those children with autism and normal structural language (ALN) scored higher than both the SLI group and the group of autistic children with poor structural language (ALI). Further analyses of group differences in non-word repetition performance and its relation to syllable length in those children who performed poorly on this test (SLI, n=18; ALI, n=8) found similar rates of error on words two or three syllables in length but significantly poorer performance on five-syllable words in the SLI group; however, given the small sample size and number of observations for each syllable length (three trials each for two to four syllables and four trials for five syllables), the latter analyses require further investigation.
The diagnostic boundaries between autism and SLI have also been questioned. In the early studies by Bartak et al. [1975, 1977], about 10% of the original SLI sample displayed some autistic characteristics. When the children from these studies were then followed into middle childhood [Cantwell, Baker, Rutter, & Mawhood, 1989] and later into adulthood [Howlin, Mawhood, & Rutter, 2000; Mawhood, Howlin, & Rutter, 2000], the authors noted that some of the SLI individuals had developed social and behavioral impairments similar to those observed in the autism group. A recent study also noted poorer quality of friendships in adolescents with SLI [Durkin & Conti-Ramsden, 2007]. Bishop and Norbury  found that some children with either SLI or pragmatic language impairment, as defined by the Children's Communication Checklist [Bishop, 1998], scored above cutoff on two of the three domains of the Autism Diagnostic Interview—Revised (ADI-R) or met criteria for autistic disorder on this measure. There was, however, also a group of children that failed to exhibit clear autistic symptoms outside of the communication domain. In a similar study by Conti-Ramsden, Simkin, and Botting , 14-year-old children with a history of SLI were evaluated on a variety of diagnostic measures, including the ADI-R, the Autism Diagnostic Observation Schedule (ADOS), and the Family History Interview. The prevalence of ASD in this group was higher than that of the general population, and a number of children exhibited milder autistic behaviors on these measures. More recently, a study by Bishop, Whitehouse, Watt, and Line  investigating the hypothesis of diagnostic substitution in autism found that in their sample of 38 individuals who had previously been diagnosed with language disorder in childhood, 13 met criteria for ASD on both the ADI-R and ADOS in adulthood. This study raises the question of whether SLI individuals in previous studies truly developed autistic symptoms later in life or whether they were misdiagnosed in childhood. These results highlight the possible continuity between autism and SLI and the lack of clear boundaries between these heterogeneous disorders.
Language Characteristics of Relatives of Individuals With Autism and Individuals With SLI
Family studies have noted language impairments in first-degree relatives of children with SLI and children with ASD, supporting a genetic basis for these deficits. Using family history questionnaires, several studies have described higher rates of language impairments in parents and siblings of SLI children when compared to relatives of typically developing children [Lahey & Edwards, 1995; Neils & Aram, 1986; Rice, Haney, & Wexler, 1998; Tallal, Ross, & Curtiss, 1989; Tomblin, 1989; van der Lely & Stollwerck, 1996]. As many as 60% of children with SLI have at least one additional family member with language impairments [Lahey & Edwards, 1995], although it is unclear whether the occurrence rates vary depending on the relationship of the family member to the proband [Rice, Wexler, & Cleave, 1995; Tomblin, 1989]. Family studies of children with autism have also noted similar features, or a “broader phenotype,” in first-degree relatives, including impairments in language functioning. Studies of twins discordant for autism have reported language difficulties in the non-affected twins [Folstein & Rutter, 1977; Le Couteur et al., 1996]. Using family history data, higher rates of communication deficits have been identified in relatives of children with autism when compared to relatives of children with Down syndrome [Bolton et al., 1994; Piven, Palmer, Jacobi et al., 1997]. These deficits were also greater in biological vs. non-biological relatives of children with autism [Szatmari et al., 2000], further supporting the hypothesis that the communication impairments observed in autism and in the broader phenotype have a shared genetic basis.
Studies in family members of children with ASD and SLI have mainly focused on two types of language deficits: those in pragmatic language, or the social use of language, and those in structural language, such as phonology, grammar, and vocabulary difficulties. Pragmatic language deficits are consistently described as part of the ASD broader phenotype. Studies using questionnaires, such as the Autism Spectrum Quotient [Bishop, Maybery, Maley et al., 2004] or the Children's Communication Checklist [Bishop, Maybery, Wong, Maley, & Hallmayer, 2006], have demonstrated clear communication deficits in some parents and siblings of children with ASD when compared to family members of typically developing children. Higher rates of poor narrative performance [Landa, Folstein, & Isaacs, 1991] and pragmatic language impairments [Landa et al., 1992; Piven, Palmer, Landa et al., 1997] have also been identified in parents of children with ASD when compared to parents of typically developing children or children with Down syndrome. More recently, Ruser et al.  noted these communication deficits on a modified version of the Pragmatic Rating Scale in both parents of children with autism and parents of children with SLI when compared to parents of children with Down syndrome. Together, these findings suggest that pragmatic deficits are evident in a subset of first-degree relatives of both children with autism and children with SLI and that they may contribute to the broader phenotypes associated with these disorders. Of note, however, one study using the Autism Spectrum Quotient failed to identify impairments in social communication in parents of children with SLI [Whitehouse, Barry, & Bishop, 2007].
Studies assessing structural language abilities in parents and siblings of individuals with SLI have described clinically impaired performance in some relatives on standardized measures with rates ranging from 21 to 63% [Conti-Ramsden, Simkin, & Pickles, 2006; Plante, Shenkman, & Clark, 1996; Tomblin & Buckwalter, 1998]. Similar deficits have also been found in phonological processing, including poor performance on a non-word repetition task [Barry, Yasin, & Bishop, 2007; Bishop et al., 1999; Bishop, North, & Donlan, 1996]. Studies evaluating structural language in relatives of autistic individuals, however, have produced mixed results. Folstein et al.  found higher rates of early language difficulties and poorer performance on a nonsense word reading task in parents, but not siblings, of children with autism vs. relatives of children with Down syndrome. Among the relatives of children with autism, parents and siblings with a history of language impairment performed more poorly than family members without a positive history on tests of verbal intelligence, reading, spelling, and nonsense word reading. Similarly, Bishop et al.  described abnormalities in structural language in some siblings of children with autism, suggesting that the broader phenotype of autism may overlap with SLI. Another study described poorer phonological processing, reading, writing, and vocabulary abilities in brothers, but not mothers, fathers, or sisters, of autistic females when compared to relatives of individuals with Down Syndrome [Plumet, Goldblum, & Leboyer, 1995]. Other studies, though, have suggested that structural language deficits may not be part of the broader autism phenotype. Pilowsky, Yirmiya, Shalev, and Gross-Tsur  investigated language abilities of siblings of children with autism, children with SLI, and children with mental retardation and found no differences between the groups on a variety of language abilities, including verbal intelligence, receptive and expressive language, and reading, writing, and spelling performance. Another study failed to identify phonological processing deficits in first-degree relatives of children with autism on non-word repetition and nonsense word reading tests [Bishop, Maybery, Wong et al., 2004]. Similarly, a recent comparison of parents of children with autism, children with SLI, and typically developing children on various language measures found no evidence of overlap between the broader phenotypes of the autism and SLI groups [Whitehouse et al., 2007]. This absence of overlap remained even after the parents of children with autism were divided based on the proband's performance on a non-word repetition task, although the sample of parents of children with autism and language impairments was small (n=9). To explain the existence of linguistic deficits in autism but not in the first-degree relatives, the authors hypothesized that these deficits are not heritable but rather a consequence of the ASD phenotype and its effect on language development.
Given that only a subset of children with ASD exhibits language profiles that overlap with those of children with SLI [Kjelgaard & Tager-Flusberg, 2001; Tager-Flusberg & Joseph, 2003], these studies [Bishop, Maybery, Wong et al., 2004; Pilowsky et al., 2003; Whitehouse et al., 2007] may have found no overlap between the broader phenotypes of these disorders because they combined samples of relatives of autistic children with and without language impairment. One of these studies attempted to investigate this in parents of autistic children but had small sample sizes, characterized language impairment in the proband using only one measure, and only included relatives of higher-functioning children [Whitehouse et al., 2007]. In addition, the majority of studies on the broader phenotype in autism investigated either parents or siblings. Only one study included probands, siblings, and parents, but it was limited to comparisons of families with children with autism to those with typically developing children and only focused on deficits in phonological processing [Bishop, Maybery, Wong et al., 2004].
In the current study, we included families of autistic children without language impairment (ALN), families of autistic children with language impairment (ALI), and families of children with SLI. We studied the proband, both parents, and the sibling closest in age to the proband in each family. All probands were thoroughly assessed to confirm diagnoses, and SLI probands who exhibited autistic symptoms (i.e., met diagnostic cutoffs for social impairments or the presence of stereotyped or repetitive behaviors) were excluded from the sample. Language impairment was defined with tests that detect clinically significant language impairments in older children [Bishop et al., 1996; Conti-Ramsden, 2003; Conti-Ramsden, Botting, & Faragher, 2001; for a review, see Coady & Evans, 2008], demonstrate heritability in SLI [Barry et al., 2007; Bishop et al., 1996, 1999], and are highly sensitive in identifying language impairment in children with autism [Kjelgaard & Tager-Flusberg, 2001]. To address whether the linguistic deficits observed in ASD are secondary to the ASD phenotype, as suggested by Whitehouse et al. , we investigated the relationship between performance on language and non-word repetition tests and scores on the algorithm domains of the ADI-R and ADOS. Group comparisons were also made on a wide variety of measures, including assessments of intelligence, receptive and expressive language, phonological processing, lexical comprehension, and reading ability, in probands, siblings, mothers, and fathers from these families. We hypothesized that ALN probands and family members would perform better than ALI and SLI families on these measures and that ALI and SLI probands and family members would perform similarly. Such findings would provide strong support for the view that the language impairments in ALI and SLI are based on the same etiology. Impaired performance in relatives of ALI children vs. relatives of ALN children would suggest that the language difficulties observed in these children are familial, whereas comparable performance would suggest that these language difficulties are not part of the broader ASD phenotype.