Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation.

The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.

A longitudinal investigation of pragmatic language across contexts in autism and related neurodevelopmental conditions.

Background: Pragmatic language, or the use of language in social contexts, is a critical skill in daily life, supporting social interactions and the development of meaningful social relationships. Pragmatic language is universally impacted in autism spectrum disorder (ASD) and pragmatic deficits are also common in other neurodevelopmental conditions, particularly those related to ASD, such as fragile X syndrome (FXS). This study used a multi-method, longitudinal approach to characterize potentially unique pragmatic profiles across different neurodevelopmental disabilities, and across contexts that varied in degree of social demand. The utility of computational linguistic analyses, as an efficient tool for capturing pragmatic abilities, was also explored. Methods: Pragmatic skills of boys with idiopathic ASD (ASD-O, n = 43), FXS with and without ASD (FXS-ASD, n = 57; FXS-O, n = 14), Down syndrome (DS, n = 22), and typical development (TD, n = 24) were compared using variables obtained from a standardized measure, narrative, and semi-naturalistic conversation at up to three time points. Results: Pragmatic language was most significantly impacted among males with ASD-O and FXS-ASD across all three contexts, with more difficulties in the least structured context (conversation), and also some differences based on FXS comorbidity. Patterns of group differences were more nuanced for boys with FXS-O and DS, with context having less of an impact. Clinical groups demonstrated minimal changes in pragmatic skills with age, with some exceptions. Computational language measurement tools showed some utility for measuring pragmatic skills, but were not as successful as traditional methods at capturing differences between clinical groups. Conclusion: Overlap and differences between ASD and other forms of neurodevelopmental disability in general, and between idiopathic and syndromic ASD in particular, have important implications for developing precisely tailored assessment and intervention approaches, consistent with a personalized medicine approach to clinical study and care in ASD.

Differences in speech articulatory timing and associations with pragmatic language ability in autism.

Background: Speech articulation difficulties have not traditionally been considered to be a feature of Autism Spectrum Disorder (ASD). In contrast, speech prosodic differences have been widely reported in ASD, and may even be expressed in subtle form among clinically unaffected first-degree relatives, representing the expression of underlying genetic liability. Some evidence has challenged this traditional dichotomy, suggesting that differences in speech articulatory mechanisms may be evident in ASD, and potentially related to perceived prosodic differences. Clinical measurement of articulatory skills has traditionally been phoneme-based, rather than by acoustic measurement of motor control. Subtle differences in articulatory/motor control, prosodic characteristics (acoustic), and pragmatic language ability (linguistic) may each be contributors to differences perceived by listeners, but the interrelationship is unclear. In this study, we examined the articulatory aspects of this relationship, in speech samples from individuals with ASD and their parents during narration. Method: Using Speechmark® analysis, we examined articulatory landmarks, fine-grained representations of articulatory timing as series of laryngeal and vocal-tract gestures pertaining to prosodic elements crucial for conveying pragmatic information. Results: Results revealed articulatory timing differences in individuals with ASD but not their parents, suggesting that although potentially not influenced by broader genetic liability to ASD, subtle articulatory differences may indeed be evident in ASD as the recent literature indicates. A follow-up path analysis detected associations between articulatory timing differences and prosody, and subsequently, pragmatic language ability. Conclusion: Together, results suggest a complex relationship where subtle differences in articulatory timing may result in atypical acoustic signals, and serve as a distal mechanistic contributor to pragmatic language ability ASD.

A profile of prosodic speech differences in individuals with autism spectrum disorder and first-degree relatives.

BACKGROUND: Impairments in prosody (e.g., intonation, stress) are among the most notable communication characteristics of individuals with autism spectrum disorder (ASD) and can significantly impact communicative interactions. Evidence suggests that differences in prosody may be evident among first-degree relatives of autistic individuals, indicating that genetic liability to ASD is expressed through prosodic variation, along with subclinical traits referred to as the broad autism phenotype (BAP). This study aimed to further characterize prosodic profiles associated with ASD and the BAP to better understand the clinical and etiologic significance of prosodic differences. METHOD: Autistic individuals, their parents, and respective control groups completed the Profiling Elements of Prosody in Speech-Communication (PEPS-C), an assessment of receptive and expressive prosody. Responses to expressive subtests were further examined using acoustic analyses. Relationships between PEPS-C performance, acoustic measurements, and pragmatic language ability in conversation were assessed to understand how differences in prosody might contribute to broader ASD-related pragmatic profiles. RESULTS: In ASD, receptive prosody deficits were observed in contrastive stress. With regard to expressive prosody, both the ASD and ASD Parent groups exhibited reduced accuracy in imitation, lexical stress, and contrastive stress expression compared to respective control groups, though no acoustic differences were noted. In ASD and Control groups, lower accuracy across several PEPS-C subtests and acoustic measurements related to increased pragmatic language violations. In parents, acoustic measurements were tied to broader pragmatic language and personality traits of the BAP. CONCLUSION: Overlapping areas of expressive prosody differences were identified in ASD and parents, providing evidence that prosody is an important language-related ability that may be impacted by genetic risk of ASD.

[Formula: see text] A cross-cultural study of visual attention in autism spectrum disorder.

Differences in visual attention have been documented in ASD, and appear linked to clinical symptoms. However, most research has been conducted in Western cultures. Because striking differences in visual attention patterns have been documented in other cultures, it is important to understand how culture may influence attentional patterns in ASD. This study compared differences in visual attention in ASD across Western and East Asian cultures, where differences in attention to contextual and global information have been repeatedly demonstrated, to investigate potential culturally-specific ASD phenotypes. One hundred thirty-two total participants included individuals with ASD (n = 24) and controls (n = 47) from Hong Kong (HK), along with a previously studied group of age- and IQ-comparable participants from the United States (n = 26 ASD; n = 35 control). Gaze was tracked while participants completed two narrative tasks that differed in social-emotional complexity. Proportions of fixations to face, bodies, and setting were examined across groups using linear mixed-effect models and a series of growth curve models. Cultural differences were found across tasks and groups. Both the ASD and control HK groups attended more to global contextual setting information, more to the body regions, and less toward faces of characters compared to US groups. Growth curve models indicated that these differences attenuated over time in certain stimuli. ASD-related effects were only observed in the more complex stimuli depicting characters with ambiguous facial expressions. Findings indicate a notable cultural influence on visual attention patterns in ASD, and underscore the importance of stimuli complexity in differentiating cultural versus diagnostic effects on attentional styles.

Neural Processing of Speech Sounds in ASD and First-Degree Relatives.

Efficient neural encoding of sound plays a critical role in speech and language, and when impaired, may have reverberating effects on communication skills. This study investigated disruptions to neural processing of temporal and spectral properties of speech in individuals with ASD and their parents and found evidence of inefficient temporal encoding of speech sounds in both groups. The ASD group further demonstrated less robust neural representation of spectral properties of speech sounds. Associations between neural processing of speech sounds and language-related abilities were evident in both groups. Parent-child associations were also detected in neural pitch processing. Together, results suggest that atypical neural processing of speech sounds is a heritable ingredient contributing to the ASD language phenotype.

One size does not fit all for parent-mediated autism interventions: A randomized clinical trial.

LAY ABSTRACT: Parent-mediated interventions support parents' use of language facilitation strategies to improve their autistic child's communication and language development. To improve the effectiveness of parent-mediated interventions, it is important to individualize interventions. This article evaluates how different components of parent-mediated interventions and mothers' learning styles influence the effectiveness of the intervention. In a randomized clinical trial, mothers were taught to use one of two types of language facilitation strategies: responsive and directive. Mothers' learning styles were characterized by the Broad Autism Phenotype (BAP) and their natural tendency to use language facilitation strategies before intervention. Findings suggest that it was easier for all mothers (irrespective of learning style) to use responsive strategies compared to directive strategies. In addition, mothers with learning styles that were not consistent with the BAP were more likely to benefit from the intervention if they did not naturally use strategies before the intervention. In contrast, mothers with learning styles that were consistent with the BAP were more likely to benefit from the intervention if they did naturally use strategies before the intervention. Teaching mothers to use responsive strategies results in greater strategy use. Consideration of BAP and mothers' natural use of language facilitation strategies may inform intervention individualization.

Childhood Academic Performance: A Potential Marker of Genetic Liability to Autism.

Autism spectrum disorder (ASD), a heritable neurodevelopmental disorder, confers genetic liability that is often expressed among relatives through subclinical, genetically-meaningful traits, or endophenotypes. For instance, relative to controls, parents of individuals with ASD differ in language-related skills, with differences emerging in childhood. To examine ASD-related endophenotypes, this study investigated developmental academic profiles among clinically unaffected siblings of individuals with ASD (n = 29). Lower performance in language-related skills among siblings mirrored previously-reported patterns among parents, which were also associated with greater subclinical ASD-related traits in themselves and their parents, and with greater symptom severity in their sibling with ASD. Findings demonstrated specific phenotypes, derived from standardized academic testing, that may represent childhood indicators of genetic liability to ASD in first-degree relatives.

Slower Peak Pupillary Response to Emotional Faces in Parents of Autistic Individuals.

Background: Atypical autonomic arousal has been consistently documented in autism spectrum disorder (ASD) and is thought to contribute to the social-communication phenotype of ASD. Some evidence suggests that clinically unaffected first-degree relatives of autistic individuals may also show subtle differences in indices of autonomic arousal, potentially implicating heritable pathophysiological mechanisms in ASD. This study examined pupillary responses in parents of autistic individuals to investigate evidence that atypical autonomic arousal might constitute a subclinical physiological marker of ASD heritability within families of autistic individuals. Methods: Pupillary responses to emotional faces were measured in 47 ASD parents and 20 age-matched parent controls. Macro-level pupillary responses (e.g., mean, peak, latency to peak) and dynamic pupillary responses over the course of the stimulus presentation were compared between groups, and in relationship to subclinical ASD-related features in ASD parents. A small ASD group (n = 20) and controls (n = 17) were also included for exploratory analyses of parent-child correlations in pupillary response. Results: Parents of autistic individuals differed in the time course of pupillary response, exhibiting a later primary peak response than controls. In ASD parents, slower peak response was associated with poorer pragmatic language and larger peak response was associated with poorer social cognition. Exploratory analyses revealed correlations between peak pupillary responses in ASD parents and mean and peak pupillary responses in their autistic children. Conclusion: Differences in pupillary responses in clinically unaffected parents, together with significant correlations with ASD-related features and significant parent-child associations, suggest that pupillary responses to emotional faces may constitute an objective physiological marker of ASD genetic liability, with potential to inform the mechanistic underpinnings of ASD symptomatology.

Verbal entrainment in autism spectrum disorder and first-degree relatives.

Entrainment, the unconscious process leading to coordination between communication partners, is an important dynamic human behavior that helps us connect with one another. Difficulty developing and sustaining social connections is a hallmark of autism spectrum disorder (ASD). Subtle differences in social behaviors have also been noted in first-degree relatives of autistic individuals and may express underlying genetic liability to ASD. In-depth examination of verbal entrainment was conducted to examine disruptions to entrainment as a contributing factor to the language phenotype in ASD. Results revealed distinct patterns of prosodic and lexical entrainment in individuals with ASD. Notably, subtler entrainment differences in prosodic and syntactic entrainment were identified in parents of autistic individuals. Findings point towards entrainment, particularly prosodic entrainment, as a key process linked to social communication difficulties in ASD and reflective of genetic liability to ASD.

Cross-linguistic patterns of speech prosodic differences in autism: A machine learning study.

Differences in speech prosody are a widely observed feature of Autism Spectrum Disorder (ASD). However, it is unclear how prosodic differences in ASD manifest across different languages that demonstrate cross-linguistic variability in prosody. Using a supervised machine-learning analytic approach, we examined acoustic features relevant to rhythmic and intonational aspects of prosody derived from narrative samples elicited in English and Cantonese, two typologically and prosodically distinct languages. Our models revealed successful classification of ASD diagnosis using rhythm-relative features within and across both languages. Classification with intonation-relevant features was significant for English but not Cantonese. Results highlight differences in rhythm as a key prosodic feature impacted in ASD, and also demonstrate important variability in other prosodic properties that appear to be modulated by language-specific differences, such as intonation.

A constellation of eye-tracking measures reveals social attention differences in ASD and the broad autism phenotype.

BACKGROUND: Social attention differences, expressed through gaze patterns, have been documented in autism spectrum disorder (ASD), with subtle differences also reported among first-degree relatives, suggesting a shared genetic link. Findings have mostly been derived from standard eye-tracking methods (total fixation count or total fixation duration). Given the dynamics of visual attention, these standard methods may obscure subtle, yet core, differences in visual attention mechanisms, particularly those presenting sub-clinically. This study applied a constellation of eye-tracking analyses to gaze data from individuals with ASD and their parents. METHODS: This study included n = 156 participants across groups, including ASD (n = 24) and control (n = 32) groups, and parents of individuals with ASD (n = 61) and control parents (n = 39). A complex scene with social/non-social elements was displayed and gaze tracked via an eye tracker. Eleven analytic methods from the following categories were analyzed: (1) standard variables, (2) temporal dynamics (e.g., gaze over time), (3) fixation patterns (e.g., perseverative or regressive fixations), (4) first fixations, and (5) distribution patterns. MANOVAs, growth curve analyses, and Chi-squared tests were applied to examine group differences. Finally, group differences were examined on component scores derived from a principal component analysis (PCA) that reduced variables to distinct dimensions. RESULTS: No group differences emerged among standard, first fixation, and distribution pattern variables. Both the ASD and ASD parent groups demonstrated on average reduced social attention over time and atypical perseverative fixations. Lower social attention factor scores derived from PCA strongly differentiated the ASD and ASD parent groups from controls, with parent findings driven by the subset of parents demonstrating the broad autism phenotype. LIMITATIONS: To generalize these findings, larger sample sizes, extended viewing contexts (e.g., dynamic stimuli), and even more eye-tracking analytical methods are needed. CONCLUSIONS: Fixations over time and perseverative fixations differentiated ASD and the ASD parent groups from controls, with the PCA most robustly capturing social attention differences. Findings highlight their methodological utility in studies of the (broad) autism spectrum to capture nuanced visual attention differences that may relate to clinical symptoms in ASD, and reflect genetic liability in clinically unaffected relatives. This proof-of-concept study may inform future studies using eye tracking across populations where social attention is impacted.

A Longitudinal Study of Parent-Child Interactions and Language Outcomes in Fragile X Syndrome and Other Neurodevelopmental Disorders.

Difficulties with pragmatic language (i.e., language in social contexts, such as conversational ability) are a noted characteristic of the language profiles of both fragile X syndrome (FXS) and autism spectrum disorder (ASD), conditions which show significant phenotypic overlap. Understanding the origins and developmental course of pragmatic language problems in FXS and other developmental conditions associated with language impairment is a critical step for the development of targeted interventions to promote communicative competence across the lifespan. This study examined pragmatic language in the context of parent-child interactions in school-age children with FXS (who did and did not meet ASD criteria on the ADOS; n = 85), idiopathic ASD (n = 32), Down syndrome (DS; n = 38), and typical development (TD; n = 39), and their parents. Parent-child communicative interactions were examined across multiple contexts, across groups, and in relationship to pragmatic language outcomes assessed 2 years later. Results showed both overlapping and divergent patterns across the FXS-ASD and idiopathic ASD child and parent groups, and also highlighted key differences in pragmatic profiles based on situational context, with more pragmatic language difficulties occurring for both ASD groups in less structured interactions. Differences in parental language styles during parent-child interactions were associated with child language outcomes, likely reflecting the complex interplay of discourse style inherent to a parent, with the inevitable influence of child characteristics on parent language as well. Together, findings help delineate the dynamic and multifactorial nature of impaired pragmatic skills among children with FXS and other neurodevelopmental disorders associated with language impairment, with potential implications for the development of targeted interventions for pragmatic communication skills.

The Phenotypic Profile Associated With the FMR1 Premutation in Women: An Investigation of Clinical-Behavioral, Social-Cognitive, and Executive Abilities.

The FMR1 gene in its premutation (PM) state has been linked to a range of clinical and subclinical phenotypes among FMR1 PM carriers, including some subclinical traits associated with autism spectrum disorder (ASD). This study attempted to further characterize the phenotypic profile associated with the FMR1 PM by studying a battery of assessments examining clinical-behavioral traits, social-cognitive, and executive abilities in women carrying the FMR1 PM, and associations with FMR1-related variability. Participants included 152 female FMR1 PM carriers and 75 female controls who were similar in age and IQ, and screened for neuromotor impairments or signs of fragile X-associated tremor/ataxia syndrome. The phenotypic battery included assessments of ASD-related personality and language (i.e., pragmatic) traits, symptoms of anxiety and depression, four different social-cognitive tasks that tapped the ability to read internal states and emotions based on different cues (e.g., facial expressions, biological motion, and complex social scenes), and a measure of executive function. Results revealed a complex phenotypic profile among the PM carrier group, where subtle differences were observed in pragmatic language, executive function, and social-cognitive tasks that involved evaluating basic emotions and trustworthiness. The PM carrier group also showed elevated rates of ASD-related personality traits. In contrast, PM carriers performed similarly to controls on social-cognitive tasks that involved reliance on faces and biological motion. The PM group did not differ from controls on self-reported depression or anxiety symptoms. Using latent profile analysis, we observed three distinct subgroups of PM carriers who varied considerably in their performance across tasks. Among PM carriers, CGG repeat length was a significant predictor of pragmatic language violations. Results suggest a nuanced phenotypic profile characterized by subtle differences in select clinical-behavioral, social-cognitive, and executive abilities associated with the FMR1 PM in women.

A cross-cultural study showing deficits in gaze-language coordination during rapid automatized naming among individuals with ASD.

Individuals with autism spectrum disorder (ASD) and their first-degree relatives demonstrate automaticity deficits reflected in reduced eye-voice coordination during rapid automatized naming (RAN), suggesting that RAN deficits may be a genetically meaningful marker of ASD language-related impairments. This study investigated whether RAN deficits in ASD extend to a language typologically distinct from English. Participants included 23 Cantonese-speaking individuals with ASD and 39 controls from Hong Kong (HK), and age- and IQ-comparable groups of previously-studied English-speaking individuals with ASD (n = 45) and controls (n = 44) from the US. Participants completed RAN on an eye tracker. Analyses examined naming time, error rate, measures of eye movement reflecting language automaticity, including eye-voice span (EVS; location of eyes versus the named item) and refixations. The HK-ASD group exhibited longer naming times and more refixations than HK-Controls, in a pattern similar to that observed in the US-ASD group. Cultural effects revealed that both HK groups showed longer EVS and more fixations than US groups. Naming time and refixation differences may be ASD-specific impairments spanning cultures/languages, whereas EVS and fixation frequency may be more variably impacted. A potential underlying mechanism of visual "stickiness" may be contributing to this breakdown in language automaticity in ASD.

Emergence of Developmental Delay in Infants and Toddlers With an FMR1 Mutation.

BACKGROUND: Children with FMR1 gene expansions are known to experience a range of developmental challenges, including fragile X syndrome. However, little is known about early development and symptom onset, information that is critical to guide earlier identification, more accurate prognoses, and improved treatment options. METHODS: Data from 8 unique studies that used the Mullen Scales of Early Learning to assess children with an FMR1 gene expansion were combined to create a data set of 1178 observations of >500 young children. Linear mixed modeling was used to explore developmental trajectories, symptom onset, and unique developmental profiles of children <5 years of age. RESULTS: Boys with an FMR1 gene full mutation showed delays in early learning, motor skills, and language development as young as 6 months of age, and both sexes with a full mutation were delayed on all developmental domains by their second birthday. Boys with a full mutation continued to gain skills over early childhood at around half the rate of their typically developing peers; girls with a full mutation showed growth at around three-quarters of the rate of their typically developing peers. Although children with a premutation were mostly typical in their developmental profiles and trajectories, mild but significant delays in fine motor skills by 18 months were detected. CONCLUSIONS: Children with the FMR1 gene full mutation demonstrate significant developmental challenges within the first 2 years of life, suggesting that earlier identification is needed to facilitate earlier implementation of interventions and therapeutics to maximize effectiveness.

A Unique Visual Attention Profile Associated With the FMR1 Premutation.

Atypical visual attention patterns have been observed among carriers of the fragile X mental retardation gene (FMR1) premutation (PM), with some similarities to visual attention patterns observed in autism spectrum disorder (ASD) and among clinically unaffected relatives of individuals with ASD. Patterns of visual attention could constitute biomarkers that can help to inform the neurocognitive profile of the PM, and that potentially span diagnostic boundaries. This study examined patterns of eye movement across an array of fixation measurements from three distinct eye-tracking tasks in order to investigate potentially overlapping profiles of visual attention among PM carriers, ASD parents, and parent controls. Logistic regression analyses were conducted to examine whether variables constituting a PM-specific looking profile were able to effectively predict group membership. Participants included 65PM female carriers, 188 ASD parents, and 84 parent controls. Analyses of fixations across the eye-tracking tasks, and their corresponding areas of interest, revealed a distinct visual attention pattern in carriers of the FMR1 PM, characterized by increased fixations on the mouth when viewing faces, more intense focus on bodies in socially complex scenes, and decreased fixations on salient characters and faces while narrating a wordless picture book. This set of variables was able to successfully differentiate individuals with the PM from controls (Sensitivity = 0.76, Specificity = 0.85, Accuracy = 0.77) as well as from ASD parents (Sensitivity = 0.70, Specificity = 0.80, Accuracy = 0.72), but did not show a strong distinction between ASD parents and controls (Accuracy = 0.62), indicating that this set of variables comprises a profile that is unique to PM carriers. Regarding predictive power, fixations toward the mouth when viewing faces was able to differentiate PM carriers from both ASD parents and controls, whereas fixations toward other social stimuli did not differentiate PM carriers from ASD parents, highlighting some overlap in visual attention patterns that could point toward shared neurobiological mechanisms. Results demonstrate a profile of visual attention that appears strongly associated with the FMR1 PM in women, and may constitute a meaningful biomarker.

Lifelong Tone Language Experience does not Eliminate Deficits in Neural Encoding of Pitch in Autism Spectrum Disorder.

Atypical pitch processing is a feature of Autism Spectrum Disorder (ASD), which affects non-tone language speakers' communication. Lifelong auditory experience has been demonstrated to modify genetically-predisposed risks for pitch processing. We examined individuals with ASD to test the hypothesis that lifelong auditory experience in tone language may eliminate impaired pitch processing in ASD. We examined children's and adults' Frequency-following Response (FFR), a neurophysiological component indexing early neural sensory encoding of pitch. Univariate and machine-learning-based analytics suggest less robust pitch encoding and diminished pitch distinctions in the FFR from individuals with ASD. Contrary to our hypothesis, results point to a linguistic pitch encoding impairment associated with ASD that may not be eliminated even by lifelong sensory experience.

Elevated Polygenic Burden for Autism Spectrum Disorder Is Associated With the Broad Autism Phenotype in Mothers of Individuals With Autism Spectrum Disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder that encompasses a complex and heterogeneous set of traits. Subclinical traits that mirror the core features of ASD, referred to as the broad autism phenotype (BAP), have been documented repeatedly in unaffected relatives and are believed to reflect underlying genetic liability to ASD. The BAP may help inform the etiology of ASD by allowing the stratification of families into more phenotypically and etiologically homogeneous subgroups. This study explores polygenic scores related to the BAP. METHODS: Phenotypic and genotypic information were obtained from 2614 trios from the Simons Simplex Collection. Polygenic scores of ASD (ASD-PGSs) were generated across the sample to determine the shared genetic overlap between the BAP and ASD. Maternal and paternal ASD-PGSs were explored in relation to BAP traits and their child's ASD symptomatology. RESULTS: Maternal pragmatic language was related to child's social communicative atypicalities. In fathers, rigid personality was related to increased repetitive behaviors in children. Maternal (but not paternal) ASD-PGSs were related to the pragmatic language and rigid BAP domains. CONCLUSIONS: Associations emerged between parent and child phenotypes, with more associations emerging in mothers than in fathers. ASD-PGS associations emerged with BAP in mothers only, highlighting the potential for a female protective factor, and implicating the polygenic etiology of ASD-related phenotypes in the BAP.

An Acoustic Characterization of Prosodic Differences in Autism Spectrum Disorder and First-Degree Relatives.

This study examined prosody through characterization of acoustic properties of the speech of individuals with ASD and their parents, during narration. A subset of utterances were low-pass filtered and rated for differences in intonation, speech rate, and rhythm. Listener ratings were minimally related to acoustic measures, underscoring the complexity of atypical prosody in ASD. Acoustic analyses revealed greater utterance-final fundamental frequency excursion size and slower speech rate in the ASD group. Slower speech rate was also evident in the ASD parent group, particularly parents with the broad autism phenotype. Overlapping prosodic differences in ASD and ASD Parent groups suggest that prosodic differences may constitute an important phenotype contributing to ASD features and index genetic liability to ASD among first-degree relatives.