Research Interests:
Research Interests:
There has been increasing attention to the assessment of minimally verbal (MV) children with autism spectrum disorder (ASD). Previous research has begun to examine the relationship between verbal abilities and emotional and behavioral... more
There has been increasing attention to the assessment of minimally verbal (MV) children with autism spectrum disorder (ASD). Previous research has begun to examine the relationship between verbal abilities and emotional and behavioral problems (EBP). The current study compared parent‐reported EBP in children of differing language levels on two instruments commonly used in ASD research and clinical practice, the Child Behavior Checklist (CBCL) and Aberrant Behavior Checklist (ABC). The study consisted of 1,937 6–18 years old children with ASD from the Simons Simplex Collection. Children were divided into three language groups, by ADOS module (Module 1 = MV, 2 = phrase speech (PS), and 3 = verbally fluent (VF)) and then compared on CBCL and ABC subscales. The ABC and CBCL showed different patterns of elevations across the language groups. MV children were reported to have more impairment than VF children on the ABC irritability, lethargy, and hyperactivity scales. Children with less language (MV and PS) exhibited less impairment on the CBCL internalizing domain than VF children, but did not differ on the externalizing domain. Post hoc comparisons showed that internalizing differences were driven by fewer children with less language exhibiting clinically elevated anxious/depressed scores compared to VF children. The present study underscores the significance of considering language when assessing EBP. Results have implications for the psychiatric screening of children with ASD, particularly those with language impairments. Researchers should exercise caution when applying EBP instruments designed for use with different populations and purposes to broad samples of children. Autism Res 2019, 12: 1367–1375. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.
Research Interests:
LAY ABSTRACT Previous research has suggested that focusing on impairments can be detrimental to the well-being of autistic individuals, yet little research has focused on strengths and positive qualities in autism. Some studies explored... more
LAY ABSTRACT Previous research has suggested that focusing on impairments can be detrimental to the well-being of autistic individuals, yet little research has focused on strengths and positive qualities in autism. Some studies explored "savant skills" (herein referred to as "extraordinary talents"), that is, skills that stand out compared to the general population. These often group everyone who has a specific talent, rather than exploring subgroups with strengths in specific areas. There has been even less research focused on personal strengths (i.e. skills that stand out relative to the individual's other abilities, but not the general population). To expand this research, we use a sample of 1470 children (ages 4-18 years) from the Simons Simplex Collection without cognitive impairment to examine the relationship between having a parent-reported skill in a specific area and performance on a standardized cognitive test. Almost half (46%) had at least one pa...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
This study explored change in social-communicative symptoms in 140 individuals with childhood autism spectrum disorder (ASD) diagnoses. Trajectories of caregiver-reported social-communicative symptoms were examined for three groups... more
This study explored change in social-communicative symptoms in 140 individuals with childhood autism spectrum disorder (ASD) diagnoses. Trajectories of caregiver-reported social-communicative symptoms were examined for three groups (verbal, delayed speech, minimally verbal) from ages 2 to 19 years. Groups showed comparable levels of social-communicative impairment at 2 years and significant decreases in overall symptom levels across the 17-year period (P < .001). Across three subdomains, main effects of time and language (P < .001) reflected patterns of overall improvement, although children with more impaired language tended to have more caregiver-reported symptoms relative to verbal peers. A significant time-by-language interaction (P < .001) reflected that trajectories of socioemotional reciprocity symptoms differed according to patterns of language development. In contrast, improvements in the nonverbal communication domain were seen across language groups, whereas defi...
Research Interests:
Research Interests:
This study examined variability in autism symptom trajectories in toddlers referred for possible autism spectrum disorder (ASD) who had frequent observations from 14 to 36 months of age. In total, 912 observations of the Autism Diagnostic... more
This study examined variability in autism symptom trajectories in toddlers referred for possible autism spectrum disorder (ASD) who had frequent observations from 14 to 36 months of age. In total, 912 observations of the Autism Diagnostic Observation Schedule (ADOS) were obtained from 149 children (103 with ASD) followed from 14 to 36 months of age. As a follow-up to a previous analysis of ADOS algorithm scores, a different analytic approach (Proc Traj) was implemented to identify several courses of symptom trajectories using ADOS Calibrated Severity Scores in a larger sample. Proc Traj is a statistical method that clusters individuals into separate groups based on different growth trajectories. Changes in symptom severity based on individual ADOS items also were examined. Trajectory analysis of overall symptom severity identified 4 clusters (non-spectrum ∼25%; worsening ∼27%; moderately-improving ∼25%; severe-persistent ∼23%). Trajectory clusters varied significantly in the proportions of confirmatory ASD diagnosis, level of baseline and final verbal and nonverbal abilities, and symptom severity. For the moderately-improving group, social communication improved, whereas restricted and repetitive behaviors were stable over time. Language and verbal and nonverbal communication improved for many children, but several social affect and restricted and repetitive behavior symptoms remained stable or worsened. Significant variability in symptom trajectories was observed among toddlers referred for possible ASD. Changes in social and restricted and repetitive behavior domain scores did not always co-occur. Similarly, item-level trajectories did not always align with trajectories of overall severity scores. These findings highlight the importance of monitoring individual symptoms within broader symptom domains when conducting repeated assessments for young children with suspected ASD.
Research Interests:
Research Interests:
This study examined early predictors of and changes in school-age academic achievement and class placement in children referred for autism spectrum disorder (ASD) at age 2. Of 111 ASD referrals, 74 were diagnosed with ASD at age 18.... more
This study examined early predictors of and changes in school-age academic achievement and class placement in children referred for autism spectrum disorder (ASD) at age 2. Of 111 ASD referrals, 74 were diagnosed with ASD at age 18. Regression analyses were performed to identify age 3 predictors of achievement in arithmetic, passage comprehension, word reading, and spelling at ages 9 and 18. Linear Mixed Models were used to examine predictors of academic growth between ages 9 and 18. Academic skills varied widely at 9 and 18, but were mostly commensurate with or higher than expected given cognitive levels. However, 22% (age 9) and 32% (age 18) of children with average/above average IQ showed below/low average achievement in at least one academic domain. Children who remained in general education/inclusion classrooms had higher achievement than those who moved to special education classrooms. Stronger cognitive skills at age 3 and 9 predicted better academic achievement and faster academic growth from age 9 to 18. Parent participation in intervention by age 3 predicted better achievement at age 9 and 18. Many children with ASD achieve basic academic skills commensurate with or higher than their cognitive ability. However, more rigorous screening for learning difficulties may be important for those with average cognitive skills because a significant minority show relative academic delays. Interventions targeting cognitive skills and parent participation in early treatment may have cascading effects on long-term academic development.
Research Interests:
Research Interests:
Literature indicates that some children with ASD may show behavioral improvements during fever; however, little is known about the behavioral profiles of these children. This study aims to (a) investigate the subset of children who show... more
Literature indicates that some children with ASD may show behavioral improvements during fever; however, little is known about the behavioral profiles of these children. This study aims to (a) investigate the subset of children who show parent-reported behavioral improvements associated with fever and (b) compare the demographic, behavioral, and genetic characteristics of this subset of children to children whose parents report no change during fever. Parents of 2,152 children from the Simons Simplex Collection provided information about whether and in which areas their child improved during fever. Children were randomly assigned into discovery or replication samples. In discovery analyses, children who reportedly improved with fever (Improve Group) were compared to those who reportedly did not improve (No Improve Group) on demographics, medical history, ASD symptoms, adaptive skills, and presence of de novo ASD-associated mutations. Significant and marginal results from discovery analyses were tested in the replication sample. Parent reports of 17% of children indicated improvements during fever across a range of domains. Discovery and replication analyses revealed that the Improve Group had significantly lower non-verbal cognitive skills (NVIQ) and language levels and more repetitive behaviors. Groups did not differ on demographic variables, parent-report of current ASD symptoms or the presence of de novo mutations. Understanding the profiles of children who improve during episodes of fever may provide insights into innovative treatments for ASD. Autism Res 2018, 11: 175-184. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. This study explored characteristics of children with ASD who are reported to improve during fever. Parents of 17% of children with ASD report improvements across a range of domains during fever including cognition, communication, repetitive behaviors, social interaction, and behavior. Children who are reported to improve during fever have significantly lower non-verbal cognitive skills and language levels and more repetitive behaviors. Understanding the profiles of children who improve during episodes of fever may provide insights into new treatments for ASD.
Research Interests:
Aside from features associated with risk of neurogenetic syndromes in general (e.g., cognitive impairment), limited progress has been made in identifying phenotype-genotype relationships in autism spectrum disorder (ASD). The objective of... more
Aside from features associated with risk of neurogenetic syndromes in general (e.g., cognitive impairment), limited progress has been made in identifying phenotype-genotype relationships in autism spectrum disorder (ASD). The objective of this study was to extend work in the Simons Simplex Collection by comparing the phenotypic profiles of ASD probands with or without identified de novo loss of function mutations or copy number variants in high-confidence ASD-associated genes or loci. Analyses preemptively accounted for documented differences in sex and IQ in affected individuals with de novo mutations by matching probands with and without these genetic events on sex, IQ, and age before comparing them on multiple behavioral domains. Children with de novo mutations (N=112) had a greater likelihood of motor delay during early development (later age at walking), but they were less impaired on certain measures of ASD core symptoms (parent-rated social communication abnormalities and cli...
Research Interests: Intelligence, Adolescent, Humans, Child, Female, and 14 moreMale, Developmental disabilities, Phenotype, Autism Spectrum Disorder, Genotype, Prognosis, Reference Values, Likelihood Functions, Case Control Studies, DNA mutational analysis, Child preschool, Psychology and Cognitive Sciences, Language Development Disorders, and Medical and Health Sciences
Minimally verbal (MV) children with autism spectrum disorder (ASD) are often assumed to be profoundly cognitively impaired and excluded from analyses due to challenges completing standardized testing protocols. A literature aimed at... more
Minimally verbal (MV) children with autism spectrum disorder (ASD) are often assumed to be profoundly cognitively impaired and excluded from analyses due to challenges completing standardized testing protocols. A literature aimed at increasing understanding of this subgroup is emerging; however, the many methods used to define MV status make it difficult to compare studies. Understanding how different instruments and definitions used to identify MV children affect sample composition is critical to advance research on this understudied clinical population. The MV status of 1,470 school-aged children was defined using five instruments commonly used in ASD research. MV sample composition was compared across instruments. Analyses examined the proportion of overlap across MV subgroups and the extent to which child characteristics varied across MV subgroups defined using different definitions or combinations of measures. A total of 257 children were classified as MV on at least one instrument. Proportion of overlap between definitions ranged from 3% to 100%. The stringency of definition (i.e. few-to-no vs. some words) was associated with differences in cognitive and adaptive functioning; more stringent definitions yielded greater consistency of MV status across instruments. Cognitive abilities ranged from profoundly impaired to average intelligence; 16% had NVIQ ≥ 70. Approximately half exhibited verbal skills commensurate with nonverbal cognitive ability, whereas half had verbal abilities significantly lower than their estimated NVIQ. Future studies of MV children must carefully consider the methods used to identify their sample, acknowledging that definitions including children with &amp;amp;amp;amp;#39;some words&amp;amp;amp;amp;#39; may yield larger samples with a wider range of language and cognitive abilities. Broadly defined MV samples may be particularly important to delineate factors interfering with language development in the subgroup of children whose expressive impairments are considerably below their estimated nonverbal cognitive abilities.
Research Interests:
Results: RB subtypes were identified and were elevated in the ASD group relative to the DD group at age 3. However, self-injurious behavior did not differ between groups. Volumetric findings indicate enlargement of most structures in the... more
Results: RB subtypes were identified and were elevated in the ASD group relative to the DD group at age 3. However, self-injurious behavior did not differ between groups. Volumetric findings indicate enlargement of most structures in the ASD relative to the TD group. Enlargement ...
Background: Calibrated severity scores have been created for Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) as a metric of the relative severity of autism-specific behaviors, as measured by this instrument (Gotham, Lord, &... more
Background: Calibrated severity scores have been created for Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) as a metric of the relative severity of autism-specific behaviors, as measured by this instrument (Gotham, Lord, & Pickles, 2009). Calibrated severity scores are available for modules 1-3 and soon will be available for module 4. The goal was to create a standardized score to compare autism symptoms within and across individuals, independent of age and developmental level. Calibrated severity scores for modules 1-3 had more uniform distributions across age and developmental level and were less influenced by demographic variables than ADOS-2 raw totals. A comparable metric is not yet available for the ADOS-2 Toddler Module (ADOS-T), used to assess toddlers between 12 and 30 months of age. Objectives: Standardize ADOS-T raw scores to approximate a metric of ASD-related symptom severity that is less influenced by developmental level, age, and other demographic variab...
This study assessed the utility of a brief assessment (the Peabody Picture Vocabulary Test-4th Edition; PPVT4) as a proxy for verbal IQ (VIQ) in large-scale studies of autism spectrum disorder (ASD). In a sample of 2,420 proband with ASD,... more
This study assessed the utility of a brief assessment (the Peabody Picture Vocabulary Test-4th Edition; PPVT4) as a proxy for verbal IQ (VIQ) in large-scale studies of autism spectrum disorder (ASD). In a sample of 2,420 proband with ASD, PPVT4:IQ correlations were strong. PPVT4 scores were, on average, 5.46 points higher than VIQ; 79% of children had PPVT4 scores within one standard deviation (+/-15) of their VIQ and 90% were similarly classified as having abilities above or below 70 on both measures. Distributions of PPVT4 and VIQ by de novo mutation status were highly similar. These results strongly support the utility of PPVT4 as a proxy for VIQ in large-scale ASD studies, particularly for genetic investigations.
Research Interests:
Recent updates have been proposed to the Autism Diagnostic Observation Schedule-2 Module 4 diagnostic algorithm. This new algorithm, however, has not yet been validated in an independent sample without intellectual disability (ID). This... more
Recent updates have been proposed to the Autism Diagnostic Observation Schedule-2 Module 4 diagnostic algorithm. This new algorithm, however, has not yet been validated in an independent sample without intellectual disability (ID). This multi-site study compared the original and revised algorithms in individuals with ASD without ID. The revised algorithm demonstrated increased sensitivity, but lower specificity in the overall sample. Estimates were highest for females, individuals with a verbal IQ below 85 or above 115, and ages 16 and older. Best practice diagnostic procedures should include the Module 4 in conjunction with other assessment tools. Balancing needs for sensitivity and specificity depending on the purpose of assessment (e.g., clinical vs. research) and demographic characteristics mentioned above will enhance its utility.
Research Interests:
Background: It is generally recognized that the development of autism spectrum disorders (ASD) is not uniform across children. Currently, two patterns of ASD onset are cited: early onset, which is characterized by delays and/or unusual... more
Background: It is generally recognized that the development of autism spectrum disorders (ASD) is not uniform across children. Currently, two patterns of ASD onset are cited: early onset, which is characterized by delays and/or unusual patterns of development from birth or shortly thereafter, and regressive onset, in which children experience a period of seemingly typical development, followed by a loss of previously acquired skills. Regressive onset has been reported in approximately one third of children with ASD. However the duration of loss, the types of skills lost, and the length of time that children had the skills prior to losing them are variable. The “gold standard” for assessing regression has been parent report, and the Autism Diagnostic Interview—Revised (ADI-R) is a commonly-used measure for this purpose. Recently, additional questions were created to capture subthreshold skill losses that do not meet the original ADI-R criteria for full losses. New prospective studies...
Daily living skills (DLS), such as personal hygiene, meal preparation, and money management, are important to independent living. Research suggests that many individuals with autism spectrum disorder exhibit impairments in daily living... more
Daily living skills (DLS), such as personal hygiene, meal preparation, and money management, are important to independent living. Research suggests that many individuals with autism spectrum disorder exhibit impairments in daily living skills relative to their cognitive skills. This study examined predictors of daily living skills attainment and trajectories of daily living skills in a longitudinal sample referred for possible autism spectrum disorder and followed from 2 to 21 years of age. Consistent with previous studies, participants with autism spectrum disorder and nonspectrum diagnoses showed continual development of daily living skills throughout childhood and adolescence. Early childhood nonverbal mental age was the strongest predictor of daily living skills attainment for both diagnostic groups. Group-based modeling suggested two distinct trajectories of daily living skills development for participants with autism spectrum disorder. Skill levels for both groups of young adu...
Research Interests:
Background: The Autism Diagnostic Observation Schedule (ADOS; Lord et al., 2000) is widely used in both research and clinical diagnostic evaluations. However, Module 4, the only module intended for adults, is limited to use with... more
Background: The Autism Diagnostic Observation Schedule (ADOS; Lord et al., 2000) is widely used in both research and clinical diagnostic evaluations. However, Module 4, the only module intended for adults, is limited to use with individuals who are verbally fluent. Modules 1 and 2, appropriate for individuals who are nonverbal or have limited language, have not been validated in adult samples. Because these instruments were intended for use with young children, many of the materials and activities were chosen to maximize opportunities for social interaction, such as requests and shared enjoyment, between the child and examiner. These activities and materials may not be interesting to and/or appropriate for use with adults. In addition, items used to score behavior in young children may not be of the same diagnostic utility in older individuals. Objectives: To adapt ADOS Modules 1 & 2 to be appropriate for use with adults who are nonverbal or have limited language. Methods: To create...
Research Interests:
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits... more
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequenc...
Research Interests:
Research Interests:
Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs) to autism spectrum disorder (ASD). However, challenges in the reliable detection of de novo insertions... more
Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs) to autism spectrum disorder (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR = 1.6; 95% CI = 1.0-2.7; p = 0.03), are more common in female probands (p = 0.02), are enriched among genes encoding FMRP targets (p = 6 × 10(-9)), and arise predominantly on the paternal chromosome (p < 0.001). On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E ...
Research Interests: DNA, Humans, Child, Female, Male, and 5 morePedigree, Phenotype, Sex Factors, DNA binding proteins, and Gtp Binding Proteins
Standardized Autism Diagnostic Observation Schedule (ADOS) scores provide a measure of autism severity that is less influenced by child characteristics than raw totals (Gotham et al. in Journal of Autism and Developmental Disorders,... more
Standardized Autism Diagnostic Observation Schedule (ADOS) scores provide a measure of autism severity that is less influenced by child characteristics than raw totals (Gotham et al. in Journal of Autism and Developmental Disorders, 39(5), 693–705 2009). However, these scores combine symptoms from the Social Affect (SA) and Restricted and Repetitive Behaviors (RRB) domains. Separate calibrations of each domain would provide a clearer picture of ASD dimensions. The current study separately calibrated raw totals from the ADOS SA and RRB domains. Standardized domain scores were less influenced by child characteristics than raw domain totals, thereby increasing their utility as indicators of Social-Communication and Repetitive Behavior severity. Calibrated domain scores should facilitate efforts to examine trajectories of ASD symptoms and links between neurobiological and behavioral dimensions.
Research Interests:
Background: The Social Responsiveness Scale (SRS) is a parent-completed screening questionnaire often used to measure autism spectrum disorders (ASD) severity. Although child characteristics are known to influence scores from other... more
Background: The Social Responsiveness Scale (SRS) is a parent-completed screening questionnaire often used to measure autism spectrum disorders (ASD) severity. Although child characteristics are known to influence scores from other ASD-symptom measures, as well as parent-questionnaires more broadly, there has been limited consideration of how non-ASD-specific factors may affect interpretation of SRS scores. Previous studies have explored effects of behavior problems on SRS specificity, but have not addressed influences on the use of the SRS as a quantitative measure of ASD-symptoms.Method: Raw scores (SRS-Raw) from parent-completed SRS were analyzed for 2,368 probands with ASD and 1,913 unaffected siblings. Regression analyses were used to assess associations between SRS scores and demographic, language, cognitive, and behavior measures.Results: For probands, higher SRS-Raw were associated with greater non-ASD behavior problems, higher age, and more impaired language and cognitive skills, as well as scores from other parent report measures of social development and ASD-symptoms. For unaffected siblings, having more behavior problems predicted higher SRS-Raw; male gender, younger age, and poorer adaptive social and expressive communication skills also showed small, but significant effects.Conclusions: When using the SRS as a quantitative phenotype measure, the influence of behavior problems, age, and expressive language or cognitive level on scores must be considered. If effects of non-ASD-specific factors are not addressed, SRS scores are more appropriately interpreted as indicating general levels of impairment, than as severity of ASD-specific symptoms or social impairment. Additional research is needed to consider how these factors influence the SRS’ sensitivity and specificity in large, clinical samples including individuals with disorders other than ASD.
Research Interests:
The Autism Diagnostic Interview-Revised (ADI-R) is commonly used to inform diagnoses of autism spectrum disorders (ASD). Considering the time dedicated to using the ADI-R, it is of interest to expand the ways in which information obtained... more
The Autism Diagnostic Interview-Revised (ADI-R) is commonly used to inform diagnoses of autism spectrum disorders (ASD). Considering the time dedicated to using the ADI-R, it is of interest to expand the ways in which information obtained from this interview is used. The current study examines how algorithm totals reflecting past (ADI-Diagnostic) and current (ADI-Current) behaviors are influenced by child characteristics, such as demographics, behavioral problems and developmental level. Children with less language at the time of the interview had higher ADI-Diagnostic and ADI-Current. ADI-Diagnostic totals were also associated with age; parents of older children reported more severe past behaviors. Recommendations are provided regarding the use of the ADI-R as a measure of ASD severity, taking language and age into account.
Research Interests:
Research Interests: Psychology, Cognitive Science, Language Acquisition, Autism, Psychometrics, and 18 moreLanguage, Intellectual Disability, Linear models, Down Syndrome, Interviews, Humans, Female, Male, Infant, Developmental disabilities, Clinical Sciences, Parents, Questionnaires, Longitudinal Studies, Age Factors, Nino, Child preschool, and Attention deficit disorder with hyperactivity
Research Interests:
Substantial revisions to the DSM-IV criteria for autism spectrum disorders (ASDs) have been proposed in efforts to increase diagnostic sensitivity and specificity. This study evaluated the proposed DSM-5 criteria for the single diagnostic... more
Substantial revisions to the DSM-IV criteria for autism spectrum disorders (ASDs) have been proposed in efforts to increase diagnostic sensitivity and specificity. This study evaluated the proposed DSM-5 criteria for the single diagnostic category of autism spectrum disorder in children with DSM-IV diagnoses of pervasive developmental disorders (PDDs) and non-PDD diagnoses. Three data sets included 4,453 children with DSM-IV clinical PDD diagnoses and 690 with non-PDD diagnoses (e.g., language disorder). Items from a parent report measure of ASD symptoms (Autism Diagnostic Interview-Revised) and clinical observation instrument (Autism Diagnostic Observation Schedule) were matched to DSM-5 criteria and used to evaluate the sensitivity and specificity of the proposed DSM-5 criteria and current DSM-IV criteria when compared with clinical diagnoses. Based on just parent data, the proposed DSM-5 criteria identified 91% of children with clinical DSM-IV PDD diagnoses. Sensitivity remained high in specific subgroups, including girls and children under 4. The specificity of DSM-5 ASD was 0.53 overall, while the specificity of DSM-IV ranged from 0.24, for clinically diagnosed PDD not otherwise specified (PDD-NOS), to 0.53, for autistic disorder. When data were required from both parent and clinical observation, the specificity of the DSM-5 criteria increased to 0.63. These results suggest that most children with DSM-IV PDD diagnoses would remain eligible for an ASD diagnosis under the proposed DSM-5 criteria. Compared with the DSM-IV criteria for Asperger&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disorder and PDD-NOS, the DSM-5 ASD criteria have greater specificity, particularly when abnormalities are evident from both parents and clinical observation.
Research Interests:
Elevated anxiety symptoms are one of the most common forms of psychopathology to co-occur with autism spectrum disorders (ASDs). The purpose of this study was to explore the association between anxiety and ASD symptoms, particularly the... more
Elevated anxiety symptoms are one of the most common forms of psychopathology to co-occur with autism spectrum disorders (ASDs). The purpose of this study was to explore the association between anxiety and ASD symptoms, particularly the degree to which the relationship is explained by insistence on sameness (IS) behaviors and/or cognitive ability. The sample included 1429 individuals aged 5:8–18:0 years who participated in the Simons Simplex Collection, a genetic consortium study of ASD. Child Behavior Checklist Anxiety Problems T-scores and Autism Diagnostic Interview-Revised “IS“ item raw totals were treated as both categorical and continuous measures of anxiety and IS, respectively. Chronological age, verbal intelligence quotient (IQ), and a variety of ASD phenotype-related and other behavioral variables were assessed for potential association with anxiety and IS. Anxiety and IS continuous variables were minimally, although significantly, associated with each other and with chronological age and verbal IQ. Neither anxiety nor IS was associated with other core autism diagnostic scores. Anxiety was associated with a variety of other psychiatric and behavioral symptoms in ASD, including irritability, attention problems, and aggression, while IS was not. Anxiety and IS appear to function as distinct constructs, each with a wide range of expression in children with ASD across age and IQ levels. Thus, both variables could be of use in ASD behavioral research or in dimensional approaches to genetic exploration. Unlike IS, however, anxiety is related to non-ASD-specific behavioral symptoms. Autism Res 2012, ●●: ●●–●●. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.
Research Interests:
Research suggests that restricted and repetitive behaviors (RRBs) can be subdivided into Repetitive Sensory Motor (RSM) and Insistence on Sameness (IS) behaviors. However, because the majority of previous studies have used the Autism... more
Research suggests that restricted and repetitive behaviors (RRBs) can be subdivided into Repetitive Sensory Motor (RSM) and Insistence on Sameness (IS) behaviors. However, because the majority of previous studies have used the Autism Diagnostic Interview-Revised (ADI-R), it is not clear whether these subcategories reflect the actual organization of RRBs in ASD. Using data from the Simons Simplex Collection (n = 1,825), we examined the association between scores on the ADI-R and the Repetitive Behavior Scale-Revised. Analyses supported the construct validity of RSM and IS subcategories. As in previous studies, IS behaviors showed no relationship with IQ. These findings support the continued use of RRB subcategories, particularly IS behaviors, as a means of creating more behaviorally homogeneous subgroups of children with ASD.
Research Interests:
Many chromosomal regions for susceptibility to autism spectrum disorders (ASDs) have been identified, but few have reached genomewide significance. In response, researchers have attempted to increase the power of their analyses by... more
Many chromosomal regions for susceptibility to autism spectrum disorders (ASDs) have been identified, but few have reached genomewide significance. In response, researchers have attempted to increase the power of their analyses by stratifying samples to increase phenotypic homogeneity. Although homogeneity has typically been defined by a single variable, resultant groups often differ in other dimensions that may be directly pertinent. Group differences in age, gender, IQ, and measures of autism severity are examined as related to Autism Diagnostic Interview-Revised (ADI-R) domains previously used for subsetting or Quantitative Trait Analysis (QTL). Participants were research participants and clinic referrals for assessment of possible autism. Assessments included the ADI-R, Autism Diagnostic Observation Schedule, Vineland Adaptive Behavior Scales, and a developmental or cognitive test. Data were collected for 983 individuals, ages 4 to 52 years, with diagnoses of autism and ASDs. Findings suggest that, of several potential grouping variables, only restricted and repetitive behaviors associated with Insistence on Sameness were independent of age, IQ, and autism severity. Results emphasize the potential unintended effects of stratification and the importance of understanding such interrelationships between phenotypic characteristics when defining subgroups or performing QTL.
Research Interests: Genetics, Autism, Language, Adolescent, Biological Sciences, and 17 moreBiological Psychiatry, Humans, Child, Biomedical Research, Interview, Female, Male, Phenotype, Autism Spectrum Disorder, Middle Aged, Adult, Sex Factors, Age Factors, Homogeneity, Severity of Illness Index, Autistic disorder, and Child preschool
Research Interests: Intelligence, Family, Biological Sciences, Biological Psychiatry, Humans, and 8 moreChild, Female, Male, IQ, Head, Adult, Asd, and Autistic disorder
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more... more
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small…
Research Interests:
Research Interests:
Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo... more
Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals. By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status. By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating. Our results, when viewed in the context of results from genome-wide association studies, demonstrate that a myriad of common variants of very small effect impacts ASD liability.
Research Interests: Genetics, Cognitive development, Social Interaction, Intellectual Disability, Multidisciplinary, and 18 moreNature, Signal Transduction, Social behavior, Humans, Child, Redes sociales, Europe, Cytoprotection, Gene Dosage, Marketing en internet, Autism Spectrum Disorder, Copy Number Variation, Negocios por Internet, Social Behavior, Ganar Dinero En Internet, Ventas En Internet, Trabajar Dese Casa, and Case Control Studies
Research Interests: Psychology, Cognitive Science, Communication, Decision Making, Communication Disorders, and 19 moreAutism, Psychometrics, Evaluation, Nonverbal Communication, Adolescent, Screening, Social behavior, Humans, Child, Questionnaire, Female, Male, ROC Curve, Clinical Sciences, Questionnaires, Signal Detection, Social Behavior, Nino, and Autistic disorder
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome... more
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
Research Interests:
Research Interests: Mathematics, Algorithms, Education, Autism, Psychometrics, and 31 morePersonality Assessment, Attention, Observation, Affect, Test Validation, Social behavior, Humans, Female, Predictive Validity, Male, Verbal behavior, Infant, Developmental disabilities, Differential Diagnosis, Awareness, Th, Autism Spectrum Disorder, Gold Standard, Psychological Tests, Spectrum, Young Children, Reproducibility of Results, Social Behavior, Developmental delay, Pilot Projects, High Sensitivity, Typical Development, Test Reliability, Diagnostic Tests, Autistic disorder, and Child preschool
We explored factors that influence parental involvement in adoption dialogues in 66 internationally adoptive, heterosexual couples with 4- to 7-year old children. Correlates of adoption involvement varied by parent sex. Mothers were more... more
We explored factors that influence parental involvement in adoption dialogues in 66 internationally adoptive, heterosexual couples with 4- to 7-year old children. Correlates of adoption involvement varied by parent sex. Mothers were more involved in talking about adoption than fathers, but adoption involvement was also correlated within couples. Emphasis on the difference between biological versus adoptive parenting, quality of the
Research Interests:
Results: RB subtypes were identified and were elevated in the ASD group relative to the DD group at age 3. However, self-injurious behavior did not differ between groups. Volumetric findings indicate enlargement of most structures in the... more
Results: RB subtypes were identified and were elevated in the ASD group relative to the DD group at age 3. However, self-injurious behavior did not differ between groups. Volumetric findings indicate enlargement of most structures in the ASD relative to the TD group. Enlargement ...