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Featured researches published by Stelios Georgiades.


Journal of the American Academy of Child and Adolescent Psychiatry | 2014

Behavioral and Cognitive Characteristics of Females and Males With Autism in the Simons Simplex Collection

Thomas W. Frazier; Stelios Georgiades; Somer L. Bishop; Antonio Y. Hardan

OBJECTIVE To examine differences in behavioral symptoms and cognitive functioning between males and females with autism spectrum disorder (ASD). METHOD We analyzed data from 2,418 probands with autism (304 females and 2,114 males) included in the Simons Simplex Collection. Sex differences were evaluated across measures of autism symptoms, cognitive and motor functioning, adaptive behavior, and associated behavior problems. Measurement bias was examined using latent variable models of symptoms. Unadjusted and propensity-adjusted analyses were computed to ensure that sex differences were not due to unbalanced sampling. Moderator and mediator analyses evaluated whether sex differences were modified by clinical characteristics or were driven by cognitive ability. RESULTS Females with ASD had greater social communication impairment, lower levels of restricted interests, lower cognitive ability, weaker adaptive skills, and greater externalizing problems relative to males. Symptom differences could not be accounted for by measurement differences, indicating that diagnostic instruments captured autism similarly in males and females. IQ reductions mediated greater social impairment and reduced adaptive behavior in females with ASD, but did not mediate reductions in restricted interests or increases in irritability. CONCLUSIONS A specific female ASD phenotype is emerging that cannot be accounted for by differential symptom measurement. The present data suggest that the relatively low proportion of high-functioning females may reflect the effect of protective biological factors or may be due to under-identification. Additional carefully accrued samples are needed to confirm the present pattern and to evaluate whether observed sex ratios in high-functioning cases are reduced if female-specific indicators of restricted interests are included.


American Journal of Medical Genetics | 2012

Sex differences in repetitive stereotyped behaviors in autism: Implications for genetic liability†

Peter Szatmari; Xiao-Qing Liu; Jeremy Goldberg; Lonnie Zwaigenbaum; Andrew D. Paterson; Marc Woodbury-Smith; Stelios Georgiades; Eric Duku; Ann Thompson

The implications of the well known sex differences in the prevalence of autism spectrum disorder (ASD) are not well understood. The aim of this paper was to investigate whether these differences might be associated with differences in genetic liability. Individuals with ASD (970 families, 2,028 individuals) were recruited as part of the Autism Genome Project (AGP). The families were differentiated into families containing a female (either female–female or male–female) and those with only males. If the sex with the lower prevalence is associated with a greater genetic liability necessary to cross sex‐specific thresholds, the males from female containing families should be more severely affected than males from male only families. Affected subjects from the different types of families with ASD were sampled and compared on the social reciprocity and repetitive behavior scores from the Autism Diagnostic Interview‐Revised (ADI‐R). In general, females had lower repetitive behavior scores than males. More importantly, males from female containing families had higher repetitive behavior scores than males from male–male families. No such differences were apparent on the social reciprocity scores. These results support the hypothesis of a multiple threshold model of genetic liability of ASD with females having a higher liability for affectation status, at least on the repetitive behavior dimension of the disorder. These data also support the dissociation of the different phenotypic dimensions of ASD in terms of its genetic architecture. The implications of these results for linkage and association studies are discussed.


Journal of Autism and Developmental Disorders | 2010

Validating the Repetitive Behavior Scale-Revised in Young Children with Autism Spectrum Disorder.

Pat Mirenda; Isabel M. Smith; Tracy Vaillancourt; Stelios Georgiades; Eric Duku; Peter Szatmari; Susan E. Bryson; Eric Fombonne; Wendy Roberts; Joanne Volden; Charlotte Waddell; Lonnie Zwaigenbaum

This study examined the factor structure of the Repetitive Behavior Scale-Revised (RBS-R) in a sample of 287 preschool-aged children with autism spectrum disorder (ASD). A confirmatory factor analysis was used to examine six competing structural models. Spearman’s rank order correlations were calculated to examine the associations between factor scores and variables of interest. The 3- and 5-factor models were selected as preferable on the basis of fit statistics and parsimony. For both models, the strongest correlations were with problem behavior scores on the Child Behavior Checklist and repetitive behavior scores on the ADI-R. Developmental index standard scores were not correlated with factors in either model. The results confirm the utility of the RBS-R as a measure of repetitive behaviors in young children with ASD.


JAMA Psychiatry | 2013

A Prospective Study of Autistic-Like Traits in Unaffected Siblings of Probands With Autism Spectrum Disorder

Stelios Georgiades; Peter Szatmari; Lonnie Zwaigenbaum; Susan E. Bryson; Jessica Brian; Wendy Roberts; Isabel M. Smith; Tracy Vaillancourt; Caroline Roncadin; Nancy Garon

CONTEXT The presence of autistic-like traits in relatives of individuals with autism spectrum disorder (ASD) is well recognized, but, to our knowledge, the emergence of these traits early in development has not been studied. OBJECTIVE To prospectively investigate the emergence of autistic-like traits in unaffected (no ASD diagnosis) infant siblings of probands diagnosed as having ASD. DESIGN Two groups of children unaffected with ASD were assessed prospectively-siblings of probands diagnosed as having ASD (high risk [HR]) and control subjects with no family history of ASD (low risk [LR]). Scores on a measure of autistic-like traits at 12 months of age were used in a cluster analysis of the entire sample. SETTING A prospective study of infant siblings of probands with ASD from 3 diagnostic centers in Canada. PARTICIPANTS The study included 170 HR and 90 LR children, none of whom was diagnosed as having ASD at age 3 years. MAIN OUTCOME MEASURES The Autism Observation Scale for Infants was used to measure autistic-like traits and derive clusters at 12 months of age. Clusters were compared on ASD symptoms, cognitive abilities, and social-emotional difficulties at age 3 years. RESULTS Two clusters were identified. Cluster 1 (n = 37; 14.2% of total sample) had significantly higher levels of autistic-like traits compared with cluster 2. Within cluster 1, 33 children came from the siblings (19.4% of HR group) and only 4 came from the control subjects (4.5% of LR group). At age 3 years, children from cluster 1 had more social-communication impairment (effect size > 0.70; P < .001), lower cognitive abilities (effect size = -0.59; P < .005), and more internalizing problems (effect size = 0.55; P = .01). Compared with control subjects, HR siblings had a relative risk of 4.3 (95% CI,1.6-11.9) for membership in cluster 1. CONCLUSIONS Study findings suggest the emergence of autistic-like traits resembling a broader autism phenotype by 12 months of age in approximately 19% of HR siblings who did not meet ASD diagnostic criteria at age 3 years.


Journal of Personality and Social Psychology | 2005

The Factor Structure of Greek Personality Adjectives

Gerard Saucier; Stelios Georgiades; Ioannis Tsaousis; Lewis R. Goldberg

Personality descriptors--3,302 adjectives--were extracted from a dictionary of the modern Greek language. Those terms with the highest frequency were administered to large samples in Greece to test the universality of the Big-Five dimensions of personality in comparison to alternative models. One- and 2-factor structures were the most stable across variable selections and subsamples and replicated such structures found in previous studies. Among models with more moderate levels of replication, recently proposed 6- and 7-lexical-factor models were approximately as well replicated as the Big Five. An emic 6-factor structure showed relative stability; these factors were labeled Negative-Valence/Honesty, Agreeableness/Positive Affect, Prowess/Heroism, Introversion/Melancholia, Even Temper, and Conscientiousness.


Journal of Autism and Developmental Disorders | 2008

Alexithymia in parents of children with autism spectrum disorder.

Peter Szatmari; Stelios Georgiades; Eric Duku; Lonnie Zwaigenbaum; Jeremy Goldberg; Terry Bennett

Given the recent findings regarding the association between alexithymia and Autism Spectrum Disorder (ASD) and the accumulating evidence for the presence of the Broader Autism Phenotype (BAP) in relatives of individuals with ASD, we further explored the construct of alexithymia in parents of children with ASD as a potential part of the BAP. We hypothesized that (a) parents of children with ASD will demonstrate higher impairment in their emotion processing when compared to controls, and (b) high impairment in emotion processing in parents will be associated with severity of symptoms in children with ASD. Psychometric and diagnostic data were collected on 188 children with a diagnosis of ASD. The Toronto Alexithymia Scale (TAS-20) was completed by 439 parents of children with ASD and a control group of 45 parents of children with Prader Willi syndrome (PW). Results show that ASD parents score higher than controls on the TAS-20 total score. Within the ASD group, children of fathers with high alexithymia score higher on repetitive behaviour symptoms compared to children of fathers with low alexithymia. The alexithymia trait appears to be one of the many building blocks that make up the BAP.


Journal of the American Academy of Child and Adolescent Psychiatry | 2016

Prospective Longitudinal Studies of Infant Siblings of Children with Autism: Lessons Learned and Future Directions

Peter Szatmari; Katarzyna Chawarska; Geraldine Dawson; Stelios Georgiades; Rebecca Landa; Catherine Lord; Daniel S. Messinger; Audrey Thurm; Alycia K. Halladay

OBJECTIVE The objectives of this review are to highlight the impact of the first decade of high-risk (HR) infant sibling work in autism spectrum disorder (ASD) and to identify potential areas of translational focus for the next decade of research. METHOD A group of clinicians and researchers in ASD working both inside and outside of the HR design met on a regular basis to review the infant sibling research, and came to an agreement on areas that had changed clinical practice and areas that had the potential to change practice with further research. The group then outlined several methodological and translational challenges that must be addressed in the next decade of research if the field is to reach its potential. RESULTS The review concluded that the HR design has yielded an understanding that ASD often, but not always, begins to emerge between 6 and 18 months, with early signs affecting social communication. Research using the HR design has also allowed a better understanding of the sibling recurrence risk (between 10% and 20%). Emerging areas of interest include the developmental trajectories of social communications skills in the early years, the expression of a milder phenotype in siblings not affected with ASD, and the possibility that early intervention with infant siblings may improve outcomes for those with ASD. Important challenges for the future include linking screening to intervention, collecting large sample sizes while ensuring cross-site reliability, and building in capacity for replication. CONCLUSION Although there are significant methodological and translational challenges for high-risk infant sibling research, the potential of this design to improve long-term outcomes of all children with ASD is substantial.


Journal of Autism and Developmental Disorders | 2011

Phenotypic Overlap Between Core Diagnostic Features and Emotional/Behavioral Problems in Preschool Children with Autism Spectrum Disorder

Stelios Georgiades; Peter Szatmari; Eric Duku; Lonnie Zwaigenbaum; Susan E. Bryson; Wendy Roberts; Eric Fombonne; Pat Mirenda; Isabel M. Smith; Tracy Vaillancourt; Joanne Volden; Charlotte Waddell; Ann Thompson; Pathways in Asd Study Team

This study examined the phenotypic overlap between core diagnostic features and emotional/behavioral problems in a sample of 335 preschool children with autism spectrum disorder (ASD). Results from principal component analysis (2 components; 49.70% variance explained) suggested substantial phenotypic overlap between core diagnostic features and emotional/behavioral problems. Component I, Emotional Behavioral Repetitive Problems, was independent of the children’s intellectual, adaptive functioning, and structural language abilities. Component II, Social Communication Deficits, was negatively related to the children’s intellectual, adaptive functioning, and structural language abilities. Both components were positively related to parental stress. This exploratory study contributes to our understanding of the ASD phenotype and provides further support for including emotional/behavioral problems as part of the clinical characterization of children with ASD.


Journal of the American Academy of Child and Adolescent Psychiatry | 2011

Identification of Genetic Loci Underlying the Phenotypic Constructs of Autism Spectrum Disorders.

Xiao Qing Liu; Stelios Georgiades; Eric Duku; Ann Thompson; Bernie Devlin; Edwin H. Cook; Ellen M. Wijsman; Andrew D. Paterson; Peter Szatmari

OBJECTIVE To investigate the underlying phenotypic constructs in autism spectrum disorders (ASD) and to identify genetic loci that are linked to these empirically derived factors. METHOD Exploratory factor analysis was applied to two datasets with 28 selected Autism Diagnostic Interview-Revised (ADI-R) algorithm items. The first dataset was from the Autism Genome Project (AGP) phase I (1,236 ASD subjects from 618 families); the second was from the AGP phase II (804 unrelated ASD subjects). Variables derived from the factor analysis were then used as quantitative traits in genome-wide variance components linkage analyses. RESULTS Six factors, namely, joint attention, social interaction and communication, nonverbal communication, repetitive sensory-motor behavior, peer interaction, and compulsion/restricted interests, were retained for both datasets. There was good agreement between the factor loading patterns from the two datasets. All factors showed familial aggregation. Suggestive evidence for linkage was obtained for the joint attention factor on 11q23. Genome-wide significant evidence for linkage was obtained for the repetitive sensory-motor behavior factor on 19q13.3. CONCLUSIONS This study demonstrates that the underlying phenotypic constructs based on the ADI-R algorithm items are replicable in independent datasets, and that the empirically derived factors are suitable and informative in genetic studies of ASD.


Autism Research | 2017

Non-ASD outcomes at 36 months in siblings at familial risk for autism spectrum disorder (ASD): A baby siblings research consortium (BSRC) study

Tony Charman; Gregory S. Young; Jessica Brian; Alice S. Carter; Leslie J. Carver; Katarzyna Chawarska; Suzanne Curtin; Karen R. Dobkins; Mayada Elsabbagh; Stelios Georgiades; Irva Hertz-Picciotto; Ted Hutman; Jana M. Iverson; Emily J.H. Jones; Rebecca Landa; Suzanne Macari; Daniel S. Messinger; Charles A. Nelson; Sally Ozonoff; Celine Saulnier; Wendy L. Stone; Helen Tager-Flusberg; Sara Jane Webb; Nurit Yirmiya; Lonnie Zwaigenbaum

We characterized developmental outcomes of a large sample of siblings at familial high‐risk of autism spectrum disorder (ASD), who themselves did not have ASD (n = 859), and low‐risk controls with no family history of ASD (n = 473). We report outcomes at age 3 years using the Mullen Scales of Early Learning, the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview—Revised (ADI‐R) and adaptive functioning on the Vineland Adaptive Behavior Scales. Around 11% of high‐risk siblings had mild‐to‐moderate levels of developmental delay, a rate higher than the low‐risk controls. The groups did not differ in the proportion of toddlers with mild‐to‐moderate language delay. Thirty percent of high‐risk siblings had elevated scores on the ADOS, double the rate seen in the low‐risk controls. High‐risk siblings also had higher parent reported levels of ASD symptoms on the ADI‐R and lower adaptive functioning on the Vineland. Males were more likely to show higher levels of ASD symptoms and lower levels of developmental ability and adaptive behavior than females across most measures but not mild‐to‐moderate language delay. Lower maternal education was associated with lower developmental and adaptive behavior outcomes. These findings are evidence for early emerging characteristics related to the “broader autism phenotype” (BAP) previously described in older family members of individuals with ASD. There is a need for ongoing clinical monitoring of high‐risk siblings who do not have an ASD by age 3 years, as well as continued follow‐up into school age to determine their developmental and behavioral outcomes. Autism Res 2017, 10: 169–178.

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Peter Szatmari

Centre for Addiction and Mental Health

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Wendy Roberts

Holland Bloorview Kids Rehabilitation Hospital

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Pat Mirenda

University of British Columbia

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