Abstract
A rise in the prevalence of diagnosed cases of autism spectrum disorder (ASD) has been reported in several studies in recent years. While this rise in ASD prevalence is at least partially related to increased awareness and broadened diagnostic criteria, the role of environmental factors cannot be ruled out, especially considering that the cause of most cases of ASD remains unknown. The study of families with multiple affected children can provide clues about ASD etiology. While the majority of research on ASD multiplex families has focused on identifying genetic anomalies that may underlie the disorder, the study of symptom severity across ASD birth order may provide evidence for environmental factors in ASD. We compared social and cognitive measures of behavior between over 300 first and second affected siblings within multiplex autism families obtained from the Autism Genetic Resource Exchange dataset. Measures included nonverbal IQ assessed with the Ravens Colored Progressive Matrices, verbal IQ assessed with the Peabody Picture Vocabulary Test, and autism severity assessed with the Social Responsiveness Scale (SRS), an instrument established as a quantitative measure of autism. The results indicated that females were more severely impacted by ASD than males, especially first affected siblings. When first and second affected siblings were compared, significant declines in nonverbal and verbal IQ scores were observed. In addition, SRS results demonstrated a significant increase in autism severity between first and second affected siblings consistent with an overall decline in function as indicated by the IQ data. These results remained significant after controlling for the age and sex of the siblings. Surprisingly, the SRS scores were found to only be significant when the age difference between siblings was less than 2 years. These results suggest that some cases of ASD are influenced by a dosage effect involving unknown epigenetic, environmental, and/or immunological factors.
Highlights
Autism together with Asperger syndrome and pervasive developmental disorder - not otherwise specified (PDD-NOS) make up the classification of autism spectrum disorder (ASD)
In doing our analysis of both the Peabody Picture Vocabulary Test (PPVT) and Ravens Colored Progressive Matrices (RCPM), we noticed a disproportionate number of second affected siblings (39.4% and 41.8%, respectively) were deemed untestable compared to first affected siblings (19.6% and 21.5%, respectively; see Table 1)
Chi-squared analyses confirmed there was a significant association between affected order and testability (PPVT x2(1) = 63.36, p,.0001; RCPM x2(1) = 61.22, p,.0001)
Summary
Autism together with Asperger syndrome and pervasive developmental disorder - not otherwise specified (PDD-NOS) make up the classification of autism spectrum disorder (ASD). Given that the first affected siblings were older at the time of testing, the influence of development may possibly explain the increase in repetitive behaviors [12] Taken together, these studies demonstrate a pattern of decreasing IQ with increasing birth order in children affected with autism. The present study sought to examine the effects of autism birth order on measures of intelligence and autism symptoms in the largest dataset of multiplex families examined to date: the Autism Genetic Resource Exchange (AGRE) dataset This dataset has been used extensively as a means to measure various trends in ASD causes and severity by analyzing the provided genotypic and phenotypic information. We report for the first time the effects of birth order across affected siblings from an analysis of a limited number of families with at least 3 affected siblings
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