Abstract
Autism spectrum disorder (ASD) is amongst the most familial of psychiatric disorders. Twin and family studies have demonstrated a monozygotic concordance rate of 70–90%, dizygotic concordance of around 10%, and more than a 20-fold increase in risk for first-degree relatives. Despite major advances in the genetics of autism, the relationship between different aspects of the behavioral and cognitive phenotype and their underlying genetic liability is still unclear. This is complicated by the heterogeneity of autism, which exists at both genetic and phenotypic levels. Given this heterogeneity, one method to find homogeneous entities and link these with specific genotypes would be to pursue endophenotypes. Evidence from neuroimaging, eye tracking, and electrophysiology studies supports the hypothesis that, building on genetic vulnerability, ASD emerges from a developmental cascade in which a deficit in attention to social stimuli leads to impaired interactions with primary caregivers. This results in abnormal development of the neurocircuitry responsible for social cognition, which in turn adversely affects later behavioral and functional domains dependent on these early processes, such as language development. Such a model begets a heterogeneous clinical phenotype, and is also supported by studies demonstrating better clinical outcomes with earlier treatment. Treatment response following intensive early behavioral intervention in ASD is also distinctly variable; however, relatively little is known about specific elements of the clinical phenotype that may predict response to current behavioral treatments. This paper overviews the literature regarding genotypes, phenotypes, and predictors of response to behavioral intervention in ASD and presents suggestions for future research to explore linkages between these that would enable better identification of, and increased treatment efficacy for, ASD.
Highlights
GENETIC BASIS OF AUTISM SPECTRUM DISORDER It has been suggested that autism spectrum disorder (ASD) is one of the most familial of psychiatric disorders, with a heritability of 80%, a monozygotic concordance rate of 70–90%, dizygotic concordance of around 10%, and more than a 20-fold increase in risk for first-degree relatives (Bailey et al, 1995; O’Roak, 2008)
Genomic analyses indicate extreme genetic heterogeneity and so far, over 100 genes have been reported in ASD with a conservative estimate of between 380 and 820 loci implicated (Betancur, 2011; Clarke and Eapen, in press), and with considerable overlap with other disorders such as intellectual disability, epilepsy, schizophrenia, and attention deficit hyperactivity disorder (ADHD)
These findings suggest that ASD is not a single-gene disorder with Mendelian inheritance but rather a complex disorder resulting from simultaneous genetic variations in multiple genes (Dawson et al, 2002; El-Fishawy, 2010) as well as complex interactions between genetic, epigenetic, and environmental factors (Eapen, 2011)
Summary
GENETIC BASIS OF AUTISM SPECTRUM DISORDER It has been suggested that autism spectrum disorder (ASD) is one of the most familial of psychiatric disorders, with a heritability of 80%, a monozygotic concordance rate of 70–90%, dizygotic concordance of around 10%, and more than a 20-fold increase in risk for first-degree relatives (Bailey et al, 1995; O’Roak, 2008). Twin and family studies have shown that genetic liability to autism is expressed in unaffected relatives of people with ASD through features that are milder but qualitatively similar to the defining characteristics of ASD, including social abnormalities, communication impairments, and repetitive behaviors (Bailey et al, 1998; Goussé et al, 2002; Losh et al, 2009).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
