Acknowledgments We would like to thank Judith Nathanson for her assistance with the illustrations. Also, we would like to thank members of the Morrow laboratory for critical reading of the manuscript. EMM has received a Career Award in Medical Science from the Burroughs Wellcome Fund and support from NIMH 1K23MH080954-05, NIGMS Inhibitors,research,lifescience,medical 5P20RR018728-09. None of the authors have a financial conflict of interest. Selected abbreviations and acronyms ASD autism spectrum disorder CNV copy number Selleck Olaparib variation FMRP fragile X mental retardation protein FXS fragile X syndrome ID intellectual disability RTT Rett syndrome TSC tuberous sclerosis UPS ubiquitin-proteasome system
Autism

is one of a spectrum of behaviorally defined “pervasive developmental disorders,”1 which are commonly referred to as autism spectrum disorder (ASD). Inhibitors,research,lifescience,medical The deficits in social communication and presence of restricted interests and repetitive behaviors result in lifelong impairments and disability. ASD has been reported to affect as many as 1 in 88 children in the

US.2 Reported prevalence rates have risen dramatically in the last two decades, though little is understood about the increase. Epidemiologic surveys Inhibitors,research,lifescience,medical of adult populations suggest that the apparent rise in numbers of affected children may not represent a true increase in prevalence rates.3 Nevertheless, there is speculation that broadened definitions, growing awareness, and diagnostic

substitution may be contributing to the apparent rise.1,4 Regardless of the cause, the current prevalence estimates suggest that there are more than 2 million individuals in the US with ASD. To date, Inhibitors,research,lifescience,medical no preventive strategies have demonstrated consistent benefits and no treatments have proven widely efficacious in treating the core Inhibitors,research,lifescience,medical symptoms of ASD. Consequently, ASD causes lifelong disabilities for affected individuals and significant burdens on their families, schools, and society.5 Research on autism lags behind that of other psychiatric disorders and medical conditions. Part of the delay may be traced to the flawed constructs of autism that followed identification of isothipendyl the disorder in 1943. Most prominent of these was the speculation that autism was caused by parenting failures of “refrigerator mothers.” Perhaps the greatest success story in autism research is the work of Dr Bernard Rimland and colleagues in the 1970s, which demonstrated that autism was actually a failure of neurodevelopment, with behavioral interventions providing potential benefits.6 That research, in combination with an emerging basic science literature, led to our current understanding of autism as a brain-based disorder with specific (if as yet undetermined) abnormalities of brain structure and/or function.