Subphenotype-Dependent Disease Markers for Diagnosis and Personalized Treatment of Autism Spectrum Disorders

Autism spectrum disorders (ASD) are a collection of neurodevelopmental disorders that are currently diagnosed solely on the basis of abnormal reciprocal language and social development as well as stereotyped behaviors. Without genetic or molecular markers for screening, individuals with ASD are typically not diagnosed before the age of 2, with milder cases diagnosed much later. Because early diagnosis is tantamount to early behavioral intervention which has been shown to improve individual outcomes, an objective biomarker test that can diagnose at-risk children perinatally is a medical imperative. The rapidly increasing prevalence of ASD in the United States (now estimated at 1 in 88 individuals) also makes early diagnosis and intervention a public health imperative. This article reviews recent genome-wide (genomic) approaches to the identification of disease markers that may be used not only for diagnosis of ASD, but also for the informed development of novel drugs that target specific core symptoms of ASD. Because of the heterogeneity of clinical manifestations associated with the ASD population, this review also addresses the importance of dividing individuals with ASD into clinically relevant subphenotypes in the quest to identify appropriate biomarkers.