Critical Periods in the Neurodevelopment of Autism

Abstract

Autism Spectrum Disorder (ASD) is a developmental disability that can create significant behavioral and communication challenges. The prevalence of ASD among children at 8 years of age is over 2%, and the prevalence is similar across ethnic groups and countries. Studies have shown that the majority of ASD children make an autoantibody to the high-affinity folate receptor in response to a dietary component. This Folate Receptor Antibody (FRA) blocks transport of folate across the Blood-Brain Barrier (BBB), resulting in a Cerebral Folate Deficiency (CFD). Parents of autistic children also have FRA at substantially higher rates than the general public, which may play a critical role during neurodevelopmental critical periods in the fetus. In clinical trials, ASD children with the FRA had improvement in their communication when placed on a daily supplement of folate in its reduced form, which can enter the brain via a low-affinity transport. We reason that supplementing folate earlier in development, including in utero development, may be most effective in reducing the severity of ASD symptoms by facilitating typical passage through critical neurodevelopmental periods.