The 2013 Strategic Plan of the Interagency Autism Coordinating Committee described regression as one of the most mysterious and troubling aspects of autism spectrum disorder (ASD) and set understanding regression as a priority for the field.

Abha Gupta’s long-term goal is to elucidate the pathophysiology of childhood disintegrative disorder (CDD), a rare, extreme form of this phenomenon. Debate exists regarding the precise definition of regression in ASD. However, there is little ambiguity about CDD since it is characterized by a severe regressive episode that is of later onset and, therefore, tends to be clear and dramatic. A better understanding of the pathophysiology of CDD will aid in the development of more targeted diagnostic tests and effective treatments for regression. This is critical since it has a catastrophic impact on those affected and is virtually unstudied.

Genetics, neuroimaging and eye tracking are being intensively studied in ASD. However, because of the rarity of CDD and the incredible technical difficulty of conducting experimental protocols such as eye tracking and brain imaging with very low-functioning individuals, an exploratory study from Gupta and colleagues that assessed a small cohort of 17 individuals with CCD is the only such study that has been published examining this disorder¹. That study, funded in part by a SFARI award, demonstrated convergence between expression of candidate genes and face-evoked brain activity unique to CDD in non-neocortical regions. Eye tracking experiments showed unexpectedly that, among individuals with ASD, individuals with CDD focused on eyes the most when shown pictures of faces. Based on this work, Gupta hypothesizes that there are distinct neural systems and biomarkers that characterize CDD relative to other ASD phenotypes.

The current project plans to recruit a larger number of families affected by CDD for clinical characterization and the collection of biospecimens for future neurogenetic analysis. Gupta’s team aims to expand the earlier CCD study cohort by recruiting additional families affected by CDD, including 50 probands, both biological parents and an estimated average of one unaffected sibling per family for a total of 200 participants. They plan to conduct medical and educational record review, collect responses from caregiver interviews and questionnaires, analyze pre- and post-regression home videos and collect saliva samples for genomic DNA extraction and banking.

The creation of this expanded CCD cohort and analyses of the data collected will have an important positive impact on our understanding of regression in ASD. Understanding CDD, with its protracted period of early normal development, provides a generous window for detection of regression risk factors. The ultimate goal is to identify ways to prevent or treat this devastating phenomenon, which has profound consequences for those affected and their families.