Scientific Challenges in the Development of Putative Autism Biomarkers

Background: With a strong genetic basis and many known comorbidities, autism is a very complex disorder. Current diagnostic methods and screening tools are somewhat subjective and are difficult to use in very young children. A biological marker that could predict autism risk or assist in early diagnosis would have great clinical utility. Additionally, biomarkers could provide targets for therapeutic intervention. While research in this field has greatly increased in recent years, progress has been limited and no biological markers for autism have been found to be universal.

Objectives: The objective of this presentation is to describe the major scientific challenges associated with the identification of biological markers for autism. Factors that may play a role in impeding progress in autism biomarker research, including the heterogeneity of autism, the presence of comorbid conditions, gender bias, and the availability of appropriate research samples, will be critically reviewed.

Methods: The complex heterogeneity of autism underscores the importance of recognizing different autism subtypes in relation to how biomarker studies are designed. A number of previous autism biomarker studies are clouded by methodological concerns, such as small samples sizes, lack of stringent diagnostic assessments, unsuitable controls, disparate age ranges between controls and cases, and the use of medications. The issue of gender-bias should also be carefully considered. If study designs do not take gender into account, we risk not only doing harm (such as extrapolating the utility of biomarkers based on male samples to females), but also missing critical opportunities to further our understanding of the etiology of autism. The implications of these issues, as well as the proposed changes for DSM-5 diagnostic criteria for autism spectrum disorders, will be reviewed in terms of sub-grouping subjects for future biomarker studies. This presentation will also provide information on available research resources including various autism biorepositories and the types of datasets, tissues and samples available to researchers wishing to engage in biomarker studies.

Results:  At the end of this presentation, attendees will be able to critically review the major scientific challenges associated with the identification of biological markers for autism.

Conclusions: The search for autism biomarkers in the laboratory is an important research endeavor that is fraught with many challenges, yet the translation of such findings into the clinic may be the real challenge and requires the investigation of large, well-characterized sample cohorts with appropriate controls. Only when these issues are addressed prior to implementing new studies, will robust and reliable biomarkers for autism be identified.