Original Research

Biomarkers for Autism Spectrum Disorders (ASD): A Meta-analysis

Ashley Ansel, Yehudit Posen, Ronald Ellis, Lisa Deutsch, Philip D. Zisman, and Benjamin Gesundheit


Objective. To compare the reported accuracy and sensitivity of the various modalities used to diagnose autism spectrum disorders (ASD) in efforts to help focus further biomarker research on the most promising methods for early diagnosis. Methods. The Medline scientific literature database was searched to identify publications assessing potential clinical ASD biomarkers. Reports were categorized by the modality used to assess the putative markers, including protein, genetic, metabolic, or objective imaging methods. The reported sensitivity, specificity, area under the curve, and overall agreement were summarized and analyzed to determine weighted averages for each diagnostic modality. Heterogeneity was measured using the I2 test. Results. Of the 71 papers included in this analysis, each belonging to one of five modalities, protein-based followed by metabolite-based markers provided the highest diagnostic accuracy, each with a pooled overall agreement of 83.3% and respective weighted area under the curve (AUC) of 89.5% and 88.3%. Sensitivity provided by protein markers was highest (85.5%), while metabolic (85.9%) and protein markers (84.7%) had the highest specificity. Other modalities showed degrees of sensitivity, specificity, and overall agree¬ments in the range of 73%–80%. Conclusions. Each modality provided for diagnostic accuracy and specificity similar or slightly higher than those reported for the gold-standard Autism Diagnostic Observation Schedule (ADOS) instrument. Further studies are required to identify the most predictive markers within each modality and to evaluate biological pathways or clustering with possible etiological relevance. Analyses will also be necessary to determine the potential of these novel biomarkers in diagnosing pediatric patients, thereby enabling early intervention.

Rambam Maimonides Med J 2019;10(4):e0021