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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Integr. Neurosci. | doi: 10.3389/fnint.2019.00031

Investigating Potential Biomarkers in Autism Spectrum Disorder

 Carolyn F. Bridgemohan1, 2, 3*,  David Cochran4, 5,  Yamini J. Howe3, 6,  Katherine Pawlowski2, Andrew W. Zimmerman4, 5,  George M. Anderson7,  Roula Choueiri4, 5,  Laura Sices8,  Karen J. Miller9, 10, Monica Ultmann9, 10,  Jessica Helt6,  Peter W. Forbes1, Laura Farfel8, 10, 11,  Stephanie J. Brewster1, Jean A. Frazier4, 5, 12 and  Ann M. Neumeyer3, 6
  • 1Boston Children's Hospital, Harvard Medical School, United States
  • 2Division of Developmental Medicine, Boston Children's Hospital, United States
  • 3Harvard Medical School, United States
  • 4UMass Memorial Medical Center, United States
  • 5University of Massachusetts Medical School, United States
  • 6Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, United States
  • 7Child Study Center, School of Medicine, Yale University, United States
  • 8Boston Medical Center, United States
  • 9Tufts University School of Medicine, United States
  • 10Floating Hospital for Children, United States
  • 11Autism Consortium, United States
  • 12Eunice Kennedy Shriver Center, United States

Background: Early identification and treatment of individuals with Autism Spectrum Disorder (ASD) improves outcomes, but specific evidence needed to individualize treatment recommendations is lacking. Biomarkers that could be routinely measured within the clinical setting could potentially transform clinical care for patients with ASD. This demonstration project employed collection of biomarker data during regular autism specialty clinical visits and explored the relationship of biomarkers with clinical ASD symptoms.
Methods: Eighty-three children with ASD, aged 5-10 years, completed a multi-site feasibility study integrating the collection of biochemical (blood serotonin, urine melatonin sulfate excretion) and clinical (head circumference, dysmorphology exam, digit ratio, cognitive and behavioral function) biomarkers during routine ASD clinic visits. Parents completed a demographic survey and the Aberrant Behavior Checklist-Community. Cognitive function was determined by record review. Data analysis utilized Wilcoxon two-sample tests and Spearman correlations.
Results: Participants were 82% male, 63% White, 19% Hispanic, with a broad range of functioning. Group means indicated hyperserotonemia. In a single regression analysis adjusting for race and median household income, higher income was associated with higher levels of blood serotonin and urine melatonin sulfate excretion levels (p=.004 and p=.04, respectively). Melatonin correlated negatively with age (p= 0.048) and reported neurologic problems (p=0.02). Dysmorphic status correlated with higher reported stereotyped behavior (p=0.02) and inappropriate speech (p=0.04).
Conclusions: This demonstration project employed collection of multiple biomarkers, allowed for examination of associations between biochemical and clinical measures, and identified several findings that suggest direction for future studies. This clinical research model has promise for integrative biomarker research in individuals with complex, heterogeneous neurodevelopmental disorders such as ASD.

Keywords: autism, ASD, biomarkers, Serotonin, Melatonin, dysmorphology, clinical research

Received: 19 Mar 2019; Accepted: 03 Jul 2019.

Edited by:

John A. Sweeney, University of Cincinnati, United States

Reviewed by:

Felix Scholkmann, University Hospital Zürich, Switzerland
Zheng Wang, University of Chinese Academy of Sciences, China  

Copyright: © 2019 Bridgemohan, Cochran, Howe, Pawlowski, Zimmerman, Anderson, Choueiri, Sices, Miller, Ultmann, Helt, Forbes, Farfel, Brewster, Frazier and Neumeyer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Carolyn F. Bridgemohan, Boston Children's Hospital, Harvard Medical School, Boston, United States, Carolyn.bridgemohan@childrens.harvard.edu