Deciduous tooth biomarkers reveal atypical fetal inflammatory regulation in autism spectrum disorder

Dani Dumitriu; Elena Baldwin; Roozie J J Coenen; Luke A Hammond; Darcy S Peterka; Lynne Heilbrun; Richard E Frye; Raymond Palmer; Hjalmar Nobel Norrman; Anna Fridell; Karl Lundin Remnelius; Johan Isaksson; Christine Austin; Paul Curtin; Sven Bölte; Manish Arora

doi:10.1016/j.isci.2023.106247

Deciduous tooth biomarkers reveal atypical fetal inflammatory regulation in autism spectrum disorder

iScience. 2023 Feb 21;26(3):106247. doi: 10.1016/j.isci.2023.106247. eCollection 2023 Mar 17.

Authors

Dani Dumitriu^{1

2

3}, Elena Baldwin², Roozie J J Coenen², Luke A Hammond⁴, Darcy S Peterka⁴, Lynne Heilbrun⁵, Richard E Frye⁶, Raymond Palmer⁵, Hjalmar Nobel Norrman⁷, Anna Fridell^{7

8}, Karl Lundin Remnelius⁷, Johan Isaksson^{7

9}, Christine Austin^{2

10}, Paul Curtin^{2

10}, Sven Bölte^{7

8

11}, Manish Arora^{2

10}

Affiliations

¹ Departments of Neuroscience and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
² Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
³ Departments of Pediatrics and Psychiatry, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY 10032, USA.
⁴ Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
⁵ Family and Community Medicine, School of Medicine, University of Texas Health Sciences Center, San Antonio, TX 78229, USA.
⁶ Department of Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ 85016, USA.
⁷ Center of Neurodevelopmental Disorder (KIND), Division of Neuropsychiatry, Department of Women's and Children's Health, Karolinska Institutet, Stockholm 171 77, Sweden.
⁸ Child and Adolescent Psychiatry Research Center, Center for Psychiatry Research, Region Stockholm, Stockholm 104 31, Sweden.
⁹ Department of Medical Sciences, Child and Adolescent Psychiatry Unit, Uppsala University, Uppsala 751 85, Sweden.
¹⁰ Linus Biotechnology Inc., New York, NY 10013, USA.
¹¹ Curtin Autism Research Group, Curtin School of Allied Health, Curtin University, Perth, WA 6102, Australia.

Abstract

Atypical regulation of inflammation has been proposed in the etiology of autism spectrum disorder (ASD); however, measuring the temporal profile of fetal inflammation associated with future ASD diagnosis has not been possible. Here, we present a method to generate approximately daily profiles of prenatal and early childhood inflammation as measured by developmentally archived C-reactive protein (CRP) in incremental layers of deciduous tooth dentin. In our discovery population, a group of Swedish twins, we found heightened inflammation in the third trimester in children with future ASD diagnosis relative to controls (n = 66; 14 ASD cases; critical window: -90 to -50 days before birth). In our replication study, in the US, we observed a similar increase in CRP in ASD cases during the third trimester (n = 47; 23 ASD cases; -128 to -21 days before birth). Our results indicate that the third trimester is a critical period of atypical fetal inflammatory regulation in ASD.

Keywords: Clinical neuroscience; Immunology.