Prenatal air pollution influences neurodevelopment and behavior in autism spectrum disorder by modulating mitochondrial physiology

Richard E. Frye, Janet Cakir, Shannon Rose, Leanna Delhey, Sirish C. Bennuri, Marie Tippett, Stepan Melnyk, S. Jill James, Raymond F. Palmer, Christine Austin, Paul Curtin, Manish Arora

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


We investigate the role of the mitochondrion, an organelle highly sensitive to environmental agents, in the influence of prenatal air pollution exposure on neurodevelopment and behavior in 96 children with autism spectrum disorder (ASD) [45 with neurodevelopmental regression (NDR); 76% Male; mean (SD) age 10 y 9 m (3 y 9 m)]. Mitochondrial function was assessed using the Seahorse XFe96 in fresh peripheral blood mononuclear cells. Second and third trimester average and maximal daily exposure to fine air particulate matter of diameter ≤2.5 µm (PM2.5) was obtained from the Environmental Protection Agency’s Air Quality System. Neurodevelopment was measured using the Vineland Adaptive Behavior Scale 2nd edition and behavior was assessed using the Aberrant Behavior Checklist and Social Responsiveness Scale. Prenatal PM2.5 exposure influenced mitochondrial respiration during childhood, but this relationship was different for those with (r = 0.25–0.40) and without (r = −0.07 to −0.19) NDR. Mediation analysis found that mitochondrial respiration linked to energy production accounted for 25% (SD = 2%) and 10% (SD = 2%) of the effect of average prenatal PM2.5 exposure on neurodevelopment and behavioral symptoms, respectively. Structural equation models estimated that PM2.5 and mitochondrial respiration accounted for 34% (SD = 4%) and 36% (SD = 3%) of the effect on neurodevelopment, respectively, and that behavior was indirectly influenced by mitochondrial respiration through neurodevelopment but directly influenced by prenatal PM2.5. Our results suggest that prenatal exposure to PM2.5 disrupts neurodevelopment and behavior through complex mechanisms, including long-term changes in mitochondrial respiration and that patterns of early development need to be considered when studying the influence of environmental agents on neurodevelopmental outcomes.

Original languageEnglish (US)
Pages (from-to)1561-1577
Number of pages17
JournalMolecular psychiatry
Issue number5
StatePublished - May 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


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