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Peer-reviewedCC BY-NC 4.0Developmental Neuroscience

Peripheral Biomarkers of Anxiety in Autism and Attention Deficit/Hyperactivity Disorder

  • Shane Cleary1,2
  • Craig Matthews1
  • Grace Teskey3
  • Dawn M.E. Bowdish3,4
  • Jennifer Crosbie5,6
  • Robert Nicolson7
  • Rosanna Weksberg8,9,10,11
  • Elizabeth Kelley12,13
  • Jessica Jones12,13,14
  • Evdokia Anagnostou9,15
  • Jane A. Foster1,2,16
16 affiliations
  1. 1Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada
  2. 2The Research Institute at St. Joe’s, Hamilton, ON, Canada
  3. 3Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
  4. 4Firestone Institute for Respiratory Health, Hamilton, ON, Canada
  5. 5Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada
  6. 6Department of Psychiatry, University of Toronto, Toronto, ON, Canada
  7. 7Lawson Health Research Institute and Western University, London, ON, Canada
  8. 8Division of Clinical and Metabolic Genetics and Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada
  9. 9Departments of Pediatrics, University of Toronto, Toronto, ON, Canada
  10. 10Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
  11. 11Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
  12. 12Center for Neuroscience Studies, Queen’s University, Kingston, ON, Canada
  13. 13Department of Psychology, Queen’s University, Kingston, ON, Canada
  14. 14Department of Psychiatry, Queen’s University, Kingston, ON, Canada
  15. 15Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada
  16. 16Center for Depression Research and Clinical Care, University of Texas Southwestern, Dallas, TX, USA
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Abstract

Introduction: Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), have high rates of comorbid anxiety disorders. Emerging evidence suggests neuroimmune signalling may partially contribute to behavioral symptoms in NDDs.

Methods: This study examined the association between neuroinflammation and anxiety symptoms in children and adolescents with NDDs. The sample comprised 134 participants (33 typically developing [TD]), 31 ADHD, 70 ASD recruited through the Province of Ontario Neurodevelopmental Disorders (POND) Network. Plasma markers of neuroinflammation were quantified using multiplex immunoassays.

Results: Anxiety scores, measured using the Child Behavior Checklist, were significantly higher in ASD and ADHD compared to TD participants. Six neuroinflammatory markers differed between diagnoses, with ASD showing elevated plasma levels of brain-derived neurotrophic factor (BDNF), interleukin-18 (IL-18), and vascular endothelial growth factor, while ADHD displayed reduced fractalkine (CXCL1), IL-6, and tumor necrosis factor-α (TNF-α) levels compared to TD. Elastic net regression identified five neuroinflammatory markers, IL-18, β-nerve growth factor (β-NGF), BDNF, soluble receptor for advanced glycation end products (sRAGE), and TNF-α, as predictors of anxiety, collectively explaining 15% of the variance in anxiety levels.

Conclusion: These findings reveal associations between peripheral neuroinflammation markers and anxiety in NDDs that reflect complex patterns beyond pro- and anti-inflammatory classifications, warranting further investigation as potential biomarkers of behavioral symptoms.

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Cite

BibTeXRIS
BibTeX
@article{cleary2026peripheral,
  title = {{Peripheral Biomarkers of Anxiety in Autism and Attention Deficit/Hyperactivity Disorder}},
  author = {Shane Cleary and Craig Matthews and Grace Teskey and Dawn M.E. Bowdish and Jennifer Crosbie and Robert Nicolson and Rosanna Weksberg and Elizabeth Kelley and Jessica Jones and Evdokia Anagnostou and Jane A. Foster},
  journal = {Developmental Neuroscience},
  year = {2026},
  month = sep,
  doi = {10.1159/dne/aclag006},
  url = {https://doi.org/10.1159/dne/aclag006},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Peripheral Biomarkers of Anxiety in Autism and Attention Deficit/Hyperactivity Disorder
AU  - Shane Cleary
AU  - Craig Matthews
AU  - Grace Teskey
AU  - Dawn M.E. Bowdish
AU  - Jennifer Crosbie
AU  - Robert Nicolson
AU  - Rosanna Weksberg
AU  - Elizabeth Kelley
AU  - Jessica Jones
AU  - Evdokia Anagnostou
AU  - Jane A. Foster
PY  - 2026
DA  - 2026/09/22
JO  - Developmental Neuroscience
DO  - 10.1159/dne/aclag006
UR  - https://doi.org/10.1159/dne/aclag006
AB  - Introduction: Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), have high rates of comorbid anxiety disorders. Emerging evidence suggests neuroimmune signalling may partially contribute to behavioral symptoms in NDDs.  Methods: This study examined the association between neuroinflammation and anxiety symptoms in children and adolescents with NDDs. The sample comprised 134 participants (33 typically developing [TD]), 31 ADHD, 70 ASD recruited through the Province of Ontario Neurodevelopmental Disorders (POND) Network. Plasma markers of neuroinflammation were quantified using multiplex immunoassays.  Results: Anxiety scores, measured using the Child Behavior Checklist, were significantly higher in ASD and ADHD compared to TD participants. Six neuroinflammatory markers differed between diagnoses, with ASD showing elevated plasma levels of brain-derived neurotrophic factor (BDNF), interleukin-18 (IL-18), and vascular endothelial growth factor, while ADHD displayed reduced fractalkine (CXCL1), IL-6, and tumor necrosis factor-α (TNF-α) levels compared to TD. Elastic net regression identified five neuroinflammatory markers, IL-18, β-nerve growth factor (β-NGF), BDNF, soluble receptor for advanced glycation end products (sRAGE), and TNF-α, as predictors of anxiety, collectively explaining 15% of the variance in anxiety levels.  Conclusion: These findings reveal associations between peripheral neuroinflammation markers and anxiety in NDDs that reflect complex patterns beyond pro- and anti-inflammatory classifications, warranting further investigation as potential biomarkers of behavioral symptoms.
SN  - 0378-5866
SN  - 1421-9859
ER  -