Peripheral biomarkers of anxiety in autism and attention deficit/hyperactivity disorder

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 behavioural symptoms in NDDs. 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. 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 (VEGF), 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. 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.