Proinflammatory mediators and their associations with medication and comorbid traits in children and adults with ADHD

Eur Neuropsychopharmacol. 2020 Dec:41:118-131. doi: 10.1016/j.euroneuro.2020.10.005. Epub 2020 Nov 5.


Peripheral immune activation can influence neurodevelopment and is increased in autism, but is less explored in attention deficit hyperactivity disorder (ADHD). Patients with ADHD often display comorbid autism traits and gastrointestinal (GI) symptoms. Plasma protein levels of two acute phase reactants, C-reactive protein (CRP) and serum amyloid A (SAA), and two endothelial adhesion molecules, soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1), which share important roles in inflammation, were analyzed in 154 patients with ADHD and 61 healthy controls. Their associations with ADHD diagnosis, severity, medication and comorbid autistic symptoms, emotion dysregulation and GI symptoms were explored. The ADHD patients had increased levels of sICAM-1 and sVCAM-1 compared to healthy controls (p = 8.6e-05, p = 6.9e-07, respectively). In children with ADHD, the sICAM-1 and sVCAM-1 levels were higher among those with ADHD medication than among children (p = 0.0037, p = 0.0053, respectively) and adults (p = 3.5e-09, p = 1.9e-09, respectively) without ADHD medication. Among the adult ADHD patients, higher sICAM-1 levels were associated with increased comorbid autistic symptoms in the domains attention to detail and imagination (p = 0.0081, p = 0.00028, respectively), and higher CRP levels were associated with more GI symptoms (p = 0.014). sICAM-1 and sVCAM-1 levels were highly correlated with each other, and so were CRP and SAA levels. To conclude, vascular inflammatory activity may be overrepresented in ADHD, with elevated sICAM-1 and sVCAM-1 levels and this may in children be a consequence of current ADHD medication, and in adults relate to increased comorbid autistic symptoms. Replication is warranted.

Keywords: ADHD; Adhesion molecules; Autism; Inflammation; Stimulants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Attention Deficit Disorder with Hyperactivity / blood*
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Attention Deficit Disorder with Hyperactivity / epidemiology*
  • Autistic Disorder / blood
  • Autistic Disorder / drug therapy
  • Autistic Disorder / epidemiology
  • Biomarkers / blood
  • Case-Control Studies
  • Central Nervous System Stimulants / therapeutic use
  • Child
  • Child, Preschool
  • Comorbidity
  • Female
  • Gastrointestinal Diseases / blood
  • Gastrointestinal Diseases / drug therapy
  • Gastrointestinal Diseases / epidemiology
  • Humans
  • Inflammation Mediators / blood*
  • Male
  • Melatonin / therapeutic use
  • Middle Aged
  • Sweden / epidemiology
  • Young Adult


  • Anti-Bacterial Agents
  • Biomarkers
  • Central Nervous System Stimulants
  • Inflammation Mediators
  • Melatonin