The association between Attention Deficit Hyperactivity Disorder (ADHD) and low-grade
inflammation has been explored in children but rarely in adults. Inflammation is characteristic
of some, but not all, patients with ADHD and might be influenced by ADHD medication
but also lifestyle factors including nutrition, smoking, and stress. It is also still
unclear if any specific symptoms are related to inflammation. Therefore, we assessed
96 inflammatory proteins in a deeply phenotyped cohort of 126 adult ADHD participants
with a stable medication status using OLINK technology. A data-based, unsupervised
hierarchical clustering method could identify two distinct biotypes within the 126
ADHD participants based on their inflammatory profile: a higher inflammatory potential
(HIP) and a lower inflammatory protein potential (LIP) group. Biological processes
that differed strongest between groups were related to the NF-κB pathway, chemokine
signaling, IL-17 signaling, metabolic alterations, and chemokine attraction. A comparison
of sample characteristics revealed that the HIP group was more likely to have higher
levels of chronic stress ( p < 0.001), a higher clinical global impression scale
score ( p = 0.030), and a higher risk for suicide ( p = 0.032). Medication status
did not influence protein levels significantly ( p ≥ 0.074), but psychotropic co-medication
( p ≤ 0.009) did. In conclusion, our data suggest the presence of two distinct biotypes
in adults with ADHD. Higher levels of inflammatory proteins in ADHD are linked to
higher levels of chronic perceived stress in a linear fashion. Further research on
inflammation in adults with ADHD should take stress levels into account.
