Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory pro-teome

Author:

Schiweck Carmen1ORCID,Schnorr Isabel,Siegl Anne,Luckhardt Sonja,Wenz Söri,Friedrichsen Hendrik,Jomaa Hiba El,Steinmann Annebirth,Kilencz Tünde,Arteaga-Henríquez Gara,Ramos-Sayalero Carolina,Ibanez-Jimenez Pol,Rosales-Ortiz Silvia,Bitter Istvan2ORCID,Fadeuilhe Christian,Ferrer Marc,Lavebratt Catharina3ORCID,Réthelyi János,Richarte Vanesa,Rommelse Nanda,Ramos-Quiroga Josep Antoni4ORCID,Vasquez Alejandro Arias5ORCID,Resch Eduard,Reif Andreas6ORCID,Matura Silke7

Affiliation:

1. Goethe University Frankfurt

2. Semmelweis University

3. Karolinska Institutet

4. Hospital Universitari Vall d'Hebron.

5. Radboudumc

6. University Hospital Frankfurt, Germany

7. Goethe University Frankfurt/M.

Abstract

Abstract 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 pheno-typed 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 psychological 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.

Publisher

Research Square Platform LLC

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