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

Isabel Schnorr, Anne Siegl, Sonja Luckhardt, Söri Wenz, Hendrik Friedrichsen, Hiba El Jomaa, Annebirth Steinmann, Tünde Kilencz, Gara Arteaga-Henríquez, Carolina Ramos-Sayalero, Pol Ibanez-Jimenez, Silvia Karina Rosales-Ortiz, István Bitter, Christian Fadeuilhe, Marc Ferrer, Catharina Lavebratt, János M Réthelyi, Vanesa Richarte, Nanda Rommelse, Josep Antoni Ramos-QuirogaAlejandro Arias-Vasquez, Eduard Resch, Andreas Reif, Silke Matura, Carmen Schiweck

Research output: Contribution to journalArticleAcademicpeer-review

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 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.

Original languageEnglish
Article number37
Number of pages14
JournalTranslational Psychiatry
Volume14
Issue number1
DOIs
Publication statusPublished - 18 Jan 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024, The Author(s).

Funding

We thank all participants for their contribution to the study. We thank Maren Ballhausen, Luisa Lambert, and Kevin Amaral for their contributions to the testing sessions and screenings at the Frankfurt site. The technical assistance of Katalin Vincze and Zsófia Horváth in sample preparation at the Budapest site is gratefully acknowledged, and finally, Frank Schmidt (Weill Cornell Medicine–Qatar) has helped with the Voronoi maps, and his help is gratefully acknowledged. This work was supported by the European Union’s Horizon 2020 Research and Innovation Program under grant agreement No. 728018. The funding source has had no involvement in the study design, data collection, interpretation of the findings, or writing of this manuscript.

FundersFunder number
Horizon 2020 Framework Programme728018
Horizon 2020 Framework Programme

    Keywords

    • Adult
    • Attention Deficit Disorder with Hyperactivity/diagnosis
    • Chemokines/therapeutic use
    • Child
    • Humans
    • Inflammation
    • Proteome
    • Smoking

    Fingerprint

    Dive into the research topics of 'Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory proteome'. Together they form a unique fingerprint.

    Cite this