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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-\u03baB 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 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), a higher clinical global impression scale score (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.030), and a higher risk for suicide (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.032). Medication status did not influence protein levels significantly (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2265\u20090.074), but psychotropic co-medication (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.009) 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.\n                  <\/jats:p>","DOI":"10.1038\/s41398-023-02729-3","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T11:03:33Z","timestamp":1705575813000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory proteome"],"prefix":"10.1038","volume":"14","author":[{"given":"Isabel","family":"Schnorr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Siegl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Luckhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f6ri","family":"Wenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Friedrichsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiba","family":"El Jomaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annebirth","family":"Steinmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00fcnde","family":"Kilencz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gara","family":"Arteaga-Henr\u00edquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Ramos-Sayalero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pol","family":"Ibanez-Jimenez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Karina","family":"Rosales-Ortiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9464-4709","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Bitter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Fadeuilhe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4987-2718","authenticated-orcid":false,"given":"Catharina","family":"Lavebratt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos M.","family":"R\u00e9thelyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanesa","family":"Richarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanda","family":"Rommelse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1622-0350","authenticated-orcid":false,"given":"Josep Antoni","family":"Ramos-Quiroga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4786-0169","authenticated-orcid":false,"given":"Alejandro","family":"Arias-Vasquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard","family":"Resch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0992-634X","authenticated-orcid":false,"given":"Andreas","family":"Reif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Matura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4215-0448","authenticated-orcid":false,"given":"Carmen","family":"Schiweck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,18]]},"reference":[{"key":"2729_CR1","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1016\/j.biopsych.2004.10.020","volume":"57","author":"J Biederman","year":"2005","unstructured":"Biederman J. 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GAH reported receiving personal fees from Janssen outside the submitted work. IB reported receiving consulting fees from Gedeon Richter and Janssen\/Janssen-Cilag; speaker\u2019s honoraria from Gedeon Richter, Hikma Pharmaceuticals, Janssen\/Janssen-Cilag, KRKA, Lundbeck, and Medichem Pharmaceuticals Inc. by Unilab; research grant from Gedeon Richter; royalties from Oxford University Press. AR reported receiving personal fees from Medice, Shire\/Takeda, SAGE\/Biogen, Boehringen Ingelheim, Janssen, and Cyclerion outside the submitted work and funding from the European Union\u2019s Horizon 2020 Research and Innovation Program under grant agreement No. 667302 and 964215. 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