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Transdiagnostic inflammatory subgroups among psychiatric disorders and their relevance to role functioning: a nested case-control study of the ALSPAC cohort
Individuals with psychotic disorders and depressive disorder exhibit altered concentrations of peripheral inflammatory markers. It has been suggested that clinical trials of anti-inflammatory therapies for psychiatric disorders should stratify patients by their inflammatory profile. Hence, we invest...
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Published in: | Translational psychiatry 2022-09, Vol.12 (1), p.377-377, Article 377 |
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description | Individuals with psychotic disorders and depressive disorder exhibit altered concentrations of peripheral inflammatory markers. It has been suggested that clinical trials of anti-inflammatory therapies for psychiatric disorders should stratify patients by their inflammatory profile. Hence, we investigated whether different subgroups of individuals exist across psychiatric disorders, based on their inflammatory biomarker signatures. We measured the plasma concentrations of 17 inflammatory markers and receptors in 380 participants with psychotic disorder, depressive disorder or generalised anxiety disorder and 399 controls without psychiatric symptoms from the ALSPAC cohort at age 24. We employed a semi-supervised clustering algorithm, which discriminates multiple clusters of psychiatric disorder cases from controls. The best fit was for a two-cluster model of participants with psychiatric disorders (Adjusted Rand Index (ARI) = 0.52 ± 0.01) based on the inflammatory markers. Permutation analysis indicated the stability of the clustering solution performed better than chance (ARI = 0.43 ± 0.11;
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p
< 0.001), and the clusters explained the inflammatory marker data better than a Gaussian distribution (
p
= 0.021). Cluster 2 exhibited marked increases in sTNFR1/2, suPAR, sCD93 and sIL-2RA, compared to cluster 1. Participants in the cluster exhibiting higher inflammation were less likely to be in employment, education or training, indicating poorer role functioning. This study found evidence for a novel pattern of inflammatory markers specific to psychiatric disorders and strongly associated with a transdiagnostic measure of illness severity. sTNFR1/2, suPAR, sCD93 and sIL-2RA could be used to stratify clinical trials of anti-inflammatory therapies for psychiatric disorders.</description><identifier>ISSN: 2158-3188</identifier><identifier>EISSN: 2158-3188</identifier><identifier>DOI: 10.1038/s41398-022-02142-2</identifier><identifier>PMID: 36085284</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/21 ; 631/378 ; 692/53 ; 692/699/476/1414 ; 692/699/476/1799 ; Adult ; Behavioral Sciences ; Biological Psychology ; Case-Control Studies ; Clinical trials ; Cohort Studies ; Humans ; Medicine ; Medicine & Public Health ; Mental disorders ; Mental Disorders - diagnosis ; Neurosciences ; Pharmacotherapy ; Psychiatry ; Psychosis ; Psychotic Disorders - diagnosis ; Receptors, Urokinase Plasminogen Activator ; Young Adult</subject><ispartof>Translational psychiatry, 2022-09, Vol.12 (1), p.377-377, Article 377</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-d1bed80ef1ef0c4c9f845e581001cd53df7172f5d870a286d0266d8057ae3a1d3</citedby><cites>FETCH-LOGICAL-c540t-d1bed80ef1ef0c4c9f845e581001cd53df7172f5d870a286d0266d8057ae3a1d3</cites><orcidid>0000-0002-7046-0630 ; 0000-0002-6299-2952 ; 0000-0003-4308-0648 ; 0000-0001-7931-9636</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2712118320/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2712118320?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,25734,27905,27906,36993,36994,44571,53772,53774,74875</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36085284$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Byrne, Jonah F.</creatorcontrib><creatorcontrib>Healy, Colm</creatorcontrib><creatorcontrib>Mongan, David</creatorcontrib><creatorcontrib>Susai, Subash Raj</creatorcontrib><creatorcontrib>Zammit, Stan</creatorcontrib><creatorcontrib>Fӧcking, Melanie</creatorcontrib><creatorcontrib>Cannon, Mary</creatorcontrib><creatorcontrib>Cotter, David R.</creatorcontrib><title>Transdiagnostic inflammatory subgroups among psychiatric disorders and their relevance to role functioning: a nested case-control study of the ALSPAC cohort</title><title>Translational psychiatry</title><addtitle>Transl Psychiatry</addtitle><addtitle>Transl Psychiatry</addtitle><description>Individuals with psychotic disorders and depressive disorder exhibit altered concentrations of peripheral inflammatory markers. It has been suggested that clinical trials of anti-inflammatory therapies for psychiatric disorders should stratify patients by their inflammatory profile. Hence, we investigated whether different subgroups of individuals exist across psychiatric disorders, based on their inflammatory biomarker signatures. We measured the plasma concentrations of 17 inflammatory markers and receptors in 380 participants with psychotic disorder, depressive disorder or generalised anxiety disorder and 399 controls without psychiatric symptoms from the ALSPAC cohort at age 24. We employed a semi-supervised clustering algorithm, which discriminates multiple clusters of psychiatric disorder cases from controls. The best fit was for a two-cluster model of participants with psychiatric disorders (Adjusted Rand Index (ARI) = 0.52 ± 0.01) based on the inflammatory markers. Permutation analysis indicated the stability of the clustering solution performed better than chance (ARI = 0.43 ± 0.11;
p
< 0.001), and the clusters explained the inflammatory marker data better than a Gaussian distribution (
p
= 0.021). Cluster 2 exhibited marked increases in sTNFR1/2, suPAR, sCD93 and sIL-2RA, compared to cluster 1. Participants in the cluster exhibiting higher inflammation were less likely to be in employment, education or training, indicating poorer role functioning. 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It has been suggested that clinical trials of anti-inflammatory therapies for psychiatric disorders should stratify patients by their inflammatory profile. Hence, we investigated whether different subgroups of individuals exist across psychiatric disorders, based on their inflammatory biomarker signatures. We measured the plasma concentrations of 17 inflammatory markers and receptors in 380 participants with psychotic disorder, depressive disorder or generalised anxiety disorder and 399 controls without psychiatric symptoms from the ALSPAC cohort at age 24. We employed a semi-supervised clustering algorithm, which discriminates multiple clusters of psychiatric disorder cases from controls. The best fit was for a two-cluster model of participants with psychiatric disorders (Adjusted Rand Index (ARI) = 0.52 ± 0.01) based on the inflammatory markers. Permutation analysis indicated the stability of the clustering solution performed better than chance (ARI = 0.43 ± 0.11;
p
< 0.001), and the clusters explained the inflammatory marker data better than a Gaussian distribution (
p
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subjects | 13/21 631/378 692/53 692/699/476/1414 692/699/476/1799 Adult Behavioral Sciences Biological Psychology Case-Control Studies Clinical trials Cohort Studies Humans Medicine Medicine & Public Health Mental disorders Mental Disorders - diagnosis Neurosciences Pharmacotherapy Psychiatry Psychosis Psychotic Disorders - diagnosis Receptors, Urokinase Plasminogen Activator Young Adult |
title | Transdiagnostic inflammatory subgroups among psychiatric disorders and their relevance to role functioning: a nested case-control study of the ALSPAC cohort |
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