{"doi":"10.1111/acps.12983","title":"A multisystem composite biomarker as a preliminary diagnostic test in bipolar disorder","abstract":"<jats:sec><jats:title>Objective</jats:title><jats:p>Diagnosis and management of bipolar disorder (<jats:styled-content style=\"fixed-case\">BD</jats:styled-content>) are limited by the absence of available laboratory tests. We aimed to combine data from different molecular levels and tissues into a composite diagnostic and state biomarker.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Expression levels of 19 candidate genes in peripheral blood, plasma levels of <jats:styled-content style=\"fixed-case\">BDNF</jats:styled-content>,<jats:styled-content style=\"fixed-case\"> NT</jats:styled-content>‐3, <jats:styled-content style=\"fixed-case\">IL</jats:styled-content>‐6 and <jats:styled-content style=\"fixed-case\">IL</jats:styled-content>‐18, leukocyte counts, and urinary markers of oxidative damage to <jats:styled-content style=\"fixed-case\">DNA</jats:styled-content> and <jats:styled-content style=\"fixed-case\">RNA</jats:styled-content> were measured in 37 adult rapid‐cycling patients with <jats:styled-content style=\"fixed-case\">BD</jats:styled-content> in different affective states during a 6‐ to 12‐month period and in 40 age‐ and gender‐matched healthy individuals in a longitudinal, repeated measures design comprising a total of 211 samples. A composite biomarker was constructed using data‐driven variable selection.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The composite biomarker discriminated between patients with <jats:styled-content style=\"fixed-case\">BD</jats:styled-content> and healthy control individuals with an area under the receiver operating characteristic curve (<jats:styled-content style=\"fixed-case\">AUC</jats:styled-content>) of 0.83 and a sensitivity of 73% and specificity of 71% corresponding with a moderately accurate test. Discrimination between manic and depressive states had a moderate accuracy, with an <jats:styled-content style=\"fixed-case\">AUC</jats:styled-content> of 0.82 and a sensitivity of 92% and a specificity of 40%.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Combining individual biomarkers across tissues and molecular systems could be a promising avenue for research in biomarker models in <jats:styled-content style=\"fixed-case\">BD</jats:styled-content>.</jats:p></jats:sec>","journal":"Acta Psychiatrica Scandinavica","year":2019,"id":667717,"datarank":0.519860385419959,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.0,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":678577,"name":"Maj Vinberg","orcid":"0000-0002-5982-1335","position":1,"is_corresponding":false},{"id":1618519,"name":"B. K. Pedersen","orcid":null,"position":2,"is_corresponding":false},{"id":1743664,"name":"H. E. Poulsen","orcid":null,"position":3,"is_corresponding":false},{"id":1743665,"name":"C. T. Ekstrøm","orcid":null,"position":4,"is_corresponding":false},{"id":227400,"name":"Lars Vedel Kessing","orcid":"0000-0001-9377-9436","position":5,"is_corresponding":false},{"id":38182,"name":"Klaus Munkholm","orcid":"0000-0001-6437-0359","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A multisystem composite biomarker as a preliminary diagnostic test in bipolar disorder","abstract":"<jats:sec><jats:title>Objective</jats:title><jats:p>Diagnosis and management of bipolar disorder (<jats:styled-content style=\"fixed-case\">BD</jats:styled-content>) are limited by the absence of available laboratory tests. We aimed to combine data from different molecular levels and tissues into a composite diagnostic and state biomarker.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Expression levels of 19 candidate genes in peripheral blood, plasma levels of <jats:styled-content style=\"fixed-case\">BDNF</jats:styled-content>,<jats:styled-content style=\"fixed-case\"> NT</jats:styled-content>‐3, <jats:styled-content style=\"fixed-case\">IL</jats:styled-content>‐6 and <jats:styled-content style=\"fixed-case\">IL</jats:styled-content>‐18, leukocyte counts, and urinary markers of oxidative damage to <jats:styled-content style=\"fixed-case\">DNA</jats:styled-content> and <jats:styled-content style=\"fixed-case\">RNA</jats:styled-content> were measured in 37 adult rapid‐cycling patients with <jats:styled-content style=\"fixed-case\">BD</jats:styled-content> in different affective states during a 6‐ to 12‐month period and in 40 age‐ and gender‐matched healthy individuals in a longitudinal, repeated measures design comprising a total of 211 samples. A composite biomarker was constructed using data‐driven variable selection.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The composite biomarker discriminated between patients with <jats:styled-content style=\"fixed-case\">BD</jats:styled-content> and healthy control individuals with an area under the receiver operating characteristic curve (<jats:styled-content style=\"fixed-case\">AUC</jats:styled-content>) of 0.83 and a sensitivity of 73% and specificity of 71% corresponding with a moderately accurate test. Discrimination between manic and depressive states had a moderate accuracy, with an <jats:styled-content style=\"fixed-case\">AUC</jats:styled-content> of 0.82 and a sensitivity of 92% and a specificity of 40%.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Combining individual biomarkers across tissues and molecular systems could be a promising avenue for research in biomarker models in <jats:styled-content style=\"fixed-case\">BD</jats:styled-content>.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30383306","pmcid":null,"openalex_id":"https://openalex.org/W2899308020","authors":[],"funders":[{"funder_name":"Fonden til Lægevidenskabens Fremme","grant_id":"11–246","title":null},{"funder_name":"Lundbeckfonden","grant_id":"R34A3696","title":null},{"funder_name":"Det Frie Forskningsråd","grant_id":"09‐073972","title":null},{"funder_name":"Fonden til Laegevidenskabens Fremme","grant_id":"11-246","title":null},{"funder_name":"Det Frie Forskningsråd","grant_id":"09-073972","title":null},{"funder_name":"Overlaege dr. med. 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