{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T10:17:30Z","timestamp":1778321850737,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T00:00:00Z","timestamp":1496361600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIMH CIDAR award","award":["P50 MH077138"],"award-info":[{"award-number":["P50 MH077138"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Individualized treatment for bipolar disorder based on neuroimaging treatment targets remains elusive. To address this shortcoming, we developed a linguistic machine learning system based on a cascading genetic fuzzy tree (<jats:styled-content style=\"fixed-case\">GFT<\/jats:styled-content>) design called the <jats:styled-content style=\"fixed-case\">LITH<\/jats:styled-content>ium Intelligent Agent (<jats:styled-content style=\"fixed-case\">LITHIA<\/jats:styled-content>). Using multiple objectively defined <jats:styled-content style=\"fixed-case\">functional magnetic resonance imaging (fMRI<\/jats:styled-content>) and proton magnetic resonance spectroscopy (<jats:sup>1<\/jats:sup>H\u2010<jats:styled-content style=\"fixed-case\">MRS<\/jats:styled-content>) inputs, we tested whether <jats:styled-content style=\"fixed-case\">LITHIA<\/jats:styled-content> could accurately predict the lithium response in participants with first\u2010episode bipolar mania.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We identified 20 subjects with first\u2010episode bipolar mania who received an adequate trial of lithium over 8\u00a0weeks and both <jats:styled-content style=\"fixed-case\">fMRI<\/jats:styled-content> and <jats:sup>1<\/jats:sup>H\u2010<jats:styled-content style=\"fixed-case\">MRS<\/jats:styled-content> scans at baseline pre\u2010treatment. We trained <jats:styled-content style=\"fixed-case\">LITHIA<\/jats:styled-content> using 18 <jats:sup>1<\/jats:sup>H\u2010<jats:styled-content style=\"fixed-case\">MRS<\/jats:styled-content> and 90 <jats:styled-content style=\"fixed-case\">fMRI<\/jats:styled-content> inputs over four training runs to classify treatment response and predict symptom reductions. Each training run contained a randomly selected 80% of the total sample and was followed by a 20% validation run. Over a different randomly selected distribution of the sample, we then compared <jats:styled-content style=\"fixed-case\">LITHIA<\/jats:styled-content> to eight common classification methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">LITHIA<\/jats:styled-content> demonstrated nearly perfect classification accuracy and was able to predict post\u2010treatment symptom reductions at 8\u00a0weeks with at least 88% accuracy in training and 80% accuracy in validation. Moreover, <jats:styled-content style=\"fixed-case\">LITHIA<\/jats:styled-content> exceeded the predictive capacity of the eight comparator methods and showed little tendency towards overfitting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results provided proof\u2010of\u2010concept that a novel <jats:styled-content style=\"fixed-case\">GFT<\/jats:styled-content> is capable of providing control to a multidimensional bioinformatics problem\u2014namely, prediction of the lithium response\u2014in a pilot data set. Future work on this, and similar machine learning systems, could help assign psychiatric treatments more efficiently, thereby optimizing outcomes and limiting unnecessary treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12507","type":"journal-article","created":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T11:27:04Z","timestamp":1496402824000},"page":"259-272","source":"Crossref","is-referenced-by-count":47,"title":["Prediction of lithium response in first\u2010episode mania using the LITHium Intelligent Agent (<scp>LITHIA<\/scp>): Pilot data and proof\u2010of\u2010concept"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0777-401X","authenticated-orcid":false,"given":"David E","family":"Fleck","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH USA"},{"name":"Center for Imaging Research University of Cincinnati College of Medicine  Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Ernest","sequence":"additional","affiliation":[{"name":"Psibernetix Inc.  Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caleb M","family":"Adler","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH USA"},{"name":"Center for Imaging Research University of Cincinnati College of Medicine  Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Aerospace Engineering and Engineering Mechanics University of Cincinnati College of Engineering and Applied Science  Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C","family":"Eliassen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH USA"},{"name":"Center for Imaging Research University of Cincinnati College of Medicine  Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Norris","sequence":"additional","affiliation":[{"name":"Center for Imaging Research University of Cincinnati College of Medicine  Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A","family":"Komoroski","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH USA"},{"name":"Center for Imaging Research University of Cincinnati College of Medicine  Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Jang","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH USA"},{"name":"Center for Imaging Research University of Cincinnati College of Medicine  Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A","family":"Welge","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J","family":"Blom","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa P","family":"DelBello","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen M","family":"Strakowski","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH USA"},{"name":"Center for Imaging Research University of Cincinnati College of Medicine  Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,6,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(02)00322-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(02)00332-4"},{"key":"e_1_2_7_4_1","volume-title":"Manic\u2010Depressive Illness: Bipolar Disorders and Recurrent Depression, Second Edition, New York","author":"Goodwin FK","year":"2007"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.156.8.1264"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2051-5545.2011.tb00046.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.12.014"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511642197.030"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010814-124502"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12426"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.133.5.429"},{"key":"e_1_2_7_12_1","volume-title":"Structured Clinical Interview for DSM\u2010IV Axis I Disorders\u2010 Patient Edition (SCID\u2010I\/P). 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