{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:07:48Z","timestamp":1773763668757,"version":"3.50.1"},"reference-count":103,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T00:00:00Z","timestamp":1673049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brain and Behavior Research Foundation with an independent investigator"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: There is no biomarker to predict lithium response. This study used CellPrint\u2122 enhanced flow cytometry to study 28 proteins representing a spectrum of cellular pathways in monocytes and CD4+ lymphocytes before and after lithium treatment in patients with bipolar disorder (BD). Materials and Methods: Symptomatic patients with BD type I or II received lithium (serum level \u2265 0.6 mEq\/L) for 16 weeks. Patients were assessed with standard rating scales and divided into two groups, responders (\u226550% improvement from baseline) and non-responders. Twenty-eight intracellular proteins in CD4+ lymphocytes and monocytes were analyzed with CellPrint\u2122, an enhanced flow cytometry procedure. Data were analyzed for differences in protein expression levels. Results: The intent-to-treat sample included 13 lithium-responders (12 blood samples before treatment and 9 after treatment) and 11 lithium-non-responders (11 blood samples before treatment and 4 after treatment). No significant differences in expression between the groups was observed prior to lithium treatment. After treatment, the majority of analytes increased expression in responders and decreased expression in non-responders. Significant increases were seen for PDEB4 and NR3C1 in responders. A significant decrease was seen for NR3C1 in non-responders. Conclusions: Lithium induced divergent directionality of protein expression depending on the whether the patient was a responder or non-responder, elucidating molecular characteristics of lithium responsiveness. A subsequent study with a larger sample size is warranted.<\/jats:p>","DOI":"10.3390\/medicina59010120","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T02:09:39Z","timestamp":1673230179000},"page":"120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry"],"prefix":"10.3390","volume":"59","author":[{"given":"Keming","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"},{"name":"Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas M.","family":"Kaye","sequence":"additional","affiliation":[{"name":"CellPrint Biotechnology, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzieh","family":"Ayati","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet","family":"Koyuturk","sequence":"additional","affiliation":[{"name":"Department of Computer and Data Sciences, Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph R.","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"},{"name":"Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Christian","sequence":"additional","affiliation":[{"name":"CellPrint Biotechnology, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1159-5607","authenticated-orcid":false,"given":"Hillard M.","family":"Lazarus","sequence":"additional","affiliation":[{"name":"Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"CellPrint Biotechnology, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-9254","authenticated-orcid":false,"given":"David","family":"Kaplan","sequence":"additional","affiliation":[{"name":"CellPrint Biotechnology, Cleveland, OH 44106, USA"},{"name":"Department of Medicine-Hematology\/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/bdi.12609","article-title":"Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder","volume":"20","author":"Yatham","year":"2018","journal-title":"Bipolar Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1097\/JCP.0000000000000927","article-title":"A pilot study of the effectiveness of lithium versus quetiapine immediate release monotherapy in patients with bipolar spectrum disorders","volume":"38","author":"Gao","year":"2018","journal-title":"J. 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