{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:06:54Z","timestamp":1787162814088,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:00:00Z","timestamp":1567987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Bipolar disorder (BD) is a complex neuropsychiatric disorder characterized by recurrent mania and depression episodes and requiring lifelong treatment with mood stabilizing drugs. Several lines of evidence, including with BD patient iPSC\u2010derived neurons, suggest that neuronal hyperexcitability may underlie the key clinical symptoms of BD. Indeed, higher mRNA levels of\n                    <jats:italic>SCN11A<\/jats:italic>\n                    , coding for the voltage\u2010gated sodium channel Na\n                    <jats:sub>V<\/jats:sub>\n                    1.9 implicated in nociception, were detected in iPSC\u2010derived neurons from BD patients, and were normalized by in vitro lithium. Here we studied\n                    <jats:italic>SCN11A<\/jats:italic>\n                    expression in peripheral blood mononuclear cells (PBMCs) from well\u2010phenotyped female BD patients and controls and evaluated their association with several clinical sub\u2010phenotypes. We observed higher mRNA levels of\n                    <jats:italic>SCN11A<\/jats:italic>\n                    in PBMCs from female BD patients with no records of alcohol dependence (\n                    <jats:italic>p<\/jats:italic>\n                    =\u2009.0050), no records of psychosis (\n                    <jats:italic>p<\/jats:italic>\n                    =\u2009.0097), or no records of suicide attempts (\n                    <jats:italic>p<\/jats:italic>\n                    =\u2009.0409). A trend was observed for higher\n                    <jats:italic>SCN11A<\/jats:italic>\n                    expression (FD = 1.91;\n                    <jats:italic>p<\/jats:italic>\n                    =\u2009.052) in BD PBMCs compared with controls. Datamining of published postmortem gene expression datasets indicated higher\n                    <jats:italic>SCN11A<\/jats:italic>\n                    expression in dorsolateral prefrontal cortex and orbitofrontal cortex tissues from BD patients compared with controls. Higher phenotype\u2010associated expression levels in PBMC from BD patients were also observed for\n                    <jats:italic>ID2<\/jats:italic>\n                    (alcohol dependence, suicide attempts) and\n                    <jats:italic>HDGFRP3<\/jats:italic>\n                    (seasonal BD pattern). Our findings suggest that higher PBMC\n                    <jats:italic>SCN11A<\/jats:italic>\n                    expression levels may be associated with certain behavioral BD sub\u2010phenotypes, including lack of alcohol dependence and psychosis, among BD patients. The Na\n                    <jats:sub>V<\/jats:sub>\n                    1.9 voltage\u2010gated sodium channel thus deserves consideration as a tentative phenotype modifier in BD.\n                  <\/jats:p>","DOI":"10.1002\/ddr.21598","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T13:01:07Z","timestamp":1568034067000},"page":"1128-1135","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<i>SCN11A<\/i>\n                    mRNA levels in female bipolar disorder PBMCs as tentative biomarker for distinct patient sub\u2010phenotypes"],"prefix":"10.1002","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7782-3185","authenticated-orcid":false,"given":"Irena","family":"Voinsky","sequence":"first","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry Sackler Faculty of Medicine, Tel\u2010Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6219-4945","authenticated-orcid":false,"given":"Michael J.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California San Diego  La Jolla California"},{"name":"VA San Diego Healthcare System  San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2424-2202","authenticated-orcid":false,"given":"Tatyana","family":"Shekhtman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California San Diego  La Jolla California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3013-2333","authenticated-orcid":false,"given":"John R.","family":"Kelsoe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California San Diego  La Jolla California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9363-1869","authenticated-orcid":false,"given":"David","family":"Gurwitz","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry Sackler Faculty of Medicine, Tel\u2010Aviv University  Tel Aviv Israel"},{"name":"Sagol School of Neuroscience, Tel Aviv University  Tel Aviv 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