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SCN11A mRNA levels in female bipolar disorder PBMCs as tentative biomarker for distinct patient sub‐phenotypes
Author(s) -
Voinsky Irena,
McCarthy Michael J.,
Shekhtman Tatyana,
Kelsoe John R.,
Gurwitz David
Publication year - 2019
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21598
Subject(s) - bipolar disorder , peripheral blood mononuclear cell , mania , young mania rating scale , medicine , psychosis , prefrontal cortex , biomarker , endocrinology , dorsolateral prefrontal cortex , lithium (medication) , psychiatry , psychology , biology , in vitro , genetics , cognition
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‐derived neurons, suggest that neuronal hyperexcitability may underlie the key clinical symptoms of BD. Indeed, higher mRNA levels of SCN11A , coding for the voltage‐gated sodium channel Na V 1.9 implicated in nociception, were detected in iPSC‐derived neurons from BD patients, and were normalized by in vitro lithium. Here we studied SCN11A expression in peripheral blood mononuclear cells (PBMCs) from well‐phenotyped female BD patients and controls and evaluated their association with several clinical sub‐phenotypes. We observed higher mRNA levels of SCN11A in PBMCs from female BD patients with no records of alcohol dependence ( p = .0050), no records of psychosis ( p = .0097), or no records of suicide attempts ( p = .0409). A trend was observed for higher SCN11A expression (FD = 1.91; p = .052) in BD PBMCs compared with controls. Datamining of published postmortem gene expression datasets indicated higher SCN11A expression in dorsolateral prefrontal cortex and orbitofrontal cortex tissues from BD patients compared with controls. Higher phenotype‐associated expression levels in PBMC from BD patients were also observed for ID2 (alcohol dependence, suicide attempts) and HDGFRP3 (seasonal BD pattern). Our findings suggest that higher PBMC SCN11A expression levels may be associated with certain behavioral BD sub‐phenotypes, including lack of alcohol dependence and psychosis, among BD patients. The Na V 1.9 voltage‐gated sodium channel thus deserves consideration as a tentative phenotype modifier in BD.