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  • To measure 18 intracellular proteins in blood cells of bipolar depressed patients and healthy controls;

  • TFour proteins in monocytes and 2 proteins in CD4+ T Cells were significantly lower in patients than in healthy controls;

  • The studied proteins are involved in prolactin, leptin, BDNF, and interleukin-3 signal pathways;

  • Studying intracellular proteins with enhanced flow cytometry may find biomarkers differentiating bipolar disorder from healthy controls.



Molecular biomarkers for bipolar disorder (BD) that distinguish it from other manifestations of depressive symptoms remain unknown. The aim of this study was to determine if a very sensitive tyramine-based signal-amplification technology for flow cytometry (CellPrint™) could facilitate the identification of cell-specific analyte expression profiles of peripheral blood cells for bipolar depression (BPD) versus healthy controls (HCs).


The diagnosis of psychiatric disorders was ascertained with Mini International Neuropsychiatric Interview for DSM-5. Expression levels for eighteen protein analytes previously shown to be related to bipolar disorder were assessed with CellPrint™ in CD4+ T cells and monocytes of bipolar patients and HCs. Implementation of protein-protein interaction (PPI) network and pathway analysis was subsequently used to identify new analytes and pathways for subsequent interrogations.


Fourteen drug-naïve or -free patients with bipolar I or II depression and 17 healthy controls (HCs) were enrolled. The most distinguishable changes in analyte expression based on t-tests included GSK3β, HMGB1, IRS2, phospho-GSK3αβ, phospho-RELA, and TSPO in CD4+ T cells and calmodulin, GSK3β, IRS2, and phospho-HS1 in monocytes. Subsequent PPI and pathway analysis indicated that prolactin, leptin, BDNF, and interleukin-3 signal pathways were significantly different between bipolar patients and HCs.


The sample size of the study was small and 2 patients were on medications.


In this pilot study, CellPrint™ was able to detect differences in cell-specific protein levels between BPD patients and HCs. A subsequent study including samples from patients with BPD, major depressive disorder, and HCs is warranted.


Original published version available at

Publication Title

Journal of Affective Disorders





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