Testing competing path models linking the biochemical variables in red blood cells from Li+ -treated bipolar patients

Nicole Williams, Brian T. Layden, Joyce Suhy, Tabitha Metreger, Kathleen Foley, Abde M. Abukhdeir, George Borge, John Crayton, Fred B. Bryant, Duarte Mota de Freitas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Objectives: Red blood cells (RBCs) from Li+-treated bipolar patients have shown abnormalities in intracellular Li+ concentration ([Li+]i), Na+/Li+ exchange rates, and membrane phospholipid levels. Based on Li+-loaded RBC studies, we hypothesized that Li+-treated bipolar patients also have varied intracellular free Mg2+ concentrations ([Mg2+]f) as compared with normotensive patients. We addressed how these experimentally determined values are intercorrelated. Assuming that Li+ treatment alters these biochemical parameters, we provide hypothetical pathways based upon structural equation modeling statistics. Methods: In RBCs from 30 Li+-treated bipolar patients, we determined [Li+]i, serum [Li+] ([Li+]c), Na+/Li+ exchange parameters, membrane phospholipid levels, [Mg2+]f, and Li+ membrane binding affinities. Comprehensive statistical analyses assessed correlations among the biochemical data. We used path analysis statistics to propose potential pathways in which the data were correlated. Results: We found significant correlations within the three Na+/Li+ exchange parameters and percentage composition of the membrane phospholipids. Additional correlations existed between [Mg2+]f and Vstd, Km, or phospholipid composition, between [Li+]i and percentage of phosphatidylcholine, and between percentage of phosphatidylserine and Km. Based on these findings, we hypothesized and statistically determined the most probable pathway through which these parameters were intercorrelated. Conclusions: Significant correlations existed between the biochemical parameters that describe the cell membrane abnormality and the Li+/Mg2+ competition hypotheses. Using path analysis statistics, we identified a biochemical pathway by which Li+ may assert its cellular effects. This study serves as an illustrative example how path analysis is a Valuable tool in determining the direction of a certain biochemical pathway.

Original languageEnglish (US)
Pages (from-to)320-329
Number of pages10
JournalBipolar Disorders
Issue number5
StatePublished - Oct 2003


  • Bipolar disorder
  • Li transport
  • Lithium
  • Path analysis statistics
  • Red blood cells

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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