Testing competing path models linking the biochemical variables in red blood cells from Li+-treated bipolar patients.
OBJECTIVE
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+]e), 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.
Williams
Nicole
N
Department of Chemistry, Loyola University Chicago, Chicago, IL 60626, USA.
Layden
Brian T
BT
Suhy
Joyce
J
Metreger
Tabitha
T
Foley
Kathleen
K
Abukhdeir
Abde M
AM
Borge
George
G
Crayton
John
J
Bryant
Fred B
FB
Mota de Freitas
Duarte
D
D000328:Adult; D001692:Biological Transport; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008094:Lithium / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D008274:Magnesium / Q000097:blood; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010743:Phospholipids / Q000097:blood; D012964:Sodium / Q000097:blood
D010743:Phospholipids; D008094:Lithium; D012964:Sodium; D008274:Magnesium