Williams Nicole, Layden Brian T, Suhy Joyce, Metreger Tabitha, Foley Kathleen, Abukhdeir Abde M, Borge George, Crayton John, Bryant Fred B, Mota de Freitas Duarte
Department of Chemistry, Loyola University Chicago, Chicago, IL 60626, USA.
Bipolar Disord. 2003 Oct;5(5):320-9. doi: 10.1034/j.1399-5618.2003.00054.x.
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.
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.
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.
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.
锂治疗双相情感障碍患者的红细胞在细胞内锂浓度（[Li⁺]i）、钠/锂交换率和膜磷脂水平方面显示出异常。基于锂负载红细胞研究，我们假设与血压正常的患者相比，锂治疗双相情感障碍患者的细胞内游离镁离子浓度（[Mg²⁺]f）也有所不同。我们探讨了这些实验测定值之间是如何相互关联的。假设锂治疗会改变这些生化参数，我们基于结构方程模型统计提供了假设途径。
在30例锂治疗双相情感障碍患者的红细胞中，我们测定了[Li⁺]i、血清锂浓度（[Li⁺]e）、钠/锂交换参数、膜磷脂水平、[Mg²⁺]f和锂膜结合亲和力。综合统计分析评估了生化数据之间的相关性。我们使用路径分析统计来提出数据相关的潜在途径。
我们发现三个钠/锂交换参数与膜磷脂的百分比组成之间存在显著相关性。[Mg²⁺]f与Vstd、Km或磷脂组成之间、[Li⁺]i与磷脂酰胆碱百分比之间以及磷脂酰丝氨酸百分比与Km之间还存在其他相关性。基于这些发现，我们假设并通过统计确定了这些参数相互关联的最可能途径。
描述细胞膜异常的生化参数与锂/镁竞争假说之间存在显著相关性。使用路径分析统计，我们确定了一条锂可能发挥其细胞效应的生化途径。本研究作为一个示例说明了路径分析是确定特定生化途径方向的有价值工具。
