Abstract
This study was undertaken to compare endogenous lithium concentrations in human blood and its components from normal donors versus bipolar patients. The patients were not on lithium therapy at the time that the blood samples were donated and had not received any lithium therapy for at least 2 yr. Blood components were separated by centrifugation. The analytical method for lithium as developed in this laboratory consists of thermal-neutron activation of freeze-dried samples. 3H is produced via the reaction 6Li+n=3H+4He, and high-sensitivity rare gas mass spectrometry is used to measure 3He formed from β-decay of 3H. Boron measurements are made concurrently using 4He from the reaction 10B+n=4He+7Li. Seven normal donors and seven patients with a diagnosis of bipolar disorder participated in this study. Measurements of lithium and boron were made in whole blood, plasma, and red cells. Red cell-plasma ratios R(Li) and R(B) were calculated after corrections were made for trapped plasma in the red cells. The results show that bipolar patients may have higher concentrations of lithium in blood, plasma, and red cells (p=0.08, 0.02, and 0.02, respectively) and may have higher R(Li) values than normal donors (p=0.01). No evidence was found for bipolar-normal differences in these four parameters for boron. Although our sample size is admittedly very small, the results clearly show that the endogenous red cell ratio R(Li) and plasma or red cell lithium concentrations may become useful diagnostic indicators for bipolar illness if the analytical methods are further developed.
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References
A. Elizur, B. Shopsin, S. Gerson, et al., Clin. Pharmacol. Ther. 13, 947–952 (1972).
J. Mendels and A. Frazer, J Psychiatry Res. 10, 9–18 (1973).
A. Flemenbaum, R. Weddige, and J. Miller, Am. J. Psychiatry 135, 336–338 (1978).
A. K. Upadhyaya, V. K. Varma, A. Sankaranarayanan, et al., Biol. Psychiatry 20, 202–205 (1985).
J. Rybakowski, M. Chlopocka, Z. Kapelski, et al., Int. Pharmacopsychiatry 9, 166–171 (1974).
L. Knorring, L. Oreland, C. Perris, et al., Pharmakopsychiat. Neuropsychopharmakol. 9, 81–84 (1976).
G. N. Pandey, E. Dorus, J. M. Davis, et al., Arch. Gen. Psychiatry 36, 902–908 (1979).
B. E. Ehrlich and J. M. Diamond, Am. J. Physiol. 237, C102-C110 (1979).
D. C. Tosteson, Sci. Am. 244, 164–174 (1981).
B. E. Ehrlich, J. M. Diamond, V. Fry, et al., J Membr. Biol. 75, 233–240 (1983).
C. L. Cazzullo, E. Smeraldi, E. Sacchetti, et al., Br. J. Psychiatry 126, 298–299 (1975).
E. Dorus, G. N. Pandey, M. Gaviria, et al., Science 205, 932–934 (1979).
E. Dorus, G. N. Pandey, R. Shaughnessy, et al., Arch. Gen. Psychiatry 37, 80–81 (1980).
E. Dorus, N. J. Cox, R. D. Gibbons, et al., ARch. Gen. Psychiatry 40, 545–552 (1983).
R. D. Barr, W. B. Clarke, R. M. Clarke, et al., J. Lab. Clin. Med. 121, 614–619 (1993).
B. J. Carroll, Arch. Gen. Psychiatry 36, 870–878 (1979).
J. M. Jefferson, J. H. Greist, D. L. Ackerman, et al., Lithium Encyclopedia for Clinical Practice, 2nd ed., American Psychiatric Press, Washington, DC (1987).
G. Muscettola, A. Di Lauro, and C. P. Giannini, J Psychiatry Res. 18, 447–456 (1984).
W. B. Clarke, C. E. Webber, M. Koekebakker, et al., J Lab. Clin. Med. 109, 155–158 (1987).
W. B. Clarke, M. Koekebakker, R. D. Barr, et al., Appl. Radiat. Isot. 38, 735–743 (1987).
W. B. Clarke, R. M. Clarke, E. K. Olson, et al., Biol. Trace Element Res. 65, 237–249 (1998).
G. V. Iyengar, W. B. Clarke, R. G. Downing, et al., in Trace Element Analytical Chemistry in Medicine and Biology. P. Bratter and P. Schramel, eds., Proceedings of the Fifth International Workshop, Walter de Gruyter, Berlin, pp. 267–269 (1988).
G. V. Igengar, W. B. Clarke, and R. G. Downing, Fresenius J. Anal. Chem. 338, 554–558 (1990).
P. De Bievre, M. Gallet, N. E. Holden, et al., J. Phys. Chem. Ref. Data 13, 809–891 (1984).
J. S. Merritt, J. G. V. Taylor, and A. W. Boyd, Nucl. Sci. Eng. 34, 195–196 (1968).
W. S. Snyder, M. J. Cook, L. R. Karhousen, et al., Report of the Task Group on Reference Man, Pergamon, Oxford (1975).
D. York, Can. J. Phys. 44, 1079–1086 (1966).
D. G. Fleishman, Z. P. Gurevich, A. A. Solyus, et al., Dokl. Akad. Nauk SSSR 254, 1497–1501 (1980) [English trans. Dokl. Biol. Sci. 254, 519–522 (1980)].
M. Dafflon, L. A. Decosterd, J. Biollaz, et al., J Affect. Disord. 54, 199–203 (1999).
J. Mendels and A. Frazer, Am. J. Psychiatry 131, 1240–1246 (1974).
M. S. Hughes, in Lithium and the Cell: Pharmacology and Biochemistry, N. J. Birch, ed. Academic, London, pp. 175–184 (1991).
W. B. Clarke and R. S. Gibson, J Food Comp. Anal. 1, 209–220 (1988).
J-L Magnin, L. A. Decosterd, C. Centeno, et al., Pharm. Acta Helv. 71, 237–246 (1996).
L. A. Decosterd, T. Buclin, M. Dafflon, et al., J. Pharm. Pharmacol. 50, 693–701 (1998).
W. B. Clarke, R. Guscott, and R. M. Lindstrom, Biol. Trace Element Res., 97, 117–124 (2004).
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Certain commercial equipment, instruments, or materials are identified in this article to specify adequately the experimental procedure. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose.
Prof. Clarke died unexpectedly on September 3, 2002.
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Clarke, W.B., Guscott, R., Downing, R.G. et al. Endogenous lithium and boron red cell-plasma ratios. Biol Trace Elem Res 97, 105–115 (2004). https://doi.org/10.1385/BTER:97:2:105
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DOI: https://doi.org/10.1385/BTER:97:2:105