Biological Trace Element Research

, Volume 97, Issue 2, pp 105–115 | Cite as

Endogenous lithium and boron red cell-plasma ratios

Normal subjects versus bipolar patients not on lithium therapy
  • W. Brian Clarke
  • Richard Guscott
  • R. Gregory Downing
  • Richard M. Lindstrom


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.

Index Entries

Endogenous lithium boron human blood red cells plasma bipolar 


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  1. 1.
    A. Elizur, B. Shopsin, S. Gerson, et al., Clin. Pharmacol. Ther. 13, 947–952 (1972).PubMedGoogle Scholar
  2. 2.
    J. Mendels and A. Frazer, J Psychiatry Res. 10, 9–18 (1973).CrossRefGoogle Scholar
  3. 3.
    A. Flemenbaum, R. Weddige, and J. Miller, Am. J. Psychiatry 135, 336–338 (1978).PubMedGoogle Scholar
  4. 4.
    A. K. Upadhyaya, V. K. Varma, A. Sankaranarayanan, et al., Biol. Psychiatry 20, 202–205 (1985).PubMedCrossRefGoogle Scholar
  5. 5.
    J. Rybakowski, M. Chlopocka, Z. Kapelski, et al., Int. Pharmacopsychiatry 9, 166–171 (1974).PubMedGoogle Scholar
  6. 6.
    L. Knorring, L. Oreland, C. Perris, et al., Pharmakopsychiat. Neuropsychopharmakol. 9, 81–84 (1976).Google Scholar
  7. 7.
    G. N. Pandey, E. Dorus, J. M. Davis, et al., Arch. Gen. Psychiatry 36, 902–908 (1979).PubMedGoogle Scholar
  8. 8.
    B. E. Ehrlich and J. M. Diamond, Am. J. Physiol. 237, C102-C110 (1979).PubMedGoogle Scholar
  9. 9.
    D. C. Tosteson, Sci. Am. 244, 164–174 (1981).PubMedCrossRefGoogle Scholar
  10. 10.
    B. E. Ehrlich, J. M. Diamond, V. Fry, et al., J Membr. Biol. 75, 233–240 (1983).PubMedCrossRefGoogle Scholar
  11. 11.
    C. L. Cazzullo, E. Smeraldi, E. Sacchetti, et al., Br. J. Psychiatry 126, 298–299 (1975).PubMedCrossRefGoogle Scholar
  12. 12.
    E. Dorus, G. N. Pandey, M. Gaviria, et al., Science 205, 932–934 (1979).PubMedCrossRefGoogle Scholar
  13. 13.
    E. Dorus, G. N. Pandey, R. Shaughnessy, et al., Arch. Gen. Psychiatry 37, 80–81 (1980).PubMedGoogle Scholar
  14. 14.
    E. Dorus, N. J. Cox, R. D. Gibbons, et al., ARch. Gen. Psychiatry 40, 545–552 (1983).PubMedGoogle Scholar
  15. 15.
    R. D. Barr, W. B. Clarke, R. M. Clarke, et al., J. Lab. Clin. Med. 121, 614–619 (1993).PubMedGoogle Scholar
  16. 16.
    B. J. Carroll, Arch. Gen. Psychiatry 36, 870–878 (1979).PubMedGoogle Scholar
  17. 17.
    J. M. Jefferson, J. H. Greist, D. L. Ackerman, et al., Lithium Encyclopedia for Clinical Practice, 2nd ed., American Psychiatric Press, Washington, DC (1987).Google Scholar
  18. 18.
    G. Muscettola, A. Di Lauro, and C. P. Giannini, J Psychiatry Res. 18, 447–456 (1984).CrossRefGoogle Scholar
  19. 19.
    W. B. Clarke, C. E. Webber, M. Koekebakker, et al., J Lab. Clin. Med. 109, 155–158 (1987).PubMedGoogle Scholar
  20. 20.
    W. B. Clarke, M. Koekebakker, R. D. Barr, et al., Appl. Radiat. Isot. 38, 735–743 (1987).CrossRefGoogle Scholar
  21. 21.
    W. B. Clarke, R. M. Clarke, E. K. Olson, et al., Biol. Trace Element Res. 65, 237–249 (1998).Google Scholar
  22. 22.
    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).Google Scholar
  23. 23.
    G. V. Igengar, W. B. Clarke, and R. G. Downing, Fresenius J. Anal. Chem. 338, 554–558 (1990).CrossRefGoogle Scholar
  24. 24.
    P. De Bievre, M. Gallet, N. E. Holden, et al., J. Phys. Chem. Ref. Data 13, 809–891 (1984).CrossRefGoogle Scholar
  25. 25.
    J. S. Merritt, J. G. V. Taylor, and A. W. Boyd, Nucl. Sci. Eng. 34, 195–196 (1968).Google Scholar
  26. 26.
    W. S. Snyder, M. J. Cook, L. R. Karhousen, et al., Report of the Task Group on Reference Man, Pergamon, Oxford (1975).Google Scholar
  27. 27.
    D. York, Can. J. Phys. 44, 1079–1086 (1966).Google Scholar
  28. 28.
    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)].PubMedGoogle Scholar
  29. 29.
    M. Dafflon, L. A. Decosterd, J. Biollaz, et al., J Affect. Disord. 54, 199–203 (1999).PubMedCrossRefGoogle Scholar
  30. 30.
    J. Mendels and A. Frazer, Am. J. Psychiatry 131, 1240–1246 (1974).PubMedGoogle Scholar
  31. 31.
    M. S. Hughes, in Lithium and the Cell: Pharmacology and Biochemistry, N. J. Birch, ed. Academic, London, pp. 175–184 (1991).Google Scholar
  32. 32.
    W. B. Clarke and R. S. Gibson, J Food Comp. Anal. 1, 209–220 (1988).CrossRefGoogle Scholar
  33. 33.
    J-L Magnin, L. A. Decosterd, C. Centeno, et al., Pharm. Acta Helv. 71, 237–246 (1996).PubMedCrossRefGoogle Scholar
  34. 34.
    L. A. Decosterd, T. Buclin, M. Dafflon, et al., J. Pharm. Pharmacol. 50, 693–701 (1998).PubMedGoogle Scholar
  35. 35.
    W. B. Clarke, R. Guscott, and R. M. Lindstrom, Biol. Trace Element Res., 97, 117–124 (2004).CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • W. Brian Clarke
    • 1
  • Richard Guscott
    • 2
  • R. Gregory Downing
    • 3
  • Richard M. Lindstrom
    • 3
  1. 1.Department of Physics and AstronomyMcMaster UniversityHamiltonCanada
  2. 2.Guscott and Taylor Mood Disorders ClinicHamiltonCanada
  3. 3.National Institute of Standards and TechnologyGaithersburg

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