This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lithium is presumed to act therapeutically in the CNS. Intracellular and CNS lithium levels are inversely related to the active counter-transport activity (Na-Li counter-transport activity). Thus, patients with low counter-transport activity have higher intracellular and CNS levels of lithium at the same plasma LI level. Brain lithium levels appear to have a higher correlation with therapeutic effect and side effects than do serum lithium levels and RBC lithium levels presumably because of differences in the level of counter-transport activity. Li7 NMR spectroscopy provides an indirect in vivo measurement of brain Li levels with reasonable accuracy (precision 5.2%, accuracy better than 7.2%). The authors hypothesize that Americans of African descent have lower Na-Li counter-transport activity than controls who are Caucasians of Western European Descent and that these between group differences are associated with increased brain/serum Li ratios, increase clinical efficacy for bipolar disorder and increase side effects as well. This is a prospective cross-sectional observational study of approximately 25 patients ages 18-54 (33 enrolled with 60% retention and 25 usable data) American of African descent (two generations of homogeneous descent) with bipolar disorder per DSM criteria who are on long acting lithium preparations and an equal number of control subjects who are Caucasians of Western European descent. Screened eligible subjects will complete psychological tests and blood tests at the BMC GCRC, then return 2-3 weeks for Li7 NMR spectroscopy and repeat blood tests at McLean's hospital. The primary outcome measure is the brain/serum Li ratio. The 2 groups will be compared using independent sample parametric of non-parametric tests. The investigators will determine secondary outcome measures of clinical efficacy and side effects by correlation with brain Li levels.
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