BRAIN LITHIUM LEVELS IN BIPOLAR INDIVIDUALS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。锂被认为对中枢神经系统有治疗作用。细胞内和中枢神经系统的锂离子水平与活性反运输活性（Na-Li反运输活性）呈负相关。因此，在血浆锂离子水平相同的情况下，反转运活性低的患者细胞内和中枢神经系统的锂离子水平较高。脑锂水平似乎比血清锂水平和红细胞锂水平与治疗效果和副作用有更高的相关性，这可能是因为反运输活性水平的差异。锂7核磁共振光谱提供了一种间接的体内脑锂水平测量方法，准确度合理（精密度5.2%，准确度优于7.2%）。作者假设非洲裔美国人的Na-Li反转运活性低于对照组的西欧裔高加索人，这些组间差异与脑/血清Li比值增加、双相情感障碍临床疗效增加以及副作用增加有关。这是一项前瞻性横断面观察性研究，纳入了大约25名年龄在18-54岁之间的患者（33名入组，保留率为60%，可用数据为25例），根据DSM标准患有双相情感障碍的非洲裔美国人（两代同质血统），服用长效锂制剂，以及同等数量的西欧高加索人对照受试者。筛选合格的受试者将在BMC GCRC完成心理测试和血液测试，然后在2-3周后返回McLean医院进行Li7核磁共振波谱和重复血液测试。主要结局指标是脑/血清Li比值。将使用非参数检验的独立样本参数对两组进行比较。研究人员将通过与脑锂水平的相关性来确定临床疗效和副作用的次要结局指标。

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.