Brain Ion Homeostasis, Lithium and Bipolar Disorder.

描述（由申请人提供）：双相情感障碍（BPD）是最衰弱和最难治疗的精神疾病之一，估计影响美国4.4%的人口。BPD的治疗包括情绪稳定药物和心理治疗的联合应用。在用于治疗BPD的情绪稳定药物中，碳酸锂是疾病不同阶段的首选治疗方法。 锂是第一种成功用于治疗精神疾病的药物。其显著的情绪调节特性是在60年前偶然发现的，至今仍知之甚少。锂有危险的副作用，包括内分泌和神经系统疾病。这些可能很难在第一次识别，有时在急性环境中致命（约15%的受试者）。因此，锂治疗需要持续监测血清锂浓度（SLC），以确保SLC保持在0.6至1.2mM的狭窄治疗范围内。然而，使用该治疗范围仅在不到50%的受试者中获得成功结局。 脑锂浓度（BLC）被认为是比SLC更好的治疗反应预测指标。锂离子是NMR活性的，因此，当使用全脑MRS时，可以用磁共振波谱（MRS）测量。然而，全脑MRS采集的使用导致BLC的准确性和再现性较低，它低估了药物的峰值浓度，并且不能提供关于药物的空间累积的至关重要的信息。 该提案旨在开发一种使用磁共振成像（MRI）进行体内三维锂成像的方法，并确定是否可以通过监测锂给药后脑钠浓度（BSC）的正常化来间接观察锂给药后BLC的增加。由于BSC的正常化很容易用MRI以定量方式测量，因此这种方法可以为更好地管理疾病和了解其在大脑中的作用机制提供工具。所提出的方法的有效性进行测试，通过在匹兹堡大学的西方精神病研究所和诊所的临床基础设施招募的BPD科目。 公共卫生相关性：本提案旨在开发一种方法，用于使用MRI技术改善双相情感障碍受试者的管理。目标是开发一种技术，允许使用MRI测量大脑中的锂蓄积，因为这被认为是比血清锂含量更好的结果预测因子（血清锂含量是目前用于管理疾病的关键临床变量）。

DESCRIPTION (provided by applicant): Bipolar Disorder (BPD) is one of the most debilitating and difficult to treat mental illnesses and it affects an estimated 4.4% of the population in the United States. Treatment of BPD involves the combined used of mood stabilizing drugs and psychotherapy. Among the mood stabilizing drugs used to treat BPD, Lithium Carbonate is an established treatment of first choice for different stages of the disease. Lithium was the first medication successfully used to treat mental illnesses. Its remarkable mood regulating properties were accidentally discovered 60 years ago and remain poorly understood to this date. Lithium has dangerous side effects that include endocrine as well as neurological ailments. These could be difficult to recognize at first and sometimes lethal in the acute setting (about 15% of subjects). Consequently, lithium treatment requires constant monitoring of serum lithium concentration (SLC) to ensure that SLC remains in the narrow therapeutic range of 0.6 to 1.2mM. However, use of this therapeutic range only leads to a successful outcome in less than 50% of the subjects. Brain Lithium Concentration (BLC) is accepted to be a better predictor of therapeutic response than SLC. The lithium ion is NMR active and, therefore, measurable with magnetic resonance spectroscopy (MRS) when whole-brain MRS is used. Use of whole-brain MRS acquisitions, however, leads to lower accuracy and reproducibility for BLC, it underestimates the peak concentration of the drug and cannot provide critically important information about the spatial accumulation of the drug. This proposal is aimed at developing a methodology for in vivo three dimensional lithium imaging using magnetic resonance imaging (MRI) and establishing if the increase in BLC that follows lithium administration can be indirectly observed by monitoring the normalization of brain sodium concentration (BSC) that it induces. Because the normalization of BSC is easily measurable in a quantitative fashion with MRI, this methodology could provide a tool for better management of the disease and understanding its mechanisms of action in the brain. The effectiveness of the proposed methodology is to be tested on BPD subjects recruited through the clinical infrastructure of the Western Psychiatric Institutes and Clinic at the University of Pittsburgh. PUBLIC HEALTH RELEVANCE: This proposal aims to develop a methodology for improving the management of Bipolar Disease Subjects using MRI technology. The goal is to develop a technique that allows the measurement of lithium accumulation in the brain with MRI as this is accepted to be a better predictor of outcome than the serum lithium content (which is a critical clinical variable currently used to manage the disease).