Probing the White Matter in Schizophrenia Using Novel MRS Techniques

描述（由申请人提供）：这是一份来自早期研究者的BRAINS 2011 R01提案，专注于精神分裂症的白质异常。大量文献强调了这种情况下白质的异常，并表明这些可能是“连接异常”（即异常连接）综合征的基础，导致该疾病的一些核心特征的出现。迄今为止，大多数研究都集中在“白质完整性降低”和髓磷脂丢失的可能性上，作为一种病理生理机制。然而，在体内几乎没有髓磷脂丢失的直接证据。最近发展的MRI/MRS技术提供了量化白质中轴突和髓鞘相关异常的机会。PI是K23职业发展奖获得者，其研究重点是质子磁共振波谱（MRS）在精神疾病中的研究。在目前的提案中，他和他的同事将在4特斯拉下实施两种这样的技术（扩散张量光谱或DTS，和磁化传递比或MTR），并从精神分裂症患者和健康对照者的右侧前额皮质的9cc纯白质体素中收集数据。具体来说，我们将使用DTS收集水扩散数据（类似于扩散张量成像或DTI研究）来复制过去关于该主题的研究，然后测量仅反映轴突变化的细胞内代谢物（n -乙酰天冬氨酸或NAA）的扩散特性。我们还将在同一研究中使用MTR检查髓磷脂含量。最后，我们将通过将DTS和MTR异常与CNTRICS倡议（Stroop任务）推荐的执行功能的前额叶依赖测量的表现相关联，来检查DTS和MTR异常的重要性。因此，我们将解剖轴突和髓鞘相关的白质异常，以提供对精神分裂症信号传导完整性的机制见解。我们假设髓磷脂水平的降低只是部分原因，轴突的变化增加了一个新的维度，在检查精神分裂症的信号传导异常时需要考虑到这一点。

DESCRIPTION (provided by applicant): This is a BRAINS 2011 R01 proposal from an early stage investigator focusing on white matter abnormalities in schizophrenia. A large literature highlights the abnormalities in white matter in this condition, and suggests that these may underlie a "dysconnection" (i.e. abnormal connection) syndrome leading to the emergence of some core features of the illness. Most research to date has focused on "reduced white matter integrity" and the possibility of myelin loss as a pathophysiological mechanism. There is little direct evidence for myelin loss in schizophrenia in vivo, however. Recently developed MRI/MRS techniques provide an opportunity quantify axon- and myelin-related abnormalities in the white matter. The PI is a K23 Career Development Award holder whose research has focused proton magnetic resonance spectroscopy (MRS) studies in psychiatric disorders. In the current proposal, he and his colleagues will implement 2 such techniques (diffusion tensor spectroscopy or DTS, and magnetization transfer ratio or MTR) at 4 Tesla and collect data from a 9cc pure white matter voxel in the right prefrontal cortex in patients with schizophrenia and healthy controls. Specifically we will use DTS to collect water diffusion data (which is analogous to diffusion tensor imaging or DTI studies) to replicate past studies on the topic, then measure the diffusion properties of an intracellular metabolite (N-acetylaspartate or NAA) which reflects axonal changes only. We will also examine myelin content using MTR in the same study. Finally, we will examine the significance of DTS and MTR abnormalities by correlating them with performance on a prefrontal-dependent measure of executive function recommended by the CNTRICS initiative, the Stroop task. Thus, we will dissect the axonal and myelin-related white matter abnormalities in a way that provides mechanistic insights into the integrity of signal conduction in schizophrenia. We hypothesize that a reduction of myelin levels is only part of the picture and that axonal changes add a new dimension which needs to be considered when examining signal conduction abnormalities in schizophrenia.