Probing the White Matter in Schizophrenia Using Novel MRS Techniques

描述（由申请人提供）：这是一份BRAINS 2011 R 01提案，来自一名早期研究者，重点关注精神分裂症中的白色物质异常。大量文献强调了这种情况下白色物质的异常，并表明这些可能是导致疾病某些核心特征出现的“连接障碍”（即异常连接）综合征的基础。迄今为止，大多数研究都集中在“减少白色物质的完整性”和髓鞘丢失作为一种病理生理机制的可能性。然而，几乎没有直接证据表明精神分裂症体内髓鞘丢失。最近开发的MRI/MRS技术提供了一个机会量化轴突和髓鞘相关的异常在白色的问题。PI是K23职业发展奖保持器持有者，其研究重点是质子磁共振波谱（MRS）在精神疾病中的研究。在目前的提议中，他和他的同事将在4特斯拉下实施2种这样的技术（扩散张量光谱或MRI，磁化转移比或MTR），并从精神分裂症患者和健康对照组的右前额皮质中的9 cc纯白色物质体素收集数据。具体来说，我们将使用ESTA来收集水扩散数据（类似于扩散张量成像或DTI研究），以复制过去的研究主题，然后测量细胞内代谢物（N-乙酰天冬氨酸或NAA）的扩散特性，仅反映轴突的变化。我们还将在同一研究中使用MTR检查髓鞘含量。最后，我们将研究的意义，通过将它们与执行功能的前额叶依赖性措施的CNTRICS倡议，Stroop任务建议的性能相关的ESTA和MTR异常。因此，我们将解剖轴突和髓鞘相关的白色物质异常，为精神分裂症信号传导的完整性提供机械见解。我们假设，髓鞘水平的降低只是图片的一部分，轴突的变化增加了一个新的维度，需要考虑在精神分裂症的信号传导异常时检查。

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.