BRAIN MRI & MRS CHANGES IN FIRST EPISODE SCHIZOPHRENIA

描述：(逐字摘自申请人的摘要)我们假设 精神分裂症早期的临床恶化是由于 从前驱期开始的有限的神经退变过程 并与阳性症状和阴性症状的持续存在有关。在……里面 我们之前的研究已经证明了这种疾病的临床进展 第一次发作的患者超过四年。初步的体积磁共振数据 从那项研究和其他几个小组支持这一假设，但 前后不一致，没有定论。此外，尽管有许多横截面 脑梗塞患者颞叶和额叶皮质NAA减少的~1H-MRS研究 对于精神分裂症，还没有纵向的H-MRS研究。因此， 拟议的研究将利用高分辨率磁共振成像， 在一项纵向研究中结合MRJ和MRS，反复测量 确定患者的临床进展是否会得到反映 通过脑组织形态和NAA的变化。具体地说，我们预测 从MRI和MRS的变化看脑部病理的进展 基线和终点评估(皮质灰质体积减少， 减少海马体，增加侧脑室和第三脑室并增加 蛛网膜下腔与颞叶、额叶内侧及前额叶促黄体生成素的降低 皮质区域和丘脑核团)将观察到 临床结果差的患者，表现为复发或持续 精神病理学和功能损害，以及谁表现出最大的临床 在扫描间隔期间恶化。我们还将检查治疗情况 作用于它是否能防止患者或 引入伪像效果(如在基底节)。最后，我们会 确定是否存在结构或代谢异常 出现在精神分裂症的第一个发病阶段，预示着长期的临床 结果。我们假设核磁共振测量到更严重的脑部病变 研究条目(如较大的侧脑室和第三脑室体积所反映的， 皮质灰质减少，额叶和额叶NAA浓度降低 近颞叶和丘脑核团)将与较差的 长期治疗结果。我们还假设治疗将是 与保存这些脑区的脑容量有关，并且 额叶和颞叶NAA浓度的维持或升高 叶状叶。 为了验证我们的假设，我们将前瞻性地检查100名确诊的患者。 在他们的精神分裂症的第一次发作中使用高分辨率磁共振和 三年内的光谱成像。治疗将标准化 使用开放标签临床治疗算法，提供最佳 使用非典型抗精神病药物进行治疗。将对患者进行评估 精神病理学、社会和工作表现以及研究中的核磁共振和磁共振波谱 入选后分别于6个月、18个月和3年进行随访。磁共振成像数据 将使用分段方法进行分析，以确定具体的音量 感兴趣的区域。NAA的测定将通过NAA、Cr和 NAAJCR.这项研究将为临床和临床治疗提供重要信息。 精神分裂症各亚型的神经病理过程及治疗 及早识别和干预的策略。

DESCRIPTION: (Verbatim from the Applicant's Abstract) We have hypothesized that the clinical deterioration observed in the early stage of schizophrenia is due to a process of limited neurodegeneration that begins in the prodromal phase and is associated with the persistence of positive and negative symptoms. In our prior study we have demonstrated the clinical progression of the illness in first episode patients over a four-year period. Preliminary volumetric MRI data from that study and from several other groups support this hypothesis but are inconsistent and inconclusive. Moreover, despite the numerous cross-sectional 'H-MRS studies of decreased NAA in temporal and frontal cortices in schizophrenia, there have been no longitudinal 'H-MRS studies. Therefore, the proposed study will utilize high resolution magnetic resonance imaging, combining MRJ and MRS in a longitudinal study with repeated measurements to determine whether the clinical progression seen in patients will be reflected by changes in brain morphology and NAA. Specifically, we predict that the progression of brain pathology seen in changes in MRI and MRS measures between baseline and end point assessments (decreasing volumes of cortical gray matter, decreasing hippocampus, increasing lateral and third ventricles and increasing subarachnoid space and decreasing lH-NAA in mesiotemporal and prefrontal cortical regions and thalamic nuclei) will be observed in a subgroup of patients with poor clinical outcomes reflected by recurrent or persistent psychopathology and functional impairment and who exhibit the greatest clinical deterioration during the scanning intervals. We also will examine trealment effects in terms of whether it prevents pathological progression in patients or introduces artifactual effects (such as in the basal ganglia). Finally, we will determine whether there are structural or metabolic abnormalities that are present at the first episode of schizophrenia which predict long-term clinical outcome. We hypothesize that MRI measures of more severe brain pathology at study entry (as reflected by greater lateral and third ventricles volumes, reduced cortical gray matter, and reduced NAA concentration in the frontal and mesiotemporal lobes and the thalamic nuclei) will be associated with poorer long term treatment outcome. We also hypothesize that treatment will be associated with preservation of brain volume in these brain regions and preservation or enhancement of NAA concentration in the frontal and temporal lobes. To test our hypotheses we will prospectively examine 100 patients ascertained in their first episode of schizophrenia using high resolution MR and spectroscopic imaging over a three-year period. Treatment will be standardized using an open label clinical treatment algorithm that provides optimal treatment with atypical antipsychotic drugs. Patients will be assessed for psychopathology, social and work performance and with MRI and MRS at study entry and at six months, eighteen months and three year of follow-up. MRI data will be analyzed using segmentation methods to determine the volume of specific regions of interest. NAA will be determined by quantitation of NAA, Cr and NAAJCr. This study will provide important information about the clinical and neuropathological course of subgroups of schizophrenia and therapeutic strategies for early identification and intervention.