BRAIN MRI & MRS CHANGES IN FIRST EPISODE SCHIZOPHRENIA

描述：（申请人摘要中的逐字记录）我们假设， 在精神分裂症早期观察到的临床恶化是由于 从前驱期开始的有限的神经退化过程 并与阳性和阴性症状的持续存在有关。在 我们先前的研究已经证明了这种疾病的临床进展， 第一次发病的病人在四年内。初步体积MRI数据 来自该研究和其他几个小组的研究支持这一假设， 不一致和不确定。此外，尽管有许多横截面 脑缺血患者颞叶和额叶皮质NAA降低的~ 1H-MRS研究 精神分裂症，没有纵向的'H-MRS研究。因此 所提出的研究将利用高分辨率磁共振成像， 在纵向研究中结合MRJ和MRS进行重复测量， 确定是否将反映患者中观察到的临床进展 通过脑形态学和NAA的变化。具体来说，我们预测， 在MRI和MRS测量的变化中观察到的脑病理学进展 基线和终点评估（皮质灰质体积的减少， 海马减少，侧脑室和第三脑室增加， 蛛网膜下腔和近中颞叶和前额叶lH-NAA减少 皮质区和丘脑核）将在一个亚组中观察到， 复发或持续性临床结局不良的患者 精神病理学和功能障碍，并表现出最大的临床 扫描间隔期间的退化。我们还将检查Treatment 是否能预防患者的病理进展， 引入人为效应（如基底神经节）。最后我们将 确定是否有结构或代谢异常， 在精神分裂症首次发作时出现，这预示着长期的临床 结果。我们假设MRI测量更严重的脑部病理， 研究进入（如由更大的侧脑室和第三脑室容积所反映的， 皮质灰质减少，额叶和海马中NAA浓度降低， 中颞叶和丘脑核）将与较差的 长期治疗效果。我们还假设治疗将 与这些脑区的脑容量保存有关， 保留或增强额颞区NAA浓度 耳垂 为了验证我们的假设，我们将前瞻性地检查100名患者， 在他们第一次精神分裂症发作时使用高分辨率MR， 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， 非典型抗精神病药物治疗。评估患者的 研究时的精神病理学、社会和工作表现以及MRI和MRS 入组后6个月、18个月和3年随访。MRI数据 将使用分割方法进行分析，以确定特定 感兴趣的区域。NAA将通过定量NAA、Cr和 NAAJCr.这项研究将提供有关临床和 精神分裂症亚群的神经病理过程和治疗 早期识别和干预策略。

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.