DOPAMINE FUNCTION AND CEREBRAL GLUCOSE METABOLISM IN PSYCHOTIC DEPRESSION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。现在可以应用脑成像方法来研究精神性抑郁障碍的神经化学基础和糖皮质激素拮抗剂的临床反应机制。精神病性抑郁症还没有广泛的研究与神经影像学方法。精神病性抑郁症的神经生物学是一个重要的研究领域，因为与非精神病性抑郁症相比，它与更大的认知障碍、治疗抵抗和死亡率相关。本研究的目的是评价米非司酮治疗对精神病性抑郁症患者脑葡萄糖代谢和多巴胺（D2）受体利用率的影响。具体而言，入组IRB批准的治疗方案“一项在未接受抗抑郁药或抗精神病药的具有精神病特征的重度抑郁症患者中评价C-1073（米非司酮）安全性和疗效的III期、随机、双盲、安慰剂对照研究”的患者将在治疗前后接受神经影像学检查。这项研究将涉及两次正电子发射（PET）扫描（基线和米非司酮治疗一周结束时）。每次PET扫描持续约3小时。每次扫描包括一次[11 C]-雷氯必利扫描和一次[18 F]-FDG扫描。将进行MR扫描以确定感兴趣区域的位置，并校正PET数据以确定脑萎缩。假设与安慰剂治疗的患者相比，米非司酮治疗将导致皮质葡萄糖代谢增加和D2受体结合增加。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. It is now possible to apply brain imaging methodology to investigate the neurochemical basis of psychotic depressive disorder and the mechanims underlying the clinical response to glucocorticoid antagonists. Psychotic depression has not been extensively studied with neuroimaging methods. The neurobiology of psychotic depression is an important area of investigaton as it is associated with greater cognitive impairment, treatment resistance and mortality than non-psychotic depression. The purpose of the study described in the protocol is to evaluate the effects of mifepriustone treatment on cerebral glusose metabolism and dopamine (D2) receptor availability in patients with psychotic depression. Specifically, patients who are enrolled in the IRB approved treatment protocol "A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Safety and Efficacy of C-1073 (Mifepristone) in Patients with Major Depressive Disorder with Psychotic Features who are not receiving Antidepressants or Antipsychotics" will undergo neuroimaging procedures prior to and following treatment. This study will involve two Positron Emission (PET) scanning sessions (baseline and at the end of one week of treatment with mifepristone). Each PET scan session lasts approximately three hours. Each scan session involves one scan with [11C]-raclopride and one scan with [18F]-FDG. An MR scan will be performed for region of interest localization and for the correction of the PET data for cerebral atrophy. It is hypothesized that mifepristone treatment will result in increased cortical glucose metabolism and increased D2 receptor binding compared to placebo treated patients.