SPECIFIC BRAIN SYSTEM MEDIATION OF MOOD AND RITUAL

强迫症（OCD）和重性抑郁症，单极型 (UD)，是常见的，慢性的，高度衰弱的精神疾病， 已经引起神经科学界极大的兴趣超过了世纪。它们存在 单独和共同发病。尽管生物学基础在今天 承认，大脑功能障碍，可能介导的症状， 强迫症和UD的表达需要进一步澄清。我们的（和其他）PET 测量局部脑葡萄糖代谢率的研究表明， 眶皮质-纹状体-丘脑回路作为一个可能的调解人， 强迫症状态，而我们的（和其他）PET工作涉及侧前额叶 UD时皮质和尾状核功能障碍。这些发现在人类 功能性神经解剖学保证了密集的随访，以了解 强迫症和UD的病理生理学可能导致新的治疗方法的开发 以及大脑如何调节复杂的 行为这就是促使这项实验提案进一步 阐明UD和OCD的大脑中介作用。 本建议的总体具体目标是提供对以下方面的坚定理解： 不同的，神经解剖学上组织的系统， 心理病理学的形式。使用PET的人类、大鼠和蜥蜴研究 放射自显影术，沿着药物和行为操纵， 用于严格测试直接来自于 强迫症和UD的皮质-纹状体-丘脑脑系统模型 我们提出的症状调解。本作品分为三个部分 交互式实验：1）UD中PET显示的葡萄糖代谢率与UD中的葡萄糖代谢率相比。 强迫症患者在使用单一药物治疗前后进行研究， 盐酸帕罗西汀2)下前额叶皮层与背前额叶皮层 电刺激对局部糖代谢和行为的影响 3）皮质-纹状体-肾上腺皮质-肾上腺皮质-纹状体-肾上腺皮质 丘脑回路调解的社会侵略仪式，和他们的 特定环境行为消退和药物诱导的衰减， 卡罗莱纳州的阿诺利斯。这项工作仍在继续，并且是 研究可能介导UD症状表达的大脑系统 和强迫症在这个实验室做了12年的NIMH的支持。

Obsessive-compulsive disorder (OCD) and major depression, unipolar type (UD), are common, chronic, highly debilitating psychiatric illnesses that have been of great interest to neuroscience for over a century. They exist separately and co-morbidly. Although biological underpinnings are today acknowledged, the brain dysfunctions that may mediate the symptomatic expression of OCD and UD need further clarification. Our (and other) PET studies measuring regional brain glucose metabolic rates implicate an orbital cortical-striatal-thalamic circuit as a possible mediator of the OCD state, while our (and other) PET work implicates lateral prefrontal cortex and caudate nucleus dysfunction in UD. These findings in human functional neuroanatomy warrant intense follow-up, for understanding the pathophysiology of OCD and UD may lead both to new treatment development strategies, and fundamental clues as to how brain mediates complex behavior. This is what motivates this proposal for experiments to further clarify UD and OCD's brain mediation. This proposal's general specific aim is to provide a firm understanding of the different, neuroanatomically organized systems that mediate these two forms of psycho-pathology. Human, rat, and lizard studies that employ PET and autoradiography, along with drug and behavioral manipulations, will be employed to rigorously test specific hypotheses that follow directly from the different cortico-striato-thalamic brain system models of OCD and UD symptom mediation we have proposed. This work is structured as three interactive experiments: l) PET-revealed glucose metabolic rates in UD vs. OCD patients studied pre- and post-treatment with a single agent, paroxetine hydrochloride. 2) Inferior vs. dorsal prefrontal cortex electrical stimulation effects on regional glucose metabolism and behavior in rats; 3) Deoxyglucose autoradiographic studies of cortico-striato- thalamic circuit mediation of social aggressive rituals, and their context-specific behavioral extinction and drug-induced attenuation, in Anolis carolinensis. This work continues and is a logical extension of work on brain systems that may mediate the symptomatic expression of UD and OCD done in this laboratory with NIMH support for l2 years.