SPECIFIC BRAIN SYSTEM MEDIATION OF MOOD AND RITUAL

强迫症(OCD)与单相型重度抑郁症 (UD)是常见的、慢性的、高度虚弱的精神疾病， 一个多世纪以来一直是神经科学研究的热点。他们存在 分别和共同病态地。尽管今天的生物学基础 公认的，大脑功能障碍可能调解症状 强迫症和UD的表达有待进一步澄清。我们(和其他)的宠物 测量局部脑葡萄糖代谢率的研究表明 眼眶皮质-纹状体-丘脑环路可能是脑电活动的中介 强迫症状态，而我们(和其他)的PET检查涉及额叶外侧 UD患者皮质和尾状核功能障碍。在人类身上的这些发现 功能神经解剖学需要紧张的随访，以了解 强迫症和UD的病理生理学可能会导致新的治疗方法的发展 策略，以及大脑如何调节复杂性的基本线索 行为。这就是这项实验提案的动机所在 阐明UD和强迫症的大脑调节作用。 这项提案的总的具体目标是提供对 不同的，神经解剖学组织的系统，调节这两个 各种形式的心理病理学。利用PET进行的人类、老鼠和蜥蜴研究 放射自显影，以及药物和行为操作，将是 用来严格测试直接从 强迫症和糖尿病不同皮质-纹状体-丘脑系统模型的建立 我们已经提出了症状调解。这项工作被组织成三个部分 互动实验：L)PET-揭示UD与 强迫症患者在治疗前和治疗后使用单一药物进行研究， 盐酸帕罗西汀。2)下前额叶皮质与背侧前额叶皮质 电刺激对局部糖代谢和行为的影响 3)皮质纹状体脱氧葡萄糖放射自显影研究。 丘脑回路对社会攻击性仪式的调节，及其 特定背景的行为灭绝和药物诱导的衰减，在 卡罗琳石斑鱼。这项工作仍在继续，是对 对可能调节UD症状表达的大脑系统的研究 以及在NIMH支持下在本实验室完成L2年的强迫症。

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.