THE PSYCHOLBIOLOGY AND TREATMENT OF OBESSIVE COMPULSIVE DISORDER IN ADULTS

成人强迫症的心理生物学和治疗

• 批准号: 6162821
• 负责人: D L MURPHY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162821
• 关键词: adult human (21+); anticonvulsants; basal ganglia; behavioral /social science research tag; behavioral genetics; brain electrical activity; clinical research; combination chemotherapy; fluoxetine; genetic polymorphism; genetic promoter element; hormone regulation /control mechanism; human subject; human therapy evaluation; magnetic field; mental disorder chemotherapy; obsessive compulsive disorder; pathologic process; psychobiology; serotonin transporter

This project is directed towards enhancement of our understanding of OCD pathophysiology and to investigate potential new treatments for this major neuropsychiatric disorder. Our studies focus on regional brain function in OCD, and on investigating possible genetic vulnerabilities to the illness. Prefrontal cortex-basal ganglia circuits are implicated in OCD. We found, using the novel technique of repetitive transcranial magnetic stimulation (rTMS) that focal stimulation of right prefrontal cortex temporarily reduced compulsive urges, suggesting the utility of rTMS as a probe of regional brain activity in OCD. The possibility that repeated rTMS sessions might have therapeutic effects in OCD is currently being explored in a controlled study. A study using a different TMS technique found preliminary evidence of deficits in intracortical inhibitory processes in OCD patients. A pilot study found that that open administration of the GABA-modulatory agent gabapentin, which may enhance intracortical inhibition, improved symptoms in OCD patients poorly responsive to fluoxetine monotherapy. A controlled study of gabapentin augmentation of fluoxetine treatment in OCD is underway. As a test of the hypothesis that injury to the basal ganglia predisposes to OCD, we are performing MRI T2 mapping and volumetric studies of the basal ganglia in OCD patients stratified by age of illness onset. Detection of a neuroimaging signature of such injury would be consistent with hypotheses of autoimmune basal ganglia injury as important in OCD etiology. We are exploring possible genetic etiologies of OCD by focusing on allelic variants which may affect neurotransmission in brain circuits relevant to OCD. A case-control study of a polymorphism in the catechol-O-methyl transferase gene (which produces functional effects on the activity of this enzyme) suggested that this polymorphism may constitute a risk factor for OCD. Preliminary analysis also suggests an association between allelic variation at the serotonin transporter promoter regon polymorphism site and OCD, constituting some of the first evidence that genetic differences in serotonin systems may predispose to OCD.

该项目旨在增强我们对强迫症的理解 病理生理学并调查潜在的新疗法 主要的神经精神障碍。我们的研究集中于区域大脑 在强迫症中的功能，并研究可能的遗传漏洞 疾病。 前额叶皮层 - 巴萨尔神经节电路涉及 在强迫症中。我们发现，使用了重复经颅的新技术 磁刺激（RTMS），右前刺激局灶性刺激 皮层暂时减少了强迫性冲动，表明 RTM作为强迫症中区域大脑活动的探测。可能性 重复的RTMS会话可能在OCD中具有治疗作用 目前正在对照研究中探讨。一项研究使用 不同的TMS技术发现了缺陷的初步证据 强迫症患者的心脏内抑制过程。 一项试点研究发现 GABA调节剂Gabapentin的公开给药， 这可能会增强心脏抑制作用，改善了强迫症的症状 患者对氟西汀单一疗法的反应不佳。 受控 OCD中氟西汀治疗的加巴喷丁的研究IS 进行。作为对基底神经节损伤的假设的检验 易于强迫症，我们正在执行MRI T2映射和体积 根据年龄分层的强迫症患者的基底神经节的研究 疾病发作。检测这种损伤的神经影像签名 将与自身免疫性基底神经节损伤的假设一致 在强迫症病因中同样重要。 我们正在探索可能的遗传 通过关注可能影响的等位基因变体，强迫症的病因 与强迫症相关的脑电路中的神经传递。一个案例对照 在儿茶醇-O-甲基转移酶基因中多态性的研究（其中 对此酶的活性产生功能影响） 这种多态性可能构成强迫症的危险因素。 初步分析还表明等位基因之间的关联 5-羟色胺转运蛋白启动子重物多态性位点的变化 OCD，构成了遗传的一些第一个证据 5-羟色胺系统的差异可能会易于强迫症。