GUANFACINE IN THE TREATMENT OF BORDERLINE PERSONALITY DISORDER

胍法辛治疗边缘性人格障碍

• 批准号: 7605364
• 负责人: ANTONIA S NEW
• 金额: $ 0.3万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605364
• 关键词: Adrenergic Agonists; Adult; Affect; Affective; Aggressive behavior; Amygdaloid structure; Attention; Attention deficit hyperactivity disorder; Behavior; Behavioral; Blinking; Borderline Personality Disorder; Brain; Brain region; Child; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Deterioration; Disease; Emotional; Emotions; Functional Magnetic Resonance Imaging; Funding; Grant; Guanfacine; Guanfacine Monohydrochloride; Hypertension; Institution; Limbic System; Measures; Modification; Patients; Perceptual disturbance; Performance; Placebos; Prefrontal Cortex; Protocols documentation; Rate; Research; Research Personnel; Resources; Risk; Short-Term Memory; Source; Stimulus; Symptoms; Testing; Time Perception; Toxic effect; United States Food and Drug Administration; United States National Institutes of Health; Vulnerable Populations; Week; blood oxygenation level dependent response; cognitive function; emotional stimulus; frontal lobe; frontal lobe function; improved; improved functioning; interest; novel; response

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. This project proposes to test the effects of guanfacine hydrochloride, a Food and Drug Administration (FDA)-approved alpha-2 adrenergic agonist, in borderline personality disorder (BPD), a prevalent and disabling disorder characterized by affective lability, impulsive aggression, cognitive-perceptual disturbances and unstable interpersonal relationships. The available treatments for BPD are notorious for their variable and limited efficacy, and many of these treatments carry significant risks of somatic toxicity and/or psychiatric deterioration. Guanfacine is a safe agent that has been used in physically vulnerable populations including children (for attention-deficit hyperactivity disorder) and medically compromised adults (for hypertension, for which it is FDA-approved). By stimulating alpha-2 adrenoreceptors in prefrontal cortex, guanfacine has been shown to enhance attention and reduce behavioral dysregulation. We believe that guanfacine represents an important, novel and promising treatment for BPD in that it has the potential to ameliorate one of the core disturbances of the disorder - relatively hypoactive or ineffective modulation of affect and behavior by the prefrontal cortex (particularly orbital frontal cortex), resulting in an imbalance between emotions arising from the amygdala/limbic system and "top-down" control in higher brain centers. Hypotheses: 1) Guanfacine will decrease impulsive aggressive symptoms and improve emotional lability in borderline personality disorder compared to placebo. 2) Borderline patients will show decreased activity at baseline in OFC and increased activity in amygdala compared to healthy comparison subjects. Borderline patients will show enhanced startle eyeblink modification in response to negative pictures compared to controls. Borderline patients will show deficits in cognitive tasks that particularly tap OFC function (e.g. the time perception task) compared to other frontal lobe function (e.g. a spatial working memory task). 3) Healthy control subjects will show stable responses in the regions of interest we are studying (OFC, amygdala) to emotional pictures over an 8 week period. 4) Guanfacine will increase activation in orbital frontal cortex and decrease amygdala activation as measured by BOLD response with fMRI in response to negative emotional pictures and decrease subjective ratings of the aversiveness of the negative pictures compared to placebo. Guanfacine will decrease the amplitude of the startle eyeblink enhancement to emotional pictures in borderline subjects, reflecting improved top-down control of amygdala activation compared to placebo. 5) Guanfacine compared to placebo will specifically improve function on those cognitive tasks that test orbital frontal activity (e.g. the time perception task) more than it will improve performance on tests of cognitive function that tap other brain regions such as dorsolateral prefrontal cortex (e.g. a spatial working memory task). Exploratory Hypothesis: (see Protocol, p. 7) 1) BPD subjects with the lowest activity in OFC in response to negative emotional stimuli and the highest enhancement of startle response to negative stimuli will be less likely to respond to guanfacine than those with responses that more closely resemble our healthy controls (e.g. more robust OFC response to negative emotional stimuli and more modest enhancement of startle response to negative stimuli).

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目提议测试食品和药物管理局（FDA）批准的盐酸瓜素盐酸盐的作用，对边缘性人格障碍（BPD）（一种普遍且残疾的疾病），这是情感不稳定，脉动性侵略性侵略性，认知性疾病障碍和不稳定的室友关系。 BPD的可用治疗方法因其可变和有限的功效而臭名昭著，其中许多治疗方法具有躯体毒性和/或精神病恶化的重大风险。鸟明是一种安全的药物，已用于身体脆弱的人群中，包括儿童（用于缺乏注意力的多动障碍）和医学上折衷的成年人（对于高血压，它是FDA批准的）。通过刺激前额叶皮质中的α-2肾上腺受体，已证明鸟法可以增强注意力并减少行为失调。我们认为，圭施碱代表了BPD的一种重要，新颖且有希望的治疗方法，因为它有可能改善该疾病的核心干扰之一 - 相对较低或无效地调节前额叶皮层（尤其是轨道额叶皮层）（尤其是轨道额皮层）的影响和行为，从而导致脑中的不平衡脑中的脑/型脑中的脑中/imby/limbicgdala''''''''''''''' 假设： 1）与安慰剂相比，与安慰剂相比，胍法汀将​​减少冲动性侵略性症状并改善边缘性人格障碍的情绪不稳定。 2）与健康的比较受试者相比，OFC的基线中的边界患者在基线时的活性下降，杏仁核的活性增加。与对照组相比，边界患者将对负面图片显示出惊吓的震颤修饰。与其他额叶功能相比，边界患者将显示出尤其是OFC功能的认知任务（例如，时间感知任务）（例如，空间工作记忆任务）。 3）健康控制受试者将在我们正在研究的（OFC，Amygdala）对情感图片的感兴趣区域中显示出稳定的反应。 4）与安慰剂相比，与安慰剂相比，通过对负面情绪图片的大胆反应来响应负面情绪图像，与fMRI相比，通过对fMRI的粗体反应来衡量鸟丝额的激活，并减少杏仁核的激活。与安慰剂相比，瓜施汀将减少惊吓震颤增强对情感图片的振幅，反映出改善了杏仁核激活的自上而下的控制。 5）与安慰剂相比，与安慰剂相比，将特别改善对测试轨道额叶活动（例如时间感知任务）的认知任务的功能，而不是可以提高认知功能测试的性能，从而利用其他大脑区域（例如背侧前额叶皮层）（例如，空间工作记忆任务）。 探索性假设：（请参阅协议，第7页） 1）与负面情绪刺激有关的BPD受试者对负面的情绪刺激的反应最低，而对负面刺激的惊吓反应最高的反应对瓜施碱的反应较小，而瓜诺法辛的反应比具有更类似于我们的健康对照的反应的人（例如，对我们的健康对照组的反应都更像（例如，对OFC对负面情绪刺激的反应更强大，对刺激性的更强大的反应对刺激的反应更加适度对刺激性刺激的反应增强了刺激的刺激）。