快感缺失、发育和情绪:表型和治疗学 (ADEPT)
快感缺失、发育和情绪:表型和治疗学 (ADEPT) 研究
ADEPT 研究的目标是了解年轻人的快感缺失,以及它如何根据针对其背后的大脑回路的治疗而发生变化。 快感缺失是一种具有挑战性的心理健康症状,涉及难以体验愉快事件的动力。 这项研究可能有助于为那些抑郁症无法通过传统疗法得到改善的人开发治疗方法。
ADEPT 研究包括两个阶段。 在第一阶段,参与者被要求通过一系列活动来衡量快感缺乏,包括 MRI 扫描、抽血、行为任务、临床访谈、问卷调查以及基于应用程序的体验和行为评估。 第 2 阶段涉及治疗活动,例如经颅磁刺激 (TMS)、积极影响训练,以及对某些人来说,氯胺酮给药。 如果参与者符合条件并且有兴趣,他们可以选择在第 1 阶段之外进行第 2 阶段的活动。
研究概览
详细说明
在这项研究中,研究人员正试图了解和改变患有抑郁症的年轻人的快感缺乏症。 许多抑郁症患者都经历过快感缺失,包括动力、精力和对愉快事件的预期困难。 经历过快感缺乏的人通常有更严重的抑郁症,经历更长的抑郁症,并且不容易通过传统疗法好转。 研究人员希望在生命早期了解快感缺乏症,以帮助年轻人沿着健康的道路发展并避免慢性病。 快感缺失与大脑奖赏回路的功能、身体的炎症以及人们的经历和行为有关,并将衡量所有这些。 研究人员还想通过使用可以改善它的治疗来了解快感缺乏症。 为此,将使用已用于治疗抑郁症的活动并针对大脑的奖励回路,这被认为是快感缺乏的根源。 最后,将在大约 1 年内测量快感缺失,以了解它如何随时间、发展或基于治疗的经验而变化。 最终,这项研究的结果可能有助于治疗抑郁症和改善人们的生活质量。
该研究正在寻找 300 名目前患有抑郁症的年轻人(15-25 岁)参与我们的研究。 在我们研究的第一阶段,将开展一系列活动来了解快感缺乏的特征,包括 MRI 扫描、抽血、行为任务、临床访谈、问卷调查以及使用手机应用程序测量现实生活体验和行为。 这称为“表型分析”,因为这些特征也称为表型。
第 1 阶段的资格审查过程将包括面谈,询问有关参与者的情绪、经历和行为的问题。 这次面试大约需要 2-3 个小时。 经许可,将对访谈进行录像,以方便对研究人员进行培训和监督。 还将向参与者询问有关健康的问题,包括治疗史。
研究程序包括大约 1 年的 4 次就诊。 出于日程安排的原因,每次访问可能会分成两个会话。 此外,该研究还将包括一项持续的基于智能手机应用程序的情绪、体验和行为评估。
访问 1 包括 MRI 扫描、关于思想、情绪和经历的问卷调查、计算机上的任务以及由训练有素的抽血师抽血。 第 2-4 次访问包括第二次 MRI 扫描、问卷调查、计算机上的任务、由训练有素的抽血师抽血以及关于情绪、经历和行为的访谈。
这项研究的第 2 阶段涉及治疗性程序,这意味着它们可以治疗抑郁症和快感缺乏症。 其中包括经颅磁刺激 (TMS),这是一种治疗抑郁症的非侵入性手术,使用磁场刺激大脑中的神经细胞。 使用 TMS 的访问将包括积极影响训练,这涉及改变行为和思想以建立积极情绪。 TMS 不能改善抑郁症的人可以接受单次静脉内(IV,或静脉内)输注氯胺酮,这是一种在医院用于麻醉的药物,可以迅速改善抑郁症。
研究类型
注册 (实际的)
阶段
- 第四阶段
联系人和位置
学习地点
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Pennsylvania
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Pittsburgh、Pennsylvania、美国、15213
- Loeffler Building
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
描述
纳入标准:
第一阶段(所有参与者)
- 目前的 DSM-5 抑郁症
- MADRS 的严重性≥ 12
- 中重度快感缺乏(75% 的样本)或低度快感缺乏(25% 的样本)
第 2 阶段(除了上述之外,还针对 TBS 和氯胺酮阶段的参与者)
• ≥ 1 次失败的抗抑郁试验(用于研究第 2 阶段的资格和对 TMS 无反应的定义,以便有资格使用氯胺酮)= 使用达到成人推荐剂量的抗抑郁药物治疗至少 6 周至少 3 周治疗周(例如,20 毫克氟西汀)
排除标准:
第一阶段(所有参与者)
- 终生精神病、双相情感障碍、自闭症谱系障碍或发育障碍
- 严重的、不稳定的神经系统疾病(例如癫痫症)
- 脑损伤伴意识丧失
- 每日尼古丁使用
- 中重度物质使用障碍,过去 6 个月。
- MRI 禁忌症(例如体内有金属)
第 2 阶段(除了上述之外,还针对 TBS 和氯胺酮阶段的参与者)
- 严重、不稳定的呼吸道或心血管疾病
- TBS 前:过去一周酗酒或过去 3 天每天饮酒超过 3 杯
- 氯胺酮前:过去 2 周内使用 MAOI
- 药物:SNRIs、安非他酮、抗精神病药或兴奋剂
- 怀孕
- 高血压
- 目前非法使用兴奋剂
- 终生消遣性使用氯胺酮或 PCP
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:顺序分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的:TMS 和 PAT
所有开放标签,没有随机化安慰剂
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一种经颅磁刺激,用于背内侧前额叶皮层 (dmPFC)
可以增强 TBS 效果的社会心理附加干预。
PA 疗法(Craske 等人,2016 年)是一种创新的认知和体验技术,专门用于解决快感缺乏,理想情况下,改变额纹状体功能的模式。
与认知行为疗法相反,PA 训练具有增强积极影响和减少消极影响的功效(Craske 等人,2018)。
这种治疗很容易应用,我们建议它将增强 TBS 引起的神经回路水平变化。
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实验性的:TMS 和 PAT,然后氯胺酮
所有开放标签,没有随机化安慰剂
|
一种经颅磁刺激,用于背内侧前额叶皮层 (dmPFC)
可以增强 TBS 效果的社会心理附加干预。
PA 疗法(Craske 等人,2016 年)是一种创新的认知和体验技术,专门用于解决快感缺乏,理想情况下,改变额纹状体功能的模式。
与认知行为疗法相反,PA 训练具有增强积极影响和减少消极影响的功效(Craske 等人,2018)。
这种治疗很容易应用,我们建议它将增强 TBS 引起的神经回路水平变化。
氯胺酮是 FDA 批准的麻醉剂,将在本研究中超说明书使用。
它常规用于儿科和成人患者,并且被认为在高得多的麻醉剂量下极其安全。
此处给药的剂量 (0.5 mg/kg) 是低得多的亚麻醉剂量,给药途径(静脉内)是麻醉中使用的标准。
已发表的研究和荟萃分析将这种剂量的静脉注射氯胺酮作为抑郁症的标签外使用,清楚地表明该人群的风险没有增加,包括最近一项针对青少年的研究(Dwyer 等人,2021 年,《美国精神病学杂志》)。
将使用单剂量的氯胺酮来确定它是否会改变本研究中评估的与快感缺乏相关的奖赏功能和额纹状体生物标志物的功能。
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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蒙哥马利-阿斯伯格抑郁评定量表(MADRS)评分
大体时间:经颅磁刺激前至后(超过2周)和氯胺酮前至后(24小时)
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该临床医生评定量表以0-60分评估抑郁严重程度,分数越高表明严重程度越重
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经颅磁刺激前至后(超过2周)和氯胺酮前至后(24小时)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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斯奈思汉密尔顿愉悦量表(SHAPS)评分
大体时间:经颅磁刺激治疗前至治疗后(超过2周)和氯胺酮治疗前至治疗后(24小时)
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这份包含14个项目的自我报告问卷测量快感缺乏,即对愉快事件缺乏动力或难以享受。总分范围从14到56分,分数越高表明症状越严重。
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经颅磁刺激治疗前至治疗后(超过2周)和氯胺酮治疗前至治疗后(24小时)
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合作者和调查者
赞助
调查人员
- 首席研究员:Erika E Forbes, PhD、University of Pittsburgh
出版物和有用的链接
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