Impaired dynamic neurobiological responses in alcoholism and early trauma to predict relapse after treatment

酗酒和早期创伤的动态神经生物学反应受损可预测治疗后的复发

• 批准号: 10331856
• 负责人: DONGJU SEO
• 金额: $ 65.1万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10331856
• 关键词: Address; Adrenal Glands; Adult; Aftercare; Alcohol consumption; Alcoholism; Alcohols; Ambulatory Care; Brain; Clinical; Cohort Studies; Communities; Cues; Data; Early-life trauma; Emotions; Exposure to; Functional Magnetic Resonance Imaging; Future; Gender; Hormones; Hydrocortisone; Hypothalamic structure; Impairment; Individual; Interview; Knowledge; Link; Matched Group; Measures; Modeling; Monitor; Neurobiology; Outcome; Participant; Pathology; Patients; Pattern; Pituitary Gland; Prefrontal Cortex; Recording of previous events; Recovery; Relapse; Reporting; Research; Role; Scanning; Series; Sex Differences; Sex Ratio; Stress; Symptoms; System; Techniques; Time; Treatment outcome; Ventral Striatum; Work; alcohol behavior; alcohol comorbidity; alcohol cue; alcohol relapse; alcohol seeking behavior; alcohol use disorder; biological systems; comorbidity; coping; design; early experience; follow-up; high risk; hypothalamic-pituitary-adrenal axis; improved; multimodal neuroimaging; multimodality; neural circuit; neural correlate; neurobiological mechanism; neuromechanism; novel; novel marker; novel strategies; predict clinical outcome; prospective; relapse prediction; relapse risk; relating to nervous system; response; smartphone Application; social; therapy resistant

Project Summary/Abstract Early trauma (ET) is a significant obstacle to alcohol recovery. Patients with alcohol use disorder (AUD) who experienced early trauma are at a higher risk of frequent and early relapse and suffer from severe clinical symptoms including emotion and stress-related difficulties. However, neural mechanisms linking alcoholism, early trauma and high relapse risk remain unclear. Two biological systems, stress-related brain circuits and the hypothalamic–pituitary–adrenal (HPA) axis system, are implicated in the pathologies of both AUD and ET. Concurrent examination of these two systems using multimodal neuroimaging techniques (e.g., simultaneous brain and stress hormone monitoring) may clarify the relationship between AUD and ET. Using this novel approach, our prior study showed that a lack of dynamic increase in the ventromedial prefrontal cortex (VmPFC) during stress was a critical predictor of ineffective coping, disrupted HPA axis response to stress, and increased alcohol consumption. Preliminary results also indicated that impaired dynamic VmPFC recovery during stress was associated with comorbid AUD/ET and early relapse. This pattern of findings leads us to hypothesize that impaired dynamic VmPFC response to stress may be a novel marker of comorbid alcoholism and early trauma, which underlies high relapse risk. Using functional magnetic resonance imaging (fMRI) combined with a prospective clinical outcome design, the proposed study aims to utilize brain-HPA axis markers of co-occurring alcoholism and early trauma and to examine whether these markers contribute to early relapse after treatment. We propose a 5-year study with four demographically-matched groups (total N=160; N=40 each; equal sex ratio); these groups will include AUD patients with and without ET and moderate drinkers with and without ET. Participants will complete an fMRI session while viewing a series of stress, alcohol, and neutral cues. After the multimodal scan, AUD patients will be engaged in eight weeks of standard, empirically-validated outpatient treatment and then prospectively followed for 90 days. To accurately capture relapse rate, we will conduct face-to-face follow-up interviews at 14, 30, and 90 days after treatment in conjunction with daily monitoring of stress and alcohol related behaviors using a smartphone app. Successful completion of the proposed aims has the potential to identify the neural mechanisms underlying comorbid alcoholism and early trauma and associated relapse risk, which may be further explored to develop new treatment targets and to improve clinical outcomes in AUD patients with early trauma.

项目摘要/摘要 早期创伤（ET）是酒精恢复的重要障碍。饮酒障碍的患者 （AUD）经历了早期创伤的人经常和早期缓解的风险更高，并且患有 严重的临床症状，包括情绪和压力有关的困难。但是，中立 连接酒精中毒，早期创伤和高继电器风险的机制尚不清楚。两个生物学 系统，与压力相关的脑回路和下丘脑 - 垂体 - 肾上腺（HPA）轴系统是 在AUD和ET的病理中实施。同时检查这两个系统 多模式神经影像学技术（例如，同时大脑和压力同时监测）可能 阐明AUD和ET之间的关系。使用这种新颖的方法，我们先前的研究表明 在压力期间，腹侧前额叶皮层（VMPFC）缺乏动态增加是关键 预测无效应对，HPA轴对压力的反应的破坏和酒精增加 消耗。初步结果还表明，压力期间动态VMPFC恢复受损 与合并的AUD/ET和早期缓解有关。这种发现的模式使我们进入 假设动态VMPFC对压力的反应受损可能是合并症的新标志物 酒精中毒和早期创伤是高救济风险的基础。使用功能磁共振 成像（fMRI）与前瞻性临床结果设计相结合，拟议的研究旨在利用 脑HPA轴标志物的同时酗酒和早期创伤，并检查这些是否是否 标记在治疗后有助于提前退休。我们提出了一项为期5年的研究，四个 人口匹配的组（总n = 160； n = 40；相等的性别比）；这些小组将包括 有或没有ET的AUD患者和不具有ET的中度饮酒者。参与者会 在观看一系列压力，酒精和中性提示的同时完成fMRI会议。之后 多模式扫描，AUD患者将参与八周的标准，经验验证 门诊治疗，然后前瞻性进行90天。为了准确捕获继电器率， 我们将在治疗后14、30和90天进行面对面的后续访谈 每天使用智能手机应用程序对压力和酒精相关的行为进行监测。成功的 拟议目标的完成有可能识别基础的神经机制 合并的酒精中毒和早期创伤和相关的继电器风险，可以进一步探讨 开发新的治疗靶标并改善早期创伤患者的临床结果。