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: 9924416
• 负责人: DONGJU SEO
• 金额: $ 63.51万
• 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/9924416
• 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; multimodality; neural circuit; neural correlate; neurobiological mechanism; neuroimaging; 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.

项目概要/摘要 早期创伤（ET）是酒精康复的重大障碍。酒精使用障碍患者 (AUD) 经历过早期创伤的人频繁和早期复发的风险较高，并且患有以下疾病 严重的临床症状，包括情绪和压力相关的困难。然而，神经 酗酒、早期创伤和高复发风险之间的联系机制仍不清楚。两个生物 系统，与压力相关的大脑回路和下丘脑-垂体-肾上腺（HPA）轴系统 与 AUD 和 ET 的病理学有关。使用以下方法同时检查这两个系统 多模式神经影像技术（例如，同步大脑和应激激素监测）可能 澄清AUD和ET之间的关系。使用这种新颖的方法，我们之前的研究表明 压力期间腹内侧前额叶皮层 (VmPFC) 缺乏动态增加是一个关键 应对无效、HPA 轴对压力的反应中断以及酒精增加的预测因素 消耗。初步结果还表明，应激期间动态 VmPFC 恢复受损 与合并症 AUD/ET 和早期复发相关。这种发现模式引导我们 假设 VmPFC 对压力的动态反应受损可能是共病的新标志 酗酒和早期创伤是高复发风险的基础。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 酒精中毒和早期创伤同时发生的脑-HPA轴标记，并检查这些是否 标记物有助于治疗后早期复发。我们建议进行一项为期 5 年的研究，其中包括 4 名 人口统计匹配组（总数 N=160；每组 N=40；性别比例相等）；这些群体将包括 伴或不伴 ET 的 AUD 患者以及伴或不伴 ET 的适度饮酒者。参与者将 完成功能磁共振成像会议，同时查看一系列压力、酒精和中性线索。之后 多模态扫描，AUD 患者将接受八周的标准、经经验验证的治疗 门诊治疗，然后前瞻性随访 90 天。为了准确掌握复发率， 我们将在治疗后14、30和90天同时进行面对面的随访 使用智能手机应用程序每天监控压力和酒精相关行为。成功的 完成拟议的目标有可能确定潜在的神经机制 共病酗酒和早期创伤以及相关的复发风险，可以进一步探讨 制定新的治疗目标并改善早期创伤 AUD 患者的临床结果。