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

项目摘要/摘要 早期创伤(ET)是酒精康复的重要障碍。酒精使用障碍患者 经历过早期创伤(AUD)的人频繁和早期复发的风险更高，并患有 严重的临床症状，包括情绪和压力相关的困难。然而，神经性的 酒精中毒、早期创伤和高复发风险之间的联系机制尚不清楚。两种生物 应激相关的大脑回路和下丘脑-垂体-肾上腺(HPA)轴系统是 与AUD和ET的病理机制有关。使用以下工具同时检查这两个系统 多模式神经成像技术(例如，同时监测大脑和应激激素)可以 明确AUD与ET的关系。使用这种新方法，我们先前的研究表明， 在应激过程中缺乏腹内侧额叶皮质(VmPFC)的动态增加是一个关键因素 应对无效、HPA轴对压力反应中断和饮酒增加的预测因子 消费。初步结果还表明，在应激过程中，vmPFC的动态恢复受到损害 与AUD/ET并存和早期复发有关。这一模式的发现引导我们 假设vmPFC对应激的动态反应受损可能是一种新的共病标志 酗酒和早期创伤，这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 同时发生酒精中毒和早期创伤的脑-HPA轴标志物，并检查这些 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，共4项 人口统计匹配的群体(总数N=160；每个N=40；性别比例相等)；这些群体将包括 有或没有ET的AUD患者和有或没有ET的适度饮酒者。参与者将 在观看一系列压力、酒精和中性暗示的同时，完成一次功能磁共振检查。后 多模式扫描，AUD患者将进行为期八周的标准、经验性验证 门诊治疗，然后前瞻性随访90天。为了准确地获取复发率， 我们将在治疗后14天、30天和90天联合进行面对面的随访 每天使用智能手机应用程序监控压力和酒精相关行为。成功 完成拟议的目标有可能确定潜在的神经机制 酒精中毒和早期创伤以及相关的复发风险，可以进一步探讨 开发新的治疗目标，改善有早期创伤的AUD患者的临床结果。

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.