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

项目总结/摘要 早期创伤（ET）是酒精恢复的重要障碍。酒精使用障碍患者 (AUD)经历过早期创伤的人更容易频繁和早期复发， 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尚不清楚。两个生物 压力相关的脑回路和下丘脑-垂体-肾上腺（HPA）轴系统， 与AUD和ET的病理学有关。同时检查这两个系统， 多模式神经成像技术（例如，脑和应激激素同时监测）可 明确AUD和ET之间的关系。使用这种新方法，我们先前的研究表明， 在压力下，腹内侧前额叶皮层（VmPFC）缺乏动态增加是一个关键因素。 无效应对、HPA轴对压力的反应中断和酒精增加的预测因子 消费初步结果还表明，受损的动态VmPFC恢复在压力 与合并AUD/ET和早期复发相关。这种发现模式使我们 假设VmPFC对应激动态反应受损可能是共病的一个新标志物， 酗酒和早期创伤，这是复发风险高的基础。使用功能性磁共振 结合前瞻性临床结局设计，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轴标记物，并检查这些标记物是否 标志物有助于治疗后的早期复发。我们建议进行为期5年的研究， 人口统计学匹配组（总计N=160;每组N=40;性别比例相等）;这些组将包括 伴有和不伴有ET的AUD患者以及伴有和不伴有ET的中度饮酒者。参与者将 完成功能磁共振成像，同时观察一系列压力、酒精和中性线索。后 多模式扫描，AUD患者将参与为期八周的标准， 门诊治疗，然后前瞻性随访90天。为了准确地捕捉复发率， 我们将在治疗后14、30和90天进行面对面的随访， 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 完成所提出的目标有可能确定神经机制的基础上， 合并酒精中毒和早期创伤以及相关的复发风险，这可能会进一步探讨， 开发新的治疗靶点，改善早期创伤的AUD患者的临床结局。

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.