Neural Circuitry Underlying Alcohol Use Disorders in Men and Women Veterans

男性和女性退伍军人酒精使用障碍的神经回路

• 批准号: 9143250
• 负责人: Claudia B. Padula
• 金额: --
• 依托单位: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-10-01 至 2021-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9143250
• 关键词: Abstinence; Alcohol or Other Drugs use; Amygdaloid structure; Anterior; Anxiety; Attention; Award; Base of the Brain; Behavior; Brain; Brain imaging; Caring; Cell Nucleus; Characteristics; Chronic; Clinical; Comorbidity; Complex; Data; Diagnosis; Diagnostic; Disease; Dorsal; Drug usage; Emotions; Evidence based treatment; Female; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Gender; General Population; Goals; Individual; Insula of Reil; Knowledge; Lead; Measures; Medial; Mediating; Mediator of activation protein; Mental Depression; Mental disorders; Mentorship; Mission; Modeling; Neurobiology; Neurosciences; Nucleus Accumbens; Outcome; Outpatients; Pathogenesis; Play; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Probability; Quality of life; Recruitment Activity; Relapse; Research; Research Activity; Research Personnel; Rewards; Risk; Role; Sampling; Seeds; Standardization; Structure; Substance Use Disorder; Symptoms; System; Technology; Testing; Time; Training; Treatment outcome; Veterans; Woman; addiction; alcohol effect; alcohol use disorder; base; career; cingulate cortex; combat; cost; craving; design; drinking; drinking behavior; effective therapy; emotion dysregulation; experience; high risk; high risk behavior; improved; individualized medicine; innovation; insight; male; men; neural circuit; neurobiological mechanism; neuroimaging; neuropsychiatric disorder; psychiatric symptom; public health relevance; relapse prediction; relapse risk; reward processing; success; tool; translational research program; treatment program; treatment strategy

 DESCRIPTION (provided by applicant): Rates of alcohol use disorders are high among combat Veterans, and alcohol use disorder (AUD) is the most prevalent and costly substance use disorder among Veterans (SAMSHA, 2012). Current AUD is estimated at 16% in recently deployed veterans seeking VA care (VHA, 2011), and is approximately four times as common among combat Veterans than in the general population (Kessler et al., 2005). Care for individuals with AUD is standardized for across Veterans. An objective care framework that identifies individuals at highest risk for relapse may improve clinical outcomes. In addition, women may be more susceptible to consequences of problematic drinking behaviors than men, despite fewer years of drinking and less total drinks consumed yet research on AUD in women Veterans is sparse. Individuals with psychiatric co-morbidities have poorer outcomes than those with AUD alone, yet most research to date has excluded those with co-morbidities, leading to research results that are not generalizable to all Veterans with AUD. Evidence suggests that one component of the neurobiological mechanisms underlying AUD include dysregulation of emotional salience and reward circuits. It is not yet known exactly how dysfunction in brain circuits contribute to AUD, and how gender and co-morbidities moderate these effects, but research that answers these questions is critical. The current diagnostic and assessment system does not provide a model for objectively identifying individuals at highest risk for relapse following treatment. The checklist of symptoms that defines AUD does not reflect underlying neurobiology, yet brain circuit function predisposes individuals to AUD (e.g., to relieve anxiety or seek reward) and the effects of AUD can produce chronic changes to these circuits even after abstinence. We also know that these circuits may be moderated by other individual characteristics such as gender and/or the presence of a psychiatric co-morbidity. Technological advances in brain imaging have revolutionized our capacity to understand the brain circuits that underlie complex behaviors such as addiction. The most significant advancement in brain imaging research has been to identify core nodes of the large-scale circuits that are dysfunctional in mental health disorders. Despite this advance, there is a critical gap in integrated brain-based models of addiction. The proposed CSR&D CDA-2 seeks to fill this gap by conducted a neuroimaging study to assess the degree to which disconnections in networks implicated in reward and emotion circuits contribute to risk of relapse following treatment. We will achieve this via three specific aims: Aim 1: Define the neural circuits of emotion and reward processing that underlie AUD in Veterans. Aim 2: Test the relationship between defined neural circuits and treatment outcome (abstinence vs. relapse) and probability of relapse risk. Aim 3: Explore the impact of gender, psychiatric co-morbidities, and craving on the model developed in Aim 2. To test these aims, we will recruit 100 Veterans (50 men and 50 women) from outpatient and residential substance use treatment programs. In order to provide the most generalizable information, we will not exclude female Veterans or those with co-occurring depression, anxiety and PTSD. Currently there are no neuroimaging studies that have examined brain circuits as they relate to relapse risk in men and women Veterans with AUD. Findings from the proposed study will be the first to determine if brain circuits underlying in AUD can be used to predict relapse in this population. This study is a foundational first step and will lay the groundwork in using innovative neuroimaging technology to identify individuals at greatest risk who may need prolonged or more precise treatment strategies. This neuroscience based translational program of research will help vulnerable Veteran populations obtain more effective treatments and achieve better outcomes.

 描述（由申请人提供）： 在战斗退伍军人中，酒精使用障碍的发生率很高，酒精使用障碍（AUD）是退伍军人中最普遍，最昂贵的药物使用障碍（Samsha，2012年）。在最近部署的退伍军人中，目前的AUD估计为16％（VHA，2011年），在战斗退伍军人中的普遍约为四倍（Kessler等，2005）。为跨退伍军人提供标准化的AUD个人的护理。确定救济风险最高的个体的客观护理框架可能会改善临床结果。此外，女性可能比男性更容易受到问题饮酒行为的后果，少年饮酒的年龄少，饮酒量较少，但对女性退伍军人的AUD进行研究却很少。具有精神病合并症的人的结果比单独使用的人的结果差，但迄今为止，大多数研究都排除了患有合并症的人，导致研究结果无法推广到所有具有AUD的退伍军人。有证据表明，AUD基础的神经生物学机制的一个组成部分包括情绪显着性和奖励电路的失调。尚不清楚脑电路中的功能障碍如何有助于AUD，以及性别和合并症如何缓解这些影响，但是回答这些问题的研究至关重要。当前的诊断和评估系统并未为客观地识别治疗后有救济风险最高的人提供模型。定义AUD的症状清单并不能反映基本的神经生物学，但是脑电路功能使人易于AUD（例如，挽救焦虑或寻求奖励），即使在禁欲后，AUD的影响也可能会对这些回路产生慢性变化。我们还知道，这些电路可能会受到其他个人特征（例如性别和/或存在精神病的合并症）的调节。大脑成像的技术进步彻底改变了我们了解诸如成瘾之类的复杂行为的大脑回路的能力。大脑成像研究中最重要的进步是确定精神健康障碍功能失调的大型电路的核心节点。尽管有这一进步， 是基于大脑的综合成瘾模型的关键差距。拟议的CSR＆D CDA-2试图通过进行神经影像学研究来填补这一空白，以评估在奖励和情感电路中实施的网络中的断开连接的程度，有助于治疗后救济的风险。我们将通过三个特定目标来实现这一目标：目标1：定义在退伍军人中遵循的情感和奖励处理的神经环节。目标2：测试定义的神经回路与治疗结果（禁欲与救济）与救济风险的可能性之间的关系。 AIM 3：探索性别，精神病合并症的影响以及对AIM 2中开发的模型的渴望。为了测试这些目标，我们将从门诊和居民的物质使用治疗计划中招募100名退伍军人（50名男性和50名女性）。为了提供最概括的信息，我们不会排除女性退伍军人或同时发生抑郁，焦虑和PTSD的那些退伍军人。目前，尚无神经影像学研究来检查脑回路，因为它们与男女退伍军人与AUD的中继风险有关。拟议的研究的结果将是第一个确定AUD中脑电路是否可以用于预测该人群中继的脑电路。这项研究是基本的第一步，将在使用创新的神经影像技术来识别可能需要长时间或更精确的治疗策略的人方面奠定基础。这项基于神经科学的研究计划将有助于脆弱的退伍军人人群获得更有效的治疗方法并取得更好的结果。