Neuroimaging of Alcohol Addiction

酒精成瘾的神经影像学

• 批准号: 10007318
• 负责人: Abdolreza Momenan
• 金额: $ 106.31万
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10007318
• 关键词: Abstinence; Alcohol consumption; Alcohol dependence; Alcohols; Amygdaloid structure; Anger; Anterior; Anxiety; Anxiety Disorders; Appearance; Base Pairing; Behavior; Behavioral; Big Data; Bilateral; Biological Markers; Brain; Brain region; Cerebellum; Collaborations; Comorbidity; Country; DNA Methylation; Data; Data Analyses; Diagnosis; Disease; Emotional; Emotions; Exposure to; Face; Facial Expression; Functional Magnetic Resonance Imaging; Funding; Genes; Genetic; Genetic Polymorphism; Grant; Hippocampus (Brain); Human; Hyperactive behavior; Hypersensitivity; Impulsivity; Individual; Individual Differences; Information Systems; Insula of Reil; Left; Machine Learning; Manuscripts; Measures; Meta-Analysis; Methylation; Modeling; Mood Disorders; Motion; National Institute of Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; Neurotransmitters; Participant; Pathology; Patients; Personality Traits; Phenotype; Psychometrics; Psychopathology; Publishing; Questionnaires; Recording of previous events; Recovery; Relapse; Reproducibility; Research; Rest; Role; Severities; Site; Standardization; Stimulus; Structure; Substance Use Disorder; Treatment Efficacy; United States National Institutes of Health; Work; addiction; alcohol use disorder; anxiety symptoms; anxious; attentional bias; behavior measurement; cingulate cortex; cingulate gyrus; depressive symptoms; discount; discounting; disorder subtype; emotional stimulus; experience; gray matter; imaging genetics; individualized medicine; innovation; instrument; morphometry; negative affect; neural correlate; neurobehavioral; neuroimaging; phenotypic data; promoter; prospective; relapse prediction; relating to nervous system; response; serotonin transporter; social; white matter

1. Structural Data Analysis b. Addiction ENIGMA. Jointly, with our counterparts at the National Institute on Drug Abuses Neuroimaging Research Branch of Dr. Elliot Stein, we initiated the NIH Addiction Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA). This initiative is part of the Addiction-ENIGMA consortium, a large, multi-site, data-pooling initiative focused on genetics and the brain that has analyzed tens of thousands of study participants at more than 100 labs in over 30 countries. We continued our collaboration with this big data consortium. As a result, two additional manuscripts were published. As part of this collaborations four studies were conducted. Three of these investigated the effect of AUD on the structural morphometry and volumes of the cortical and subcortical brain regions. The fourth study (Kong et al.) investigated the reproducibility of the neuroimaging structural finings. 2. Cerebellar recovery of alcohol dependent patients during short term abstinence We are continuing our work that started as a collaboration with Dr. George Fein of Neurobehavioral Research, Inc. (NRI) in a funded U01 grant to develop and apply a 30 parcel active appearance model of the cerebellum on prospective motion tracking and corrected structural MRIs. We are currently analyzing structural and functional brain recovery of short-term abstinence and treatment. 3. Omnibus Alcohol Neuroimaging Assessments The purpose of this study is to obtain a standard set of assessments, including brain behavioral, structural, functional, and connectivity (structural and functional) information, on all NIAAA research participants to a) to determine how individual differences in brain structure and evoked responses relate to generalized trait personality and behavior differences (as assessed by psychometric questionnaire instruments and behavioral measures); and b) to determine whether these individual differences relate specifically to genetic polymorphisms in genes governing neurotransmitter activity. We have been analyzing some of this data in further understanding the pathology of alcohol addiction. This in turn might enable us to identify and establish an Addictions Neuroimaging Assessment (ANiA) (Voon et al. 2019, submitted to Lancet). Create a standardized neuroimaging assessment to provideAD subtyping phenotypes using information from: o Resting state and task driven functional connectivity; o Neurocircuitries associated with AD domains; o Gray and white matter structural integrity of the human brain in various stages of this heterogeneous disease. o Develop a big data system that enables the use of ANA and ANiA assessments and phenotypic data. o Determine the neural correlates (i.e. networks) associated with the domains and neuroclinical measures of alcohol use disorders. o Utilize innovative approaches such as machine learning to assist in individualized patient treatment, treatment efficacy, and relapse prediction. We have been analyzing some of this data in further understanding the pathology of alcohol addiction. a. Negative Affects in Anxious Patients with Alcohol Use Disorder. Studies have shown association between substance use disorders and mood and anxiety disorders. Compared to neutral faces, amygdala preferentially responds to fearful faces in contrast to neutral faces and habituates rapidly. Anxiety prone individuals have shown greater bilateral amygdala and insula activity to negative emotional faces. The amygdala response to emotional faces in patients with AUD has been somewhat contradictory. Some studies, including our own lab, have shown that anxious patients with AUD show a blunted response to emotional stimuli during fMRI in anterior cingulate cortex, amygdala, and hippocampus. While, others have characterized patients with AUD as having a greater tendency to experience negative emotion and impulsivity and a lack of social constraint. In this preliminary study we have examined the association between an alcohol use severity, anxiety score, and alterations in brain activation during exposure to negative facial emotion stimuli. Our initial results indicate a stronger association between STAI-T anxiety score and alcohol use severity as measured by AUDIT score in participants with both AUD and anxiety symptoms in comparison to control subjects and AUD participants without anxiety. The neuroimaging data suggests patients with AUD and anxiety symptoms show hypersensitivity to negative affects as demonstrated by response to angry facial expression stimuli. The hyperactivation of caudate might point to increased valuation of this type of emotions. On the other hand, the hypoactivation of anterior cingulate gyrus may suggest an inability of anxious AUD participants to normalize their response to fearful stimuli. The hyperactivity of AUD in left precuneus demonstrates the potential attention bias across AUD to negative affects. (MacIlvane et al., under review) b. Threat processing and Association with Serotonin Transporter. DNA methylation of the serotonin transporter gene (SLC6A4) has implications in brain functions. In this study which is a collaboration with Dr. Lohoffs CGET the association between SLC6A4 promoter methylation and threat-related amygdala activation, measures of alcohol use, and depressive symptom severity is investigated. Results did not reveal an association between SLC6A4 promoter methylation and threat-related amygdala activation in HCs or individuals with AUD. However, one of the methylation sites (CpG #19 - located 84 base pairs upstream of the TSS), which was previously associated with threat-related amygdala reactivity in healthy individuals, was significantly increased in individuals with AUD compared to controls and significantly correlated with measures of alcohol use and depressive symptoms. (Muench et al, 2019) c. In a collaborative study with Dr. Ramchandanis HP we examine the role of comorbid psychopathology on delay discounting as a biomarker of impulsivity. Individuals without a history of alcohol dependence showed significantly lower rates of delay discounting than individuals with current alcohol dependence but no comorbid psychopathology. Steeper delay is associated with increased likelihood of a diagnosis of current alcohol dependence when comorbidities were accounted for. But, no conclusive association was found in alcohol only dependent participants. (Gowin et al., 2019)

1。结构数据分析 b。成瘾的谜。在美国国家药物滥用研究所神经影像研究学院的同行，艾略特·斯坦（Elliot Stein）博士通过荟萃分析（Enigma）开始了NIH成瘾，从而增强了神经成像遗传学。该倡议是成瘾 - 富集联盟的一部分，这是一项大型，多站点的数据宣传计划，重点是遗传学和大脑，分析了30多个国家 /地区超过100个实验室的成千上万的研究参与者。我们继续与这个大数据联盟的合作。结果，另外两次手稿出版了。 作为这项合作的一部分，进行了四项研究。其中三个研究了AUD对皮质和皮质下脑区域的结构形态测定法和体积的影响。第四项研究（Kong等人）研究了神经影像罚款的可重复性。 2。在短期禁欲期间，小脑恢复依赖酒精的患者 我们正在继续与Neurobehavioral Research，Inc。（NRI）的George Fein博士（NRI）合作的工作，在资助的U01赠款中，开发和应用30个包裹的小脑主动外观模型，对前瞻性运动跟踪和校正结构MRIS进行。我们目前正在分析短期禁欲和治疗的结构和功能性脑恢复。 3。综合酒精神经影像学评估 这项研究的目的是获得一系列标准的评估，包括所有NIAAA研究参与者的大脑行为，结构，功能和连接性（结构和功能）信息，以确定a）以确定大脑结构的个体差异和唤起反应中的个体差异如何与广义性状性格差异（通过心理学测量询问仪器仪器和行为仪器测量评估）； b）确定这些个体差异是否与控制神经递质活性的基因中的遗传多态性有关。 我们一直在分析其中的一些数据，以进一步了解酒精成瘾的病理。 反过来，这可能使我们能够识别并建立成瘾神经影像评估（ANA）（Voon等人，2019年，提交给柳叶刀）。创建标准化的神经影像学评估，以使用以下信息来为Providead亚型表型。 o休息状态和任务驱动的功能连接； o与AD域相关的神经记录； o这种异质疾病的各个阶段，人脑的灰色和白质结构完整性。 o开发一个可以使用ANA和ANA评估和表型数据的大数据系统。 o确定与酒精使用障碍的结构域和神经周围度量相关的神经相关性（即网络）。 o利用机器学习等创新方法来帮助个性化的患者治疗，治疗功效和复发预测。 我们一直在分析其中的一些数据，以进一步了解酒精成瘾的病理。 一个。 焦虑的酒精饮用障碍患者的负面影响。 研究表明，药物使用障碍与情绪和焦虑症之间的关联。与中性面孔相比，杏仁核优先反应可怕的面孔，而中性面孔和习惯迅速。容易发生的焦虑症患者表现出更大的双侧杏仁核和岛状活动对负面情绪的面孔。 AUD患者对情感面孔的杏仁核反应有些矛盾。一些研究（包括我们自己的实验室）表明，在fMRI前扣带回皮质，杏仁核和海马的焦虑症患者对情绪刺激的反应钝。而其他人则将AUD的患者描述为具有负面情绪和冲动性以及缺乏社会约束的倾向。在这项初步研究中，我们研究了酒精使用严重程度，焦虑评分与暴露于负面面部情绪刺激期间大脑激活的变化之间的关联。我们的最初结果表明，与对照受试者和没有焦虑的对照受试者和AUD参与者相比，通过审计评分来衡量的Stai-T焦虑评分与酒精使用严重程度之间的相关性更强。神经影像学数据表明，AUD和焦虑症状的患者表现出对负面影响的超敏反应，如对愤怒的面部表达刺激的反应所证明。尾状的过度激活可能表明这种情绪的估值提高。另一方面，前扣带回回的过度激活可能表明焦虑的AUD参与者无法正常于其对可怕刺激的反应。 AUD在左侧的过程中的多动症证明了整个AUD对负面影响的潜在注意力偏差。 （Macilvane等人，正在审查） b。 威胁处理和与5-羟色胺转运蛋白的关联。 5-羟色胺转运蛋白基因（SLC6A4）的DNA甲基化对脑功能具有影响。在这项研究中，这是与Lohoffs博士的合作，CGET CGET SLC6A4启动子甲基化与威胁相关的杏仁核激活，酒精使用措施以及抑郁症状严重程度之间的关联。结果没有揭示HCS或AUD个体中SLC6A4启动子甲基化与威胁相关的杏仁核激活之间的关联。然而，与对照组相比，AUD的个体中，TSS上游的甲基化位点之一（CPG＃19-位于TSS上游的84个碱基对）与健康个体中与威胁相关的杏仁核反应性的相关性显着增加，并且与酒精使用和抑郁症状的程度显着相关。 （Muench等，2019） c。 在与Ramchandanis HP博士的合作研究中，我们研究了合并症心理病理学对延迟折现作为冲动性生物标志物的作用。没有酒精依赖病史的人比当前酒精依赖但没有合并症的精神病理学的人明显低于延迟打折的速度。当合并症解释合并症时，较陡的延迟与当前酒精依赖的诊断可能性增加有关。但是，仅在酒精依赖参与者中没有发现结论性关联。 （Gowin等，2019）