Neuroimaging mechanisms of overlap between alcoholism and bipolar disorder

酗酒和双相情感障碍重叠的神经影像机制

• 批准号: 8541684
• 负责人: James Joseph Prisciandaro
• 金额: $ 15.84万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-10 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8541684
• 关键词: Acetylcysteine; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; Alcoholism; Alcohols; Anterior; Area; Award; Beverages; Biometry; Bipolar Disorder; Brain; Brain region; Clinical; Clinical Research; Collaborations; Comorbidity; Control Groups; Corpus striatum structure; Country; Development; Diagnosis; Diagnostic; Emotions; Environment; Epidemiology; Equipment; Evaluation; Event; Faculty; Fellowship; Functional Magnetic Resonance Imaging; Funding; Glutamatergic Agents; Glutamates; Goals; Grant; Health Care Costs; Human; Image; Impulsivity; Individual; Inferior; Informatics; International; Knowledge; Learning; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Medical; Medical Education; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Methods; Modeling; Mood Disorders; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neurosciences; Outcome; Outcome Measure; Participant; Pharmaceutical Preparations; Pilot Projects; Population; Postdoctoral Fellow; Procedures; Protons; Psychiatry; Psychologist; Public Health; Regulation; Relative (related person); Research; Research Infrastructure; Research Institute; Research Personnel; Research Training; Resistance; Rewards; Scanning; Scientist; Services; Signal Transduction; South Carolina; Substance Use Disorder; System; Task Performances; Techniques; Testing; Training; Translational Research; United States National Institutes of Health; Universities; addiction; alcohol cue; alcohol exposure; alcohol sensitivity; base; behavior measurement; blood oxygen level dependent; career; college; craving; design; disorder control; effective therapy; executive function; frontal lobe; genetic variant; improved; medical schools; neural patterning; neurobehavioral; neurochemistry; neuroimaging; neurotransmission; new therapeutic target; non-alcoholic; patient oriented; patient oriented research; primary outcome; problem drinker; professor; programs; public health relevance; relating to nervous system; research study; response; skills; transmission process

DESCRIPTION (provided by applicant): Dr. Prisciandaro is a postdoctoral fellow in the Clinical Neuroscience Division (CND) of the Department of Psychiatry at the Medical University of South Carolina (MUSC); he will join the faculty as an Assistant Professor upon completion of his fellowship in July, 2012. Dr. Prisciandaro seeks a Mentored Patient-Oriented Research Career Development Award (K23), through the National Institutes of Health-National Institute on Alcohol Abuse and Alcoholism (NIH/NIAAA), to facilitate his career as an independent investigator conducting patient-oriented research in individuals with co-occurring alcohol use and bipolar disorders. Candidate: Dr. Prisciandaro is a clinical psychologist with extensive training in substance use and mood disorders research and practice, quantitative methods, and initial training in functional Magnetic Resonance Imaging (fMRI). His long-term career goal is to become an independent clinical scientist in the area of patient- oriented substance use and mood disorders research, with an emphasis on using neuroimaging to develop and test mechanistic models of co-occurring alcohol use and bipolar disorders. In order to realize this goal, Dr. Prisciandaro requires additional training. During the proposed award, Dr. Prisciandaro will 1) obtain sophisticated knowledge of the neurobiology of alcohol use and bipolar disorders, 2) learn how to design, conduct, and analyze fMRI and proton Magnetic Resonance Spectroscopy (1H-MRS) experiments to investigate the neurobiology of alcohol use and bipolar disorders, 3) augment existing clinical research skills, and 4) improve grantsmanship in order to successfully compete for an Independent Research Award (R01). Environment: MUSC ranks among the top 10 medical schools in the country for addiction education, and the MUSC College of Medicine has 7 departments ranked in the top 25 nationally in NIH funding including the Department of Psychiatry. Addictions collaborations span several departments and include 4 NIH center and 2 T32 addiction-research training grants. Across departments, over 30 faculty are engaged in addiction research; a number of these faculty will be mentors. Dr. Prisciandaro's proposed mentors/collaborators are international and national experts, including Drs. Raymond Anton, Jane Joseph, Truman Brown, Kathleen Brady, Mary Phillips (offsite), Alan Swann (offsite), Peter Kalivas, Hugh Myrick, and Bryan Tolliver. Study procedures will take place through the Clinical Neuroscience Division (CND). The CND (Dr. Brady-Director) will provide the infrastructure for the execution of the proposed research. Neuroimaging will be conducted at MUSC's Center for Advanced Imaging Research (CAIR; Dr. Brown-Director). CAIR's Siemens 3T Trio MRI, with integrated fMRI paradigm equipment, operates with a 100% mandate for research and is accompanied by comprehensive informatics support. Seminars, pilot project programs, and research services are further available through MUSC's Center for Drug and Alcohol Programs, Department of Neurosciences, South Carolina Clinical and Translational Research Institute, and Division of Biostatistics and Epidemiology. Research: Bipolar disorder (BD) is the Axis I psychiatric condition most strongly associated with substance use disorders (SUD); co-occurring BD and SUD are associated with devastating clinical outcomes. Research suggests that dysregulated glutamate transmission may be partially responsible for co-occurring SUD and BD, both directly and through its impact on neurobehavioral deficits that are common to both SUD and BD. Though promising, this hypothesis is based on indirect evidence, as there have been virtually no neuroimaging studies involving individuals with co-occurring BD and SUD. The proposed study will provide a first evaluation of anterior cingulate (ACC) glutamate, impulsivity (response inhibition), and reward sensitivity (sensitivity to alcohol cues) as contributors to comorbidity between BD and alcohol dependence (AD) using 1H-MRS and fMRI in individuals with co-occurring AD and euthymic BD, individuals with euthymic BD alone, individuals with AD alone, and a matched control group. In Aim 1, we predict that individuals with co-occurring AD and BD will have significantly different ACC glutamate (by 1H-MRS) relative to individuals with AD or BD alone.InAim 2, we predict that individuals with co-occurring AD and BD will demonstrate significantly less ACC/frontal (e.g., right inferior frontal cortex) bran activity (by fMRI Bold response) when asked to inhibit a prepotent response relative to individuals with AD or BD alone. In Aim 3, we predict that individuals with co- occurring AD and BD will have significantly greater ventral striatal and ACC/frontal activity (by fMRI) when exposed to alcohol cues relative to individuals with AD or BD alone. Control subjects are expected to have the most normal levels of ACC glutamate, highest levels of ACC/frontal activity to response inhibition, and lowest levels of striatal and frontal activity to alcohol cues Comparisons between AD and BD will be exploratory given that these groups have never been compared. The relationship between ACC glutamate (by 1H-MRS), neural activation to alcohol cues (fMRI) and response inhibition (fMRI), and AD/BD diagnosis will be explored. The proposed study will provide evidence for or against glutamate neurotransmission as a key brain system underlying co-occurring AD and BD, and will provide a paradigm for examining the mechanistic effects of glutamatergic drugs for the treatment of AD, BD, and AD+BD.

描述（由申请人提供）：Prisciandaro博士是南卡罗来纳州医科大学（MUSC）精神病学系临床神经科学部（CND）的博士后研究员；他将于2012年7月完成团契后加入该教师。Prisciandaro博士通过国家卫生研究所的酒精滥用与酒精中毒研究所（NIH/NIAAA）（NIH/NIAAA）寻求一个受患者的研究职业发展奖（K23），以促进与患者的独立研究人员一起研究，并促进了与患者的独立研究，并促进了与患者进行研究。候选人：Prisciandaro博士是一名临床心理学家，对药物使用和情绪障碍的广泛培训研究和实践，定量方法以及功能磁共振成像（fMRI）的初步培训。他的长期职业目标是成为以患者为导向的药物使用和情绪障碍研究领域的独立临床科学家，重点是利用神经影像来开发和测试同时发生的酒精使用和双极疾病的机械模型。为了实现这一目标，Prisciandaro博士需要额外的培训。在拟议的奖励期间，Prisciandaro博士将1）获得有关酒精使用和双相情感障碍神经生物学的复杂知识，2）学习如何设计，进行和分析fMRI和Proton磁共振光谱谱（1H-MRS）实验，以调查酒精使用和双极性疾病的神经生物学的研究，3）成功竞争独立研究奖（R01）。环境：MUSC在成瘾教育中排名该国的十大医学院之一，MUSC医学院在包括精神病学系在内的NIH资金中有7个部门在全国排名前25位。成瘾合作范围跨越了多个部门，包括4个NIH中心和2个T32成瘾研究培训补助金。在整个部门，有30多名教职员工从事成瘾研究；这些教师中的许多将是导师。 Prisciandaro博士提议的导师/合作者是国际和国家专家，包括博士。雷蒙德·安东（Raymond Anton），简·约瑟夫（Jane Joseph），杜鲁门·布朗（Truman Brown），凯瑟琳·布雷迪（Kathleen Brady），玛丽·菲利普斯（Mary Phillips），玛丽·菲利普斯（Mary Phillips），艾伦·斯旺（Alan Swann），艾伦·斯旺（Alan Swann），彼得·卡利瓦斯（Peter Kalivas），休·迈里克（Hugh Myrick）和布莱恩·托利弗（Bryan Tolliver）。研究程序将通过临床神经科学部（CND）进行。 CND（Brady-Dimector博士）将为执行拟议的研究提供基础设施。神经影像学将在MUSC的高级成像研究中心（CAIR； Brown-Director）进行。 CAIR的Siemens 3T三重奏MRI具有综合的fMRI范式设备，具有100％的研究任务，并伴随着全面的信息学支持。通过MUSC的药物和酒精计划中心，神经科学系，南卡罗来纳州临床和转化研究所以及生物统计学和流行病学部门，可以通过MUSC毒品和酒精计划中心，神经科学系，神经科学系以及生物统计学和流行病学系进一步获得研讨会，试点项目计划和研究服务。研究：双相情感障碍（BD）是与药物使用障碍最密切相关的轴I精神病（SUD）；同时发生的BD和SUD与毁灭性的临床结果有关。研究表明，非调节谷氨酸的传播可能是直接以及通过其对SUD和BD共同的神经性缺陷的影响而对同时发生的SUD和BD的部分原因。尽管很有希望，但这一假设是基于间接证据的，因为实际上没有涉及同时发生BD和SUD的个体的神经影像学研究。 The proposed study will provide a first evaluation of anterior cingulate (ACC) glutamate, impulsivity (response inhibition), and reward sensitivity (sensitivity to alcohol cues) as contributors to comorbidity between BD and alcohol dependence (AD) using 1H-MRS and fMRI in individuals with co-occurring AD and euthymic BD, individuals with euthymic BD alone, individuals with AD alone, and a matched control 团体。在AIM 1中，我们预测，与仅具有AD或BD的个体相比，具有同时发生的AD和BD的个体将具有明显不同的ACC谷氨酸（通过1H-MR）。或单独使用BD。在AIM 3中，我们预测，与单独使用AD或BD的个体相对于酒精提示，当AD和BD共同出现的人（通过fMRI）将具有更大的腹侧纹状体和ACC/额叶活动（通过fMRI）。预计对照对照受试者的ACC谷氨酸水平最正常，ACC/额叶活动的最高水平对响应抑制作用，鉴于这些群体从未被比较，因此将探索AD和BD之间的纹状体和额叶活动水平最低。将探索ACC谷氨酸（通过1H-MR），酒精提示（fMRI）和反应抑制（fMRI）和AD/BD诊断之间的关系。拟议的研究将为AD和BD共发生的关键大脑系统提供证据或反对谷氨酸神经传递的证据，并将为检查谷氨酸能药物在AD，BD和AD+BD的治疗方面提供范式来检查谷氨酸能药物的机械作用。