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.

简介(申请人提供)：Prisciandaro博士是南卡罗来纳医科大学精神病学系临床神经科学部(CND)博士后研究员；他将于2012年7月完成奖学金后加入教职员工，担任助理教授。Prisciandaro博士寻求通过国家卫生研究院-国家酒精滥用和酒精中毒研究所(NIH/NIAAA)获得以患者为导向的研究职业发展奖(K23)，以促进他作为一名独立调查员的职业生涯，在同时存在酒精使用和双相情感障碍的个人中进行面向患者的研究。候选人：Prisciandaro博士是一名临床心理学家，在物质使用和情绪障碍的研究和实践、量化方法以及功能磁共振成像(FMRI)的初步培训方面接受过广泛的培训。他的长期职业目标是成为以患者为导向的物质使用和情绪障碍研究领域的独立临床科学家，重点是使用神经成像来开发和测试酒精使用和双相情感障碍共生的机制模型。为了实现这一目标，普里西安达罗博士需要额外的培训。在拟议的奖项期间，Prisciandaro博士将1)获得酒精使用和双相情感障碍的神经生物学方面的复杂知识，2)学习如何设计、实施和分析功能磁共振成像和质子磁共振波谱(1H-MRS)实验，以研究酒精使用和双相情感障碍的神经生物学，3)增强现有的临床研究技能，以及4)提高勇气，以便成功角逐独立研究奖(R01)。环境：马萨诸塞州南加州大学在成瘾教育方面跻身全国十大医学院之列，MUSC医学院有7个系在NIH资助的全国前25名中排名，其中包括精神病学系。成瘾合作跨越了几个部门，包括4个NIH中心和2个T32成瘾研究培训补助金。在各个部门，有30多名教职员工从事成瘾研究；其中一些教职员工将担任导师。Prisciandaro博士推荐的导师/合作者是国际和国内专家，包括Raymond Anton博士、Jane Joseph博士、Truman Brown博士、凯瑟琳Brady博士、Mary Phillips博士(场外)、Alan Swann博士(场外)、Peter Kalivas博士、Hugh Myrick博士和Bryan Tolliver博士。研究程序将通过临床神经科学部(CND)进行。CND(Brady-Director博士)将为执行拟议的研究提供基础设施。神经成像将在南加州大学高级成像研究中心(CAIR；Brown博士主任)进行。CAIR的西门子3T Trio MRI拥有集成的功能磁共振成像范式设备，100%负责研究，并伴随着全面的信息学支持。研讨会、试点项目计划和研究服务可通过南加州大学药物和酒精项目中心、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和流行病学部进一步提供。研究：双相情感障碍(BD)是一种与物质使用障碍(SUD)关系最密切的Axis I精神疾病；BD和SUD并存与毁灭性的临床结果有关。研究表明，谷氨酸传递失调可能是SUD和BD共同发生的部分原因，直接或通过其对SUD和BD共同的神经行为缺陷的影响。尽管前景看好，但这一假说是基于间接证据的，因为几乎没有涉及患有BD和SUD的个体的神经影像研究。这项拟议的研究将首次使用1H-MRS和fMRI评估前扣带回(ACC)谷氨酸、冲动(反应抑制)和奖赏敏感性(对酒精线索的敏感性)作为BD和酒精依赖(AD)共病的贡献者，这些患者包括同时患有AD和心境良好的BD的个体、单独患有心境良好的BD的个体、单独患有AD的个体和匹配的对照组。在目标1中，我们预测与AD或BD患者相比，AD和BD共病患者的ACC谷氨酸水平(通过1H-MRS)将显著不同。在目标2中，我们预测当被要求抑制相对于AD或BD单独患者的优势反应时，AD和BD患者的ACC/额叶(例如，右下额叶皮质)麸皮活性将显著降低。在目标3中，我们预测，与单独患有AD或BD的人相比，在酒精提示下，患有AD和BD的人的腹侧纹状体和ACC/额叶活动(通过fMRI)将显著增加。预计对照组受试者的ACC谷氨酸水平最正常，对反应抑制的ACC/额叶活动水平最高，纹状体和额叶活动对酒精的最低水平提示AD和BD之间的比较将是探索性的，因为这些组从未被比较过。通过1H-MRS，探讨ACC谷氨酸、对酒精刺激的神经激活(FMRI)和反应抑制(FMRI)与AD/BD诊断的关系。这项拟议的研究将为支持或反对谷氨酸神经传递作为AD和BD共生的关键大脑系统提供证据，并将为研究治疗AD、BD和AD+BD的谷氨酸能药物的机制提供一个范例。