Role of Beta2-nAChR in Bipolar Disorder

Beta2-nAChR 在双相情感障碍中的作用

• 批准号: 8282691
• 负责人: Irina Esterlis
• 金额: $ 17.02万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8282691
• 关键词: Acute; Age; Attention; Award; Biological; Biological Markers; Bipolar Disorder; Brain imaging; Brain region; Cognition; Cognitive; Cognitive deficits; Communities; Comorbidity; Data; Depressed mood; Development; Development Plans; Disease; Emission-Computed Tomography; Extramural Activities; Family; Functional disorder; General Population; Goals; Grant; Health Care Costs; Hippocampus (Brain); Human; Image; Impaired cognition; Impairment; Individual; Investigation; Lead; Major Depressive Disorder; Manic; Manuscripts; Measures; Mediating; Medical; Memory; Mental Depression; Mental disorders; Mentors; Methods; Molecular; Molecular Mechanisms of Action; Mood Disorders; Moods; Neurobehavioral Manifestations; Nicotine; Nicotinic Receptors; Noise; Patient Self-Report; Performance; Pharmacotherapy; Photons; Population; Positron-Emission Tomography; Psychiatry; Quality of life; Radiology Specialty; Research Personnel; Risk; Role; Scanning; Schizophrenia; Sensory Receptors; Smoker; Smoking; Substance Addiction; Substance Use Disorder; Substance abuse problem; Suicide; Symptoms; System; Techniques; Testing; Thalamic structure; Time; Tobacco; Tobacco Dependence; Tobacco smoke; Tobacco smoking; Tobacco use; Training; Withdrawal; base; career; career development; cholinergic; cognitive function; depressive symptoms; design; disturbance in affect; in vivo; innovation; meetings; mood regulation; mortality; neuroimaging; nicotinic receptor beta2; non-smoker; novel; receptor; response; sex; skills; smoking cessation; tobacco abstinence; training project; trait

DESCRIPTION (provided by applicant): This K01 application proposes support essential for Dr. Esterlis' career development as she transitions to an independent investigator in neuroreceptor imaging of mood and comorbid substance use disorders. The proposed career award plan is designed to further her scientific development as an expert neuroimager, with increased expertise in mood disorders and mood-substance disorder comorbidity, including the conduct of two unique receptor imaging studies. Dr. Esterlis' career development plan focuses on rigorous training in methods of single photon emission computerized tomography (SPECT) and positron emission tomography (PET) brain imaging, including noise- correction techniques and quantitative skills, and application of these techniques to the neuroimaging of biological basis of mood disorders. Training will include an integration of individual meetings with mentors and collaborators in the Departments of Psychiatry and Radiology, intramural and extramural didactics, presentations at scientific meetings and manuscript and grant submissions. The scientific focus of the proposed project is the investigation of a novel mechanism that may be involved in the pathophysiology of bipolar disorder (BD) and comorbid tobacco dependence. Tobacco dependence is three times as prevalent in BD as compared to general population, however, the reasoning behind this comorbidity is not well understood nor are there well-established efficacious treatments for smoking cessation or associated depression symptoms in BD. Thus, there is an urgent need for investigation of new molecular mechanisms for pharmacotherapeutic targets. Emerging evidence implicates the nicotinic acetylcholine receptor (nAChR) system in the pathophysiology of BD and its mood and cognitive symptoms. Thus, we propose an innovative study of the relationship between tobacco smoking and mood and cognitive dysfunction in BD, which may be mediated by the 22 subunit of the nAChR system. Nonsmokers (n=20) and smokers (n=20) with BD and matched controls will participate in a [123I]5-IA-85380 SPECT scan to determine 22-nAChR availability. Mood and cognitive assessments will be administered to smokers before smoking cessation, after 24h smoking cessation, and again on SPECT scan day, and at corresponding times to nonsmokers. Differences in the magnitude and distribution of the 22-nAChR in BD versus controls will be measured, as well as in BD smokers versus nonsmokers. Relationships to mood and cognitive symptoms will be assessed. {{{Furthermore, proposed career training project will provide data on the distribution of the metabotropic glumatamatergic system (mGluR5) in the same BD subjects and will enable a unique investigation of a multi-receptor involvement in BD.

描述（由申请人提供）：该K01申请提出了埃斯特利斯博士的职业发展至关重要的支持，因为她将其在情绪和合并药物使用障碍的神经感受器成像中转变为独立的研究者。拟议的职业奖计划旨在进一步发展她作为专家神经imimager的科学发展，并在情绪障碍和情绪增生障碍合并症方面提高了专业知识，包括进行了两项独特的受体成像研究。 Esterlis博士的职业发展计划着重于单个光子发射计算机断层扫描（SPECT）和正电子发射断层扫描（PET）脑成像的严格培训，包括噪声校正技术和定量技能，以及这些技术在情绪障碍生物学基础的神经图像中的应用。培训将包括与精神病学和放射学，壁内和壁外教学部门的导师和合作者的个人会议的整合，在科学会议以及手稿上的演讲以及赠款提交。 拟议项目的科学重点是研究一种新机制，该机制可能参与了躁郁症（BD）和合并症烟草依赖性的病理生理学。与普通人群相比，烟草依赖性在BD中是普遍存在的三倍，但是，这种合并症背后的推理尚未得到充分理解，也没有公认的有效治疗方法来戒烟或BD中相关的抑郁症状。因此，迫切需要研究药物治疗靶标的新分子机制。新兴证据暗示了BD的病理生理及其情绪和认知症状中的烟碱乙酰胆碱受体（NACHR）系统。因此，我们提出了一项创新的研究，对BD中的烟草吸烟与情绪与认知功能障碍之间的关系，这可能是由NACHR系统的22个亚基介导的。非吸烟者（n = 20）和具有BD和匹配对照的吸烟者（n = 20）将参与[123i] 5-ia-85380 SPECT扫描，以确定22-NACHR的可用性。在戒烟，24h戒烟后，在SPECT扫描日，以及与非吸烟者的相应时间，将对吸烟者进行情绪和认知评估。将测量BD与对照组中22-NACHR的大小和分布的差异，以及BD吸烟者与非吸烟者的差异。将评估与情绪和认知症状的关系。 {{{{此外，提议的职业培训项目将提供有关同一BD受试者中代谢性glumatamatematemgic System（MGLUR5）分布的数据，并将对BD中的多受体介入进行独特的研究。