GENETIC UNDERPINNINGS OF BRAIN ABNORMALITIES IN MOOD DISORDERS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：该方案是Jair Soares博士的研究小组目前批准的用于双相和单相障碍脑成像研究的IRB方案的配套方案。对于每一位同意参加苏亚雷斯博士的成像方案的患者，都将收集一份血液样本，用于未来的基因研究，该研究将开始探索特定的基因多态与那些被识别的大脑异常之间的相关性，这些脑部异常将通过这些正在进行的成像研究(成像内表型)来确定。 研究计划：我们将招募540名患者参与我们的成像研究。这是一项附加研究，涉及为未来的基因研究获取血液样本。一旦患者同意参与成像方案，他们将有可能通过这一特定方案参与附加遗传学研究。这项研究将开始研究情绪障碍患者体内解剖和神经化学大脑异常的遗传基础。这种异常目前正在我们正在进行的成像研究中被发现，随着这些脑成像研究的发展，可能会被证明是未来情绪障碍遗传学研究的有用的成像内表型。这项研究将是我们目前批准的成像协议的补充，其主要目标将是探索性的，因为人们对调节这些疾病中大脑异常的特定基因多态知之甚少。 方法：拟议研究的具体目的是：(1)检查目前已发现的BARING衍生神经营养因子(BDNF)基因的多态是否与双相和单相情绪障碍受试者额缘脑回路的解剖和神经化学异常有关；(2)随着参与大脑发育的基因或调节信号转导通路的基因的新的多态被识别，我们想在探索性的基础上检查这些多态是否与双相和单相情绪障碍受试者的解剖和神经化学脑成像异常有关。 临床意义：一旦我们从正在进行的成像研究中积累了更多的双相和单相患者和健康个体的样本，并对这些患者中最有希望的成像内表型有了更好的了解，我们将能够开始检查调节大脑发育的特定基因对已识别的脑异常的影响。这一方案可以很大程度上帮助阐明情绪障碍中大脑异常的遗传基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: This protocol is a companion to the currently approved IRB protocols for the brain imaging studies in bipolar and unipolar disorders conducted by Dr. Jair Soares' research group. For every consenting patient who participates in Dr. Soares' imaging protocols, a blood sample will be collected for future genetic studies, which will begin to explore the relevance of specific genetic polymorphisms, as those are identified, in brain abnormalities that will be identified through these ongoing imaging studies (imaging endophenotypes). RESEARCH PLAN: We will enroll 540 patients who will participate in our imaging studies. This is an add-on study that involves obtaining a blood sample for future genetic studies. Once patients agree to participation in the imaging protocols, they will be offered the possibility of participating in the add-on genetics study through this specific protocol. This study will start to examine the genetic underpinnings of in vivo anatomical and neurochemical brain abnormalities in mood disorder patients. Such abnormalities are currently being identified in our ongoing imaging studies, and as these brain imaging studies evolve, may turn out to be useful imaging endophenotypes for future genetic investigations in mood disorders. This study will be an add-on to our currently approved imaging protocols, and its main goal will be exploratory, as very little is known about specific genetic polymorphisms that modulate brain abnormalities in these illnesses. METHODS: The specific aims of the proposed study are: (1) Examine whether currently identified polymorphisms for the baring-derived neurotrophic factor (BDNF) are associated with anatomical and neurochemical brain abnormalities in fronto-limbic brain circuits identified in bipolar and unipolar mood disorder subjects; (2) As new polymorphisms for genes involved in brain development, or genes that modulate signal transduction pathways, and dopaminergic and serotonergic pathways in the brain are identified, we want to examine, on an exploratory basis, whether such polymorphisms are associated with anatomical and neurochemical brain imaging abnormalities in bipolar and unipolar mood disorder subjects. CLINICAL RELEVANCE: Once we have accumulated a larger sample of bipolar and unipolar patients and healthy individuals from our ongoing imaging studies, and have a better understanding of most promising imaging endophenotypes in these patients, we will be able to start examining the influence of specific genes that regulate brain development on the identified brain abnormalities. This protocol can be greatly relevant to help elucidate genetic underpinnings of brain abnormalities in mood disorders.