In Vivo Neurochemistry and Electrophysiology of Bipolar Disorder and its Treatment

双相情感障碍及其治疗的体内神经化学和电生理学

• 批准号: 9294806
• 负责人: Rajapillai Laban Isaac Pillai
• 金额: $ 3.38万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9294806
• 关键词: Affective; Aftercare; Agonist; Animals; Auditory Evoked Potentials; Auditory area; Autopsy; Binding; Biological; Biological Markers; Bipolar Disorder; Bipolar II; Brain; Brain imaging; Defect; Dependence; Diagnosis; Direct Costs; Disease; Electroencephalography; Electrophysiology (science); Facilities and Administrative Costs; Female; Fiber; Functional disorder; Gender; General Population; Genes; Genetic Polymorphism; Goals; Heterogeneity; Human; Individual; Link; Lithium; Loudness; Major Depressive Disorder; Manic; Measures; Methods; Midbrain structure; Molecular; Mood stabilizers; Patient Care; Pharmacological Treatment; Physiological; Pilot Projects; Play; Positron-Emission Tomography; Prevalence; Recurrence; Role; Selective Serotonin Reuptake Inhibitor; Serotonergic System; Serotonin; Serotonin Receptor 5-HT1A; Signal Transduction; Specificity; TPH2; Testing; Time; Tracer; Unipolar Depression; United States; Woman; cost; depressive symptoms; dorsal raphe nucleus; gender difference; genetic analysis; hypomania; imaging study; improved; in vivo; insight; male; men; neurochemistry; predicting response; predictive of treatment response; receptor; receptor binding; response; serotonin transporter; suicide rate; symptom treatment; symptomatic improvement; transmission process; treatment response

Project Summary Bipolar disorder is a widespread and debilitating condition, yet its pathophysiology is poorly understood. Lithium is a widely used treatment, but its mechanism remains similarly uncertain. Evidence from animal studies, as well as human in vivo positron emission tomography (PET) studies, suggests that serotonin plays a large role in the disorder. In particular, the serotonin transporter (5-HTT) and the serotonin 1A (5-HT1A) receptor have been shown to function abnormally in bipolar subjects. In addition, an electroencephalography (EEG) paradigm known as the Loudness Dependence of the Auditory Evoked Potential (LDAEP), which is thought to relate inversely to serotonergic transmission, is altered in bipolar disorder. My study aims to examine the relationship between 5- HTT/5-HT1A activity and treatment response to lithium in bipolar disorder. I will examine this using both PET and EEG, to assess the neurochemical and electrophysiological profiles of serotonin function. A pilot study of five individuals with major depressive disorder showed a very strong correlation between LDAEP amplitude and 5- HT1A binding. Our results suggest that LDAEP may be a reliable indicator, not only of general serotonin function, but of specific binding potential. My study will test this hypothesis in the setting of bipolar disorder. First, the binding potential of 5-HTT and 5-HT1A receptors will be examined with PET and correlated with LDAEP amplitudes. A strong correlation will indicate a greater contribution of the receptor to the electrical signal. With this approach, I hope to improve the specificity of LDAEP analysis. Second, LDAEP will be examined in bipolar subjects before and after lithium treatment. Changes in LDAEP amplitude will provide evidence for changes in the serotonergic system. Initial amplitudes will also be correlated with treatment response to examine if LDAEP can serve as a response predictor. Finally, both PET and EEG will be used to assess differences between males and females in bipolar symptoms and treatments. As the disorder manifests itself differently between genders, I hope to improve understanding of this phenomenon. Greater biological understanding could help to advance pharmacological treatment. If positive results are found in this study, my findings may help explain the pathophysiology of bipolar disorder, while opening up EEG as a less expensive, more widely accessible, and noninvasive alternative to PET. In addition, by correlating EEG signal and 5-HT1A, I may be able to establish a cortical surrogate for subcortical receptor activity.

项目概要 双相情感障碍是一种广泛存在且使人衰弱的疾病，但其病理生理学却知之甚少。 锂是一种广泛使用的治疗方法，但其机制仍然同样不确定。来自动物研究的证据， 以及人体体内正电子发射断层扫描 (PET) 研究表明，血清素发挥着重要作用 在混乱中。特别是，血清素转运蛋白 (5-HTT) 和血清素 1A (5-HT1A) 受体已被 显示在双相情感障碍受试者中功能异常。此外，已知的脑电图（EEG）范式 作为听觉诱发电位的响度依赖性 (LDAEP)，它被认为与 血清素能传递在双相情感障碍中发生改变。我的研究旨在检验 5- HTT/5-HT1A 活性和双相情感障碍对锂的治疗反应。我将使用 PET 和 脑电图，评估血清素功能的神经化学和电生理学特征。五项试点研究 患有重度抑郁症的个体在 LDAEP 幅度和 5- HT1A 结合。我们的结果表明，LDAEP 可能是一个可靠的指标，不仅是一般血清素功能的指标， 但具有特定的结合潜力。我的研究将在双相情感障碍的背景下检验这一假设。首先， 将使用 PET 检查 5-HTT 和 5-HT1A 受体的结合潜力并与 LDAEP 相关 幅度。强相关性表明受体对电信号的贡献更大。和 这种做法，希望能提高LDAEP分析的特异性。其次，LDAEP将在双相情感障碍中进行检查 锂治疗前后的受试者。 LDAEP 振幅的变化将为以下变化提供证据 血清素能系统。初始振幅也将与治疗反应相关，以检查 LDAEP 是否 可以作为响应预测器。最后，PET 和 EEG 将用于评估男性之间的差异 以及女性的双相情感障碍症状和治疗。由于这种疾病在性别之间的表现不同，我 希望加深对这一现象的认识。更好的生物学理解有助于推进 药物治疗。如果这项研究发现积极的结果，我的发现可能有助于解释 双相情感障碍的病理生理学，同时将脑电图作为一种更便宜、更容易获得的方法 PET 的无创替代方案。此外，通过关联脑电图信号和 5-HT1A，我也许能够建立一个 皮质下受体活性的替代物。