In Vivo Neurochemistry and Electrophysiology of Bipolar Disorder and its Treatment

项目摘要 双相情感障碍是一种普遍的、使人衰弱的疾病，但对其病理生理学知之甚少。 锂是一种广泛使用的治疗方法，但其机制同样不确定。来自动物研究的证据， 以及人体内的正电子发射断层扫描(PET)研究表明，5-羟色胺起着很大的作用 在混乱中。特别是，5-羟色胺转运体(5-HTT)和5-羟色胺1A(5-HT1A)受体 在双相情感障碍受试者中表现出功能异常。此外，已知的脑电(EEG)范例 如听觉诱发电位(LDAEP)的响度依赖，被认为与 5-羟色胺能传递，在双相情感障碍中改变。我的研究旨在考察5- 双相情感障碍患者HTT/5-HT1a活性与锂治疗反应我将使用PET和 EEG，以评估5-羟色胺功能的神经化学和电生理特征。五项初步研究 重度抑郁症患者LDAEP波幅与5-羟色胺有很强的相关性 HT1a结合。我们的结果表明，LDAEP可能是一个可靠的指标，不仅是一般的5-羟色胺功能， 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， 5-HTT和5-HT1a受体的结合潜力将用PET进行检测，并与LDAEP相关联 波幅。强烈的相关性将表明受体对电信号的贡献更大。使用 这种方法，希望能提高LDAEP分析的特异性。第二，LDAEP将在两极状态下进行检查 受试者锂治疗前后。LDAEP波幅的变化将为 血清素能系统。初始波幅也将与治疗反应相关联，以检查LDAEP 可以作为反应的预测器。最后，PET和EEG都将被用来评估男性之间的差异 和女性的躁郁症和治疗。由于这种障碍在不同性别之间表现不同，我 希望提高对这一现象的认识。更多的生物学理解可能有助于推动 药物治疗。如果在这项研究中发现了积极的结果，我的发现可能有助于解释 双相情感障碍的病理生理学，同时开放脑电图作为一种更便宜、更广泛的可获得的方法，以及 PET的非侵入性替代品。此外，通过将脑电信号和5-HT1a联系起来，我可能能够建立一个 皮质下受体活性的皮质替代物。

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.