Toward the identification of biomarkers of bipolar disorder

描述(申请人提供)：双相情感障碍(BP)是世界范围内最虚弱和最常见的疾病之一。患有BP的患者在抑郁时经常到临床服务机构就诊，但经常被误诊为单相抑郁(UPD)，导致治疗不足和预后不良。因此，提高诊断BP的准确性，特别是在抑郁症期间，是帮助改善BP患者心理健康的关键长期目标。通过识别反映BP病理生理过程的生物标志物-情绪调节受损、注意力受损和注意力分散-可以促进这一目标的实现，这些生物标志物在抑郁症和缓解期持续存在，在UPD中并不常见。作为迈向这一目标的第一步，本研究采用横断面设计和脑功能成像来测量患有传统BPI亚型功能异常的个体，这些异常存在于BPI抑郁和缓解以及BPI特有的情绪处理(杏仁核为中心)和工作记忆和注意力(背外侧前额叶皮质，DLPFC为中心)的大脑系统中。其次，我们将采用纵向设计来衡量这些大脑系统异常的变化与BPI和UPD在6个月内抑郁严重程度变化之间的关系。我们将检查1.40个缓解的BPI；2.40个抑郁的BPI；3.40个UPD；以及4.40个健康个体。6个月后，我们将对每组20名学生进行复查。我们将限制患者参与者服用的药物组合为少量，以便描述与特定药物相关的异常神经活动。我们假设：1.BPI缓解期和BPI抑郁者将表现出杏仁核对积极和消极情绪刺激的异常增加和DLPFC活性的降低，以及工作记忆中DLPFC活性的降低；2.UPD患者将表现出对负面情绪刺激而不是积极情绪刺激的杏仁核活动增加；3.随着时间的推移，抑郁程度的降低将与BPI中工作记忆期间DLPFC活性的降低有关，但在UPD患者中对负面情绪刺激的杏仁核活动将降低。相关性：BPI是一种常见的、使人衰弱的、可能致命的疾病，经常被误诊为UPD。这项研究旨在确定BPI的生物标志物，这些标志物反映抑郁症和缓解期常见的病理生理脑过程，并对BPI具有特异性，作为实现提高诊断准确性以帮助改善疾病患者心理健康的长期目标的第一阶段。

DESCRIPTION (provided by applicant): Bipolar disorder (BP) is one of the most debilitating and common illnesses worldwide. Individuals with BP frequently present to clinical services when depressed, but are often misdiagnosed with unipolar depression (UPD), leading to inadequate treatment and poor outcome. Increased accuracy in diagnosing BP, especially during depression, is therefore a key long term goal to help improve the mental health of individuals with BP. The attainment of this goal can be facilitated by identifying biomarkers reflecting pathophysiologic processes in BP - impaired emotion regulation, impaired attention and distractibility - that persist during depression and remission and are not common to UPD. As a first step toward this goal, this study employs a cross-sectional design and functional brain imaging to measure in individuals with the traditional BPI subtype functional abnormalities in brain systems underlying emotion processing (amygdala-centered) and working memory and attention (dorsolateral prefrontal cortex, DLPFC-centered) common to BPI depression and remission and BPI-specific. Second, we will employ a longitudinal design to measure relationships between changes in these brain system abnormalities and changes in depression severity over 6 months in BPI versus UPD. We will examine 1. 40 remitted BPI; 2. 40 depressed BPI; 3. 40 UPD; and 4. 40 healthy individuals. We will re- examine 20 individuals per group 6 months later. We will restrict medication combinations taken by patient participants to a small number to allow delineation of abnormal neural activity related to specific medications. We hypothesize that 1. BPI remitted and BPI depressed individuals will show abnormally increased amygdala and decreased DLPFC activity to positive and negative emotional stimuli, and decreased DLPFC activity during working memory; 2. UPD individuals will show increased amygdala activity to negative but not positive emotional stimuli; 3. decreased depression severity over time will be associated with decreased DLPFC activity during working memory in BPI, but with decreased amygdala activity to negative emotional stimuli in UPD. Relevance: BPI is a common, debilitating and potentially fatal disorder, often misdiagnosed as UPD. This study is directed at identifying biological markers of BPI that reflect pathophysiologic brain processes common to depression and remission and specific to BPI, as a first stage toward the long term goal of increasing diagnostic accuracy to help improve the mental heath of those with the disorder.