Toward the identification of biomarkers of bipolar disorder

描述（由申请人提供）：双相情感障碍（BP）是世界上最使人衰弱和最常见的疾病之一。BP患者在抑郁时经常出现在临床服务中，但经常被误诊为单极抑郁症（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患者心理健康的一个关键的长期目标。这一目标的实现可以通过识别反映BP病理生理过程的生物标志物来促进-情绪调节受损，注意力和注意力受损-在抑郁和缓解期间持续存在，并且在UPD中并不常见。作为实现这一目标的第一步，本研究采用横断面设计和功能性脑成像来测量具有传统BPI亚型的个体在情绪处理（以杏仁核为中心）和工作记忆和注意力（背外侧前额叶皮层，dlpfc为中心）的脑系统功能异常，这些功能异常与BPI抑郁和缓解以及BPI特异性相关。其次，我们将采用纵向设计来测量BPI与UPD患者在6个月内这些脑系统异常变化与抑郁严重程度变化之间的关系。我们将检查1。40个汇出的BPI；2. BPI下降40；3. 40乌利希期刊指南;和4。40个健康个体。6个月后，我们将对每组20人进行复查。我们将限制患者参与者服用的药物组合数量，以允许描述与特定药物相关的异常神经活动。我们假设1。BPI缓解者和BPI抑郁者对正、负情绪刺激的杏仁核异常增加，DLPFC活动异常下降，工作记忆时DLPFC活动异常下降；2. UPD个体在消极情绪刺激下杏仁核活动增加，而在积极情绪刺激下没有；3. 随着时间的推移，抑郁严重程度的降低将与BPI中工作记忆期间DLPFC活动的降低有关，但与UPD中杏仁核对负面情绪刺激的活动减少有关。相关性：BPI是一种常见的、使人衰弱并可能致命的疾病，常被误诊为UPD。本研究旨在识别反映抑郁症和缓解期常见的脑病理生理过程和BPI特异性的BPI生物学标志物，作为提高诊断准确性以帮助改善患者心理健康的长期目标的第一步。

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.