Differentiating Unipolar and Bipolar Depression in Young Adults Using fMRI

描述(由申请人提供)：关于情绪障碍的神经生物学，一个巨大的未解之谜是--为什么一些患者只患有抑郁症(单相抑郁或UD，也称为重度抑郁症)，而另一些患者既患有抑郁症，又患有躁狂的相反情绪状态(双相情感障碍或BD)？在临床环境中，UD和BD抑郁症(BDD)都很难区分，只能通过获得详细的纵向病史来识别(低)躁狂期来区分。然而，在年轻患者中，在病程早期，这种病史要么很难诱发，要么不存在，因为BD的最初几个发作通常是抑郁症。随着时间的推移，通常是在多年的误诊和不适当的治疗之后，一部分抑郁症受试者开始出现明显的(低度)躁狂发作，并暴露出他们实际上患有BD。因此，尤其是在年轻患者中，迫切需要确定BDD和UD之间的神经生物学差异，以及发生BD(HRUD)的高危UD患者和低风险发生BD(LRUD)的UD患者之间的差异。近十年来，研究人员一直在进行皮质边缘连接和活动的功能磁共振成像(FMRI)研究，最近的研究发现，BD和UD的静息状态连接异常以及任务诱导的激活异常。初步数据显示，这些措施可能有助于区分BDD和UD。这项建议将研究40例BDD、120例UD(60例HRUD和60例LRUD)年轻患者(16-25岁)和40名密切匹配的健康对照组(HC)的皮质杏仁核连接和激活异常。此外，为了研究不同组间的横断面差异，还将通过对HRUD和LRUD受试者进行为期24个月的抗抑郁药物治疗，并定期进行随访评估，对BDD相关异常进行探索性前瞻性验证。受试者将定期接受评估，看是否出现(低于)阈值的(低)躁狂症状。将调查基线成像措施与(低)躁狂症或坦率转变为双相情感障碍的(亚)阈值症状的发展之间的关系。这项建议的创新方面是：它解决了未服用药物的BDD和UD患者之间研究不足的领域，使用功能磁共振测量来研究电路水平异常；研究了年轻患者，其中这个问题是最重要的；采用横断面和前瞻性研究设计；并与NIMH研究领域标准(RDoC)项目的目标一致，调查了：1)HRUD和BDD受试者之间的相似性；以及2)基线成像措施与(低)躁狂症的发展之间的关系，使用持续的症状增加指标，而不仅仅是基于DSM-IV诊断的二分法。这项研究将对理解情绪障碍的神经生物学以及如何区分年轻的BDD和UD患者产生重要影响。

DESCRIPTION (provided by applicant): One of the great unsolved mysteries regarding neurobiology of mood disorders is - why do some patients suffer only from episodes of depression (unipolar depression or UD, also known as major depression) while others suffer from episodes of both depression and the opposite mood state of mania (bipolar disorder or BD)? In the clinical setting, both UD and BD depression (BDD) are difficult to differentiate and can only be teased apart by obtaining a detailed longitudinal history to identify periods of (hypo) mania. However, in young patients, early in the course of the illness, this history is either very difficult to elicit or not present because the first few episodes of BD are usually of depression. Only with time, and usually after years of misdiagnosis and inappropriate treatment, a proportion of the depressed subjects start suffering from episodes of overt (hypo)mania and reveal themselves to be actually suffering from BD. Therefore, there is a critical need to identify, particularly in young patients, neurobiological differences between BDD and UD as well as differences between UD patients at a high risk for developing BD (HRUD) and UD patients with low risk of developing BD (LRUD). The investigators have been conducting functional magnetic resonance imaging (fMRI) studies of corticolimbic connectivity and activity for nearly a decade and in recent studies have identified resting state connectivity abnormalities as well as task-induced activation abnormalities in BD and UD. Preliminary data suggests that these measures may be helpful in differentiating between BDD and UD. This proposal will investigate corticoamygdalar connectivity and activation abnormalities in 40 BDD, 120 UD (60 HRUD and 60 LRUD) young patients (16 - 25 yrs of age) and 40 closely matched healthy controls (HC). Besides, investigating cross-sectional differences between groups, an exploratory prospective validation of the BDD related abnormalities would also be conducted by treating the HRUD and LRUD subjects with antidepressants for 24 months with follow-up assessments at regular intervals. Subjects will be assessed periodically for emergence of (sub)threshold symptoms of (hypo)mania. The relationship between baseline imaging measures and development of (sub)threshold symptoms of (hypo)mania or frank conversion to a bipolar diagnosis will be investigated. Innovative aspects of this proposal are: it addresses the understudied area of difference between unmedicated BDD and UD patients using fMRI measures to study circuit level abnormalities; studies young patients in which the issue is most important; uses a cross-sectional as well as prospective study design; and in line with aims of the NIMH Research Domain Criteria (RDoC) project investigates: 1)the similarities between HRUD and BDD subjects; and 2) the relationship between baseline imaging measures and the development of (hypo)mania using a continuous measure of increase in symptoms rather than only as a dichotomous measure based on DSM-IV diagnosis. This study will have a critical impact both on the understanding of the neurobiology of mood disorders as well as on how to differentiate between young BDD and UD patients.