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的一大未解之谜是——为什么有些患者只患有抑郁症发作（单极抑郁症或UD，也称为重度抑郁症），而另一些患者则患有抑郁症发作和相反的情绪状态躁狂（双相情感障碍或BD）？在临床环境中，UD和BD抑郁症（BDD）很难区分，只能通过获得详细的纵向病史来确定（轻度）躁狂期来区分。然而，在年轻患者中，在病程早期，这种病史要么很难引出，要么不存在，因为双相障碍的最初几次发作通常是抑郁症。只是随着时间的推移，通常经过多年的误诊和不适当的治疗，一部分抑郁受试者开始出现明显（轻度）躁狂发作，并显示自己实际上患有双相障碍。因此，迫切需要确定，特别是在年轻患者中，BDD和UD之间的神经生物学差异，以及患BD高风险的UD患者（HRUD）和患BD低风险的UD患者（LRUD）之间的差异。近十年来，研究人员一直在进行皮质边缘连通性和活动的功能磁共振成像（fMRI）研究，最近的研究已经确定了BD和UD的静息状态连通性异常以及任务诱导的激活异常。初步数据表明，这些措施可能有助于区分BDD和UD。本研究将研究40例BDD、120例UD（60例HRUD和60例LRUD）年轻患者（16 - 25岁）和40例密切匹配的健康对照（HC）的皮质杏仁核连通性和激活异常。此外，研究各组间的横断面差异，通过对hdd和LRUD患者使用抗抑郁药物治疗24个月并定期随访评估，对BDD相关异常进行探索性前瞻性验证。将定期评估受试者是否出现（次）阈值躁狂症状。基线影像测量与（次）阈值躁狂症状的发展或坦率地转换为双相诊断之间的关系将被调查。该提案的创新之处在于：它解决了未用药BDD和UD患者之间差异的研究不足的领域，使用功能磁共振成像测量来研究电路水平异常；研究最重要的年轻患者；采用横断面和前瞻性研究设计；根据NIMH研究领域标准（RDoC）项目的目的，调查：1)HRUD和BDD受试者之间的相似性；2)基线成像测量与（轻度）躁狂症发展之间的关系，使用症状增加的连续测量，而不仅仅是基于DSM-IV诊断的二分测量。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BDD和UD患者产生关键影响。

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.