Differentiating Unipolar and Bipolar Depression in Young Adults Using fMRI

摘要 关于情绪障碍的神经生物学，最大的未解之谜之一是--为什么有些病人 仅患有抑郁症发作（单极抑郁症或UD，也称为重度抑郁症）， 其他人患有抑郁症和相反的躁狂情绪状态（双相情感障碍或BD）。 在临床上，UD和BD抑郁症（BDD）都很难区分，只能被取笑 除了通过获得详细的纵向历史，以确定（hypo）躁狂的时期。然而，在年轻的 在疾病早期，这种病史要么很难引出，要么不存在，因为 BD的最初几次发作通常是抑郁症。只是随着时间的推移，通常是在多年的误诊和 不适当的治疗，一部分抑郁症的受试者开始遭受发作的公开， （hypo）躁狂，并显示自己实际上是患有BD。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 BD高风险UD患者（HRUD）和BD低风险UD患者之间的差异 （LRUD）。研究人员一直在进行功能性磁共振成像（fMRI）研究， 近十年来，皮质边缘的连接和活动，在最近的研究中， 连接异常以及BD和UD中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。这项建议会 研究40例BDD、80例UD（40例HRUD和40例 LRUD）年轻成人患者（21 - 35岁）与40名匹配的健康对照（HC）进行比较。除了 调查组间的横截面差异，BDD的探索性前瞻性验证 还将通过用抗抑郁药治疗80名UD受试者6周来进行相关的异常检查。 然后再自然地追踪他们18个月。将经常对受试者进行评估 出现（轻）躁狂被确定为BD诊断的转换者。差异 转换器和非转换器上的成像措施将进行调查和分析 成像测量是否与随时间推移的转化风险相关。本建议的创新方面 是：它解决了未使用药物的BDD和UD患者使用fMRI的差异研究不足的领域 研究电路水平异常的措施;研究问题最重要的年轻人; 调查（根据新的NIMH研究领域标准（RDoC）项目的目标）的相似性 HRUD和BDD受试者之间的差异;并使用横断面和前瞻性研究设计来探索 影像学指标预测从UD转为BD诊断风险的能力。的结果 这项研究也将对情绪障碍的神经生物学的理解产生关键影响 就像在临床上如何区分年轻人中的BDD和UD患者一样困难。

ABSTRACT 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, 80 UD (40 HRUD and 40 LRUD) young adult patients (21 - 35 yrs of age) compared to 40 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 80 UD subjects with antidepressants for 6 months and then following them up naturalistically for another 18 months. Subjects will be assessed frequently for emergence of (hypo)mania to be identified as converters to a BD diagnosis. Differences between converters and non-converters on the imaging measures will be investigated and an analysis will be conducted whether the imaging measures correlate with risk of conversion over time. Innovative aspects of this proposal are: it addresses the understudied area of differences between unmedicated BDD and UD patients using fMRI measures to study circuit level abnormalities; studies young adults in which the issue is most important; investigates (in line with aims of the new NIMH Research Domain Criteria (RDoC) project) the similarities between HRUD and BDD subjects; and uses a cross-sectional as well as prospective study design to explore the power of the imaging measures to predict the risk of conversion from UD to BD diagnosis. Findings from this study will have a critical impact both on the understanding of the neurobiology of mood disorders as well as on the difficult clinical issue of how to differentiate between BDD and UD patients in young adults.