Differentiating Unipolar and Bipolar Depression in Young Adults Using fMRI

使用功能磁共振成像区分年轻人的单相和双相抑郁症

• 批准号: 8488479
• 负责人: Amit Anand
• 金额: $ 38.53万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-05 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8488479
• 关键词: Address; Age; Amygdaloid structure; Anterior; Antidepressive Agents; Area; Biological; Bipolar Depression; Bipolar Disorder; Clinical; DSM-IV; Data; Depressed mood; Development; Diagnosis; Dorsal; Emotions; Etiology; Face; Functional Magnetic Resonance Imaging; Future; Image; Insula of Reil; Investigation; Lateral; Major Depressive Disorder; Manic; Measures; Mental Depression; Mood Disorders; Mood stabilizers; Moods; National Institute of Mental Health; Neurobiology; Patients; Pattern; Prospective Studies; Recording of previous events; Research; Research Design; Research Personnel; Rest; Risk; Schedule; Schizophrenia; Symptoms; Syndrome; Time; Unipolar Depression; Validation; base; cingulate cortex; follow-up; high risk; hypomania; innovation; prospective; young adult

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.

描述（由申请人提供）：关于情绪障碍神经生物学的一个尚未解决的谜团之一是 - 为什么有些患者只遭受抑郁症发作（单极抑郁或UD，也称为严重抑郁症），而其他患者则遭受抑郁症和相反情绪状态的躁狂状态（双极障碍或BD）的痛苦？在临床环境中，UD和BD抑郁症（BDD）都难以区分，只能通过获得详细的纵向病史来嘲笑以识别（hypo）躁狂症的时期。但是，在年轻患者中，在疾病的早期，这种病史要么很难引起，要么不存在，因为BD的前几集通常是抑郁症。只有随着时间的流逝，通常是经过多年的误诊和不适当的治疗后，一部分沮丧的受试者开始患有明显的（hypo）躁狂症发作，并揭示自己实际上是患有BD的。因此，迫切需要识别BDD和UD之间的神经生物学差异，以及患有BD的高风险（HRUD）的UD患者与患有BD较低风险的UD患者（LRUD）（LRUD）之间的差异。研究人员一直在进行近十年对皮质降低的连通性和活性的功能磁共振成像（fMRI）研究，并且在最近的研究中，BD和UD中的静止状态连通性异常以及任务诱导的激活异常。初步数据表明，这些度量可能有助于区分BDD和UD。该提案将研究40个BDD，120 UD（60 HRUD和60 LRUD）的年轻患者（16-25岁）和40个紧密匹配的健康对照（HC）的皮质型和激活异常。此外，研究组之间的横截面差异，还将通过定期进行抗抑郁药治疗HRUD和LRUD受试者，对BDD相关异常进行探索性的前瞻性验证24个月，并定期进行随访评估。将定期评估受试者（次）躁狂症的（亚）阈值症状的出现。将研究基线成像措施与（sub）（sub）阈值症状的发展（低）躁狂症或坦率转化为双极诊断之间的关系。该提案的创新方面是：它通过使用fMRI措施研究电路水平异常的措施解决了未经监测的BDD和UD患者之间的差异领域；研究该问题最重要的年轻患者；使用横截面和前瞻性研究设计；并符合NIMH研究领域标准（RDOC）项目的目标：1）HRUD和BDD受试者之间的相似性； 2）基线成像指标与（降低）躁狂的发展之间的关系是使用症状增加的连续度量，而不仅仅是基于DSM-IV诊断的二分法。这项研究将对对情绪障碍神经生物学的理解以及如何区分年轻BDD和UD患者的理解产生关键影响。