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最大未解之谜之一是 - 为什么有些患者仅患有抑郁症发作（单相抑郁症或 UD，也称为重度抑郁症），而其他患者则同时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识别（低）躁狂时期来区分。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 BD 的前几次发作通常是抑郁症。只是随着时间的推移，通常是经过多年的误诊和不适当的治疗，一部分抑郁症患者开始出现明显的（轻）躁狂发作，并显示自己实际上患有双相情感障碍。因此，迫切需要确定 BDD 和 UD 之间的神经生物学差异，尤其是年轻患者，以及 BD 高风险 UD 患者 (HRUD) 和 BD 低风险 UD 患者 (LRUD) 之间的差异。近十年来，研究人员一直在对皮质边缘连接和活动进行功能磁共振成像 (fMRI) 研究，最近的研究发现了 BD 和 UD 的静息态连接异常以及任务诱发的激活异常。初步数据表明，这些措施可能有助于区分 BDD 和 UD。该提案将调查 40 名 BDD、120 名 UD（60 名 HRUD 和 60 名 LRUD）年轻患者（16 - 25 岁）和 40 名密切匹配的健康对照 (HC) 的皮质杏仁核连接和激活异常。此外，为了调查组间的横截面差异，还将通过使用抗抑郁药治疗 HRUD 和 LRUD 受试者 24 个月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。将定期评估受试者是否出现（低）躁狂的（亚）阈值症状。将研究基线影像学测量与（轻）躁狂（低）阈值症状的发展或坦率转变为双相情感障碍诊断之间的关系。该提案的创新之处在于：它利用功能磁共振成像措施来研究回路水平异常，解决了未接受药物治疗的 BDD 和 UD 患者之间尚未研究的差异领域；研究该问题最重要的年轻患者；使用横断面和前瞻性研究设计；根据 NIMH 研究领域标准 (RDoC) 项目的目标，调查：1) HRUD 和 BDD 科目之间的相似性； 2) 使用症状增加的连续测量而不是仅作为基于 DSM-IV 诊断的二分测量来确定基线影像测量与（轻）躁狂发展之间的关系。这项研究将对情绪障碍的神经生物学的理解以及如何区分年轻的 BDD 和 UD 患者产生重大影响。