Neuroimaging MAO-B in Medication Free and Treatment Resistant Major Depressive Disorder Using Novel MAO-B Tracer [11C]SL2511.88

使用新型 MAO-B 示踪剂对无药物治疗和难治性重度抑郁症进行神经影像 MAO-B [11C]SL2511.88

• 批准号: 10053730
• 负责人: JEFFREY H MEYER
• 金额: $ 23.09万
• 依托单位: CENTRE FOR ADDICTION AND MENTAL HEALTH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-11-10 至 2022-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10053730
• 关键词: Affect; Age; Anterior; Antioxidants; Apoptosis; Astrocytes; Benzylamines; Biological Markers; Brain; Brain region; Cessation of life; Chemicals; Chronic; Chronic stress; Clinic; Clinical; Corpus striatum structure; Data; Dopamine; Dorsal; Future; Genetic Markers; Genetic Transcription; Glucocorticoids; Health; Hormones; Impaired cognition; Impairment; Intention; Major Depressive Disorder; Measures; Metabolism; Monoamine Oxidase B; Moods; Motivation; Nerve Degeneration; Neurons; Norepinephrine; Nuclear; Oxidative Stress; Peripheral; Pharmaceutical Preparations; Phenethylamines; Play; Positive Valence; Positron-Emission Tomography; Predisposition; Prefrontal Cortex; Process; Proteins; Recording of previous events; Resistance; Rodent; Role; Selective Serotonin Reuptake Inhibitor; Serotonin; Stress; System; Therapeutic Effect; Tracer; Ventral Striatum; brain cell; cingulate cortex; cognitive control; cognitive system; common treatment; cost; density; early onset; improved; indexing; inhibitor/antagonist; monoamine; neuroimaging; novel; oxidation; protein biomarkers; response; reuptake; single episode major depressive disorder; therapeutic target; therapy resistant; transcription factor

Project Summary/Abstract Monoamine oxidase B (MAO-B) is a highly abundant protein in the brain that generates oxidative stress, removes monoamines such as dopamine and norepinephrine that support normal mood, and influences the predisposition towards apoptosis. MAO-B levels and activity are highly correlated and increase after chronic stress hormone exposure. MAO-B activity is increased in rodent brain after chronic unpredictable stress, however, MAO-B has not been studied in the most common early onset (age<45 years) major depressive disorder (MDD). Using [11C]SL25.1188 positron emission tomography, we propose to study whether MAO-B VT is elevated in key brain regions in early onset MDD during medication free major depressive episodes; (MDE; n=31), and in medication free major depressive episodes with a history of treatment resistance (n=31) as well as age matched healthy controls (from n=46). The intention is to make a convincing case that MAO-B levels are frequently elevated in key affect modulating regions during MDE, especially treatment resistant MDE. Such results could be applied to develop strategies for matching MDE cases of elevated MAO-B level towards MAO-B inhibitor treatments in the clinic through identifying low cost predictors of elevated MAO-B level (such as the clinical and RDOC measures proposed and/or additional peripheral protein or genetic biomarkers in future study).

项目摘要/摘要 单胺氧化酶B(MAO-B)是大脑中一种高度丰富的蛋白质，它能产生 氧化应激，去除单胺，如多巴胺和去甲肾上腺素 正常情绪，并影响对细胞凋亡的倾向。MAO-B水平和活动 是高度相关的，并且在长期应激激素暴露后增加。MAO-B活动是 在慢性不可预测的应激后，啮齿动物大脑中MAO-B的含量增加，然而，MAO-B并没有被 研究对象为最常见的早发性(45岁)严重抑郁障碍(MDD)。 使用[11C]SL25.1188正电子发射断层扫描，我们建议研究MAO-B VT是否 非药物治疗的重度抑郁症早期发病的MDD患者关键脑区升高 发作；(MDE；n=31)，以及在非药物治疗中有以下病史的主要抑郁发作 耐药组(31例)和年龄匹配的健康对照组(46例)。这个 目的是提出一个令人信服的理由，即MAO-B水平在关键影响因素中经常升高 MDE过程中的调节区，尤其是耐药MDE。这样的结果可能是 应用于制定MAO-B水平升高的MDE病例与MAO-B匹配的策略 通过寻找MAO-B水平升高的低成本预测因素在临床上应用抑制剂治疗 (例如建议的临床和RDoC措施和/或额外的外周蛋白或 未来研究中的遗传生物标记物)。