Cortical/Subcortical Circuits in Late-Life Depression

描述(申请人提供)：拟议研究的目的是通过将磁共振成像(MRI)得出的脑生化指标与相关的认知指标相结合，检查皮质-皮质下回路在晚年重度抑郁障碍(MDD)病理生理学中的生物学地位。我们建议在3特斯拉扫描仪上使用磁共振波谱(MRS)来评估MDD患者和对照组双侧背外侧白质和皮质下核团中N-乙酰天冬氨酸、胆碱和肌醇的绝对水平和标准化水平。磁化转移(MT)是一种补充技术，将用于检查额叶白质和皮质下区域的髓鞘和相关大分子蛋白的状态。执行功能、工作记忆、语言和非语言学习和回忆--反映额叶背外侧和皮质下功能的领域--的测量也将从我们的患者和对照组获得。将生化指标与相关的认知指标结合起来，将有助于我们批判性地检查皮质-皮质下回路在MDD病理生理学中的地位。虽然晚年MDD的临床影响已被广泛认识，但其生物学基础仍然缺乏特征。额叶白质和皮质下核团在晚年MDD发病机制中的作用尚未引起足够的重视，这些研究将有助于我们阐明导致晚年MDD的机制和途径。

DESCRIPTION (provided by applicant): The objective of the proposed study is to examine the biological status of cortical-subcortical circuits in the pathophysiology of late-life major depressive disorder (MDD) by integrating magnetic resonance imaging (MRI) derived measures of brain biochemistry with relevant measures of cognition. We propose to use magnetic resonance spectroscopy (MRS) on a 3 Tesla scanner to estimate absolute and normalized levels of N-Acetyl Aspartate, Choline and Myoinositol in the dorsolateral white matter and subcortical nuclei bilaterally in patients with MDD and controls. Magnetization transfer (MT) is a complementary technique that will be used to examine the status of myelin and related macromolecular proteins in the frontal white matter and subcortical regions. Measures of executive function, working memory, verbal and non-verbal learning and recall -- domains that reflect dorsolateral frontal lobe and subcortical functioning will also be obtained from our patient and control groups. Integrating biochemical measures with relevant cognitive indices will help us to critically examine the status of cortical-subcortical circuits in the pathophysiology of MDD. While the clinical impact of late-life MDD is widely acknowledged, its biological basis remains poorly characterized. The role of the frontal white matter and subcortical nuclei in the etiology of late-life MDD has received scant attention and the proposed studies will help us elucidate the mechanisms and pathways that lead to MDD in late-life.