Cortical/Subcortical Circuits in Late-Life Depression

描述（由申请方提供）：拟定研究的目的是通过整合磁共振成像（MRI）衍生的脑生物化学指标与相关认知指标，检查晚期重度抑郁症（MDD）病理生理学中皮质-皮质下回路的生物学状态。我们建议在3特斯拉扫描仪上使用磁共振波谱（MRS）来估计MDD患者和对照组双侧背外侧白色物质和皮质下核中N-乙酰天冬氨酸、胆碱和肌醇的绝对和标准化水平。磁化转移（MT）是一种补充技术，将用于检查髓鞘和相关的大分子蛋白质在额叶白色物质和皮质下区域的状态。执行功能，工作记忆，语言和非语言学习和回忆的措施-反映背外侧额叶和皮层下功能的领域也将从我们的患者和对照组获得。整合相关的认知指标的生化措施，将有助于我们批判性地研究状态的皮质-皮质下回路的病理生理学的MDD。虽然老年MDD的临床影响得到广泛认可，但其生物学基础仍缺乏表征。额叶白色物质和皮质下核团在老年抑郁症病因学中的作用很少受到关注，拟议的研究将有助于我们阐明导致老年抑郁症的机制和途径。

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.