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.
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