The aims and goals are similar to those proposed in the parent application. Briefly, we plan to measure 1) CNS glutamate using single voxel and chemical-shift, multivoxel, MRS, 2) microstructural white matter integrity using diffusion tensor imaging/tract-based spatial statistics and myelin mapping, 3) peripheral and central biomarkers of inflammation and 4) depressive symptoms and cognition in 65 medication-free depressed and 35 controls aged 35-65. A sample of 80 subjects (55 depressed, 25 controls) have already been studied. We propose support to recruit 10 more depressed and 10 more controlled subjects. Issues specific to this request: Our study has faced closure between the months of March-September 2020 due to COVID-19-related shutdown. However, all staff salaries have been paid in full due to understandable and compassionate reasons. We request recouping the salary paid for the past 7 months and restart up costs. The full impact of the study could be fully realized by augmenting the sample with 20 more patients ? resulting in a completion sample of 100. We have provided power analysis in support of this conclusion.
Is unchanged from the parent application. Older depressed patients also have an increased vulnerability to inflammation which may contribute to both depression and dementia through increasing extracellular CNS glutamate. The goal of the proposed research is to test the hypothesis that aging and inflammation interact in depression to lead to increased CNS glutamate which in turn is associated with accelerated white matter pathology and alterations in behavior and cognition.
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