Abstract

This project is central to the Conte center. All other projects are linked to this project in a conceptual and a practical sense. This project follows up on our findings that lesions disrupt the functioning of the mood circuit in elderly patients with depression. The project utilizes multimodal imaging Diffusion tensor imaging (DTI), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) along with cognitive testing and genetics to study the connectivity and dysregulation of the mood circuit. Based on findings from our earlier work we evaluate the nature of the changes in the fiber tracts connecting amygdala, Orbital prefrontal cortex, dorsolateral prefrontal cortex, striatum and its relationship to neurocognitive changes. We evaluate whether glutamate is reduced in the anterior cingulate and orbital prefrontal cortex in patients with depression using MRS. In addition we evaluate changes in brain structure and function as it relates to serotonin transporter promoter region allelic variants. This project uses state of the art image processing and will lead to a greater understanding of the neuroanatomical substrates of depression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH060451-09
Application #
7901666
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
9
Fiscal Year
2009
Total Cost
$333,776
Indirect Cost

  Institution

Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Petyuk, Vladislav A; Chang, Rui; Ramirez-Restrepo, Manuel et al. (2018) The human brainome: network analysis identifies HSPA2 as a novel Alzheimer’s disease target. Brain 141:2721-2739
Sims, Rebecca (see original citation for additional authors) (2017) Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet 49:1373-1384
Jun, Gyungah R; Chung, Jaeyoon; Mez, Jesse et al. (2017) Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimers Dement 13:727-738
Hohman, Timothy J; Bush, William S; Jiang, Lan et al. (2016) Discovery of gene-gene interactions across multiple independent data sets of late onset Alzheimer disease from the Alzheimer Disease Genetics Consortium. Neurobiol Aging 38:141-150
Jun, G; Ibrahim-Verbaas, C A; Vronskaya, M et al. (2016) A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry 21:108-17
Jacobsen, Jacob Pr; Rudder, Meghan L; Roberts, Wendy et al. (2016) SSRI Augmentation by 5-Hydroxytryptophan Slow Release: Mouse Pharmacodynamic Proof of Concept. Neuropsychopharmacology 41:2324-34
Ebbert, Mark T W; Boehme, Kevin L; Wadsworth, Mark E et al. (2016) Interaction between variants in CLU and MS4A4E modulates Alzheimer's disease risk. Alzheimers Dement 12:121-129
Hohman, Timothy J; Cooke-Bailey, Jessica N; Reitz, Christiane et al. (2016) Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk. Alzheimers Dement 12:233-43
Saha, Sayoni; Hatch, Daniel J; Hayden, Kathleen M et al. (2016) Appetite and Weight Loss Symptoms in Late-Life Depression Predict Dementia Outcomes. Am J Geriatr Psychiatry 24:870-8
Jacobsen, Jacob P R; Krystal, Andrew D; Krishnan, K Ranga R et al. (2016) Adjunctive 5-Hydroxytryptophan Slow-Release for Treatment-Resistant Depression: Clinical and Preclinical Rationale. Trends Pharmacol Sci 37:933-944

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