This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Depression and cardiovascular disease are often comorbid. Clinical studies report impairment of endothelial functions and increased inflammatory markers (risk factor for cardiovascular disease) in depressed patients. Moreover, structural neuroimaging studies demonstrate that depressed patients have more blood vessel pathology in the frontal white matter than age-matched non-depressed controls. However, no studies of vascular morphology and related growth factors at the microscopic and molecular level have been conducted in depression to date. Our preliminary data on microscopic analysis of vessel number and morphology in postmortem brain tissue reveal significant increases in the density of abnormal vessels in the prefrontal cortex (PFC) in depression. These vascular changes were observed in the same subjects that were used in our previous cell counting studies on reductions in the density of neurons and glial cells. Moreover, our recent gene expression studies in these depressed subjects reveal downregulation of genes for fibroblast growth factor (FGF) and brain-derived neurotrophic factor (BDNF), and rodent studies indicate that these factors are reduced in stressed animals and elevated after treatment with electroconvulsive shock or antidepressants. Thus, we hypothesize that in depression there are alterations in vascular morphology that are associated with deficits in angiogenic and neurotrophic factors as well as pathology of neurons and glial cells in the PFC. We further hypothesize that these changes are due to the depressive disorder itself and not due to treatment with antidepressant medication, therefore they will not be observed in the PFC of monkeys treated with antidepressants. This proposal will be the first quantitative microscopic study of cortical vasculature in major depression. It will likely reveal a link between dysfunctional genes and the expression of angiogenic and neurotrophic factors and the pathology of blood vessels, neurons and glial cells in the prefrontal cortex of depressed individuals. This may reveal novel cellular and molecular targets of antidepressant action and possibly lead to the design of more effective medications for depressed patients with vascular disease.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017701-10
Application #
8360506
Study Section
Special Emphasis Panel (ZRR1-RI-5 (01))
Project Start
2011-07-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
10
Fiscal Year
2011
Total Cost
$206,643
Indirect Cost
Name
University of Mississippi Medical Center
Department
Psychiatry
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
Stoppelbein, Laura; McRae, Elizabeth; Greening, Leilani (2017) A Longitudinal Study of Hardiness as a Buffer for Posttraumatic Stress Symptoms in Mothers of Children with Cancer. Clin Pract Pediatr Psychol 5:149-160
Greening, Leilani; Stoppelbein, Laura; Cheek, Kara (2017) Racial/ethnic disparities in the risk of posttraumatic stress disorder symptoms among mothers of children diagnosed with cancer and Type-1 diabetes mellitus. Psychol Trauma 9:325-333
Ginley, Meredith K; Bagge, Courtney L (2017) Psychiatric heterogeneity of recent suicide attempters: A latent class analysis. Psychiatry Res 251:1-7
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Stewart, Courtney; Yu, Yue; Huang, Jun et al. (2016) Effects of high intensity noise on the vestibular system in rats. Hear Res 335:118-127
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Fisher, Lauren B; Overholser, James C; Dieter, Lesa (2015) Methods of committing suicide among 2,347 people in Ohio. Death Stud 39:39-43
Stoppelbein, Laura; Greening, Leilani (2015) A longitudinal study of the role of cortisol in posttraumatic stress disorder symptom clusters. Anxiety Stress Coping 28:17-30
Duncan, Jeremy; Wang, Niping; Zhang, Xiao et al. (2015) Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain. Neurotox Res 28:18-31
Johnson, Shakevia; Duncan, Jeremy; Hussain, Syed A et al. (2015) The IFN?-PKR pathway in the prefrontal cortex reactions to chronic excessive alcohol use. Alcohol Clin Exp Res 39:476-84

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