This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Treatment of LLD is an important public health issue. The number of elderly (60 years and older) is a rapidly growing segment of the population and late life depression produces significant morbidity and mortality. LLD is a hetergenous disorder with poorly understood risk factors for development. It has been proposed that vascular disease may contribute to the development of a late-onset depression syndrome, in some individuals, by affecting white matter pathways and subcortical structures involved in mood regulation. LLD can be categorized along two major axes: one group of subjects has been described clinically with executive dysfunction; another group of subjects has been described with MRI-defined vascular depression. It is not known to what extent the same etiological mechanisms account for both sets of findings and to what extent these groups overlap. T2 hyperintensities (T2H) are increased in patients with vascular risk factors. Some recent studies have indicated that T2H may have prognostic value in treatment studies and are correlated with poor reatment outcome. Other recent studies have shown that patients with clinically defined vascular depression and executive dysfunction, as evidenced by lower scores on Initiation-Preseveration tests, have slower and less complete treatment response to antidepressants. Characterizing focal structural and neurospycholgical brain abnormalities holds promise to elucidate the pathophysiology of medication resistance to acute antidepressant treatment. At the same time we will determine whether using easily administrered tests of frontal deficits, such as Initiation-Perseveration (IP) scores and T2H severity, determined on the Fazekas scale, hold promise as practical, office based predictors of treatment outcome. Preliminary data suggests that IP deficits, severity of frontal deep white matter hyperintensities (FDWMH) and subcortical gray matter hyperintensities (SCGMH) may be predicitve of poor treatment outcome. In outpatients with LLD, we aim to evaluate the relationship of MRI-defined hyperintensities and clinical response in a prospective, controlled treatment trial using sertaline and to compare the neuropsycholgical performance of patients with greater lesion severity scores on MRI to those with lower lesion severity scores. The following important secondary aims will also be pursued: to determine the effect of lesion volume and location on lowering treatment response, to determine the relationship between sertraline response and executive dysfunction using IP scores and a composite 'frontal' neuropsychological battery and to test the effect of the interaction between MRI changes and executive dysfunction and VRFs in predicting poor treatment response. Exploratory aims are to test the effect of MRI lesion severity on other outcome measures. Elderly outpatients with LLD will be evaluated and treated prospectively, and broad inclusion/exclusion criteria will be used to facilitate generalizability. In addition the study will be conducted at two sites to increase the power of the study and to further increase generalizability to the large population of elderly with LLD.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000036-46
Application #
7377182
Study Section
Special Emphasis Panel (ZRR1-CR-4 (02))
Project Start
2006-04-01
Project End
2007-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
46
Fiscal Year
2006
Total Cost
$3,748
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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