In this second revision of our competitive renewal application, we propose to continue our work to enhance diagnostic accuracy in late-life mental illness. In addition, we propose new initiatives to identify physiologic indicators of prognosis in dementia and depression, and to develop physiologic predictors of antidepressant treatment response. The hypotheses are designed to address problems of clinical importance, and are based upon significant pilot data. In response to the Committee's critique, we have made significant revisions to this application. We have: 1) made our hypotheses more specific regarding the diagnosis and treatment of depression; 2) increased the number of subjects in the depressed group from 100 of 180; 3) eliminated ECT as a possible treatment; 4) revised our data analysis procedures to control for possible confounding variables, including baseline levels of function; 5) added more detail regarding mechanisms underlying our hypotheses; and 6) included new pilot data that support our hypotheses, and the clinical applications of our techniques. This proposal aims to: first, complete validation of QEEG as a method for the differential diagnosis of dementia and depression; second, use QEEG methods to identify indicators of prognosis in dementia and depression; third, develop neurophysiologic predictors of antidepressant treatment response; and, fourth, examine the functional significance of white- matter lesions with integrated MRI/QEEG, and assess the role of lesions in development of mental illness. We will test four hypotheses: 1) QEEG cordance and coherence are sensitive and specific measures for the diagnosis of dementia of the Alzheimer's type (DAT), multi-infarct dementia (MID), mixed DAT/MID dementia (MIX), and depression (DEP); 2) Low coherence at baseline will be associated with increased psychiatric symptoms and decreased functional status at follow-up in patients with dementia or DEP; 3) Changes in cordance during the course of antidepressant treatment will predict response to medication; and, 4) A combination of coherence and MRI lesion volume will identify those patients and normal controls (CON) at increased risk for recurrent depression, and cognitive and/or functional decline. We will accomplish these aims through a four-step plan. First, we will continue follow-up of our existing cohort of DAT, MID, and CON subjects, focusing on the evolution of functional disability and behavioral symptoms in relation to QEEG variables, and upon autopsy validation of clinical and QEEG- based diagnoses. Second, we will recruit new subjects with mild dementia or DEP, to prospectively examine the sensitivity and specificity of QEEG for diagnosis of these illnesses, and to identify QEEG predictors of treatment outcome and long-term prognosis. Third, we will intensively examine DEP subjects during the course of treatment to identify predictors of antidepressant response. Fourth, we will perform three-dimensional analysis of serial QEEG/MRI studies in DEP and CON subjects to identify the type and/or location of white-matter disease associated with altered brain function. Serial study will determine characteristics of lesions that adversely affect long-term prognosis, as well as the usefulness of QEEG for monitoring the evolution of white-matter disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH040705-12
Application #
2674844
Study Section
Mental Disorders of Aging Review Committee (MDA)
Project Start
1986-03-01
Project End
2000-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
12
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Other Domestic Higher Education
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Morgan, Melinda L; Cook, Ian A; Rapkin, Andrea J et al. (2007) Neurophysiologic changes during estrogen augmentation in perimenopausal depression. Maturitas 56:54-60
Hunter, Aimee M; Leuchter, Andrew F; Morgan, Melinda L et al. (2006) Changes in brain function (quantitative EEG cordance) during placebo lead-in and treatment outcomes in clinical trials for major depression. Am J Psychiatry 163:1426-32
Morgan, Melinda L; Witte, Elise A; Cook, Ian A et al. (2005) Influence of age, gender, health status, and depression on quantitative EEG. Neuropsychobiology 52:71-6
Cook, Ian A; Leuchter, Andrew F; Morgan, Melinda L et al. (2005) Changes in prefrontal activity characterize clinical response in SSRI nonresponders: a pilot study. J Psychiatr Res 39:461-6
Morgan, Melinda L; Cook, Ian A; Rapkin, Andrea J et al. (2005) Estrogen augmentation of antidepressants in perimenopausal depression: a pilot study. J Clin Psychiatry 66:774-80
Stubbeman, William F; Leuchter, Andrew F; Cook, Ian A et al. (2004) Pretreatment neurophysiologic function and ECT response in depression. J ECT 20:142-4
Cook, Ian A; Leuchter, Andrew F; Morgan, Melinda L et al. (2004) Longitudinal progression of subclinical structural brain disease in normal aging. Am J Geriatr Psychiatry 12:190-200
Krell, Heather V; Leuchter, Andrew F; Morgan, Melinda et al. (2004) Subject expectations of treatment effectiveness and outcome of treatment with an experimental antidepressant. J Clin Psychiatry 65:1174-9
Leuchter, Andrew F; Morgan, Melinda; Cook, Ian A et al. (2004) Pretreatment neurophysiological and clinical characteristics of placebo responders in treatment trials for major depression. Psychopharmacology (Berl) 177:15-22
Marie-Mitchell, Ariane; Leuchter, Andrew F; Chou, Chih-Ping et al. (2004) Predictors of improved mood over time in clinical trials for major depression. Psychiatry Res 127:73-84

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