ERPs Cognitive Dysfunction and Treatment Response of Geriatric Depression

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DESCRIPTION (provided by applicant): This study focuses on frontal processing abnormalities in geriatric depression and their relationship to treatment response. Its aims evolved empirically from our studies suggesting that executive dysfunction (a clinical expression of frontal dysfunction) is: 1. Common in geriatric depression; 2. associated with a clinical presentation of depression consistent with frontal dysfunction and with microstructural white matter (WM) abnormalities lateral to the anterior cingulate cortex (ACC); and 3. contributes to disability. We also observed that indices of frontal dysfunction, including ACC dysfunction, predict poor response of late-life depression to antidepressants. A logical next step was a search for frontal processing abnormalities associated with poor antidepressant response. To this end, we conducted ERP studies following tasks activating the dorsal and the rostral ACC subdivisions, which led to the proposed hypotheses. The primary hypotheses postulate that large error-related negativity (ERN) and small error positivity (Pe) amplitude following the Color-Word Stroop response-inhibition task and an "emotional Go/Nogo" discrimination task of sad and neutral words predict change in depressive symptoms, remission and response rates and change in function in depressed elders treated with escitalopram. We will explore whether ERN and Pe amplitudes change during the treatment course and examine whether their change is associated with change in executive functions and in severity of depression. These hypotheses will be tested in 120 subjects with major depression stratified according to age (65-74 and 75-84 years) and executive dysfunction (Stroop), who will undergo a 12-week, controlled, open escitalopram trial with a target daily dose of 20 mg after a 2 week drug washout, placebo lead-in. The subjects will have EEG recording at baseline and weeks 4 and 8, and a comprehensive systematic evaluation of psychopathology and of clinical parameters that influence the course of depression (baseline, 8 weeks, and 12 weeks). Depressive symptomatology, functional status, and side effects will be rated weekly. On heuristic level, we expect that our findings will provide the impetus for translational research leading to novel treatment development and a change in clinical trials methodology. On a clinical level, identifying ERP abnormalities associated with poor antidepressant response and persistent disability may inform treatment planning, especially if the implicated ERP parameters are correlated with scores of simple-to-administer neuropsychological tests. Such patients could be targeted for a vigilant clinical follow-up and a comprehensive treatment plan including a plan for successive pharmacological trials.