This is a request for an ADAMHA Research Scientist Award. Sleep changes in late-life depression may be permanent or may recover only slowly. Hence, to clarify the relation of persistent sleep abnormalities, pathogenesis, and illness course, we propose three related longitudinal studies of: Study 1 - 200 elderly (60-80 yo) patients with recurrent unipolar depression participating in an already funded maintenance therapies research protocol (MH43832-01, C.F. Reynolds, P.I.); Study 2 - 80 elderly subjects (60-80 yo) with spousal bereavement (n=40) and bereavement-related depression (n=40); and Study 3 - 60 healthy elderly (60-80yo) non- depressed, non-bereaved controls. Participants in all three studies will have repeated (four to seven) sleep EEG assessments over a two to three year period to determine if, as hypothesized: 1a) abnormal pretreatment (T1) measures of REM sleep cyclicity/density predict elevated risk of relapse and recurrence of major depression; 1b) EEG sleep abnormalities persisting into continuation therapy (T2) and into maintenance therapy (T3-T7) predict elevated risk of relapse and recurrence, respectively; 2a) depressed bereaved differ from non-depressed bereaved elderly in baseline (T1) and followup (T2-T5) measures of REM sleep cyclicity/density; 2b) baseline (T1) and followup (T2-T5) abnormalities of REM sleep in bereavement predict a more protracted course (and need for psychiatric intervention); and 3) longitudinal changes in sleep/sleep quality (T1-T4) of healthy elderly controls are related to subclinical depressed mood. Multiple logistic regression and survival analyses will model the hypothesized relation of REM sleep abnormalities (independent variable) to outcome: recurrence/non-recurrence of depression (Study 1); or presence/absence of RDC-defined major depression at 1 and 2 years after spousal bereavement. A repeated-measures MANOVA will contrasts the long- term evolution of selected sleep variables (sensitive to aging, depressed mood, or both) in recurrent depression, bereavement, bereavement-related depression and controls. Exploratory data analyses will assess possible interrelations among biological controls. Exploratory data analyses will assess possible interrelations among biological REM sleep abnormalities, severity of psychopathology, and disruption in social rhythms.
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