Investigators of the Duke CRC/PE propose to continue and expand activities developed during the first two years of this award. The primary goal of the Duke Center has been to define and validate a limited number of depressive subtypes in late life that are clinically relevant and prime for further study because of recent advances in neurosciences, nosology, and epidemiology, as well as biologic and psychologic approaches to therapy. Specifically, the Duke Center will continue to recruit 100 elderly (60+ years of age) and middle-aged (35-50 years of age) psychiatric and medical inpatients and begin the recruitment of 50 psychiatric outpatients each year of the project (two-thirds elderly and one-third middle- aged) for the purpose of supporting a series of focused research projects. Three hundred and ninety subjects have been recruited to the Duke Center to date and have been allocated to a series of ongoing pilot studies which include: (1) the phenomenology of late-life depression (including a study of 180 community volunteer); (2) a study of potential biological markers for depression in late life, specifically, dexamethasone supression, tritiated imipramine binding, and serotonin uptake; (3) a study of pharmacokinetic differences which may underlie reported age- related differences in tricyclic (nortriptyline) response and a validation of the CNS significance of platelet uptake features and uptake kinetics relative to repeated tricyclic antidepressant administration; and (4) an investigation of the efficacy and toxic effects of pulse unilateral nondominant ECT in the elderly. Four subtypes of late-life depression have been targeted for study: (1) major depressive episodes, (2) dysthymia, (3) mixed anxiety and depressive disorders (atypical depression), and (4) dysphoria not associated with the above three subtypes. New pilot projects proposed for the CRC include: (1) a study of the outcome of depressive subtypes utilizing two methods of classification (standard criteria and grade-of membership analysis), (2) a study of the effects of cognitive-oriented therapy in late-life depression, and (3) further explorations into the psychobiology of late-life depression. Progress to date and plans for future studies make possible a more definitive approach to reliable and valid nosological classification of depression in later years.
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