This is a request for a continuation of my ADAMHA Research Scientist Award. Receiving this continuation will permit me to further my research programs in psychoneuroendocrinology, which have grown and developed over the past 20 years. My studies focus on the neuroendocrinology of depressive disorders, with particular reference to (1) assessing the utility of endocrine testing and sleep electrophysiology as aids in the diagnosis of endogenous depression and (2) determining the underlying mechanisms of neuroendocrine disturbances in depression. There are several objectives for the next five years. The first is to finish the data analyses and reports of our major study of a long- form neuroendocrine protocol (nocturnal blood sampling, TRH and LHRH stimulation tests, dexamethasone suppression test (DST) conducted on 40 definite endogenous depressed patients and 40 matched normal control subjects. Additional hormones planned for analysis include metabolically free serum fractions of steroid hormones and melatonin. Based on this work, we have developed a new, sensitive, and specific short-form sleep-endocrine protocol, which combines sleep electrophysiology, a 0.5 mg 8-hr DST, and a TRH stimulation test. The second objective of this research is to validate the clinical utility of this protocol by applying it to several diagnostic categories of depressed patients, including endogenous and nonendogenous depressives, dysthymics, and other comparison groups. A third objective is to continue my collaboration with Dr. Russell Poland for the study of more fundamental neuroendocrine aspects of depression, including the relationship of bioactive to immunoactive ACTH secretion. Finally, I plan to continue gaining experience with a new experimental paradigm, the use of fetal neuron transplants to introduce neurotransmitters into different areas of the brain involved in neuroendocrine regulation, to attempt to elucidate the roles in neuroendocrine function of different neurotransmitters at specific neuroanatomical sites.
