This program project competing renewal focuses on affective illness in childhood and early adolescence. The evidence accumulated during this period indicates that juvenile depression has extremely high associated morbidity and mortality and is continuous with adult affective illness. This project has demonstrated biological correlates in prepubertal depression similar to those reported among adult affectively ill subjects including: (1) blunted growth hormone response to provocative stimuli, a likely """"""""trait marker"""""""" for depressive illness, (2) abnormalities in the cortisol and prolactin response to L-5-HTP, a serotonergic probe, and (3) in a subset of prepubertal children, adult-like sleep abnormalities. This proposal contains four projects and four supporting cores. The projects are: (1) """"""""Neurobiological Correlates of Depression: Predictive Validity, Specificity, and Localization of Abnormalities,"""""""" (2) """"""""Physiological Maturation of Sleep and Neuroendocrine Regulation,"""""""" (3) """"""""Biology and Family Adversity in Prepubertal Depression,"""""""" and (4) """"""""Quantitative EEG Sleep Analyses"""""""". These projects emphasize: (1) continued follow-up of this valuable cohort of children to examine the predictive validity of the extensive psychobiologic, psychiatric, and family data gathered previously; (2) examination of the discriminant validity of these measures vis a vis children with non-affective psychiatric disorders; (3) refinement, extension, and localization of these psychobiologic measures; (4) examination of maturational effects in these psychobiologic systems in an intensive longitudinal design in normal children as they enter puberty and both cross-sectionally and longitudinally in depressed children; (5) rigorous assessment of family environment and family interaction in combination with these biologic measures--a potentially powerful combined approach not previously used in this population; and (6) development and application of digital signal processing techniques to EEG sleep measures to examine maturational changes in sleep and sleep regulation in depression. Together, these projects seek to extend our understanding of selected promising biologic measures, add a new domain of measures (family environment and family interaction) and focus on the interval of pubertal maturation, to advance our knowledge of the psychobiology of early onset affective disorders. Ultimately these studies may: help to distinguish various subtypes of depression; allow more accurate prediction of morbid risk and treatment response, relapse, or recurrence; provide diagnostic confirmation; and/or lead to a better understanding of the pathophysiology of this disorder.
Showing the most recent 10 out of 82 publications
