The importance of physiologic, metabolic, and endocrine studies for the understanding of anorexia nervosa (AN) remains a disputed subject. Recent reports on neuroendocrine changes in vasopressin (AVP) and norepinephrine (NE), CT scans, cognitive processing, and physical features (e.g., hypothermia) identified prolonged dysfunctions in weight-recovered anorectics. The majority of these reports are almost exclusively descriptive and no integrated biologic theory has been proposed to explain these putative """"""""slowly-reversible"""""""" phenomena and their role in the pathogenesis and maintenance of AN. In this grant we will assess the hypothesis that """"""""residual"""""""" biologic abnormalities resulting from starvation/cold-acclimatization processes and nausea/malaise-induced processes leading to conditioned food avoidance may perpetuate entrenched stereotyped behaviors and quasi-delusional thinking. The main residual biological variables that will be studied are: 1) cold-acclimatization induced thermoregulatory alterations such as nonshivering thermogenesis related to brown adipose tissue, and change in diurnal regulation; 2) marked fluctuations in skin and core temperatures and thermogenic hormones in response to ambient cold challenges (e.g., cold pressor test, climatic chamber); 3) postprandial effects of a caloric stimulus related to thermic changes, psychological state, and gastrointestinal discomfort; 4) NMR-detected enlarged cerebral sulci and ventricles related to basal hormone changes, and possibly, to cognitive performance; and 5) gradual return of metabolic function, body temperature, diurnal cycles and the menstrual cycle. We will characterize these weight-dependent changes that occur in our AN population at two different periods: 1) early in their treatment at admission (greater than 20% below IBW) and 2) following recovery of weight loss to within 5% IBW. Weight-dependent changes in thermoregulation (e.g., hypothermia) and cognitive processing (e.g., cognitive neuromotor tasks) will be assessed biweekly. Experimental perturbations are designed to characterize the relation of plasma ACTH, cortisol, AVP, NE and E to specific """"""""persisting"""""""" features, e.g., temperature fluctuations, vomiting).
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