PNAS[1] research

PNAS[1] research - Pronounced and sustained central...

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Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: Relation to hypercortisolism and corticotropin-releasing hormone Ma-Li Wong a,b , Mitchel A. Kling b,d , Peter J. Munson e , Samuel Listwak a , Julio Licinio a , Paolo Prolo a , Brian Karp a , Ian E. McCutcheon f , Thomas D. Geracioti, Jr. g , Michael D. DeBellis h , Kenner C. Rice i , David S. Goldstein j , Johannes D. Veldhuis k , George P. Chrousos l , Edward H. Oldfield f , Samuel M. McCann m , and Philip W. Gold a,c a Clinical Neuroendocrinology Branch, National Institute of Mental Health, and e Analytical Biostatistics Section, Laboratory of Structural Biology, Division of Computer Research and Technology, and i Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, and j Clinical Neuroscience Branch and f Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, and l Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; d Department of Psychiatry, Baltimore Veterans Affairs Medical Center and University of Maryland School of Medicine, Baltimore, MD 21201; g Department of Psychiatry, University of Cincinnati Medical Center, Cincinnati, OH 45267; h Department of Child and Adolescent Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; k Department of Internal Medicine and National Science Foundation Center for Biological Timing, University of Virginia Health Sciences Center, Charlottesville, VA 22908; and m Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808-4124 Contributed by Samuel M. McCann, November 9, 1999 Both stress-system activation and melancholic depression are char- acterized by fear, constricted affect, stereotyped thinking, and similar changes in autonomic and neuroendocrine function. Because norepi- nephrine (NE) and corticotropin-releasing hormone (CRH) can pro- duce these physiological and behavioral changes, we measured the cerebrospinal fluid (CSF) levels each hour for 30 consecutive hours in controls and in patients with melancholic depression. Plasma adre- nocorticotropic hormone (ACTH) and cortisol levels were obtained every 30 min. Depressed patients had significantly higher CSF NE and plasma cortisol levels that were increased around the clock. Diurnal variations in CSF NE and plasma cortisol levels were virtually super- imposable and positively correlated with each other in both patients and controls. Despite their hypercortisolism, depressed patients had normal levels of plasma ACTH and CSF CRH. However, plasma ACTH and CSF CRH levels in depressed patients were inappropriately high, considering the degree of their hypercortisolism. In contrast to the significant negative correlation between plasma cortisol and CSF CRH levels seen in controls, patients with depression showed no statistical relationship between these parameters. These data indicate that
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PNAS[1] research - Pronounced and sustained central...

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