title: Cerebrospinal fluid corticotropin-releasing factor (CRF) and vasopressin concentrations predict pituitary response in the CRF stimulation test: a multiple regression analysis.
abstract: There is considerable evidence that stress-related psychiatric disorders, including depression and post-traumatic stress disorder (PTSD), are associated with hypersecretion of corticotropin-releasing factor (CRF) within the central nervous system (CNS). One line of evidence that is consistent with central CRF hypersecretion in these disorders is the blunted adrenocorticotropin hormone (ACTH) response to intravenous CRF administration, likely a consequence, at least in part, of downregulation of anterior pituitary CRF receptors. The present study tests the hypothesis that elevated cerebrospinal fluid (CSF) concentrations of CRF and a secondary ACTH secretagogue, arginine vasopressin (AVP), are associated with diminished adenohypophyseal responses in a standard CRF stimulation test. CSF concentrations of CRF and AVP, and plasma ACTH responses to the administration of 1 microg/kg ovine CRF (oCRF) were measured in healthy adult women with and without current major depression and/or a history of significant childhood abuse. The primary outcome measure was ACTH area under the curve (AUC) in the CRF stimulation test. Multiple linear regression was performed to identify the impact of CSF CRF and AVP concentrations upon the pituitary response to CRF stimulation. The regression model explained 56.5% of the variation in the ACTH response to CRF stimulation. The relationship of CSF concentrations of CRF to ACTH responses to CRF were best described by a third-order function that was inversely correlated over most of the range of studied values. The association of ACTH response with CSF concentration of AVP and the dose of oCRF followed second-order kinetics. These findings support the hypothesis that central CRF hypersecretion is associated with a blunted ACTH response to exogenously administered CRF, explaining almost 60% of the variation in the ACTH response to CRF.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Woodruff Memorial Research Building, 1639 Pierce Drive, Suite 4000, Atlanta, GA 30322, USA.
authors.forename: D Jeffrey
authors.initials: DJ
authors.lastname: Newport
authors.forename: Christine
authors.initials: C
authors.lastname: Heim
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owens
authors.forename: James C
authors.initials: JC
authors.lastname: Ritchie
authors.forename: Clayton H
authors.initials: CH
authors.lastname: Ramsey
authors.forename: Robert
authors.initials: R
authors.lastname: Bonsall
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Miller
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D019540:Area Under Curve; D016001:Confidence Intervals; D003346:Corticotropin-Releasing Hormone / Q000134:cerebrospinal fluid* / Q000494:pharmacology; D005260:Female; D005544:Forecasting; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D012044:Regression Analysis; D014667:Vasopressins / Q000134:cerebrospinal fluid*
chemical_list: D014667:Vasopressins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone