Cerebrospinal fluid corticotropin-releasing factor (CRF) and vasopressin concentrations predict pituitary response in the CRF stimulation test: A multiple regression analysis

D. Jeffrey Newport, Christine Marcelle Heim, Michael J. Owens, James C. Ritchie, Clayton H. Ramsey, Robert Bonsall, Andrew H. Miller, Charles B. Nemeroff

Research output: Contribution to journalArticle

41 Citations (Scopus)

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 centralnervous system (CNS). One line of evidencethat is consistent with centralCRFhypersecretion in these disorders is the blunted adrenocorticotropin hormone (ACTH) response tointravenous CRF administration, likely a consequence, at least in part, of downregulation of anterior pituitary CRF receptors. The presentstudy tests the hypothesis that elevated cerebrospinal fluid (CSF) concentrations of CRF and a secondary ACTH secretagogue, argininevasopressin (AVP), are associated with diminished adenohypophysealresponses in a standard CRF stimulation test. CSF concentrationsof CRF and AVP, and plasma ACTH responses to the administration of 1 mg/kg ovine CRF (oCRF) were measured in healthy adultwomen with and without current major depression and/or a history of significant childhood abuse. The primary outcome measure wasACTH area underthe curve (AUC) in the CRF stimulation test. Multiple linear regression was performed to identify the impact of CSFCRF and AVP concentrations upon the pituitary response to CRF stimulation. The regression modelexplained 56.5% of the variation inthe ACTH response to CRF stimulation. The relationship of CSF concentrations of CRF to ACTH responses to CRF were best describedby a third-order function that was inversely correlated over most of the range of studied values. The association of ACTH response withCSF concentration of AVP and the dose of oCRF followed second-order kinetics. These findings support the hypothesis that centralCRFhypersecretion is associated with a blunted ACTH response to exogenously administered CRF, explaining almost 60% ofthe variation inthe ACTH response to CRF.

Original languageEnglish (US)
Pages (from-to)569-576
Number of pages8
JournalNeuropsychopharmacology
Volume28
Issue number3
DOIs
StatePublished - Jan 1 2003

Fingerprint

Corticotropin-Releasing Hormone
Vasopressins
Cerebrospinal Fluid
Regression Analysis
Adrenocorticotropic Hormone
Hormones
Sheep
Depression
Corticotropin-Releasing Hormone Receptors
Post-Traumatic Stress Disorders
Psychiatry
Linear Models
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Newport, D. Jeffrey ; Heim, Christine Marcelle ; Owens, Michael J. ; Ritchie, James C. ; Ramsey, Clayton H. ; Bonsall, Robert ; Miller, Andrew H. ; Nemeroff, Charles B. / Cerebrospinal fluid corticotropin-releasing factor (CRF) and vasopressin concentrations predict pituitary response in the CRF stimulation test : A multiple regression analysis. In: Neuropsychopharmacology. 2003 ; Vol. 28, No. 3. pp. 569-576.
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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 centralnervous system (CNS). One line of evidencethat is consistent with centralCRFhypersecretion in these disorders is the blunted adrenocorticotropin hormone (ACTH) response tointravenous CRF administration, likely a consequence, at least in part, of downregulation of anterior pituitary CRF receptors. The presentstudy tests the hypothesis that elevated cerebrospinal fluid (CSF) concentrations of CRF and a secondary ACTH secretagogue, argininevasopressin (AVP), are associated with diminished adenohypophysealresponses in a standard CRF stimulation test. CSF concentrationsof CRF and AVP, and plasma ACTH responses to the administration of 1 mg/kg ovine CRF (oCRF) were measured in healthy adultwomen with and without current major depression and/or a history of significant childhood abuse. The primary outcome measure wasACTH area underthe curve (AUC) in the CRF stimulation test. Multiple linear regression was performed to identify the impact of CSFCRF and AVP concentrations upon the pituitary response to CRF stimulation. The regression modelexplained 56.5{\%} of the variation inthe ACTH response to CRF stimulation. The relationship of CSF concentrations of CRF to ACTH responses to CRF were best describedby a third-order function that was inversely correlated over most of the range of studied values. The association of ACTH response withCSF concentration of AVP and the dose of oCRF followed second-order kinetics. These findings support the hypothesis that centralCRFhypersecretion is associated with a blunted ACTH response to exogenously administered CRF, explaining almost 60{\%} ofthe variation inthe ACTH response to CRF.",
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Cerebrospinal fluid corticotropin-releasing factor (CRF) and vasopressin concentrations predict pituitary response in the CRF stimulation test : A multiple regression analysis. / Newport, D. Jeffrey; Heim, Christine Marcelle; Owens, Michael J.; Ritchie, James C.; Ramsey, Clayton H.; Bonsall, Robert; Miller, Andrew H.; Nemeroff, Charles B.

In: Neuropsychopharmacology, Vol. 28, No. 3, 01.01.2003, p. 569-576.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cerebrospinal fluid corticotropin-releasing factor (CRF) and vasopressin concentrations predict pituitary response in the CRF stimulation test

T2 - A multiple regression analysis

AU - Newport, D. Jeffrey

AU - Heim, Christine Marcelle

AU - Owens, Michael J.

AU - Ritchie, James C.

AU - Ramsey, Clayton H.

AU - Bonsall, Robert

AU - Miller, Andrew H.

AU - Nemeroff, Charles B.

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