title: Diminished glucocorticoid negative feedback in polydipsic hyponatremic schizophrenic patients.
abstract: BACKGROUND
  The mechanism and significance of diminished glucocorticoid negative feedback in schizophrenia is unknown but is more commonly observed in schizophrenic patients with primary polydipsia. Polydipsic patients, especially those who are also hyponatremic, exhibit other neuroendocrine abnormalities that have been linked to hippocampal pathology.
  
  
  OBJECTIVE
  The objective of the study was to determine the effect of cortisol on plasma ACTH under conditions thought to be most sensitive to hippocampal influences.
  
  
  METHODS
  The design was repeated measures.
  
  
  METHODS
  The study was conducted at an inpatient clinical research center.
  
  
  METHODS
  Participants included eight polydipsic hyponatremic and eight polydipsic normonatremic as well as six schizophrenic patients without water imbalance. Eight healthy community volunteers matched for age and gender were also studied.
  
  
  METHODS
  Metyrapone (750 mg) was administered orally at 1430 and 1900 h. Beginning at 1930 h, hydrocortisone was infused over 150 min at 0.03 mg/kg.h. Blood samples and other measures were obtained at 20-min intervals from 1850 to 2320 h.
  
  
  METHODS
  Plasma ACTH and cortisol were measured.
  
  
  RESULTS
  ACTH levels did not decline significantly during the cortisol infusion in the polydipsic hyponatremic group. For any given level of cortisol, ACTH levels were higher in the hyponatremic group. Although levels declined after cortisol in the other three groups, the decline was greatest in patients without water imbalance.
  
  
  CONCLUSIONS
  The marked impairment in glucocorticoid negative feedback in polydipsic hyponatremic schizophrenic patients is consistent with hippocampal mineralocorticoid dysfunction.
authors.affiliation: Department of Psychiatry, University of Chicago and Psychiatric Institute, Chicago, Illinois 60637, USA. m-goldman@uchicago.edu
authors.forename: Morris B
authors.initials: MB
authors.lastname: Goldman
authors.forename: Gordon
authors.initials: G
authors.lastname: Wood
authors.forename: Megan B
authors.initials: MB
authors.lastname: Goldman
authors.forename: Michelle
authors.initials: M
authors.lastname: Gavin
authors.forename: Stacey
authors.initials: S
authors.lastname: Paul
authors.forename: Suhaila
authors.initials: S
authors.lastname: Zaheer
authors.forename: Ghazala
authors.initials: G
authors.lastname: Fayyaz
authors.forename: Ramani S
authors.initials: RS
authors.lastname: Pilla
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D014150:Antipsychotic Agents / Q000008:administration & dosage; D002090:Butyrophenones / Q000008:administration & dosage; D004326:Drinking / Q000502:physiology*; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005938:Glucocorticoids / Q000097:blood*; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000097:blood; D007010:Hyponatremia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D014883:Water-Electrolyte Imbalance / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000893:Anti-Inflammatory Agents; D014150:Antipsychotic Agents; D002090:Butyrophenones; D005938:Glucocorticoids; D000324:Adrenocorticotropic Hormone; C008522:metylperon; D006854:Hydrocortisone