The overall goal is to establish the mechanism of episodic water intoxication that occurs so commonly in chronic schizophrenia and, in particular, to determine if the responsible defects in water balance are linked to the psychosis, per se. The preliminary study identified two basal abnormalities in water excretion in polydipsic, hyponatremic chronic psychotics when compared to matched non-polydipsic, normonatremic psychiatric controls. One abnormality was a defect in the kidney's capacity to dilute urine, and the other was in the osmoregulation of the hypothalamic hormone, arginine vasopressin (AVP). The abnormalities were not severe enough to account for the episodes of more severe hyponatremia that accompany water intoxication. The first proposed study will evaluate whether an idiosyncratic response to neuro-leptics causes these basal abnormalities by determining water balance in polydipsic, hyponatremic chronic psychotics on and off neuroleptics compared to normal controls. The second study will determine whether, instead, chronic polydipsia causes these abnormalities by comparing water balance in hyponatremic chronic psychotics; polydipsic normonatremic psychotics matched for severity of polydipsia; and normal controls. The third study will evaluate whether the basal abnormality in osmoregulation worsens during spontaneous episodes of severe hyponatremia, and if this worsening is accompanied by an increase in plasma homovanillic acid (HVA) and exacerbation of the psychosis. Water balance, plasma HVA, and psychosis ratings will be assessed in polydipsic, hyponatremic psychotics under basal conditions and during a spontaneous episode of severe hyponatremia. These studies should clarify the etiology of the basal abnormalities in water excretion as well as the episodes of water intoxication in chronic psychotics; may contribute to improved treatment of disorders of water metabolism; and may further understanding of the neurochemical basis of schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29MH043618-01A1
Application #
3474838
Study Section
Psychopathology and Clinical Biology Research Review Committee (PCB)
Project Start
1989-09-01
Project End
1992-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Goldman, Morris B (2009) The mechanism of life-threatening water imbalance in schizophrenia and its relationship to the underlying psychiatric illness. Brain Res Rev 61:210-20
Goldman, M B; Robertson, G L; Luchins, D J et al. (1997) Psychotic exacerbations and enhanced vasopressin secretion in schizophrenic patients with hyponatremia and polydipsia. Arch Gen Psychiatry 54:443-9
Goldman, M B; Robertson, G L; Hedeker, D (1996) Oropharyngeal regulation of water balance in polydipsic schizophrenics. Clin Endocrinol (Oxf) 44:31-7
Goldman, M B; Robertson, G L; Luchins, D J et al. (1996) The influence of polydipsia on water excretion in hyponatremic, polydipsic, schizophrenic patients. J Clin Endocrinol Metab 81:1465-70
Goldman, M B; Blake, L; Marks, R C et al. (1993) Association of nonsuppression of cortisol on the DST with primary polydipsia in chronic schizophrenia. Am J Psychiatry 150:653-5
Goldman, M B; Marks, R C; Blake, L et al. (1992) Estimating daily urine volume in psychiatric patients: empiric confirmation. Biol Psychiatry 31:1228-31