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.
