Fig. 1.

Acute psychosis aggravates reset osmostat in hyponatremic polydipsic patients. Following three weeks of optimal treatment on an inpatient psychiatric research unit, osmoregulation (dotted lines) in six hyponatremic polydipsic (red) and eight matched normonatremic polydipsic (blue) patients was similar and near normal. A transient psychotic exacerbation was then induced with intravenous methylphenidate. While severity of induced psychosis was similar, peak arginine vasopressin (AVP) plasma levels were higher in those subjects with hyponatremia (solid squares) despite their lower sodium levels. Moreover, as the figure illustrates, these peak AVP levels in the hyponatremic subjects (but not the normonatremics half-filled squares) were proportional to concurrent plasma sodium (solid red line: P_Na= 10.2P_AVP + 114 mEq/L; r = 0.80), consistent with reset osmostat. The resetting appears so severe (i.e. new set point = 114mEq/l) that it would induce water intoxication in the presence of even modest polydipsia. Thus these findings provide a plausible explanation for the observations first made in the early 20^th century that acute psychosis in some chronic psychotic patients impairs water excretion and contributes to water intoxication (Data derived from Goldman et al., 1996, 1997). See Supplemental Information for primer on water imbalance and reset osmostat. Normal range of AVP relative to concurrent plasma osmolality is shown in grey.