Divergent effects of two different doses of intranasal oxytocin on facial affect discrimination in schizophrenic patients with and without polydipsia

Rationale Hyponatremia and dexamethasone resistance in polydipsic schizophrenic patients are attributable to changes in hippocampal-modulated antidiuretic and stress hormone activity, respectively. The relationship of the neuroendocrine findings to the psychiatric illness, however, is unknown. An impaired ability to identify facial emotions has been linked to core features of schizophrenia and to diminished levels of the closely related hormone, oxytocin, in the polydipsic subset. Intranasal oxytocin enhances facial affect discrimination in healthy subjects. Objective The aim of this study is to explore if oxytocin reverses impaired facial affect discrimination in schizophrenic patients with, relative to that in patients without, polydipsia. Methods Intranasal oxytocin (10 or 20 IU) and placebo were administered on three occasions to five polydipsic schizophrenic patients, eight nonpolydipsic patients, and 11 healthy controls. Subsequently, subjects rated the presence and intensity of six facial emotions. Results Emotion recognition fell in both patient groups following 10 IU of oxytocin due to an increased propensity to identify all emotions regardless of whether they were displayed. By contrast, emotion recognition improved following 20 IU in polydipsic relative to nonpolydipsic patients due primarily to divergent effects on the bias to identify fear in nonfearful faces. Conclusion The effects of 20 IU oxytocin support the hypothesis that altered neuroendocrine function in polydipsic patients contributes to their psychiatric illness. Further studies are warranted to confirm these findings and assess if oxytocin treatment improves social functioning in this subset. This is the first psychopharmacologic study to compare different doses of oxytocin in the same subject, thus the significance of the opposing responses is unclear.