Deepa Purushothaman, MD

ackground Increased self-interest and/or distrust in others are reported as possible reasons for decreased cooperation in paranoia1. While a few studies have examined trust behavior in schizophrenia altruistic behavior is underexplored in Schizophrenia. Altruism characterized by decreased self-interest, an evolutionarily advantageous human quality, is critical for social cooperation. Recent studies in healthy humans have suggested vasopressin to play critical role in altruistic behavior2. However, the effect of vasopressin on altruistic behavior in SCZ is not examined till date. In this study we examined the effect of vasopressin on altruistic behavior in schizophrenia using a neuroeconomics paradigm, dictator game. Methods 30 patients with DSM IV TR SCZ (age 32.73 ± 6.66; M:F = 16:14) and 30 matched healthy volunteers (HV) (age 31.23 ± 5.48;M:F= 17:13; p>0.05) participated in the study. Clinical severity was assessed using Scale for assessment of negative symptoms, scale for assessment of positive symptoms and Calgary depression rating scale. Childhood trauma was assessed using Adverse childhood experience (ACE)3 questionnaire. After clinical assessments, patients participated in a double blinded counterbalanced crossover study. Equal amount of vasopressin (40 IU) or saline placebo were administered to the patients. Participants were made to choose one from 5 Dictator game scenarios4,5 (of money units 150,180, 200, 210 and 210 each; allocation of funds varying in level of altruism). HV performed dictator game once without administration of vasopressin or placebo. We compared the performance of patients in placebo condition with that of HV using independent t-test. Effect of vasopressin vs placebo in patients was examined using paired t-test. Relation between clinical variables and performance in dictator game was examined using Pearson’s correlation analysis. Results Patients with SCZ, compared to HV shared significantly lower money units in dictator game ((SCZ-43.67 ± 37.37; HV - 90.67±25.86; t=5.67; p<0.001). SCZ shared significantly higher money units with intranasal Vasopressin (54.67 ± 36.93) compared to placebo (43.67 ± 37.37; t=; p= 0.013). Mean change in money units shared with vasopressin had a trend level negative correlation with ACE questionnaire score (r= -0.37; p=0.046) suggesting those with higher childhood trauma had greater response to vasopressin. There was no relation with other clinical variables. Discussion To the best of our knowledge, this is the first study examining the effects of the prosocial neuropeptide Vasopressin on Dictator game behavior in Schizophrenia. The results suggest that patients with SCZ have lower altruistic behavior compared to HV which improved partially with intranasal vasopressin. Whether the magnitude of improvement seen with single dose of vasopressin will increase with repeated doses need to be examined in systematic trials. The possible interaction between childhood adversity and response to vasopressin need to be examined in future. Findings of the study provide rationale to examine potential utility of vasopressin or its’ analogues in the treatment of SCZ.