M67. The Neural Effects of Oxytocin on Social Decision-Making in Schizophrenia: An fMRI Study

Abstract

Background: Functional impairment is a defning feature of schizophrenia. A likely contributor to the functional outcome is social cognition and patients with schizophrenia show defcits in social cognitive abilities. Therapeutic interventions that remediate social cognitive abilities may serve to improve the functional outcome of schizophrenia. However, such therapeutic interventions are not currently available. Oxytocin (OXT), a neuropeptide produced in the hypothalamus, plays an important role in social behaviors and many studies have examined the behavioral effects of OXT on social cognitive abilities in schizophrenia with promising results. There is however a paucity of data on the neural basis of OXT effects in schizophrenia and in this study we sought to investigate the neural effects of OXT in schizophrenia during social decision-making. Methods: Twenty right-handed male participants with DSM-IV schizo-phrenia were enrolled in a double-blind placebo-controlled, crossover fMRI study and were randomly allocated to a single intranasal dose of either 40 IU OXT or saline placebo (PBO). Participants completed 2 sessions of fMRI during which they performed a forced-choice stochastically reward decision-making task that incorporated emotionally valenced and neutral faces as social variables. Results: fMRI data were preprocessed and analyzed using Statistical Parametric Mapping 12 and MATLAB R2014a. A region of interest analysis was performed using small volume correction (SVC) within a mask for the left and right amygdala. We found signifcantly more neural activity in the PBO condition over the OXT condition in the left amygdala (x =-25, y =-4, z =-14, t(38) = 4.89, P =.002, k = 52, FWE peak level corrected for SVC). The right amygdala was also signifcantly more active in the PBO condition over the OXT condition (x = 27, y =-8, z =-14, t(38) = 3.74, P =.020, k = 11, FWE peak level corrected for SVC). Conclusion: We showed that OXT suppressed amygdala activation during emotionally valenced social decision-making in patients with schizophrenia. Amygdala has major contributions to social cognitive abilities; it processes emotion from faces, it codes and assigns salience to environmental stimuli, it processes ambiguity and uncertainty in the environment and contributes to reward learning. Suppression of amygdala's neural activation by OXT suggests that OXT may reduce the salience of emotionally laden stimuli in schizophrenia and may also help with the regulation of anxiety associated with ambiguity in social situations involving decision-making. These effects may contribute to the facilitation of social engagement and social interactions in patients with schizophrenia.