Abstract
Individuals with schizophrenia have functionally significant deficits in automatic and controlled social cognition, but no currently available pharmacologic treatments reduce these deficits. The neuropeptide oxytocin has multiple prosocial effects when administered intranasally in humans and there is growing interest in its therapeutic potential in schizophrenia. We administered 40 IU of oxytocin and saline placebo intranasally to 29 male subjects with schizophrenia and 31 age-matched, healthy controls in a randomized, double-blind, placebo-controlled, cross-over study. Social cognition was assessed with The Awareness of Social Inference Test (TASIT) and the Reading the Mind in the Eyes Test (RMET). We examined the effects of oxytocin administration on automatic social cognition (the ability to rapidly interpret and understand emotional cues from the voice, face, and body); controlled social cognition (the ability to comprehend indirectly expressed emotions, thoughts, and intentions through complex deliberations over longer time periods); and a control task (the ability to comprehend truthful dialog and perform general task procedures) in individuals with and without schizophrenia using mixed factorial analysis of variance models. Patients with schizophrenia showed significant impairments in automatic and controlled social cognition compared to healthy controls, and administration of oxytocin significantly improved their controlled, but not automatic, social cognition, F(1, 58)=8.75; p=0.004. Conversely, oxytocin administration had limited effects on social cognition in healthy participants. Patients and controls performed equally well and there were no effects of oxytocin administration on the control task. Intact social cognitive abilities are associated with better functional outcomes in individuals with schizophrenia. Our data highlight the potentially complex effects of oxytocin on some but not all aspects of social cognition, and support the exploration of intranasal oxytocin as a potential adjunct treatment to improve controlled social cognition in schizophrenia.
Highlights
Social cognition, the ability to understand the thoughts and intentions of others, is critical for effectively navigating the social world
Given the heterogeneity of effects of oxytocin on social cognition in previous studies in schizophrenia, the neural and functional separation between automatic and controlled social cognitive processes, and the paucity of studies investigating the effects of OT administration on controlled-social cognition in schizophrenia or that include matched healthy controls, we examined the effects of OT administration on automatic and controlled social cognition in patients with SZ and HC
We found a main effect for Group (F(1, 58) = 45.85, p < 0.001) reflecting the fact that patients with SZ showed worse performance overall compared to HC’s on our tests of social cognition, but no significant main effect for Drug (F(1, 58) = 2.94, p = 0.09)
Summary
The ability to understand the thoughts and intentions of others, is critical for effectively navigating the social world. Advances in cognitive affective neuroscience have made it clear that understanding patient behavior in this domain requires the use of constructs that break social cognition down into subcomponents that reflect distinct neurologic systems. The automatic system operates quickly and unconsciously, is sensitive to subliminal cues, depends primarily on sensory processing, learns slowly, and is associated with basic person perception and immediate social cue detection (Bar et al, 2006) as measured by such tests as the Reading the Mind in the Eyes Test (RMET) (Bora et al, 2009). The higher-level, reflective controlled processing system operates on socioemotional information slowly and requires reflective consciousness, is insensitive to subliminal cues, depends on linguistic semantic processing, learns quickly, and makes more complex inferences based on deliberations performed over longer time periods (Lieberman, 2007)
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