M74. fMRI of Social Aversion in Early Psychosis and Psychosis Risk

Abstract

Abstract Background: Social impairment is prevalent and disabling in established psychosis as well as during the psychosis prodrome. Neuroimaging studies in healthy people have identified a set of interconnected regions involved in social cognition, aversive processing, and emotion regulation, including the amygdala, ventromedial prefrontal cortex (vmPFC), and anterior insular cortex (AIC). We hypothesize that across the psychosis spectrum from risk to frank schizophrenia, dysfunction in these regions and associated circuitry is associated with aberrant aversive learning and with negative symptoms that cause social impairment. Here we report results of a 3T fMRI study testing this hypothesis using a social aversive conditioning paradigm. Methods: fMRI participants (n = 81) were youth and young adults (age 10–30) in 3 demographically-matched groups: frank psychosis (PSY, n = 22), clinical risk (CR, n = 27) and healthy control (HC, n = 32). During fMRI, participants performed the aversive conditioning paradigm we report here, as well as a reversal paradigm and resting-state imaging. Male faces with neutral expressions served as conditioned stimuli (CS), and a loud scream was the aversive unconditioned stimulus (US), co-terminating with 50% contingency. fMRI analysis focused on the difference in regional activation between aversive (CS+, trials without a US) and neutral (CS−) conditions. We examined categorical group differences as well as dimensional relationships to negative, positive, and anxiety symptoms. Results: Subjective ratings of the faces as well as autonomic measures (pupil dilation) confirmed conditioning effects in HC, with reduced CS+ vs CS− discrimination in both PSY and CR groups. Across all subjects, AIC showed CS+ > CS− activation, while vmPFC activated to CS− but deactivated to CS+ (CS+ CS− response, with transient activation at stimulus onset and again at the time when US might appear. Relative to HC, both CR and PSY showed decreased differentiation of CS+ < CS− in the vmPFC. Across CR and PSY, amygdala conditioning was positively correlated with negative symptom severity. Conclusion: These results demonstrate similar social aversive conditioning abnormalities in both established psychosis and those at clinical risk, providing further support for the spectrum conceptualization of psychosis. On average, psychosis spectrum individuals exhibit a failure to engage ventromedial prefrontal cortex during aversive conditioning. This prefrontal region is critical for emotional regulation including modulating threat responses, and may underpin impaired behavioral discrimination. Negative symptom severity is associated with exaggerated amygdala conditioning, suggesting that negative symptoms may be related to heightened aversive learning rather than a failure of discrimination.