Neural correlates of aberrant emotional salience predict psychotic symptoms and global functioning in high-risk and first-episode psychosis

Neurobiological and behavioral findings suggest that psychosis is associated with corticolimbic hyperactivity during the processing of emotional salience. This has not been widely studied in the early stages of psychosis, and the impact of these abnormalities on psychotic symptoms and global functioning is unknown. We sought to address this issue in 18 patients with first-episode psychosis (FEP), 18 individuals at ultra high risk of psychosis (UHR) and 22 healthy controls (HCs). Corticolimbic response and subjective ratings to emotional and neutral scenes were measured using functional magnetic resonance imaging. The clinical and functional impact of corticolimbic abnormalities was assessed with regression analyses. The FEP and UHR groups reported increased subjective emotional arousal to neutral scenes compared with HCs. Across groups, emotional vs neutral scenes elicited activation in the dorsomedial prefrontal cortex, inferior frontal gyrus/anterior insula and amygdala. Although FEP and UHR participants showed reduced activation in these regions when viewing emotional scenes compared with controls, this was driven by increased activation to neutral scenes. Corticolimbic hyperactivity to neutral scenes predicted higher levels of positive symptoms and poorer levels of functioning. These results indicate that disruption of emotional brain systems may represent an important biological substrate for the pathophysiology of early psychosis and UHR states.