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

Abstract

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.

Keywords: amygdala; at-risk mental state; emotional salience; fMRI; psychosis.

© The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Figures

Fig. 1

Average arousal ratings (3 = highly aroused, 2 = slightly aroused, 1 = not at all aroused) for each emotional condition in individuals with an FEP, subjects at UHR and control subjects (HC). *Significant difference between groups at P < 0.05. Error bars represent standard error.

Fig. 2

Results of whole-brain analyses and amygdala ROI analysis of the main effect of Emotional vs Neutral contrast across the three groups (FEP, UHR and HCs). Regions are described in Table 2, (A) rendered views and (B) section views.

Fig. 3

Main activation clusters (P < 0.05 FWE) and parameter estimates (mean and standard error) for each emotional condition (emotional > neutral; neutral > fixation) and group in the voxel with max. t value. Mean parameter estimates are shown for voxel [−40 36 2] in the left inferior frontal gyrus/anterior insula, for voxel [18 46 30] in the dmPFC and voxels [24 −6 −16] and [−22 −6 −12], respectively, in the right and left amygdala. AMY, amygdala; IFG/aINS, inferior frontal gyrus/anterior insula; L, left; R, right.

Fig. 4

Scatterplots of (A1) average CAARMS positive symptoms and (A2) average GAF levels of functioning as a function of dmPFC activation in UHR individuals; (B1) average PANSS positive symptoms as a function of right amygdala activation and (B2) as a function of IFG/aINS activation in FEP patients. AMY, amygdala. IFG/aINS, inferior frontal gyrus/anterior insula; L, left; R, right.