Altered brain and physiological stress responses in early psychosis

Abstract

Stress is proposed to be a crucial factor in the onset and presentation of psychosis. The early stage of psychosis provides a window into how stress interacts with the emergence of psychosis. Yet, how people with early psychosis respond to stress remains unclear. The current study examined how stress responses (brain, physiological, self-report) differ in early psychosis. Forty participants (20 early psychosis [EP], 20 healthy controls [HC]) completed a stress task in the scanner that involved viewing stressful and neutral-relaxing images. Physiological responses (cortisol, heart rate) and self-report of stress were also assessed. Region of Interest analyses were conducted with brain regions previously shown to be activated during the stress task (amygdala, hippocampus, striatum, hypothalamus, prefrontal cortex [dorsolateral, ventrolateral, medial orbital]). Linear mixed models were used to test for effects of group (EP, HC) and emotion (stress, neutral-relaxing). HC had higher hippocampus activation to stress versus neutral-relaxing conditions while EP did not show a difference (group x emotion interaction, p = 0.04). There were also significant main effects of group with EP having higher amygdala activation (p = 0.01), ventrolateral prefrontal cortex activation (vlPFC, p = 0.03), self-report of stress (p = 0.01), and heart rate (p < 0.001). Our study found preliminary evidence that people with early psychosis showed heightened response to stressful and non-threatening situations, across multiple levels of stress responses. Our findings suggest a novel perspective on stress alterations in early psychosis and highlight the importance of considering both stressful and non-stressful situations.

Keywords: Amygdala; Brain activation; Hippocampus; Physiological responses; Prefrontal cortex; Schizophrenia.

Figure 1:

fMRI Stress Task The Stress Task contained two blocks: Stress and Neural-relaxing. Each block had a baseline (three 1-minute runs of fixation cross), provocation (six 1-minute runs of images), and recovery phase (4-minute run). Examples of pictures shown for each condition are shown above. The red asterisks represent the three times cortisol was collected throughout each block. Self-report ratings of stress were collected at the beginning of the block, after each scan during baseline and provocation phases, and at the end of the block as indicated by the black lines. Heart rate was collected during each scan during baseline and provocation phases, as indicated by the striped white and black lines.

Figure 2:

Groups differed in brain activation of hippocampus, amygdala, and vlPFC Bar graphs display the predicted values of percent signal change for the three brain regions with significant group effects: hippocampus, amygdala, and ventrolateral prefrontal cortex (vlPFC). The stress condition (stress versus baseline) is shown in red, and the neutral-relaxing condition (neutral-relaxing versus baseline) is in blue. Healthy controls are shown on the left and the early psychosis group on the right. Standard error bars are displayed.

Figure 3:

Elevated heart rate in early psychosis group relative to healthy controls Average heart rate is displayed for each group for each condition across time. The stress condition is shown on the left and the neutral-relaxing is shown on the right. Healthy controls are shown in blue, and the early psychosis group is in red. Standard error bars are displayed.