Sex differences in the effect of stress on response to food reward cues

Abstract

OBJECTIVE: The overlap in literature on stress and human reward processing is relatively small but growing as its significance becomes increasingly implicated in the obesity epidemic. The greater prevalence of obesity, especially severe obesity, among females than males suggests that there may be sex differences in hormones driving eating behaviors and in food reward processing. There is an important gap in the literature – a paucity of studies employing robust psychosocial stressors in combination with a food-related reward neuroimaging task to examine sex differences in the effect of psychosocial stress on hormones and food reward processing in humans. We hypothesized that male and female healthy subjects exposed to stressful situations during the Maastricht Acute Stress Test (MAST) will show sex differences in physiological, subjective self-report, and neural measures. The physiological variables measured ghrelin and cortisol reactivity. Subjective self-report variables measured perceived threat (pre-/post-task appraisals), state anxiety (pre-/post-scan state anxiety), and visual analogue scale ratings of appetite and mood (hunger/sadness/tension). The neural variables utilized a food incentive delay (FID) task that measured hedonic value (valence ratings of reward vs. neutral cue, success, or fail), incentive motivation (reaction time to reward vs. neutral success), and reward sensitivity (blood-oxygen-level-dependent activation during functional magnetic resonance imaging in response to food reward vs. neutral anticipation and receipt) in predefined brain regions of interest (ROIs): the caudate, nucleus accumbens, putamen, amygdala, and hypothalamus. METHODS: A total of 42 healthy subjects between the ages of 21 and 45 with body mass index between 18 and 35 were enrolled. Each participant completed a stress visit, during which the stress version of the MAST was administered, and a no-stress visit, during which the no-stress version of the MAST was administered. The order of visits for each subject was randomly assigned. Demographic data as well as physiological, subjective self-report, and neural measures were obtained at each visit. RESULTS: Subjects experienced greater percent increase in cortisol from pre-MAST to post-MAST at the stress visit than the no-stress visit. At the stress visit, post-MAST raw cortisol levels were significantly higher in males than in females and pre-FID raw ghrelin levels were significantly higher in females than males. Subjects endorsed higher perceived threat, lower pre-scan state anxiety, and more negative post-MAST mood at the stress visit compared to the no-stress visit. During the stress visit, no significant sex differences were found in perceived threat, state anxiety, or mood. Lastly, there were no main effects of visit or sex on appetite, valence ratings, and functional response in the ROIs. Across visits, females reacted significantly slower than males to food reward and neutral cues. There was a significant effect of phase on functional response in the amygdala, but not in any other ROIs, with subjects across visits showing significantly greater amygdala activation in response to food reward (vs. neutral) receipt than anticipation. DISCUSSION: Our study revealed, as predicted, that there was a significant effect of stress on cortisol and ghrelin, and on subjective self-reported perceived threat, pre-scan state anxiety, and post-MAST mood. At the stress visit, compared to the no-stress visit, subjects showed greater increase in cortisol and reported higher perceived threat, lower pre-scan state anxiety, and more negative post-MAST mood, indicating that the stressful impact of the MAST induced the intended physiological consequences. Sex differences were observed in the effect of stress on cortisol at post-MAST time point (T20) and on ghrelin at pre-FID time point (T80). Our findings support sex differences in ghrelin and cortisol response to stress in agreement with previous studies’ findings. We failed to reject the null hypothesis that there is no effect of stress on appetite, valence ratings, reaction times, and functional response in the ROIs in response to food reward (vs. neutral) anticipation and receipt. We also did not find significant sex differences, or interactions involving sex, in perceived threat, state anxiety, appetite, mood, or valence ratings. Notably, we did not detect statistically significant sex differences in blood-oxygen-level-dependent signal activation in the caudate, nucleus accumbens, putamen, amygdala, or hypothalamus in response to reward (vs. neutral) anticipation and receipt. Future research can extend our findings by examining individual and potential sex differences in pervasive trait-level qualities to better understand the role of emotional eating tendencies on ghrelin, and reward anticipation and receipt