Increased hypothalamic–pituitary–adrenal drive is associated with decreased appetite and hypoactivation of food-motivation neurocircuitry in anorexia nervosa

Abstract

Objective Corticotropin releasing hormone (CRH)-mediated hypercortisolemia has been demonstrated in anorexia nervosa (anorexia), a psychiatric disorder characterized by food restriction despite low body weight. While CRH is anorexigenic, downstream cortisol stimulates hunger. Using a food-related fMRI paradigm, we have demonstrated hypoactivation of brain regions involved in food motivation in women with anorexia, even after weight-recovery. The relationship between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and appetite, and the association with food motivation neurocircuitry hypoactivation is unknown in anorexia. We investigated the relationship between HPA activity, appetite and food motivation neurocircuitry hypoactivation in anorexia. Design Cross-sectional study of 36 women [13 anorexia (AN), 10 weight-recovered AN (ANWR), 13 healthy controls (HC)]. Methods Peripheral cortisol and ACTH levels were measured fasting and 30, 60, and 120min after a standardized mixed meal. The Visual Analogue Scale was used to assess homeostatic and hedonic appetite. fMRI was performed during visual processing of food and non-food stimuli to measure brain activation pre- and post-meal. Results In each group, serum cortisol levels decreased following the meal. Mean fasting, 120min post-meal, and nadir cortisol levels were high in AN vs. HC. Mean postprandial ACTH levels were high in ANWR compared to HC and AN. Cortisol levels were associated with lower fasting homeostatic and hedonic appetite, independent of BMI and depressive symptoms. Cortisol levels were also associated with between-group variance in activation in food-motivation brain regions (e.g., hypothalamus, amygdala, hippocampus, OFC and insula). Conclusions HPA activation may contribute to the maintenance of anorexia by suppression of appetitive drive.

Blunted neuroendocrine stress reactivity in young women with eating disorders

“…Since cortisol concentrations were negatively associated with hunger and appetite ratings in all participants, these findings suggest that enhanced HPAA activity reflects malnutrition in untreated individuals with AN. Similar studies in patients [28][29][30][31]76] support this interpretation and a study in fasting healthy individuals suggests that these processes are generalizable to a non-clinical population [77]. Thus, we suggest that patients in the study by Monteleone et al [30] might have been malnourished to a larger extent than patients in our study, resulting in an enhanced HPAA response to the TSST.…”

“…A recent study, however, linked malnutrition and elevated HPAA reactivity. More specifically, while no differences in cortisol responses to a standardized mixed meal were found between healthy individuals and weight-recovered AN outpatients, patients with untreated AN showed significantly higher cortisol concentrations [76]. Since cortisol concentrations were negatively associated with hunger and appetite ratings in all participants, these findings suggest that enhanced HPAA activity reflects malnutrition in untreated individuals with AN.…”

Eating Disorders in Children and Adolescents: State of the Art Review

“…16,24,45 Neurologic Malnutrition significantly affects the brain in children and adolescents because of the dynamic changes that are occurring in cognitive and structural braindevelopmentduringthisperiod. [87][88][89][90][91][92][93][94][95][96][97][98][99][100][101] Severely ill patients with AN have been shown to have reduced brain tissue volume and impaired neuropsychological functioning. 87 One study demonstrated persistent gray-white matter deficits and cerebrospinal fluid levels elevations on magnetic resonance imaging of weight restored patients with AN.…”

“…123,124 Finally, translational research is underway targeting known deficits in neurocognitive processes, neurotransmitters affected in EDs, and neuroanatomic changes found on imaging studies to tailor treatment and improve treatment response in patients with EDs. [88][89][90][91][92][93][94][95][96][97][98][99][100][101] Family-Based Treatment…”

Hypothalamic-pituitary-adrenal axis hypersensitivity in female rats on a post-weaning high-fat diet after chronic mild stress

“…Animal experiments have shown that food restriction increased adrenal gland weight and serum CORT levels after overnight fasting in rats (36), and enhanced HPA axis activity resulting in appetite loss and anorexia nervosa (39). Mixed results have been reported by studies assessing the effects of HFD exposure on CORT during developmental stages under basal conditions and after stress challenge (2,40).…”