Increased hypothalamic-pituitary-adrenal drive is associated with decreased appetite and hypoactivation of food-motivation neurocircuitry in anorexia nervosa.
OBJECTIVE
Corticotrophin-releasing hormone (CRH)-mediated hypercortisolemia has been demonstrated in anorexia nervosa (AN), a psychiatric disorder characterized by food restriction despite low body weight. While CRH is anorexigenic, downstream cortisol stimulates hunger. Using a food-related functional magnetic resonance imaging (fMRI) paradigm, we have demonstrated hypoactivation of brain regions involved in food motivation in women with AN, even after weight recovery. The relationship between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and appetite and the association with food-motivation neurocircuitry hypoactivation are unknown in AN. We investigated the relationship between HPA activity, appetite, and food-motivation neurocircuitry hypoactivation in AN.


METHODS
Cross-sectional study of 36 women (13 AN, ten weight-recovered AN (ANWR), and 13 healthy controls (HC)).


METHODS
Peripheral cortisol and ACTH levels were measured in a fasting state and 30, 60, and 120 min after a standardized mixed meal. The visual analog scale was used to assess homeostatic and hedonic appetite. fMRI was performed during visual processing of food and non-food stimuli to measure the brain activation pre- and post-meal.


RESULTS
In each group, serum cortisol levels decreased following the meal. Mean fasting, 120 min post-meal, and nadir cortisol levels were high in AN vs HC. Mean postprandial ACTH levels were high in ANWR compared with HC and AN subjects. 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 the food-motivation brain regions (e.g. hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula).


CONCLUSIONS
HPA activation may contribute to the maintenance of AN by the suppression of appetitive drive.
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Bulfinch 457-D, Boston, Massachusetts 02114, USA.
Elizabeth A
EA
Lawson
Laura M
LM
Holsen
Rebecca
R
Desanti
McKale
M
Santin
Erinne
E
Meenaghan
David B
DB
Herzog
Jill M
JM
Goldstein
Anne
A
Klibanski
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000097:blood; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000855:Anorexia / Q000503:physiopathology* / Q000523:psychology*; D000886:Anthropometry; D001066:Appetite / Q000502:physiology*; D015992:Body Mass Index; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003863:Depression / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005502:Food; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007028:Hypothalamic Hormones / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D009042:Motivation / Q000502:physiology; D009424:Nervous System Physiological Phenomena; D010907:Pituitary Hormones / Q000097:blood; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D019518:Postprandial Period / Q000502:physiology; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D007028:Hypothalamic Hormones; D010907:Pituitary Hormones; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone