OR21-4 Increased Hypothalamic-Pituitary-Adrenal Drive is Associated with Decreased Appetite and Hypoactivation of Food Motivation Neurocircuitry in Anorexia Nervosa

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR21-HPA Axis: New Clinical Developments
Clinical
Sunday, June 16, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 12:00 PM
Room 134 (Moscone Center)
Elizabeth A Lawson*1, Laura M Holsen2, Rebecca DeSanti1, McKale Santin1, Erinne Meenaghan1, David B Herzog3, Jill M Goldstein2 and Anne Klibanski1
1Massachusetts General Hospital/Harvard Medical School, Boston, MA, 2Brigham and Women's Hospital/Harvard Medical School, Boston, MA, 3Massachusetts General Hospital/Harvard Medical School
Corticotropin releasing hormone (CRH)-mediated hypercortisolemia has been demonstrated in anorexia nervosa, a disorder characterized by restricted food intake despite low body weight. Although CRH has anorexigenic effects, the downstream stress hormone cortisol stimulates hunger. We have previously shown hypoactivation of brain regions involved in food motivation in women with anorexia nervosa, even after weight recovery using a novel fMRI paradigm. We hypothesized that CRH-mediated hypercortisolemia may contribute to dysregulation of food motivation circuitry in this disorder. We studied 36 women [13 anorexia nervosa (AN), 10 weight-recovered AN (ANWR), 13 healthy controls (HC)] of comparable age to characterize the relationship between HPA measures, appetite and food motivation neurocircuitry in anorexia nervosa. BMI was lower in AN (17.7±0.3 kg/m2) than ANWR (21.9±0.7 kg/m2) and HC (22.5±0.4 kg/m2) (p<0.0001). Peripheral cortisol and ACTH levels were measured fasting and 30, 60, and 120 min after a standardized meal. The Visual Analogue Scale was used to assess appetite. fMRI was performed during visual processing of food and non-food stimuli to measure brain activation pre- and post-meal. Mean fasting, 120 min post-meal, and nadir cortisol levels were high in AN vs. HC (p<0.02). Mean ACTH levels were higher in AN and in ANWR vs. HC after the meal (p<0.03). Cortisol secretion was associated with lower homeostatic (R=-0.55 , p=0.0006) and hedonic (R=-0.49, p=0.003) appetite in the fasting state, independent of BMI and depressive symptoms. Cortisol secretion was also associated with between-group variance in activation in food-motivation brain regions, including the hypothalamus (control center for appetitive signals) (pre-meal HC>AN 26%, HC>ANWR 14%), amygdala (important for learning satiety cues, assessing reward value) (pre-meal HC>AN 45%, HC>ANWR 42%; post-meal HC>AN 16%), hippocampus (implicated in processing food-related memories) (pre-meal HC>AN 24%), OFC (integrates emotion, reward expectation) (pre-meal HC>AN 46%) and insula (houses the primary taste cortex, integrates visceral signals, modulates motivational behavior) (premeal HC>AN 12%, HC>ANWR 12%). We conclude that HPA activation may contribute to the maintenance of anorexia nervosa by suppression of appetitive drive.

Nothing to Disclose: EAL, LMH, RD, MS, EM, DBH, JMG, AK

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Harvard Catalyst | The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR025758); Harvard K12 HD051959 Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Program supported by National Institutes of Health Office of Research in Women's Health (ORWH); NIH K23 MH092560.